Yuzhong Chengguanzhen, China
Yuzhong Chengguanzhen, China

Chongqing Medical University , previously referred to as the Chongqing University of Medical science , was established in 1956 in Chongqing, China. It was originally a branch of the Shanghai First Medical College . Wikipedia.


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Sun Y.,University of California at Davis | Do H.,University of California at Davis | Gao J.,University of California at Davis | Gao J.,Yunnan Normal University | And 4 more authors.
Current Biology | Year: 2013

Sensing of an electric field (EF) by cells - galvanotaxis - is important in wound healing [1], development [2], cell division, nerve growth, and angiogenesis [3]. Different cell types migrate in opposite directions in EFs [4], and the same cell can switch the directionality depending on conditions [5]. A tug-of-war mechanism between multiple signaling pathways [6] can direct Dictyostelium cells to either cathode or anode. Mechanics of motility is simplest in fish keratocytes, so we turned to keratocytes to investigate their migration in EFs. Keratocytes sense electric fields and migrate to the cathode [7, 8]. Keratocyte fragments [9, 10] are the simplest motile units. Cell fragments from leukocytes are able to respond to chemotactic signals [11], but whether cell fragments are galvanotactic was unknown. We found that keratocyte fragments are the smallest motile electric field-sensing unit: they migrate to the anode, in the opposite direction of whole cells. Myosin II was essential for the direction sensing of fragments but not for parental cells, while PI3 kinase was essential for the direction sensing of whole cells but not for fragments. Thus, two signal transduction pathways, one depending on PI3K, another on myosin, compete to orient motile cells in the electric field. Galvanotaxis is not due to EF force and does not depend on cell or fragment size. We propose a "compass" model according to which protrusive and contractile actomyosin networks self-polarize to the front and rear of the motile cell, respectively, and the electric signal orients both networks toward cathode with different strengths. © 2013 Elsevier Ltd.


Wang D.-Y.,Peking University | Zhang Q.,Peking University | Liu Y.,Peking University | Lin Z.-F.,Hangzhou Normal University | And 3 more authors.
Plant Cell | Year: 2010

The mechanisms that regulate mitochondrial inheritance are not yet clear, even though it is 100 years since the first description of non-Mendelian genetics. Here, we quantified the copy numbers of mitochondrial DNA (mtDNA) in the gametic cells of angiosperm species. We demonstrate that each egg cell from Arabidopsis thaliana, Antirrhinum majus, and Nicotiana tabacum possesses 59.0, 42.7, and 73.0 copies of mtDNA on average, respectively. These values are equivalent to those in Arabidopsis mesophyll cells, at 61.7 copies per cell. On the other hand, sperm or generative cells from Arabidopsis, A. majus, and N. tabacum possess minor amounts of mtDNA, at 0.083, 0.47, and 1 copy on average, respectively. We further reveal a 50-fold degradation of mtDNA during pollen development in A. majus. In contrast, markedly high levels of mtDNA are found in the male gametic cells of Cucumis melo and Pelargonium zonale (1296.3 and 256.7 copies, respectively). Our results provide direct evidence for mitochondrial genomic insufficiency in the eggs and somatic cells and indicate that a male gamete of an angiosperm may possess mtDNA at concentrations as high as 21-fold (C. melo) or as low as 0.1% (Arabidopsis) of the levels in somatic cells. These observations reveal the existence of a strong regulatory system for the male gametic mtDNA levels in angiosperms with regard to mitochondrial inheritance. © 2010 American Society of Plant Biologists.


Wang D.,Chongqing Medical University
Annals of the Academy of Medicine Singapore | Year: 2010

Introduction: We prospectively evaluated the staging of benign prostate hyperplasia (BPH) to decide transurethral resection of prostate (TURP) therapeutic modality and the fi nal outcomes in patients with lower urinary tract symptoms (LUTS) suggestive of BPH. Materials and Methods: Male patients above 50 years old presented with LUTS suggestive of BPH were included in this study. The initial assessment included the International Prostatic Symptoms Score (IPSS) and the Quality of Life (QOL) index, digital rectal examination (DRE). Transabdominal ultrasound was done to measure the prostate volume, intravesical prostatic protrusion (IPP) and the post void residual (PVR) urine. BPH was classifi ed according to the degree of IPP using grades 1 to 3. The staging of BPH was performed according to the presence or absence of bothersome symptoms (QOL ≥3) and signifi cant obstruction (PVR >100ml). Patients with stage I BPH with no bothersome symptoms and no signifi cant obstruction were generally observed. Those with stage II BPH, bothersome symptoms but no signifi cant obstruction, received pharmacotherapy in the fi rst instance, and were offered TURP if symptoms persisted or worsened. Patients with signifi cant obstruction, persistent PVR >100ml, irrespective of symptoms would be classifi ed as stage III, and were advised to undergo TURP as an option. Lastly, those with stage IV (complications of BPH) were strongly recommended to undergo TURP. Results: A total of 408 patients were recruited in this study and after a mean follow-up of 30 months (range, 6 to 84), 96 (24%) eventually had TURP. Sixteen(13%), 50(21%), 28(64%) and 2(100%) patients who underwent TURP were initially diagnosed as stage I, II, III and IV, respectively. Eighty-seven (91%) of the 96 patients signifi cantly improved to stage I BPH post TURP. Conclusions: These results showed that the staging of BPH can assist in the tailoring of treatment for patients with LUTS suggestive of BPH, with good outcome in 91% post TURP.


Han T.,Shanghai University | Han P.,U.S. Center for Disease Control and Prevention | Peng W.,Chongqing Medical University | Wang X.-R.,Shandong University
Pharmaceutical Biology | Year: 2013

Context: Depression is one of the most common psychiatric diseases. Acorus tatarinowii Schott (Araceae) has shown many bioactivities in treatment of senile dementia and epilepsy. However, there is no report on antidepressant-like effects of the essential oil (EO) and its major components on animals under standardized experimental procedures. Objective: This study was designed to investigate the antidepressant properties of EO and asarones from the rhizomes of A. tatarinowii. Materials and methods: Gas chromatography-mass spectrometry (GC/MS) was used to determine the composition of EO. The forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) were used to evaluate the antidepressant-like effects of EO and asarones. EO [30, 60, 120 or 240 mg/kg, per os (p.o.)], asarones (α-asarone and β-asarone) [5, 10 and 20mg/kg, intraperitoneal (i.p.)] and imipramine (15mg/kg, i.p.) were administered at 1h, 30min and 30min before the test, respectively. Results: From the results of GC/MS, it was found that the main components of the EO were α-asarone (9.18%) and β-asarone (68.9%). From the results of FST and TST, the immobility time can be reduced to 166±17s (p<0.01) and 146±15s (p<0.05) by EO at the dose of 120mg/kg. Moreover, significant antidepressant-like effects were shown by α-asarone with the immobility time of 178±15s (p<0.05) and 159±17s (p<0.01) in FST, or 147±12 (p<0.05) and 134±12s (p<0.01) in TST at the dose of 10 and 20mg/kg. β-Asarone also displayed antidepressant-like effects with an immobility time of 179±18s (p<0.05) in FST or 142±14 (p<0.05) in TST at 20mg/kg. However, no change in ambulation was observed in the OFT. Conclusion: The results obtained indicate that the EO and asarones from the rhizomes of A. tatarinowii can be considered as a new therapeutic agent for curing depression. © 2013 Informa Healthcare USA, Inc.


Zhang C.,Umeå University | Zhang C.,National University of Singapore | Liu Y.,Chongqing Medical University | Gilthorpe J.,Umeå University | van der Maarel J.R.C.,National University of Singapore
PLoS ONE | Year: 2012

Increasing evidence supports the contribution of local inflammation to the development of Alzheimer's disease (AD) pathology, although the precise mechanisms are not clear. In this study, we demonstrate that the pro-inflammatory protein S100A9 interacts with the Aβ1-40 peptide and promotes the formation of fibrillar β-amyloid structures. This interaction also results in reduced S100A9 cytotoxicity by the binding of S100A9 toxic species to Aβ1-40 amyloid structures. These results suggest that secretion of S100A9 during inflammation promotes the formation of amyloid plaques. By acting as a sink for toxic species, plaque formation may be the result of a protective response within the brain of AD patients, in part mediated by S100A9. © 2012 Zhang et al.


Liu H.-L.,Tongji University | Zhang Y.-H.,Chongqing Medical University
Chemosphere | Year: 2010

Accurate description of hormetic dose-response curves (DRC) is a key step for the determination of the efficacy and hazards of the pollutants with the hormetic phenomenon. This study tries to use support vector regression (SVR) and least squares support vector regression (LS-SVR) to address the problem of curve fitting existing in hormesis. The SVR and LS-SVR, which are entirely different from the non-linear fitting methods used to describe hormetic effects based on large sample, are at present only optimum methods based on small sample often encountered in the experimental toxicology. The tuning parameters (C and p1 for SVR, gam and sig2 for LS-SVR) determining SVR and LS-SVR models were obtained by both the internal and external validation of the models. The internal validation was performed by using leave-one-out (LOO) cross-validation and the external validation was performed by splitting the whole data set (12 data points) into the same size (six data points) of training set and test set. The results show that SVR and LS-SVR can accurately describe not only for the hermetic J-shaped DRC of seven water-soluble organic solvents consisting of acetonitrile, methanol, ethanol, acetone, ether, tetrahydrofuran, and isopropanol, but also for the classical sigmoid DRC of six pesticides including simetryn, prometon, bromacil, velpar, diquat-dibromide monohydrate, and dichlorvos. © 2009 Elsevier Ltd. All rights reserved.


Huang S.,Chongqing Medical University | Li L.,Chongqing Medical University | Xin D.,Peking University
Tumor Biology | Year: 2014

Increased expression of pituitary tumor-transforming gene 1 (PTTG1) occurs during mitosis-related sister chromatid segregation, and characterizes various tumor cells, including prostate cancer. Whereas the mechanism remains unclarified. Here, the PTTG1 levels in a prostate cancer cell line, PC3, were modulated by the expression of PTTG1 transgene or shRNA, showing that the PTTG1 levels affected the proliferation of prostate cancer cells, in vitro and in vivo. Moreover, a significant decrease in mothers against decapentaplegic homolog 3 (SMAD3), a key component of transforming growth factor β (TGFβ) signaling pathway, was induced by PTTG1 overexpression. Since SMAD3 is a ubiquitous cell-cycle inhibitor, our data suggest that PTTG1 may promote the proliferation of prostate cancer cells by inhibiting SMAD3-mediated TGFβ signaling. To identify a causal link, we expressed SMAD3 in PTTG1-overexpressing PC3 cells and found that SMAD3 expression inhibited the augmented cancer cell proliferation by PTTG1overexpression. Furthermore, SMAD3 inhibition by short hairpin RNA (ShRNA) completely rescued the cancer cell proliferation in PTTG1 ShRNA-treated PC3 cells. Taken together, our data suggest that PTTG1 promotes the proliferation of prostate cancer cells via the inhibition of SMAD3. SMAD3 thus appears to be a novel therapeutic target for suppressing the growth of prostate cancer. © 2014 International Society of Oncology and BioMarkers (ISOBM).


Li L.,Chongqing Medical University | Xiao H.,Chongqing Medical University | Lin C.,Chongqing Medical University | Wang Y.,Chongqing Medical University | And 6 more authors.
Clinical Cancer Research | Year: 2014

Purpose: The EGF receptor tyrosine kinase inhibitors (EGFR-TKI) have become a standard therapy in patients with EGFR-Activating mutations. Unfortunately, acquired resistance eventually limits the clinical effects and application of EGFR-TKIs. Studies have shown that suppression of epithelial-mesenchymal transition (EMT) and the interleukin (IL)-6/STAT3 pathway may abrogate this acquired mechanism of drug resistance of TKIs. This study aims to investigate the effect of metformin on sensitizing EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal. Experimental Design: The effect of metformin on reversing TKI resistance was examined in vitro and in vivo using MTT, BrdUrd incorporation assay, invasion assay, flow cytometry analysis, immunostaining, Western blot analysis, and xenograft implantation. Results: In this study, metformin, a widely used antidiabetic agent, effectively increased the sensitivity of TKI-resistant lung cancer cells to erlotinib or gefitinib. Metformin reversed EMT and decreased IL-6 signaling activation in TKI-resistant cells, while adding IL-6 to those cells bypassed the anti-TKI-resistance effect of metformin. Furthermore, overexpression or addition of IL-6 to TKI-sensitive cells induced TKI resistance, which could be overcome by metformin. Finally, metformin-based combinatorial therapy effectively blocked tumor growth in xenografts with TKI-resistant cancer cells, which was associated with decreased IL-6 secretion and expression, EMT reversal, and decreased IL-6-signaling activation in vivo. Conclusion: Metformin, generally considered nontoxic and remarkably inexpensive, might be used in combination with TKIs in patients with non-small cell lung cancer, harboring EGFR mutations to overcome TKI resistance and prolong survival. Clin Cancer Res. © 2014 American Association for Cancer Research.


The aim of this study is to determine whether early viral dynamics and evolution predict outcome of primary acute hepatitis C virus (HCV) infection. HCV- and human immunodeficiency virus-negative injection drug users were enrolled prospectively and followed monthly to identify acute HCV infection using RNA detection. Subjects with more than 1 month between HCV-RNA-negative and -positive visits were excluded to ensure stringent acute infection. Differences in medians of log-transformed viral RNA levels and evolutionary rates in each gene of a 5′-hemigenomic amplicon were assessed using Mann-Whitney's rank-sum test. Correlation coefficient was calculated using Spearman's rank order. Initial viremia level was 50-fold higher in subjects with spontaneous clearance (compared with persistence) of primary acute HCV infection (median, 7.1 versus 5.4 log 10 IU/mL; P = 0.002). Initial viremia level in subjects with interleukin (IL)28B-C allele at rs12979860 and clearance was higher than that in subjects with IL28B-T allele and persistence (P = 0.001). Evolutionary rates in the hypervariable region 1 (HVR1) region of the E2 gene were significantly higher in self-resolvers than those in persistence subjects during early infection, whereas other genes or regions had comparable rates. All major substitutions in HVR1 in persistence subjects were convergent changes, whereas over the same time interval clearance subjects displayed divergent evolution, indicating different immune responses between the two groups. Conclusion: Spontaneous clearance of acute HCV infection is predicted by high initial viremia as well as favorable IL28B genotype and is associated with rapid envelope-sequence evolution. This linkage of host genetics, viral dynamics, and evolution provides new directions for mechanistic studies. © 2012 American Association for the Study of Liver Diseases.


Xiong B.,Peking University | Ma L.,The Third Hospital of Mianyang | Huang W.,The Ninth Peoples Hospital Of Chongqing City | Zhao Q.,Peking University | And 2 more authors.
Journal of Gastrointestinal Surgery | Year: 2015

Conclusions: RTME is safe and feasible and may be an alternative treatment for RC. More international multicenter prospective large sample RCTs investigating the long-term oncological and functional outcomes are needed to determine the advantages of RTME over LTME in RC.Results: Eight studies were identified that included 1229 patients in total, 554 (45.08 %) in the RTME group and 675 (54.92 %) in the LTME group. Compared with LTME, RTME was associated with lower conversion rate (OR 0.23, 95 % CI [0.10, 0.52]; P = 0.0004), lower positive rate of circumferential resection margins (CRM) (2.74 % vs 5.78 %, OR 0.44, 95 % CI [0.20, 0.96], P = 0.04), and lesser incidence of erectile dysfunction (ED) (OR 0.09, 95 % CI [0.02, 0.41]; P = 0.002). Operation time, estimated blood loss, recovery outcome, postoperative morbidity and mortality, length of hospital stay, number of lymph nodes harvested, distal resection margin (DRM), proximal resection margin (PRM), and local recurrence had no significant differences between the two groups.Background: Robotic surgery has been used successfully in many branches of surgery, but there is little evidence in the literature on its use in rectal cancer (RC). We conducted this meta-analysis of randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) to evaluate whether the safety and efficacy of robotic total mesorectal excision (RTME) in patients with RC are equivalent to those of laparoscopic TME (LTME).Methods: Pubmed, Embase, Cochrane Library, Ovid, and Web of Science databases were searched. Studies clearly documenting a comparison of RTME with LTME for RC were selected. Operative and recovery outcomes, early postoperative morbidity, and oncological parameters were evaluated. © 2014, The Society for Surgery of the Alimentary Tract.


Teng Z.,Nanjing University | Su X.,Nanjing University of Posts and Telecommunications | Zheng Y.,Chongqing Medical University | Sun J.,Nanjing University | And 6 more authors.
Chemistry of Materials | Year: 2013

We demonstrate a self-transformation approach for the synthesis of ordered mesoporous silica hollow spheres with radially oriented mesochannels. The method is simple and facile, in which mesostructured silica spheres synthesized in a Stöber solution can spontaneously transform to hollow structure when they are incubated with water. The formation of the hollow structure does not require any sacrificial templates, emulsion droplets, or surface protective agents. The obtained mesoporous silica hollow spheres possess controllable diameter, tunable shell thickness, high specific surface area, and uniform mesopore. Transmission electron microscopy (TEM) observations show that the formation of the hollow spheres undergoes a selective etching process in the inner section. 29Si NMR spectra and detailed reactions demonstrate that the solid-to-hollow transformation of the Stöber silica spheres in water is attributed to the difference in the degree of condensation of silica between their outer layer and inner section. Cytotoxicity and histological assays confirm that the obtained mesoporous silica hollow spheres possess good biocompatibility. Besides, the capability of the hollow spheres as contrast agents for untrasound imaging is conducted in vitro. Moreover, yolk-shell microspheres with a Fe3O4@nSiO2 core and a mesoporous silica shell are successfully prepared based on the facile self-transformation strategy, which provides a general method to create various yolk-shell structured multifunctional composites for different applications. © 2012 American Chemical Society.


Wang Z.,Chongqing Medical University | Wang Y.,ZYX Biotech Company | Farhangfar F.,Regenetech Inc. | Zimmer M.,Chongqing Medical University | Zhang Y.,ZYX Biotech Company
PLoS ONE | Year: 2012

Wound healing is primarily controlled by the proliferation and migration of keratinocytes and fibroblasts as well as the complex interactions between these two cell types. To investigate the interactions between keratinocytes and fibroblasts and the effects of direct cell-to-cell contact on the proliferation and migration of keratinocytes, keratinocytes and fibroblasts were stained with different fluorescence dyes and co-cultured with or without transwells. During the early stage (first 5 days) of the culture, the keratinocytes in contact with fibroblasts proliferated significantly faster than those not in contact with fibroblasts, but in the late stage (11th to 15th day), keratinocyte growth slowed down in all cultures unless EGF was added. In addition, keratinocyte migration was enhanced in co-cultures with fibroblasts in direct contact, but not in the transwells. Furthermore, the effects of the fibroblasts on keratinocyte migration and growth at early culture stage correlated with heparin-binding EGF-like growth factor (HB-EGF), IL-1α and TGF-β1 levels in the cultures where the cells were grown in direct contact. These effects were inhibited by anti-HB-EGF, anti-IL-1α and anti-TGF-β1 antibodies and anti-HB-EGF showed the greatest inhibition. Co-culture of keratinocytes and IL-1α and TGF-β1 siRNA-transfected fibroblasts exhibited a significant reduction in HB-EGF production and keratinocyte proliferation. These results suggest that contact with fibroblasts stimulates the migration and proliferation of keratinocytes during wound healing, and that HB-EGF plays a central role in this process and can be up-regulated by IL-1α and TGF-β1, which also regulate keratinocyte proliferation differently during the early and late stage. © 2012 Wang et al.


Huang Z.,Chongqing Medical University | van Velkinburgh J.C.,Van Velkinburgh Initiative for Collaboratory BioMedical Research | Ni B.,Chongqing Medical University | Wu Y.,Chongqing Medical University
Liver International | Year: 2012

T helper 17 (Th17) cells are a newly identified subset of T helper cells that play important roles in host defense against extracellular bacteria, as well as in the pathogenesis of autoimmune disease. Research interest in these cells was piqued when hepatitis B virus (HBV)-infected patients were found to have significantly elevated Th17 cell frequency, and it was proposed that these proinflammatory effectors may promote the HBV disease process. Subsequent studies have revealed that Th17 cells drive immune-mediated pathology of HBV infection, and that IL-23 amplifies the Th17 cell responses and liver inflammation. As a result, new pathways of HBV-mediated liver damage have been elucidated, along with promising new targets of molecular therapeutic strategies. Ongoing research is also providing significant insights into the target cells and underlying mechanisms of Th17-secreted cytokines, including IL-17A, IL-21 and IL-22. Future studies are expected to fully uncover the cytokine-related mechanisms mediating HBV-induced liver inflammation, and to determine the yet unknown cell source of IL-23. This review will draw upon the most up-to-date available data to discuss the putative roles and detailed mechanisms of IL-23/Th17 cell axis in HBV infection-mediated liver pathogenesis. © 2012 John Wiley & Sons A/S.


Hui C.,Chongqing Medical University | Qi X.,Chongqing Medical University | Qianyong Z.,Chongqing Medical University | Xiaoli P.,Chengdu Medical College | And 2 more authors.
PLoS ONE | Year: 2013

Background: Studies have suggested the chemopreventive effects of flavonoids on carcinogenesis. Yet numbers of epidemiologic studies assessing dietary flavonoids and breast cancer risk have yielded inconsistent results. The association between flavonoids, flavonoid subclasses (flavonols, flavan-3-ols, etc.) and the risk of breast cancer lacks systematic analysis. Objective: We aimed to examine the association between flavonoids, each flavonoid subclass (except isoflavones) and the risk of breast cancer by conducting a meta-analysis. Design: We searched for all relevant studies with a prospective cohort or case-control study design published before July 1st, 2012, using Cochrane library, MEDLINE, EMBASE and PUBMED. Summary relative risks (RR) were calculated using fixed- or random-effects models. All analyses were performed using STATA version 10.0. Results: Twelve studies were included, involving 9 513 cases and 181 906 controls, six of which were prospective cohort studies, and six were case-control studies. We calculated the summary RRs of breast cancer risk for the highest vs lowest categories of each flavonoid subclass respectively. The risk of breast cancer significantly decreased in women with high intake of flavonols (RR = 0.88, 95% CI 0.80-0.98) and flavones (RR = 0.83, 95% CI: 0.76-0.91) compared with that in those with low intake of flavonols and flavones. However, no significant association of flavan-3-ols (RR = 0.93, 95% CI: 0.84-1.02), flavanones (summary RR = 0.95, 95% CI: 0.88-1.03), anthocyanins (summary RR = 0.97, 95% CI: 0.87-1.08) or total flavonoids (summary RR = 0.98, 95% CI: 0.86-1.12) intake with breast cancer risk was observed. Furthermore, summary RRs of 3 case-control studies stratified by menopausal status suggested flavonols, flavones or flavan-3-ols intake is associated with a significant reduced risk of breast cancer in post-menopausal while not in pre-menopausal women. Conclusions: The present study suggests the intake of flavonols and flavones, but not other flavonoid subclasses or total flavonoids, is associated with a decreased risk of breast cancer, especially among post-menopausal women. © 2013 Hui et al.


Hu X.,Chongqing Medical University | Fan J.,Chongqing Medical University | Chen S.,Shanghai JiaoTong University | Yin Y.,Chongqing Medical University | Zrenner B.,Medizinische Klinik I
Journal of Clinical Hypertension | Year: 2015

The aim of this study was to review the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with obstructive sleep apnea (OSA) and hypertension. Biomedical databases were searched for randomized controlled trials (RCTs) comparing CPAP with control among these patients. Seven RCTs reporting 24-hour ambulatory BP were identified for meta-analysis. CPAP was associated with significant reductions in 24-hour ambulatory systolic blood pressure (SBP) (-2.32 mm Hg; 95% confidence interval [CI], -3.65 to -1.00) and diastolic blood pressure (DBP) (-1.98 mm Hg; 95% CI, -2.82 to -1.14). CPAP led to more significant improvement in nocturnal SBP than that in diurnal SBP. Subgroup analysis showed that patients with resistant hypertension or receiving antihypertensive drugs benefited most from CPAP. Meta-regression indicated that CPAP compliance, age, and baseline SBP were positively correlated with decrease in 24-hour DBP, but not reduction in 24-hour SBP. © 2015 Wiley Periodicals, Inc.


Jing X.,Chongqing Medical University | Cao X.,Chongqing Medical University | Wang L.,Chongqing Medical University | Lan T.,University of Illinois at Urbana - Champaign | And 2 more authors.
Biosensors and Bioelectronics | Year: 2014

A sensitive and selective electrochemical method was developed for the detection of DNA methylation, determination of DNA methyltransferase (MTase) activity and screening of MTase inhibitor. Methylene blue (MB) was employed as electrochemical indicator and DNA-modified gold nanoparticles (AuNPs) were used as signal amplification unit because the DNA strands in this composite have strong adsorption ability for MB. First, the thiolated single-stranded DNA S1 was self-assembled on gold electrode, hybridization between the lower portion of DNA S1 and its complementary DNA S2 formed an identical double-stranded tetranucleotide target sequence for both DNA adenine methylation (Dam) MTase and methylation-resistant endonuclease Mbo I, then the upper portion of DNA S1 was hybridized with its complementary DNA S3 modified on AuNPs to bring the DNA S3-AuNPs amplification units onto the electrode. The DNA S1/S2/S3-AuNPs bioconjugate has lots of DNA strands, and they can adsorb abundant MB. Mbo I endounuclease could not cleave the identical target sequence after it was methylated by Dam MTase. On the contrary, the sequence without methylation could be cleaved, which would decrease the amount of adsorbed MB. The presence of redox-active MB was detected electrochemically by differential pulse voltammetry (DPV). Thus, the activity of Dam MTase and methylation status were sensitively converted to the DNA S3-AuNPs amplified DPV signals. The DPV signal demonstrated a linear relationship with logarithm of Dam concentration ranging from 0.075 to 30. U/mL, achieving a detection limit of 0.02. U/mL (S/. N=3). Also, screening of Dam MTase inhibitor 5-fluorouracil was successfully investigated using this fabricated sensor. © 2014 Elsevier B.V.


Jiang T.,University of Arizona | Jiang T.,Fudan University | Tian F.,Shanghai JiaoTong University | Zheng H.,Chongqing Medical University | And 5 more authors.
Kidney International | Year: 2014

The generation of reactive oxygen species has a pivotal role in both acute and chronic glomerular injuries in patients with lupus nephritis. As the transcription factor Nrf2 is a major regulator of the antioxidant response and is a primary cellular defense mechanism, we sought to determine a role of Nrf2 in the progression of lupus nephritis. Pathological analyses of renal biopsies from patients with different types of lupus nephritis showed oxidative damage in the glomeruli, accompanied by an active Nrf2 antioxidant response. A murine lupus nephritis model using Nrf2 +/+ and Nrf2 -/- mice was established using pristine injection. In this model, Nrf2 -/- mice suffered from greater renal damage and had more severe pathological alterations in the kidney. In addition, Nrf2 +/+ mice showed ameliorative renal function when treated with sulforaphane, an Nrf2 inducer. Nrf2 -/- mice had higher expression of transforming growth factor β1 (TGFβ1), fibronectin, and iNOS. In primary mouse mesangial cells, the nephritogenic monoclonal antibody R4A activated the nuclear factor-kappa B (NF-κB) pathway and increased the level of reactive oxygen species, iNOS, TGFβ1, and fibronectin. Knockdown of Nrf2 expression aggravated all aforementioned responses induced by R4A. Thus, these results suggest that Nrf2 improves lupus nephritis by neutralizing reactive oxygen species and by negatively regulating the NF-κB and TGFβ1 signaling pathways. © 2013 International Society of Nephrology.


Mei F.,University of California at San Francisco | Fancy S.P.J.,University of California at San Francisco | Shen Y.-A.A.,University of California at San Francisco | Niu J.,Chongqing Medical University | And 12 more authors.
Nature Medicine | Year: 2014

Functional screening for compounds that promote remyelination represents a major hurdle in the development of rational therapeutics for multiple sclerosis. Screening for remyelination is problematic, as myelination requires the presence of axons. Standard methods do not resolve cell-autonomous effects and are not suited for high-throughput formats. Here we describe a binary indicant for myelination using micropillar arrays (BIMA). Engineered with conical dimensions, micropillars permit resolution of the extent and length of membrane wrapping from a single two-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for detection of concentric wrapping observed as 'rings' of myelin. The platform is formatted in 96-well plates, amenable to semiautomated random acquisition and automated detection and quantification. Upon screening 1,000 bioactive molecules, we identified a cluster of antimuscarinic compounds that enhance oligodendrocyte differentiation and remyelination. Our findings demonstrate a new high-throughput screening platform for potential regenerative therapeutics in multiple sclerosis. © 2014 Nature America, Inc.


Fan M.-Q.,Chongqing Medical University | Huang C.-B.,Chongqing Medical University | Gu Y.,Shanghai JiaoTong University | Xiao Y.,Chongqing Medical University | And 2 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2013

Background: Growing evidences indicate microRNAs play important roles in cancer development, progression, metastasis and may constitute robust biomarkers for cancer prognosis. The aim of this study was to identify the clinical and functional association of microRNA-20a (miR-20a) in hepatocellular carcinoma (HCC). Methods. MiR-20a was detected using Taqman real-time polymerase chain reaction. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-20a with survival of patients. The potential functions of miR-20a on proliferation were evaluated by proliferation and flow cytometry analysis. The direct target gene of miR-20a was also identified by luciferase reporter assays. Results: MiR-20a was lower in primary HCC than normal liver, and were further decreased in those with post-liver transplantation (LT) HCC recurrence compared with those with non-recurrence (p = 0.001). Patients with lower miR-20a expression had significantly poorer recurrence-free survival (RFS, Log rank p < 0.001) and overall survival (OS, Log rank p < 0.001). Multivariate analysis revealed that lower miR-20a was an independent predictor of poor prognosis. MiR-20a restoration could suppress HepG2 and SMMC-7721 cells proliferation and induce cell cycle G1 arrest and apoptosis. Subsequent investigations revealed that miR-20a directly targeted myeloid cell leukemia sequence 1 (Mcl-1) and reduced the endogenous protein level of Mcl-1 in HCC cells. Conclusions: MiR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Down-regulation of miR-20a increases the proliferation abilities of HCC cells. Our findings suggest miR-20a may represent a novel potential therapeutic target and biomarker for survival of HCC patients. © 2013 Fan et al.; licensee BioMed Central Ltd.


Liu X.,Duke University | He Y.,Chongqing Medical University | Li F.,Duke University | Huang Q.,Shanghai JiaoTong University | And 3 more authors.
Molecular Cell | Year: 2015

Apoptosis is typically considered an anti-oncogenic process since caspase activation can promote the elimination of genetically unstable or damaged cells. We report that a central effector of apoptosis, caspase-3, facilitates rather than suppresses chemical- and radiation-induced genetic instability and carcinogenesis. We found that a significant fraction of mammalian cells treated with ionizing radiation can survive despite caspase-3 activation. Moreover, this sublethal activation of caspase-3 promoted persistent DNA damage and oncogenic transformation. In addition, chemically induced skin carcinogenesis was significantly reduced in mice genetically deficient in caspase-3. Furthermore, attenuation ofEndoG activity significantly reduced radiation-induced DNA damage and oncogenic transformation, identifying EndoG as a downstream effector of caspase-3 in this pathway. Our findings suggest that rather than acting as a broad inhibitor of carcinogenesis, caspase-3 activation may contribute to genome instability and play a pivotal role in tumor formation following damage. © 2015 Elsevier Inc.


Li J.,University of California at San Francisco | Li J.,Chongqing Medical University | Huang N.F.,Stanford University | Zou J.,University of California at San Francisco | And 5 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2013

Objective-Transdifferentiation of fibroblasts to endothelial cells (ECs) may provide a novel therapeutic avenue for diseases, including ischemia and fibrosis. Here, we demonstrate that human fibroblasts can be transdifferentiated into functional ECs by using only 2 factors, Oct4 and Klf4, under inductive signaling conditions. Approach and Results-To determine whether human fibroblasts could be converted into ECs by transient expression of pluripotency factors, human neonatal fibroblasts were transduced with lentiviruses encoding Oct4 and Klf4 in the presence of soluble factors that promote the induction of an endothelial program. After 28 days, clusters of induced endothelial (iEnd) cells seemed and were isolated for further propagation and subsequent characterization. The iEnd cells resembled primary human ECs in their transcriptional signature by expressing endothelial phenotypic markers, such as CD31, vascular endothelial-cadherin, and von Willebrand Factor. Furthermore, the iEnd cells could incorporate acetylated low-density lipoprotein and form vascular structures in vitro and in vivo. When injected into the ischemic limb of mice, the iEnd cells engrafted, increased capillary density, and enhanced tissue perfusion. During the transdifferentiation process, the endogenous pluripotency network was not activated, suggesting that this process bypassed a pluripotent intermediate step. Conclusions-Pluripotent factor-induced transdifferentiation can be successfully applied for generating functional autologous ECs for therapeutic applications. © 2013 American Heart Association, Inc.


Li F.,Beijing Institute of Biotechnology | Li F.,Chongqing Medical University | Lan Y.,Beijing Institute of Biotechnology | Wang Y.,Beijing Institute of Biotechnology | And 9 more authors.
Developmental Cell | Year: 2011

Cerebrovascular dysfunction is strongly associated with neonatal intracranial hemorrhage (ICH) and stroke in adults. Cerebrovascular endothelial cells (ECs) play important roles in maintaining a stable cerebral circulation in the central nervous system by interacting with pericytes. However, the genetic mechanisms controlling the functions of cerebral ECs are still largely unknown. Here, we report that disruption of Smad4, the central intracellular mediator of transforming growth factor-β (TGF-β) signaling, specifically in the cerebral ECs, results in perinatal ICH and blood-brain barrier breakdown. Furthermore, the mutant vessels exhibit defective mural cell coverage. Smad4 stabilizes cerebrovascular EC-pericyte interactions by regulating the transcription of N-cadherin through associating with the Notch intracellular complex at the RBP-J binding site of the N-cadherin promoter. These findings uncover a distinct role of endothelial Smad4 in maintaining cerebrovascular integrity and suggest important implications for genetic or functional deficiencies in TGF-β/Smad signaling in the pathogenesis of cerebrovascular dysfunction. © 2011 Elsevier Inc.


Gao Z.W.,Linyi Peoples Hospital | Gao Z.W.,Chongqing Medical University | Zhang D.L.,Qingdao University | Guo C.B.,Chongqing Medical University
Current Cancer Drug Targets | Year: 2010

The focus of this study was to develop additive or synergistic agents to chemosensitize the existing chemotherapeutic drug in human non-small cell lung cancer (NSCLC). In this study employing analyses of the NF-κB/I-κB kinase (IKK) signal cascade in a number of NSCLC cell lines, we report the identification and characterization of parthenolide. Parthenolide is a sesquiterpene lactone that can antagonize paclitaxel-mediated NF-κB nuclear translocation and activation through selectively targeting I-κB kinase (IKK) activity. Our results showed that parthenolide dramatically lowered the effective dose of Paclitaxel needed to induce cytotoxicity of a wide range of NSCLC cell lines. An examination of pathways common to Paclitaxel and parthenolide signaling revealed that this synergy was related to modulation of the NF-κB/I-κB kinase (IKK) signal cascade through IKKß. Parthenolide alone induced apoptosis via the mitochondria/caspase pathway. Moreover, in a human orthotopic NSCLC xenograft model, a well-tolerated combination induces tumor regression. These data strengthen the rationale for the use of parthenolide to decrease the apoptotic threshold via a caspase-dependent process and support the use of concurrent low doses of paclitaxel in the treatment of NSCLC with paclitaxel chemoresistance. © 2010 Bentham Science Publishers Ltd.


Wang Y.-C.,Chongqing Medical University | Zhou Y.,Chongqing Medical University | Fang H.,Chongqing Medical University | Lin S.,Chengdu Medical College | And 7 more authors.
Annals of Neurology | Year: 2014

Objective Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH)-induced secondary brain injury. However, the upstream events that initiate inflammatory responses following ICH remain elusive. Our previous studies suggested that Toll-like receptor 4 (TLR4) may be the upstream signal that triggers inflammatory injury in ICH. In addition, recent clinical findings indicated that both TLR2 and TLR4 may participate in ICH-induced brain injury. However, it is unclear how TLR2 functions in ICH-induced inflammatory injury and how TLR2 interacts with TLR4. Methods The role of TLR2 and TLR2/TLR4 heterodimerization in ICH-induced inflammatory injury was investigated in both in vivo and in vitro models of ICH. Results TLR2 mediated ICH-induced inflammatory injury, which forms a heterodimer with TLR4 in both in vivo and in vitro models of ICH. Hemoglobin (Hb), but not other blood components, triggered inflammatory injury in ICH via assembly of TLR2/TLR4 heterodimers. MyD88 (myeloid differentiation primary response gene 88), but not TRIF (Toll/IR-1 domain-containing adaptor protein inducing interferon-beta), was required for ICH-induced TLR2/TLR4 heterodimerization. Mutation of MyD88 Arg196 abolished the TLR2/TLR4 heterodimerization. Interpretation Our results suggest that a novel TLR2/TLR4 heterodimer induced by Hb initiates inflammatory injury in ICH. Interfering with the assembly of the TLR2/TLR4 heterodimer may be a novel target for developing effective treatment of ICH. Ann Neurol 2014;75:876-889 © 2014 American Neurological Association.


Xu G.-L.,Chongqing Medical University | Chen J.,Chongqing Medical University | Yang F.,Chongqing Medical University | Li G.-Q.,Chongqing Medical University | And 2 more authors.
Hepatology | Year: 2014

Viral fulminant hepatitis (FH) remains a serious clinical problem with very high mortality. Lacking understanding of FH pathogenesis has in essence hindered efficient clinical treatment. Inferring from a correlation observed between the genetic differences in the complement component 5 (C5) and the susceptibility of mouse strains to murine hepatitis virus strain-3 (MHV-3) infections, we propose that excessive complement activation plays a critical role in the development of FH. We show that MHV-3 infection causes massive complement activation, along with a rapid increase in serum C5a levels and quick development of FH in susceptible strains. Mice deficient in the C5a receptor (C5aR) or the susceptible strains treated with C5aR antagonists (C5aRa) exhibit significant attenuation of the disease, accompanied by a remarkable reduction of hepatic fibrinogen-like protein 2 (Fgl2), a hallmark protein that causes necrosis of infected livers. In accordance, biopsy of FH patients shows a dramatic increase of Fgl2 expression, which correlates with C5aR up-regulation in the liver. In vitro C5a administration accelerates MHV-3-induced Fgl2 secretion by macrophages. Furthermore, inhibiting ERK1/2 and p38 efficiently blocks C5a-mediated Fgl2 production during viral infections. Conclusion: These data provide evidence that mouse susceptibility to MHV-3-induced FH may rely on C5a/C5aR interactions, for which ERK1/2 and p38 pathways participate in up-regulating Fgl2 expression. Inhibition of C5a/C5aR interactions is expected to be beneficial in the clinical treatment of FH patients. © 2014 by the American Association for the Study of Liver Diseases.


Li M.,Chongqing Medical University | Li M.,Chengdu Medical College | Chen C.,Chongqing Medical University | Zhou Z.,Chongqing Medical University | And 2 more authors.
Cell Calcium | Year: 2012

Adult hippocampal neurogenesis plays an important role in brain function and neurological diseases. Adult neural progenitor cell (aNPC) proliferation is a critical first step in hippocampal neurogenesis. However, the mechanisms that modulate aNPC proliferation have not been fully identified. Ample evidence has demonstrated that cell proliferation is dependent on the intracellular Ca 2+ concentration. We hypothesized that store-operated Ca 2+ channels (SOCs), which are ubiquitously expressed in all cell types, participate in aNPC proliferation. We found that store-operated Ca 2+ entry (SOCE) was involved in the proliferation of aNPCs and that 2-APB, Gd 3+ and SKF96365, antagonists of SOCE and canonical transient receptor potential (TRPC), respectively, inhibited the increase in SOCE and aNPC proliferation. We therefore analyzed the expression of TRPCs in aNPCs and showed that TRPC1 is the most significantly upregulated member under proliferative conditions. Interestingly, knockdown of TRPC1 and using an antibody against TRPC1 markedly reduced the degree of SOCE and aNPC proliferation. In parallel, we observed the suppression of aNPC proliferation was found to be associated with cell cycle arrest in G0/G1 phase. Furthermore, gene expression microarray analysis revealed a selective up- or downregulation of 10 genes in aNPCs following TRPC1 silencing. Knockdown of Orai1 or STIM1 also induced a significant inhibition of SOCE and proliferation in aNPCs, and all three proteins were colocalized in the plasma membrane region of cells. Together, these results indicate that SOCE represents a principal mechanism regulating the proliferation of aNPCs and that TRPC1 is an essential component of this pathway. This discovery may be important in improving adult hippocampal neurogenesis and treating cognitive deficits. © 2012 Elsevier Ltd.


Fu W.,Centers for Disease Control and Prevention | Fu W.,Chongqing Medical University | Forster T.,Centers for Disease Control and Prevention | Mayer O.,Centers for Disease Control and Prevention | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2010

Microorganisms develop biofilms on indwelling medical devices and are associated with device-related infections, resulting in substantial morbidity and mortality. This study investigated the effect of pretreating hydrogel-coated catheters with Pseudomonas aeruginosa bacteriophages on biofilm formation by P. aeruginosa in an in vitro model. Hydrogel-coated catheters were exposed to a 10 log10 PFU ml-1 lysate of P. aeruginosa phage M4 for 2 h at 37°C prior to bacterial inoculation. The mean viable biofilm count on untreated catheters was 6.87 log10 CFU cm-2 after 24 h. The pretreatment of catheters with phage reduced this value to 4.03 log 10 CFU cm-2 (P < 0.001). Phage treatment immediately following bacterial inoculation also reduced biofilm viable counts (4.37 log10 CFU cm-2 reduction; P < 0.001). The regrowth of biofilms on phage-treated catheters occurred between 24 and 48 h, but supplemental treatment with phage at 24 h significantly reduced biofilm regrowth (P < 0.001). Biofilm isolates resistant to phage M4 were recovered from catheters pretreated with phage. The phage susceptibility profiles of these isolates were used to guide the development of a five-phage cocktail from a larger library of P. aeruginosa phages. The pretreatment of catheters with this cocktail reduced the 48-h mean biofilm cell density by 99.9% (from 7.13 to 4.13 log10 CFU cm-2; P < 0.001), but fewer biofilm isolates were resistant to these phages. These results suggest the potential of applying phages, especially phage cocktails, to the surfaces of indwelling medical devices for mitigating biofilm formation by clinically relevant bacteria. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Hale J.S.,Emory University | Youngblood B.,Emory University | Latner D.R.,Emory University | Latner D.R.,Centers for Disease Control and Prevention | And 7 more authors.
Immunity | Year: 2013

CD4+ T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for long-lived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh cell lineage after antigen clearance. By using adoptive transfer of antigen-specific memory CD4+ T cell subpopulations in the lymphocytic choriomeningitis virus infection model, we found that there are distinct memory CD4+ T cell populations with commitment to either Tfh- or Th1-cell lineages. Our conclusions are based on gene expression profiles, epigenetic studies, and phenotypic and functional analyses. Our findings indicate that CD4+ memory T cells " remember" their previous effector lineage after antigen clearance, being poised to reacquire their lineage-specific effector functions upon antigen reencounter. These findings have important implications for rational vaccine design, where improving the generation and engagement of memory Tfh cells could be used to enhance vaccine-induced protective immunity. © 2013 Elsevier Inc.


Deng W.,Chongqing Medical University | Li C.-Y.,Chongqing Medical University | Tong J.,Chongqing Medical University | Zhang W.,Chengdu Medical College | Wang D.-X.,Chongqing Medical University
Respiratory Research | Year: 2012

Background: Stimulation of epithelial sodium channel (ENaC) increases Na +transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo.Methods: A model of ALI (LPS at a dose of 5.0 mg/kg) with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF), total lung water content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting.Results: In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway.Conclusions: Our study demonstrated that insulin alleviated pulmonary edema and enhanced AFC by increasing the expression of ENaC that dependent upon PI3K/Akt pathway by inhibition of Nedd4-2. © 2012 Deng et al; licensee BioMed Central Ltd.


Lu L.-Q.,Chengdu Medical College | Liao W.,Chongqing Medical University
Molecular Medicine Reports | Year: 2015

The present study aimed to identify differentially expressed genes (DEGs) associated with pediatric allergic asthma, and to analyze the functional pathways of the selected target genes, in order to explore the pathogenesis of the disease. The GSE18965 gene expression profile was downloaded from the Gene Expression Omnibus database and was preprocessed. This gene expression profile consisted of seven normal samples and nine samples from patients with pediatric allergic asthma. The DEGs between the normal and pediatric allergic asthma samples were screened using limma package in R, and the cut-off value was set at false discovery rate <0.05 and log fold change >1. Following hierarchical clustering of the DEGs based on the expression profiles, the up- and downregulated genes underwent a functional enrichment analysis by topological approach (P<0.05), using the Database for Annotation, Visualization and Integrated Discovery. A total of 127 DEGs were identified between the normal and pediatric allergic asthma samples. The up- and downregulated genes were significantly enriched in the actin filament-based process and the monosaccharide metabolic process, respectively. Seven downregulated DEGs (M6PR, TPP1, GLB1, NEU1, ACP2, LAMP1 and HGSNAT) were identified in the lysosomal pathway, with P=6.4x10-9. These results suggested that variation in lysosomal function, triggered by the seven downregulated genes, may lead to aberrant functioning of the T lymphocytes, resulting in asthma. Further research regarding the treatment of pediatric allergic asthma through targeting lysosomal function is required.


Gao Y.-A.,Chongqing Medical University | Gao Y.-A.,Interventional Imaging | Huang Y.,Interventional Imaging | Zhang R.,Interventional Imaging | And 4 more authors.
Radiology | Year: 2014

Purpose: To compare prostatic arterial embolization (PAE) and transurethral resection of the prostate (TURP) in the care of patients with benign prostatic hyperplasia (BPH). Materials and Methods: This prospective randomized clinical trial was approved by the institutional review board. A total of 114 patients provided written informed consent and were randomly assigned to undergo PAE (n = 57) or TURP (n = 57). The groups were compared regarding relevant adverse events and complications. Functional results-including improvement of International Prostate Symptom Score (IPSS), quality of life (QOL), peak urinary flow, postvoiding residual urine volume, prostate-specific antigen (PSA) level, and prostate volume-were assessed at 1-, 3-, 6-, 12-, and 24-month follow-up between January 20, 2007, and January 31, 2012. Student t test, x2 test, Fisher exact test, and repeated measures analysis of variance were used, as appropriate. Results: Overall technical success rates for TURP and PAE were 100% and 94.7%, respectively; the clinical failure rates were 3.9% and 9.4%, respectively. The six functional results showed improvements after TURP and PAE at all follow-up time points when compared with preoperative values (P = .001). However, the TURP group showed greater degrees of improvement in the IPSS, QOL, peak urinary flow, and postvoiding residual urine volume at 1 and 3 months, as well as greater reductions in the PSA level and prostate volume at all follow-up time points, when compared with the PAE group (P < .05). The PAE group showed more overall adverse events and complications (P = .029), mostly related to acute urinary retention (25.9%), postembolization syndrome (11.1%), and treatment failures (5.3% technical; 9.4% clinical). Conclusion: Both procedures resulted in significant clinical improvements in the treatment of BPH. However, the advantages of the PAE procedure must be weighed against the potential for technical and clinical failures in a minority of patients. © 2014 RSNA.


