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Harbin, China

Harbin Medical University is a public university located in Harbin, Heilongjiang, China. Wikipedia.


Yang S.,Harbin Medical University
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2012

Many publications have evaluated the correlation between Cytochrome P450 1A1 (CYP1A1) Ile462Val polymorphism and cervical cancer risk, but the results remain inconclusive. To provide a more robust estimate of this effect, a meta-analysis was carried out. We systematically searched PubMed, Embase and CBM databases for studies published before May 2012. The association between CYP1A1 Ile462Val polymorphism and cervical cancer risk was assessed by calculating pooled odds ratios (OR) with its 95 % confidence intervals (95 % CI). On the basis of our inclusion criteria, ten studies with a total of 2,423 individuals were included in the meta-analysis. Overall, CYP1A1 Ile462Val polymorphism was associated with increased risk of cervical cancer (Val versus Ile, OR = 1.43; 95 % CI, 1.03-1.97; ValVal versus IleIle, OR = 2.43; 95 % CI, 1.19-4.95; ValVal+ValIle versus IleIle, OR = 1.59; 95 % CI, 1.00-2.53). Ethnic subgroup analyses showed a significant association was found in Caucasians (Val versus Ile, OR = 2.03; 95 % CI, 1.17-3.51; ValVal versus IleIle, OR = 2.74; 95 % CI, 1.30-5.75; ValVal+ValIle versus IleIle, OR = 2.50; 95 % CI, 1.33-4.70), but not in Asians. In conclusion, this meta-analysis suggests that CYP1A1 Ile462Val polymorphism plays an important role in susceptibility to cervical cancer. Further studies with large sample size and careful design need performing to identify this association more comprehensively. Source


Wei S.-Q.,University of Montreal | Qi H.-P.,Harbin Medical University | Luo Z.-C.,University of Montreal | Fraser W.D.,University of Montreal
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2013

Objective: To estimate the associations between maternal vitamin D status and adverse pregnancy outcomes. Study design: We searched electronic databases of the human literature in PubMed, EMBASE and the Cochrane Library up to October, 2012 using the following keywords: "vitamin D" and "status" or "deficiency" or "insufficiency" and "pregnancy". A systematic review and meta-analysis were conducted on observational studies that reported the association between maternal blood vitamin D levels and adverse pregnancy outcomes including preeclampsia, gestational diabetes mellitus (GDM), preterm birth or small-for-gestational age (SGA). Results: Twenty-four studies met the inclusion criteria. Women with circulating 25-hydroxyvitamin D [25(OH)D] level less than 50nmol/l in pregnancy experienced an increased risk of preeclampsia [odds ratio (OR) 2.09 (95% confidence intervals 1.50-2.90)], GDM [OR 1.38 (1.12-1.70)], preterm birth [OR 1.58 (1.08-2.31)] and SGA [OR 1.52 (1.08-2.15)]. Conclusion: Low maternal vitamin D levels in pregnancy may be associated with an increased risk of preeclampsia, GDM, preterm birth and SGA. © 2013 Informa UK Ltd All rights reserved. Source


Chen G.,Jilin University | Wang H.,Harbin Medical University | Xie S.,Jilin University | Ma J.,Jilin University | Wang G.,Jilin University
Oncology Reports | Year: 2013

Signal transducer and activator of transcription 1 (STAT1) regulates cell proliferation and survival. The present study aimed to investigate the role of STAT1 in the development and progression of human hepatocellular carcinoma (HCC). The levels of STAT1 expression in 36 HCC and 12 non-HCC liver tissues were examined by immunohistochemistry. The effect of STAT1 overexpression or silencing on the proliferation and apoptosis of HCC cells was determined by MTT and flow cytometric assays. The effect of STAT1 overexpression or silencing on the levels of p53 and cyclin E expression was determined by quantitative PCR and western blot assays. The level of STAT1 expression in the HCC tissues was significantly lower compared to the level in the non-HCC liver tissues and was negatively associated with the histological grade of HCC and serum HBsAg, anti-HCV and α-fetoprotein positivity in HCC patients. Induction of STAT1 overexpression significantly inhibited HepG2 cell proliferation and enhanced HCC cell apoptosis, accompanied by upregulation of p53 expression and STAT1 phosphorylation, but a reduction in cyclin E expression in HepG2 cells. In contrast, knockdown of STAT1 by introduction of STAT1-specific siRNA promoted HepG2 cell proliferation, but inhibited HCC cell apoptosis, accompanied by significant downregulation of p53 expression, but enhancement of cyclin E expression in vitro. Our data suggest that STAT1 may inhibit HCC growth by regulating p53-related cell cycling and apoptosis. Source


Hu Y.Z.,Harbin Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

To investigate the therapeutic mechanism of baicalin on rat brain glioma. Deep brain glioma models were established by injection of glioma cell line C6 cells into the brain of Wistar rats. The rats at 7 days after modeling were randomly divided into tumor control group (0.9% NaCl solution 30 mg×kg(-1)×d(-1) gavage)and experimental groups. The experimental rats was divided into 3 groups: low dose group (50 mg×kg(-1)×d(-1)), middle dose group (100 mg×kg(-1)×d(-1)) and high dose group (200 mg×kg(-1)×d(-1)), given the baicalin by gavage. Pathological and electron microscopic changes were observed. The expressions of p53 and Bcl-2 were determined by immunohistochemistry, and the changes of MRI, the average survival time and body weight of the rats in each group after treatments were analyzed. Compared with the control group, the tumor diameter and volume of high dose group rats before sacrifice were significantly reduced (P < 0.01), and the survival time was significantly prolonged (P < 0.01). Immunohistochemistry revealed strong positive expression rate of mutant p53 (84.47 ± 3.74)% and moderately positive rate (47.28 ± 2.38)% in the control group, significantly higher than that in the negative group (12.91 ± 1.07)% (P < 0.01). The positive rate of mutant p53 of the high dose group was (46.42 ± 2.19)%, significantly lower than that of the control group (84.47 ± 3.74)% (P < 0.01). The expression rate of Bcl-2 in the control group was strongly positive (86.51 ± 4.17)% and moderate positive (48.19 ± 2.11)%, significantly higher than that of the negative group (10.36 ± 1.43)% (P < 0.01). Electron microscopy revealed that baicalin caused damages of the cell nuclei and organelles in the gliomas. Baicalin has significant inhibitory effect on glioma in vivo, and its mechanism may be related to cell apoptosis induced by down-regulated expression of mutant p53, but not related with Bcl-2 expression. Source


Yang L.,Guangzhou University | Liu B.,Guangzhou University | Huang B.,Guangzhou University | Deng J.,Soochow University of China | And 9 more authors.
Human Molecular Genetics | Year: 2013

WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that has been reported to lose function due to genetic alterations in several cancers. WWOX maps to the common chromosomal fragile site FRA16D and several copy number variations (CNVs) were found within this gene. In this study, we investigated the association between the CNVs of WWOX and lung cancer risk in four independent case-control studies, which are on 2942 lung cancer cases and 3074 cancer-free controls of southern, eastern and northern Chinese. A common CNV-67048 was genotyped by the Taqman real-time PCR, and its biological effect was accessed with protein expression and sequencing assays. We found that in comparison with the common 2-copy genotype, the carriers of loss variant genotypes (1-copy or 0-copy) had a significantly increased risk of lung cancer (adjusted OR =; 1.39, 95%; CI =; 1.24-1.55, P = 9.01*10-9) in a dose-response manner (Ptrend = 1.12 * 10-10), and the WWOX protein expressions in lung cancer tissues were significantly lower (P = 0.036), accompanying a higher rate of exons absence (P = 0.021) in subjects with loss genotypes of CNV-67048. Our data suggest that the loss genotypes of CNV-67048 in WWOX predispose their carriers to lung cancer; this might be related with altered WWOX gene expression and exons absence in them. © The Author 2013. Published by Oxford University Press. All rights reserved. Source


Liu B.M.,Harbin Medical University
Genetics and molecular research : GMR | Year: 2012

Association between the XRCC1 Arg399Gln polymorphism and susceptibility to gastric cancer has been investigated; overall, the results have been inconclusive. We made a meta-analysis of 13 case-control studies, including 3278 cases and 6243 controls. Crude odds ratios (OR) with 95% confidence intervals (95%CI) were used to assess this possible association. We found no evidence of a significant association between the XRCC1 Arg399Gln polymorphism and gastric cancer risk (in the additive inheritance model, OR = 0.986, 95%CI = 0.831-1.156, in the dominant inheritance model, OR = 1.044, 95%CI = 0.890-1.224 and in the recessive inheritance model, OR = 0.975, 95%CI = 0.894-1.063). We conclude that the XRCC1 Arg399Gln polymorphism is not a risk factor for developing gastric cancer. Source


Ning J.,Harbin Medical University
European journal of histochemistry : EJH | Year: 2012

Ubiquitin-specific protease 22 (USP22), a novel ubiquitin hydrolase, has been implicated in oncogenesis and cancer progression in various types of human cancer. However, the clinical significance of USP22 expression in non-small cell lung cancer (NSCLC) has not been determined. In the present study, USP22 messenger RNA (mRNA) and protein levels were analyzed by quantitative real-time polymerase chain reaction (PCR) and western blot analysis in 30 cases of NSCLC and in corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect USP22 protein expression in 86 primary tumor tissues derived from clinically annotated NSCLC cases at stage I-II. In our analysis we found that both USP22 mRNA and protein levels in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues and that there was a significant correlation between the expression of USP22 mRNA and protein (P=0.000, κ=0.732). In addition, a high-level of USP22 expression was observed in 53.3% (39 out of 86) cases and it was correlated with large tumor size (P=0.029) and lymph node metastasis (P=0.026). Patients with tumors displaying a high-level of USP22 expression showed significantly shorter survival (P=0.006, log-rank test). Importantly, multivariate analysis showed that high USP22 protein expression was an independent prognostic factor for NSCLC patients (P=0.003). In sum, our data suggest that USP22 plays an important role in NSCLC progression at the early stage, and that overexpression of USP22 in tumor tissues could be used as a potential prognostic marker for patients with early clinical stage of NSCLC. Source


Fan X.,Harbin Institute of Technology | Jiao G.,Harbin Institute of Technology | Gao L.,Harbin Medical University | Jin P.,Harbin Institute of Technology | Li X.,Harbin Institute of Technology
Journal of Materials Chemistry B | Year: 2013

We report a green and facile procedure of synthesizing a graphene nanosheet-carbon nanotube-iron oxide nanoparticle hybrid (GN-CNT-Fe 3O4) as a promising platform for the loading and delivery of anticancer drugs. The obtained GN-CNT-Fe3O4 hybrid exhibited superparamagnetic properties with the saturation magnetization of 19.824 emu g-1. This hybrid nanostructure possesses a superior capability of binding the anticancer drug 5-fluorouracil (5-FU) with a high loading capacity of up to 0.27 mg mg-1 with a 5-FU concentration of 0.5 mg mL-1, and also possesses a pH-activated release profile. Moreover, cellular uptake studies show that the resulting GN-CNT-Fe 3O4 hybrid can be internalized efficiently by HepG2 cells. In vitro cytotoxicity tests suggest that the obtained GN-CNT-Fe 3O4 hybrid is nontoxic for Chang liver cells, even at the high concentration of 80 μg mL-1, however, the 5-FU-loaded GN-CNT-Fe3O4 hybrid showed significant cytotoxic effects in HepG2 cells. The results show that this novel 3D hybrid is a promising candidate for anti-cancer drug delivery systems. © 2013 The Royal Society of Chemistry. Source


Yao C.,University of Electronic Science and Technology of China | Li H.,University of Electronic Science and Technology of China | Shen X.,University of Electronic Science and Technology of China | He Z.,University of Electronic Science and Technology of China | And 3 more authors.
PLoS ONE | Year: 2012

Background: Hundreds of genes with differential DNA methylation of promoters have been identified for various cancers. However, the reproducibility of differential DNA methylation discoveries for cancer and the relationship between DNA methylation and aberrant gene expression have not been systematically analysed. Methodology/Principal Findings: Using array data for seven types of cancers, we first evaluated the effects of experimental batches on differential DNA methylation detection. Second, we compared the directions of DNA methylation changes detected from different datasets for the same cancer. Third, we evaluated the concordance between methylation and gene expression changes. Finally, we compared DNA methylation changes in different cancers. For a given cancer, the directions of methylation and expression changes detected from different datasets, excluding potential batch effects, were highly consistent. In different cancers, DNA hypermethylation was highly inversely correlated with the down-regulation of gene expression, whereas hypomethylation was only weakly correlated with the up-regulation of genes. Finally, we found that genes commonly hypomethylated in different cancers primarily performed functions associated with chronic inflammation, such as 'keratinization', 'chemotaxis' and 'immune response'. Conclusions: Batch effects could greatly affect the discovery of DNA methylation biomarkers. For a particular cancer, both differential DNA methylation and gene expression can be reproducibly detected from different studies with no batch effects. While DNA hypermethylation is significantly linked to gene down-regulation, hypomethylation is only weakly correlated with gene up-regulation and is likely to be linked to chronic inflammation. © 2012 Yao et al. Source