News Article | December 13, 2016
Site: www.eurekalert.org

Some cancers are caused by loss of enzymes that should keep cell growth in check. On the flip side, some are caused by over-activation of enzymes that enhance cell growth. Yet drugs that inhibit the overactive enzymes have failed to work against liver cancer. In mouse models, researchers at University of California San Diego School of Medicine have discovered a potential reason -- counterintuitively, lack of both types of these enzymes can lead to liver disease and cancer. In human liver tumor samples, they also found that deficiencies in these two enzymes, called Shp2 and Pten, are associated with poor prognosis. The study, published December 13 by Cell Reports, provides a new understanding of how liver cancer develops, a new therapeutic approach and new mouse model for studying the disease. "When it comes to liver cancer, I think we've been making strategic mistakes," said senior author Gen-Sheng Feng, PhD, professor of pathology and biological sciences at UC San Diego. "In cancer development, we always thought about two distinct families of enzymes -- one promotes cancer, one inhibits it. Many drugs have been developed to block the cancer-promoting pathways, but we and others are now finding that many classical pro-cancer proteins are actually inhibitors." Based on Shp2's well-known role in promoting tumor formation, researchers have long assumed that drugs that block the enzyme would inhibit tumor formation. But Feng's team previously found the opposite to be true -- loss of the Shp2 enzyme can promote liver cancer. In contrast, in a study published last year , Feng and team discovered that removing both Shp2 and Pten, a tumor-suppressing enzyme, neutralized leukemia development. "So the roles of tumor-promoting and tumor-suppressing enzymes are not as simple as we thought," Feng said. "This also explains many unwanted side effects with drugs that target these enzymes. Their consequences can differ depending on cell type." In this latest study, Feng and team found that Shp2 and Pten cooperate to suppress liver tumor formation in experimental mice. When the researchers deleted both the Shp2 and Pten genes specifically in the mice's liver cells, early-onset liver disease (non-alcoholic steatohepatitis, or NASH) was more severe and liver tumors occurred earlier and more frequently than in control mice with one or both enzymes functioning. Normal mice did not experience any tumors. In mice lacking either Pten or Shp2, liver tumors began to appear after approximately seven or 12 months. But for mice lacking both enzymes, 80 percent spontaneously developed liver tumors in five months; 100 percent had tumors at seven months. The increased severity of liver disease and frequency of liver cancer in these models is likely because lack of Shp2 and Pten enzymes activates molecules involved in lipid metabolism, inflammation and fibrosis, the researchers said. After their surprising results in mice, the researchers wondered if the same phenomenon occurs in human liver cancers. They analyzed 335 human liver tumor samples and found that approximately 52 percent of the tumors were low in both Shp2 and Pten enzyme levels. Those patients with low Shp2 and Pten enzyme levels in the tumors had a poorer prognosis than those with higher levels of one or both enzymes -- at 50 months after surgery, approximately 60 percent of patients with low Shp2 and Pten were alive, compared to approximately 90 percent of patients with high Shp2 and Pten levels. These results provide new information about how liver cancer arises and a new target for drug development. But the findings also offer a new laboratory model for studying the disease. Previously, Feng's team and others would use chemical carcinogens to induce liver cancer in mouse models. Instead of taking this artificial approach, Feng said researchers can now generate more realistic mouse models of non-alcoholic fatty liver disease and liver cancer simply by removing the Pten and Shp2 enzymes. "Liver cancer is more complicated than we thought. These pathways, when over-activated, stimulate tumor development, but so does inhibiting them," Feng said. "That's why we can't rush to conclusions like we have in the past. But now that we have a good model that mimics the human pathogenic process and we can use that to work out the mechanisms that lead to liver disease and cancer, and search for novel drug targets." Co-authors of this study include: Xiaolin Luo, Kaisa L. Hanley, Helen He Zhu, Kirsten N. Malo, Carolyn Hernandez, Nissi M. Varki, Nazilla Alderson, Catherine Chu, Shuangwei Li, Rohit Loomba, UC San Diego; Rui Liao, UC San Diego, Fudan University, and Chongqing Medical Unversity; Xufu Wei, UC San Diego, and Chongqing Medical University; Jia Fan, Shuang-Jian Qiu, Fudan University.


Tong W.-D.,Chongqing Medical University | Ludwig K.A.,Medical College of Wisconsin
World Journal of Gastroenterology | Year: 2013

Anorectal malformations (ARM) are common anomalies in neonates. Diagnostic and therapeutic delays in the management of ARM may lead to colonic perforation, and even death. Physical examination of the perineum is often sufficient to diagnose ARM in neonates. Notwithstanding, delayed diagnosis of ARM has become increasingly familiar to surgeons, as evidenced by the number of recent publications on this topic in the literature. In this commentary, we discuss spontaneous colonic perforation due to delayed diagnosis of ARM in neonates, and highlight the importance of early diagnosis in assuring good outcomes with surgical management. At this point, a thorough examination of the perineum during the initial newborn assessment is mandatory, particularly in those patients presenting with abdominal signs or symptoms. © 2013 Baishideng. All rights reserved.


Wang W.,Wenzhou University | Cai Y.,Wenzhou University | Wu M.,Wenzhou University | Wang K.,Chongqing Medical University | Li Z.,CAS Institute of Botany
Nonlinear Analysis: Real World Applications | Year: 2012

In this paper, we investigate the complex dynamics of a reactiondiffusion S-I model incorporating demographic and epidemiological processes with zero-flux boundary conditions. By the method of Lyapunov function, the global stability of the disease free equilibrium and the epidemic equilibrium was established. In addition, the conditions of Turing instability were obtained and the Turing space in the parameters space were given. Based on these results, we present the evolutionary processes that involves organism distribution and their interaction of spatially distributed population with local diffusion, and find that the model dynamics exhibits a diffusion-controlled formation growth to "holes, holesstripes, stripes, spotsstripes and spots" pattern replication. Furthermore, we indicate that the diseases' spread is getting smaller with R 0 increasing, and the increasing the diffusion of infectious will increase the speed of diseases spreading. Our results indicate that the diffusion has a great influence on the spread of the epidemic and extend well the finding of spatiotemporal dynamics in the epidemic model. © 2012 Elsevier Ltd. All rights reserved.


Du L.,Chongqing Medical University | Kijlstra A.,Maastricht University | Kijlstra A.,Wageningen UR Livestock Research | Yang P.,Chongqing Medical University
Progress in Retinal and Eye Research | Year: 2016

Vogt-Koyanagi-Harada (VKH) disease is one of the major vision-threatening diseases in certain populations, such as Asians, native Americans, Hispanics and Middle Easterners. It is characterized by bilateral uveitis that is frequently associated with neurological (meningeal), auditory, and integumentary manifestations. Although the etiology and pathogenesis of VKH disease need to be further elucidated, it is widely accepted that the clinical manifestations are caused by an autoimmune response directed against melanin associated antigens in the target organs, i.e. the eye, inner ear, meninges and skin. In the past decades, accumulating evidence has shown that genetic factors, including VKH disease specific risk factors (HLA-DR4) and general risk factors for immune mediated diseases (IL-23R), dysfunction of immune responses, including the innate and adaptive immune system and environmental triggering factors are all involved in the development of VKH disease. Clinically, the criteria of diagnosis for VKH disease have been further improved by the employment of novel imaging techniques for the eye. For the treatment, early and adequate corticosteroids are still the mainstream regime for the disease. However, immunosuppressive and biological agents have shown benefit for the treatment of VKH disease, especially for those patients not responding to corticosteroids.This review is focused on our current knowledge of VKH disease, especially for the diagnosis, pathogenesis (genetic factors and immune mechanisms), ancillary tests and treatment. A better understanding of the role of microbiome composition, genetic basis and ongoing immune processes along with the development of novel biomarkers and objective quantitative assays to monitor intraocular inflammation are needed to improve current management of VKH patients. © 2016.


Yuan J.,Chongqing Medical University | Chen Y.,Chongqing Medical University | Hirsch E.,University of Strasbourg
Neurological Sciences | Year: 2012

The resection of the epileptogenic area of brain is very important and useful for the treatment of uncontrolled epilepsy, especially for the patients with stereotyped partial seizures. The critical point for successful epilepsy surgery is the precise identification of epileptogenic zone. Actually, we cannot precisely localize the epileptogenic zone in about 25 % of patient with refractory seizures based on the noninvasive examination; thus for these patients, we mainly use the intracranial EEG to localize the epileptogenic zone which could be useful in 10-15 % of surgical candidates. The intracranial electrodes which are most used currently are depth electrodes, subdural strip electrodes, and subdural grid electrodes. The subject of this paper is to discuss and compare the indications, construction, insertion, interpretation, limitations, risks and accuracy of each of these methods. © 2012 Springer-Verlag.


Lei Y.,University of Sichuan | Lei Y.,Chongqing Medical University | Wang K.,University of Sichuan | Deng L.,University of Sichuan | And 3 more authors.
Medicinal Research Reviews | Year: 2015

Inflammation is an essential immune response characterized by pain, swelling, redness, heat, and impaired function. A controlled acute inflammatory response is necessary to fight off infection and overcome injury. However, if the inflammatory process persists and enters into the chronic state, it can lead to local and systemic deleterious effects counterproductive to healing and instead constitutes a new pathology. Typically, inflamed tissues are associated with an elevated level of reactive species (reactive oxygen species (ROS)/reactive nitrogen species (RNS)). These ROS/RNS are generated during the respiratory burst of immune cells and are important factors in defense against invading pathogens. Additionally, reactive species are now known to trigger oxidative/nitrosative modifications of biomolecules. While most of these modifications lead to irreparable damage, some are subtle and fully reversible. The reversible modifications can initiate signaling cascades known as "redox signaling." This redox signaling tightly modulates the inflammatory response. Thus, understanding the complex role of ROS/RNS-induced redox signaling in inflammation will assist in the design of relevant therapeutic intervention strategies for inflammation-associated diseases. This review will highlight the impact of oxidative stress and redox signaling on inflammation and inflammation-associated diseases, with a focus on redox modifications of inflammation-related proteins. © 2014 Wiley Periodicals, Inc.


Cheng G.,Chongqing Medical University | Huang C.,Third Hospital of Mianyang | Deng H.,Chongqing Medical University | Wang H.,Third Hospital of Mianyang
Internal Medicine Journal | Year: 2012

This study examined the association of diabetes with the onset of dementia (including Alzheimer's disease (AD), vascular dementia (VD) and any dementia) and mild cognitive impairment (MCI) by using a quantitative meta-analysis of longitudinal studies. EMBASE and MEDLINE were searched for articles published up to December 2010. All studies that examined the relationship between diabetes and the onset of dementia or MCI were included. Pooled relative risks were calculated using fixed and random effects models. Nineteen studies met our inclusion criteria for this meta-analysis, and 6184 subjects with diabetes and 38530 subjects without diabetes were included respectively. All subjects were without dementia or MCI at baseline. The quantitative meta-analysis showed that subjects with diabetes had higher risk for AD (relative risk (RR):1.46, 95% confidence interval (CI): 1.20-1.77), VD (RR: 2.48, 95% CI: 2.08-2.96), any dementia (RR: 1.51, 95% CI: 1.31-1.74) and MCI (RR: 1.21, 95% CI: 1.02-1.45) than those without. The quantitative meta-analysis showed that diabetes was a risk factor for incident dementia (including AD, VD and any dementia) and MCI. © 2012 The Authors. Internal Medicine Journal © 2012 Royal Australasian College of Physicians.


Wang Y.,New Mexico State University | Wang Y.,Chongqing Medical University | Gilbreath III T.M.,University of California at Irvine | Kukutla P.,New Mexico State University | And 2 more authors.
PLoS ONE | Year: 2011

The mosquito gut represents an ecosystem that accommodates a complex, intimately associated microbiome. It is increasingly clear that the gut microbiome influences a wide variety of host traits, such as fitness and immunity. Understanding the microbial community structure and its dynamics across mosquito life is a prerequisite for comprehending the symbiotic relationship between the mosquito and its gut microbial residents. Here we characterized gut bacterial communities across larvae, pupae and adults of Anopheles gambiae reared in semi-natural habitats in Kenya by pyrosequencing bacterial 16S rRNA fragments. Immatures and adults showed distinctive gut community structures. Photosynthetic Cyanobacteria were predominant in the larval and pupal guts while Proteobacteria and Bacteroidetes dominated the adult guts, with core taxa of Enterobacteriaceae and Flavobacteriaceae. At the adult stage, diet regime (sugar meal and blood meal) significantly affects the microbial structure. Intriguingly, blood meals drastically reduced the community diversity and favored enteric bacteria. Comparative genomic analysis revealed that the enriched enteric bacteria possess large genetic redox capacity of coping with oxidative and nitrosative stresses that are associated with the catabolism of blood meal, suggesting a beneficial role in maintaining gut redox homeostasis. Interestingly, gut community structure was similar in the adult stage between the field and laboratory mosquitoes, indicating that mosquito gut is a selective eco-environment for its microbiome. This comprehensive gut metatgenomic profile suggests a concerted symbiotic genetic association between gut inhabitants and host. © 2011 Wang et al.


Cai H.,South China University of Technology | Yang Z.,Chongqing Medical University | Cao X.,Childrens Hospital Boston | Xia W.,VA Hospital | Xu X.,Harvard University
IEEE Transactions on Image Processing | Year: 2014

We present a new method in image segmentation that is based on Otsu's method but iteratively searches for subregions of the image for segmentation, instead of treating the full image as a whole region for processing. The iterative method starts with Otsu's threshold and computes the mean values of the two classes as separated by the threshold. Based on the Otsu's threshold and the two mean values, the method separates the image into three classes instead of two as the standard Otsu's method does. The first two classes are determined as the foreground and background and they will not be processed further. The third class is denoted as a to-be-determined (TBD) region that is processed at next iteration. At the succeeding iteration, Otsu's method is applied on the TBD region to calculate a new threshold and two class means and the TBD region is again separated into three classes, namely, foreground, background, and a new TBD region, which by definition is smaller than the previous TBD regions. Then, the new TBD region is processed in the similar manner. The process stops when the Otsu's thresholds calculated between two iterations is less than a preset threshold. Then, all the intermediate foreground and background regions are, respectively, combined to create the final segmentation result. Tests on synthetic and real images showed that the new iterative method can achieve better performance than the standard Otsu's method in many challenging cases, such as identifying weak objects and revealing fine structures of complex objects while the added computational cost is minimal. © 2014 IEEE.


Tan N.,Chongqing Medical University | Zheng D.,The First Peoples Hospital of Yibin | Ye J.,Chongqing Medical University
European Journal of Ophthalmology | Year: 2014

Purpose: To compare the performance of accommodative, multifocal, and monofocal intraocular lenses (IOLs). Methods: In this clinical control study, 3 types of IOL were implanted in 128 eyes of 86 patients with age-related cataract who underwent phacoemulsification. Accommodative (Tetraflex), multifocal (ZMA00), and monofocal (Akreos Advanced Optics [AO]) IOLs were implanted into 43, 40, and 45 eyes, respectively. The uncorrected, best-corrected distance, contrast sensitivity, and distance-corrected intermediate and near visual acuity (UCDVA, BCDVA, CSVA, DCIVA, and DCNVA, respectively), amplitude of pseudoaccommodation, and patient satisfaction were measured at 1, 3, and 12 months after surgery. Results: Differences in CSVA at all contrast degrees, UCDVA, and BCDVA among the 3 groups were not significant. Patients in the Akreos AO group exhibited a poorer DCIVA and DCNVA and experienced less pseudoaccommodation compared to patients in the other 2 groups at 3 and 12 months after surgery (p<0.01). Patients in the ZMA00 group exhibited a better DCIVA and experienced more pseudoaccommodation than patients in the Tetraflex group (3 months: P<0.05, 12 months: p<0.01 for both outcomes). Three months after surgery, total spectacle independence was achieved by 84.4%, 60.7%, and 17.2% of the ZMA00, Tetraflex, and Akreos AO group patients, respectively. Conclusions: All 3 types of IOLs allowed greater distance visual acuity; however, multifocal IOLs produced better DCIVA and DCNVA and more pseudoaccommodation and spectacle independence. Accommodative IOLs ranked second. Neither accommodative nor multifocal IOLs reduced CSVA. © 2014 Wichtig Publishing.


Li J.-X.,Chongqing Medical University | Li J.-X.,U.S. Center for Disease Control and Prevention | Mao Q.-Y.,National Institute for Food and Drug Control | Liang Z.-L.,National Institute for Food and Drug Control | And 2 more authors.
Expert Review of Vaccines | Year: 2014

The widespread epidemics of enterovirus 71 (EV71) seriously affected the Western Pacific Region. Young children, especially those younger than 3 years are the most susceptible population to the EV71-associated diseases. Several Asian countries have begun to focus on the research and development of EV71 vaccines. Five inactivated whole-virus EV71 candidate vaccines (three were manufactured in mainland China based on a C4 genotype strain, one in Taiwan based on a B4 genotype strain and one in Singapore based on a B2 genotype strain) have been assessed in clinical trials. Three candidate vaccines developed in mainland China have already completed Phase III clinical trials recently. The tested EV71 vaccine could provide good efficacy, satisfactory safety, and high immunogenicity. Thus, inactivated EV71 vaccines are expected to become the first available vaccines against EV71 in the near future. © 2014 Informa UK, Ltd.


Chen X.,Chongqing Medical University | Zhao Y.,Nanjing Southeast University | Wu X.,Chongqing Medical University | Qian G.,Chongqing Medical University
Shock | Year: 2011

Single Ig IL-1 receptor-related molecule (SIGIRR) is one of the members of the Toll-like receptor (TLR)-IL-1 receptor superfamily. Previous studies demonstrated that SIGIRR can function as a negative regulator of IL-1 and LPS signaling. The purpose of this study was to evaluate the effect of enhanced expression of SIGIRR on LPS-induced acute lung injury. We constructed a recombinant adenoviral vector expressing murine SIGIRR (Ad.mSIGIRR) and a control adenoviral vector containing no transgene (Ad.V). A total of 4 × 10 plaque-forming units of Ad.mSIGIRR or Ad.V adenoviral vector were administered intranasally to BALB/c mice. Forty-eight hours later, all the mice were administered a single dose of LPS via i.p. injection to induce lung injury. Lungs and blood were harvested at several time points. The expression of SIGIRR in lung, the histological changes in the lung, the levels of TNF-α in serum and lung, the concentration of nitric monoxide (NO) in lung, and the activity of myeloperoxidase and nuclear transcription factor κB in the lung were examined. A second cohort of mice was followed for survival for 7 days. Administration of Ad.mSIGIRR increased the expression of SIGIRR in lung tissue, as determined by reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry. Administration of Ad.mSIGIRR significantly suppressed the inflammatory reaction to LPS, attenuated the lung pathological changes, and improved the survival of mice, relative to a control adenovirus. These findings suggest that modulating the expression level of SIGIRR may be a promising potential treatment for acute lung injury. Copyright © 2011 by the Shock Society.


Zhu J.,Chongqing Medical University | Huang H.,Chongqing Medical University | Dong S.,Military School of Engineering | Ge L.,Harvard University | And 2 more authors.
Theranostics | Year: 2014

Aptamers are novel oligonucleotides with flexible three-dimensional configurations that recognize and bind to their cognate targets, including tumor surface receptors, in a high-affinity and highly specific manner. Because of their unique intrinsic properties, a variety of aptamer-mediated nanovehicles have been developed to directionally transport anti-cancer drugs to tumor sites to minimize systemic cytotoxicity and to enhance permeation by these tumoricidal agents. Despite advances in the selection and synthesis of aptamers and in the conjugation and self-assembly of nanotechnologies, current chemotherapy and drug delivery systems face great challenges. These challenges are due to the limitations of aptamers and vehicles and because of complicated tumor mechanisms, including heterogeneity, anti-cancer drug resistance, and hypoxia-induced aberrances. In this review, we will summarize current approaches utilizing tumor surface hallmarks and aptamers and their roles and mechanisms in therapeutic nanovehicles targeting tumors. Delivery forms include nanoparticles, nanotubes, nanogels, aptamer-drug conjugates, and novel molecular trains. Moreover, the obstacles posed by the aforementioned issues will be highlighted, and possible solutions will be acknowledged. Furthermore, future perspectives will be presented, including cutting-edge integration with RNA interference nanotechnology and personalized chemotherapy, which will facilitate innovative approaches to aptamer-based therapeutics.© Ivyspring International Publisher.


Duan F.-T.,Sun Yat Sen University | Qian F.,Chongqing Medical University | Fang K.,Sun Yat Sen University | Lin K.-Y.,Sun Yat Sen University | And 2 more authors.
Molecular Cancer | Year: 2013

Background: MicroRNA-133b (miR-133b), which is a muscle-specific microRNA, has been reported to be downregulated in human colorectal carcinoma (CRC) when compared to adjacent non-tumor tissue. However, its diagnostic value and role in CRC have yet to be described. CXC chemokine receptor-4 (CXCR4), which participates in multiple cell processes such as cell invasion-related signaling pathways, was predicted to be a potential target of miR-133b. The aim of this study was to investigate the associations and functions of miR-133b and CXCR4 in CRC initiation and invasion.Methods: Mature miR-133b and CXCR4 expression levels were detected in 31 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 6 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate CXCR4 as a putative target gene of miR-133b. Regulation of CXCR4 expression by miR-133b was assessed using qRT-PCR and Western blot analysis, and the effects of exogenous miR-133b and CXCR4 on cell invasion and migration were evaluated in vitro using the SW-480 and SW-620 CRC cell lines.Results: A significant downregulation of miR-133b was observed in 93.55% of CRC tissues, and the expression of miR-133b was much lower in metastatic tumors (stage C and D, stratified by the Modified Dukes Staging System) than in primary tumors (stage A and B). In contrast, CXCR4 protein expression significantly increased in 52.63% of CRC samples, and increased CXCR4 expression in CRC was associated with advanced tumor stage. CXCR4 was shown to be a direct target of miR-133b by luciferase reporter assays, and transfection of miR-133b mimics inhibited invasion and stimulated apoptosis of SW-480 and SW-620 CRC cells.Conclusions: Our study demonstrated that downregulated miR-133b contributed to increased cell invasion and migration in CRC by negatively regulating CXCR4. These findings may be significant for the development of therapy target for CRC. © 2013 Duan et al.; licensee BioMed Central Ltd.


Riahi R.,University of Arizona | Wang S.,University of Arizona | Long M.,University of Arizona | Long M.,Chongqing Medical University | And 4 more authors.
ACS Nano | Year: 2014

The photothermal effect of plasmonic nanostructures has numerous applications, such as cancer therapy, photonic gene circuit, large cargo delivery, and nanostructure-enhanced laser tweezers. The photothermal operation can also induce unwanted physical and biochemical effects, which potentially alter the cell behaviors. However, there is a lack of techniques for characterizing the dynamic cell responses near the site of photothermal operation with high spatiotemporal resolution. In this work, we show that the incorporation of locked nucleic acid probes with gold nanorods allows photothermal manipulation and real-time monitoring of gene expression near the area of irradiation in living cells and animal tissues. The multimodal gold nanorod serves as an endocytic delivery reagent to transport the probes into the cells, a fluorescence quencher and a binding competitor to detect intracellular mRNA, and a plasmonic photothermal transducer to induce cell ablation. We demonstrate the ability of the gold nanorod-locked nucleic acid complex for detecting the spatiotemporal gene expression in viable cells and tissues and inducing photothermal ablation of single cells. Using the gold nanorod-locked nucleic acid complex, we systematically characterize the dynamic cellular heat shock responses near the site of photothermal operation. The gold nanorod-locked nucleic acid complex enables mapping of intracellular gene expressions and analyzes the photothermal effects of nanostructures toward various biomedical applications. © 2014 American Chemical Society.


Fang K.,Sun Yat Sen University | Qian F.,Chongqing Medical University | Chen Y.-Q.,Sun Yat Sen University
Current Molecular Medicine | Year: 2012

Relapse after current treatment is one of the main limitations to the complete cure of leukemia, and a concept that leukemia stem cell (LSC) is the major cause of relapse has been proposed. LSCs are derived from normal hematopoietic stem cells (HSCs), residing at the apex of leukemia cells and hiding in the bone marrow (BM) niche to evade chemotherapy. Novel therapy is strongly needed based on the unique features of LSCs to directly target these cells. MicroRNAs (miRNAs), a class of small non-coding RNAs, are now known to play important roles on cancer stem cell maintenance and differentiation. Because of the ability of miRNAs to inactivate either specific genes or entire gene families, strategies based on differential expression levels of miRNAs in LSCs as dominant activators or suppressors of gene activity have emerged as promising new candidate approaches for eradicating LSCs. In this review, we highlight new findings regarding the roles of miRNAs in LSC maintenance of quiescence repression, self-renewal, surface marker targeting, and the LSCBM niche interaction. We also discuss recent advances and future challenges to use LSC specific miRNAs as potential therapeutic molecules in eradicating LSCs. © 2012 Bentham Science Publishers.


Zheng Q.-Y.,The Military General Hospital of Beijing PLA | Jin F.-S.,Chongqing Medical University | Yao C.,Nanjing Medical University | Zhang T.,The Military General Hospital of Beijing PLA | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2012

Ursolic acid (UA) has shown the anti-tumor properties against a number of human cancers both in vivo and in vitro, however, its effect in bladder cancer and the corresponding mechanisms of action remain largely unknown. Here we found that UA dose-dependently induced growth inhibition and apoptosis in human bladder cancer T24 cells, and activation of AMP-activated protein kinase (AMPK) may contribute to the process. Our Western-blot results demonstrated a significant AMPK activation after UA treatment in T24 cells. Notably, knockdown of AMPKα by the targeted shRNA largely inhibited UA-induced T24 cell growth inhibition and apoptosis, while an AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) or a constitutively active form of AMPK mimic UA's effect. We found the ceramide level was increased after UA treatment in T24 cells, and UA-induced AMPK activation and T24 cell apoptosis were inhibited by ceramide synthase inhibitor fumonisin B1, and was enhanced by exogenously adding cell permeable short-chain ceramide (C6), suggesting that ceramide might serve as an upstream signal for AMPK activation. Further, activation of AMPK by UA promoted c-Jun N-terminal kinase (JNK) activation, but inhibited mTOR complex 1 (mTORC1) signaling to cause survivin down-regulation. Our study suggests that activation of AMPK by UA contributes to growth inhibition and apoptosis in human bladder cancer cells. © 2012 Elsevier Inc.


Jiang Z.,Chongqing Medical University | Yang P.,Chongqing Medical University | Hou S.,Chongqing Medical University | Du L.,Chongqing Medical University | And 3 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Purpose: IL-23 has been shown to be involved in the pathogenesis of Behcet's disease (BD) through promoting IL-17 production. This study examined whether IL-23R polymorphisms were associated with susceptibility to this disease in a Chinese Han population. Methods: Four single-nucleotide polymorphisms (SNP), rs7517847, rs11209032, rs 1343151 and rs17375018 were genotyped in 338 BD patients and 407 age, sex and ethnically matched healthy controls using a PCR restriction fragment length polymorphism assay. Results: A significantly increased prevalence of the homozygous rs17375018 GG genotype and G allele was found in BD patients compared with controls (corrected p (pc)<0. 001,odds ratio (OR) 1.86, 95% CI 1.39 to 2.49; pc<0.001, OR 1.57, 95% CI 1.25 to 1.98, respectively). The frequencies of the AA genotype and A allele of the SNP rs11209032 were significantly higher in BD patients compared with controls (pc=0.024, OR 1.69, 95% CI 1.21 to 2.35; p c<0.001, OR 1.48, 95% CI 1.21 to 1.82, respectively). In addition, the results showed a significantly decreased frequency of the AGCG haplotype in BD patients compared with controls (pc=0.0016, OR 0.59, 95% CI 0.45 to 0.77). Conclusions: This study, for the first time, identified a strong association of an SNP of IL-23R, rs17375018, with BD. The results also suggested that both rs11209032 AA and rs17375018 GG of IL-23R are predisposing genotypes for BD and that the AGCG haplotype may provide protection against BD.


Mei Q.,Hunan Normal University | Li F.,Hunan Normal University | Quan H.,Chongqing Medical University | Liu Y.,Chongqing Medical University | Xu H.,Nanjing University
Cancer Science | Year: 2014

Osteosarcoma typically arises in tissues of mesenchymal origin, and is the most malignant bone tumor characterized by high local aggressiveness, with poor therapeutic outcome. Busulfan has been widely used to treat CML. So far, there are no reports on the therapeutic effect of busulfan on osteosarcoma. Here, we showed that busulfan dose-dependently reduced the cell viability and proliferation, and induced cell apoptosis, senescence, and reactive oxygen species levels in two osteosarcoma cell lines. Moreover, a series of loss-of-function and gain-of-function experiments further indicated that busulfan may have its anti-osteosarcoma effect by upregulating the microRNA-200 (miR-200) family which subsequently downregulated its target genes ZEB1 and ZEB2. Furthermore, treatment with busulfan potentially inhibited the growth of implanted osteosarcoma in nude mice. Taken together, our data suggest that busulfan may have an anti-osteosarcoma effect through downregulating ZEB1 and ZEB2 through activating the miR-200 family, highlighting a possibility of using busulfan as a novel therapy for osteosarcoma. Busulfan may have its anti-osteosarcoma effect via downregulating ZEB1 and ZEB2 through activating microRNA-200 family, highlighting a possibility of using Busulfan as a novel therapy for osteosarcoma. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.


Zheng F.,Sun Yat Sen University | Liao Y.-J.,Sun Yat Sen University | Cai M.-Y.,Sun Yat Sen University | Liu Y.-H.,Guangdong Provincial Peoples Hospital | And 9 more authors.
Gut | Year: 2012

Background: Recent profile studies of microRNA (miRNA) expression have documented a deregulation of miRNA (miR-124) in hepatocellular carcinoma (HCC). Objective: To determine the status of miR-124 expression and its underlying mechanisms in the pathogenesis of HCC. Methods: The expression levels of miR-124 were first examined in HCC cell lines and tumour tissues by real-time PCR. The in vitro and in vivo functional effect of miR-124 was examined further. A luciferase reporter assay was conducted to confirm target associations. Results: The expression levels of miR-124 were frequently reduced in HCC cells and tissues, and low-level expression of miR-124 was significantly associated with a more aggressive and/or poor prognostic phenotype of patients with HCC (p<0.05). In HCC cell lines, stable overexpression of miR-124 was sufficient to inhibit cell motility and invasion in vitro, and suppress intrahepatic and pulmonary metastasis in vivo. In addition, ectopic overexpression of miR-124 in HCC cells inhibited epithelialemesenchymal cell transition, formation of stress fibres, filopodia and lamellipodia. Further studies showed that miR-124 could directly target the 3′-untranslated region (3′-UTR) of both ROCK2 and EZH2 mRNAs, and suppress their mRNA and protein expressions. These findings suggest that miR-124 plays a critical role in regulating cytoskeletal events and epithelialemesenchymal cell transition and, ultimately, inhibits the invasive and/or metastatic potential of HCC, probably by its direct target on ROCK2 and EZH2 genes. These results provide functional and mechanistic links between the tumour suppressor miRNA-124 and the two oncogenes ROCK2 and EZH2 on the aggressive nature of HCC. Conclusion: These data highlight an important role for miR-124 in the regulation of invasion and metastasis in the molecular aetiology of HCC, and suggest a potential application of miR-124 in prognosis prediction and cancer treatment.


Xu L.,Chongqing Medical University | Sun F.-Q.,Shanxi Medical University | Wang Z.-H.,Shanxi Medical University
Acta Obstetricia et Gynecologica Scandinavica | Year: 2011

Objective. To assess the efficacy and safety of radical trachelectomy (RT) and radical hysterectomy (RH) for patients with early cervical cancer. Design. Systematic review with meta-analysis. Population. Women who had early cervical cancer. Methods. Prospective controlled clinical trials comparing RT with RH were identified using a predefined search strategy. Recurrence, five-year recurrence-free survival rate, five-year overall survival rate, postoperative mortality, intraoperative and postoperative complications between the two operations were compared by using the methods provided by the Cochrane Handbook for Systematic Reviews of Interventions. Results. Three controlled clinical trials involving 587 participants were included. Meta-analysis showed that there was no significant difference between the two groups in recurrence rate [1.38; 95% confidence interval (CI) 0.58-3.28, p=0.47], five-year recurrence-free survival rate (1.17; 95% CI 0.54-2.53, p=0.69), five-year overall survival rate (0.86; 95% CI 0.30-2.43, p=0.78), postoperative mortality (1.14; 95% CI 0.42-3.11, p=0.80), intraoperative complications (1.66; 95% CI 0.11-25.28, p=0.72), postoperative complications (0.52; 95% CI 0.11-2.48, p=0.41), blood transfusion (0.29; 95% CI 0.06-1.36, p=0.12) and number of harvested lymph nodes. However, RT, compared with RH, reduced blood loss and shortened duration to normal urine residual volume and postoperative hospital stay. Moreover, RT may achieve to normal conception rates, while RH makes patients sterile. Conclusions. Radical trachelectomy has similar efficacy and safety to RH as the surgical treatment for early cervical cancer. Moreover, it reduced blood loss and shortened the duration to normal urine residual volumes and postoperative hospital stay. Radical trachelectomy can be used to treat early stage cervical cancer as an alternative operation for patients who wish to preserve fertility. © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.


Zhang L.,Leiden University | Zhou F.,Leiden University | Drabsch Y.,Leiden University | Gao R.,Xiamen University | And 7 more authors.
Nature Cell Biology | Year: 2012

The stability and membrane localization of the transforming growth factor-β (TGF-β) type I receptor (TβRI) determines the levels of TGF-β signalling. TβRI is targeted for ubiquitylation-mediated degradation by the SMAD7-SMURF2 complex. Here we performed a genome-wide gain-of-function screen and identified ubiquitin-specific protease (USP) 4 as a strong inducer of TGF-β signalling. USP4 was found to directly interact with TβRI and act as a deubiquitylating enzyme, thereby controlling TβRI levels at the plasma membrane. Depletion of USP4 mitigates TGF-β-induced epithelial to mesenchymal transition and metastasis. Importantly, AKT (also known as protein kinase B), which has been associated with poor prognosis in breast cancer, directly associates with and phosphorylates USP4. AKT-mediated phosphorylation relocates nuclear USP4 to the cytoplasm and membrane and is required for maintaining its protein stability. Moreover, AKT-induced breast cancer cell migration was inhibited by USP4 depletion and TβRI kinase inhibition. Our results uncover USP4 as an important determinant for crosstalk between TGF-β and AKT signalling pathways. © 2012 Macmillan Publishers Limited. All rights reserved.


Liu Y.,Xiamen University | Wang D.,Molecular Biology Research Center | Li F.,Chongqing Medical University | Shi G.,Xiamen University
Immunology and Cell Biology | Year: 2015

Gαq, the α-subunit of Gq protein, is ubiquitously expressed in mammalian cells. It initially attracted attention for its physiological significance in cardiovascular system. In recent years, studies have also indicated the important roles of Gαq in regulating immunity, supplying us a new insight into the mechanism of immune regulation. T helper type 17 (Th17) cells are potent inducers of tissue inflammation. Many studies have shown that Th17 cells are major effector cells in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions such as rheumatoid arthritis (RA). One of our previous studies has shown that Gαq negatively controls the disease activity of RA. However, how Gαq controls the pathogenesis of autoimmune disease is not clear. Whether this effect is via the regulation of Th17 differentiation is still not known. We aimed to find out the role of Gαq in control of Th17 differentiation. We investigated the relationship between Gαq and Th17 in RA patients. We then investigated the mechanism of how Gαq regulated Th17 differentiation by using Gnaq-/- mice. We observed that the expression of Gαq was negatively associated with interleukin-17A expression in RA patients, indicating that Gαq negatively controlled the differentiation of Th17 cells. By using Gnaq-/- mice, we demonstrated that Gαq inhibited the differentiation of Th17 cell via regulating the activity of extracellular signal-regulated kinase-1/2 to control the expression of STAT3 (signal transducer and activator of transcription 3) and RORα (RAR-related orphan receptor-α). These data suggest the possibility of targeting Gαq to develop a novel therapeutic regimen for autoimmune disease.


Liu X.,Chongqing Medical University | Liu X.,Jilin University | Wang C.,Chongqing Medical University | Ye Z.,Chongqing Medical University | And 2 more authors.
Investigative Ophthalmology and Visual Science | Year: 2013

PURPOSE. To investigate the role of Toll-like receptors (TLRs) 2, 3, 4, and 8 in the pathogenesis of Behcet's disease (BD). METHODS. Sixteen patients with active ocular BD and 16 healthy volunteers were included in this study. Total RNA was isolated from PBMCs to determine mRNA levels of TLRs, including TLR2, TLR3, TLR4, and TLR8. Cell surface receptor activity of these TLRs was investigated by FACS analysis. Monocytes and näi{dotless}ve T cells from patients and controls were cultured with or without TLR ligands, such as LPS, PGN, R848, or PolyI:C. Culture supernatants were collected and IL-17, IL-1b, and IL-23 were analyzed by ELISA. RESULTS. A markedly higher expression at the mRNA and protein level of TLR2, TLR3, TLR4, and TLR8 was observed in active BD patients as compared with controls. Significantly higher levels of IL-1b and IL-23 were detected in the supernatants of monocytes stimulated with LPS or PGN. A significantly higher level of IL-17 was observed in the supernatants of näi{dotless}ve T cells and monocytes stimulated with LPS or PGN in BD patients as compared with controls. Upon stimulation with R848 or PolyI:C, the levels of IL-17 in the supernatants of näi{dotless}ve T cells and monocytes and IL-23 levels in the supernatants of monocytes were not different between BD patients and controls. CONCLUSIONS. A higher expression of TLRs may be involved in the pathogenesis of BD. © 2013 The Association for Research in Vision and Ophthalmology, Inc.


Xiong C.,General Hospital of Guangzhou Military Command | Huang B.,Chongqing Medical University | Cun Y.,Chongqing Medical University | Aghdasi B.G.,University of California at Los Angeles | Zhou Y.,Chongqing Medical University
Clinical Orthopaedics and Related Research | Year: 2014

Background: Type 1 Modic changes are characterized by edema, vascularization, and inflammation, which lead to intervertebral disc degeneration. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine closely related to the inflammatory cytokines detected in degenerative intervertebral disc tissues. However, the existence and role of MIF and its receptor CD74 in intervertebral disc degeneration have not been elucidated. Questions/purposes: We asked whether (1) MIF and its receptor CD74 are expressed in cartilage end plates with Type 1 Modic changes, (2) MIF is associated with cartilage end plate degeneration, (3) the MIF antagonist (S, R)-3(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) suppresses MIF-induced inflammatory cytokine release, and (4) inflammatory cytokines are released by cartilage end plate chondrocytes via CD74 by activating the CD74 antibody (CD74Ab). Methods: We examined MIF and CD74 expression by human cartilage end plate chondrocytes and tissues with Type 1 Modic changes from eight patients using immunocytofluorescence and immunohistochemistry. MIF production by the chondrocytes was assessed by ELISA and PCR. We compared cytokine release by chondrocytes treated with MIF in the presence or absence of exogenous ISO-1 by ELISA. Cytokine release by chondrocytes after treatment with CD74Ab was determined by ELISA. Results: MIF was expressed in degenerated human cartilage end plate tissues and chondrocytes. Lipopolysaccharide and tumor necrosis factor α (TNF-α) upregulated MIF expression and increased MIF secretion in chondrocytes in a dose-dependent manner. MIF increased the secretion of IL-6, IL-8, and prostaglandin E2 (PGE2) in a dose-dependent manner. ISO-1 reduced the secretion of IL-6, IL-8, and PGE2. CD74Ab activated CD74 and induced release of inflammatory cytokines. Conclusions: Chondrocytes in cartilage end plate with Type 1 Modic changes express MIF and its receptor CD74. MIF might promote the inflammatory response through CD74. MIF-induced cytokine release appears to be suppressed by ISO-1, and CD74Ab could induce cytokine release. Clinical Relevance: The MIF/CD74 pathway may represent a crucial target for treating disc degeneration since inhibiting the function of MIF with its antagonist ISO-1 can reduce MIF-induced inflammation and exert potent therapeutic effects. © 2014 The Association of Bone and Joint Surgeons®.


Xu H.,University of Alabama at Birmingham | Xu H.,Chongqing Medical University | Zhang Z.,University of Alabama at Birmingham | Li M.,University of Alabama at Birmingham | Zhang R.,University of Alabama at Birmingham
Journal of Biological Chemistry | Year: 2010

MDM2 plays a major role in cancer development and progression via both p53-dependent and -independent functions. One of its p53-independent functions is the induction of the ubiquitin-independent proteasomal degradation of p21Waf1. The present study was designed to characterize the mechanism(s) by which MDM2 induces p21Waf1 degradation. We first determined the regions of MDM2 required for p21Waf1 degradation using pulldown assays and Western blotting and then examined the mechanisms using limited proteolysis and fluorescence resonance energy transfer assays. We found that the MDM2-p21Waf1 interaction depended on the central domain of MDM2 and that nuclear localization of both proteins was necessary for p21 Waf1 degradation. Specifically, amino acids 226-250 of MDM2were required for p21Waf1 binding and degradation, and amino acids 251-260 were necessary for p21Waf1 degradation. The latter region induced a conformation change in p21Waf1, increasing its interaction with the C8 subunit of the proteasome, leading to its degradation. When MDM2 lacked either segment (aa 226-250 or aa 251-260), its capacity to promote p21Waf1 degradation and cell cycle progression was significantly reduced. In summary, the present study elucidated a previously unknown mechanism by which MDM2 promotes the degradation of an intact protein (p21Waf1) through an ubiquitin-independent proteasomal degradation pathway. Because MDM2 also increases the degradation of other proteins in a ubiquitinindependent manner, this mechanism may underlie part of its tumorigenic properties. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Deng C.-Q.,Chongqing Medical University | Deng C.-Q.,Shanxi Medical University | Deng G.-H.,Chongqing Medical University | Wang Y.-M.,Chongqing Medical University
World Journal of Gastroenterology | Year: 2013

AIM: To characterize high mobility group box chromosomal protein 1 (HMGB1) polymorphisms in patients infected with hepatitis B virus (HBV) and determine the different patterns in patient subgroups. METHODS: A total of 1495 unrelated Han Chinese HBV carriers were recruited in this hospital-based case- control study. The HMGB11176 G/C polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: A significant association was observed between HMGB1 1176 G/C polymorphism and outcome of HBV infection. The subjects bearing 1176G/G genotype had an increased risk of susceptibility to chronic hepatitis B, liver cirrhosis and severe hepatitis B when compared with those bearing at least one 1176C allele. CONCLUSION: Patients with 1176G/G genotype of HMGB1 gene are more likely to have a progressive status in HBV infection. © 2013 Baishideng. All rights reserved.


Zhang C.,Military School of Engineering | Dou C.,Military School of Engineering | Dou C.,Chongqing Medical University | Xu J.,Chongqing Medical University | Dong S.,Military School of Engineering
Journal of Cellular Physiology | Year: 2014

As a member of the mononuclear phagocyte system, osteoclasts (OC) absorb the bone matrix and participate in bone modeling by keeping a balance with osteoblasts (OB) and stromal cells. Mature OC derive from the fusion of mononuclear osteoclasts (mOC) and the fusion is considered as the indispensable process for the osteoclastogenesis and absorbing activity of OC. DC-STAMP (dendritic cell-specific transmembrane protein) has been validated playing a key role in the fusion of mOC. DC-STAMP is mainly expressed in OC, macrophages and dendritic cells (DC). While DC-STAMP was discovered in DC, more attentions have been paid to DC-STAMP in OC in this decade. This review will mainly focus on the function of DC-STAMP in OC. Studies on DC-STAMP in DC may also provide new sight for the study of DC-STAMP in OC. Since the function of DC-STAMP is still poorly understood and few studies have been implemented for illustration, many issues are still unknown and need to be revealed. We will also discuss these questions in this review. © 2014 Wiley Periodicals, Inc.


Liao K.,Chongqing Medical University | Li J.,The Fifth Peoples Hospital of Chongqing | Wang Z.,Chongqing Medical University
International Journal of Clinical and Experimental Pathology | Year: 2014

Lung cancer is the most common cause of cancer-related death in the world. The main types of lung cancer are small cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC); non small cell lung carcinoma (NSCLC) includes squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma, Non small cell lung carcinoma accounts for about 80% of the total lung cancer cases. Dihydroartemisinin (DHA) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of DHA on cell growth and proliferation in lung cancer cells remain to be elucidated. Here, we demonstrate that DHA inhibited cell proliferation in the A549 lung cancer cell line through suppression of the AKT/Gsk-3β/cyclin D1 signaling pathway. DHA significantly inhibited cell proliferation of A549 cells in a concentration and time dependent manner as determined by MTS assay. Flow cytometry analysis demonstrated that DHA treatment of A549 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. These results suggest that DHA is a potential natural product for the treatment of lung cancer.