Zhao Y.,Harbin Medical University
American Journal of Epidemiology | Year: 2013

Adenomatous polyposis coli gene (APC) polymorphisms may influence the risk for colorectal neoplasia. However, results thus far have been inconclusive. We performed a systematic literature search of the Medline, Embase, Cochrane Collaboration, and HuGE databases and reviewed the references of pertinent articles through May 2012. Odds ratios with 95% confidence intervals were used to estimate the association between 3 APC polymorphisms (D1822V, E1317Q, and I1307K) and colorectal neoplasia. In total, 40 studies from 1997 to 2010 were included in this meta-analysis, and individuals with the D1822V variant homozygote VV genotype had a slight decrease in the risk for colorectal neoplasia compared with the wild-type homozygote DD genotype (pooled odds ratio = 0.87, 95% confidence interval: 0.77, 0.99). There was a small association between the APC E1317Q polymorphism and a risk for colorectal neoplasia (variant vs. wild-type: pooled odds ratio = 1.41, 95% confidence interval: 1.14, 1.76), particularly for colorectal adenomas (variant vs. wild-type: odds ratio = 2.89, 95% confidence interval: 1.83, 4.56). Compared with those who carried the wild-type I1307K, Ashkenazi Jews who carried the I1307K variant were at a significantly increased risk for colorectal neoplasia, with a pooled odds ratio of 2.17 (95% confidence interval: 1.64, 2.86). Our study suggests that APC is a candidate gene for colorectal neoplasia susceptibility. © 2013 © The Author 2013. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Source


Lu B.,University of Groningen | Mahmud H.,University of Groningen | Maass A.H.,University of Groningen | Yu B.,Harbin Medical University | And 3 more authors.
PLoS ONE | Year: 2010

BI 2536 is a new anti-mitotic drug that targets polo-like kinase 1 (Plk1) and is currently under clinical development for cancer therapy. The effect of this drug on cancer cells has been extensively investigated, but information about the effects on primary dividing cells and differentiated non-dividing cells is scarce. We have investigated the effects of this drug on primary neonatal rat cardiac fibroblasts and on differentiated cardiomyocytes and explored the possibility to use this drug to enrich differentiated cell populations in vitro. BI 2536 had a profound effect on cardiac fibroblast proliferation in vitro and arrested these cells in mitosis with an IC50 of about 43 nM. Similar results were observed with primary human cells (HUVEC, IC50 = 30 nM), whereas the cancer cell line HeLa was more sensitive (IC50 of 9 nM). Further analysis revealed that prolonged mitotic arrest resulted in cell death for about 40% of cardiac fibroblasts. The remaining cells showed an interphase morphology with mostly multi- and micro-nucleated nuclei. This indicates that a significant number of primary fibroblasts are able to escape BI 2536 induced mitotic arrest and apparently become aneuploid. No effects were observed on cardiomyocytes and hypertrophic response (growth) upon endothelin-1 and phenylephrine stimulation was normal in the presence of BI 2536. This indicates that BI 2536 has no adverse effects on terminally differentiated cells and still allows proliferation independent growth induction in these cells. In conclusion, cardiomyocytes could be enriched using BI 2536, but the formation of aneuploidy in proliferating cells most likely limits this in vitro application and does not allow its use in putative cell based therapies. © 2010 Lu et al. Source


Liu L.,Harbin Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2013

Prostate cancer (PCa) is a common disease in elderly men, its incidence ranking the second among all malignancies in males in Western countries and increasing in China in the last decade. Tumor metastasis is the main cause of death of PCa patients. In the development and progression of tumor, the tumorous cells in the infiltration area interact with their microenvironment, undergo epithelial-mesenchymal transition (EMT) and consequently cause distant metastases. So to study the role of EMT in the development and progression of tumor is of great significance for the treatment of PCa. This article reviews the relevant literature of the last 3 years and gives an overview of the factors affecting EMT in prostate cancer, aiming at a therapeutic target. Source


Xu X.-H.,Harbin Medical University | Xu X.-H.,Glaxosmithkline | Zhong Z.,Glaxosmithkline
Acta Pharmacologica Sinica | Year: 2013

With the general decline of pharmaceutical research productivity, there are concerns that many components of the drug discovery process need to be redesigned and optimized. For example, the human immortalized cell lines or animal primary cells commonly used in traditional drug screening may not faithfully recapitulate the pathological mechanisms of human diseases, leading to biases in assays, targets, or compounds that do not effectively address disease mechanisms. Recent advances in stem cell research, especially in the development of induced pluripotent stem cell (iPSC) technology, provide a new paradigm for drug screening by permitting the use of human cells with the same genetic makeup as the patients without the typical quantity constraints associated with patient primary cells. In this article, we will review the progress made to date on cellular disease models using human stem cells, with a focus on patient-specific iPSCs for neurological diseases. We will discuss the key challenges and the factors that associated with the success of using stem cell models for drug discovery through examples from monogenic diseases, diseases with various known genetic components, and complex diseases caused by a combination of genetic, environmental and other factors. © 2013 CPS and SIMM. Source


Jia Y.,Monash University | Jia Y.,Peking University | Morand E.F.,Monash University | Song W.,Monash University | And 4 more authors.
Journal of Cellular Physiology | Year: 2013

Annexin-A1 (AnxA1) is a glucocorticoid-induced protein with multiple actions in the regulation of inflammatory cell activation. The contribution of AnxA1 to human cell biology is not well understood. We investigated the contribution of AnxA1 and its receptor, formyl-peptide receptor 2 (FPR2), to the regulation of inflammatory responses in human normal lung fibroblasts (NLF). Silencing constitutive AnxA1 expression in NLF using small interfering RNA (siRNA) was associated with moderate but significant increases in tumor necrosis factor (TNF)-induced proliferation and interleukin (IL)-6 production, accompanied by reduction of ERK and NF-κB activity. AnxA1 regulation of ERK and NF-κB activation was associated with effects on proliferation. Blocking FPR2 using the specific antagonist WRW4 mimicked the effects of AnxA1 silencing on TNF-induced proliferation, IL-6, ERK, and NF-κB activation. AnxA1 silencing also impaired inhibitory effects of glucocorticoid on IL-6 production and on the expression of glucocorticoid-induced leucine zipper (GILZ), but blocking FPR2 failed to mimic these effects of AnxA1 silencing. These data suggest that AnxA1 regulates TNF-induced proliferation and inflammatory responses in lung fibroblasts, via effects on the ERK and NF-κB pathways, which depend on FPR2. AnxA1 also mediates effects of glucocorticoids and GILZ expression, but these effects appear independent of FPR2. These findings suggest that mimicking AnxA1 actions might have therapeutic potential in chronic inflammatory lung diseases. © 2012 Wiley Periodicals, Inc. Source


Lu C.,Harbin Medical University | Lu C.,University of Michigan | Li X.-Y.,University of Michigan | Hu Y.,University of Michigan | And 2 more authors.
Blood | Year: 2010

Human mesenchymal stem cells (hMSCs) localized to bone marrow, nonhematopoietic organs, as well as perivascular niches are postulated to traffic through type I collagen-rich stromal tissues to first infiltrate sites of tissue damage, inflammation, or neoplasia and then differentiate. Nevertheless, the molecular mechanisms supporting the ability of hMSCs to remodel 3-dimensional (3D) collagenous barriers during trafficking or differentiation remain undefined. Herein, we demonstrate that hMSCs degrade and penetrate type I collagen networks in tandem with the expression of a 5-member set of collagenolytic matrix metalloproteinases (MMPs). Specific silencing of each of these proteases reveals that only a single membrane-tethered metalloenzyme, termed MT1-MMP, plays a required role in hMSC-mediated collagenolysis, 3D invasion, and intravasation. Further, once confined within type I collagen-rich tissue, MT1-MMP also controls hMSC differentiation in a 3D-specific fashion. Together, these data demonstrate that hMSC invasion and differentiation programs fall under the control of the pericellular collagenase, MT1-MMP. © 2010 by The American Society of Hematology. Source


Sun C.,Harbin Medical University
Wei sheng yan jiu = Journal of hygiene research | Year: 2013

To investigate whether curcumin intake could improve kidney, liver pathological changes in type 2 diabetes (T2DM) rats. 100 male Wistar rats were randomly divided into two groups: 10 rats in the control group; 90 in the T2DM model rats, the using low-dose treptozotocin (30 mg/kg BW) combined high sugar and high fat diet to induce T2DM model. After the success of the model induction, 39 T2DM rats met the selection criteria, which were randomly divided into 4 groups: T2DM model control group, low-dose curcumin group (50 mg/kg BW), curcumin dose group (150 mg/kg BW) and curcumin high-dose group (250 mg/kg BW), given intervention. After 45 days treatment, rats from each group were randomly selected four for pathological testing and observation of kidney and liver changes. Compared with the control group, the results showed that blood glucose and lipids in T2DM model group were significantly increased (P < 0.05). Compared to the T2DM control group, curcumin treatment significant improved kidney and liver pathological changes. Curcumin can improve liver and kidney pathological changes in T2DM rats. Source


Zhang R.,Tongji University | Dai L.-Z.,Tongji University | Xie W.-P.,Nanjing Medical University | Yu Z.-X.,Central South University | And 7 more authors.
Chest | Year: 2011

Background: In a previous study of Chinese patients with idiopathic pulmonary arterial hypertension (IPAH) in the nontargeted therapy era (defined as the time before 2006 when new pulmonary arterial hypertension-specific drugs were not available in China), we reported 1- and 3-year survival estimates of only 68% and 39%, respectively. However, it is not yet known whether the survival of patients with pulmonary arterial hypertension is improved in the modern treatment era (defined in China as after 2006). Methods: A retrospective cohort study was undertaken in 276 consecutive patients with newly diagnosed incident IPAH and connective tissue disease-related pulmonary arterial hypertension (CTDPAH) who were referred between 2007 and 2009. Baseline characteristics and survival rates in the two groups were compared. Results: The 1- and 3-year survival estimates were 92.1% and 75.1%, respectively, in patients with IPAH, and 85.4% and 53.6%, respectively, in patients with CTDPAH. Patients with CTDPAH had a significantly lower mean pulmonary artery pressure, more pericardial effusion, and more severe impairment of the diffusion capacity of the lung for carbon monoxide than patients with IPAH. A diagnosis of CTDPAH, World Health Organization functional class III or IV, single-breath diffusion capacity of the lung for carbon monoxide, < 80% predicted, and the presence of pericardial effusion were independent predictors of mortality. The 1- and 3-year survival rates of male patients were 93.5% and 77.5%, respectively, in those with IPAH, and 71.1% and 47.4%, respectively, in those with CTDPAH. Conclusions: The survival rates of patients with pulmonary arterial hypertension have improved in China in the modern treatment era, despite the high costs of treatment and financial constraints. However, the survival rates of patients with CTDPAH are inferior to those of patients with IPAH. Our study also indicates poorer survival rates in male patients with CTDPAH. © 2011 American College of Chest Physicians. Source


BACKGROUND/PURPOSE:: The aim of our research was to investigate the potential role of brain-derived neurotrophic factor (BDNF) in diabetic retinopathy (DR). Measurement of serum circulating levels of BDNF and analysis of polymorphism of BDNF gene (Val66Met) were applied and compared with diabetic patients without DR. METHODS:: From February 2014 and March 2015, all eligible patients with Type 2 diabetic mellitus at our hospital were consecutively recruited (N = 404). Their serum BDNF levels were detected by enzyme-linked immunosorbent assay. BDNF val66met polymorphism genotyping was conducted according to the laboratoryʼs standard protocol. At baseline, demographic and clinical data were taken. The relationship of BDNF with DR was investigated with the use of logistic regression models. Receiver operating characteristic curves were used to test the overall accuracy of BDNF and other markers. RESULTS:: Diabetic patients with DR and vision-threatening DR had significantly lower BDNF levels on admission (P < 0.0001 both). The BDNF genotyping results showed that there was no difference between the diabetic patients with DR and those without DR. Multivariate logistic regression analysis adjusted for common risk factors showed that serum BDNF levels were independent risk factors for DR (odds ratio = 0.86; 95% confidence interval [CI]: 0.80–0.92; P < 0.0001) and vision-threatening DR (odds ratio = 0.79; 95% CI: 0.75–0.85; P < 0.0001). Brain-derived neurotrophic factor improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.69 (95% CI: 0.60–0.76) to 0.85 (95% CI: 0.79–0.90; P < 0.01) and for vision-threatening DR from 0.77 (95% CI: 0.67–0.87) to 0.86 (95% CI: 0.80–0.92; P < 0.01). CONCLUSION:: The present study demonstrated that, rather than Val66Met polymorphism, decreased serum levels of BDNF were associated with DR and vision-threatening DR in Chinese Type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications. © 2016 by Ophthalmic Communications Society, Inc. Source


Ren Z.,Harbin Medical University | Qiu A.,Harbin Childrens Hospital
Singapore Medical Journal | Year: 2014