Chen Y.,Chongqing Medical University | Chen Y.,Sun Yat Sen University | Yang P.,Chongqing Medical University | Li F.,Chongqing Medical University | Kijlstra A.,Maastricht University
PLoS ONE | Year: 2011

Th17 cells have emerged as a key factor in the pathogenesis of uveitis as well as other autoimmune disorders. They secrete a number of cytokines including IL-17A, IL-17F and IL-22 and until now the effects of these cytokines on resident cells of the eye were not yet clear. The purpose of this study was to investigate the effects of Interleukin (IL)-17A, IL-17F and IL-22 on the production of inflammatory mediators and barrier function of retinal pigment epithelium cells. We showed that ARPE-19 cells, a spontaneously arisen cell line of retinal pigment epithelium (RPE), constitutively expressed IL-17RC and IL-22R, but not IL-17RA. IL-17A significantly enhanced the production of CXCL8, CCL2, CCL20 and IL-6 by these cells. IL-17F had a similar effect on the production of CXCL8, CCL2 and IL-6 by ARPE-19 cells, but did not influence the expression of CCL20. Both IL-17A and IL-17F significantly decreased the transepithelial electrical resistance (TER) of the ARPE-19 monolayer and increased the diffusion rate of fluorescein isothiocyanate (FITC)-dextran. They also disrupted the distribution of the junction proteins zonula occludens (ZO)-1 and occludin at the interface of adjacent cells. IL-22 did not have a detectable effect on the production of the tested inflammatory mediators by ARPE-19 cells, TER of the ARPE-19 monolayer, the diffusion rate of FITC-dextran or the distribution of ZO-1 and occludin. This study demonstrates that IL-17A and IL-17F, but not IL-22, significantly promoted ARPE-19 cells to secrete inflammatory mediators and compromised the ARPE-19 monolayer barrier function in association with a disrupted distribution of ZO-1 and occludin. These results suggest that both IL-17A and IL-17F may play a role in posterior segment inflammation of the eye. © 2011 Chen et al.


Zheng Q.-Y.,The Military General Hospital of Beijing PLA | Li P.-P.,Southern Medical University | Jin F.-S.,Chongqing Medical University | Yao C.,Nanjing Medical University | And 3 more authors.
Cellular Signalling | Year: 2013

Here we studied the cellular mechanisms of ursolic acid's anti-bladder cancer ability by focusing on endoplasmic reticulum stress (ER stress) signaling. We show that ursolic acid induces a significant ER stress response in cultured human bladder cancer T24 cells. ER stress inhibitor salubrinal, or PERK silencing, diminishes ursolic acid-induced anti-T24 cell effects. Salubrinal inhibits ursolic acid-induced CHOP expression, Bim ER accumulation and caspase-3 activation in T24 cells. Ursolic acid induces IRE1-TRAF2-ASK1 signaling complex formation to activate pro-apoptotic ASK1-JNK signaling. We suggest that ER stress contributes to ursolic acid's effects against bladder cancer cells. © 2012 Elsevier Inc.


Yang B.,Chongqing Medical University | Kang X.,Chengdu Military General Hospital | Xing Y.,Chongqing Medical University | Dou C.,Military School of Engineering | And 4 more authors.
FEBS Letters | Year: 2014

MicroRNA-145 has been shown to regulate chondrocyte homeostasis. It seems that miR-145 is implicated in cartilage dysfunction in Osteoarthritis (OA). However, the functional role of miR-145 in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage has never been clarified. Here, we show that miR-145 expression increased in OA chondrocytes and in response to IL-1β stimulation. We confirm that mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, is directly regulated by miR-145. Modulation of miR-145 affects the expression of Smad3 causing a change of its downstream target gene expression as well as IL-1β-induced ECM degradation in OA chondrocytes. This indicates that miR-145 contributes to impaired ECM in OA cartilage probably in part via targeting Smad3. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Yang Y.C.,Ghent University | Yang Y.C.,Chongqing Medical University | Zhang N.,Ghent University | Van Crombruggen K.,Ghent University | And 3 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2012

Airway diseases such as chronic rhinosinusitis, asthma, and chronic obstructive pulmonary disorder are characterized by inflammation and remodeling. Among inflammatory and extracellular matrix regulatory cytokines, transforming growth factor-beta (TGF-β) stands central, as it possesses both important immunomodulatory and fibrogenic activities, and should be considered a key for understanding inflammation and remodeling processes. This review will briefly summarize the recent findings on the role of TGF-β1, from the view points of inflammation and remodeling, and discuss the role of TGF-β in the upper and lower airway diseases. This may reveal new perspectives in the understanding of airway inflammation and remodeling processes and may open innovative treatment strategies for the regulation of TGF-β1. © 2012 John Wiley & Sons A/S.


Hou S.,Chongqing Medical University | Kijlstra A.,Maastricht University | Yang P.,Chongqing Medical University
Progress in molecular biology and translational science | Year: 2015

Uveitis is usually considered as an intraocular inflammation characterized by variety of clinical features. Behcet's disease (BD), Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU), and birdshot chorioretinopathy (BCR) are examples of noninfectious forms of uveitis. Although the precise pathogenesis remains unclear, accumulating evidence shows that complex genetic backgrounds coupled with an aberrant immune response may be implicated in the development of uveitis. The complement and pattern recognition systems are both important factors of the innate immune system and are involved in the pathogenesis of uveitis. Copy number variants (CNVs) of complement component 4 have been found to be associated with BD and VKH syndrome, but not with AAU. Several CNVs and gene polymorphisms of toll-like receptors were found to be associated with BD. Leukocytes are an important part of the adaptive immune system and various molecules on these cells play an important role in the development of uveitis. Genes encoding for human leukocyte antigens (HLAs) have been shown to be associated with certain uveitis entities, including BD (HLA-B51), VKH syndrome (HLA-DR4, DRB1/DQA1), AAU (HLA-B27), and BCR (HLA-A29). Genome wide association studies showed that the IL-23R locus was a shared risk factor for multiple uveitis entities including BD, AAU, and VKH syndrome. In addition, various other non-HLA genes are also associated with BD or VKH syndrome, such as IL-10, STAT4, STAT3, and UBAC2. These studies support the hypothesis that genetic factors play a key role in the pathogenesis of uveitis. © 2015 Elsevier Inc. All rights reserved.


Chen Y.,Sun Yat Sen University | Chen Y.,Chongqing Medical University | Kijlstra A.,Maastricht University | Yang P.,Chongqing Medical University
Molecular Vision | Year: 2011

Purpose: To investigate the signaling pathways involved in interleukin (IL)-17A -mediated production of interleukin 8 (CXCL8), chemokine (C-C motif) ligand 2 (CCL2), and interleukin 6 (IL-6) by ARPE-19 cells, a spontaneously arisen cell line of retinal pigment epithelium (RPE). Methods: Flow cytometry analysis and western blot were used to detect the phosphorylation of extracellular signalregulated kinases 1/2 (Erk1/2), p38 mitogen activated protein kinase (MAPK) and protein kinase B (PKB; Akt) in ARPE-19 cells stimulated with IL-17A. These cells were further pretreated with a series of kinase inhibitors and followed by incubation with IL-17A. CXCL8, CCL2, and IL-6 in the supernatant were quantified by enzyme-linked immunosorbent assay (ELISA). Results: Coculture of ARPE-19 cells with IL-17A resulted in significant increases in Erk1/2, p38 MAPK, and Akt phosphorylation. Inhibition of p38MAPK, phosphoinositide 3-kinase (PI3K)-Akt and nuclear factor-kappaB (NF-κB), with the inhibitors SB203580, LY294002 and pyrrolydine dithiocarbamate (PDTC) respectively, reduced IL-17 (100 ng/ ml) mediated production of CXCL8, CCL2, and IL-6 in a concentration dependent manner. Inhibition of Erk1/2 with PD98059 decreased the expression of the tested three inflammatory mediators when using low doses of IL-17A (0-10 ng/ ml) but not at higher concentrations. Conclusions: IL-17A-induced production of inflammatory mediators by ARPE-19 cells involves Erk1/2, p38MAPK, PI3K-Akt and NF-κB pathways. © 2011 Molecular Vision.


Luo J.,Chongqing Medical University | Ren X.,Chongqing Institute for Food and Drug Control | Yu T.,Chongqing Medical University
International Journal of Radiation Biology | Year: 2015

Purpose: To evaluate the efficacy of extracorporeal ultrasound-guided high intensity focused ultrasound (HIFU) based upon data in controlled clinical trials in China. Materials and methods: Data in 75 controlled trials involving in 833 cases of benign and 4559 cases of malignant diseases were re-evaluated. Results: In uterine fibroid, ectopic pregnancy and chyluria, the efficacy of HIFU was similar to that of surgery or drugs. The survival rate of HIFU plus radiotherapy was less than that of radical surgery in operable liver cancer. In inoperable liver cancer, the survival benefit of HIFU was similar to that of radio frequency, transarterial chemoembolization or γ-knife. In pancreatic cancer, HIFU and chemotherapy produced similar survival rates, and HIFU did not improve the effect of chemotherapy or radiotherapy. HIFU did not enhance hormone therapy in prostate cancer. Preoperative HIFU increased rates of complete removal and of survival in retroperitoneal sarcoma, and increased the response rate in breast cancer. The response rate agreed with the survival benefit (κ = 0.71, p = 0.0002). Conclusions: HIFU should be curtailed in resectable cases and be an alternative in inoperable cases; a combination regimen should not be recommended. The Response Evaluation Criteria in Solid Tumors can be applied to HIFU. © 2015 Informa UK, Ltd.


Wong C.K.,Chinese University of Hong Kong | Cao J.,Chinese University of Hong Kong | Yin Y.B.,Chongqing Medical University | Lam C.W.K.,Chinese University of Hong Kong | Lam C.W.K.,Macau University of Science and Technology
European Respiratory Journal | Year: 2010

Basophils are the accessory cell type for T-helper (Th)2 induction and initiators in immunoglobulin E-mediated chronic allergic inflammation. Basophils and Th17 cells accumulate at the inflammatory sites, such as the airways of allergic asthmatic patients. We investigated the activation of interleukin (IL)-17A on the primary human basophils/KU812 basophilic cells and primary human bronchial epithelial cells/BEAS-2B bronchial epithelial cells. Cytokines, chemokines, adhesion molecules and intracellular signalling molecules were assayed by ELISA or flow cytometry. Co-culture of bronchial epithelial cells and basophils could significantly induce the release of IL-6, an epithelial inflammatory cytokine, and CCL2, a chemokine for basophils, esosinophils and monocytes. Such induction was synergistically enhanced by IL-17A, and direct interaction between these two cells was necessary for IL-17A-induced IL-6 and CCL2 release. Surface expression of intercellular adhesion molecule-1 on bronchial epithelial cells was also upregulated upon their interaction. The interaction of basophils and bronchial epithelial cells under IL-17A stimulation was differentially regulated by extracellular signal-regulated kinase, c-Jun N-terminal protein kinase, p38 mitogen-activated protein kinase and nuclear factor-κB pathways. These findings suggest a novel immunopathological role of Th17 cells and basophils in allergic asthma through the activation of granulocyte-mediated inflammation initiated by the direct interaction between basophils and bronchial epithelial cells. Copyright©ERS Journals Ltd 2010.


Hu K.,Chongqing Medical University | Hou S.,Chongqing Medical University | Jiang Z.,Chongqing Medical University | Kijlstra A.,Maastricht University | Yang P.,Chongqing Medical University
Investigative Ophthalmology and Visual Science | Year: 2012

PURPOSE. Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) polymorphisms have been demonstrated as a common risk factor for a number of autoimmune diseases. The aim of this study was to investigate the association of JAK2 and STAT3 polymorphisms with Behçet's disease (BD) in a Han Chinese population. METHODS. A case-control study was performed in 503 Chinese patients with BD and 615 healthy controls. The genotypes of three single-nucleotide polymorphisms (SNPs) (rs10758669, rs7857730, rs10119004) in the JAK2 and four SNPs (rs6503695, rs744166, rs2293152, and rs12948909) in the STAT3 gene were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCRRFLP). In all, 10% of the samples were sequenced to validate the result of PCR-RFLP. The χ 2 test was performed to compare allele and genotype distributions and Bonferroni correction was applied for multiple comparisons. RESULTS. A deviation from the Hardy-Weinberg equilibrium was not found in all controls tested. A significantly increased frequency of the GG genotype of the STAT3 rs2293152 was observed in patients with BD (Bonferroni-corrected P value = 0.021). None of the tested SNPs of JAK2 was associated with BD. Stratification analysis according to oral ulceration, genital ulceration, skin lesions, and arthritis for BD did not reveal an association. CONCLUSIONS. These results suggest that a STAT3 genetic polymorphism is associated with the susceptibility to BD. © 2012 The Association for Research in Vision and Ophthalmology, Inc.


Fan X.,Chongqing Medical University | Sun D.,Chongqing Medical University | Tang X.,Chongqing Medical University | Cai Y.,Chongqing Medical University | And 4 more authors.
Medicinal Research Reviews | Year: 2014

Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by deposition of insoluble β-amyloid peptides, intracellular neurofibrillary tangles, and the loss of diverse neurons. Current pharmacological treatments for AD relieve symptoms without affecting the major pathological characteristics of the disease. Therefore, it is essential to develop new and effective therapies. Stem-cell types include tissue-specific stem cells, such as neural stem cells and mesenchymal stem cells, embryonic stem cells derived from blastocysts, and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells. Recent preclinical evidence suggests that stem cells can be used to treat or model AD. The mechanisms of stem cell based therapies for AD include stem cell mediated neuroprotection and trophic actions, antiamyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model AD, investigate sporadic and familial AD pathogenesis, and screen for anti-AD drugs. Although considerable progress has been achieved, a series of challenges must be overcome before stem cell based cell therapies are used clinically for AD patients. This review highlights the recent experimental and preclinical progress of stem-cell therapies for AD, and discusses the translational challenges of their clinical application. © 2014 Wiley Periodicals, Inc.


Huang Y.,Chongqing Medical University | Yang M.,Chongqing Medical University | Yang H.,Urologic | Zeng Z.,Chongqing Medical University
Experimental Cell Research | Year: 2010

Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), as a novel IFN-β/RA-inducible gene product, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis. Recently, it has been reported that the apoptotic effects and apoptosis-related gene induction of GRIM-19 can be attenuated by GW112, indicating that GRIM-19 and GW112 are involved in a common signal transduction pathway. To investigate the signaling mechanisms that link GRIM-19 to GW112 and their functional role in tumor cell invasion and metastasis, we utilized adenovirus-mediated overexpression of GRIM-19 in the gastric cancer SGC-7901 cell line. We observed that enhanced expression of GRIM-19 not only downregulated GW112 but also decreased NF-κB binding activity. As a result, we found that tumor cell adhesion, migration, invasion and liver metastasis were inhibited. Additionally, upregulation of GRIM-19 also suppressed secretion of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase (MMP)-2, 9 and vascular endothelial growth factor (VEGF). These results indicate that GRIM-19 acts as an upstream regulator of GW112 to block NF-κB binding activity, thereby inhibiting gastric cancer cell migration, invasion and metastasis. We conclude that adenoviral transfer of the GRIM-19 gene may be an efficacious approach to controlling the invasion and metastasis of human gastric cancer. © 2010 Elsevier Inc.


Luo H.,Chongqing Medical University | Yang G.,Chongqing Medical University | Yu T.,Chongqing Medical University | Luo S.,Chongqing Health Center for Women and Children | And 4 more authors.
Endocrine-Related Cancer | Year: 2014

Cancer-associated fibroblasts (CAFs) are crucial co-mediators of breast cancer progression. Estrogen is the predominant driving force in the cyclic regulation of the mammary extracellular matrix, thus potentially affecting the tumor-associated stroma. Recently, a third estrogen receptor, estrogen (G-protein-coupled) receptor (GPER), has been reported to be expressed in breast CAFs. In this study, GPER was detected by immunohistochemical analysis in stromal fibroblasts of 41.8% (59/141) of the primary breast cancer samples. GPER expression in CAFs isolated from primary breast cancer tissues was confirmed by immunostaining and RT-PCR analyses. Tamoxifen (TAM) in addition to 17b-estradiol (E2) and the GPER agonist G1 activated GPER, resulting in transient increases in cell index, intracellular calcium, and ERK1/2 phosphorylation. Furthermore, TAM, E2, and G1 promoted CAF proliferation and cell-cycle progression, both ofwhich were blocked by GPER interference, the selective GPER antagonist G15, the epidermal growth factor receptor (EGFR) inhibitor AG1478, and the ERK1/2 inhibitor U0126. Importantly, TAM as well as G1 increased E2 production in breast CAFs via GPER/EGFR/ERK signaling when the substrate of E2, testosterone, was added to the medium. GPER-induced aromatase upregulation was probably responsible for this phenomenon, as TAM-and G1-induced CYP19A1 gene expression was reduced by GPER knockdown and G15, AG1478, and U0126 administration. Accordingly, GPER-mediated CAF-dependent estrogenic effects on the tumor-associated stroma are conceivable, and CAF is likely to contribute to breast cancer progression, especially TAM resistance, via a positive feedback loop involving GPER/EGFR/ERK signaling and E2 production. © 2014 Society for Endocrinology.


Yang P.,Chongqing Medical University | Zhang N.,Chongqing Medical University | Li F.,Chongqing Medical University | Chen Y.,Chongqing Medical University | Kijlstra A.,Maastricht University
Retina | Year: 2012

PURPOSE: To present the manifestations of syphilitic uveitis in Chinese patients. METHODS: This is a retrospective case series of 35 eyes of 19 patients with syphilitic uveitis. The data of these patients including complaints, ocular and systemic manifestations, human immunodeficiency virus status, results of auxiliary examinations, treatment, and follow-up were reviewed. RESULTS: Nineteen consecutive Chinese patients were diagnosed with syphilitic uveitis by serologic tests. Four patients had circulating human immunodeficiency virus antibodies. Ocular involvement was found in 35 eyes. Posterior segment involvement was found in 30 eyes of 17 patients (85.7%), whereas anterior segment involvement was found in 14 eyes of 8 patients (40.0%). Thirty eyes of 17 patients (85.7%) presented with vitreous opacities and 28 eyes of 16 patients (80.0%) with retinitis. Papillitis and retinal vasculitis were found in 10 eyes of 6 patients (28.6%) and 7 eyes of 4 patients (20.0%), respectively. Multiple precipitates on the retina and posterior vitreous membrane were observed in six eyes of three patients. A large iris granuloma was observed in one eye. CONCLUSION: Posterior uveitis was the most common ocular finding in these investigated Chinese patients with syphilis. Coinfection of syphilis and human immunodeficiency virus was less common in these patients. Syphilis should be considered in the differential diagnosis of patients presenting with large iris granulomas. © Lippincott Williams & Wilkins.


Tian Y.,Chongqing Medical University | Wang C.,Chongqing Medical University | Ye Z.,Chongqing Medical University | Xiao X.,Chongqing Medical University | And 2 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

Purpose. 1,25-Dihydroxyvitamin D3 (VitD3) has been shown to have immunoregulatory properties in animal models. In this study, we investigated its inhibitory effect on the immune response in Behçet's disease (BD) patients and the possible mechanisms involved. Methods. Naive CD4+ T cells from active BD patients and normal controls were cultured under Th17 polarizing conditions in the presence or absence of VitD3, and cytokine production was determined by ELISA and flow cytometry. mRNA expression of several factors related to Th17 cell function was determined by real-time PCR. RNA interference for IFN regulatory factor 8 (IRF-8) was performed to study whether it was involved in the inhibitory effect of VitD3 on Th17 cell differentiation. The effect of VitD3-treated dendritic cells (DCs) on CD4+ T cell response was determined by ELISA and flow cytometry. Results. Stimulation of naive CD4+ T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in active BD patients. The addition of VitD3 significantly inhibited Th17 cell differentiation both in BD patients and in normal controls. The knockdown of IRF-8 by RNA interference significantly decreased the suppressive effect of VitD3 on Th17 differentiation. VitD3 was able to inhibit the gene expression of RORC, IL-17, IL-23R, CCR6, and Th1 cell differentiation, but upregulated IL-10 expression. VitD3-treated DCs significantly inhibited the Th17 and Th1 response. Conclusions. The findings suggest that the inhibitory effect of VitD3 on the Th17 and Th1 response was mediated via both T cells and DCs and that the IRF-8 pathway is involved in the direct inhibition of VitD3 on Th17 cell differentiation. © 2012 The Association for Research in Vision and Ophthalmology, Inc.


Yu T.,Chongqing Medical University | Yang Y.,Chongqing Medical University | Zhang J.,Chongqing Medical University | He H.,Sichuan Provincial Peoples Hospital | Ren X.,Chongqing Institute for Food and Drug Control
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2015

Cisplatin resistance is a challenge in the treatment of ovarian cancer. The aim of this study was to explore if ultrasound can overcome chemoresistance and enhance chemosensitization due to cyclosporin A. Ultrasound and/or cyclosporin A were employed to overcome cisplatin resistance in human ovarian cancer cell line COC1/DDP. Mechanisms were explored from the perspective of: DNA damage, intracellular platinum level, detoxification, and genes related to drug efflux and DNA repair. In vivo therapeutic efficacy was validated in a short-term model (subrenal cell-clot transplantation) in mice and the survival benefit was investigated in an orthotopic cancer model in mice using HO-8910PM cells. The findings were: (i) ultrasound enhanced the effect of cisplatin leading to a lower cell-survival rate (IC50 decreased from 3.19 to 0.35 μg/ml); (ii) ultrasound enhanced cisplatin via direct (increasing the intercellular level of active platinum) and indirect (decreasing the glutathione level, and expression of LRP and ERCC1 genes) mechanisms that intensified cisplatin-induced DNA damage, thus enhancing cell apoptosis and necrosis; (iii) cisplatin followed by ultrasound led to small tumor sizes in the short-term model without exacerbation of the systemic toxicity, and prolonged the survival times in the orthotopic model; and (iv) ultrasound synergized the sensitization due to cyclosporin A in vitro and in vivo. These data demonstrated that ultrasound combined with cyclosporin A overcame cisplatin resistance in ovarian cancer. © 2015 Elsevier B.V. All rights reserved.


Kijlstra A.,Maastricht University | Tian Y.,Maastricht University | Tian Y.,Chongqing Medical University | Kelly E.R.,Maastricht University | Berendschot T.T.J.M.,Maastricht University
Progress in Retinal and Eye Research | Year: 2012

Lutein is concentrated in the primate retina, where together with zeaxanthin it forms the macular pigment. Traditionally lutein is characterized by its blue light filtering and anti-oxidant properties. Eliminating lutein from the diet of experimental animals results in early degenerative signs in the retina while patients with an acquired condition of macular pigment loss (Macular Telangiectasia) show serious visual handicap indicating the importance of macular pigment. Whether lutein intake reduces the risk of age related macular degeneration (AMD) or cataract formation is currently a strong matter of debate and abundant research is carried out to unravel the biological properties of the lutein molecule. SR-B1 has recently been identified as a lutein binding protein in the retina and this same receptor plays a role in the selective uptake in the gut. In the blood lutein is transported via high-density lipoproteins (HDL). Genes controlling SR-B1 and HDL levels predispose to AMD which supports the involvement of cholesterol/lutein transport pathways. Apart from beneficial effects of lutein intake on various visual function tests, recent findings show that lutein can affect immune responses and inflammation. Lutein diminishes the expression of various ocular inflammation models including endotoxin induced uveitis, laser induced choroidal neovascularization, streptozotocin induced diabetes and experimental retinal ischemia and reperfusion. In vitro studies show that lutein suppresses NF kappa-B activation as well as the expression of iNOS and COX-2. Since AMD has features of a chronic low-grade systemic inflammatory response, attention to the exact role of lutein in this disease has shifted from a local effect in the eye towards a possible systemic anti-inflammatory function. © 2012 Elsevier Ltd.


Yu H.,Chongqing Medical University | Liu Y.,Chongqing Medical University | Bai L.,Chongqing Medical University | Kijlstra A.,Maastricht University | Yang P.,Chongqing Medical University
Journal of Molecular Medicine | Year: 2014

Previous studies have identified miR-182, miR-27a, FoxO1, and IL2RA as regulatory factors for Treg cell development and function. In order to investigate the association of miR-182, miR-27a, FoxO1, and IL2RA gene polymorphisms with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population, a two-stage association study was performed in 820 BD, 900 VKH patients, and 1,800 controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. In the first stage study, association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 400 BD, 400 VKH patients, and 600 controls. The results showed significantly decreased frequencies of the miR-182/rs76481776 CC genotype and C allele in BD (P=3.36×10-4, OR=0.55; P=4.74×10 -4, OR=0.59) and VKH patients (P=1.11×10-4, OR=0.53; P=1.26×10-4, OR=0.56). No significant association of the other nine SNPs with BD or VKH was observed. In the second stage study, association analysis of miR-182/rs76481776 was performed in 420 BD, 500 VKH patients, and 1,200 controls. The second stage and combined studies confirmed the association of miR-182/rs76481776 with BD (CC genotype: P=3.25×10-7, OR=0.58; C allele: P=1.81×10-7, OR=0.60) and VKH (CC genotype: P=7.89×10-8, OR=0.57; C allele: P=2.52×10-8, OR=0.59). Real-time PCR analysis showed a significantly increased expression of miR-182 in TT/CT cases compared to CC cases in anti-CD3/CD28 antibodies-stimulated CD4+ T cells (P=2.1×10-2). In conclusion, this study suggests that miR-182, but not miR-27a, FoxO1, and IL2RA, contributes to the genetic susceptibility of BD and VKH. Key Message: • MiR-182 contributes to genetic susceptibility of BD and VKH. • No significant association of miR-27a, FoxO1, and IL2RA with BD or VKH was observed. • Significantly increased expression of miR-182 in TT/CT cases compared to CC cases was observed. © 2014 Springer-Verlag.


Wang C.,Chongqing Medical University | Ye Z.,Chongqing Medical University | Kijlstra A.,Maastricht University | Zhou Y.,Chongqing Medical University | Yang P.,Chongqing Medical University
Clinical and Experimental Immunology | Year: 2014

Summary: Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of dioxin-containing pollutants, but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behçet's disease (BD) patients. In this study, we showed that AhR activation by FICZ and ITE down-regulated the expression of co-stimulatory molecules including human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD patients showed a higher level of interleukin (IL)-1β, IL-6, IL-23 and tumour necrosis factor (TNF)-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases. © 2014 British Society for Immunology.


Zhou Q.,Chongqing Medical University | Hou S.,Chongqing Medical University | Liang L.,Chongqing Medical University | Li X.,Chongqing Medical University | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Aim MicroRNA-146a (miR-146a) is involved in certain immune-mediated diseases. Transcription factor Ets-1 strongly affects miR-146a promoter activity and directly regulates miR-146a expression. This study was performed to investigate the association of miR-146a and Ets-1 gene polymorphisms with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) disease in a Chinese Han population. Methods A total of 809 patients with BD, 613 patients with VKH and 1132 normal controls were genotyped for miR-146a/rs2910164, rs57095329 and rs6864584, Ets-1/rs1128334 and rs10893872 using a PCR restriction fragment length polymorphism assay. miR-146a expression was examined in peripheral blood mononuclear cells (PBMCs) by real-time PCR. Cytokine production by PBMCs was measured by ELISA. Results A significantly decreased frequency of the homozygous rs2910164 CC genotype and C allele was observed in patients with BD compared with controls (pc a=1.24×10-5, OR 0.61; pc a=1.33×10-4, OR 0.75, respectively). MiR-146a expression in GG cases was 2.45-fold and 1.99-fold higher, respectively, than that in CC cases and GC cases. There was no association of the other four single nucleotide polymorphisms (SNPs) with BD. There was also no association of these five SNPs with its main clinical features. No associations were found with the five SNPs tested or with its clinical manifestations in VKH disease. Interleukin (IL)-17, tumour necrosis factor (TNF)α and IL-1β production from rs2910164 CC cases was markedly lower than that in GG cases. No effect of genotype was observed on IL-6 and monocyte chemoattractant protein (MCP)-1 production and IL-8 expression was slightly higher in CC cases. Conclusions Our study identified a strong association of rs2910164 of miR-146a with BD in a Chinese population and decreased expression of miR-146a and certain proinflammatory cytokines in individuals carrying the CC genotype.


Zhang X.,Chinese PLA General Hospital | Ji J.,Zhejiang Provincial Corps Hospital | Liu B.,Chongqing Medical University
Journal of International Medical Research | Year: 2013

Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) studying the clinical benefit of chemotherapy with surgical intervention over chemotherapy alone for the treatment of spinal tuberculosis. Methods: Relevant RCTs were identified by computerized database searches. Trial eligibility and methodological quality were assessed and data were extracted and analysed using odds ratios with 95% confidence intervals. The primary outcome measure was kyphosis angle. Results: The literature search identified two RCTs conducted in the 1970s and 1980s and a Cochrane Database Systematic Review published in 2006. There were no significant between-group differences in kyphosis angle, bony fusion, bone loss or development of neurological deficit. Conclusions: There is no obvious statistically significant clinical precedence to suggest that routine surgery will improve the prognosis of patients with spinal tuberculosis. © The Author(s) 2013.


Ye Z.,Chongqing Medical University | Wang C.,Chongqing Medical University | Kijlstra A.,Maastricht University | Zhou X.,Chongqing Medical University | Yang P.,Chongqing Medical University
Current Molecular Medicine | Year: 2014

Interleukin 37 has been found to play a significant regulatory role in the innate immune response. It is not yet known whether IL-37 has also been involved in the development of Behcet's disease (BD), a chronic systemic inflammatory disease. To examine the role of IL-37 in the pathogenesis of BD, a number of experiments were performed. IL-37 expression in peripheral blood mononuclear cells (PBMCs) from BD patients and normal controls was measured by RT-PCR and flow cytometry. Monocyte-derived Dendritic Cells (DCs) were cultured with or without IL-37 and levels of cytokines in the culture supernatants were measured by ELISA. The DC surface markers, reactive oxygen species (ROS) production and mitogen-activated protein kinase (MAPK) activation were measured by flow cytometry. The effect of IL-37-treated DCs on the development of CD4+ T cells was measured by ELISA and flow cytometry. The results show that both IL-37 mRNA level and protein expression were significantly decreased in PBMCs from active BD patients compared to normal controls. DCs stimulated with rIL-37 showed a decreased expression of IL-6, IL-1β and TNF-α, and a higher production of IL-27. rIL-37 significantly inhibited the production of ROS by DCs and reduced the activation of ERK1/2, JNK and P38 MAPK in DCs. rIL-37-treated DCs remarkably inhibited Th17 and Th1 cell responses as compared to control DCs. rIL-37 did not affect the expression of DC surface markers (CD40, CD86, CD80 and HLA-DR) or IL-10 production by DCs. We conclude that a decreased IL-37 expression in active BD patients may trigger the production of pro-inflammatory cytokines and ROS in association with activation of Th1 and Th17 cells by DCs. © 2014 Bentham Science Publishers.


Huang Z.-P.,Harvard University | Chen J.,Harvard University | Seok H.Y.,Harvard University | Zhang Z.,Harvard University | And 5 more authors.
Circulation Research | Year: 2013

Rationale: The adult heart is composed primarily of terminally differentiated, mature cardiomyocytes that express signature genes related to contraction. In response to mechanical or pathological stress, the heart undergoes hypertrophic growth, a process defined as an increase in cardiomyocyte cell size without an increase in cell number. However, the molecular mechanism of cardiac hypertrophy is not fully understood. Objective: To identify and characterize microRNAs that regulate cardiac hypertrophy and remodeling. Methods and Results: Screening for muscle-expressed microRNAs that are dynamically regulated during muscle differentiation and hypertrophy identified microRNA-22 (miR-22) as a cardiac-and skeletal muscle-enriched microRNA that is upregulated during myocyte differentiation and cardiomyocyte hypertrophy. Overexpression of miR-22 was sufficient to induce cardiomyocyte hypertrophy. We generated mouse models with global and cardiac-specific miR-22 deletion, and we found that cardiac miR-22 was essential for hypertrophic cardiac growth in response to stress. miR-22-null hearts blunted cardiac hypertrophy and cardiac remodeling in response to 2 independent stressors: isoproterenol infusion and an activated calcineurin transgene. Loss of miR-22 sensitized mice to the development of dilated cardiomyopathy under stress conditions. We identified Sirt1 and Hdac4 as miR-22 targets in the heart. Conclusions: Our studies uncover miR-22 as a critical regulator of cardiomyocyte hypertrophy and cardiac remodeling. © 2013 American Heart Association, Inc.


Feng K.,Chongqing Medical University | Feng K.,General Hospital | Yan J.,Chongqing Medical University | Li X.,Chongqing Medical University | And 5 more authors.
Journal of Hepatology | Year: 2012

Background & Aims: The aim of this study was to compare the efficacy of radiofrequency ablation (RFA) with surgical resection (RES) in the treatment of small hepatocellular carcinoma (HCC). Methods: A total of 168 patients with small HCC with nodular diameters of less than 4 cm and up to two nodules were randomly divided into RES (n = 84) and RFA groups (n = 84). Outcomes were carefully monitored and evaluated during the 3-year follow-up period. Results: The 1-, 2-, and 3-year survival rates for the RES and RFA groups were 96.0%, 87.6%, 74.8% and 93.1%, 83.1%, 67.2%, respectively. The corresponding recurrence-free survival rates for the two groups were 90.6%, 76.7%, 61.1% and 86.2%, 66.6%, 49.6%, respectively. There were no statistically significant differences between the two groups in overall survival rate (p = 0.342) or recurrence-free survival rate (p = 0.122). Multivariate analysis demonstrated that the independent risk factors associated with survival were multiple occurrences of tumors at different hepatic locations (relative risk of 2.696; 95% CI: 1.189-6.117; p = 0.018) and preoperative indocyanine green retention rate at 15 min (ICG-15) (relative risk of 3.853; 95% CI: 1.647-9.015; p = 0.002). Conclusions: In patients with small hepatocellular carcinomas, percutaneous RFA may provide therapeutic effects similar to those of RES. However, percutaneous RFA is more likely to be incomplete for the treatment of small HCCs located at specific sites of the liver, and open or laparoscopic surgery may be the better choice. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Yang X.,Chongqing Medical University | Zhu H.,General Hospital | Hu Z.,Chongqing Medical University
Vaccine | Year: 2010

Recent evidence suggested that angiogenesis played a pivotal role in the development of hepatocellular carcinoma cells (HCC), thus the therapy strategy targeting antiangiogenesis has been regarded as promising method for HCC therapy. Tumor endothelial marker 8 (TEM8) is a recently described protein that is preferentially expressed within tumor endothelium. However, the antiangiogenesis therapy of HCC based on TEM8 has not been reported. In this study, the recombinant adenovirus encoding TEM8 was constructed, and the DCs were transduced with the Ad-TEM8. In addition, the modified DCs were transferred into the BALB/c mice to determine whether DCs transduced with TEM8 could elicit a potent antitumor immunogenic response in vivo. The results demonstrated that DCs transduced with Ad-TEM8 induced specific CTLs effectively, which could secrete IFN-γ and lyse HCC. Furthermore, the modified DCs could effectively protect BALB/c mice from lethal challenges against HCC, reduce tumor growth and increase the mice life span by decreasing tumor vasculature density. These data suggest that the Ad-TEM8 modified DCs may induce antitumor immunity by disrupting tumor vasculature and may thus be used as an efficient therapy strategy to influence tumor development in clinical applications. © 2010 Elsevier Ltd.


Nan Y.,University of Maryland University College | Nan G.,University of Maryland University College | Nan G.,Chongqing Medical University | Zhang Y.-J.,University of Maryland University College
Viruses | Year: 2014

Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR). Host PRR for RNA viruses include Toll-like receptors (TLR) and retinoic acid-inducible gene I (RIG-I) like receptors (RLR). Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Miao H.,Chongqing Medical University | Zhang Y.,Chongqing Medical University | Lu Z.,Chongqing Medical University | Yu L.,University of Maryland University College | Gan L.,Chongqing Medical University
Molecular Endocrinology | Year: 2012

Hepatic insulin resistance (IR) is associated with liver inflammatory diseases, but molecular mechanisms for the association remained elusive. IR is known to increase activity of forkhead boxcontaining protein O subfamily-1 (FOXO1), a transcription factor that was recently shown to enhance proinflammatory cytokine production in macrophages and adipocytes. Here we report that overexpression of constitutively active FOXO1 markedly increased chemokine ligand 20 (CCL20) expression and secretion in HepG2 hepatoma cells treated with TNF-α. The opposite was seen when endogenous FOXO1 was silenced. FOXO1 did not bind CCL20 promoter directly; instead, it potentiated CCL20 transcription through increasing the binding of p65/p50 heterodimer to a functional nuclear factor- κB site in the human CCL20 promoter. The conditional medium from TNF- α -treated HepG2 cells stimulated migration of human peripheral blood mononuclear cells. This stimulation was significantly enhanced when FOXO1 was overexpressed, and attenuated when FOXO1 was silenced. CCL20 antibody partly blocked the synergistic effect of FOXO1 and TNF- α on peripheral blood mononuclear cells migration. Additionally, TNF- α antagonizes the insulin/Akt signal transduction, thus leading to activation of FOXO1, which is capable of mediating a transcriptional activation role in response to TNF- α on CCL20 gene expression in HepG2 cells and promotes lymphocyte chemotaxis. Furthermore, we found that FOXO1 and CCL20 were coordinately up-regulated in the insulin resistant and inflammatory cell-infiltrated liver of db/db mice, an animal model that displayed hepatic and systemic low-grade inflammation. In conclusion, our data suggest that FOXO1 links IR to lymphocyte chemotaxis in the insulin-resistant hepatocytes and livers by amplifying nuclear factor- κB-dependent hepatic CCL20 production. © 2012 by The Endocrine Society.


Hu S.,Chongqing Medical University | Zhao F.,Youyang Peoples Hospital | Wang Q.,Chongqing Medical University | Chen W.-X.,Chongqing Medical University
Clinical Chemistry and Laboratory Medicine | Year: 2014

The aim of this study was to evaluate the diagnostic value of anti-mitochondrial antibodies (AMAs) and/or the M2 subtype (AMA-M2) in patients with primary biliary cirrhosis (PBC). AMA/AMA-M2 data were obtained by searching electronic databases. Studies showing AMA/AMA-M2 results in patients with PBC and control groups with other liver diseases or healthy livers were included. The quality of the involved studies was assessed using the QUADAS tool. The pooled sensitivity and specificity were calculated, and stratified analysis was performed according to possible heterogeneity sources. The pooled AMA (all methods) sensitivity and specificity were 84.5% (95% confidence interval (CI) 83.3%-85.6%) and 97.8% (95% CI 97.6%-98.0%), respectively. The positive and negative likelihood ratios were 25.201 (95% CI 17.583-36.118) and 0.162 (95% CI 0.131-0.199), respectively. The current evidence suggests that AMA and AMA-M2 show favorable accuracy for the diagnosis of PBC with high specificity and sensitivity. AMA is a better and more comprehensive marker than AMA-M2. The accuracy established in this meta-analysis is based on clinical studies using patient cohorts from different ethnicities.


Dal Pra I.,University of Verona | Chiarini A.,University of Verona | Gui L.,Chongqing Medical University | Chakravarthy B.,National Research Council Canada | And 4 more authors.
Neuroscientist | Year: 2015

Evidence has begun emerging for the "contagious" and destructive Aβ42 (amyloid-beta42) oligomers and phosphorylated Tau oligomers as drivers of sporadic Alzheimer's disease (AD), which advances along a pathway starting from the brainstem or entorhinal cortex and leading to cognition-related upper cerebral cortex regions. Seemingly, Aβ42 oligomers trigger the events generating the neurotoxic Tau oligomers, which may even by themselves spread the characteristic AD neuropathology. It has been assumed that only neurons make and spread these toxic drivers, whereas their associated astrocytes are just janitorial bystanders/scavengers. But this view is likely to radically change since normal human astrocytes freshly isolated from adult cerebral cortex can be induced by exogenous Aβ25-35, an Aβ42 proxy, to make and secrete increased amounts of endogenous Aβ42. Thus, it would seem that the steady slow progression of AD neuropathology along specific cognition-relevant brain networks is driven by both Aβ42 and phosphorylated Tau oligomers that are variously released from increasing numbers of "contagion-stricken" members of tightly coupled neuron-astrocyte teams. Hence, we surmise that stopping the oversecretion and spread of the two kinds of "contagious" oligomers by such team members, perhaps via a specific CaSR (Ca2+-sensing receptor) antagonist like NPS 2143, might effectively treat AD. © The Author(s) 2014.


Wu J.,Chongqing Medical University | Liu D.,Chongqing Medical University | Tu W.,University of Hong Kong | Song W.,Chongqing Medical University | And 2 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background Wiskott-Aldrich syndrome (WAS) is a severe disorder characterized by thrombocytopenia, eczema, immunodeficiency, and increased risk of autoimmune disease and lymphoid malignancies. The immunodeficiency caused by a lack of WAS protein expression has been mainly attributed to defective T-cell functions. Whether WAS mutations differentially influence the T-cell receptor (TCR) diversity of different T-cell subsets is unknown.Objective We aimed to identify the degree and pattern of skewing in the variable region of the TCR β-chain (Vβ) in different T-cell subsets from patients with WAS.Methods The TCR repertoire diversity in total peripheral T cells, sorted CD4+ and CD8+ T cells, and CD45RA+ (CD45RA+CD45RO- cells) and CD45RO+ (CD45RA-CD45RO+ cells) CD4+ and CD8+ T cells from patients with WAS and age-matched healthy control subjects was analyzed and compared by using spectratyping of complementarity-determining region 3. The complementarity-determining region 3 of TCRβ transcripts in CD45RA+CD4+ and CD45RA+CD8+ T cells, CD45RO+CD4+ T cells, CD8+ terminally differentiated effector memory T (Temra) cells, and naive CD8+ T cells (CD8+CD45RO-CCR7+ cells) from patients and control subjects were analyzed and compared by using high-throughput sequencing.Results The TCR repertoire diversity in CD45RO+CD4+ T cells and CD8+ Temra cells of patients with WAS was significantly skewed in comparison with that seen in age-matched control subjects.Conclusion Our results indicate that WAS gene mutations selectively influence TCR repertoire development or expansion in CD45RO+ (memory) CD4+ T cells. © 2014 American Academy of Allergy, Asthma & Immunology.


Hu Y.,Wuhan University | Zhao Z.,Wuhan University | Wan Q.,Chongqing Medical University
Bioelectrochemistry | Year: 2011

A novel electrochemical immunosensor built on three dimensional carbon nanotube-conducting polymer (CNT-CP) network is reported for detection of Hepatitis B surface antigen (HBsAg) in human serum. The CNT-CP network is prepared by drop-drying of CNT solution on glassy carbon electrode, followed by electrochemical polymerization of poly (pyrrole propionic acid) (pPPA) film to crosslink and stabilize the CNTs, wherein the CNTs form the backbone of the network, and offer great specific surface areas for antibody attachment, and confer good conductivity for electrochemical detection, while the conducting film integrates the carbon nanotubes into a stable network due to its self-limiting growth behavior and provides abundant carboxyl groups for covalent immobilization of probe proteins. As a unique matrix, the CNT-CP network enables sensitive electrochemical detection of HBsAg biomarker by using alkaline phosphatase (ALP)-conjugated secondary antibodies under sandwich format coupling with the ALP substrate solution, p-aminophenyl phosphate (PAPP), reaching a detection limit of 0.01 ng/mL with a dynamic range of 5 orders of magnitude. © 2011 Elsevier B.V.


Yang X.-C.,University of Massachusetts Amherst | Yang X.-C.,Chongqing Medical University | Samanta B.,University of Massachusetts Amherst | Agasti S.S.,University of Massachusetts Amherst | And 5 more authors.
Angewandte Chemie - International Edition | Year: 2011

Small but mighty: Current methods for generating oil-in-water emulsions provide nanoparticle-stabilized capsules (NPSCs) that are too large for efficient delivery. Electrostatic and hydrogen-bonding interactions were combined to create stable NPSCs with diameters of around 100-nm. Their potential as delivery vehicles was demonstrated through dye studies with HeLa cells. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Jiang X.,Wuhan University | Deng K.-Q.,Wuhan University | Luo Y.,Chongqing Medical University | Jiang D.-S.,Wuhan University | And 6 more authors.
Hypertension | Year: 2015

Cardiac hypertrophy, a common early symptom of heart failure, is regulated by numerous signaling pathways. Here, we identified tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein in tumor necrosis factor-related signaling cascades, as a key regulator of cardiac hypertrophy in response to pressure overload. TRAF3 expression was upregulated in hypertrophied mice hearts and failing human hearts. Four weeks after aortic banding, cardiac-specific conditional TRAF3-knockout mice exhibited significantly reduced cardiac hypertrophy, fibrosis, and dysfunction. Conversely, transgenic mice overexpressing TRAF3 in the heart developed exaggerated cardiac hypertrophy in response to pressure overload. TRAF3 also promoted an angiotensin II- or phenylephrine-induced hypertrophic response in isolated cardiomyocytes. Mechanistically, TRAF3 directly bound to TANK-binding kinase 1 (TBK1), causing increased TBK1 phosphorylation in response to hypertrophic stimuli. This interaction between TRAF3 and TBK1 further activated AKT signaling, which ultimately promoted the development of cardiac hypertrophy. Our findings not only reveal a key role of TRAF3 in regulating the hypertrophic response but also uncover TRAF3-TBK1-AKT as a novel signaling pathway in the development of cardiac hypertrophy and heart failure. This pathway may represent a potential therapeutic target for this pathological process. © 2015 American Heart Association, Inc.


Gu W.-J.,Guangxi Medical University | Tie H.-T.,Chongqing Medical University | Liu J.-C.,Guangxi Medical University | Zeng X.-T.,Hubei University of Medicine
Critical Care | Year: 2014

Introduction: Ultrasound guidance has emerged as an adjunct for central vein catheterization in both adults and children. However, the use of ultrasound guidance for radial arterial catheterization has not been well established. We conducted a systematic review and meta-analysis to evaluate the efficacy of ultrasound guidance for radial artery catheterization.Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) comparing ultrasound guidance with other techniques (palpation or Doppler) in adult or pediatric patients requiring radial artery catheterization were included. The primary outcome was first-attempt success.Results: Seven RCTs enrolling 546 patients met the inclusion criteria, and all the selected trials were considered as at high risk of bias. Ultrasound-guided radial artery catheterization was associated with an increased first-attempt success (relative risk (RR) 1.55, 95% confidence interval (CI) 1.02 to 2.35). There was significant heterogeneity among the studies (I2 = 74%). Ultrasound-guided radial artery catheterization in small children and infants also provided an increased chance for first-attempt success (RR 1.94, 95% CI 1.31 to 2.88). Ultrasound guidance further significantly reduced mean attempts to success (weighted mean difference (WMD) -1.13, 95% CI -1.58 to -0.69), mean time to success (WMD -72.97 seconds, 95% CI -134.41 to -11.52), and incidence of the complication of hematoma (RR 0.17, 95% CI 0.07 to 0.41).Conclusions: Ultrasound guidance is an effective and safe technique for radial artery catheterization, even in small children and infants. However, the results should be interpreted cautiously due to the heterogeneity among the studies. © 2014 Gu et al.; licensee BioMed Central Ltd.


Chen S.,Chongqing Medical University | Yin Y.,Chongqing Medical University | Ling Z.,Chongqing Medical University | Ling Z.,Johns Hopkins University | And 2 more authors.
Heart | Year: 2014

Objective Current literature shows there is widespread controversy regarding the indications and outcomes of using an intra-aortic balloon pump (IABP); furthermore, little is known about the late effects of IABP use. Design To determine whether IABP use can have beneficial effects for patients undergoing high risk reperfusion therapies, by conducting a meta-analysis of randomised trials. Setting Databases of Pubmed, Cochrane Library, and Clinicaltrials.gov were searched up to 15 June 2013. Patients Patients undergoing high risk reperfusion therapies. Interventions Randomised clinical trials comparing IABP with no IABP were considered eligible for this meta-analysis. Main outcome measures Primary outcomes were early (30-day) and long term (≥6-month) mortality. Results Among the 1079 articles retrieved, 10 randomised studies with 2037 high risk patients were included in the quantitative analysis. Meta-analysis revealed that early mortality rate did not differ between the IABP group and the non-IABP group (OR 0.79, 95% CI 0.48 to 1.29). However, long term mortality was significantly reduced in the IABP group (OR 0.63, 95% CI 0.45 to 0.9), and this effect seemed more pronounced in the subset of patients treated with contemporary percutaneous coronary intervention (OR 0.55, 95% CI 0.38 to 0.80). Further analysis found that IABP use was associated with a reduced risk of 30-day re-ischaemia rate (OR 0.62, 95% CI 0.42 to 0.91) and the composite outcome of re-ischaemia and heart failure events (OR 0.75, 95% CI 0.58 to 0.98). No significant heterogeneity was observed. Conclusions This meta-analysis suggests that adjunctive IABP use in high risk reperfusion therapy can improve long term survival.


Li Y.,Chongqing Medical University | Li Y.,University of Arizona | Marshall C.M.,University of Arizona | Rees H.C.,University of Arizona | And 3 more authors.
Journal of the International AIDS Society | Year: 2014

Introduction: To assess evidence of an association between intimate partner violence (IPV) and HIV infection among women. Methods: Medline/PubMed, Embase, Web of Science, EBSCO, Ovid, Cochrane HIV/AIDS Group's Specialized Register and Cochrane Central Register of Controlled Trials were searched up to 20 May 2013 to identify studies that examined the association between IPV and HIV infection in women. We included studies on women aged ≥15 years, in any form of sexually intimate relationship with a male partner. Results: Twenty-eight studies [(19 cross-sectional, 5 cohorts and 4 case-control studies) involving 331,468 individuals in 16 countries - the US (eight studies), South Africa (four studies), East Africa (10 studies), India (three studies), Brazil (one study) and multiple low-income countries (two studies)] were included. Results were pooled using RevMan 5.0. To moderate effect estimates, we analyzed all data using the random effects model, irrespective of heterogeneity level. Pooled results of cohort studies indicated that physical IPV [pooled RR (95% CI): 1.22 (1.01, 1.46)] and any type of IPV [pooled RR (95% CI): 1.28 (1.00, 1.64)] were significantly associated with HIV infection among women. Results of cross-sectional studies demonstrated significant associations of physical IPV with HIV infection among women [pooled OR (95% CI): 1.44 (1.10, 1.87)]. Similarly, results of crosssectional studies indicated that combination of physical and sexual IPV [pooled OR (95% CI): 2.00 (1.24, 3.22) and any type of IPV [pooled OR (95% CI): 1.41 (1.16, 1.73)] were significantly associated with HIV infection among women. Conclusions: Available evidence suggests a moderate statistically significant association between IPV and HIV infection among women. To further elucidate the strength of the association between IPV and HIV infection among women, there is a need for high-quality follow-up studies conducted in different geographical regions of the world, and among individuals of diverse racial/cultural backgrounds and varying levels of HIV risks. © 2014 Li Y et al; licensee International AIDS Society.


Chen G.-J.,Chongqing Medical University | Xiong Z.,State University of New York at Buffalo | Yan Z.,State University of New York at Buffalo
Molecular Neurodegeneration | Year: 2013

Background: Accumulation of β-amyloid (Aβ) and cholinergic deficiency are two prominent features of Alzheimer's disease (AD). To understand how Aβ-induced dysfunction of the nicotinic system may contribute to cognitive impairment in AD, we examined the effect of Aβ on nicotinic regulation of synaptic transmission and neuronal excitability in prefrontal cortex (PFC), a brain region critical for cognitive processes. Results: We found that activation of nicotinic acetylcholine receptors (nAChRs) with nicotine increased the inhibitory postsynaptic currents recorded in PFC pyramidal neurons, which was associated with the nicotine-induced increase in the excitability of PFC layer I GABAergic interneurons. Both effects of nicotine were disrupted by Aβ. However, Aβ did not impair nicotinic regulation of excitatory neurotransmission in PFC interneurons. The nicotinic effect on synaptic inhibition was also lost in transgenic mice with five familial Alzheimer's disease mutations. Inhibiting PKC attenuated nicotinic regulation of inhibitory, but not excitatory, neurotransmission. Conclusions: Our study suggests that Aβ selectively impairs nicotinic regulation of inhibitory inputs to PFC pyramidal neurons, which might be due to its interference with PKC activation. Thus, in the PFC circuits of AD, the balance between inhibition and excitation under the control of nAChRs may be disturbed by Aβ. © 2013 Chen et al.; licensee BioMed Central Ltd.


Xiong B.-H.,Chongqing Medical University | Cheng Y.,Chongqing Medical University | Ma L.,Chongqing Huaxi Hospital | Zhang C.-Q.,Chongqing Medical University
Cancer Investigation | Year: 2014

Patients with locally advanced gastric cancer (AGC) have a poor outcome. We performed an updated meta-analysis to assess the effect of neoadjuvant chemotherapy (NAC). By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC combined surgery versus surgery alone in advanced gastric and gastroesophageal cancer would be included. All calculations and statistical tests were performed. Twelve RCTs with a total of 1,820 patients were included. All patients had resectable gastric or gastroesophageal cancer and received NAC. NAC can slightly improve the survival rate "OR = 1.32, 95% confidence interval (CI): 1.07-1.64, P = 0.01", little, or no significant benefits were suggested in subgroup analyses between different population and regimens either. It can significantly improved the 3-year progression-free survival (PFS) "OR: 1.85 (1.39, 2.46), p < .0001", tumor down-staging rate "OR: 1.71 (1.26, 2.33), p = .0006" and R0 resection rate "OR: 1.38 (1.08, 1.78) p = .01" of patients with AGC. There were no difference between the two arms, in terms of relapse rates "OR: 1.03 (0.60, 1.78), p = 0.92", operative complications "OR: 1.20 (0.90, 1.58), p = 0.21", perioperative mortality "OR: 1.14 (0.64, 2.05), p = 0.65", and grade 3/4 adverse effects. NAC can significantly down-stage the tumor and improve R0 resection rate of patients with gastric and gastroesophageal cancer. It is safe and feasible, and can be tolerated. NAC can slightly improve the survival rate. It needs further prospective multinational multicenter RCTs to define the clinical benefits of NAC and the most effective strategies for gastric and gastroesophageal cancer. © 2014 Informa Healthcare USA, Inc.


Samanta D.,Johns Hopkins University | Gilkesa D.M.,Johns Hopkins University | Chaturvedia P.,Johns Hopkins University | Xiang L.,Johns Hopkins University | And 2 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Triple negative breast cancers (TNBCs) are defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 expression, and are treated with cytotoxic chemotherapy such as paclitaxel or gemcitabine, with a durable response rate of less than 20%. TNBCs are enriched for the basal subtype gene expression profile and the presence of breast cancer stem cells, which are endowed with self-renewing and tumor-initiating properties and resistance to chemotherapy. Hypoxia-inducible factors (HIFs) and their target gene products are highly active in TNBCs. Here, we demonstrate that HIF expression and transcriptional activity are induced by treatment of MDA-MB-231, SUM-149, and SUM-159, which are human TNBC cell lines, as well as MCF-7, which is an ER+/PR+ breast cancer line, with paclitaxel or gemcitabine. Chemotherapy-induced HIF activity enriched the breast cancer stem cell population through interleukin-6 and interleukin-8 signaling and increased expression of multidrug resistance1. Coadministration of HIF inhibitors overcame the resistance of breast cancer stem cells to paclitaxel or gemcitabine, both in vitro and in vivo, leading to tumor eradication. Increased expression of HIF-1α or HIF target genes in breast cancer biopsies was associated with decreased overall survival, particularly in patients with basal subtype tumors and those treated with chemotherapy alone. Based on these results, clinical trials are warranted to test whether treatment of patients with TNBC with a combination of cytotoxic chemotherapy and HIF inhibitors will improve patient survival. © 2014, National Academy of Sciences. All rights reserved.


Xiong B.,Chongqing Medical University | Xiong B.,Chongqing Huaxi Hospital | Ma L.,Chongqing Huaxi Hospital | Zhang C.,Chongqing Medical University
Surgical Oncology | Year: 2012

Background: Robotic gastrectomy (RG) for gastric cancer remains controversial. The main aim of this meta-analysis was to compare the safety and efficacy of robotic gastrectomy (RG) and conventional laparoscopic gastrectomy (LG) for gastric cancer. Methods: Literature searches of electronic databases (PubMed, Embase, Cochrane Library Ovid, and Web of Science databases) and manual searches up to December 30, 2011 were performed. Comparative clinical trials were eligible if they reported perioperative outcomes for RG and LG for gastric cancer. Fixed and random effects models were used. The RevMan 5.1 was used for pooled estimates. Results: Three NRCTs enrolling 918 patients (268 in the RG group and 650 in the LG group) were included in the meta-analysis. RG for gastric cancer was associated with a significantly longer operative time (WMD: 68.77, 95% CI: 35.09-102.45; P < 0.0001), but significantly less intraoperative blood loss (WMD: -41.88, 95% CI: -71.62 to -12.14; P = 0.006). We found no significant differences in the number of lymph nodes (WMD: -0.71, 95% CI: -6.78 to 5.36; P = 0.82), overall morbidity (WMD: 0.74, 95% CI: 0.47 to 1.16; P = 0.19), perioperative mortality rates (WMD: 1.80, 95% CI: 0.30 to 10.89; P = 0.52) and length of hospital stay (WMD: 0.42, 95% CI: -1.87 to 0.79; P = 0.42) between the two groups. Conclusions: It may be concluded that RG is a safe and effective alternative to LG and is justifiable under the setting of clinical trials. Additional RCTs that compare RG and LG and investigate the long-term oncological outcomes are required to determine potential advantages or disadvantages of RG. © 2012 Elsevier Ltd. All rights reserved.


Xiang L.,Chongqing Medical University | Xiang L.,Johns Hopkins University | Gilkes D.M.,Johns Hopkins University | Hu H.,Johns Hopkins University | And 4 more authors.
Oncotarget | Year: 2015

Hypoxia-inducible factor 1a (HIF-1α) expression is a hallmark of intratumoral hypoxia that is associated with breast cancer metastasis and patient mortality. Previously, we demonstrated that HIF-1 stimulates the expression and activity of TAZ, which is a transcriptional effector of the Hippo signaling pathway, by increasing TAZ synthesis and nuclear localization. Here, we report that direct protein-protein interaction between HIF-1α and TAZ has reciprocal effects: HIF-1α stimulates transactivation mediated by TAZ and TAZ stimulates transactivation mediated by HIF-1α. Inhibition of TAZ expression impairs the hypoxic induction of HIF-1 target genes, such as PDK1, LDHA, BNIP3 and P4HA2 in response to hypoxia, whereas inhibition of HIF-1α expression impairs TAZ-mediated transactivation of the CTGF promoter. Taken together, these results complement our previous findings and establish bidirectional crosstalk between HIF-1α and TAZ that increases their transcriptional activities in hypoxic cells.


Xiong B.,Chongqing Medical University | Cheng Y.,Chongqing Medical University | Ma L.,Chongqing Huaxi Hospital | Zhang C.,Chongqing Medical University
International Journal of Oncology | Year: 2013

The aim of this study was to determine a role of microRNA-21 (miR-21) in colorectal cancer (CRC) and to elucidate the regulation of phosphatase and tensin homologue (PTEN) gene by miR-21. MiR-21 expression was investigated in 30 CRC samples and five CRC cell lines. In this study, we show that the expression of miR-21 was overexpressed in CRC compared with adenomas and normal tissues. Patients with poor differentiation, lymph node metastasis and advanced TNM stage showed significantly high expression of miR-21. Inhibition of miR-21 in the HCT116 cell line reduced cellular proliferation, migration and invasion, induced apoptosis and inhibited cell cycle progression. The PTEN protein levels in CRC tissues and cells had an inverse correlation with miR-21 expression. Anti-miR-21-transfected cells increased PTEN protein expression without changing the PTEN mRNA level and increased a luciferase-reporter activity. MiR-21 targets PTEN at the post-transcriptional level and regulates cell proliferation and invasion in CRC. It may serve as a novel therapeutic target in CRC.


Xiong B.,Chongqing Medical University | Ma L.,Chongqing Huaxi Hospital | Cheng Y.,Chongqing Medical University | Zhang C.,Chongqing Medical University
European Journal of Surgical Oncology | Year: 2014

Abstract Aims To assess the efficacy and safety of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC). Methods By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC-combined surgery versus surgery alone in AGC were included. All calculations and statistical tests were performed using RevMan 5.0 software. Results 12 RCTs with a total of 1820 patients were included. All patients had locally advanced but resectable gastric cancer and received NAC. NAC can slightly improve the survival rate (OR = 1.32, 95% confidence interval (CI): 1.07-1.64, P = 0.01), with little or no significant benefits in subgroup analyses between either different population or regimens. NAC can significantly improve the 3-year progression-free survival (PFS) (OR: 1.85, 95% CI: 1.39-2.46, p < 0.0001), tumor down-staging rate (OR: 1.71, 95% CI: 1.26, 2.33, p = 0.0006) and R0 resection rate (OR: 1.38, 95% CI: 1.08-1.78, P = 0.01) of patients with AGC. There was no difference between the two arms, in terms of relapse rates (OR: 1.03, 95% CI: 0.60-1.78, p = 0.92), operative complications (OR: 1.20, 95% CI: 0.90-1.58, p = 0.21), perioperative mortality (OR: 1.14, 95% CI: 0.64-2.05, p = 0.65) and grade 3/4 adverse effects: gastrointestinal problem (OR: 0.57, 95% CI: 0.25-1.30, p = 0.18), leukopenia (OR: 0.88, 95% CI: 0.41-1.91, p = 0.75), thrombocytopenia (OR: 1.27, 95% CI: 0.27-5.93, p = 0.76). Conclusion NAC is effective and safe. However, further prospective multi-national and multi-center RCTs are still needed in order to investigate the long-term oncological and functional outcomes to define the clinical benefits of NAC and the most effective strategies for AGC. © 2014 Elsevier Ltd. All rights reserved.


Xiong B.,Chongqing Medical University | Ma L.,Chongqing Huaxi Hospital | Zhang C.,Chongqing Medical University | Cheng Y.,Chongqing Medical University
Journal of Surgical Research | Year: 2014

Background Robotic surgery has been used successfully in many branches of surgery; but there is little evidence in the literature on its use in rectal cancer (RC). We conducted this meta-analysis that included randomized controlled trials and nonrandomized controlled trials of robotic total mesorectal excision (RTME) versus laparoscopic total mesorectal excision (LTME) to evaluate whether the safety and efficacy of RTME in patients with RC are equivalent to those of LTME. Materials and methods Pubmed, Embase, Cochrane Library, Ovid, and Web of Science databases were searched. Studies clearly documenting a comparison of RTME with LTME for RC were selected. Operative and recovery outcomes, early postoperative morbidity, and oncological parameters were evaluated. Results Eight studies were identified that included 1229 patients in total, 554 (45.08%) in the RTME and 675 (54.92%) in the LTME. Meta-analysis suggested that the conversion rate to open surgery in RTME was significantly lower than in LTME (P = 0.0004). There were no significant differences in operation time, estimated blood loss, recovery outcome, postoperative morbidity and mortality, length of hospital stay, and the oncological accuracy of resection and local recurrence between the two groups. The positive rate of circumferential resection margins (P = 0.04) and the incidence of erectile dysfunction (P = 0.002) were lower in RTME compared with LTME. Conclusions RTME for RC is safe and feasible, and the short- and medium-term oncological and functional outcomes are equivalent or preferable to LTME. It may be an alternative treatment for RC. More multicenter randomized controlled trials investigating the long-term oncological and functional outcomes are required to determine the advantages of RTME over LTME in RC. © 2014 Elsevier Inc. All rights reserved.


Liao K.,Chongqing Medical University | Wang H.,Chongqing Medical University | Chen Q.,Xinjiang Medical University | Wu Z.,Xi'an Jiaotong University | Zhang L.,Chongqing Medical University
Journal of Gastrointestinal Surgery | Year: 2014

Background: The use of prosthetic grafts for superior mesenteric-portal vein reconstruction (SMPVR) after pancreaticoduodenectomy (PD) with venous resection remains controversial. We evaluated the effectiveness and safety of using polytetrafluoroethylene (PTFE) interposition grafts for SMPVR after PD. Methods: We identified 76 patients who underwent PD with segmental vein resection for pancreatic head and periampullary neoplasms at three centers between January 2007 and June 2012. The venous reconstruction technique depended on the length of venous involvement. Forty-two and 34 patients underwent SMPVR with primary anastomosis and SMPVR with PTFE interposition grafts, respectively. The postoperative morbidity, mortality, and patency were compared. For the patients with pancreatic ductal adenocarcinoma (n = 65), survival was compared between the SMPVR with primary anastomosis (n = 36) and SMPVR with PTFE interposition graft groups (n = 29). Results: Patients undergoing SMPVR with PTFE grafts had larger tumor sizes (3.4 ± 0.9 cm, 2.9 ± 0.9 cm, P = 0.016), longer operative durations (492.9 ± 107.5 min, 408.8 ± 78.8 min, P < 0.001), and greater blood loss (986.8 ± 884.5 ml, 616.7 ± 485.5 ml, P = 0.040) compared to those undergoing SMPVR with primary anastomosis. However, 30-day postoperative morbidity and mortality did not differ (29.4 and 2.9 %, respectively, for PTFE grafts and 33.3 and 7.1 %, respectively, for primary anastomosis). There were no cases of graft infection. The estimated cumulative patency of SMPVR 6 and 12 months after surgery did not differ (87.9 and 83.5 % after PTFE grafts, respectively, and 94.4 and 86.4 % after primary anastomosis, respectively). For patients who underwent surgery for pancreatic ductal adenocarcinoma, there were no significant differences in the median survival time (11 vs. 12 months) or the 1-, 2-, and 3-year survival rates (35.7, 12.5, and 4.2 vs. 36.4, 17.3, and 8.7 %, respectively) for the PTFE and primary anastomosis groups. Conclusions: PTFE grafts could provide a safe and effective option for venous reconstruction after PD in patients with segmental vein resection. © 2014 The Society for Surgery of the Alimentary Tract.


Liu Q.,University of Illinois at Springfield | Liu Q.,Chongqing Medical University | Huang J.,University of Illinois at Springfield | Huang J.,University of Mississippi Medical Center | And 8 more authors.
Nucleic Acids Research | Year: 2013

Protein-coding genes account for only a small part of the human genome, whereas the vast majority of transcripts make up the non-coding RNAs including long non-coding RNAs (lncRNAs). Accumulating evidence indicates that lncRNAs could play a critical role in regulation of cellular processes such as cell growth and apoptosis as well as cancer progression and metastasis. LncRNA loc285194 was previously shown to be within a tumor suppressor unit in osteosarcoma and to suppress tumor cell growth. However, it is unknown regarding the regulation of loc285194. Moreover, the underlying mechanism by which loc285194 functions as a potential tumor suppressor is elusive. In this study, we show that loc285194 is a p53 transcription target; ectopic expression of loc285194 inhibits tumor cell growth both in vitro and in vivo. Through deletion analysis, we identify an active region responsible for tumor cell growth inhibition within exon 4, which harbors two miR-211 binding sites. Importantly, this loc285194-mediated growth inhibition is in part due to specific suppression of miR-211. We further demonstrate a reciprocal repression between loc285194 and miR-211; in contrast to loc285194, miR-211 promotes cell growth. Finally, we detect downregulation of loc285194 in colon cancer specimens by quantitative PCR arrays and in situ hybridization of tissue microarrays. Together, these results suggest that loc285194 is a p53-regulated tumor suppressor, which acts in part through repression of miR-211. © 2013 The Author(s).


Cheng X.,Chongqing Medical University | Wu J.,Chongqing Medical University | Geng M.,Chinese PLA General Hospital | Xiong J.,Chongqing Medical University
Neurobiology of Aging | Year: 2014

Alzheimer's disease (AD) is the most common form of dementia. Accumulation of amyloid-beta (Aβ) peptides is regarded as the critical component associated with AD pathogenesis, which is derived from the amyloid precursor protein (APP) cleavage. Recent studies suggest that synaptic activity is one of the most important factors that regulate Aβ levels. It has been found that synaptic activity facilitates APP internalization and influences APP cleavage. Glutamatergic, cholinergic, serotonergic, leptin, adrenergic, orexin, and gamma-amino butyric acid receptors, as well as the activity-regulated cytoskeleton-associated protein (Arc) are all involved in these processes. The present review summarizes the evidence for synaptic activity-modulated Aβ levels and the mechanisms underlying this regulation. Interestingly, the immediate early gene product Arc may also be the downstream signaling molecule of several receptors in the synaptic activity-modulated Aβ levels. Elucidating how Aβ levels are regulated by synaptic activity may provide new insights in both the understanding of the pathogenesis of AD and in the development of therapies to slow down the progression of AD. © 2014 Elsevier Inc.


Zeng Y.-Q.,Kunming Medical University | Wang Y.-J.,Chongqing Medical University | Zhou X.-F.,Kunming Medical University | Zhou X.-F.,University of South Australia
Frontiers in Neurology | Year: 2014

Background: Alzheimer's disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The clearance of Aß from the brain and anti-inflammation are potential important strategies to prevent and treat disease. In a previous study, we demonstrated the grape seed extract (GSE) could reduce brain Aß burden and microglia activation, but which polyphenol plays a major role in these events is not known. Here, we tested pharmacological effects of (-)epicatechin, one principle polyphenol compound in GSE, on transgenic AD mice. Methods: APP/PS1 transgenic mice were fed with (-)epicatechin diet (40 mg/kg/day) and curcumin diet (47 mg/kg/day) at 3 months of age for 9 months, the function of liver, Aß levels in the brain and serum, AD-type neuropathology, plasma levels of inflammatory cytokines were measured. Results: Toward the end of the experiment, we found long-term feeding of (-)epicatechin diet was well tolerated without fatality, changes in food consumption, body weight, or liver function. (-)Epicatechin significantly reduced total Aß in brain and serum by 39 and 40%, respectively, compared with control diet. Microgliosis and astrocytosis in the brain of Alzheimer's mice were also reduced by 38 and 35%, respectively. The (-)epicatechin diet did not alter learning and memory behaviors in AD mice. Conclusion: This study has provided evidence on the beneficial role of (-)epicatechin in ameliorating amyloid-induced AD-like pathology in AD mice, but the impact of (-)epicatechin on tau pathology is not clear, also the mechanism needs further research. © 2014 Zeng, Wang and Zhou.


Li A.,Chongqing University of Technology | Wang J.,Chongqing University of Technology | Wu M.,Chongqing Medical University | Zhang X.,Chongqing University of Technology | Zhang H.,Chongqing University of Technology
European Journal of Pharmacology | Year: 2015

Proliferation of hepatic stellate cells (HSCs) is vital for the development of fibrosis during liver injury. In this study, we describe that arctigenin (ATG), a major bioactive component of Fructus Arctii, exhibited selective cytotoxic activity via inhibiting platelet-derived growth factor-BB (PDGF-BB)-activated HSCs proliferation and arrested cell cycle at G0/G1 phase, which could not be observed in normal human hepatocytes in vitro. The cyclin-dependent kinase (CDK) 4/6 activities could be strongly inhibited by ATG through down-regulation of cyclin D1 and CDK4/6 expression in early G1 phase arrest. In the ATG-treated HSCs, the expression level of p27Kip1 and the formation of CDK2-p27Kip1 complex were also increased. p27Kip1 silencing significantly attenuated the effect of ATG, including cell cycle arrest and suppression of proliferation in activated HSCs. We also found that ATG suppressed PDGF-BB-induced phosphorylation of Akt and its downstream transcription factor Forkhead box O 3a (FOXO3a), decreased binding of FOXO3a to 14-3-3 protein, and stimulated nuclear translocation of FOXO3a in activated HSCs. Furthermore, knockdown of FOXO3a expression by FOXO3a siRNA attenuated ATG-induced up-regulation of p27Kip1 in activated HSCs. All the above findings suggested that ATG could increase the levels of p27Kip1 protein through inhibition of Akt and improvement of FOXO3a activity, in turn inhibited the CDK2 kinase activity, and eventually caused an overall inhibition of HSCs proliferation. © 2014 Elsevier B.V. All rights reserved.


Du X.,Chongqing Medical University | Xie Y.,Chongqing Medical University | Xian C.J.,University of South Australia | Chen L.,Chongqing Medical University
Journal of Cellular Physiology | Year: 2012

Fibroblast growth factor (FGF)/FGF (FGFR) signaling is an important pathway involved in skeletal development. Missense mutations in FGFs and FGFRs were found clinically to cause multiple congenital skeleton diseases including chondrodysplasia, craniosynostosis, syndromes with dysregulated phosphate metabolism. FGFs/FGFRs also have crucial roles in bone fracture repair and bone regeneration. Understanding the molecular mechanisms for the role of FGFs/FGFRs in the regulation of skeletal development, genetic skeletal diseases, and fracture healing will ultimately lead to better treatment of skeleton diseases caused by mutations of FGFs/FGFRs and fracture. This review summarizes the major findings on the role of FGF signaling in skeletal development, genetic skeletal diseases and bone healing, and discusses issues that remain to be resolved in applying FGF signaling-related measures to promote bone healing. This review has also provided a perspective view on future work for exploring the roles and action mechanisms of FGF signaling in skeletal development, genetic skeletal diseases, and fracture healing. © 2012 Wiley Periodicals, Inc.


Zhang L.,PLA Fourth Military Medical University | Yang X.-Q.,Chinese PLA General Hospital | Cheng J.,Chongqing Medical University | Hui R.-S.,Chongqing Medical University | Gao T.-W.,PLA Fourth Military Medical University
Clinical Immunology | Year: 2010

Both T-helper 17 cells (Th17) and CD4+CD25+ regulatory T cells (Treg) play important roles in the pathogenesis of psoriasis. However, the relationship between Th17 and Treg cells and their dynamic variations in psoriasis remain unclear. In this study, we found that both Th17 and FoxP3+ Treg cells were increased in psoriasis patients both in the peripheral circulation and skin tissue lesions and were positively correlated with disease severity. The ratio of Th17 to Treg cells in skin tissue lesions was inversely correlated with PASI scores, while it was positively correlated with PASI scores in the circulation. IL-17 secretion by CD4+ T cells was not regulated by Treg cells, even though Treg cells exhibited significant inhibition on CD4+ T cells proliferation and IFN-γ production. These findings provide new information regarding the association between Th17 and Treg cells, which will further our understanding of the pathogenesis of psoriasis. © 2009 Elsevier Inc. All rights reserved.


Liu Y.,Chongqing Medical University | Zhao T.,PLA Fourth Military Medical University | Yang Z.,Chongqing Medical University | Li Q.,Chongqing Medical University
International Journal of Experimental Pathology | Year: 2014

Summary: There is accumulating evidence which demonstrates that chronic cerebral ischaemia can induce white matter lesions (WMLs), and microglia-activation-mediated cytokines and proteases releasing during the ischaemia might play a vital role in pathogenesis. In addition, hypoxia-induced upregulated expression of fractalkine promotes the activation of microglia and their migration to the lesions through interaction with its receptor CX3CR1. However, the specific mechanisms involved in fractalkine/CX3CR1-mediated microglial activation have not been fully identified. In the present study, we constructed lentivirus encoding shRNA against CX3CR1 and transduced into microglial cells in under hypoxic conditions. Moreover, we analysed the proliferation, cytokine secretion and signal-pathway activation of the microglia. We found that CX3CR1 RNAi-mediated gene downregulation could attenuate hypoxic-induced microglial proliferation, cytokine secretion [including tumuor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)] and matrix metalloproteinase-2 (MMP-2) synthesis. These effects were shown to be nediated through p38MAPK/PKC activation. Therefore, our results reveal a novel mechanism of fractalkine/CX3CR1 involvement in activation of microglia. Thus CX3CR1 RNAi might provide a therapeutic strategy which could be useful in chronic cerebral ischaemia. © 2014 International Journal of Experimental Pathology.


Yang B.,Chongqing Medical University | Guo H.,Chongqing Medical University | Zhang Y.,Chongqing Medical University | Zhang Y.,Chengdu Military General Hospital | And 3 more authors.
PLoS ONE | Year: 2011

Chondrogenic differentiation of mesenchymal stem cells (MSCs) is accurately regulated by essential transcription factors and signaling cascades. However, the precise mechanisms involved in this process still remain to be defined. MicroRNAs (miRNAs) regulate various biological processes by binding target mRNA to attenuate protein synthesis. To investigate the mechanisms for miRNAs-mediated regulation of chondrogenic differentiation, we identified that miR-145 was decreased during transforming growth factor beta 3 (TGF-β3)-induced chondrogenic differentiation of murine MSCs. Subsequently, dual-luciferase reporter gene assay data demonstrated that miR-145 targets a putative binding site in the 3′-UTR of SRY-related high mobility group-Box gene 9 (Sox9) gene, the key transcription factor for chondrogenesis. In addition, over-expression of miR-145 decreased expression of Sox9 only at protein levels and miR-145 inhibition significantly elevated Sox9 protein levels. Furthermore, over-expression of miR-145 decreased mRNA levels for three chondrogenic marker genes, type II collagen (Col2a1), aggrecan (Agc1), cartilage oligomeric matrix protein (COMP), type IX collagen (Col9a2) and type XI collagen (Col11a1) in C3H10T1/2 cells induced by TGF-β3, whereas anti-miR-145 inhibitor increased the expression of these chondrogenic marker genes. Thus, our studies demonstrated that miR-145 is a key negative regulator of chondrogenic differentiation by directly targeting Sox9 at early stage of chondrogenic differentiation. © 2011 Yang et al.


Yang Z.,Chongqing Medical University | Zhao T.,PLA Fourth Military Medical University | Zou Y.,Chongqing Medical University | Zhang J.H.,Chongqing Medical University | Feng H.,Chongqing Medical University
Immunology Letters | Year: 2014

Much evidence demonstrates that microglia mediated neuroinflammation is an important contributor to the inflammatory injury in intracerebral hemorrhage (ICH). Therefore, the compounds that can inhibit neuroinflammation are greatly needed. In the current study, we examined whether curcumin, present in a Chinese medicinal plant, could prevent ICH induced microglia activation and confer protection against neurotoxicity.The cytokines of microglia were measured by ELISA, p38MAPK/PKC and NF-κB were measured by Western blot and EMSA. Microglial toxicity was assessed using MTT and FACS assays. And neurological function was evaluated by animal behavioristics. We found that curcumin prevented ICH-induced inflammatory molecules through NF-κB activation via the p38MAPK/PKC pathway in vitro. In addition, curcumin protected hippocampal HT22 cells from indirect toxicity mediated by ICH-treated microglia cells. Further, curcumin also attenuated ICH-induced neurological deficit and cerebral water content in vivo. Together, our findings suggest that curcumin could suppress ICH induced inflammatory injury and represent a novel herbal sources for ICH therapeutical strategy. © 2014 Elsevier B.V.


Wang Y.,Baylor College of Medicine | Wang Y.,Chongqing Medical University | Liang A.,Baylor College of Medicine | Luo J.,Baylor College of Medicine | And 5 more authors.
Journal of the American Society of Nephrology | Year: 2014

Neointima formation causes the failure of 60% of arteriovenous fistulas (AVFs) within 2 years. Neointimaforming mechanisms are controversial but possibly linked to excess proinflammatory responses and dysregulated Notch signaling. To identify howAVFs fail, we anastomosed the carotid artery to the internal jugular vein in normal and uremic mice and compared these findings with those in failedAVFs frompatients with ESRD. Endothelial cells (ECs) of AVFs in uremic mice or patients expressed mesenchymal markers (FSP-1 and/or a-SMA) and exhibited increased expression and nuclear localization of Notch intracellular domain compared with ECs of AVFs in pair-fed control mice. Furthermore, expression of VE-Cadherin decreased, whereas expression of Notch1 and -4, Notch ligands, the downstream transcription factor of Notch, RBP-Jk, and Notch target genes increased in ECs of AVFs in uremic mice. In cultured ECs, ectopic expression of Notch ligand or treatment with TGF-ß1 triggered the expression of mesenchymal markers and induced endothelial cell barrier dysfunction, both of whichwere blocked by Notch inhibition or RBP-Jκ knockout. Furthermore, Notch-induced defects in barrier function, invasion of inflammatory cells, and neointima formation were suppressed in mice with heterozygous knockdown of endothelial-specific RBP-Jk. These results suggest that increased TGF-ß1, a complication of uremia, activates Notch in endothelial cells of AVFs, leading to accelerated neointima formation and AVF failure. Suppression of Notch activation could be a strategy for improving AFV function in uremia. Copyright © 2014 by the American Society of Nephrolog.


Yang Z.,Chongqing Medical University | Zhao T.-Z.,PLA Fourth Military Medical University | Zou Y.-J.,Chongqing Medical University | Zhang J.H.,Chongqing Medical University | Feng H.,Chongqing Medical University
PLoS ONE | Year: 2014

As phagocytic cells of central nervous system, excessive activation or cell death of microglia is involved in a lot of nervous system injury and degenerative disease, such as stroke, epilepsy, Parkinson's disease, Alzheimer's disease. Accumulating evidence indicates that hypoxia upregulates HIF-1a expression leading to cell death of microglia. However, the exact mechanism of cell death induced by hypoxia in microglia is not clear. In the current study, we showed that hypoxia induced cell death and autophagy in microglia. The suppression of autophagy using either pharmacologic inhibitors (3-methyladenine, bafilomycin A1) or RNA interference in essential autophagy genes (BECN1 and ATG5) decreased the cell death induced by hypoxia in microglia cells. Moreover, the suppression of HIF-1α using either pharmacologic inhibitors (3-MA, Baf A1) or RNA interference decreased the microglia death and autophagy in vitro. Taken together, these data indicate that hypoxia contributes to autophagic cell death of microglia through HIF-1α, and provide novel therapeutic interventions for cerebral hypoxic diseases associated with microglia activation. © 2014 Yang et al.


Wu J.,PLA Fourth Military Medical University | Ru N.-Y.,PLA Fourth Military Medical University | Zhang Y.,PLA Fourth Military Medical University | Li Y.,PLA Fourth Military Medical University | And 5 more authors.
Oncogene | Year: 2011

Epithelial-mesenchymal transition (EMT) induced by transforming growth factor-Β (TGF-Β) is implicated in hepatocarcinogenesis and hepatocellular carcinoma (HCC) metastasis. HAb18G/CD147, which belongs to the CD147 family, is an HCC-associated antigen that has a crucial role in tumor invasion and metastasis. The goal of this study was to investigate the role of HAb18G/CD147 during EMT in hepatocarcinogenesis. Human normal hepatic cell lines QZG and L02, primary mouse hepatocytes and nude mouse models were used to determine the role of HAb18G/CD147 in EMT, and the involvement of the TGF-Β-driven pathway. A dual-luciferase reporter assay and ChIP were used to investigate the transcriptional regulation of the CD147 gene. Samples from patients with liver disease were assessed to determine the relationship between HAb18G/CD147 and typical markers for EMT. Our results show that upregulation of HAb18G/CD147 is induced by TGF-Β coupled with downregulation of E-cadherin and upregulation of N-cadherin and vimentin. The expression of HAb18G/CD147 is controlled by the cell survival PI3K/Akt/GSK3Β signaling pathway, and is directly regulated by the transcription factor Slug. Transfection of CD147 also induces an elevated expression of TGF-Β. CD147-transfected hepatocytes have mesenchymal phenotypes that accelerate tumor formation and tumor metastasis in vivo. Immunohistochemistry analysis shows a negative correlation between HAb18G/CD147 and E-cadherin expression (r s 0.3622, P0.0105), and a positive correlation between HAb18G/CD147 and Slug expression (r s 0.3064, P0.0323) in human HCC tissues. Our study uncovers a novel role of HAb18G/CD147 in mediating EMT in the process of HCC progression and showed that CD147 is a Slug target gene in the signaling cascade TGF-ΒPI3K/AktGSK3ΒSnailSlugCD147. Our results suggest that CD147 may be a potential target for the treatment and prevention of HCC. © 2011 Macmillan Publishers Limited All rights reserved.


Nam J.,Korea University | Huang H.,Chongqing Medical University | Lim H.,Korea University | Lim C.,Korea University | Shin S.,Korea University
Analytical Chemistry | Year: 2013

Malaria is a serious disease that threatens the public health, especially in developing countries. Various methods have been developed to separate malaria-infected red blood cells (i-RBCs) from blood samples for clinical diagnosis and biological and epidemiological research. In this study, we propose a simple and label-free method for separating not only late-stage but also early-stage i-RBCs on the basis of their paramagnetic characteristics due to the malaria byproduct, hemozoin, by using a magnetic field gradient. A polydimethylsiloxane (PDMS) microfluidic channel was fabricated and integrated with a ferromagnetic wire fixed on a glass slide. To evaluate the performance of the microfluidic device containing the ferromagnetic wire, lateral displacement of NaNO2-treated RBCs, which also have paramagnetic characteristics, was observed at various flow rates. The results showed excellent agreement with theoretically predicted values. The same device was applied to separate i-RBCs. Late-stage i-RBCs (trophozoites and schizonts), which contain optically visible black dots, were separated with a recovery rate of approximately 98.3%. In addition, using an optimal flow rate, early-stage (ring-stage) i-RBCs, which had been difficult to separate because of their low paramagnetic characteristics, were successfully separated with a recovery rate of 73%. The present technique, using permanent magnets and ferromagnetic wire in a microchannel, can effectively separate i-RBCs in various developmental stages so that it could provide a potential tool for studying the invasion mechanism of the malarial parasite, as well as performing antimalarial drug assays. © 2013 American Chemical Society.


Sun A.,Xinxiang University | Qi Q.,Chongqing Medical University | Qi Q.,The 371th Hospital of PLA | Wang X.,Xinxiang University | Bie P.,Chongqing Medical University
Biosensors and Bioelectronics | Year: 2014

For the first time, a sensitive electrochemical aptasensor for thrombin (TB) was developed by using porous platinum nanotubes (PtNTs) labeled with hemin/G-quadruplex and glucose dehydrogenase (GDH) as labels. Porous PtNTs with large surface area exhibited the peroxidase-like activity. Coupling with GDH and hemin/G-quadruplex as NADH oxidase and HRP-mimicking DNAzyme, the cascade signal amplification was achieved by the following ways: in the presence of glucose and NAD+ in the working buffer, GDH electrocatalyzed the oxidation of glucose with the production of NADH. Then, hemin/G-quadruplex as NADH oxidase catalyzed the oxidation of NADH to in situ generate H2O2. Based on the corporate electrocatalysis of PtNTs and hemin/G-quadruplex toward H2O2, the electrochemical signal was significantly amplified, allowing the detection limit of TB down to 0.15pM level. Moreover, the proposed strategy was simple because the intercalated hemin offered the readout signal, avoiding the adding of additional redox mediator as signal donator. Such an electrochemical aptasensor is highly promising for sensitive detection of other proteins in clinical diagnostics. © 2014 Elsevier B.V.


Hu J.,Fudan University | Qian G.-S.,Chongqing Medical University | Bai C.-X.,Fudan University | Bai C.-X.,Guangzhou University
Cancer | Year: 2015

The incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is the leading cause of cancer death in China, possibly because of the inadequate early diagnosis of lung cancer. Reaching a consensus on early diagnostic strategies for lung cancer in China is an unmet needed. Recently, much progress has been made in lung cancer diagnosis, such as screening in high-risk populations, the application of novel imaging technologies, and the use of minimally invasive techniques for diagnosis. However, systemic reviews of disease history, risk assessment, and patients' willingness to undergo invasive diagnostic procedures also need to be considered. A diagnostic strategy for lung cancer should be proposed and developed by a multidisciplinary group. A comprehensive evaluation of patient factors and clinical findings should be completed before treatment. © 2015 American Cancer Society.


Chen Y.,Chongqing Medical University | Chen Y.,Loma Linda University | Zhang Y.,Loma Linda University | Tang J.,Loma Linda University | And 5 more authors.
Stroke | Year: 2015

BACKGROUND AND PURPOSE - : Norrin and its receptor Frizzled-4 have important roles in the blood-brain barrier development. This study is to investigate a potential role and mechanism of Norrin/Frizzled-4 on protecting blood-brain barrier integrity after subarachnoid hemorrhage (SAH). METHODS - : One hundred and seventy-eight male Sprague-Dawley rats were used. SAH model was induced by endovascular perforation. Frizzled-4 small interfering RNA was injected intracerebroventricularly 48 hours before SAH. Norrin was administrated intracerebroventricularly 3 hours after SAH. SAH grade, neurological scores, brain water content, Evans blue extravasation, western blots, and immunofluorescence were used to study the mechanisms of Norrin and its receptor regulation protein TSPAN12, as well as neurological outcome. RESULTS - : Endogenous Norrin and TSPAN12 expression were increased after SAH, and Norrin was colocalized with astrocytes marker glial fibrillary acidic protein in cortex. Exogenous Norrin treatment significantly alleviated neurobehavioral dysfunction, reduced brain water content and Evans blue extravasation, promoted β-catenin nuclear translocation, and increased Occludin, VE-Cadherin, and ZO-1 expressions. These effects were abolished by Frizzled-4 small interfering RNA pretreated before SAH. CONCLUSIONS - : Norrin protected blood-brain barrier integrity and improved neurological outcome after SAH, and the action of Norrin appeared mediated by Frizzled-4 receptor activation, which promoted β-catenin nuclear translocation, which then enhanced Occludin, VE-Cadherin, and ZO-1 expression. Norrin might have potential to protect blood-brain barrier after SAH. © 2015 American Heart Association, Inc.


Guo Z.-D.,Chongqing Medical University | Sun X.-C.,Chongqing Medical University | Zhang J.H.,Loma Linda University
Acta Neurochirurgica, Supplementum | Year: 2011

Subarachnoid hemorrhage (SAH) is an important cause of death and disability worldwide. To date, there is not a definitive treatment that completely prevents brain injury after SAH. Recently, early brain injury (EBI) has been pointed out to be the primary cause of mortality in SAH patients. Apoptosis that occurs in neuronal tissues and cerebral vasculature after SAH plays an essential role in EBI. Matrix metalloproteinase 9 (MMP-9) has been found to increase in many cerebral vascular diseases. There have been reports that MMP-9 can mediate apoptosis, which called anoikis in cerebral ischemia models, through cleaving main components of the extracellular matrix (ECM), especially laminin. Therefore, minocycline, which has been found to inhibit MMP-9, may be protective to brain injury after SAH. We based our hypothesis on the fact that SAH possesses some aspects that are similar to those of cerebral ischemia. It is conceivable that MMP-9 may also be involved in the pathological process of EBI after SAH, and minocycline can relieve anoikis and improve EBI after SAH. © 2011 Springer-Verlag/Wien.


Mo Z.,Chongqing Medical University | Liu M.,Chongqing Medical University | Yang F.,Shenzhen Childrens Hospital | Luo H.,Chongqing Medical University | And 3 more authors.
Breast Cancer Research | Year: 2013

Introduction: Tamoxifen is widely used to treat hormone-dependent breast cancer, but its therapeutic benefit is limited by the development of drug resistance. Here, we investigated the role of estrogen G-protein coupled receptor 30 (GPR30) on Tamoxifen resistance in breast cancer.Methods: Primary tumors (PTs) of breast cancer and corresponding metastases (MTs) were used to evaluate the expression of GPR30 and epidermal growth factor receptor (EGFR) immunohistochemically. Tamoxifen-resistant (TAM-R) subclones derived from parent MCF-7 cells were used to investigate the role of GPR30 in the development of tamoxifen resistance, using MTT assay, western blot, RT-PCR, immunofluorescence, ELISA and flow cytometry. TAM-R xenografts were established to assess anti-tumor effects of combination therapy with GPR30 antagonist G15 plus 4-hydroxytamoxifen (Tam), using tumor volume measurement and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).Results: In 53 human breast cancer specimens, GPR30 expression in MTs increased compared to matched PTs; in MTs, the expression patterns of GPR30 and EGFR were closely related. Compared to parent MCF-7 cells, TAM-R cells had greater growth responses to 17β-estradiol (E2), GPR30 agonist G1 and Tam, and significantly higher activation of Mitogen-activated protein (MAP) kinases; but this increased activity was abolished by G15 or AG1478. In TAM-R cells, GPR30 cell-surface translocation facilitated crosstalk with EGFR, and reduced cAMP generation, attenuating inhibition of EGFR signaling. Combination therapy both promoted apoptosis in TAM-R cells and decreased drug-resistant tumor progression.Conclusions: Long-term endocrine treatment facilitates the translocation of GPR30 to cell surfaces, which interferes with the EGFR signaling pathway; GPR30 also attenuates the inhibition of MAP kinases. These factors contribute to tamoxifen resistance development in breast cancer. Combination therapy with GPR30 inhibitors and tamoxifen may provide a new therapeutic option for drug-resistant breast cancer. © 2013 Mo et al.; licensee BioMed Central Ltd.


Liu C.,Southwest University | Wu C.,Southwest University | Yang Q.,Southwest University | Gao J.,Chongqing Medical University | And 3 more authors.
Immunity | Year: 2016

Hemorrhagic stroke and brain microbleeds are caused by cerebrovascular ruptures. Fast repair of such ruptures is the most promising therapeutic approach. Due to a lack of high-resolution in vivo real-time studies, the dynamic cellular events involved in cerebrovascular repair remain unknown. Here, we have developed a cerebrovascular rupture system in zebrafish by using multi-photon laser, which generates a lesion with two endothelial ends. In vivo time-lapse imaging showed that a macrophage arrived at the lesion and extended filopodia or lamellipodia to physically adhere to both endothelial ends. This macrophage generated mechanical traction forces to pull the endothelial ends and facilitate their ligation, thus mediating the repair of the rupture. Both depolymerization of microfilaments and inhibition of phosphatidylinositide 3-kinase or Rac1 activity disrupted macrophage-endothelial adhesion and impaired cerebrovascular repair. Our study reveals a hitherto unexpected role for macrophages in mediating repair of cerebrovascular ruptures through direct physical adhesion and mechanical traction. Luo and colleagues reveal a hitherto unexpected role of macrophages in the repair of brain vascular ruptures. Once rupture of brain blood vessel occurs, macrophages come to mediate the repair of the rupture through direct physical adhesion to the breaking points and generation of mechanical traction forces. © 2016 Elsevier Inc.