Introduction: Sleep problems are a prominent feature in children with attention deficit hyperactivity disorder (ADHD). Unlike existing studies that focused on extreme samples (i.e. normal vs. ADHD), our study investigated the associations of sleep-related behaviours and ADHD features in nonclinical Chinese preschoolers. Methods: All participants were recruited via advertisements and screened for eligibility through a telephone interview prior to an onsite visit. The maternal reports of the Conners' Parent Rating Scale (CPRS) and Pediatric Sleep Questionnaire (PSQ) were acquired from 110 Chinese preschoolers aged six years. Regression models were used to examine the association between CPRS and PSQ scores. Results: The results obtained from regression models on the CPRS and PSQ scores of the 110 participants showed that none of the sleep-related behavioural measures (i.e. sleep-related breathing disorder [SRBD], snoring, daytime sleepiness, restless legs syndrome) was associated with inattention in our sample. However, worse SRBD was associated with higher hyperactivity. Conclusion: Our study underpins the importance of understanding the relationship between sleep-related behaviours and ADHD characteristics before the usual age of clinical diagnosis in children with ADHD. Source


Ma Y.,Harbin Medical University
Journal of cancer research and clinical oncology | Year: 2014

The aim of this study was to identify proteins associated with gastric cancer lymph node metastasis and explore the clinicopathological significance of these proteins. Gastric cancer tissues were obtained from 24 patients with high or low lymph node metastatic potential. Total cellular proteins were separated by two-dimensional gel electrophoresis (2-DE), analyzed by MALDI/TOF-TOF MS, and identified by a database search. Expression of 14-3-3β and profilin-1 was then immunohistochemically verified in paraffin-embedded gastric cancer tissues from 128 patients and analyzed by multivariate logistic regression models, Kaplan-Meier curves, and Cox proportional hazard models. A total of 26 differentially expressed proteins were identified, 20 of which were overexpressed and 6 of which were underexpressed. 14-3-3β and profilin-1 were upregulated in gastric cancer tissues with and without lymph node metastasis, respectively. Expression of 14-3-3β protein was associated, but profilin-1 expression was inversely associated with gastric cancer lymph node metastasis. Multivariate analysis showed that overexpression of 14-3-3β and reduced expression of profilin-1 were independent risk factors for gastric cancer lymph node metastasis, while 14-3-3β overexpression was an independent prognostic factor for gastric cancer patients. The current study identified 26 differentially expressed proteins. Further studies showed that both 14-3-3β and profilin-1 protein may be useful biomarkers for prediction of gastric cancer lymph node metastasis and that expression of 14-3-3β was a prognostic marker for gastric cancer patients. Source


Li Q.,Tianjin University of Science and Technology | Yu N.,General Hospital of Shenyang Military Command | Wang Y.,Tianjin University of Science and Technology | Sun Y.,Heilongjiang University of Chinese Medicine | And 2 more authors.
Carbohydrate Polymers | Year: 2013

Box-Behnken design including independent variables such as extraction temperature (60-80 C), extraction time (20-40 min) and ratio of water to raw material (30-50 mL/g) was used to optimize the extraction process of Bruguiera gymnorrhiza polysaccharides (BGPs). The experimental data were fitted to a second-order polynomial equation using multiple regression analysis. The optimum conditions were predicted as follows: extraction temperature 71 C, extracting time 31.4 min, and ratio of water to raw material 42. Under these conditions, the yield of BGPs obtained was (16.43 ± 0.08)%, which was in good agreement with the predicted value 16.47%. Additionally, characterization of BGPs was obtained by FT-IR analysis. The antioxidant activities of BGPs were evaluated in vitro. BGPs demonstrated appreciable antioxidant potential on superoxide anion radical, ABTS radical, and hydroxyl radical scavenging. These may provide theoretical basis for further system research and rational development and utilization of mangrove resources. © 2013 Elsevier Ltd. All rights reserved. Source


Our previous studies demonstrated that caclium-sensing receptor (CaR) stimulation elicited phospholipase C (PLC)-mediated inositol triphosphate (IP(3)) formation, leading to an elevation in [Ca(2+)](i) released from the endo(sarco)plasmic reticulum (ER) to induce ER stress and perturbations of ER function, which cause cardiomyocyte apoptosis during ischemia/reperfusion (I/R). The aim of this study was to determine whether the protection of post-conditioning (PC) from I/R heart injury involved relieving calcium-sensing receptor (CaR)-induced ER stress. Male Wistar rats were subjected to 30 min of ischemia followed by 2 h of reperfusion. The rats were post-conditioned after the 30 min of ischemia by three cycles of 10 s of reperfusion followed by 10 s of ischemia at the onset of reperfusion. Meanwhile, GdCl(3), an activator of CaR, and NPS-2390, a specific inhibitor, were administered. We found that the PC and PC with NPS-2390 groups improved the recovery of cardiac function during reperfusion compared to the IR and PC groups with GdCl(3), respectively. [Ca(2+)](i) and [Ca(2+)](ER) were determined using Fluo-4 AM and Fluo-5N AM, respectively, using laser confocal microscopy. [Ca(2+)](i) was significantly increased, whereas [Ca(2+)](ER) was significantly decreased in the I/R and PC groups with GdCl(3). The rate of apoptotic cells was significantly decreased as shown by TUNEL (Terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling) assay in PC and PC with NPS-2390 groups compared to the I/R and PC groups with GdCl(3). In the I/R and PC groups with GdCl(3), the activated fragments of caspase-12, the cleavage products of activating transcription factor 6 (ATF6) and phospho-JNK (c-Jun NH(2)-terminal kinase) were increased compared to the PC and PC with GdCl(3) groups. These results demonstrated that PC could protect the myocardium from I/R injury by inhibiting CaR-induced sarcoplasmic reticulum stress. Source


Liu B.,Harbin Institute of Technology | Cheng H.D.,Harbin Institute of Technology | Cheng H.D.,Utah State University | Huang J.,Harbin Institute of Technology | And 3 more authors.
Pattern Recognition | Year: 2010

Region of interest (ROI) is a region used to extract features. In breast ultrasound (BUS) image, the ROI is a breast tumor region. Because of poor image quality (low SNR (signal/noise ratio), low contrast, blurry boundaries, etc.), it is difficult to segment the BUS image accurately and produce a ROI which precisely covers the tumor region. Due to the requirement of accurate ROI for feature extraction, fully automatic classification of BUS images becomes a difficult task. In this paper, a novel fully automatic classification method for BUS images is proposed which can be divided into two steps: "ROI generation step" and "ROI classification step". The ROI generation step focuses on finding a credible ROI instead of finding the precise tumor location. The ROI classification step employs a novel feature extraction and classification strategy. First, some points in the ROI are selected as the "classification checkpoints" which are evenly distributed in the ROI, and the local texture features around each classification checkpoint are extracted. For each ROI, all the classification checkpoints are classified. Finally, the class of the BUS image is determined by analyzing every classification checkpoint in the corresponding ROI. Both steps were implemented by utilizing a supervised texture classification approach. The experiments demonstrate that the proposed method is very robust to the segmentation of BUS images, and very effective and useful for classifying breast tumors. © 2009 Elsevier Ltd. All rights reserved. Source


Liu B.,Harbin Institute of Technology | Cheng H.D.,Harbin Institute of Technology | Cheng H.D.,Utah State University | Huang J.,Harbin Institute of Technology | And 3 more authors.
Pattern Recognition | Year: 2010

Because of its low signal/noise ratio, low contrast and blurry boundaries, ultrasound (US) image segmentation is a difficult task. In this paper, a novel level set-based active contour model is proposed for breast ultrasound (BUS) image segmentation. At first, an energy function is formulated according to the differences between the actual and estimated probability densities of the intensities in different regions. The actual probability densities are calculated directly. For calculating the estimated probability densities, the probability density estimation method and background knowledge are utilized. The energy function is formulated with level set approach, and a partial differential equation is derived for finding the minimum of the energy function. For performing numerical computation, the derived partial differential equation is approximated by the central difference and non-re-initialization approach. The proposed method was operated on both the synthetic images and clinical BUS images for studying its characteristics and evaluating its performance. The experimental results demonstrate that the proposed method can model the BUS images well, be robust to noise, and segment the BUS images accurately and reliably. © 2010 Elsevier Ltd. All rights reserved. Source


Ma N.,Harbin Medical University
Molecular and cellular biochemistry | Year: 2012

Most intronic micro-RNAs are coexpressed with their host genes, suggesting that they may play similar roles. The function of miR-483 remains unknown, although it is embedded in an intron of Igf2 gene, which is an activator of hepatocellular carcinoma proliferation. In the present study, we provide evidence that Igf2-derived miR-483 can induce proliferation in hepatocellular carcinoma cells. The miR-483 promotion of proliferation was analysed by soft agar colony formation assay and proliferation curve assay. The effect of miR-483 on Socs3 expression was examined by Western blot and a reporter assay. Our results revealed that Igf2-derived intronic miR-483 was identified by the application of 94G6, an inhibitor of Igf2 at the transcriptional level. All results from the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) MTT assay, the proliferation curve assay and the soft agar colony formation assay showed that miR-483 promoted the proliferation of hepatocellular carcinoma cells. Finally, Socs3, a putative target predicted by bioinformatics, was regulated by miR-483 at mRNA and protein levels. Direct binding with the 3' UTR was identified by a luciferase activity assay. Our findings demonstrate that Igf2-derived intronic miR-483, through downregulation of its target Socs3, regulates hepatoma cell proliferation and thus may serve as a potential target for hepatocellular carcinoma therapy. Source


He Y.H.,Harbin Medical University
Molecular and cellular biochemistry | Year: 2012

Adipocyte differentiation and adipogenesis are closely related to obesity and obesity-induced metabolic disorders. The calcium-sensing receptor (CaSR) has been reported to play an antilipolytic role in human adipocyte and regulate cell differentiation in many tissues. However, the effects of CaSR on adipocyte differentiation and adipogenesis have not been clarified. In the study, we observed that activation of CaSR significantly promoted adipocyte differentiation and adipogenesis in human SW872 adipocytes. Gene expression analysis revealed that the CaSR activation increased the transcription factor proliferator-activated receptor γ (PPARγ) and its downstream genes including CCAAT element binding protein α (C/EBPα), adipose fatty acid-binding protein (aP2), and lipoprotein lipase. The activity of glycerol-3-phosphate dehydrogenase was also increased after the stimulation of CaSR. In addition, levels of cyclic AMP and calcium which have been shown to regulate PPARγ gene expression were significantly affected by the activation of CaSR. These effects could be suppressed by CaSR small interfering RNA (CaSR-siRNA). In conclusion, our findings suggest that activation of CaSR promotes differentiation and adipogenesis in adipocytes, which might be achieved by upregulating PPARγ and its downstream gene expressions. Therefore, CaSR in adipocytes may be involved in the pathogenesis of obesity by promoting adipocyte differentiation and adipogenesis. Source


Li Y.,Harbin Medical University
Journal of Convergence Information Technology | Year: 2012

In recent years, the KDD (knowledge discovery in database) has been regarded as a process of useful knowledge from the database. In the research field of KDD, sequential data mining of an important issue is my useful knowledge such as patterns, rules, and structured described as an expert in the field. Although timing data mining can find out useful knowledge, in the given data, it is difficult to find such knowledge of the cooperation between data miners, system developers, and domain experts. In this paper, we present an implementation of the integrated time-series data mining environment. Then, the system obtains valuable knowledge for a medical expert from a chronic hepatitis dataset as a case study of medical time-series rule mining. Source


Sun B.,Harbin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2013

To investigate the feasibility and clinical value of the step-up approach for severe acute pancreatitis (SAP). Clinical data of 121 SAP patients admitted between January 2002 and December 2011 were retrospectively analyzed. Fifty-eight patients (37 males and 21 females, aged from 20 to 72 years, mean 47.6 years) in the group of direct open necrosectomy from January 2002 to December 2006 were performed laparotomy through removal of all necrotic tissue. Sixty-three patients (42 males and 21 females, aged from 19 to 78 years, mean 46.2 years) of step-up approach from January 2007 to December 2011 underwent percutaneous catheter drainage through retroperitoneum or omental bursa guided by B-type ultrasonography for the first therapy, and then, according to the pathogenetic condition, if necessary, followed by a small incisional necrosectomy along the drainage tube. The two groups were compared for the rates of postoperative complications, death, transfusion and length of stay, medical costs. The rates of total postoperative complications, organ dysfunction, alimentary tract fistula and incisional hernia in step-up approach group were significantly lower than those of direct open necrosectomy group (31.7% vs. 62.1%, 14.3% vs. 37.5%, 6.3% vs. 19.0%, 9.5% vs. 29.3%; χ(2) = 4.43 to 11.17, P = 0.001 to 0.035). The other complications had no significant differences between the two groups (P > 0.05). Patients in step-up approach group had a lower rates of transfusion (44.4% vs. 70.7%, χ(2) = 8.488, P = 0.004), fewer medical costs of transfusion and hospital stay, compared with those in direct open necrosectomy group ((2525 ± 4573) yuan vs. (4770 ± 6867) yuan, t = 2.131, P = 0.035; (171 213 ± 50 917) yuan vs. (237 874 ± 67 832) yuan, t = 2.496, P = 0.014). There were no significant differences of length of stay and mortality between two groups (P > 0.05). Step-up approach for SAP which can reduce the rates of postoperative complications, transfusion and medical costs has significant feasibility and great clinical value. Source