Zhang Y.-Y.,Southwest University | Mi J.-L.,Peoples Hospital of Suining | Zhou C.-H.,Southwest University | Zhou X.-D.,Chongqing Medical University
European Journal of Medicinal Chemistry | Year: 2011

A series of novel fluconazoliums were synthesized and their bioactive evaluation as potential antibacterial and antifungal agents were described. Some target compounds displayed good and broad-spectrum antimicrobial activities with low MIC values ranging from 0.25 to 64 μg/mL against all the tested strains, including three Gram-positive bacteria (Staphylococcus aureus, MRSA and Bacillus subtilis), three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Bacillus proteus) as well as two fungi (Candida albicans and Aspergillus fumigatus). Among all tested title compounds, the octyl, dichlorobenzyl, naphthyl and naphthalimino derivatives gave comparable or even better antibacterial and antifungal efficiency in comparison with the reference drugs Fluconazole, Chloromycin and Norfloxacin. © 2011 Elsevier Masson SAS. All rights reserved.


Chen S.,Zhejiang University | Yang Q.,Chongqing Medical University | Chen G.,Soochow University of China | Zhang J.H.,Loma Linda University
Translational Stroke Research | Year: 2014

Intracerebral hemorrhage (ICH) is a common and severe neurological disorder, which is associated with high rates of mortality and morbidity. Despite extensive research into the pathology of ICH, there are still no clinically approved neuroprotective treatments. Currently, increasing evidence has shown that inflammatory responses participate in the pathophysiological processes of brain injury following ICH. In this editorial, we summarized some promising advances in the field of inflammation and ICH, which contained animal and human investigations; discussed the role of neuroinflammation, systemic inflammatory responses, and some potential targets; and focused on the challenges of translation between pre-clinical and clinical studies and potential anti-inflammatory therapeutic approaches after ICH. © 2014, Springer Science+Business Media New York.


Li Y.,Southwest University | Zhong Z.,Chongqing Medical University | Chai Y.,Southwest University | Song Z.,Southwest University | And 5 more authors.
Chemical Communications | Year: 2012

A novel strategy for simultaneous determination of three liver cancer biomarkers based on three redox labels with distinct voltammetric peaks was described. Gold nanoparticles coated carbon nanotubes were used as carriers to immobilize redox probes labeled antibodies and to amplify the signals. © 2012 The Royal Society of Chemistry.


Bai L.,Southwest University | Bai L.,Chongqing Medical University | Chai Y.,Southwest University | Pu X.,Chongqing Medical University | Yuan R.,Southwest University
Nanoscale | Year: 2014

Endotoxin, also known as lipopolysaccharide (LPS), is able to induce a strong immune response on its internalization into mammalian cells. To date, aptamer-based biosensors for LPS detection have been rarely reported. This work describes a new signal-on electrochemical aptasensor for the ultrasensitive detection of LPS by combining the three-way DNA hybridization process and nanotechnology-based amplification. With the help of DNA1 (associated with the concentration of target LPS), the capture probe hybridizes with DNA1 and the assistant probe to open its hairpin structure and form a ternary "Y" junction structure. The DNA1 can be released from the structure in the presence of nicking endonuclease to initiate the next hybridization process. Then a great deal of cleaved capture probe produced in the cyclic process can bind with DNA2-nanocomposite, which contains the electroactive toluidine blue (Tb) with the amplification materials graphene (Gra) and gold nanoparticles (AuNPs). Thus, an enhanced electrochemical signal can be easily read out. With the cascade signal amplification, this newly designed protocol provides an ultrasensitive electrochemical detection of LPS down to the femtogram level (8.7 fg mL -1) with a linear range of 6 orders of magnitude (from 10 fg mL -1 to 50 ng mL-1). Moreover, the high sensitivity and specificity make this method versatile for the detection of other biomolecules by changing the corresponding sequences of the capture probe and the assistant probe. © 2014 The Royal Society of Chemistry.


Fang B.,Southwest University | Zhou C.-H.,Southwest University | Rao X.-C.,Chongqing Medical University
European Journal of Medicinal Chemistry | Year: 2010

A series of novel amine-derived bis-azole compounds were designed by the systematical structural modification of Fluconazole and synthesized by a convenient and efficient method, and the antimicrobial activities for all prepared compounds were evaluated in vitro against six representative bacterial strains and two fungal strains. Bioactive results indicated that some synthesized compounds exhibited moderate or even better activities in comparison with the reference drugs. Especially, bis-imidazole 5b and its salts gave significant antibacterial efficacy against all tested bacteria strains including MRSA, while bis-triazoles 4b-c and their corresponding salts exhibited better activities against Candida albicans, Bacillus proteus than standard drugs Fluconazole and Norfloxacin respectively. Unexpectedly, bis-bromides 3a-f presented excellent activities against all tested microbial strains. A series of novel amine-derived bis-azoles were synthesized and evaluated for antibacterial and antifungal activities. Some synthesized compounds exhibited better antibacterial and antifungal efficacy than clinical drugs Fluconazole, Norfloxacin and Chloramphenicol. © 2010 Elsevier Masson SAS. All rights reserved.


He Z.,Loma Linda University | He Z.,Chongqing Medical University | Ostrowski R.P.,Loma Linda University | Sun X.,Chongqing Medical University | And 4 more authors.
Stroke | Year: 2012

Background and Purpose-: Endoplasmic reticulum stress triggers apoptotic cascades in neurons of the central nervous system after subarachnoid hemorrhage. The aim of this work was to study the mechanism of neuroprotection conferred by targeting cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the acute brain injury following subarachnoid hemorrhage. Methods-: A total of 172 rats were used. Endovascular perforation induced subarachnoid hemorrhage. Two small interfering RNAs for CHOP were injected 24 hours before hemorrhage induction. At 24 or 72 hours, rats were neurologically evaluated and euthanized. The brains were recovered for molecular biology and histology studies. Results-: Western blot analysis revealed effective silencing of CHOP associated with suppression of Bim-Caspase-3 apoptotic pathway. Moreover, the antiapoptotic Bcl2 was found upregulated with CHOP siRNA treatment. A reduced number of TUNEL-positive cells in the subcortex and in the hippocampus reflected histological protection. CHOP siRNA treatment ameliorated intracranial sequelae of and improved functional performance. Conclusions-: We conclude that CHOP silencing alleviates early brain injury following subarachnoid hemorrhage via inhibiting apoptosis and that CHOP siRNA treatment has a clinical potential for patients with this type of hemorrhagic stroke. © 2011 American Heart Association, Inc.


Lei B.,Chongqing Medical University | Lei B.,University of Missouri
PLoS ONE | Year: 2012

Purpose: The rodent retina does not exhibit a positive OFF-response in the electroretinogram (ERG), which makes it difficult to evaluate its OFF-pathway functions in vivo. We studied the rod-driven OFF pathway responses by using a dark-adapted 10-Hz flicker ERG procedure in mouse. Materials and Methods: Conventional ERGs and 10-Hz dark-adapted flicker ERGs were obtained in wild-type mice (C57BL/6), in mice with pure rod (cpfl1) or pure cone (rho-/-) function, and in nob1 mice which have a selective ON-pathway defect. To isolate the response from ON or OFF pathway, glutamate analogs 2-amino-4-phosphobutyric acid (APB, an ON pathway blocker) and cis-2, 3-piperidine-dicarboxylic acid (PDA, an OFF pathway blocker), were injected intravitreally. Results: The amplitude-intensity profile of the dark-adapted 10-Hz flicker ERG in the wild-type mice exhibits two peaks at middle and high light intensities. The two peaks represent rod- and cone-driven responses respectively. In APB-treated C57BL/6 mice and in nob1 mice, the dark-adapted ERG b-waves were absent. However, both rod- and cone-driven OFF pathway responses were evident with flicker ERG recording. At middle light intensities that activate only rod system, the flicker ERG responses in saline-injected nob1 mice were similar to those in APB-injected cpfl1 mice and wild-type mice. These responses are sensitive to PDA. The amplitudes of these rod-driven OFF pathway responses were approximately 20% of the total rod-driven flicker ERG responses. Conclusion: We demonstrate that the rod-OFF bipolar cell pathway is functional in the outer retina. The dark-adapted flicker ERG is practical for the evaluation of rod- and cone-driven responses, and the residual OFF pathway signals in subjects with ON pathway defects. © 2012 Bo Lei.


Pu W.,Chongqing Medical University | Zhao H.,Chongqing Medical University | Huang C.,Southwest University | Wu L.,Chongqing Medical University | And 2 more authors.
Analytica Chimica Acta | Year: 2013

A simple, cost-effective and rapid method for visual detection of arginine based on the citrate-capped gold nanoparticles (AuNPs) aggregation has been developed in this paper. Arginine is the only amino acid with guanidino group, and has the highest isoelectric point (pI) at about 10.8. At pH 9.62, negatively charged citrate-capped AuNPs are well dispersed because of strong electrostatic repulsion. However, positively charged arginine (pH


Ristagno G.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Li Y.,Chongqing Medical University | Fumagalli F.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Finzi A.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Quan W.,ZOLL Medical Corporation
Resuscitation | Year: 2013

Introduction: The capability of amplitude spectrum area (AMSA) to predict the success of defibrillation (DF) was retrospectively evaluated in a large database of out-of-hospital cardiac arrests. Methods: Electrocardiographic data, including 1260 DFs, were obtained from 609 cardiac arrest patients due to ventricular fibrillation. AMSA sensitivity, specificity, accuracy, and positive and negative predictive values (PPV, NPV) for predicting DF success were calculated, together with receiver operating characteristic (ROC) curves. Successful DF was defined as the presence of spontaneous rhythm ≥40. bpm starting within 60. s from the DF. In 303 patients with chest compression (CC) depth data collected with an accelerometer, changes in AMSA were analyzed in relationship to CC depth. Results: AMSA was significantly higher prior to a successful DF than prior to an unsuccessful DF (15.6. ±. 0.6 vs. 7.97. ±. 0.2. mV-Hz, p<. 0.0001). Intersection of sensitivity, specificity and accuracy curves identified a threshold AMSA of 10. mV-Hz to predict DF success with a balanced sensitivity, specificity and accuracy of almost 80%. Higher AMSA thresholds were associated with further increases in accuracy, specificity and PPV. AMSA of 17. mV-Hz predicted DF success in two third of instances (PPV of 67%). Low AMSA, instead, predicted unsuccessful DFs with high sensitivity and NPV >97%. Area under the ROC curve was 0.84. CC depth affected AMSA value. When depth was <1.75. in., AMSA decreased for consecutive DFs, while it increased when the depth was >1.75. in. (p<. 0.05). Conclusions: AMSA could be a useful tool to guide CPR interventions and predict the optimal timing of DF. © 2013 Elsevier Ireland Ltd.


Liu Y.,Southwest University | Liu Y.,Chongqing Medical University | Huang C.Z.,Southwest University
ACS Nano | Year: 2013

A comprehensive understanding of the growth mechanism of nanoalloys is beneficial in designing and synthesizing nanoalloys with precisely tailored properties to extend their applications. Herein, we present the investigation in this aspect by real-time monitoring of the in situ growth of single Ag@Hg nanoalloys, through direct amalgamation of Ag nanoparticles with elemental mercury, by dark-field scattering microscopy. Four typically shaped Ag nanoparticles, such as rods, triangular bipyramids, cubes, and spheres, were used as seeds for studying the growth of Ag@Hg nanoalloys. The scattered light of Ag nanoparticles of different shapes, on exposure to the growth solution, exhibited a noticeable blue-shift followed by a red-shift, suggesting the growth of Ag@Hg nanoalloys. The formation of Ag@Hg nanoalloys was confirmed by scanning electron microscopy, high-resolution transmit electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and elemental mapping and line scanning. Further analysis of the time-dependent spectral data and morphological change of single nanoparticles during the growth led to the visual identification of the growth mechanism of single Ag@Hg nanoalloys. Three important steps were involved: first, rapid adsorption of Hg atoms onto Ag nanoparticles; second, initial diffusion of Hg atoms into Ag nanoparticles, rounding or shortening the particles; third, further diffusion of Hg atoms leading to the formation of spherical Ag@Hg nanoalloys. On the basis of these results, Ag@Hg nanoalloys with given optical properties can be synthesized. Moreover, dark-field scattering microscopy is expected to be a powerful tool used for real-time monitoring of the in situ growth of other metal nanoparticles. © 2013 American Chemical Society.


Ma Q.,Loma Linda University | Chen S.,Loma Linda University | Chen S.,Zhejiang University | Hu Q.,Loma Linda University | And 4 more authors.
Annals of Neurology | Year: 2014

Objective The NLRP3 (NALP3, cryopyrin) inflammasome, a key component of the innate immune system, facilitates caspase-1 and interleukin (IL)-1β processing, which amplifies the inflammatory response. Here, we investigated whether NLRP3 knockdown decreases neutrophil infiltration, reduces brain edema, and improves neurological function in an intracerebral hemorrhage (ICH) mouse model. We also determined whether mitochondrial reactive oxygen species (ROS) governed by mitochondrial permeability transition pores (mPTPs) would trigger NLRP3 inflammasome activation following ICH. Methods ICH was induced by injecting autologous arterial blood (30μl) into a mouse brain. NLRP3 small interfering RNAs were administered 24 hours before ICH. A mPTP inhibitor (TRO-19622) or a specific mitochondria ROS scavenger (Mito-TEMPO) was coinjected with the blood. In naive animals, rotenone, which is a respiration chain complex I inhibitor, was applied to induce mitochondrial ROS production, and followed by TRO-19622 or Mito-TEMPO treatment. Neurological deficits, brain edema, enzyme-linked immunosorbent assay, Western blot, in vivo chemical cross-linking, ROS assay, and immunofluorescence were evaluated. Results ICH activated the NLRP3 inflammasome. NLRP3 knockdown reduced brain edema and decreased myeloperoxidase (MPO) levels at 24 hours, and improved neurological functions from 24 to 72 hours following ICH. TRO-19622 or Mito-TEMPO reduced ROS, NLRP3 inflammasome components, and MPO levels following ICH. In naive animals, rotenone administration induced mPTP formation, ROS generation, and NLRP3 inflammasome activation, which were then reduced by TRO-19622 or Mito-TEMPO. Interpretation The NLRP3 inflammasome amplified the inflammatory response by releasing IL-1β and promoting neutrophil infiltration following ICH. Mitochondria ROS may be a major trigger of NLRP3 inflammasome activation. The results of our study suggest that the inhibition of the NLRP3 inflammasome may effectively reduce the inflammatory response following ICH. © 2014 American Neurological Association.


Wang Y.,Chongqing Medical University | Wang X.,Chongqing Medical University | Kong Y.,Chongqing Medical University | Zhang J.H.,Loma Linda University | Zeng Q.,Chongqing Medical University
Obesity | Year: 2010

This study investigated a possible association between early nutritional status during the famine, and the risk of overweight and obesity in adulthood in Chongqing Chinese population. The body weight, height, and BMI data were obtained from records of population (17,023) that had annual physical evaluations in the Public Health Center (in our hospital). Subjects born during 1956-1964 were divided into three groups: toddler group, all subjects who were born 1-3 years before the famine (1956-1958); gestational group, who were born during the famine period (1959-1961), and control group, who were born after the famine (1962-1964). The body weight and BMI were significantly higher, but the body height was significantly lower in the toddler and gestational groups (P 0.05) in the female population as compared to the control group. The odds ratio of being overweight in females is more pronounced in the toddler group (1.48 times, 95% confidence interval (CI): 1.288-1.689) than in the gestational group (1.26 times, 95% CI: 1.089-1.457). The odds ratio of being obese in females is significantly higher in the toddler group (1.46 times, 95% CI: 1.288-1.689) than the control group. For males, the famine had no impact at all on the adulthood body weight in males. The Great Chinese Famine that affected the Chongqing population during 1959-1961 leads to shorter and overweight females, and the former is a risk factor for increased BMI in Chongqing. Second, the famine seems to be producing shorter but slimmer males in Chongqing. Furthermore, toddler's and maternal's malnutrition during the famine had important late consequences on the health status.


Yang R.,Southwest University | Wu Y.,Southwest University | Wang M.,Southwest University | Sun Z.,Southwest University | And 3 more authors.
Oncotarget | Year: 2015

Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions. We found that HDAC9 is over-expressed in prognostically poor glioblastoma patients. Knockdown HDAC9 decreased proliferation in vitro and tumor formation in vivo. HDAC9 accelerated cell cycle in part by potentiating the EGFR signaling pathway. Also, HDAC9 interacted with TAZ, a key downstream effector of Hippo pathway. Knockdown of HDAC9 decreased the expression of TAZ. We found that overexpressed TAZ in HDAC9-knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro and in vivo. We demonstrated that HDAC9 promotes tumor formation of glioblastoma via TAZ-mediated EGFR pathway activation, and provide the evidence for promising target for the treatment of glioblastoma.


Peng K.,Chongqing Medical University | Zhao H.,Chongqing Medical University | Yuan Y.,Southwest University | Yuan R.,Southwest University | Wu X.,Chongqing Medical University
Biosensors and Bioelectronics | Year: 2014

The amplified sensitive detection of protein is essential to biomedical research as well as clinical diagnosis. Here, we developed an ultrasensitive mediator-free triple-enzyme cascade electrocatalytic aptasensor for thrombin detection on the basis of exonuclease-assisted target recycling and hybridization chain reaction (HCR) amplification strategy. The double strands constructed by the hybridization of thrombin binding aptamer (S1) with its complementary strand (S2) were firstly assembled on the electrode. Upon addition of target to the system, the S1 recognized thrombin and left off electrode to make space for assembly of hybrid-primer probe (H0). Then, the H0 triggered the HCR to form the multi-functional hemin/G-quadruplex DNAzyme nanowires. In the mediator-free triple-enzyme cascade electrocatalytic amplification system, the hemin/G-quadruplex DNAzyme nanowires here simultaneously played three roles: the redox probe, NADH oxidase and HRP-mimicking DNAzyme, respectively, which effectively avoided the fussy redox probe and enzyme labeling process, serving a useful alternative or supplement to conventional assays that typically suffer from complexity and poor sensitivity. Additionally, in order to improve the assembly amount of hemin/G-quadruplex DNAzyme nanowire, the exonuclease-assisted target recycling amplification was used for the continuous removal of S1. As a result, the proposed method can detect thrombin specifically with a detection limit as low as 20fM. © 2013 Elsevier B.V.


Wang Z.,Xuzhou Central Hospital | Guo J.,Chongqing Medical University
Cell Biochemistry and Biophysics | Year: 2013

Mechanical loading is known to promote osteocyte survival, whereas glucocorticoid treatment results in osteocyte apoptosis. Here, we report that BMP-7, which was secreted by osteocyte in response to mechanical loading, exerts anti-apoptotic effect against dexamethasone-induced apoptosis of osteocytes. We further show that the anti-apoptotic effect of BMP-7 is mainly mediated through receptor BMPR2 and is associated with the activation of PI3K/AKT/GSK3β pathway. © 2013 Springer Science+Business Media New York.


Luo P.,Chongqing Medical University | Liu Y.,Chongqing Medical and Pharmaceutical College | Xia Y.,Chongqing Medical University | Xu H.,Chongqing Medical University | Xie G.,Chongqing Medical University
Biosensors and Bioelectronics | Year: 2014

A sensitive electrochemical biosensor was developed to detect toxin A (TOA) of Clostridium difficile based on an aptamer selected by the systematic evolution of ligands using exponential enrichment and gold nanoparticles (GNPS) synthesized by Bacillus stearothermophilus. The thiolated single-stranded DNA used as the capture probe (CP) was first self-assembled on a Nafion-thionine-GNPS-modified screen-printed electrode (SPE) through an Au-thiol interaction. The horseradish peroxidase (HRP)-labeled aptamer probe (AP) was then hybridized to the complementary oligonucleotide of CP to form an aptamer-DNA duplex. In the absence of TOA, the aptamer-DNA duplex modified the electrode surface with HRP, so that an amperometric response was induced based on the electrocatalytic properties of thionine. This was mediated by the electrons that were generated in the enzymatic reaction of hydrogen peroxide under HRP catalysis. After the specific recognition of TOA, an aptamer-TOA complex was produced rather than the aptamer-DNA duplex, forcing the HRP-labeled AP to dissociate from the electrode surface, which reduced the catalytic capacity of HRP and reduced the response current. The reduction in the response current correlated linearly with the concentration of TOA in the range of 0-200. ng/mL. The detection limit was shown to be 1. nM for TOA. This biosensor was applied to the analysis of TOA and showed good selectivity, reproducibility, stability, and accuracy. © 2013 Elsevier B.V.


Li R.,Chongqing Medical University | Wu X.,Chongqing Medical University | Wei H.,Southwest University of Political Science and Law | Tian S.,The First Peoples Hospital of Jiulongpo of Chongqing
Oncology Letters | Year: 2013

Side population (SP) cells are a subset of stem cells that have been isolated from several different gastrointestinal cancer cell lines. Using flow cytometry and the DNA-binding dye Hoechst 33342, we isolated SP cells from SGC-7901 human gastric tumor cell lines and found that they comprise 2.3±0.78% of the tumor cells. Using the Cell Counting Kit-8 (CCK-8) assay, we demonstrated that SP cells have a stronger proliferative activity than non-SP cells. Additionally, we observed tumor mass formation following the cultivation of SP cells in serum-free medium, indicating the capability of these cells for self-renewal. SP cells were observed to undergo non-symmetrical division, which is characteristic of stem cells. A drug resistance assay revealed that SP cells have a high survival rate when exposed to the chemotherapy drug 5-fluorouracil; the results of western blot analysis suggest that this stems from the abundant expression of the chemoresistance- associated proteins ABCG2 and Bcl-2. We also used fluorescence quantitative PCR to reveal that SP cells have relatively high expression levels of the stem cell-related genes Musashi-1 and CD44. In vivo experiments in mice revealed that the subcutaneous injection of 2 × 103 SP cells resulted in the formation of tumors, while the injection of 2 × 104 non-SP cells did not. Cumulatively, our results suggest that gastric tumorigenesis associated with SGC-7901 may partly be driven by the activity of SP cells, which exhibit certain biological characteristics of stem cells. Our results also show that the SP cell sorting method is an effective means for isolating and identifying gastric cancer stem cells during early screening. © 2013 Spandidos Publications Ltd. All rights reserved.


Luo Z.,Chongqing Medical University | Zhang S.,Massachusetts Institute of Technology
Chemical Society Reviews | Year: 2012

Chirality is absolutely central in chemistry and biology. The recent findings of chiral self-assembling peptides' remarkable chemical complementarity and structural compatibility make it one of the most inspired designer materials and structures in nanobiotechnology. The emerging field of designer chemistry and biology further explores biological and medical applications of these simple d,l- amino acids through producing marvellous nanostructures under physiological conditions. These self-assembled structures include well-ordered nanofibers, nanotubes and nanovesicles. These structures have been used for 3-dimensional tissue cultures of primary cells and stem cells, sustained release of small molecules, growth factors and monoclonal antibodies, accelerated wound-healing in reparative and regenerative medicine as well as tissue engineering. Recent advances in molecular designs have also led to the development of 3D fine-tuned bioactive tissue culture scaffolds. They are also used to stabilize membrane proteins including difficult G-protein coupled receptors for designing nanobiodevices. One of the self-assembling peptides has been used in human clinical trials for accelerated wound-healings. It is our hope that these peptide materials will open doors for more and diverse clinical uses. The field of chiral self-assembling peptide nanobiotechnology is growing in a number of directions that has led to many surprises in areas of novel materials, synthetic biology, clinical medicine and beyond. © 2012 The Royal Society of Chemistry.


Zhou J.,Chongqing Medical University | Yi L.,Chongqing Medical University | Ouyang Q.,Chongqing Medical University | Xu L.,Chongqing Medical University | And 2 more authors.
Cellular Signalling | Year: 2014

We recently found that neurotensin (NTS) and its primary receptor NTSR1 play a crucial role in glioblastoma cell proliferation and invasion. However, very little is known regarding the functional role of NTS/NTSR1 signaling in glioblastoma stem cells (GSCs). Here, we showed that NTSR1 is highly expressed in GSCs than its non-GSC counterparts. Pharmacological blockade with SR48692 or lentivirus mediated knockdown of NTSR1 efficiently reduced the sphere-forming ability and expression of stem cell markers such as nestin and Sox2 in GSCs isolated from glioblastoma cell line and glioblastoma tissues. Conversely, treated GSCs with NTS led to increase of tumor sphere formation. Mechanistically, we demonstrated that EGFR-dependent enhancement of IL-8 secretion is responsible for the effect of NTS signaling in the regulation of stem-like traits. Finally, we showed that NTSR1 or IL-8 knockdown decreased the phosphorylation of transcriptional factor STAT3 at Tyr705, which is a major transcription factor implicated in the regulation of GSC stem-like traits. Although both CXCR1 and CXCR2 inhibition reduced the tumor sphere formation, we found that CXCR1, but not CXCR2, is primarily responsible for STAT3 phosphorylation. Taken together, our findings suggest that NTS/IL-8/CXCR1/STAT3 signaling is crucial for the maintenance of stem-like traits in GSCs and provides a potential therapeutic target for glioblastoma therapy. © 2014 Elsevier Inc.


Cheng O.,Loma Linda University | Cheng O.,Chongqing Medical University | Ostrowski R.P.,Loma Linda University | Wu B.,Loma Linda University | And 3 more authors.
Stroke | Year: 2011

Background and Purpose- Hyperbaric oxygen (HBO) preconditioning (PC) allows brain protection against transient global ischemia. In the present study, we hypothesize that the mechanism of HBO-PC involves the induction of cyclooxygenase-2 (COX-2) in cerebral tissues before ischemia, which leads to a suppression of COX-2 and its downstream targets after global ischemic insult. Methods- One hundred twenty-nine male Sprague Dawley rats (body weight 280-300 grams) were allocated to the naive control group and the sham operation group, and 3 groups of animals were subjected to 15-minute 4-vessel occlusion: untreated, preconditioned with HBO 2.5 atmospheres absolutes for 1 hour daily for 5 days, preconditioned as mentioned and administered with COX-2 inhibitor NS-398 (1 mg/kg body weight intraperitoneal) before each preconditioning session, and normal rats preconditioned with HBO without ischemia. The mortality, the incidence of seizures, and T-maze scores were recorded. The quantitative cell count in Nissl stain and TUNEL was conducted on day 7 after ischemia. The brain expression of COX-2 was analyzed with Western blotting and immunofluorescence staining. Results- HBO-PC increased the number of surviving neurons in the Cornu Ammonis area 1, which was associated with the reduced COX-2 expression in the hippocampus and in the cerebral cortex at 1 and 3 days after ischemia. HBO-PC improved functional performance and tended to decrease mortality and the frequency of seizures. These beneficial effects of HBO-PC were abolished by the COX-2 selective inhibitor NS-398. Conclusions- HBO-PC reduced COX-2 expression and provided brain protection after global ischemia. Administration of COX-2 inhibitor with HBO before ischemia abolished preconditioning effect, thereby implicating COX-2 as a mediator of HBO-PC in the ischemic brain. © 2011 American Heart Association, Inc.


Duan W.,City University of Hong Kong | Guo P.,Luzhou Medical College | Gan P.,Chongqing Medical University
PLoS ONE | Year: 2015

The present study aims to examine the relationship between trait resilience and virtues in the context of trauma. A total of 537 participants who attended the preliminary investigation and completed the Life Events Checklist were screened. Of these participants, 142 suffered from personal traumatic experiences in the past year; these individuals were qualified and invited to respond to online questionnaires to assess trait resilience, virtues (i.e., Conscientiousness, Vitality, and Relationship), post-traumatic stress disorder (PTSD) symptoms, and post-traumatic growth (PTG). The following questionnaires were used: Connor-Davidson Resilience Scale-Revised, Chinese Virtues Questionnaire, PTSD Checklist-Specific, and Post-traumatic Growth Inventory-Chinese. Only 95 participants who manifested self-reported PTSD symptoms and PTG were involved in the current analyses. Trauma was positively and significantly correlated with PTSD in the current sample. Results indicated that trait resilience was positively associated with virtues and PTG; by contrast, PTSD scores were negatively but not significantly related to most of these factors. The three virtues contributed to PTG to a greater extent than trait resilience in non-PTSD and PTSD groups. However, trait resilience remained a significant predictor in the PTSD group even when the three virtues were controlled. The relationship between trait resilience and PTG was moderated by PTSD type (non-PTSD group vs. PTSD group). Our results further suggested that trait resilience and virtues were conceptually related but functionally different constructs. Trait resilience and virtues are positively related; thus, these factors contributed variances to PTG in the context of trauma; however, trait resilience is only manifested when virtues are controlled and when individuals are diagnosed as PTSD. Furthermore, implications and limitations of this study are discussed. © 2015 Duan et al.


Chen H.,Chinese University of Hong Kong | Ruan Y.C.,Chinese University of Hong Kong | Xu W.M.,Chinese University of Hong Kong | Chen J.,Chinese University of Hong Kong | And 2 more authors.
Human Reproduction Update | Year: 2012

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated Cl. - and HCO. 3 - conducting channel, mutations of which are known to be associated with male infertility. However, the underlying mechanisms remain elusive. Methods: Literature databases were searched for papers on the topics related to CFTR and male fertility and infertility with relevant keywords. Unpublished data from authors' laboratory were also included for analysis. Results: Clinical evidence shows increased mutation frequency or reduced CFTR expression in men with congenital bilateral absence of vas deferens (CBAVD) or sperm abnormalities, such as azoospermia teratospermia and oligoasthenospermia. Studies on primary rodent Sertoli cells and germ cells, as well as testes from CFTR knockout mice or a cryptorchidism model, yield findings indicating the involvement of CFTR in spermatogensis through the HCO. 3 -/sAC/cAMP/CREB(CREM) pathway and the NF-κB/COX-2/PGE. 2 pathway. Evidence also reveals a critical role of CFTR in sperm capacitation by directly or indirectly mediating HCO. 3 - entry that is essential for capacitation. CFTR is emerging as a versatile player with roles in mediating different signaling pathways pertinent to various reproductive processes, in addition to its long-recognized role in electrolyte and fluid transport that regulates the luminal microenvironment of the male reproductive tract. CONCLUSIONS: CFTR is a key regulator of male fertility, a defect of which may result in different forms of male infertility other than CBAVD. It would be worthwhile to further investigate the potential of developing novel diagnostic and contraceptive methods targeting CFTR. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Liu Y.,Luzhou Medical College | Gong J.-P.,Chongqing Medical University | Li W.-F.,Chongqing Medical University
Chinese Medical Sciences Journal | Year: 2014

Results Six randomized control trials consistent with the inclusion criteria were selected and reviewed. Ustekinumab 45 mg group and 90 mg group could get better therapeutic effect compared with the placebo group (all P<0.00001). Furthermore, ustekinumab 90 mg group was more effective than ustekinumab 45 mg group (P=0.01). Adverse effects in the 6 trials were mentioned including headache, upper respiratory tract infection, nasopharyngtis, infection, serious infection, cardiovascular events, and malignant tumors. There were no statistically significant differences of these adverse effects among three groups (all P>0.05), except that infection rate in ustekinumab 45 mg group was higher than the placebo group (P=0.02).Conclusions Ustekinumab is an effective and safe therapeutic method for plaque psoriasis. However, further longer time analysis of safety is needed.Objective To evaluate the efficacy and safety of ustekinumab in the therapy of plaque psoriasis.Methods Literatures published up to November 2013 were collected from Cochrane library, MEDLINE, and PubMed which were related with ustekinumab for plaque psoriasis. The efficacy was estimated using relative risk of Psoriasis Area and Severity Index (PASI) 75 response rate at the week 12 endpoint in clinical trials, and adverse effects were also analyzed. Meta-analysis was carried out by using Review Manager 5.1. © 2014 Chinese Academy Medical Sciences.


Song C.,Chongqing Medical University | Xie G.,Chongqing Medical University | Wang L.,Chongqing Medical University | Liu L.,Chongqing Medical University | And 2 more authors.
Biosensors and Bioelectronics | Year: 2014

An ultrasensitive and selective electrochemical immunosensor was developed for the detection of Epstein Barr virus nuclear antigen 1 (EBNA-1). Firstly, a suspension of graphene sheets (GS) and multi-walled carbon nanotubes (MWCNTs) was prepared with the aid of chitosan (CS) solution and then modified on a glassy carbon electrode (GCE). Gold nanoparticles (AuNPs) were then electrodeposited onto the surface of the GS-MWCNTs film by cyclic voltammetry (CV) to immobilize the captured antibodies. After that, specific sandwich immunoreactions were formed among the captured antibody, EBNA-1, and secondary antibody, DNA-coated carboxyl multi-wall carbon nanotubes (DNA-MWCNTs-Ab2). DNA initiator strands (S0) and secondary antibodies linked to the MWCNTs and double-helix DNA polymers were obtained by hybridization chain reaction (HCR), and here S0 on the MWCNTs propagates a chain reaction of hybridization events between two alternating hairpins to form a nicked double-helix. Finally, electroactive indicator doxorubicin hydrochloride was intercalated into the CG-GC steps between the HCR products and could produce an electrochemical signal, which was monitored by differential pulse voltammetry (DPV). Under optimum conditions, the amperometric signal increased linearly with the target concentrations (0.05-6.4ngmL-1), and the immunosensor exhibited a detection limit as low as 0.7pgmL-1 (S/N=3). The proposed method showed acceptable stability and reproducibility, as well as favorable recovery for EBNA-1 in human serum. The proposed immunosensor provides a novel avenue for signal amplification and potential applications in bioanalysis and clinical diagnostics. © 2014 Elsevier B.V.


Zhang B.,Chinese University of Hong Kong | Chen J.,Chongqing Medical University | Cheng A.S.L.,Chinese University of Hong Kong | Ko B.C.B.,Hong Kong Polytechnic University
PLoS ONE | Year: 2014

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is implicated in plethora of biological processes, including metabolism, aging, stress response, and tumorigenesis. Telomerase (TERT) is essential for telomere maintenance. Activation of TERT is considered a crucial step in tumorigenesis, and therefore it is a potential therapeutic target against cancer. We have recently found that SIRT1 expression is highly elevated in hepatocellular carcinoma, and the depletion of SIRT1 leads to substantial reduction in TERT mRNA and protein expression. However, the underlying molecular mechanism of SIRT1-dependent TERT expression remains uncharacterized. Here, we elucidated if SIRT1 regulates TERT expression via transcriptional, epigenetic and post-transcriptional mechanisms. We report that depletion of SIRT1 does not lead to significant change in transcriptional activity and CpG methylation patterns of the TERT promoter, nor does it affect mRNA stability or 3′-UTR regulation of TERT. Intriguingly, depletion of SIRT1 is associated with substantial induction of acetylated histone H3-K9 and reduction of trimethyl H3-K9 at the TERT gene, which are known to be associated with gene activation. Our data revealed that SIRT1 regulates histone acetylation and methylation at the TERT promoter. We postulated that SIRT1 may regulate TERT expression via long-range interaction, or via yet unidentified histone modifications. © 2014 Zhang et al.


Li L.,Chongqing Medical University | Sheng Y.,Luzhou Medical College | Lv L.,Chongqing Medical University | Gao J.,Chongqing Medical University
PLoS ONE | Year: 2013

Background: MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Single nucleotide polymorphisms (SNPs) in miRNAs may contribute to cancer susceptibility due to changes in the microRNA's properties and/or maturation. The present study aimed to investigate the association between two miRNA polymorphisms (miR-499 rs3746444 and miR-149 rs2292832) and gastrointestinal (GI) cancer risk. Methodology/Principal Findings: We conducted a search of case-control studies in PubMed, Wiley Online Library, Web of Science and the CNKI database. Eleven rs3746444 studies and six rs2292832 studies were included in our meta-analysis. The only obvious association between the miR-499 polymorphism and colorectal cancer susceptibility was found in the homozygote comparison (GG vs. AA: OR = 1.66, 95% CI: 1.02-2.70, Ph = 0.10, P = 0.04). No significant association was found in the subgroup analysis for ethnicity and risk of hepatocellular and gastric cancer. A marginally elevated GI cancer risk was discovered in the recessive model for miR-149 (TT vs. TC+CC: OR = 1.15, 95% CI: 1.03-1.30, Ph = 0.68, P = 0.02). Stratifying the results by ethnicity revealed a slight association between the recessive model and the Asian population (TT vs. TC+CC: OR = 1.14, 95% CI: 1.01-1.29, Ph = 0.79, P = 0.03). Conclusions/Significance: The present meta-analysis indicates that miR-499 may be associated with the risk to colorectal cancer. MiR-149 may confer a marginally increased risk of susceptibility to gastrointestinal cancer, especially for Asians. © 2013 Li et al.


Peng J.,West China Hospital | Huang X.,West China Hospital | Zheng P.-F.,Chongqing Medical University | Chen Y.-C.,West China Hospital | Chen Y.-C.,Chongqing Medical University
Organic Letters | Year: 2013

An assembly of MBH carbonates of cyclohexen-2-one and alkylidenemalononitriles was investigated by the catalysis of a tertiary amine, which efficiently provides aromatic chromene derivatives with dense functionalities through a domino Rauhut-Currier-type reaction, cyclization, and isomerization process under metal-free conditions. © 2013 American Chemical Society.


Mao B.,Chongqing Medical University | Zhang Z.,Chongqing Medical University | Zhang Z.,Wuhan General Hospital of Guangzhou Command | Wang G.,Chongqing Medical University
International Journal of Oncology | Year: 2015

B-cell translocation gene 2 (BTG2), the first gene identified in the BTG/TOB gene family, is involved in many biological activities in cancer cells acting as a tumor suppressor. The BTG2 expression is downregulated in many human cancers. It is an instantaneous early response gene and plays important roles in cell differentiation, proliferation, DNA damage repair, and apoptosis in cancer cells. Moreover, BTG2 is regulated by many factors involving different signal pathways. However, the regulatory mechanism of BTG2 is largely unknown. Recently, the relationship between microRNAs and BTG2 has attracted much attention. MicroRNA-21 (miR-21) has been found to regulate BTG2 gene during carcinogenesis. In this review, we summarize the latest findings in the investigations of biological functions of BTG2 and regulation of its expression, with an emphasis on miR-21 in regulation of BTG2 gene in various cancers. B-cell translocation gene 2 (BTG2), also known as PC3 or TIS21, belongs to the antiproliferative (APRO) gene family. Several studies have demonstrated that BTG2 is involved in a large number of physiological and pathological processes, such as cell differentiation, proliferation, apoptosis, and other cellular functions, acting as a tumor suppressor. In this review, we summarize the latest findings in BTG2 studies, highlighting the mechanisms for the regulatory effects of microRNAs (miRNAs) on BTG2 gene expression in the most common human cancers.


Xiao Y.-C.,West China Hospital | Yue C.-Z.,West China Hospital | Chen P.-Q.,West China Hospital | Chen Y.-C.,West China Hospital | Chen Y.-C.,Chongqing Medical University
Organic Letters | Year: 2014

An asymmetric dearomatic Diels-Alder protocol for various heteroarenes, such as benzofuran, benzothiophene, or even furan, has been developed via π-system activation. This method involves in situ generation of formal trienamine species embedding a heteroaromatic moiety, and an array of chiral fused frameworks with high molecular complexity and skeletal diversity were efficiently constructed in good to excellent stereoselectivity by the catalysis of a cinchona-based primary amine. © 2014 American Chemical Society.


Gu J.,West China Hospital | Ma C.,West China Hospital | Li Q.-Z.,West China Hospital | Du W.,West China Hospital | And 2 more authors.
Organic Letters | Year: 2014

A stereoselective inverse-electron-demand aza-Diels-Alder cycloaddition process of cyclic 1-aza-1,3-butadienes and α,β-unsaturated aldehydes has been developed via dienamine catalysis. This reaction exhibits excellent β,γ- regioselectivity for enal substrates with substantial structural diversity and broad functionalities, readily producing highly enantioenriched fused piperidine derivatives and enabling efficient sequential construction of complex polycyclic frameworks. © 2014 American Chemical Society.


Chen H.-W.,Wenzhou Medical College | Liu G.-D.,Chongqing Medical University | Wu L.-J.,Wenzhou Medical College
PLoS ONE | Year: 2014

Objective: Terrible triad injury of the elbow (TTIE), comprising elbow dislocation with radial head and coronoid process fracture, is notoriously challenging to treat and has typically been associated with complications and poor outcomes. The objective of this systematic review was to summarize the most recent available evidence regarding functional outcomes and complications following surgical management of TTIE. Methods: Medline, EMBASE, Cochrane Library, and Google Scholar were searched to identify relevant studies, which were included if they were retrospective or prospective in design, involved participants who had TTIE, and were published in English. Outcomes of interest were functional outcomes and complications. Results: Sixteen studies, involving 312 patients, were included in the systematic review. Mean follow up after surgery was typically 25 to 30 months. Mean Mayo elbow performance scores ranged from 78 to 95. Mean Broberg-Morrey scores ranged from 76 to 90. Mean DASH scores ranged from 9 to 31. The proportion of patients who required reoperation due to complications ranged from 0 to 54.5% (overall = 70/312 [22.4%]). Most of these complications were related to hardware fixation problems, joint stiffness, joint instability, and ulnar neuropathy. The most common complications that did not require reoperation were heterotopic ossification (39/312 [12.5%] patients) and arthrosis (35/312 [11.2%] patients). Conclusions: The results of this systematic review indicate that functional outcomes after surgery for TTIE are generally satisfactory and that complications are common. Further research is warranted to determine which surgical techniques optimize functional outcomes and reduce the risk of complications. © 2014 Chen et al.


Liu D.,Guiyang Medical College | He Z.,Chongqing Medical University | Wu L.,Guiyang Medical College | Fang Y.,Guiyang Medical College
Journal of Pharmacological Sciences | Year: 2012

The heme oxygenase-1 (HO-1) / carbon monoxide (CO) system has been presumed as a therapeutic target for preventing atherosclerosis. However, the exact mechanism(s) underlying this system remains largely undefined. This study aims to examine the influence of induction/inhibition of HO-1 on atherosclerotic plaque using pharmacological approaches and to elucidate potential mechanisms. Rabbits were randomly assigned to receive a standard diet (control group), high fat diet (HFD), HFD plus HO inducer hemin (HFD + H group), and HFD plus an HO inhibitor, zinc protoporphyrin-9 (ZnPP9, HFD + Z group). Atherosclerotic plaque was evaluated using oil red O staining and histological analyses. Immunohistochemistry, western blotting, and RT-PCR were employed to study the expression of HO-1 and endothelin-1 (ET-1). Levels of CO, nitric oxide (NO), eNOS/iNOS activities, NF-κB activity, and TNF-α level were determined. No significant differences of serum lipid levels were observed among the HFD, HFD + Z, and HFD + H groups. In rabbits, HFD induced typical atherosclerotic plaque and increased intima/media thickness ratio, which was markedly reduced in the HFD + H group and further aggravated in the HFD + Z group. Furthermore, hemin increased HO-1 expression, CO levels, and eNOS activity, while decreasing iNOS levels, ET-1 expression, NF-κB activity, and TNF-α level. ZnPP9 caused opposite effects. Induction of the endogenous HO-1/CO system by hemin can prevent atherosclerosis though increasing CO levels, regulating eNOS activity, NF-κB activity, TNF-α levels, and ET-1 levels in rabbits. Our results add new evidence for the importance of HO-1 in the genesis and development of atherosclerosis and provide several possible mechanisms underlying the antiatherosclerosis effects of HO-1. © The Japanese Pharmacological Society.


Wang Q.,Chongqing Medical University | Chen Z.,Chongqing Medical University | Diao X.,Chongqing Medical University | Huang S.,Mayo Cancer Center
Cancer Letters | Year: 2011

In this study, we demonstrated that YM155, a novel survivin suppressant, induced both apoptosis, and autophagy that was shown by conversion of cytosolic-associated protein light chain 3 (LC3I) into autophagosome-associated form (LC3II) and a punctate fluorescence pattern of an ectopic GFP-LC3 protein. The lysosomal inhibitor chloroquine further accumulated YM155-induced LC3II, indicating an increase of autophagic flux. Ectopic expression of survivin significantly attenuated YM155-induced apoptosis and autophagy, whereas survivin siRNA induced autophagy. Furthermore, inhibition of either early or late events of autophagy attenuated YM155-induced apoptosis, demonstrating that induction of autophagy proceeds apoptosis. In conclusion, suppression of survivin by YM155 induces autophagy-dependent apoptosis, and YM155-induced autophagy plays a pro-apoptotic role thereby unveiling a novel mechanism of YM155 in prostate cancer cells. © 2010 Elsevier Ireland Ltd.


Zhan G.,West China Hospital | He Q.,West China Hospital | Yuan X.,West China Hospital | Chen Y.-C.,West China Hospital | Chen Y.-C.,Chongqing Medical University
Organic Letters | Year: 2014

A direct catalytic asymmetric γ-regioselective vinylogous Michael addition of allyl alkyl ketones to maleimides has been developed through dienamine catalysis of a simple chiral 1,2-diphenylethanediamine, giving multifunctional products in excellent enantioselectivity and with high yields. The success of this catalytic strategy relies on the unique inducing effect of deconjugated β,γ-C=C bond, which facilitates the formation of the otherwise unfavored extended dienamine species. © 2014 American Chemical Society.


Xu C.S.,Chinese University of Hong Kong | Xu C.S.,Chongqing Medical University | Leung A.W.N.,Chinese University of Hong Kong
Laser Physics Letters | Year: 2010

Hypericin from Hypericum perforatum plants shows an important promise in the photodynamic therapy on malignant tumor. The present study investigated that light-activated hypericin induced the cellular destruction of nasopharyngeal carcinoma cells. The result showed that hypericin resulted in a drug- and light-dose dependent cytotoxicity in the CNE-2 cells, meaning the photocytotoxicity of hypericin depends on both of the drug concentration (0-2.5 μM) and light-doses (1-8 J/cm2). We further investigated the apoptosis of the CNE-2 cells 8 hours after photosensitization of hypericin using fluorescence microscopy with Hoechst 33258 staining. Flow cytometry with annexin VFITC and PI staining was used to analyze early and late apoptosis. These data demonstrated that light-activated hypericin could significantly lead to the cellular destruction of the CNE-2 cells and induce early apoptosis as a prominent mode of cell death. © 2010 by Astro Ltd.


Xu C.S.,Chinese University of Hong Kong | Leung A.W.N.,Chinese University of Hong Kong | Liu L.,Chinese University of Hong Kong | Xia X.S.,Chongqing Medical University
Laser Physics Letters | Year: 2010

Pheophorbide a (Pa) from Chinese herbal medicine Scutellaria Barbata and Silkworm Excreta shows an important promise in the photodynamic therapy on malignant tumor. The present study investigated that LED-activated Pa induced the cellular destruction of colon cancer HT-29 cells. The results showed that Pa resulted in a drug-dose dependent photocytotoxicity in the HT-29 cells, meaning the photocytotoxicity of Pa depends on the drug concentration (0-2 /kM). We further investigated the apop-tosis of the HT-29 cells 18 hours after photosensitization of Pa using a confocal laser scanning microscopy with Hoechst 33258 staining. These data demonstrated that LED-activated Pa could significantly induce the cellular destruction of the HT-29 cells. © 2010 by Astro Ltd.


Lian J.,Chongqing Medical University | Ni Z.,Chongqing Medical University | Dai X.,Chongqing Normal University | Su C.,Chongqing Medical University | And 3 more authors.
Molecular Cancer Therapeutics | Year: 2012

The natural BH3-mimetic (-)-gossypol shows promising efficacy in ongoing phase II/III clinical trials for human prostate cancer. Here, we show for the first time, that treatment with (-)-gossypol and multikinase inhibitor sorafenib synergistically suppresses the growth of androgen-independent prostate cancer cells (AI-PC) in vitro and in vivo. Our data suggest that sorafenib attenuates (-)-gossypol-induced Mcl-1 upregulation in AI-PCs. In this way, it serves as a potent chemosensitizer to affect cell death. Interestingly, (-)-gossypol and sorafenib induce cell death via two distinct pathways among different AI-PCs; DU145 cells via apoptosis and PC-3 via autophagy. The appointed death pathway may depend on the level of proapoptotic protein Bak, although the level of antiapoptotic protein Bcl-2 plays some role in it. DU145 cells with high Bak level prefer apoptosis induction, whereas PC-3 cells with low Bak prefer the induction of autophagy. Furthermore, inhibiting nondominant death pathways, that is, autophagy in DU145 and apoptosis in PC-3, enhances cell killing by (-)-gossypol/sorafenib combination therapy. Ultimately, our data expose a new action for sorafenib as an enhancer of (-)-gossypol-induced cell growth suppression and reveal a novel cell death mode by Bak activation manners in AI-PCs. These new insights may facilitate the rational design of clinical trials by selecting patients most likely to benefit from the Bcl-2-targeted molecular therapy. ©2011 AACR.


Chen L.,Chongqing Medical University | Wu J.,Chongqing Medical University | Pier E.,Tufts University | Zhao Y.,Harvard University | Shen Z.,Chongqing Medical University
Journal of Investigative Dermatology | Year: 2013

The connection between infections and acute guttate psoriasis (AGP) outbreaks/chronic plaque psoriasis (CPP) exacerbation has been known for years. Impaired function of FOXP3+Tregs in psoriasis has been identified. However, the mechanisms behind these two observations have not been fully interpreted. In the present study, we provide evidence to support chemokine CCL3 as one of the vital links between infections and FOXP3 stability in the psoriatic microenvironment. We found that serum CCL3, strongly induced by microorganism infections including streptococcus, was closely correlated with FOXP3 levels in CD4+CD25+T cells of patients with psoriasis. CCL3 manipulated FOXP3 stability in a concentration-dependent bidirectional manner. High-concentration CCL3 decreased FOXP3 stability by promoting FOXP3's degradation through K48-linkage ubiquitination. This degradation was mainly dependent on upregulation of Serine 473 phosphorylation of the PKBα/Akt1 isoform, and almost independent of mTORC1 (mammalian target of rapamycin complex 1) activity. On the other hand, low-concentration CCL3 could enhance FOXP3 stability by the maintenance of the PKC pathway and the restriction of the PKB/Akt pathway. We further demonstrated that enhancing FOXP3 stability by low-concentration CCL3 attributed, at least partly, to the prevention of cytoplasmic Sin1, a vital component of mTORC2, nuclear translocation. Our results suggest vital roles for CCL3-mTORC2-isoform PKB/Akt1 S473 phosphorylation axis in FOXP3+Tregs and the development of psoriasis. © 2013 The Society for Investigative Dermatology.


Wu D.,Chongqing Medical University | Yang M.,Chongqing Medical University | Chen Y.,Chongqing Medical University | Jia Y.,Chongqing Medical University | And 4 more authors.
Diabetes | Year: 2014

Nesfatin-1, an 82-amino acid neuropeptide, has recently been characterized as a potent metabolic regulator. However, the metabolic mechanisms and signaling steps directly associated with the action of nesfatin-1 have not been well delineated. We established a loss-of-function model of hypothalamic nesfatin-1/NUCB2 signaling in rats through an adenoviral-mediated RNA interference. With this model, we found that inhibition of central nesfatin-1/NUCB2 activity markedly increased food intake and hepatic glucose flux and decreased glucose uptake in peripheral tissue in rats fed either a normal chow diet (NCD) or a high-fat diet (HFD). The change of hepatic glucose fluxes in the hypothalamic nesfatin-1/NUCB2 knockdown rats was accompanied by increased hepatic levels of glucose-6-phosphatase and PEPCK and decreased insulin receptor, insulin receptor substrate 1, and AKT kinase phosphorylation. Furthermore, knockdown of hypothalamic nesfatin-1 led to decreased phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) and the subsequent suppressor of cytokine signaling 3 levels. These results demonstrate that hypothalamic nesfatin-1/NUCB2 plays an important role in glucose homeostasis and hepatic insulin sensitivity, which is, at least in part, associated with the activation of the mTOR-STAT3 signaling pathway. © 2014 by the American Diabetes Association.


Liu R.,Chongqing Medical University | Li L.,Chongqing Medical University | Yang M.,Chongqing Medical University | Boden G.,Temple University | Yang G.,Chongqing Medical University
Mayo Clinic Proceedings | Year: 2013

Objective: To assess the efficacy and safety of hyperbaric oxygenation (HBO) therapy as adjunctive treatment for diabetic foot ulcers with a systematic review and meta-analysis of the literature. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched to find relevant articles published up to April 20, 2012, without restriction as to language or publication status. All controlled trials that evaluated adjunctive treatment with HBO therapy compared with treatment without HBO for chronic diabetic foot ulcers were selected. A meta-analysis was performed to assess the efficacy and safety of hyperbaric oxygen in managing foot ulcers. Results: Thirteen trials (a total of 624 patients), including 7 prospective randomized trials, performed between January 1, 1966, and April 20, 2012, were identified as eligible for inclusion in the study. Pooling analysis revealed that, compared with treatment without HBO, adjunctive treatment with HBO resulted in a significantly higher proportion of healed diabetic ulcers (relative risk, 2.33; 95% CI, 1.51-3.60). The analysis also revealed that treatment with HBO was associated with a significant reduction in the risk of major amputations (relative risk, 0.29; 95% CI, 0.19-0.44); however, the rate of minor amputations was not affected (P=.30). Adverse events associated with HBO treatment were rare and reversible and not more frequent than those occurring without HBO treatment (P=.37). Conclusions: This meta-analysis reveals that treatment with HBO improved the rate of healing and reduced the risk of major amputations in patients with diabetic foot ulcers. On the basis of these effects, we believe that quality of life could be improved in selected patients treated with HBO. © 2013 Mayo Foundation for Medical Education and Research.


Tao X.,Chongqing Medical University | Liu J.,Chongqing Medical University | Chen L.,Wuhan General Hospital of Guangzhou Military Region | Zhou Y.,Chongqing Medical University | Tang K.,Chongqing Medical University
Cellular Physiology and Biochemistry | Year: 2015

Background/Aims: The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1) in the differentiation of tendon stem cells (TSCs) and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair. Methods: Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs) using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined. Results: EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair. Conclusion: EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries. © 2015 S. Karger AG, Basel.


Yang M.,Chongqing Medical University | Zhang Z.,Chongqing Medical University | Wang C.,Chongqing Medical University | Li K.,Chongqing Medical University | And 4 more authors.
Diabetes | Year: 2012

Nesfatin-1, derived from nucleobindin 2, was recently identified as an anorexigenic signal peptide. However, its neural role in glucose homeostasis and insulin sensitivity is unknown. To evaluate the metabolic impact and underlying mechanisms of central nesfatin-1 signaling, we infused nesfatin-1 in the third cerebral ventricle of high-fat diet (HFD)-fed rats. The effects of central nesfatin-1 on glucose metabolism and changes in transcription factors and signaling pathways were assessed during euglycemic-hyperinsulinemic clamping. The infusion of nesfatin-1 into the third cerebral ventricle markedly inhibited hepatic glucose production (HGP), promoted muscle glucose uptake, and was accompanied by decreases in hepatic mRNA and protein expression and enzymatic activity of PEPCK in both standard diet-and HFD-fed rats. In addition, central nesfatin-1 increased insulin receptor (InsR)/insulin receptor substrate-1 (IRS-1)/AMP-dependent protein kinase (AMPK)/Akt kinase (Akt)/target of rapamycin complex (TORC) 2 phosphorylation and resulted in an increase in Fos immunoreactivity in the hypothalamic nuclei that mediate glucose homeostasis. Taken together, these results reveal what we believe to be a novel site of action of nesfatin-1 on HGP and the PEPCK/InsR/IRS-1/AMPK/Akt/TORC2 pathway and suggest that hypothalamic nesfatin-1 action through a neural-mediated pathway can contribute to increased peripheral and hepatic insulin sensitivity by decreasing gluconeogenesis and promoting peripheral glucose uptake in vivo. © 2012 by the American Diabetes Association.


Wang W.E.,Chongqing Medical University | Chen X.,Temple University | Houser S.R.,Temple University | Zeng C.,Chongqing Medical University
Clinical Science | Year: 2013

Stem cell therapy has emerged as a promising strategy for cardiac and vascular repair. The ultimate goal is to rebuild functional myocardium by transplanting exogenous stem cells or by activating native stem cells to induce endogenous repair. CS/PCs (cardiac stem/progenitor cells) are one type of adult stem cell with the potential to differentiate into cardiac lineages (cardiomyocytes, smooth muscle cells and endothelial cells). iPSCs (induced pluripotent stem cells) also have the capacity to differentiate into necessary cells to rebuild injured cardiac tissue. Both types of stem cells have brought promise for cardiac repair. The present review summarizes recent advances in cardiac cell therapy based on these two cell sources and discusses the advantages and limitations of each candidate. We conclude that, although both types of stem cells can be considered for autologous transplantation with promising outcomes in animal models, CS/PCs have advanced more in their clinical application because iPSCs and their derivatives possess inherent obstacles for clinical use. Further studies are needed to move cell therapy forward for the treatment of heart disease. © The Authors Journal compilation. © 2013 Biochemical Society.


Tan M.,North Sichuan Medical College | Tan M.,Chongqing Medical University | Zhu J.-C.,Chongqing Medical University | Du J.,North Sichuan Medical College | And 2 more authors.
Critical Care | Year: 2011

Introduction: Traumatic brain injury (TBI) is associated with a profound immunological dysfunction manifested by a severe shift from T-helper type 1 (Th1) to T-helper type 2 (Th2) response. This predisposes patients to infections, sepsis, and adverse outcomes. Probiotic bacteria have been shown to balance the Th1/Th2 cytokines in allergic murine models and patients. For the present study, we hypothesized that the enteral administration of probiotics would adjust the Th1/Th2 imbalance and improve clinical outcomes in TBI patients.Methods: We designed a prospective, randomized, single-blind study. Patients with severe TBI and Glasgow Coma Scale scores between 5 and 8 were included, resulting in 26 patients in the control group and 26 patients in the probiotic group. All patients received enteral nutrition via a nasogastric tube within 24 to 48 hours following admission. In addition, the probiotic group received 10 9bacteria of viable probiotics per day for 21 days. The associated serum levels of Th1/Th2 cytokines, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, nosocomial infections, length of ICU stay, and 28-day mortality rate were studied.Results: The patients responded to viable probiotics, and showed a significantly higher increase in serum IL-12p70 and IFNγ levels while also experiencing a dramatic decrease in IL-4 and IL-10 concentrations. APACHE II and SOFA scores were not significantly affected by probiotic treatment. Patients in the probiotic group experienced a decreased incidence of nosocomial infections towards the end of the study. Shorter ICU stays were also observed among patients treated with probiotic therapy. However, the 28-day mortality rate was unaffected.Conclusions: The present study showed that daily prophylactic administration of probiotics could attenuate the deviated Th1/Th2 response induced by severe TBI, and could result in a decreased nosocomial infection rate, especially in the late period.Trial registration: ChiCTR-TRC-10000835. © 2011 Tan et al.; licensee BioMed Central Ltd.


Li W.,Shantou University | Li Q.,Chongqing Medical University
Endocrine Journal | Year: 2012

To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and β cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. β cell function was estimated by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03±1.05 vs. 5.44±0.97 mmol/L, P<0.05), lower M value but similar HOMA-βad index, while overweight/ obese PCOS women had higher levels of both FPG (5.24±0.58 vs. 4.90±0.39, P<0.05) and PPG (6.15±0.84 vs. 5.44±0.97 mmol/L, P<0.05), and lower levels of both M value and HOMA-βad index. Linear regression and ROC analysis found BMI was independently associated with M value and HOMA-βad index in PCOS women separately, and the cutoff of BMI indicating impaired β cell function of PCOS women was 25.545kg/m2. In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m2 indicated impaired β cell function in PCOS women with normal glucose tolerance. © The Japan Endocrine Society.


Luo S.,Chongqing Medical University | Lei H.,Chongqing Medical University | Qin H.,Ohio State University | Xia Y.,Ohio State University
Current Pharmaceutical Design | Year: 2014

Nitric oxide (NO) is a gaseous signaling molecule and effector in various biological processes. In mammalian cells, NO is produced by a family of NO synthases (NOS). Three NOS isoforms have been identified as: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). In addition to NO, NOS also produces superoxide anion. This phenomenon is named NOS uncoupling as superoxide generation mainly occurs when NOS is not coupled with its cofactor or substrate. nNOS was first found to produce superoxide under L-arginine depletion condition. Further studies demonstrated that superoxide production is a general feature of all three NOS isoforms. In particular, superoxide generated from uncoupled eNOS has been found to play critical roles in the process of various cardiovascular diseases. Although NOS was first found to produce superoxide only when uncoupled with its cofactor or substrate, recent studies reveal that oxygen reduction to superoxide is an intrinsic process amid NO synthesis. Tetrahydrobiopterin plays a controlling role in preventing superoxide release from the eNOS oxygenase domain. Besides tetrahydrobiopterin, the regulation of eNOS uncoupling by the interactions with other proteins, protein phosphorylation, S-glutathionylation, and endogenous L-arginine derivatives, will be discussed in this review. © 2014 Bentham Science Publishers.


Chen H.,Fudan University | Wang Y.,Chongqing Medical University | Bai C.,Fudan University | Wang X.,Fudan University
Journal of Proteomics | Year: 2012

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortally and morbidity, associated with acute exacerbations (AECOPD) resulted from smoking, infection or air pollution. Systemic inflammation has been considered as one of major pathophysiologic alterations in AECOPD. The present study aimed at developing disease-specific biomarker evaluation by integrating proteomic profiles of inflammatory mediators in AECOPD with clinical and biological informatics. Plasma samples from 18 subjects including healthy people or patients with stable COPD or AECOPD were collected to measure 507 inflammatory mediators using antibody microarray. Clinical informatics was achieved by a Digital Evaluation Score System (DESS) for assessing severity of patients. 20 mediators were significantly different between 3 groups (p < 0.05), of which, Cerberus 1, Growth Hormone R, IL-1. F6, IL-17B R, IL-17D, IL-19, Lymphotoxin beta, MMP-10, Thrombopoietin and TLR4 were correlated with DESS scores (p < 0.05). There was a down-regulation of systemic inflammatory responses in AECOPD. The integration of proteomic profile with clinical informatics as part of clinical bioinformatics is important to screen disease-specific and disease-staged biomarkers. This article is part of a Special Issue entitled: Proteomics: The clinical link. © 2012.


Liu T.-Y.,Chongqing Medical University | Xie M.,Gladstone | Chen Y.-C.,Chongqing Medical University | Chen Y.-C.,University of Sichuan
Chemical Society Reviews | Year: 2012

Chiral Lewis basic tertiary amines or phosphines can enable properly modified Morita-Baylis-Hillman (MBH) adducts to undergo asymmetric allylic substitutions with a wide range of nucleophiles. In addition, assisted by a Brønsted base, chiral Lewis bases can also catalytically convert modified MBH adducts into allylic ylides, which can be engaged in a variety of asymmetric annulation reactions. This tutorial review will focus on such chiral Lewis base-catalysed asymmetric transformations of MBH adducts, especially those developed over the past five years, allowing for the rapid construction of densely functionalised chiral molecules with high levels of regio- and stereoselectivities. © 2012 The Royal Society of Chemistry.


Shen Z.,Chongqing Medical University | Hoffman J.D.,Floating Hospital for Children | Hao F.,Chongqing Medical University | Pier E.,Tufts University
Oncologist | Year: 2012

Genetic syndromes with dermatologic findings and multisystemic involvement (e.g., visceral cancer predisposition) are underrecognized. Patients may have incomplete penetrance and variable expressivity; some patients may solely exhibit subtle skin signs, which create a diagnostic challenge for physicians. Interdisciplinary diagnostic knowledge is required for the early diagnosis and monitoring of patients with these syndromes. Cutaneous changes in the face-one of the most highly exposed areas-can be easily noticed by patients themselves, their families and friends, and physicians; these changes may serve as early indicators of genetic syndromes with malignancies. In this article, we present examples of genetic syndromes with malignancies for which a thorough faciocutaneous examination is helpful in establishing a diagnosis. These examples include lentiginosis-related syndromes (e.g., Peutz-Jeghers syndrome, Carney complex), photosensitivity-related syndromes (Bloom syndrome, Rothmund-Thomson syndrome), and hamartoma-related syndromes (Cowden syndrome, multiple endocrine neoplasia syndrome, tuberous sclerosis complex, Gardner syndrome, Muir-Torre syndrome). The characteristics of these faciocutaneous clues are summarized and discussed. Objective evaluation of these faciocutaneous clues in combination with other clinical information (e.g., family history, histopathological findings, combination with other concomitant faciocutaneous lesions) is emphasized to narrow the diagnosis. The list of genetic syndromes with faciocutaneous manifestations is still expanding. Increased awareness of faciocutaneous markers can alert physicians to underlying syndromes and malignancies, render earlier screening and detection of associated medical issues, and allow for genetic counseling of family members. ©AlphaMed Press.


Ma X.,Chongqing Medical University | Ma X.,Vanderbilt University | Zhang B.,Vanderbilt University | Zheng W.,Vanderbilt University
Gut | Year: 2014

Objective: In the past two decades, approximately 1000 reports have been published regarding associations between genetic variants in candidate genes and risk of colorectal cancer (CRC). Study results are inconsistent. We aim to provide a synopsis of the current understanding of genetic factors for CRC risk through systematically evaluating results from previous studies. Design: We searched PubMed and Google Scholar to identify papers that investigated associations between genetic variants and CRC risk and published through 25 December 2012. With data from 950 papers, we conducted 910 meta-analyses for 267 genetic variants in 150 candidate genes with at least three data sources. We used Venice criteria and false-positive report probability tests to grade levels of cumulative epidemiological evidence of significant associations with CRC risk. Results: Sixty-two variants in 50 candidate genes showed a nominally significant association with CRC risk (p<0.05). Cumulative epidemiological evidence for a significant association with CRC risk was graded strong for eight variants in five genes (adenomatous polyposis coli (APC), CHEK2, DNMT3B, MLHl and MUTYH), moderate for two variants in two genes (GSTM1 and TERT), and weak for 52 variants in 45 genes. Additionally, 40 variants in 33 genes showed convincing evidence of no association with CRC risk in metaanalyses including at least 5000 cases and 5000 controls. Conclusions: Approximately 4% of genetic variants evaluated to date in candidate-gene association studies showed moderate to strong cumulative epidemiological evidence of an association with CRC risk. These genetic variants, if confirmed, may explain approximately 5% of familial CRC risk.


Zhang L.,Chongqing Medical University | Yang M.,Chongqing Medical University | Ren H.,Chongqing Medical University | Hu H.,Chongqing Medical University | And 3 more authors.
Liver International | Year: 2013

Background & Aims: Liraglutide, a Glucagon-like peptide-1(GLP-1) analogue with 97% sequence identity to human GLP-1, increases insulin secretion and insulin sensitivity. Its effect on non-alcoholic fatty liver disease (NAFLD) remains poorly understood. In this study, we examined whether liraglutide can protect against inflammatory stress by inhibiting activation of c-Jun N-terminal protein kinase (JNK). Methods: ApoE KO and adiponectin (Acrp30) knockdown mice fed a high-fat diet (HFD) were treated with liraglutide (1 mg/kg, twice daily) for 8 weeks. Liver tissue was procured for histological examination, real-time RT-PCR and Western blot analysis. Results: The results showed that the combination of HFD, Acrp30 knockdown and ApoE deficiency had additive effects on the development of insulin resistance (IR) and NAFLD. Administration of liraglutide prevented the development of HFD and hypoadiponectinaemia-induced IR and NAFLD in this model. Liraglutide also attenuated the expression of proinflammatory cytokines or transcription factor, including TNF-α and NF-κB65, and the expression of two lipogenesis-related genes, Acetyl-CoA Carboxylase (ACC) and fatty acid synthase (FAS). These changes were accompanied by elevated plasma of Acrp30, increased Acrp30 mRNA, AMP Kinase phosphorylation, and decreased mitogen-activated protein kinase 4 (MKK4) mRNA expression and JNK phosphorylation. Conclusions: Our study also showed potent inhibitory effects of liraglutide on MKK4/JNK signalling which may be a mechanism for the observed improved insulin sensitivity and inflammatory stress induced by HFD and hypoadiponectinaemia. © 2013 John Wiley & Sons A/S.


Cheng W.,Chongqing Medical University | Cheng W.,Nanjing University | Yan F.,Jiangsu Institute of Cancer Prevention and Cure | Ding L.,Nanjing University | And 3 more authors.
Analytical Chemistry | Year: 2010

A cascade signal amplification strategy was proposed for detection of protein target at ultralow concentration by combining the rolling circle amplification (RCA) technique with oligonucleotide functionalized quantum dots (QDs), multiplex binding of the biotin?strepavidin system, and anodic stripping voltammetric detection. The RCA product containing tandem-repeat sequences could serve as excellent template for periodic assembly of QDs, which presented per protein recognition event to numerous quantum dot tags for electrochemical readout. Both the RCA and the multiplex binding system showed remarkable amplification efficiency, very little nonspecific adsorption, and low background signal. Using human vascular endothelial growth factor as a model protein, the designed strategy could quantitatively detect protein down to 16 molecules in a 100 ?L sample with a linear calibration range from 1 aM to 1 pM and was amenable to quantification of protein target in complex biological matrixes. The proposed cascade signal amplification strategy would become a powerful tool for proteomics research and clinical diagnostics. © 2010 American Chemical Society.


Gu W.-J.,Nanjing University | Wu X.-D.,Chongqing Medical University | Wang F.,General Hospital of Jinan Military Command | Ma Z.-L.,Nanjing University | Gu X.-P.,Nanjing University
Chest | Year: 2016

BACKGROUND: Potential benefits and possible risks associated with ultrasound guidance compared with traditional palpation for radial artery catheterization are not fully understood. METHODS: We searched PubMed, Embase, and the Cochrane Library through July 2015 to identify randomized controlled trials that evaluated ultrasound guidance compared with traditional palpation for radial artery catheterization. Primary outcome was first-Attempt failure. Secondary outcomes included mean attempts to success, mean time to success, and hematoma complications. A random-effects model was used to estimate relative risks (RRs) with 95% CIs. RESULTS: Twelve trials used dynamic two-dimensional (2-D) ultrasound guidance (N = 1,992) and two used Doppler ultrasound guidance (N = 666). Compared with traditional palpation, dynamic 2-D ultrasound guidance was associated with a reduced first-Attempt failure (RR, 0.68; 95% CI, 0.52-0.87). Trial sequential analysis showed that the cumulative z curve crossed the trial sequential monitoring boundary for benefit establishing sufficient and conclusive evidence. Dynamic 2-D ultrasound guidance further reduced mean attempts to success, mean time to success, and hematoma complications. No evidence of publication bias was detected. Compared with traditional palpation, Doppler ultrasound guidance had no benefit on first-Attempt failure (RR, 1.00; 95% CI, 0.87-1.15), which was confirmed by trial sequential analysis as the cumulative z curve entered the futility area. CONCLUSIONS: The use of dynamic 2-D ultrasound guidance for radial artery catheterization decreases first-Attempt failure, mean attempts to success, mean time to success, and the occurrence of hematoma complications. Dynamic 2-D ultrasound guidance is recommended as an adjunct to aid radial arterial catheterization. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.


Li J.,Chongqing Medical University | Zhao Y.-D.,Chongqing Medical University | Zeng J.-W.,Zunyi Medical College | Chen X.-Y.,Chongqing Medical University | And 2 more authors.
Journal of Affective Disorders | Year: 2014

Background Depression is a frequent mood disorder that affects around a third of stroke patients and has been associated with poorer outcome. Our aim was to determine whether there is a relationship between serum Brain-derived neurotrophic factor (BDNF) levels and post-stroke depression (PSD). Methods Two hundred and sixteen ischemic stroke patients admitted to the hospital within the first 24 h after stroke onset were consecutively recruited and followed up for 3 months. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for post-stroke depression at day 90. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of BDNF at admission. Multivariate analyses were performed using logistic regression models. Results In our study, 59 patients (27.3%) were diagnosed as having major depression at 3 months. Patients with major depression showed lower levels of serum BDNF [8.1 (5.6-9.4) vs. 13.7 (10.4-16.5)ng/ml, P<0.0001] at admission. In multivariate analyses, serum BDNF was an independent predictor of PSD at 3 months [odds ratio (OR): 0.79(0.72-0.87), P=0.003]. Serum levels of BDNF≤10.2 ng/ml were independently associated with post-stroke (OR, 11.5; 95% CI, 5.6-23.4, P<0.0001), after adjustment for possible variables. Conclusion The present study demonstrates a strong relationship between serum BDNF levels at admission and the development of PSD within 3 months. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options. © 2014 Elsevier B.V. All rights reserved.


Luo C.,Chongqing Medical University | Tang H.,Chongqing Medical University | Cheng W.,Chongqing Medical University | Yan L.,Chongqing Medical University | And 4 more authors.
Biosensors and Bioelectronics | Year: 2013

A specific and sensitive methodology was developed successfully for quantitative detection of Enterobacteriaceae bacteria by integrating Exonuclease III-assisted target recycling amplification with a simple electrochemical DNA biosensor. After target DNA hybridizes with capture DNA, Exonuclease III can selectively digest the capture DNA, which releases the target to undergo a new hybridization and cleavage cycle on sensor surface, leading to a successful target recycling. Finally, the left capture DNA is recognized by detection probe to produce the detectable signal, which decreases with the increasing target DNA concentration. Under the optimal conditions, the proposed strategy could detect target DNA down to 8.7fM with a linear range from 0.01pM to 1nM, showing high sensitivity. Meanwhile, the sensing strategy was successfully used for detection of Enterobacteriaceae bacteria down to 40CFUmL-1 in milk samples. This strategy presented a simple, rapid and sensitive platform for Enterobacteriaceae bacteria detection and would become a versatile and powerful tool for food safety, biothreat detection and environmental monitoring. © 2013 Elsevier B.V.


Cheng S.-Y.,Chongqing Medical University | Zhao Y.-D.,Chongqing Medical University | Li J.,Chongqing Medical University | Chen X.-Y.,Chongqing Medical University | And 2 more authors.
Psychoneuroendocrinology | Year: 2014

Background: Depression is a frequent mood disorder that affects around 33% of stroke patient. Our aim was to test the possible association between plasma glutamate and the development of post-stroke depression (PSD) in Chinese patients. Methods: The subjects were first-ever acute ischemic stroke (AIS) patients who were hospitalized during the period from November 2011 to September 2013. Clinical information and stroke severity was collected at admission. Neurological and neuropsychological evaluations were conducted at the 3-month follow-up. Plasma glutamate levels were analyzed at baseline using liquid chromatography followed by tandem mass spectrometry. Glutamate oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and blood markers were also tested. Multivariate analyses were performed using logistic regression models. Results: During the study period, 209 patients were included in the analysis. Seventy patients (33.5%) were diagnosed as having major depression at 3 month. Patients with major depression showed higher levels of plasma glutamate [299 (235-353) vs. 157 (108-206). μM, P<. 0.0001] and lower GOT [14 (11-20) vs. 21 (15-32). U/L, P<. 0.0001] at admission. In multivariate analyses, plasma glutamate and GOT were independent predictors of PSD at 3 months [odds ratio (OR): 1.03 (1.02-1.04), P<. 0.0001; 0.84 (0.75-0.97), P= 0.003]. Plasma levels of glutamate >205. μM were independently associated with PSD (OR, 21.3; 95% CI, 8.28-67.36, P<. 0.0001), after adjustment for possible variables. Conclusion: The present study demonstrates a strong relationship between plasma glutamate and GOT levels at admission and the development of PSD within 3 months. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options. © 2014 Elsevier Ltd.


Chen C.,Chongqing Medical University | Tambe D.T.,Harvard University | Deng L.,Changzhou University | Yang L.,Chongqing Medical University
American Journal of Physiology - Cell Physiology | Year: 2013

To withstand physiological loading over a lifetime, human synovial joints are covered and protected by articular cartilage, a layer of low-friction, load-bearing tissue. The unique mechanical function of articular cartilage largely depends on the composition and structural integrity of the cartilage matrix. The matrix is produced by highly specialized resident cells called chondrocytes. Under physiological loading, chondrocytes maintain the balance between degradation and synthesis of matrix macromolecules. Under excessive loading or injury, however, degradation exceeds synthesis, causing joint degeneration and, eventually, osteoarthritis (OA). Hence, the mechanoresponses of chondrocytes play an important role in the development of OA. Despite its clear importance, the mechanobiology of articular chondrocytes is not well understood. To summarize our current understanding, here we review studies of the effect of mechanical forces on mechanical and biological properties of articular chondrocytes. First, we present the viscoelastic properties of the cell nucleus, chondrocyte, pericellular matrix, and chondron. Then we discuss how these properties change in OA. Finally, we discuss the responses of normal and osteoarthritic chondrocytes to a variety of mechanical stimuli. Studies reviewed here may provide novel insights into the pathogenesis of OA and may help in development of effective biophysical treatment. © 2013 the American Physiological Society.


Chen Y.,Chongqing Medical University | Chen Y.,Stem Cell Institute Leuven | Verfaillie C.M.,Stem Cell Institute Leuven
Liver International | Year: 2014

MicroRNAs are a class of small non-coding RNAs involved in the transcriptional and post-transcriptional regulation of gene expression. The function of miRNAs in liver disease including hepatocellular carcinoma (HCC), hepatitis, and alcoholic liver disease, have been widely studied and extensively reviewed. Increasing evidence demonstrates that miRNAs also play a critical role in normal liver development and in the fine-tuning of fundamental biological liver processes. In this review, we highlight the most recent findings on the role of miRNAs in liver specification and differentiation, liver cell development, as well as in the many metabolic functions of the liver, including glucose, lipid, iron and drug metabolism. These findings demonstrate an important role of miRNAs in normal liver development and function. Further researches will be needed to fully understand how miRNAs regulate liver generation and metabolic function, which should then lead to greater insights in liver biology and perhaps open up the possibility to correct errors that cause liver diseases or metabolic disorders. © 2014 John Wiley and Sons A/S.


Zhang G.,Zhejiang Cancer Hospital | He J.-L.,Chongqing Medical University | Xie X.-Y.,Chongqing Medical University | Yu C.,Chongqing Medical University
International Journal of Molecular Medicine | Year: 2012

Activated microglia producing reactive nitrogen species, inflammatory factors, reactive oxygen species (ROS) and other neurovirulent factors, can lead to the development of neurodegenerative diseases. Certain compounds can inhibit the activation of microglia. However, the mechanisms remain unclear. In the present study, we investigated the inhibitory effect of geniposide on the production of ROS and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated N9 murine microglial cells through the p38, ERK1/2 and nuclear factor-κB (NF-κB) signaling pathways. After the N9 cells were pre-treated with the vehicle or geniposide and exposed to LPS for the time indicated, the MTT conversion test was used to assess cell viability. Suitable concentrations were chosen and adjusted according to the experiments. Extracellular nitric oxide (NO) release was measured by Griess reaction. The formation of ROS and intracellular NO was evaluated by fluorescence imaging. NOS activities were determined using commercially available kits. The morphology of the N9 cells was examined by hematoxylin and eosin staining. The expression of iNOS mRNA was examined by RT-PCR. The protein levels of iNOS, p38 mitogen-activated protein kinase (MAPK), ERK1/2 and NF-κB, inhibitory factor-κB-α (IκB-α) were determined by western blot analysis. The results showed that geniposide attenuated the activation of N9 cells and inhibited the overproduction of NO, intracellular ROS and the expression of iNOS induced by LPS in the cells. In addition, geniposide blocked the phosphorylation of p38, ERK1/2 and inhibited the drop-off of IκB induced by LPS in the cells. These data indicate that geniposide has therapeutic potential for the treatment of neurodegenerative diseases, and that it exerts its effects by inhibiting inflammation.


Wang Y.,CAS Beijing National Laboratory for Molecular | Zhao Q.,CAS Beijing National Laboratory for Molecular | Zhang H.,Chongqing Medical University | Yang S.,Chongqing Medical University | Jia X.,CAS Beijing National Laboratory for Molecular
Advanced Materials | Year: 2014

The extracellular matrix is mimicked by a novel dendrimer-based hydrogel, which exhibits a highly interconnected porous network, enhanced mechanical stiffness, and a low swelling ratio. The hydrogel system supports the proliferation and differentiation of mesenchymal stem cells without any cytotoxic effects. This dendrimer-based hydrogel may serve as a model for developing new advanced materials with applications in tissue engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Gortner L.,Saarland University | Shen J.,Chongqing Medical University | Tutdibi E.,Saarland University
Klinische Padiatrie | Year: 2013

Background: Gender differences in overall neonatal survival and in short term pulmonary outcome have been reported. Furthermore gender differences in childhood chronic lung disorders have been described all in favor of females. Methods: A typical survey on published data regarding gender differences in lung development has been carried out. Results: 1. Structural aspects of lung development: Lung development is regulated by a number of genes, being differently active in the terminal saccular and alveolar period. Gender differences have been described among others for regulation of vascular-endothelial and platelet derived growth factors (VEGF) and platelet-derived growth factor (PDGF), which are active during early lung development with a permissive effect of estrogens mediated by estrogen receptor beta (ER-β). 2. Functional aspects of lung development: Functional components of lung development mainly include surfactant synthesis. Regulation of surfactant protein synthesis was shown to be positively regulated by estrogens, thus favoring lung maturation in females. 3. Lung development and pregnancy complications: Inflammatory alterations induced by LPS lead to larger lung volumes under experimental conditions in females, whereas pulmonary prognosis after impaired intrauterine growth is not affected as clearly by gender. Conclusion: Epidemiological findings indicating an impaired male prognosis in neonatal lung disorders which can at least in part be explained by above described experimental findings. Increased estrogen concentrations in females acting via ER-β may be a key for understanding these findings. © Georg Thieme Verlag KG Stuttgart · New York.


Zhang F.,Nanjing University | Huang G.,Chongqing Medical University | Hu B.,Nanjing University | Song Y.,Nanjing University | Shi Y.,Nanjing University
Clinical and Experimental Immunology | Year: 2011

Recent studies show that thymic stromal lymphopoietin (TSLP) plays a critical role in the upstream phase of the allergic cascade to induce T helper type 2 cell (Th2)-dominant allergic diseases. However, the effect of blocking TSLP signalling with the soluble TSLP receptor (TSLPR), TSLPR-immunoglobulin (Ig), on asthma development needs further investigation. Here, we examined the effects of TSLPR-Ig on asthmatic airway inflammation and dendritic cell (DC) function. TSLPR-Ig (comprising the extracellular domain of murine TSLPR and an IgG2a Fc tail) purified from transfected COS-7 cells reduced the expression of CD40, CD80 and CD86 on TSLP-activated DCs in vitro. We also investigated the mechanisms underlying TSLPR-Ig-mediated amelioration of allergic airway inflammation in a murine asthma model. When TSLP signalling was blocked by intratracheal administration of TSLPR-Ig prior to sensitization, allergen-specific serum IgE levels, airway tissue inflammation, inflammatory cell infiltration and Th2 cytokine levels in the bronchiolar lavage fluid (BALF) were reduced significantly. This was because of the TSLP-Ig-mediated down-regulation of co-stimulatory molecule expression on pulmonary DCs. We also transferred bone marrow-derived mature DCs (mDCs) into the airways of asthmatic mice. Intratracheal administration of TSLPR-Ig prior to the transfer of mDCs reduced eosinophilic airway inflammation and Th2 differentiation significantly. Collectively, these data suggest that local use of TSLPR-Ig prevents airway inflammation, at least in part, by regulating DC function, and that blocking TSLP signalling using TSLPR-Ig may be a novel strategy for the treatment of asthma bronchiale. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.


Zhang S.,Chongqing Medical University | Liu P.,Chongqing Medical University | Chen L.,Nanjing Medical University | Wang Y.,Chongqing Medical University | And 2 more authors.
Biomaterials | Year: 2015

Adipose-derived stem cells (ADSCs) represent a valuable source of stem cells for regenerative medicine, but the loss of their stemness during invitro expansion remains a major roadblock. We employed a microgravity bioreactor (MB) to develop a method for biomaterial-free-mediated spheroid formation to maintain the stemness properties of ADSCs. ADSCs spontaneously formed three-dimensional spheroids in the MB. Compared with monolayer culture, the expression levels of E-cadherin and pluripotent markers were significantly upregulated in ADSC spheroids. Spheroid-derived ADSCs exhibited increased proliferative ability and colony-forming efficiency. By culturing the spheroid-derived ADSCs in an appropriate induction medium, we found that the multipotency differentiation capacities of ADSCs were significantly improved by spheroid culture in the MB. Furthermore, when ADSCs were administered to mice with carbon tetrachloride-induced acute liver failure, spheroid-derived ADSCs showed more effective potentials to rescue liver failure than ADSCs derived from constant monolayer culture. Our results suggest that spheroid formation of ADSCs in an MB enhances their stemness properties and increases their therapeutic potential. Therefore, spheroid culture in an MB can be an efficient method to maintain stemness properties, without the involvement of any biomaterials for clinical applications of invitro cultured ADSCs. © 2014 Elsevier Ltd.


Shen H.,Chongqing Fifth Hospital | Chen Y.,Chongqing Medical University | Lu K.-Z.,Chongqing Medical University | Chen J.,Chongqing Medical University
Journal of Surgical Research | Year: 2015

Background Shivering is the most common complication during the recovery period after general anesthesia, and there is no clear consensus about the best strategy for its prophylactic. The aim of the study was to evaluate the efficacy of parecoxib in prevention of postoperative shivering. Methods Eighty patients with American Society of Anesthesiologists physical status I-II, who were scheduled for minor urological surgeries under general anesthesia, were randomly assigned to two groups (n = 40 in each group): group P received 40 mg of parecoxib by intravenous bolus injection and group S received the same volume of normal saline in the same way just after the induction of anesthesia. Hemodynamic parameters and body temperatures including tympanic and axillary temperature were monitored. The occurrence of shivering and pain intensity score were recorded during the recovery period. Results Parecoxib significantly reduced the incidence and severity of shivering in comparison with the placebo. Postoperative shivering was observed in 22 patients in group S (55%), compared with nine in group P (22.5%) (P = 0.003). In addition, pain intensity scores were lower in group P during recovery period; consequently, less rescue analgesics were required in group P when compared with group S (P = 0.001). Regarding the body temperature, it was found that core temperature decreased but peripheral temperature increased significantly in both groups. There was no significant difference between groups in all time intervals. Conclusions Prophylactic administration of parecoxib produces dual effects on antishivering and postoperative analgesia. This implies that cyclooxygenase 2-prostaglandin E2 pathways may be involved in the regulation of shivering. © 2015 Elsevier Inc. All rights reserved.


Wang X.,Mount Sinai School of Medicine | Wang X.,Chongqing Biomean Technology Ltd. Co. | Wu D.,Mount Sinai School of Medicine | Yang L.,Mount Sinai School of Medicine | And 2 more authors.
Free Radical Biology and Medicine | Year: 2013

Ethanol induces hypoxia and elevates HIF-1α in the liver. CYP2E1 plays a role in the mechanisms by which ethanol generates oxidative stress, fatty liver, and liver injury. This study evaluated whether CYP2E1 contributes to ethanol-induced hypoxia and activation of HIF-1α in vivo and whether HIF-1α protects against or promotes CYP2E1-dependent toxicity in vitro. Wild-type (WT), CYP2E1-knock-in (KI), and CYP2E1 knockout (KO) mice were fed ethanol chronically; pair-fed controls received isocaloric dextrose. Ethanol produced liver injury in the KI mice to a much greater extent than in the WT and KO mice. Protein levels of HIF-1α and downstream targets of HIF-1α activation were elevated in the ethanol-fed KI mice compared to the WT and KO mice. Levels of HIF prolyl hydroxylase 2, which promotes HIF-1α degradation, were decreased in the ethanol-fed KI mice in association with the increases in HIF-1α. Hypoxia occurred in the ethanol-fed CYP2E1 KI mice as shown by an increased area of staining using the hypoxia-specific marker pimonidazole. Hypoxia was lower in the ethanol-fed WT mice and lowest in the ethanol-fed KO mice and all the dextrose-fed mice. In situ double staining showed that pimonidazole and CYP2E1 were colocalized to the same area of injury in the hepatic centrilobule. Increased protein levels of HIF-1α were also found after acute ethanol treatment of KI mice. Treatment of HepG2 E47 cells, which express CYP2E1, with ethanol plus arachidonic acid (AA) or ethanol plus buthionine sulfoximine (BSO), which depletes glutathione, caused loss of cell viability to a greater extent than in HepG2 C34 cells, which do not express CYP2E1. These treatments elevated protein levels of HIF-1α to a greater extent in E47 cells than in C34 cells. 2-Methoxyestradiol, an inhibitor of HIF-1α, blunted the toxic effects of ethanol plus AA and ethanol plus BSO in the E47 cells in association with inhibition of HIF-1α. The HIF-1α inhibitor also blocked the elevated oxidative stress produced by ethanol/AA or ethanol/BSO in the E47 cells. These results suggest that CYP2E1 plays a role in ethanol-induced hypoxia, oxidative stress, and activation of HIF-1α and that HIF-1α contributes to CYP2E1-dependent ethanol-induced toxicity. Blocking HIF-1α activation and actions may have therapeutic implications for protection against ethanol/CYP2E1-induced oxidative stress, steatosis, and liver injury. © 2013 Elsevier Inc. All rights reserved.


OBJECTIVE: To confirm the effectivity of Bifidobacterium infantis-mediated herpes simplex virus thymidine kinase/ganciclovir suicide gene system on the treatment of renal cell carcinoma in nude mice and further explore the mechanisms.MATERIALS AND METHODS: A B infantis thymidine kinase (B infantis-TK) suicide gene system was constructed in our previous study. Tumor-bearing nude mice were randomized into 4 groups and injected with normal saline, B infantis, B infantis/pGEX-1λT, and B infantis-TK, respectively, via tail vein, followed by intraperitoneal injection of ganciclovir. The treatment effects were evaluated by the terminal deoxynucleotidyl transferase-mediated deoxynucleotide triphosphate nick end labeling assay, quantitative reverse transcriptase polymerase chain reaction, and Western blotting. Side effects were also recorded.RESULTS: Compared with the other 3 treatments, the treatment with B infantis-TK resulted in a significant effective antitumor activity and stronger apoptotic response. Western blot analysis showed that the expression levels of Rel A and Bcl-xL were significantly lower, whereas those of caspase 3 and Bax were significantly higher in tumor tissues resected from group B infantis-TK, which were consistent with the quantitative reverse transcriptase-polymerase chain reaction results.CONCLUSION: The B infantis-TK/ganciclovir therapy system exhibits an effective antitumor activity by promoting tumor cell apoptosis through both the intrinsic and the extrinsic apoptotic pathways. Copyright © 2014 Elsevier Inc. All rights reserved.


Lu J.-Y.,General Hospital of Beijing Military Region | Sheng J.-Q.,Chongqing Medical University
World Journal of Gastroenterology | Year: 2015

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers due to inherited mutations in mismatch repair (MMR) genes. During the last decades, there have been great advances in research on Chinese Lynch syndrome. This review mainly focuses on the genetic basis, clinicopathologic features, diagnosis, intervention, chemoprevention, and surveillance of Lynch syndrome in China. In addition to frequently altered MMR genes, such as MLH1 , MSH2 , MSH6 , and MLH3 , other MMR-associated genes, such as those encoding human exonuclease 1, transforming growth factor β receptor 2, and alanine aminopeptidase, metastasisassociated protein 2, adenomatosis polyposis coli down-regulated 1, and hepatic and glial cell adhesion molecule have also been implicated in Chinese Lynch syndrome. Most Chinese researchers focused on the clinicopathologic features of Lynch syndrome, and it is noticeable that the most frequent extracolonic tumor in northeast China is lung cancer, which is different from other areas in China. The Chinese diagnostic criteria for Lynch syndrome have been established to identify gene mutation or methylation. With regard to chemoprevention, celecoxib may be effective to prevent polyps relapse in Lynch syndrome carriers. Additionally, a colonoscopy-based surveillance strategy for the prevention and early detection of neoplasms in Lynchsyndrome carriers has been proposed. © 2015 Baishideng Publishing Group Inc. All rights reserved.