Yang Z.,University of California at San Diego | Tatham A.J.,University of California at San Diego | Zangwill L.M.,University of California at San Diego | Weinreb R.N.,University of California at San Diego | And 3 more authors.
American Journal of Ophthalmology | Year: 2015

Purpose To evaluate the diagnostic accuracies of swept-source optical coherence tomography (OCT) wide-angle and peripapillary retinal nerve fiber layer (RNFL) thickness measurements for glaucoma detection. Design Cross-sectional case-control study. Methods In this study we enrolled 144 glaucomatous eyes of 106 subjects and 66 eyes of 42 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Glaucoma was defined by the presence of repeatable abnormal standard automated perimetry results and/or progressive glaucomatous optic disc change on masked grading of stereophotographs. Wide-angle and peripapillary RNFL thicknesses were assessed using swept-source OCT. Peripapillary RNFL thickness was also evaluated using spectral-domain OCT. Areas under the receiver operating characteristic (ROC) curves were calculated to evaluate the ability of the different swept-source OCT and spectral-domain OCT parameters to discriminate between glaucomatous and healthy eyes. Results Mean (±standard deviation) average spectral-domain OCT wide-angle RNFL thicknesses were 50.5 ± 5.8 μm and 35.0 ± 9.6 μm in healthy and glaucomatous eyes, respectively (P < 0.001). Corresponding values for swept-source OCT peripapillary RNFL thicknesses were 103.5 ± 12.3 μm and 72.9 ± 16.5 μm, respectively (P < 0.001). Areas under the ROC curves of swept-source OCT wide-angle and peripapillary RNFL thickness were 0.88 and 0.89, respectively. Swept-source OCT performed similar to average peripapillary RNFL thickness obtained by spectral-domain OCT (area under the ROC curve of 0.90). Conclusion Swept-source OCT wide-angle and peripapillary RNFL thickness measurements performed well for detecting glaucomatous damage. The diagnostic accuracies of the swept-source OCT and spectral-domain OCT RNFL imaging protocols evaluated in this study were similar. © 2015 Elsevier Inc. ALL RIGHTS RESERVED. Source


Tang J.,Harbin Medical University
International journal of nanomedicine | Year: 2011

Genistein, one of the major isoflavones, has received great attention as a phytoestrogen and potential cancer chemoprevention agent. However, the dissolution and bioavailability of genistein from solid oral preparations is low due to its poor water solubility. In order to improve the oral bioavailability of genistein, genistein nanoparticles were prepared by the nanoprecipitation technique using Eudragit(®) E100 as carriers and an optimized formulation of mass ratio (genistein:Eudragit E100, 1:10). The mean particle size of genistein nanoparticles was approximately 120 nm when diluted 100 times with distilled water. The drug-loaded nanoparticles were spherical on observation by transmission electric microscopy. Encapsulation efficiency and drug loading of the genistein nanoparticles were approximately 50.61% and 5.02%, respectively. Release of drug from the genistein nanoparticles was two times greater than that from the conventional capsules. After administration of genistein suspension or genistein nanoparticles at a single dose of 100 mg/kg to fasted rats, the relative bioavailability of genistein from the nanoparticles compared with the reference suspension was 241.8%. These results suggested that a nanoparticle system is a potentially promising formulation for the efficient delivery of poorly water-soluble drugs by oral administration. Source


Cui X.-S.,Jilin University | Xu Y.-N.,Chungbuk National University | Shen X.-H.,Harbin Medical University | Zhang L.-Q.,Jilin University | And 2 more authors.
Cellular Reprogramming | Year: 2011

Low efficiency of somatic cell nuclear transfer (SCNT) is attributed to incomplete reprogramming of transferred nuclei into oocytes. Trichostatin A (TSA), a histone deacetylase inhibitor, has been used to enhance nuclear reprogramming following SCNT. However, the molecular mechanism of TSA for the improvement of the preimplantation embryo and fetal development following SCNT is not known. The present study investigates embryo viability and gene expression of cloned bovine preimplantation embryos in the presence and absence of TSA compared to embryos produced by in vitro fertilization or parthenogenetic activation. Our results indicated that TSA treatment significantly improved total and inner cell mass (ICM) cell number and ratio of ICM:trophectoderm (TE) and also decreased the apoptotic index including total, ICM, and ratio of ICM:TE. Four apoptotic-related genes, Bcl-xL, survivin, Bcl2-associated X protein (Bax), and caspase 3 (Casp3), and four pluripotency/differentiation related genes, Oct4, SRY (sex determining region Y)-box 2 (Sox2), Cdx2, and colony-stimulating factor 1 receptor (Csf1r), were measured by real-time RT-PCR. TSA treatment resulted in the high expression of antiapoptotic gene Bcl-xL and low expression of pro-apoptotic gene Bax compared to untreated NT embryos, fertilized embryos, or parthenotes. Furthermore, mRNA expression of Cdx2 was higher in NT-TSA embryos than in NT and in vitro fertilization (IVF) counterparts. Additionally, low expression of microRNA (mir)-21 in NT embryos was enhanced following TSA treatment. These results suggest that TSA positively regulates nuclear reprogramming, and TSA may increased resistance or reduced signal for induction of apoptosis. © 2011 Mary Ann Liebert, Inc. Source


Gao R.,Chinese Academy of Sciences | Yang Y.,Chinese Academy of Sciences | Han Y.,General Hospital of Shenyang Military Command | Huo Y.,Peking University | And 12 more authors.
Journal of the American College of Cardiology | Year: 2015