Zhang Z.,Chongqing Medical University | Zhang Z.,University of Tübingen | Zhang Z.-Y.,University of Tübingen | Wu Y.,Chongqing Medical University | Schluesener H.J.,University of Tübingen
Brain Research | Year: 2012

A robust neuroinflammation, contributing to the development of secondary injury, is a common histopathological feature of traumatic brain injury (TBI). Characterization of leukocytic subpopulations contributing to the early infiltration of the damaged tissue might aid in further understanding of lesion development. Reactive macrophages/microglia can exert protective or damaging effects in TBI. CD163 is considered a marker of M2 (alternatively activated) macrophages. Therefore we investigated the accumulation of CD163+ macrophages/microglia in the brain of TBI rats. TBI was induced in rats using an open skull weight-drop contusion model and the accumulation of CD163 + cells was analyzed by immunohistochemistry. In normal rat brains, CD163 was expressed by meningeal, choroid plexus and perivascular macrophages. Significant parenchymal CD163+ cell accumulation was observed two days post TBI and continuously increased in the investigated survival time. The accumulated CD163+ cells were mainly distributed to the lesional areas and exhibited macrophage phenotypes with amoeboid morphologic characteristics but not activated microglial phenotypes with hypertrophic morphology and thick processes. Double-labeling experiments showed that most CD163+ cells co-expressed heme oxygenase-1 (HO-1). In addition, in vitro incubating of macrophage RAW264.7 cells or primary peritoneal macrophages with hemoglobin- haptoglobin (Hb-Hp) complex suppressed LPS-induced inflammatory macrophages phenotype and induced CD163 and HO-1 upregulation, indicating that CD163+ macrophages/microglia in TBI might have anti-inflammatory effects. And further study is necessary to identify functions of these cells in TBI. © 2012 Elsevier B.V. All rights reserved.


Luo Z.,Nanyang Technological University | Ding X.,Chongqing University | Hu Y.,Chongqing University | Wu S.,Nanyang Technological University | And 10 more authors.
ACS Nano | Year: 2013

In order to selectively target malignant cells and eliminate severe side effects of conventional chemotherapy, biocompatible and redox-responsive hollow nanocontainers with tumor specificity were fabricated. The mechanized nanocontainers were achieved by anchoring mechanically interlocked molecules, i.e., [2]rotaxanes, onto the orifices of hollow mesoporous silica nanoparticles via disulfide bonds as intermediate linkers for intracellular glutathione-triggered drug release. The [2]rotaxane employed was mainly composed of U.S. Food and Drug Administration approved tetraethylene glycol chains, α-cyclodextrin, and folic acid. In this study, folate groups on the mechanized hollow nanocontainers act as both the tumor-targeting agents and stoppers of the [2]rotaxanes. Detailed investigations showed that anticancer drug doxorubicin loaded mechanized nanocontainers could selectively induce the apoptosis and death of tumor cells. The drug-loaded nanocontainers enhanced the targeting capability to tumor tissues in vitro and inhibited the tumor growth with minimal side effects in vivo. The present controlled and targeted drug delivery system paves the way for developing the next generation of nanotherapeutics toward efficient cancer treatment. © 2013 American Chemical Society.


Liao Y.,Huazhong University of Science and Technology | Liu P.,Huazhong University of Science and Technology | Guo F.,Huazhong University of Science and Technology | Zhang Z.-Y.,University of Tübingen | Zhang Z.,Chongqing Medical University
PLoS ONE | Year: 2013

Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage. © 2013 Liao et al.


Yao C.,University of Tokyo | Yao C.,Chongqing Medical University | Sasaki H.M.,University of Tokyo | Ueda T.,University of Tokyo | And 3 more authors.
Molecular Cell | Year: 2015

Small interfering RNAs (siRNAs) direct cleavage of complementary target RNAs via an RNA-induced silencing complex (RISC) that contains Argonatute2 protein at its core. However, what happens after target cleavage remains unclear. Here we analyzed the cleavage reaction by Drosophila Argonaute2-RISC using single-molecule imaging and revealed a series of intermediate states in target recognition, cleavage, and product release. Our data suggest that, after cleavage, RISC generally releases the 5' cleavage fragment from the guide 3' supplementary region first and then the 3' fragment from the seed region, highlighting the reinforcement of the seed pairing in RISC. However, this order can be reversed by extreme stabilization of the 3' supplementary region or mismatches in the seed region. Therefore, the release order of the two cleavage fragments is influenced by the stability in each region, in contrast to the unidirectional base pairing propagation from the seed to the 3' supplementary region upon target recognition. © 2015 Elsevier Inc.


Wei Y.,Nanyang Technological University | Wei Y.,Chongqing Medical University | Yoshikai N.,Nanyang Technological University
Journal of the American Chemical Society | Year: 2013

We describe here a [3+3]-type condensation reaction of O-acetyl ketoximes and α,β-unsaturated aldehydes that is synergistically catalyzed by a copper(I) salt and a secondary ammonium salt (or amine). This redox-neutral reaction allows modular synthesis of a variety of substituted pyridines under mild conditions with tolerance of a broad range of functional groups. The reaction is driven by a merger of iminium catalysis and redox activity of the copper catalyst, which would initially reduce the oxime N-O bond to generate a nucleophilic copper(II) enamide and later oxidize a dihydropyridine intermediate to the pyridine product. © 2013 American Chemical Society.


Xu X.,University of Pittsburgh | Xu X.,Chongqing Medical University | Vatsyayan J.,University of Pittsburgh | Gao C.,University of Pittsburgh | And 2 more authors.
EMBO Reports | Year: 2010

Eukaryotic translation initiation factor 4E (eIF4E) is the cap-binding protein that binds the 5′ cap structure of cellular messenger RNAs (mRNAs). Despite the obligatory role of eIF4E in cap-dependent mRNA translation, how the translation activity of eIF4E is controlled remains largely undefined. Here, we report that mammalian eIF4E is regulated by SUMO1 (small ubiquitin-related modifier 1) conjugation. eIF4E sumoylation promotes the formation of the active eIF4F translation initiation complex and induces the translation of a subset of proteins that are essential for cell proliferation and preventing apoptosis. Furthermore, disruption of eIF4E sumoylation inhibits eIF4E-dependent protein translation and abrogates the oncogenic and antiapoptotic functions associated with eIF4E. These data indicate that sumoylation is a new fundamental regulatory mechanism of protein synthesis. Our findings suggest further that eIF4E sumoylation might be important in promoting human cancers. © 2010 European molecular biology organization.


Li Y.,University College London | Li D.,University College London | Ying X.,Chongqing Medical University | Khaw P.T.,University College London | Raisman G.,University College London
GLIA | Year: 2015

A radial array of fortified astrocytes (FASTs) is the load bearing structure of the rat optic nerve head (ONH). At the retinal end the ONH is suspended on a fluid filled extracellular space occupied by modified pigment cells which generate a glomerular-like formation of villi. We propose that regulation of fluid in and out of this space may contribute to buffering the normal fluctuations of intraocular pressure. The energy requirement for the fluid transfer process is provided by the dense vascularity of the ONH and is reflected in the giant mitochondria of the FASTs. We propose that glaucoma occurs when a maintained rise in pressure overwhelms the capacity of this regulatory system. Under these circumstances the FAST array becomes detached from its anchorage in the surrounding ONH sheath. Progressively driven backwards by the pressure, the FASTs degenerate. We propose that the degeneration of the FASTs is associated with ischemic damage caused by the backward stretching of their blood supply. Retraction of the FAST processes deprives the retinal ganglion cell axons of their energy support, resulting in axotomy. We consider that our previously observed rescue of axons and FASTs by transplantation of olfactory ensheathing cells is due to replacement of this lost energy source. © 2015 Wiley Periodicals, Inc.


Yang B.,Chongqing Medical University | Zhou X.,Chongqing Medical University | Lan C.,Hainan Provincial Peoples Hospital
BMC Gastroenterology | Year: 2015

Background: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Post-infectious IBS (PI-IBS) is caused by an acute gastrointestinal infection preceding the onset of symptoms. However, the pathophysiology of PI-IBS is not clear, and the purpose of this study was to investigate the probable immune mechanisms of PI-IBS. Methods: C57BL/6 mice were randomly assigned to either an infection group or a control group. Mice in the infection group were infected with Trichinella spiralis to establish a model of PI-IBS (500 Trichinella), while control mice received only salt solution. Visceral sensitivity of colorectal distention in mice was evaluated by abdominal withdrawal reflex scores and intestinal inflammation was assessed using hematoxylin-eosin staining; at day 56 post-infection, the mRNA and protein levels of specific cytokines in the gut segments were detected using reverse-transcription polymerase chain reaction and enzyme-linked immunoabsorbent assay. Results: Levels of interferon γ and interleukin (IL)-17 in the PI-IBS group were significantly increased in the duodenum and ileum, and IL-10 was decreased in the jejunum, ileum, and colon compared with control mice. However, the expression level of IL-1β was not significantly different between the two groups. Conclusions: The present study suggests that the local low-grade inflammation and immune activation that are an important component of the pathophysiology of PI-IBS are primarily induced and maintained by specific cytokines. © Yang et al.; licensee BioMed Central.


He H.,Chongqing Medical University | He H.,Sichuan Provincial Peoples Hospital | Huang H.,Chongqing Medical University | Yu T.,Chongqing Medical University
International Journal of Radiation Biology | Year: 2014

Purpose: To explore methodological modifications in the detection of DNA damage in sonochemotherapy for cisplatin-resistant human ovarian cancer cells using the comet assays. Materials and methods: Chemoresistant cells COC1/DDP were subjected to sonochemotherapy and DNA damage detected with the alkaline and neutral comet assays. Results: In the alkaline assay, the percentage of comets formed was less than that of dead cells, and most values for the percentage of comets formed were < 5% when using the default value to identify comets, showing an underestimation. These values were corrected when adjusting the threshold to the 95th percentile in control cells. In the neutral assay, this modification was not needed. Tail length (TL), tail moment (TM) and Olive tail moment (OTM) dramatically varied between comets. The 75th percentiles of TL, TM and OTM in the alkaline assay, and 90th percentiles in the neutral assay, correlated with the percentage of comets formed, thereby reflecting the temporal shift in DNA damage. Quantification of the interaction using the percentage of comets formed was consistent with that using the percentage of dead cells. Conclusions: The percentage of comets formed can be used to assess DNA damage in sonochemotherapy against chemoresistant cells when adjusting the threshold. © 2014 Informa UK, Ltd.


Si J.,Rhode Island Hospital | Si J.,Nanjing Medical University | Ge Y.,Rhode Island Hospital | Zhuang S.,Rhode Island Hospital | And 3 more authors.
Kidney International | Year: 2013

Adrenocorticotropic hormone (ACTH) has a renoprotective effect in chronic kidney disease; however, its effect on acute kidney injury (AKI) remains unknown. In a rat model of tumor necrosis factor (TNF)-induced AKI, we found that ACTH gel prevented kidney injury, corrected acute renal dysfunction, and improved survival. Morphologically, ACTH gel ameliorated TNF-induced acute tubular necrosis, associated with a reduction in tubular apoptosis. While the steroidogenic response to ACTH gel plateaued, the kidney-protective effect continued to increase at even higher doses, suggesting steroid-independent mechanisms. Of note, ACTH also acts as a key agonist of the melanocortin system, with its cognate melanocortin 1 receptor (MC1R) abundantly expressed in renal tubules. In TNF-injured tubular epithelial cells in vitro, ACTH reinstated cellular viability and eliminated apoptosis. This beneficial effect was blunted in MC1R-silenced cells, suggesting that this receptor mediates the anti-apoptotic signaling of ACTH. Moreover, ACTH gel protected mice against cecal ligation puncture-induced septic AKI better than α-melanocyte- stimulating hormone: a protein equal in biological activity to ACTH except for steroidogenesis. Thus, ACTH has additive renoprotective actions achieved by both steroid-dependent mechanisms and MC1R-directed anti-apoptosis. ACTH may represent a novel therapeutic strategy to prevent or treat AKI. © 2013 International Society of Nephrology.


Wu Y.,Chongqing Medical University | Wu Y.,University of British Columbia | Song W.,Chongqing Medical University | Song W.,University of British Columbia
FASEB Journal | Year: 2013

Abnormal expression of regulator of calcineurin 1 (RCAN1) has been implicated in Alzheimer's disease (AD) and Down's syndrome (DS). There are two major isoforms of RCAN1, isoforms 1 and 4. RCAN1 isoform 1 is predominantly expressed in the brain, particularly in neurons. In this report, we showed that there are two translation start codons in RCAN1 exon 1 serving as a functional translation initiation site to generate a longer 41-kDa isoform 1 (RCAN1.1L) and a shorter 31-kDa isoform 1 (RCAN1.1S). The first translation initiation site has higher translation efficiency than the downstream second one, and the translation initiation of two AUG sites is by a Cap-dependent mechanism. Short-term expression of RCAN1.1L protected SH-SY5Y cells from oxidative stress-induced apoptosis by inhibiting caspase-3 activation. However, long-term accumulation of RCAN1.1L in SH-SY5Y cells promoted oxidative stress-induced apoptosis via caspase-3 activation, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that the apoptosis ratio was increased to 499.03 ± 47.56% in SH-1.1L cells compared with 283.93 ± 28.66% in control cells. Furthermore, we found that RCAN1.1L is significantly elevated in the AD brains and patients with DS. RCAN1.1S is expressed at a low level in both human cells and brain tissues. Our results defined the regulatory mechanism underlying RCAN1 expression and the roles of RCAN1.1 in oxidative stress-induced neurodegeneration in AD and DS pathogenesis. © FASEB.


Wu Y.,University of British Columbia | Wu Y.,Chongqing Medical University | Ly P.T.T.,University of British Columbia | Song W.,University of British Columbia | Song W.,Chongqing Medical University
Molecular Neurobiology | Year: 2014

AD, a devastating neurodegenerative disorder, is the most common cause of dementia in the elderly. Patients with AD are characterized by three hallmarks of neuropathology including neuritic plaque deposition, neurofibrillary tangle formation, and neuronal loss. Growing evidences indicate that dysregulation of regulator of calcineurin 1 (RCAN1) plays an important role in the pathogenesis of AD. Aberrant RCAN1 expression facilitates neuronal apoptosis and Tau hyperphosphorylation, leading to neuronal loss and neurofibrillary tangle formation. This review aims to describe the recent advances of the regulation of RCAN1 expression and its physiological functions. Moreover, the AD risk factors-induced RCAN1 dysregulation and its role in promoting neuronal loss, synaptic impairments and neurofibrillary tangle formation are summarized. Furthermore, we provide an outlook into the effects of RCAN1 dysregulation on APP processing, Aβ generation and neuritic plaque formation, and the possible underlying mechanisms, as well as the potential of targeting RCAN1 as a new therapeutic approach. © 2014, Springer Science+Business Media New York.


Wang T.,CAS Institute of Biophysics | Wang T.,University of Chinese Academy of Sciences | Ding J.,CAS Institute of Biophysics | Zhang Y.,CAS Institute of Biophysics | And 2 more authors.
Acta Crystallographica Section D: Biological Crystallography | Year: 2013

The type VI secretion system (T6SS) is a bacterial protein-export machine that is capable of delivering virulence effectors between Gram-negative bacteria. The T6SS of Pseudomonas aeruginosa transports two lytic enzymes, Tse1 and Tse3, to degrade cell-wall peptidoglycan in the periplasm of rival bacteria that are competing for niches via amidase and muramidase activities, respectively. Two cognate immunity proteins, Tsi1 and Tsi3, are produced by the bacterium to inactivate the two antibacterial effectors, thereby protecting its siblings from self-intoxication. Recently, Tse1-Tsi1 has been structurally characterized. Here, the structure of the Tse3-Tsi3 complex is reported at 1.914;Å resolution. The results reveal that Tse3 contains a C-terminal catalytic domain that adopts a soluble lytic transglycosylase (SLT) fold in which three calcium-binding sites were surprisingly observed close to the catalytic Glu residue. The electrostatic properties of the substrate-binding groove are also distinctive from those of known structures with a similar fold. All of these features imply that a unique catalytic mechanism is utilized by Tse3 in cleaving glycosidic bonds. Tsi3 comprises a single domain showing a β-sandwich architecture that is reminiscent of the immunoglobulin fold. Three loops of Tsi3 insert deeply into the groove of Tse3 and completely occlude its active site, which forms the structural basis of Tse3 inactivation. This work is the first crystallographic report describing the three-dimensional structure of the Tse3-Tsi3 effector-immunity pair. © 2013 International Union of Crystallography Printed in Singapore - all rights reserved. © 2013.


Zhang J.,University of Michigan | Zhang J.,Chongqing Medical University | Ellsworth K.,University of Michigan | Ma P.X.,University of Michigan
Macromolecular Rapid Communications | Year: 2012

We report the synthesis of a hydrophilic copolymer with one polyethylene glycol (PEG) block and one β-cyclodextrin (β-CD) containing block by a "click" reaction between azido-substituted β-CD and propargyl flanking copolymer. 1H NMR study suggested a highly efficient conjugation of β-CD units by this approach. The obtained copolymer was used as a host macromolecule to construct assemblies in the presence of hydrophobic guests. For assemblies containing a hydrophobic polymer, their size can be simply adjusted by simply changing the content of hydrophobic component. By serving as a guest molecule, hydrophobic drugs can also be loaded accompanying the formation of nanoparticles, and the drug payload is releasable. Therefore, the copolymer synthesized herein can be employed as a carrier for drug delivery. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Guo F.,Chongqing Medical University | Lai Y.,New York University | Tian Q.,New York University | Lin E.A.,New York University | And 2 more authors.
Arthritis and Rheumatism | Year: 2010

Objective. To determine 1) whether a protein interaction network exists between granulin-epithelin precursor (GEP), ADAMTS-7/ADAMTS-12, and cartilage oligomeric matrix protein (COMP); 2) whether GEP interferes with the interactions between ADAMTS-7/ADAMTS-12 metalloproteinases and COMP substrate, including the cleavage of COMP; 3) whether GEP affects tumor necrosis factor α (TNFα)-mediated induction of ADAMTS-7/ADAMTS-12 expression and COMP degradation; and 4) whether GEP levels are altered during the progression of arthritis. Methods. Yeast two-hybrid, in vitro glutathione S-transferase pull-down, and coimmunoprecipitation assays were used to 1) examine the interactions between GEP, ADAMTS-7/ADAMTS-12, and COMP, and 2) map the binding sites required for the interactions between GEP and ADAMTS-7/ADAMTS-12. Immunofluorescence cell staining was performed to visualize the subcellular localization of GEP and ADAMTS-7/ADAMTS-12. An in vitro digestion assay was employed to determine whether GEP inhibits ADAMTS-7/ADAMTS-12-mediated digestion of COMP. The role of GEP in inhibiting TNFα-induced ADAMTS-7/ADAMTS-12 expression and COMP degradation in cartilage explants was also analyzed. Results. GEP bound directly to ADAMTS-7 and ADAMTS-12 in vitro and in chondrocytes, and the 4 C-terminal thrombospondin motifs of ADAMTS-7/ADAMTS-12 and each granulin unit of GEP mediated their interactions. Additionally, GEP colocalized with ADAMTS-7 and ADAMTS-12 on the cell surface of chondrocytes. More importantly, GEP inhibited COMP degradation by ADAMTS-7/ADAMTS-12 in a dose-dependent manner through 1) competitive inhibition through direct protein-protein interactions with ADAMTS-7/ADAMTS-12 and COMP, and 2) inhibition of TNFα-induced ADAMTS-7/ADAMTS-12 expression. Furthermore, GEP levels were significantly elevated in patients with either osteoarthritis or rheumatoid arthritis. Conclusion. Our observations demonstrate a novel protein-protein interaction network between GEP, ADAMTS-7/ADAMTS-12, and COMP. Furthermore, GEP is a novel specific inhibitor of ADAMTS-7/ADAMTS-12-mediated COMP degradation and may play a significant role in preventing the destruction of joint cartilage in arthritis. © 2010, American College of Rheumatology.


Wei X.,Chongqing Medical University | Xiang T.,Chongqing Medical University | Ren G.,Chongqing Medical University | Tan C.,Chongqing Medical University | And 3 more authors.
Cellular Signalling | Year: 2013

The hepatitis B virus x (HBx) protein has been implicated in HBV-related hepatocellular carcinoma (HCC) pathogenesis. However, whether HBx regulates miRNA expression that plays important roles in gene regulation during hepatocarcinogenesis remains unknown. The expression of microRNA-101 (miR-101) in HBV-related HCC tissues and HCC cells was evaluated by real-time PCR. The direct target of miR-101, DNA methyltransferase 3A (DNMT3A), was identified in silico and validated using a 3'-UTR reporter assay. miR-101 was functionally characterized in cells with transiently altered miR-101 expression. HBx expression was found to have a significant inverse correlation with miR-101 expression in HBx-expressing HepG2 compared to control HepG2 cells. miR-101 expression was frequently down-regulated in HBV-related HCC tissues compared to adjacent noncancerous hepatic tissues and had a significant inverse correlation with DNMT3A expression in HBV-related HCCs. Further characterization of miR-101 revealed that it negatively regulated DNA methylation partly through targeting DNMT3A. HBx-mediated miR-101 down-regulation and DNMT3A up-regulation supported the enhanced DNA methylation of several tumor-suppressor genes in HBx-expressing cells. Our studies demonstrating the deregulation of miR-101 expression by HBx may provide novel mechanistic insights into HBV-mediated hepatocarcinogenesis and identify a potential miRNA-based targeted approach for treating HBV-related HCC. © 2012 Elsevier Inc.


Chen Y.,CAS Shanghai Institute of Ceramics | Chen H.,CAS Shanghai Institute of Ceramics | Zeng D.,Chongqing Medical University | Tian Y.,Chongqing Medical University | And 2 more authors.
ACS Nano | Year: 2010

A potential platform for simultaneous anticancer drug delivery and MRI cell imaging has been demonstrated by uniform hollow inorganic core/shell structured multifunctional mesoporous nanocapsules, which are composed of functional inorganic (Fe3O4, Au, etc.) nanocrystals as cores, a thin mesoporous silica shell, and a huge cavity in between. The synthetic strategy for the creation of huge cavities between functional core and mesoporous silica shell is based on a structural difference based selective etching method, by which solid silica middle layer of Fe2O3@SiO 2@mSiO2 (or Au@SiO2@mSiO2) composite nanostructures was selectively etched away while the mesoporous silica shell could be kept relatively intact. The excellent biocompatibility of obtained multifunctional nanocapsules (Fe3O4@mSiO2) was demonstrated by very low cytotoxicity against various cell lines, low hemolyticity against human blood red cells and no significant coagulation effect against blood plasma. The cancer cell uptake and intracellular location of the nanocapsules were observed by confocal laser scanning microscopy and bio-TEM. Importantly, the prepared multifunctional inorganic mesoporous nanocapsules show both high loading capacity (20%) and efficiency (up to 100%) for doxorubicin simultaneously because of the formation of the cavity, enhanced surface area/pore volume and the electrostatic interaction between DOX molecules and mesoporous silica surface. Besides, the capability of Fe3O 4@mSiO2 nanocapsules as contrast agents of MRI was demonstrated both in vitro and in vivo, indicating the simultaneous imaging and therapeutic multifunctionalities of the composite nanocapsules. Moreover, the concept of multifunctional inorganic nanocapsules was extended to design and prepare Gd-Si-DTPA grafted Au@mSiO2 nanocapsules for nanomedical applications, further demonstrating the generality of this strategy for the preparation of various multifunctional mesoporous nanocapsules. © 2010 American Chemical Society.


Duan X.,Chongqing Medical University | Kadakia A.R.,University of Michigan
Archives of Orthopaedic and Trauma Surgery | Year: 2012

Recurrence of the deformity is unfortunately a common occurrence following surgical treatment of hallux valgus. The underlying reason for recurrence is multifactorial and includes surgeon's factor, patient's factor, and deformity components that were not addressed at the index procedure. Salvage of recurrence can be challenging for both the patient and the surgeon. Successful treatment requires understanding the underlying reason for the failure of initial treatment and correcting bony alignment, restoring the joint congruity, and balancing soft tissues. We present an algorithmic approach to revision hallux valgus surgery. © 2011 Springer-Verlag.


Wang X.,CAS Shanghai Institute of Ceramics | Chen H.,CAS Shanghai Institute of Ceramics | Chen Y.,CAS Shanghai Institute of Ceramics | Ma M.,CAS Shanghai Institute of Ceramics | And 6 more authors.
Advanced Materials | Year: 2012

An inorganic enhancement agent (EA) for high-intensity focused ultrasound (HIFU) imaging based on mesoporous silica nanocapsules is presented. The pronounced coagulative necrosis effects demonstrate, both in vitro and in vivo, that the EA can be developed as a highly promising theranostic agent for effective HIFU imaging and therapy owing to its high stability, efficient perfluorohexane loading and release, enhanced tumor ablation capability, and easy uptake by target tissues. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Niu D.,East China University of Science and Technology | Liu Z.,Chongqing Medical University | Li Y.,East China University of Science and Technology | Luo X.,East China University of Science and Technology | And 4 more authors.
Advanced Materials | Year: 2014

It can be larger: A facile self-assembly/solvothermal approach to synthesize monodispersed, large-pore (>12 nm) silica nanospheres (LPSNs) with ordered, accessible, and interconnected pore channels has been successfully developed by utilizing an amphiphilic block copolymer (polystyrene-b-poly (acrylic acid), PS-b-PAA) as pore template and cetyltrimethylammonium bromide (CTAB) as structure-stabilizing agent. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Zhang J.,University of Michigan | Zhang J.,Chongqing Medical University | Ma P.X.,University of Michigan
Polymer | Year: 2011

Double hydrophilic copolymers (PEG-b-PCDs) with one PEG block and another block containing β-cyclodextrin (β-CD) units were synthesized by macromolecular substitution reaction. Via a dialysis procedure, complex assemblies with a core-shell structure were prepared using PEG-b-PCDs in the presence of a hydrophobic homopolymer poly(β-benzyl l-aspartate) (PBLA). The hydrophobic PBLA resided preferably in the cores of assemblies, while the extending PEG chains acted as the outer shell. Host-guest interaction between β-CD and hydrophobic benzyl group was found to mediate the formation of the assemblies, where PEG-b-PCD and PBLA served as the host and guest macromolecules, respectively. The particle size of the assemblies could be modulated by the composition of the host PEG-b-PCD copolymer. The molecular weight of the guest polymer also had a significant effect on the size of the assemblies. The assemblies prepared from the host and guest polymer pair were stable during a long-term storage. These assemblies could also be successfully reconstituted after freeze-drying. The assemblies may therefore be used as novel nanocarriers for the delivery of hydrophobic drugs. © 2011 Elsevier Ltd. All rights reserved.


Wang X.,CAS Shanghai Institute of Ceramics | Chen H.,CAS Shanghai Institute of Ceramics | Zheng Y.,Chongqing Medical University | Ma M.,CAS Shanghai Institute of Ceramics | And 4 more authors.
Biomaterials | Year: 2013

Au nanoparticles-coated, perfluorohexane-encapsulated and PEGylated mesoporous silica nanocapsule-based enhancement agents (MSNCAu-PFH-PEG, abb. as MAPP) have been synthesized, for the ultrasound-induced cytoclasis, contrast-intensified ultrasound (US) imaging and US-guided high intensity focused ultrasound (HIFU) surgical therapy. Both the US-induced thermal effect and US triggered release of loaded model drug with MAPP under US exposure indicated the excellent US sensitivity of MAPP and its applicability for the combined chemo-/thermal therapy and future potential for HIFU ablation; US imaging under different modes verify the attractive US contrast intensification by using MAPP; US-guided HIFU therapy ex vivo and in vivo with MAPP is found to be highly efficient on rabbit VX2 xenograft tumor ablation due to the high thermal energy accumulation and increased mechanical/thermal effects from US-induced PFH bubble cavitations. MAPP can be promisingly used as an inorganic theranostic platform for contrast-intensified US imaging, combined chemotherapy and efficient HIFU tumor ablation under the guidance by the intensified US. © 2012 Elsevier Ltd.


Niu D.,East China University of Science and Technology | Wang X.,CAS Shanghai Institute of Ceramics | Li Y.,East China University of Science and Technology | Zheng Y.,Chongqing Medical University | And 6 more authors.
Advanced Materials | Year: 2013

Multifunctional organic/inorganic hybrid nanovesicles, fabricated by a facile self-assembly/sol-gel approach, display a unique morphology (figure) and satisfactory stability under physiological conditions. By co-encapsulation of superparamagnetic magnetite nanoparticles and a liquid perfluorocarbon, the nanovesicles can be used not only as a dual-modality ultrasound/magnetic resonance contrast agent for accurate cancer diagnosis and monitoring, but also as a therapeutic enhancement agent for effective high-intensity focused ultrasound (HIFU) ablation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Guo F.,Chongqing Medical University | Lin E.A.,New York University | Liu P.,Chongqing Medical University | Lin J.,Chongqing Medical University | Liu C.,New York University
Cellular Signalling | Year: 2010

Upregulation of the inducible nitric oxide synthase (iNOS) gene is associated with many pathological conditions such as endoplasmic reticulum (ER) stress, and X-box binding protein 1 (XBP1) is critical in mediating ER-stress responsive genes, including iNOS. Nonetheless, the mechanism by which XBP1 regulates iNOS during ER stress remains unexplored. Here we show that the active/spliced form of XBP1 protein, XBP1S, directly binds to the AABS (A-activator-binding site) in the iNOS promoter in vitro and in living cells. XBP1S exhibits dose-dependent activation of iNOS-specific reporter gene activity and endogenous iNOS expression. XBP1S is elevated whereas the unspliced form of XBP1, XBP1U, reduced in ER stress in HepG2 cells. In addition, XBP1U binds to XBP1S and this complex is associated with the iNOS promoter in response to ER stress. Furthermore, XBP1U acts as a negative mediator and suppresses XBP1S-mediated induction of iNOS. Collectively, we present the first evidence demonstrating the regulation of iNOS gene induction by the interaction between the spliced and unspliced forms of XBP1 in response to ER stress. © 2010 Elsevier Inc.


Zhang C.,Chongqing Medical University | Li C.,University of Michigan | He F.,Chongqing Medical University | Cai Y.,Chongqing Medical University | And 2 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2011

Objective: Purification and characterization of cancer stem cells (CSCs) can lead to the identification of targets for therapeutic interventions of cancer. With regard to gastric cancer, studies have not yet defined and characterized CSCs. Methods: The expression of the cell surface markers CD44 and CD24 was examined in gastric cell lines AGS and gastric cancer tissues from five patients with fluorescence-activated cell sorting analysis (FACS). The tumorigenic properties, self-renewal, and differentiated progeny in the two distinct cell populations CD44+CD24+ and CD44-CD24- were identified in vivo serial transplantation and in vitro culture. Real-time RT-PCR was used to assess the expression of sonic hedgehog (SHH), patched 1 (PTCH1), and GLI3 signaling molecules in CD44+CD24+ and CD44-CD24- cells. Results: As few as 200 CD44+CD24+ cells injected in NOD-SCID mice were able to generate tumors in 50% of mice (6 of 12), while tumors did not form in mice until at least 10,000 CD44-CD24- cells were injected, where only one of 12 mice formed a tumor, further verifying that CD44+CD24+ gastric cancer cells have the capacity to both self-renew and produce differentiated progeny. Moreover, SHH, PTCH1, and GLI3 mRNA expression increased significantly in the CD44+CD24+ subpopulation when compared with the CD44-CD24- subpopulation. Conclusions: These studies strongly suggest that the CD44+CD24+ subpopulation of human gastric cancer cell lines, AGS, is gastric cancer stem cells. © 2011 Springer-Verlag.


Zhang J.,Chongqing Medical University | Ma P.X.,University of Michigan
Nano Today | Year: 2010

Supramolecular nano-structures assembled by polymeric amphiphiles have been intensively studied during the last two decades. Such nanocarriers may be engineered to possess on-demand bio-responsitivity for the prevention, diagnosis, and treatment of human diseases. The successful development of several nano-assembly-based polymer therapeutics further encouraged scientists to develop nano-vehicles to achieve controlled release, enhanced efficacy, improved specificity and reduced toxicity. Different from the abundant existing literatures on the hydrophobically or electrostatically driven self-assemblies and their therapeutic applications, this article reviews host-guest interaction mediated nano-assemblies, especially those constructed using cyclodextrins as the host entities. The excellent biocompatibility, complexation capacity, and chemical-sensitivity of cyclodextrin make cyclodextrin-containing polymers attractive to construct host-guest nano-assemblies. Such nanocarriers may be advantageous also because of the broad availability of cyclodextrins, their flexibility for structure/property modulation and their chemical-responsive characteristics. © 2010 Elsevier Ltd.


Fan Y.,Chongqing Medical University | Weng Y.-G.,Deutsches Herzzentrum Berlin | Huebler M.,Deutsches Herzzentrum Berlin | Cowger J.,University of Michigan | And 5 more authors.
Journal of the American College of Cardiology | Year: 2011

Objectives: This study aimed to determine the pre-implantation predictors for in-hospital mortality in children with ventricular assist device (VAD) support. Background: Candidate selection is of critical importance for improved outcomes in patients supported with VAD. However, risk factors for post-VAD survival in children are still not clearly understood. Methods: From June 1996 to December 2009, 92 children underwent implantation of a long-term VAD at Germany Heart Institute Berlin. Data on all these patients were retrospectively analyzed, and pre-operative risk factors for in-hospital survival after VAD implantation were identified by multivariate logistic regression. Results: Of the 92 subjects, the median age at implantation was 7 years (range 12 days to 18 years), and the median support time was 35 days (range 1 to 591 days). The overall survival rate to transplantation or recovery of ventricular function was 63%. Independent predictors of in-hospital mortality in children included congenital etiology (odds ratio [OR]: 11.2; 95% confidence interval [CI]: 2.6 to 47.5), norepinephrine requirement (OR: 6.9; 95% CI: 1.4 to 31), C-reactive protein level >6.3 mg/dl (OR: 4.9; 95% CI: 1.1 to 22.1), and central venous pressure >17 mm Hg (OR: 4.6; 95% CI: 1.1 to 20). Conclusions: Congenital etiology, pre-operative norepinephrine requirement, higher serum C-reactive protein, and central venous pressure were associated with increased in-hospital mortality in children with VAD support. Optimal candidate selection and timing of VAD insertion may be of great importance for improved outcomes in children with advanced heart failure. © 2011 American College of Cardiology Foundation.


Xiao H.,Zhejiang University | Jiang N.,Chongqing Medical University | Zhou B.,Chongqing Medical University | Liu Q.,Chongqing Medical University | Du C.,Chongqing Medical University
Cancer Science | Year: 2015

The transcriptional coactivator with PDZ binding motif (TAZ) has been reported to be one of the nuclear effectors of Hippo-related pathways. TAZ is expressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in hepatocellular carcinoma (HCC). In the current study, we show that TAZ regulates cellular proliferation and epithelial-mesenchymal transition (EMT) of HCC. TAZ is overexpressed in HCC tissues and cell lines and upregulation of TAZ correlates with a lower overall survival rate of HCC patients after hepatic resection. TAZ knockdown results in inhibition of cancer cell proliferation through decreases in expression of stem cell markers (OCT4, Nanog, and SOX2). Reduction in HCC cell migration and invasion is also evident through reversal of EMT by increases E-cadherin expression, decreases in N-cadherin, vimentin, Snail, and Slug expression, and suppression of MMP-2 and MMP-9 expression. In a xenograft tumorigenicity model, TAZ knockdown could effectively inhibit tumor growth and metastasis through reversal of the EMT pathway. In conclusion, TAZ is associated with the proliferation and invasiveness of HCC cells, and the TAZ gene may contribute to a novel therapeutic approach against HCC. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.


Liu M.,Chongqing Medical University | Bian C.,Chongqing Medical University | Zhang J.,Chongqing Medical University | Wen F.,Mississippi College
Scientific Reports | Year: 2014

The relationship between Apolipoprotein E (ApoE) genotype and the risk of Alzheimer's disease (AD) is relatively well established in Caucasians, but less established in other ethnicities. To examine the association between ApoE polymorphism and the onset of AD in Chinese population, we searched the commonly used electronic databases between January 2000 and November 2013 for relevant studies. Total 20 studies, including 1576 cases and 1741 controls, were retrieved. The results showed statistically significant positive association between risk factor ε4 allele carriers and AD in Chinese population (OR = 3.93, 95% CI = 3.37-4.58, P < 0.00001). Genotype ApoE ε4/ε4 and ε4/ε3 have statistically significant association with AD as well (ε4/ε4: OR = 11.76, 95% CI = 6.38-21.47, P < 0.00001; ε4/ε3: OR = 3.08, 95% CI = 2.57-3.69, P < 0.00001). Furthermore, the frequency of the ApoE ε3 is lower in AD than that in the health controls, and the difference of ε3 allele is also statistically significant (OR = 0.42, 95% CI = 0.37-0.47, P < 0.00001). No significant heterogeneity was observed among all studies. This meta-analysis suggests that the subject with at least one ApoE ε4 allele has higher risk suffering from AD than controls in Chinese population. The results also provide a support for the protection effect of ApoE ε3 allele in developing AD.


Liu K.,Chongqing Medical University | Zhou R.,Chongqing Medical University | Wang B.,Chongqing Medical University | Mi M.-T.,Chongqing Medical University
American Journal of Clinical Nutrition | Year: 2014

Background: The results of human clinical trials investigating the effects of resveratrol on glucose control and insulin sensitivity are inconsistent. Objective: We aimed to quantitatively evaluate the effects of resveratrol on glucose control and insulin sensitivity. Design: We performed a strategic literature search of PubMed, Embase, MEDLINE, and the Cochrane Library (updated to March 2014) for randomized controlled trials that estimated the effects of resveratrol on glucose control and insulin sensitivity. Study quality was assessed by using the Jadad scale. Weighted mean differences were calculated for net changes in glycemic measures by using fixed-effects or random-effects models. We performed prespecified subgroup and sensitivity analyses to evaluate potential heterogeneity. Meta-regression analyses were conducted to investigate dose effects of resveratrol on fasting glucose and insulin concentrations in nondiabetic subjects. Results: Eleven studies comprising a total of 388 subjects were included in this meta-analysis. Resveratrol consumption significantly reduced fasting glucose, insulin, glycated hemoglobin, and insulin resistance (measured by using the homeostatic model assessment) levels in participants with diabetes. No significant effect of resveratrol on glycemic measures of nondiabetic participants was found in the metaanalysis. Subgroup and sensitivity analyses indicated that the pooled effects of resveratrol on fasting glucose and insulin concentrations in nondiabetic participants were not affected by body mass index, study design, resveratrol dose, study duration, or Jadad score. Conclusions: Resveratrol significantly improves glucose control and insulin sensitivity in persons with diabetes but does not affect glycemic measures in nondiabetic persons. Additional high-quality studies are needed to further evaluate the potential benefits of resveratrol in humans. © 2014 American Society for Nutrition.


Feng K.,Chongqing Medical University | Ma K.-S.,Chongqing Medical University
World Journal of Gastroenterology | Year: 2014

Hepatocellular carcinoma (HCC) is a malignant disease that substantially affects public health worldwide. It is especially prevalent in east Asia and sub-Saharan Africa, where the main etiology is the endemic status of chronic hepatitis B. Effective treatments with curative intent for early HCC include liver transplantation, liver resection (LR), and radiofrequency ablation (RFA). RFA has become the most widely used local thermal ablation method in recent years because of its technical ease, safety, satisfactory local tumor control, and minimally invasive nature. This technique has also emerged as an important treatment strategy for HCC in recent years. RFA, liver transplantation, and hepatectomy can be complementary to one another in the treatment of HCC, and the outcome benefits have been demonstrated by numerous clinical studies. As a pretrans-plantation bridge therapy, RFA extends the average waiting time without increasing the risk of dropout or death. In contrast to LR, RFA causes almost no intra-abdominal adhesion, thus producing favorable conditions for subsequent liver transplantation. Many studies have demonstrated mutual interactions between RFA and hepatectomy, effectively expanding the operative indications for patients with HCC and enhancing the efficacy of these approaches. However, treated tumor tissue remains within the body after RFA, and residual tumors or satellite nodules can limit the effectiveness of this treatment. Therefore, future research should focus on this issue. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Zhu T.,Chongqing Medical University | Zhang W.,Chongqing Medical University | Wang D.-X.,Chongqing Medical University
Injury | Year: 2012

Activity of the epithelial sodium channels (ENaCs) in the lung tissue plays a critical role on sodium/fluid homeostasis and the lung fluid clearance. The serum- and glucocorticoid-inducible kinase-1 (SGK1), one of the critical regulation proteins of ENaC, is activated by insulin and growth factors possibly through 3-phosphoinositide-dependent kinase PDK1 or/and phosphatidylinositol 3-kinase (PI3K). However, it is uncertain whether insulin shows its stimulatory action on ENaC by activation of SGK1 in lipopolysaccharide (LPS)-induced acute lung injury (ALI) condition. In our study, Wistar rats were injected with LPS to induce ALI. Evans blue dye albumin (EBA) concentration was used to measure pulmonary oedema. For detecting the ratio of phospho-SGK1/SGK1 and α-ENaC protein, Western blot was performed. Real-time polymerase chain reaction (RT-PCR) was used to assess α-ENaC messenger RNA (mRNA). Immunohistochemistry was used to locate and quantitate α-ENaC expression. The EBA concentration was markedly increased by LPS alone but significantly reduced in rats that also received insulin injection. The ratio of phospho-SGK1/SGK1 was raised significantly in the insulin group and insulin + LPS group, compared with the control group and the LPS group, respectively. Furthermore, α-ENaC was up-regulated by insulin treatment. Simultaneously, injection with LPS significantly reduced α-ENaC expression. These findings demonstrated that insulin up-regulates ENaC in vivo possibly resulting from activation of SGK1. © 2012 Elsevier Ltd.


Li S.,Chongqing Medical University | Zhu X.,Chongqing Medical University | Zhang W.,Chongqing Medical University | Xie G.,Chongqing Medical University | Feng W.,Chongqing Medical University
Applied Surface Science | Year: 2012

In this paper, an amperometric electrochemical biosensor for the detection of hydrogen peroxide (H 2O 2), based on gold nanoparticles (GNPs)/thionine (Thi)/GNPs/multi-walled carbon nanotubes (MWCNTs)-chitosans (Chits) composite film was developed. MWCNTs-Chits homogeneous composite was first dispersed in acetic acid solution and then the GNPs were in situ synthesized at the composite. The mixture was dripped on the glassy carbon electrode (GCE) and then the Thi was deposited by electropolymerization by Au-S or Au-N covalent bond effect and electrostatic adsorption effect as an electron transfer mediator. Finally, the mixture of GNPs and horseradish peroxidase (HRP) was assembled onto the modified electrode by covalent bond. The electrochemical behavior of the modified electrode was investigated by scanning electron microscope, cyclic voltammetry and chronoamperometry. This study introduces the in situ-synthesized GNPs on the other surface of the modified materials in H 2O 2 detection. The linear response range of the biosensor to H 2O 2 concentration was from 5 × 10 -7 mol L -1 to 1.5 × 10 -3 mol L -1 with a detection limit of 3.75 × 10 -8 mol L -1 (based on S/N = 3). © 2011 Elsevier B.V. All rights reserved.


Liu C.,Chongqing Medical University | Wang X.-Z.,Chongqing Medical University | Sun X.-B.,Chongqing Medical University
Early Human Development | Year: 2013

The prevalence of recurrent miscarriage (RM) is about 1-3% of women; the pathogenesis of RM is not fully understood yet. This study aims to assess the sperm antigen specific regulatory T cells (Treg) in women with RM. Methods: A group of women with RM was recruited into this study. The sperm antigen was extracted from the semen samples of each woman's husband. The sperm antigen specific T cell response was assessed by flow cytometry. Results: Low frequency of sperm specific Tregs and high frequency of T helper (Th)1 cells were detected in RM women as compared with women without RM. The sperm specific Tregs in RM women expressed less Ubc13. Knockdown of Ubc13 from Tregs converted the Tregs to effector T cells. Conclusions: Immune deregulation may play an important role in RM. © 2012 Elsevier Ltd.


Chen J.,Chongqing Medical University | Huang Q.,Chongqing Medical University | Wang F.,Chongqing Medical University
Tumor Biology | Year: 2014

Glioblastoma is the most aggressive malignant primary brain tumor in humans, with extremely poor patient survival. Although previous studies have demonstrated that expression of matrix metalloproteinase-9 (MMP9) in glioblastoma promotes cancer metastasis, the upstream molecular signaling cascades that control activation of MMP9 remain largely unknown. Here, we used a human glioblastoma line, A-172, to examine molecular signaling to activate MMP9. We found that epidermal growth factor (EGF)-induced activation of epidermal growth factor receptor (EGFR) in A-172 cells activated MMP9, resulting in an increase in cancer invasiveness. A specific inhibitor for EGFR efficiently blocked EGF-induced activation of MMP9 and then cancer invasiveness. Moreover, an inhibitor for phosphatidylinositol 3-kinase (PI-3 K)/protein kinase B (Akt) significantly inhibited the EGF-induced activation of MMP9. Furthermore, nuclear exclusion of a major Akt downstream target, Forkhead box protein O1 (FoxO1), was induced by Akt activation, which could be inhibited by either an EGFR inhibitor or by PI-3 K/Akt inhibitor. An expression of a constitutive nuclear form of FoxO1 significantly inhibited MMP9 activation induced by EGF. Taken together, these findings suggest that EGF/EGFR signaling activates downstream PI-3 K/Akt to induce FoxO1 nuclear exclusion, which activates MMP9 to promote glioblastoma invasiveness. Thus, FoxO1 appears to be a novel therapeutic target for inhibiting metastasis of glioblastoma. © 2014 International Society of Oncology and BioMarkers (ISOBM).


Zhong G.,Chongqing Medical University | Wang Y.,Chongqing Medical University | Zhang Y.,Chongqing Medical University | Guo J.J.,University of Cincinnati | Zhao Y.,Chongqing Medical University
PLoS ONE | Year: 2015

Background: Previous studies showed inconsistent results on the association of smoking with all-cause dementia and vascular dementia (VaD), and are limited by inclusion of a small number of studies and unexplained heterogeneity. Our review aimed to assess the risk of all-cause dementia, Alzheimer's disease (AD) and VaD associated with smoking, and to identify potential effect modifiers. Methods and Findings: The PubMed, Embase, Cochrane Library and Psychinfo databases were searched to identify studies that provided risk estimates on smoking and incidence of dementia. A random-effects model was used to yield pooled results. Thirty-seven studies were included. Compared with never smokers, current smokers showed an increased risk of all-cause dementia (risk ratio (RR) 1.30, 95%confidence interval (CI) 1.18-1.45), AD (RR 1.40, 95% CI 1.13-1.73) and VaD (RR 1.38, 95% CI 1.15-1.66). For all-cause dementia, the risk increased by 34%for every 20 cigarettes per day (RR 1.34, 95% CI 1.25-1.43). Former smokers did not show an increased risk of all-cause dementia (RR 1.01, 95% CI 0.96-1.06), AD (RR 1.04, 95% CI 0.96-1.13) and VaD (RR 0.97, 95% CI 0.83-1.13). Subgroup analyses indicated that (1) the significantly increased risk of AD from current smoking was seen only in apolipoprotein E ε4 noncarriers; (2) current smokers aged 65 to 75 years at baseline showed increased risk of allcause dementia and AD compared to those aged over 75 or under 65 years; and (3) sex, race, study location and diagnostic criteria difference in risk of dementia was not found. Conclusions:Smokers show an increased risk of dementia, and smoking cessation decreases the risk to that of never smokers. The increased risk of AD from smoking is more pronounced in apolipoprotein E ε4 noncarriers. Survival bias and competing risk reduce the risk of dementia from smoking at extreme age. © 2015 Zhong et al.


Xiang L.,Chongqing Medical University
Journal of biomedicine & biotechnology | Year: 2012

Efficient osteogenetic differentiation and bone formation from muscle-derived stem cells (MDSCs) should have potential clinical applications in treating nonunion fracture healing or bone defects. Here, we investigate osteogenetic differentiation ability of MDSCs induced by bone morphogenetic protein 9 (BMP9) in vitro and bone formation ability in rabbit radius defects repairing model. Rabbit's MDSCs were extracted by type I collagenase and trypsin methods, and BMP9 was introduced into MDSCs by infection with recombinant adenovirus. Effects of BMP9-induced osteogenetic differentiation of MDSCs were identified with alkaline phosphatase (ALP) activity and expression of later marker. In stem-cell implantation assay, MDSCs have also shown valuable potential bone formation ability induced by BMP9 in rabbit radius defects repairing test. Taken together, our findings suggest that MDSCs are potentiated osteogenetic stem cells which can be induced by BMP9 to treat large segmental bone defects, nonunion fracture, and/or osteoporotic fracture.


Respiratory syncytial virus (RSV) is the most common pathogen responsible for lower respiratory diseases in children. So far, there is no effective treatment or preventative vaccine available for RSV infection, although ribavirin and dexamethasone are commonly prescribed. Resveratrol has been shown to inhibit the replication of several other viruses, thus the effect of resveratrol on RSV-induced inflammatory mediators in 9HTEo cell cultures was evaluated, and possible mechanisms of action were explored and compared with dexamethasone and ribavirin. Incubation with resveratrol resulted in decreased IL-6 production and partial inhibition of RSV replication. Resveratrol treatment also inhibited virus-induced TIR-domain-containing adapter-inducing interferon-β (TRIF) and TANK binding kinase 1 (TBK1) protein expression. These data demonstrate the ability of resveratrol to inhibit cytokine production by RSV in airway epithelial cells, indicating that it might be a therapeutic agent with both anti-inflammatory and antiviral potential for the treatment of RSV infection.


Wang Z.,Chongqing Medical University
Ultrasonics Sonochemistry | Year: 2015

This perspective, for the first time, proposed the theoretical basis for the minimally-invasive and non-invasive medicine. It sets the goal of medical treatment that is to minimize harm to patients and to maximize the natural self-healing power for fighting against the disease. It took a historical review on the technological developments shaped by the minimally-invasive and non-invasive ideology with a focus on the course of research, development and clinical deployment of the high-intensity focused ultrasound (HIFU) ablation therapy by the Chinese research team. It also summarized the highlights of the "1st Yangtze International Summit of Minimally-invasive and Non-invasive Medicine 2013" and the mandate of the newly inaugurated International Society of the Minimally-invasive and Noninvasive Medicine (ISMINIM). It provides a perspective on the future development of this emerging field and its impact on human civilization. © 2015 Elsevier B.V. All rights reserved.


Zhang Y.,Chongqing Medical University | Li Y.,Chongqing Medical University | Qiu F.,Chongqing Medical University | Qiu Z.,Chongqing Medical University
Electrophoresis | Year: 2010

Human urinary exosomes are 30-100 nm vesicles that originate as the internal vesicles in multivesicular bodies from every renal epithelial cell type facing the urinary track and may serve as a suitable noninvasive starting material for biomarker discovery relevant to a variety of renal disease. To comprehensively explore the low-abundance proteome, combinatorial peptide ligand libraries, combined with peptide OFFGEL electrophoresis were employed for the enrichment and separation of relatively low-abundant proteins in urinary exosomes. After analysis by nanoHPLC-chip-MS/MS, 512 proteins were identified, including a large number of proteins with extreme molecular weight or extreme pI value, which could not be well mapped by using traditional 2-D-gel-based separation methods. This in-depth analysis of low-abundant proteins in urinary exosomes led to an increased understanding of molecular composition of these little vesicles and may be helpful for the discovery of novel biomarker. Our work also provides an effective strategy of concentration and identification of low-abundance proteome from complex bio-samples. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Zhang L.-Y.,Chongqing Medical University
Medical Journal of Chinese People's Liberation Army | Year: 2015

Disastrous blast injury is a rare type injury, but an increasing incidence happened worldwide due to various reasons, often causing mass casualties incidents (MCIs). However, most clinicians have no treatment experience in managing blast injury. The present paper introduces the classification and severity prediction, as well as systematically describes medical rescue strategies for blast injuries, including on-site triage and in-hospital trauma emergency treatments such as trauma emergency care, and emergency care for lung and gastrointestinal tract blast injuries. © 2015 People's Military Medical Press. All rights reserved.


Zhang L.-Y.,Chongqing Medical University
Chinese Journal of Traumatology - English Edition | Year: 2016

Explosion has become one of the most common causes of death of the combat casualties. I made a comment on one case of autopsy whose cause of death was the accidental denotation of a 355 g rifle grenade and reviewed the clinical approaches and strategies of the blast injury. © 2016 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V.


Luo Y.,Chongqing Medical University | Zou Y.,Chongqing Medical University | Gao Y.,Chongqing Medical University
Respiration | Year: 2012

High-altitude pulmonary edema (HAPE) is a severe disease caused by high-altitude hypoxia. Since some individuals are more susceptible to high altitude than others, the incidence is variable and cannot be predicted. Furthermore, multiple genes can contribute to the occurrence of HAPE, making it even more difficult to predict. The genes associated with HAPE include those in the renin-angiotensin-aldosterone system pathway, the nitric oxide pathway and the hypoxia-inducible factor pathway. Other genes associated with HAPE include tyrosine hydroxylase (TH), vascular endothelial growth factor (VEGF), pulmonary surfactant proteins and β2-adrenergic receptor. The association of the polymorphisms of these genes with HAPE susceptibility has previously been investigated. Among the genes evaluated, polymorphisms of NOS3, ACE, CYP11B2, Hsp70 and endothelin-1 and pulmonary surfactant proteins A1 and A2 were shown to be associated with HAPE incidence, while associations between TH, VEGF and HAPE remain to be fully elucidated. Novel technological approaches, including genome-wide association studies and next-generation sequencing, are currently being used to identify new HAPE susceptibility genes. The goal of this review article is to summarize the current literature and to define the outstanding areas of research that need to be explored to advance our ability to predict when HAPE will occur. Copyright © 2012 S. Karger AG, Basel.


Zhou J.-Y.,Chongqing Medical University | Zhou J.-Y.,Baylor College of Medicine | Chan L.,Baylor College of Medicine | Zhou S.-W.,Chongqing Medical University
Current Vascular Pharmacology | Year: 2014

Omentin is an adipokine preferentially produced by visceral adipose tissue with insulin-sensitizing effects. Its expression is reduced in obesity, insulin resistance and type 2 diabetes. Omentin is also positively related with adiponectin, high-density lipoprotein levels and negatively related with body mass index, waist circumference, insulin resistance, triglyceride and leptin levels. Lower plasma omentin levels contribute to the pathogenesis of insulin resistance, type 2 diabetes and cardiovascular diseases in obese or overweight patients. Omentin has anti-inflammatory, antiatherogenic, anti-cardiovascular disease and antidiabetic properties. With respect to vascular biology, omentin causes vasodilatation of blood vessels and attenuates C-reactive protein-induced angiogenesis. The ability of omentin to reduce insulin resistance in conjunction with its anti-inflammatory and anti-atherogenic properties makes it a promising therapeutic target. Thus, omentin may have beneficial effects on the metabolic syndrome and could potentially be used as a biologic marker and/or pharmacologic agent/target in this respect. © 2014 Bentham Science Publishers.


Xiao R.,Chongqing Medical University | Teng M.,Chongqing Medical University | Zhang Q.,Chongqing Medical University | Shi X.-h.,Chongqing Medical University | Huang Y.-s.,Chongqing Medical University
PLoS ONE | Year: 2012

Background: Autophagy plays a major role in myocardial ischemia and hypoxia injury. The present study investigated the effects of autophagy on cardiac dysfunction in rats after severe burn. Methods: Protein expression of the autophagy markers LC3 and Beclin 1 were determined at 0, 1, 3, 6, and 12 h post-burn in Sprague Dawley rats subjected to 30% total body surface area 3rd degree burns. Autophagic, apoptotic, and oncotic cell death were evaluated in the myocardium at each time point by immunofluorescence. Changes of cardiac function were measured in a Langendorff model of isolated heart at 6 h post-burn, and the autophagic response was measured following activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI) were also applied to the ex vivo heart model to examine the roles of these factors in post-burn cardiac function. Results: Autophagic cell death was first observed in the myocardium at 3 h post-burn, occurring in 0.008 ± 0.001% of total cardiomyocytes, and continued to increase to a level of 0.022 ± 0.005% by 12 h post-burn. No autophagic cell death was observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycin enhanced autophagy and decreased cardiac function in isolated hearts 6 h post-burn, while 3-MA exerted the opposite response. Enalaprilat, losartan, and DPI all inhibited autophagy and enhanced heart function. Conclusion: Myocardial autophagy is enhanced in severe burns and autophagic cell death occurred early at 3 h post-burn, which may contribute to post-burn cardiac dysfunction. Angiotensin II and reactive oxygen species may play important roles in this process by regulating cell signaling transduction. © 2012 Xiao et al.


Xiong K.-L.,Chongqing Medical University | Zhu Y.-S.,Chongqing Medical University | Zhang W.-G.,Chongqing Medical University
Brain Imaging and Behavior | Year: 2014

Concussion is the most common form of traumatic brain injury (TBI), but diagnosis remains controversial because the brain appears quite normal in conventional computed tomography and magnetic resonance imaging (MRI). These conventional tools are not sensitive enough to detect diffuse traumatic axonal injury, and cannot depict aberrations in mild TBIs. Advanced MRI modalities including diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS), make it possible to detect brain injuries in TBI. The purpose of this review is to provide the latest information regarding the visualization and quantification of important abnormalities in TBI and new insights into their clinical significance. Advanced imaging modalities allow the discovery of biomarkers of injury and the detection of changes in brain injury over time. Such tools will likely be used to evaluate treatment efficacy in research. Combining multiple imaging modalities would not only provide greater insight into the underlying physiological changes in TBI, but also improve diagnostic accuracy in predicting outcomes. In this review we present evidence of brain abnormalities in TBI based on investigations using MRI, including DTI and MRS. Our review provides a summary of some of the important studies published from 2002 to 2012 on the topic of MRI findings in head trauma. With the growing realization that even mild head injury can lead to neurocognitive deficits, medical imaging has assumed preeminence for detecting abnormalities associated with TBI. Advanced MRI modalities such as DTI and MRS have an important role in the diagnosis of lesions for TBI patients. © 2014, Springer Science+Business Media New York.


Li Y.,Chongqing Medical University | Cao J.,Chongqing Medical University
BMC Public Health | Year: 2012

Background: Suicide is a major public health issue in China. Studies of suicide risk factors have reported both inconsistent and inconclusive results. This review aimed to determine suicide risk factors in China. Methods. Medline/PubMed, EMBASE, CNKI (China National Knowledge Infrastructure) and VIP (Chinese Journal of Science and Technology of VIP) were searched for relevant reports. Two investigators independently assessed the eligibility of identified studies and extracted data. Pooled odds ratios (and 95% confidence intervals) were calculated for each factor with Revman 5.0. Results: Forty-four studies with 192,362 subjects were included. The pooled results indicated that mood disorders and stressful life events (physical illness, suicide of relatives) increased the risk of suicide ideation among the entire population. Socio-family environment (single or remarried parent, study pressure and academic achievement) and unhealthy behaviors (smoking, alcohol drinking, and drug use) were risk factors for suicide ideation among youth. Unhealthy behaviors (smoking and alcohol drinking), mood disorders, and stressful life events (suicide of relatives) were the main risk factors for attempted suicide. Persons living in rural areas, and those with lower education, mood disorders, and/or a history of negative life events had a higher risk of completed suicide. In China, before 2000, females had a significantly higher rate of completed suicide than males, while after 2000, no significant gender difference was found. Conclusions: Socio-family environment, lifestyle, life events and psychiatric/psychological factors are associated with suicidal behaviors in China. Further case-control or cohort studies are needed to better understand suicide behaviors in China. Meanwhile, there is an urgent need for comprehensive studies of suicide interventions among high-risk populations. © 2012 Li et al.; licensee BioMed Central Ltd.


Hou C.L.,Chongqing Medical University
Genetics and molecular research : GMR | Year: 2012

We constructed a plasmid containing a protein transduction domain (PTD) and a human A20 (hA20) gene fragment; the fusion protein was obtained by highly expressing this plasmid in the yeast Pichia pastoris GS115. The plasmid was obtained by adding 9xArg and EcoRI recognition sites to the end of the primer, and 6xHis-Tag and NotI recognition sites to its end. After sequencing, the hA20 gene fragment was inserted into plasmid pPIC9k to construct expression vector pPIC9k-PTD-hA20; then, we transfected GS115 with the vector and induced PTD-hA20 protein expression. We purified protein from the yeast fermentation supernatant using a nickel column. Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose medium (30 mM glucose) and in high glucose medium containing different concentrations of protein. Apoptosis of HUVECs was assayed by TUNEL 72 h later. The biological activity tests indicated that the fusion protein not only passed through the cell membrane freely, but also inhibited apoptosis of HUVECs induced by high glucose levels. We conclude that the fusion protein PTD-hA20 has potential for clinical use.


Cai Z.-Y.,Anhui Medical University | Yan Y.,Chongqing Medical University | Chen R.,Anhui Medical University
Neuroscience Bulletin | Year: 2010

Objective: To study the neuroprotective mechanism of minocycline against vascular cognitive impairment after cerebral ischemia. Methods: The rat model with vascular cognitive impairment was established by permanent bilateral common carotid artery occlusion (BCCAO). The observing time-points were determined at 4, 8 and 16 weeks after BCCAO. Animals were randomly divided into sham-operated group (n = 6), model group (subdivided into 3 groups: 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6), and minocycline group (subdivided into 3 groups: 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6). Minocycline was administered by douche via stomach after BCCAO until sacrifice. Glial fibrillary acidic protein (GFAP) was examined by Western blotting and immunohistochemistry. Levels of cyclooxygenase-2 (COX-2) and nuclear factor-kappaB (NF-κB) were measured by immunohistochemistry. IL-1β and TNF-α levels were tested with ELISA method. Results: Levels of GFAP, COX- 2, NF-κB, IL-1β and TNF-α were all up-regulated after permanent BCCAO, which could be significantly inhibited by minocycline. Conclusion: Minocycline could ameliorate the inflammation and oxidative stress in the hippocampus of the vascular cognitive impairment rat model. © 2010 Shanghai Institutes for Biological Sciences, CAS and Springer Berlin Heidelberg.


Xing Y.,Chongqing Medical University | Fan X.,Chongqing Medical University | Ying D.,Chongqing Medical University
Journal of Neurochemistry | Year: 2010

Liver X receptor α (LXRα) and β (LXRβ) are members of the nuclear receptor superfamily of ligand-activated transcription factors, and expressed in the CNS. We have previously demonstrated that LXRβ is essential for migration of later-born neurons during cerebral cortex development, although the underlying mechanism is not clear. The cerebellum is organized in an exquisitely foliated structure with a simple layered cytoarchitecture and considered to be a good model to study morphogenesis of lamination and neuronal migration. Here, we found that T0901317, a potent LXR receptor agonist, administration to neonatal C57/BL6 mice, increased dendritic growth of Purkinje cell, although the appearance of the cerebellar cortex was not affected. We further demonstrated T0901317 treatment promoted the migration of granule neurons from the external granular layer to the internal granular layer during cerebellum development. Bergmann glial fibers serve as scaffolds for granule cells inward migration during cerebellum postnatal development. T0901317 treatment also inhibited premature differentiation of Bergmann glia during cerebellum development, which is related to the decreased levels of TGF-β1 and Smad4 in the cerebellum. Taken together, our findings suggest that endogenous LXR affects differentiation process of Bergmann glia and subsequently leads to promote the migration of granule neurons. © 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.


Ou J.-J.,Chongqing Medical University | Wu F.,Chongqing Medical University | Liang H.-J.,Chongqing Medical University
Cancer Biology and Therapy | Year: 2010

The objective of this study was to investigate whether tumor derived fibronectin alternatively spliced EDA domain has a lymphangiogenic potency on human lymphatic endothelial cells (LECS) in tumor generation to facilitate tumor lymphatic metastasis. LECS were cultured in three-dimentional culture system and treated with SW480 supernant which was highly rich in EDA, the result demonstrated that SW480 supernant could facilitate tube-like formations of LeCs evidently when compared with controls. Integrinα9 was identified by immunofluorescence to be a specific receptor for EDA because we found co-locozation of EDA and integrinα9 on LECS as well as significant upregulation of integrinα9 in SW480 supernant treated group. Western blot and immunofluorescence revealed that EDA also had important roles accommodating the expressions of some key regulators of lymphangiogenesis such as Prox1 and F-actin so as to facilitate motility and sprouting of LECS. In addition, it had been confirmed that all of these effects could be inhibited markedly by EDA antibody (IST-9). Based on these findings, we assert that EDA derived from tumor cells has an important role in facilitating lymphangiogenesis of malignant tumor. Furthermore, EDA pathway may provide a potent target for tumor lymphatic metastasis therapy. © 2010 Landes Bioscience.


Yu S.-S.,Chongqing Medical University | Zhao J.,Chongqing Medical University | Zheng W.- P.,Chongqing Medical University | Zhao Y.,Chongqing Medical University
Brain Research | Year: 2010

4-hydroxybenzyl alcohol (4-HBA), one of the major active phenolic constituents of Gastrodia elata Blume, a very important traditional Chinese medicinal herb, has been shown to be an effective agent against the central and peripheral nervous disorders. In this study, we attempted to explore the possible mechanisms underlying the neuroprotection against transient focal cerebral ischemia by 4-HBA.4-HBA (25, 50 mg/kg) was given 30 min before focal ischemia in rats caused by middle cerebral artery occlusion (1 h of occlusion, 24 h of reperfusion). Under the treatment of 50 mg/kg 4-HBA, total (100.76 ± 2.90 mm3), cortical (64.91 ± 1.46 mm3), and sub-cortical (38.77 ± 2.78 mm3) infarct volumes were significantly decreased in comparison to ischemia-reperfusion values. Neurological evaluation and Nissl-staining of the 4-HBA group were improved significantly compared to the untreated ischemia group. TUNEL-positive cells were reduced significantly in 4-HBA treated group. Results of immunofluorescence staining analysis and Western immunoblot indicated that 4-HBA increased the expression of Bcl-2 and inhibited the activation of caspase-3 ultimately inhibiting apoptosis. These results suggested that 4-HBA ameliorated ischemic injury induced by transient focal cerebral ischemia in rats, and this neuroprotective effect may be partly related to attenuate apoptosis pathway. © 2009 Elsevier B.V. All rights reserved.


Objective: To evaluate the efficacy of intermittent pneumatic compression (IPC) in the prevention of venous thromboembolism (VTE) in medical critically ill patients. Methods: A prospective, randomized, controlled study was conducted. One hundred and sixty-two medical critically ill patients were randomly assigned to IPC group and control group by random number table after admitted to intensive care unit (ICU) from June 2008 to June 2010. Patients under anticoagulation medicine therapy were excluded. Patients in the IPC group were treated with IPC to prevent VTE after ICU admission. No measures were taken to prevent VTE in the control group. The rate of VTE Cdeep vein thrombosis (DVT) and pulmonary embolism (PE)], duration of mechanical ventilation (MV), the length of stay in ICU, rate of non-sudden cardiac death and ICU mortality rate and related side-effects of IPC were compared during the subsequent 28 days between two groups. Results: Compared with control group, IPC group was shown to have a significantly lower rate of DVT [3.80% (3/79) vs. 19.28% (16/83), P < 0.01], lower rate of PE [0 (0/79) vs. 9.64% (8/83), P<0.01] and lower rate of non-sudden cardiac death [1.26% (1/79) vs. 7.23% (6/83), P<0.01]. Compared with control group, duration of MV (days: 8±6 vs. 9±8) and length of stay in ICU (days: 9±7 vs. 10±7) were shorter, and the ICU mortality rate of 28 days (24.05% vs. 31.32%) was lower in the IPC group, but they were not statistically significant (all P>0.05). No related side-effects were found in the IPC group. Conclusion: IPC can prevent VTE, and lower the rate of non-sudden cardiac death, and it is safe in medical critically ill patients.


To explore the relationship between therapeutic dosage of ultrasound ablation in treatment of uterine fibroids and imaging characteristics of bloody supply of uterine fibroids by color Doppler ultrasound imaging. One hundred and forty-two patients with 168 fibroids were treated by ultrasound ablation. Before treatment, bloody supply of fibroids were classified into grade 0 - 4 by ultrasonography. Three patients lost follow-up with contrast MRI exam within 1 month after treatment, so 165 fibroids were enrolled in this study. Bloody supplies were 9 fibroids in grade 0, 34 fibroids in grade 1, 35 fibroids in grade 2, 55 fibroids in grade 3 and 32 fibroids in grade 4. After 1 month treatment, the treated area without blood supply and ratio of ablation were measured by contrast MRI to evaluate the efficacy of thermal ablation and compare status of blood supple based different therapeutic dosage. According to International Reditherapy for Society (SIR) standard, adverse effect and score of pain were evaluated. (1) Ratio of ablation based: ratios of ablation were 79% in grade 0, 89% in grade 1, 92% in grade 2, 86% in grade 3, 71% in grade 4. It reached statistical difference when blood supply of grade 0 compared with those of grade 2 and 3 (P < 0.05) and blood supply of grade 4 compared with those of grade 1, 2, 3 (P < 0.05). (2) Factor of energy efficiency: factor of energy efficiency were 13.19 J/mm(3) in degree 0, 9.54 J/mm(3) in degree 1, 12.91 J/mm(3) in degree 2, 17.83 J/mm(3) in degree 3 and 28.10 J/mm(3) in degree 4. Factor of energy of ablation in degree 4 was significantly higher than those in degree 1, 2 and 3 blood supply (P < 0.05). It exhibit the positive relationship between blood supply and factor of energy of ablation (r = 0.354, P < 0.01). (3) Score of pain and adverse effect: nearly 85% (120/142) patients could tolerate this treatment very well. Those scores of pain were in range of 0 to 4. All patients did not extend their hospitalization and C to F of SIR standard was not recorded. blood supply of myoma measured by ultrasound could predict dosage of ultrasound ablation, it could help select indicated well patients.


Chen G.-Q.,Chongqing Medical University | Yang H.,Chongqing Medical University
Chinese Journal of Traumatology - English Edition | Year: 2011

Duodenal trauma is uncommon but nowadays seen more and more frequently due to the increased automobile accidents and violent events. The management of duodenal trauma can be complicated, especially when massive injury to the pancreatic-duodenal-biliary complex occurs simultaneously. Even the patients receive surgeries in time, multiple postoperative complications and high mortality are common. To know and manage duodenal trauma better, we searched the recent related literature in PubMed by the keywords of duodenal trauma, therapy, diagnosis and abdomen. It shows that because the diagnosis and management are complicated and the mortality is high, duodenal trauma should be treated in time and tactfully. And application of new technology can help improve the management. In this review, we discussed the incidence, diagnosis, management, and complications as well as mortality of duodenal trauma.


Dong Y.,Chongqing Medical University | Yu J.-L.,Chongqing Medical University
World Journal of Pediatrics | Year: 2011

Background: Preterm birth rate continues to rise around the world mainly at the expense of late preterm newborns, recently defi ned as births between the gestational age of 34 weeks and 36-6/7 weeks. Late preterm infants are considered to have significantly more short-term and longterm adverse outcomes than term infants. Data sources: Articles concerning morbidity, mortality and long-term outcomes of late preterm infants were retrieved from PubMed/MEDLINE published during the period of 2000-2010. Results: Late preterm infants are the fastest growing subgroup of neonates, comprising the majority of all preterm births. Compared with term infants, they have significantly higher risk of morbidity, mortality and adverse long-term outcomes well beyond infancy into adulthood. However, epidemiology and etiology of late preterm births, the magnitude of their morbidity, the long-term life quality, and public health impact have not been well studied. Conclusions: The growing number of late preterm neonates substantiates the importance to better understand and medically approach this special preterm subgroup. A long-term evaluation, monitoring and followup of late preterm infants are needed to optimize neonatal care and improve human health status. © Children's Hospital, Zhejiang University School of Medicine, China and Springer-Verlag Berlin Heidelberg 2011. All rights reserved.


Yang P.,Chongqing Medical University
Chinese Journal of Ophthalmology | Year: 2015

Uveitis, as one of the major cause of blindness worldwide, seriously harms patients' vision and quality of life. The social and economic burden caused by uveitis cannot be ignored. Remarkable achievements in basic and clinical uveitis research were gained after decades of unremitting efforts by Chinese ophthalmologists. A number of original results and breakthroughs were achieved in researches on Behcet's disease, VKH syndrome and other important types of disease that lead to blindness. We are integrating the power of the Chinese Ocular Immunology Association, conducting multi-center collaborative research, and establishing the uveitis sample bank of Chinese. We need to train more uveitis specialists in the future, establish diagnostic and treatment practices of different types of uveitis, accelerate the research on main diseases which lead to blindness, further enhance the overall level of uveitis study, and enhance China's research position in international uveitis. Copyright © 2015 by the Chinese Medical Association.


Zhu Z.,Chongqing Medical University
Frontiers of medicine | Year: 2013

Hypertension is a serious public health problem worldwide. More than 60% of the risk factors for hypertension are associated with metabolic disturbances. Metabolic abnormalities increase the risk for hypertension and cause high blood pressure. Improving metabolic disturbances is beneficial for hypertension treatment. Due to the importance of metabolic abnormalities in the pathogenesis of hypertension, we propose a concept of metabolic hypertension. In this review, we discuss and review the clinical types, pathogenesis, risk evaluation and management of metabolic hypertension. Elucidation of the mechanism of metabolic hypertension should facilitate the design of novel pharmacotherapeutics and dedicated antihypertensive manipulations.


Ye Y.J.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2010

To investigate the immune responses and the protection induced by the transgenic Alfalfa (Medicago sativa) containing Eg95-EgA31 fusion gene of Echinococcus granulosus against Eg protoscoleces. The leaf protein was extracted from the transgenic alfalfa by heat-coagulation method, its concentration was prepared for 20 g/L. BALB/c mice were immunized intranasally or orally with the leaf protein once per 3 days for 2 months.At the same time, the leaf protein transfected with pBI-121 blank vector and the normal leaf protein without foreign antigen was served as control. The mice were then challenged intraperitoneally with Eg protoscoleces (50 protoscoleces per mouce)on week 8 after the last vaccination and sacrified on week 24 postinfection to count the rate of reduced hydatid cyst. The specific antibody (IgE, IgG and its subclasses)in the sera collected from the eyeballs was evaluated by ELISA. Splenocytes were separated and cultured in vitro with EgAg, ConA or LPS stimulus.The substes of CD4(+); and CD8(+); T cells were measured by FCM. The splenocytes' proliferation was determined by MTT method.Then the cells were collected, stained by PI and Annexin V-FITC, and analyzed by FCM to get the splenocytes' apoptotic rate.The supernatant was collected to measure the level of IL-12, IL-10, IFN-gamma and TNF-alpha by ELISA. Compared with the control group, The hydatid cyst weight in the oral immunization group decreased by 64.1%; the splenocytes' apoptotic rate got obviously lower than that in the control group; the splenocytes' proliferation increased significantly, the CD4(+); subsets and the ratio of the CD4(+);/CD8(+); did so, and the similar trend about the specific antibody titer and the level of cytokines could be seen in this group. Apoptosis of splenocytes may be inhibited in mice by immunization with the transgenic alfalfa, splenocytes' proliferation and Th1 response can be induced in the mice against the challenge of Eg protoscoleces. CD4(+); T cell and the specific antibody(IgG, IgG2b and IgE) may play important roles in the protection induced by the transgenic alfalfa vaccine.


Li L.M.,Chongqing Medical University
Zhen ci yan jiu = Acupuncture research / [Zhongguo yi xue ke xue yuan Yi xue qing bao yan jiu suo bian ji] | Year: 2013

To observe the synchronism difference of brain region activities in response to acupuncture stimulation of Zusanli (ST 36) in healthy volunteer subjects with different acupuncture analgesia sensitivity, so as to study the central factors influencing acupuncture intervention outcomes. Forty-five healthy volunteer subjects with different constitutions (different sensitivities in response to needling stimulation) were divided into insensitive group, normal group and sensitive group (n = 15). The pressure pain threshold (PPT) of the Zusanli (ST 36) region before and after acupuncture stimulation of ST36 was assessed using visual analog scale (VAS). Two weeks later after acupuncture stimulation of ST 36, resting-state fMRI images were acquired by using a nuclear magnetic resonance imaging system and analyzed by using DPARSFV 2.1 software package, software SPM 8 and REST 1.7. The cerebral regional homogeneity (ReHo) of the subjects was then calculated by Resting-State fMRI Data Analysis Toolkit (REST). Compared with pre-acupuncture, PPT levels of the normal and sensitive groups were significantly increased after acupuncture of ST 36 (P < 0.05), and that of the insensitive group had no significant change (P > 0.05). Following acupuncture stimulation of ST 36, the insensitive group only showed a significant decreased ReHo in the left fusiform gyrus, left inferior temporal gyrus, bilateral postcentral gyrus, and left anterior central gyrus. In the normal group, a significantly increased ReHo was found in left brainstem, the right cerebellum posterior lobe, right parahippocampa gyrus, right fusiform gyrus, left angular gyrus, temporal lobe and the left frontal lobe; and a significantly decreased ReHo in the occipital lobes and the right superior temporal gyrus after acupuncture stimulation of ST 36. In the sensitive group, a markedly increased ReHo was found in the left brainstem, bilateral cerebellum posterior lobes, left inferior temporal gyrus, basal ganglia, the left insular lobe, anterior cingutate, frontal lobe, inferior parietal lobule, and the right supplementary motor area, and an obviously decreased ReHo found in the bilateral occipital lobes, fusiform gyrus, posterior central gyrus, the right posterior cingutate, the left temporal lobe and the left paracentral lobule, etc. after acupuncture of ST 36. Constitution-associated needling sensation may be an important influential factor for acupuncture analgesia in normal subjects. The change of ReHo in different cerebral areas is probably responsible for the difference of acupuncture analgesia in different constitution people.


Bian S.Z.,Chongqing Medical University
The journal of headache and pain | Year: 2013

This prospective and observational study aimed to identify demographic, physiological and psychological risk factors associated with high-altitude headache (HAH) upon acute high-altitude exposure. Eight hundred fifty subjects ascended by plane to 3700 m above Chengdu (500 m) over a period of two hours. Structured Case Report Form (CRF) questionnaires were used to record demographic information, physiological examinations, psychological scale, and symptoms including headache and insomnia a week before ascending and within 24 hours after arrival at 3700 m. Binary logistic regression models were used to analyze the risk factors for HAH. The incidence of HAH was 73.3%. Age (p =0.011), physical labor intensity (PLI) (p =0.044), primary headache history (p <0.001), insomnia (p <0.001), arterial oxygen saturation (SaO2) (p =0.001), heart rate (HR) (p =0.002), the Self-Rating Anxiety Scale (SAS) (p <0.001), and the Epworth Sleepiness Scale (ESS) (p <0.001) were significantly different between HAH and non-HAH groups. Logistic regression models identified primary headache history, insomnia, low SaO2, high HR and SAS as independent risk factors for HAH. Insomnia, primary headache history, low SaO2, high HR, and high SAS score are the risk factors for HAH. Our findings will provide novel avenues for the study, prevention and treatment of HAH.


Zeng C.,Chongqing Medical University | Zeng C.,Shantou Medical College
Clinical Science | Year: 2010

Dual antiplatelet therapy with aspirin and clopidogrel, a P2Y12 antagonist, is a cornerstone for treatment of patients with stroke, peripheral arterial disease and acute coronary artery disease, followed with or without percutaneous coronary intervention. In the present issue of Clinical Science, Giachini and co-workers found that clopidogrel could normalize the increased phenylephrine-induced vascular contraction and the impaired acetylcholine-induced vasodilation in mesenteric arteries from AngII (angiotensin II)-infused Sprague-Dawley rats. This might develop a new area for clopidogrel application; however, whether clopidogrel can improve arterial function in patients with hypertension or diabetes, or if clopidogrel outweighs the beneficial effect of aspirin in those patients, remains an open field for future inquiry. © The Authors Journal compilation © 2010 Biochemical Society.


Zhu Y.,Chongqing Medical University | Tang R.-K.,Chongqing Medical University | Zhao P.,Chongqing Medical University | Zhu S.-S.,Chongqing Medical University | And 2 more authors.
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2013

Purpose: To compare the short- and long-term clinical outcomes of the double-bundle (DB) anterior cruciate ligament (ACL) reconstruction with those of single-bundle (SB) ACL reconstruction. Methods: An electronic search of the database PubMed (1966-September 2011), EMBASE (1984-September 2011), and Cochrane Controlled Trials Register (CENTRAL; 3rd Quarter, 2011) was undertaken to identify relevant studies. Main clinical outcomes were knee stability measurements including KT-1000 arthrometer measurement, Pivot shift test, and Lachman test, and clinical outcome measurements including International Knee Documentation Committee (IKDC), Lysholm knee score, Tegner activity score, and complications. Results: Eighteen studies were finally included in this meta-analysis, which were all classified as high risk of bias according to the Collaboration's recommended tool. It is seen that compared to SB ACL reconstruction, DB ACL reconstruction results in a KT-1000 arthrometer outcome 0. 63 and 1. 00 mm closer to the normal knee in a short- and long-term follow-up, respectively. Our results also reveal that DB-treated patients have a significantly higher negative rate of the pivot shift test (p < 0. 00001 and = 0. 006 in a short- and long-term follow-up, respectively) and Lachman test (n. s. and p < 0. 0001 in a short- and long-term follow-up, respectively) compared to SB-treated patients. As for the clinical outcome measurements, a significant difference is found between SB versus DB ACL reconstruction regarding the IKDC (p = 0. 006 and < 0. 0001 in a short- and long-term follow-up, respectively) and complications (p = 0. 03), while there is no significant difference between the two groups regarding Lysholm knee score (n. s.) and Tegner activity score (n. s.). Conclusion: Overall, double-bundle ACL reconstruction yields better clinical outcomes when compared to single-bundle ACL reconstruction. Levels of evidence: II. © 2012 Springer-Verlag.


Liu K.,Chongqing Medical University | Zhou R.,Chongqing Medical University | Wang B.,Chongqing Medical University | Chen K.,Chongqing Medical University | And 3 more authors.
American Journal of Clinical Nutrition | Year: 2013

Background: The results of studies investigating the effect of green tea on glucose control and insulin sensitivity in humans are inconsistent. Objective: We aimed to quantitatively evaluate the effect of green tea on glucose control and insulin sensitivity. Design: We performed a strategic literature search of PubMed, EMBASE, and the Cochrane Library (updated to January 2013) for randomized controlled trials that evaluated the effects of green tea and green tea extract on glucose control and insulin sensitivity. Study quality was assessed by using the Jadad scale. Weighted mean differences were calculated for net changes in glycemic measures by using fixed-effects or random-effects models. We conducted prespecified subgroup and sensitivity analyses to explore potential heterogeneity. Meta-regression analyses were conducted to investigate dose effects of green tea on fasting glucose and insulin concentrations. Results: Seventeen trials comprising a total of 1133 subjects were included in the current meta-analysis. Green tea consumption significantly reduced the fasting glucose and hemoglobin A1c (Hb A1c) concentrations by -0.09 mmol/L (95% CI: -0.15, -0.03 mmol/L; P < 0.01) and -0.30% (95% CI: -0.37, -0.22%; P < 0.01), respectively. Further stratified analyses from high Jadad score studies showed that green tea significantly reduced fasting insulin concentrations (-1.16 μIU/mL; 95% CI: -1.91, 20.40 μIU/mL; P = 0.03). Conclusions: This meta-analysis suggested that green tea had favorable effects, ie, decreased fasting glucose and Hb A1c concentrations. Subgroup analyses showed a significant reduction in fasting insulin concentrations in trials with high Jadad scores. © 2013 American Society for Nutrition.


In this study a novel sensitive nanogold particle sensor enhancement based on mixed self-assembled monolayers was explored and used to construct a Surface Plasmon Resonance (SPR) immunosensor to detect Ischemia Modified Albumin (IMA). Compared with a direct binding SPR assay at a limit of detection (LOD) of 100 ng/L, gold nanoparticles (AuNPs) of 10 nm dramatically improved the LOD of IMA to 10 ng/L. Meanwhile, no interfering substance that may lead to false positive results was identified. These results suggested that the SPR biosensor presented superior properties, and provided a simple label-free strategy to increase assay sensitivity for further acute coronary syndrome (ACS) diagnosis.


Zhao X.,Chongqing Medical University | Huang L.,Chongqing Medical University
Experimental and Therapeutic Medicine | Year: 2013

Cardiovascular diseases are the most common cause of death in the world. The development of heart failure is mainly due to the loss of cardiomyocytes following myocardial infarction and the absence of endogenous myocardial repair. Numerous studies have focused on cardiac stem cells (CSCs) due to their therapeutic benefit, particularly in the treatment of heart failure. It has previously been demonstrated that CSCs are able to promote the regeneration of cardiomyocytes in animals following myocardial infarction. However, the underlying mechanism(s) remain unclear. This review mainly discusses the cardioprotective effect of CSCs and the effect of CSCs on the function of cardiomyocytes, and compares the efficacies of CSCs from rats, mice and humans, thereby contributing to an improved understanding of CSCs as a promising treatment option for heart failure.


Li L.,Chongqing Medical University | Jiang J.,Chongqing Medical University
Frontiers of Medicine in China | Year: 2011

Adult stem cells hold great promise for wound healing and tissue regeneration. Mesenchymal stem cells (MSCs), for example, have been shown to play a role in tissue repair. Research has shown that endogenous bone marrow MSCs or exogenously delivered MSCs migrate to the sites of injury and participate in the repair process. The precise mechanisms underlying migration of MSCs into the injured tissue are still not fully understood, although multiple signaling pathways and molecules were reported, including both chemoattractive factors and endogenous electric fields at wounds. This review will briefly summarize the regulatory facors and signaling transduction pathways involved in migration of MSCs. A better understanding of the molecular mechanisms involved in the migration of MSCs will help us to develop new stem cell-based therapeutic strategies in regenerative medicine. © Higher Education Press and Springer-Verlag Berlin Heidelberg 2011.


Bie M.,Chongqing Medical University | Wei Z.-Q.,Chongqing Medical University
International Journal of Colorectal Disease | Year: 2013

Purpose: This study aims to introduce a new anastomotic technique-transanal pull-through combined with single stapling technique (PT-SST), and evaluate the value in the sphincter-preserving operation for lower rectal carcinoma. Methods: Between January 2004 and September 2011, 131 consecutive patients had sphincter-preserving operations using PT-SST and double stapling technique (DST) for low colorectal anastomosis. The data was prospectively collected. Results: There are 45 patients (male 26, median = 55 years) in PT-SST group and 86 (male 46, median = 55 years) in the DST group. Anastomotic leakage took place in three patients in DST group, while no anastomotic leakage happened in PT-SST group. There are recurrences in pelvic cavity for one patient (2.2 %), in anastomotic stoma for no patient, and hepatic metastasis for four patients (8.9 %) in PT-SST group; while there are recurrences in pelvic cavity for three patients (3.5 %), in anastomotic stoma for two patients (2.3 %), and hepatic metastasis for seven patients (8.1 %) in DST group. No significant difference was indicated in the terms of the recurrence and hepatic metastasis between the two groups. Patients were satisfied with functional results. Conclusions: This new technique can solve some technique problems of DST and has at least comparable outcomes compared with DST. It is a safe and feasible procedure for performing low anastomosis with high rate of sphincter preservation. It can be used especially for patients with small pelvis. © 2013 Springer-Verlag Berlin Heidelberg.


Wang L.,Chongqing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2010

To investigate the levels and functions of Th17 cells and CD4(+); CD25(+); Foxp3(+); regulate cells(Treg) and explore their role in pathogenesis of primary nephrotic syndrome (PNS) in children. Children with PNS were divided into simple type nephritic syndrome group (SNS) (n = 20), and nephritic type nephritic syndrome group (NNS) (n = 15). 20 healthy subjects were selected as control group. The circulating frequencies of Th17 cells and Treg were measured by FCM. Real-time PCR were used to analyze the mRNA expressions of RORC, IL-23p19 and Foxp3 in peripheral blood mononuclear cells. The serum of IL-1, IL-6, TGF-1 were measured by ELISA. Circulating frequencies of Th17 cells, the mRNA levels of RORC, IL-23p19 and the serum of IL-1, IL-6 were higher in SNS and NNS groups than control group (P < 0.05), and they were higher in NNS group than SNS group (P < 0.05). Compared with control group, the circulating frencencies of Treg cells, the Foxp3mRNA levels and the serum levels of TGF-1 were lower in NNS and SNS groups (P < 0.05), and the circulating frencencies of Treg cells, the Foxp3mRNA levels were lower in NNS group than SNS group (P < 0.05), but NNS and SNS group had no statistical difference in the serum levels of TGF-1 (P > 0.05). Imbalance of Th17 and Treg cells might contribute to the pathogenesis of PNS in children and have associated with clinical presentation, pathological type, glucocorticoid sensitivity and prognosis of the disease.


Luo Y.,Chongqing Medical University | Zhu J.,Chongqing Medical University | Gao Y.,Chongqing Medical University
Molecular BioSystems | Year: 2012

Upon rapid ascent to a high altitude, non-acclimatized individuals, although healthy, are highly prone to contracting high-altitude pulmonary edema (HAPE). Early diagnosis is difficult and there is no reliable biomarker available. We used proton (1H) NMR metabolomics to profile the altered metabolic patterns of blood plasma from HAPE patients. The plasmas of ten patients with HAPE and ten individuals without HAPE were collected and compared using 1H NMR spectroscopy. Data were evaluated with several multivariate statistical analyses, including the principal components, the orthogonal partial least-squares discriminant, and the orthogonal signal correction partial least-squares discriminant. Multivariate statistical analyses revealed a significant disparity between subjects with HAPE and those in the control group. Compared to the plasma of the controls, the HAPE patients had significant increases in valine, lysine, leucine, isoleucine, glycerol phosphoryl choline, glycine, glutamine, glutamic acid, creatinine, citrate, and methyl histidine. These were accompanied by decreases in α- and β-glucose, trimethylamine, and the metabolic products of lipids. The data demonstrate that metabolomics may be effective for the diagnosis of HAPE in the future, and can be used for further understanding HAPE pathogenesis. © 2012 The Royal Society of Chemistry.


He M.,Chongqing Medical University
Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji | Year: 2011

RNA interference (RNAi) is an important topic of epigenetics research in post-genome period. RNAi works as a post-DNA replication regulator for gene expression, and it is related to the occurrence and development of malignant tumors. The most usual participators of RNAi are MicroRNA (miRNA) and small interference RNA (siRNA). This review summarizes the basic theory of miRNA and siRNA, and provides recent progresses of RNAi research on gastric cancer. RNAi analysis and technique not only act as powerful tools for studying gene function and action mechanism, but also have diagnostic and therapeutic potential in gastric cancer, even in all kinds of tumors.


Lu M.,Chongqing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2010

Titania and Ag containing nano-hydroxyapatite/polyamide 66 (TiO2-Ag-nHA/PA66) composite bone filling material has good biocompatibility and biological safety. To investigate the antibacterial effect and Ag+ release characteristics of TiO2-Ag-nHA/PA66 composite bone filling material containing different concentrations of Ag+ in vitro. The n-HA/PA66 composite bone filling material A1 (material A1) was prepared by co-polymerization method, and TiO2-Ag-nHA/PA66 composite bone filling materials A2 and A3 (materials A2 and A3) were prepared by the same way containing Ag+ of 0.22wt% and 0.64wt%, respectively, and the TiO2 content was 2.35wt%. The materials A2 and A3 were respectively immersed in 50 mL simulated body fluid (SBF), and Ag+ concentration was measured by atomic absorption spectrometry at 1, 3, 7, 14, 21, and 49 days. The inhibition ring test and colony count method were used to evaluate antibiotic effect against Staphylococcus aureus and Escherichia coli, the anti-adhesion capacity of Staphylococcus aureus and Escherichia coli was observed by scanning electron microscope (SEM). There was no significant difference in the Ag+ concentration between materials A2 and A3 at 1 day and 3 days (P > 0.05); and there were significant differences in the Ag+ concentration between materials A2 and A3 after 7 days (P < 0.05). The inhibition ring diameters of materials A2 and A3 to Staphylococcus aureus and Escherichia coli reached the maximum at 1 day, which were (13.40 +/- 2.88), (9.40 +/- 1.14) mm and (23.60 +/- 1.14), (18.80 +/- 0.84) mm, showing significant difference (P < 0.05) between materials A2 and A3 respectively; and then, the diameter of inhibition ring reduced with the time. The antibacterial effect of materials A2 and A3 against Staphylococcus aureus and Escherichia coli lasted 15, 33 days and 9, 24 days, respectively. No inhibition ring was observed around material A1 all the time. And the inhibitory rates of materials A2 and A3 were 89.74% +/- 3.62%, 94.18% +/- 2.05% and 78.65% +/- 5.64%, 85.96% +/- 2.50%; showing significant differences (P < 0.05) among materials A1, A2, and A3. SEM showed that bacterial adhesion of materials A2 and A3 was obviously fewer than that of material A1. TiO2-Ag-nHA/PA66 composite bone filling material has antibacterial property against Staphylococcus aureus and Escherichia coli, and it has a good release effect in SBF.


Zhang Z.,Chongqing Medical University
Journal of Spinal Disorders and Techniques | Year: 2015

STUDY DESIGN:: A retrospect