Background The everolimus-eluting bioresorbable vascular scaffold (BVS) is designed to achieve results comparable to metallic drug-eluting stents at 1 year, with improved long-term outcomes. Whether the 1-year clinical and angiographic results of BVS are noninferior to current-generation drug-eluting stents has not been established. Objectives This study sought to evaluate the angiographic efficacy and clinical safety and effectiveness of BVS in a randomized trial designed to enable approval of the BVS in China. Methods Eligible patients with 1 or 2 de novo native coronary artery lesions were randomized to BVS or cobalt-chromium everolimus-eluting stents (CoCr-EES) in a 1:1 ratio stratified by diabetes and the number of lesions treated. Angiographic and clinical follow-up were planned at 1 year in all patients. The primary endpoint was angiographic in-segment late loss (LL), powered for noninferiority with a margin of 0.15 mm. Results A total of 480 patients were randomized (241 BVS vs. 239 CoCr-EES) at 24 sites. Acute clinical device success (98.0% vs. 99.6%; p = 0.22) and procedural success (97.0% and 98.3%; p = 0.37) were comparable in BVS- and CoCr-EES-treated patients, respectively. The primary endpoint of in-segment LL at 1 year was 0.19 ± 0.38 mm for BVS versus 0.13 ± 0.38 mm for CoCr-EES; the 1-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of BVS compared with CoCr-EES (pnoninferiority = 0.01). BVS and CoCr-EES also had similar 1-year rates of target lesion failure (cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization; 3.4% vs. 4.2%, respectively; p = 0.62) and definite/probable scaffold/stent thrombosis (0.4% vs. 0.0%, respectively; p = 1.00). Conclusions In the present multicenter randomized trial, BVS was noninferior to CoCr-EES for the primary endpoint of in-segment LL at 1 year. (A Clinical Evaluation of Absorb Bioresorbable Vascular Scaffold [Absorb BVS] System in Chinese Population - ABSORB China Randomized Controlled Trial [RCT]; NCT01923740) © 2015 American College of Cardiology Foundation. Source


Stabile L.P.,University of Pittsburgh | He G.,Harbin Medical University | Lui V.W.Y.,University of Pittsburgh | Henry C.,University of Pittsburgh | And 5 more authors.
Clinical Cancer Research | Year: 2013

Purpose: Strategies to inhibit the EGF receptor (EGFR) using the tyrosine kinase inhibitor erlotinib have been associated with limited clinical efficacy in head and neck squamous cell carcinoma (HNSCC). Co-activation of alternative kinases may contribute to erlotinib resistance. Experimental Design: We generated HNSCC cells expressing dominant-active c-Src (DA-Src) to determine the contribution of c-Src activation to erlotinib response. Results: Expression of DA-Src conferred resistance to erlotinib in vitro and in vivo compared with vectortransfected control cells. Phospho-Met was strongly upregulated by DA-Src, and DA-Src cells did not produce hepatocyte growth factor (HGF). Knockdown of c-Met enhanced sensitivity to erlotinib in DA-Src cells in vitro, as did combining a c-Met or c-Src inhibitor with erlotinib. Inhibiting EGFR resulted in minimal reduction of phospho-Met in DA-Src cells, whereas complete phospho-Met inhibition was achieved by inhibiting c-Src. A c-Met inhibitor significantly sensitized DA-Src tumors to erlotinib in vivo, resulting in reduced Ki67 labeling and increased apoptosis. In parental cells, knockdown of endogenous c-Src enhanced sensitivity to erlotinib, whereas treatment with HGF to directly induce phospho-Met resulted in erlotinib resistance. The level of endogenous phospho-c-Src inHNSCCcell lines was also significantly correlated with erlotinib resistance. Conclusions: Ligand-independent activation of c-Met contributes specifically to erlotinib resistance, not cetuximab resistance, in HNSCC with activated c-Src, where c-Met activation is more dependent on c-Src than on EGFR, providing an alternate survival pathway. Addition of a c-Met or c-Src inhibitor to erlotinib may increase efficacy of EGFR inhibition in patients with activated c-Src. © 2012 AACR. Source


Lang L.,Biomedical Imaging Center | Li W.,Biomedical Imaging Center | Guo N.,Biomedical Imaging Center | Ma Y.,Biomedical Imaging Center | And 6 more authors.
Bioconjugate Chemistry | Year: 2011

[ 18F]FPPRGD2, an F-18 labeled dimeric cyclic RGDyK peptide, has favorable properties for PET imaging of angiogenesis by targeting the α vβ 3 integrin receptor. This radiotracer has been approved by the FDA for use in clinical trials. However, the time-consuming multiple-step synthetic procedure required for its preparation may hinder the widespread usage of this tracer. The recent development of a method using an F-18 fluoride-aluminum complex to radiolabel peptides provides a strategy for simplifying the labeling procedure. On the other hand, the easy-to-prepare [ 68Ga]-labeled NOTA-RGD derivatives have also been reported to have promising properties for imaging α vβ 3 integrin receptors. The purpose of this study was to prepare [ 18F]FPPRDG2, [ 18F]FAl-NOTA-PRGD2, and [ 68Ga]Ga-NOTA-PRGD2 and to compare their pharmacokinetics and tumor imaging properties using small animal PET. All three compounds showed rapid and high tracer uptake in U87MG tumors with high target-to-background ratios. The uptake in the liver, kidneys, and muscle were similar for all three tracers, and they all showed predominant renal clearance. In conclusion, [ 18F]FAl-NOTA-PRGD2 and [ 68Ga]Ga-NOTA-PRGD2 have imaging properties and pharmacokinetics comparable to those of [ 18F]FPPRGD2. Considering their ease of preparation and good imaging qualities, [ 18F]FAl-NOTA-PRGD2 and [ 68Ga]NOTA-PRGD2 are promising alternatives to [ 18F] FPPRGD2 for PET imaging of tumor α vβ 3 integrin expression. © 2011 American Chemical Society. Source


Wu J.,Shanghai JiaoTong University | Zhang Y.-C.,Shanghai JiaoTong University | Suo W.-H.,Shanghai JiaoTong University | Liu X.-B.,Harbin Medical University | And 3 more authors.
Oncogene | Year: 2010

Anion exchanger-1 (AE1), an erythroid-specific membrane protein, mediates the Cl /HCO 3 exchange across the plasma membrane and regulates intracellular pH. We have found that AE1 was unexpectedly expressed in gastric cancer cells and participated in the tumorigenesis of the cancer. Here, we focus on the induction of AE1 expression and its role in gastric carcinogenesis as well as in the differentiation of K562 cells. The results show that expression of AE1 is not related to genetic mutation or the mRNA level, but rather, that it is modulated by miR-24. miR-24 decreases the expression of AE1 through binding to the 3′UTR of AE1 mRNA. Transfection of an miR-24 into gastric cancer cells reduced the elevation of the AE1 protein, which resulted in return of AE1-sequestrated p16 to the nucleus, thereby inhibiting proliferation of the cells. Furthermore, the miR-24 inhibitor cooperated with hemin to induce the expression of AE1 in K562 cells and differentiation of the cells, which is consistent with results obtained from the cells cultured at pH 7.6 or from forced stable expression of AE1. These findings establish a novel regulation of miR-24-related AE1 expression in gastric carcinogenesis and erythropoiesis. © 2010 Macmillan Publishers Limited All rights reserved. Source


Li Z.,Dalian University of Technology | Lian M.,Harbin Medical University | Yang F.,Dalian University of Technology | Meng Q.,Dalian University of Technology | Gao Z.,Dalian University of Technology
European Journal of Organic Chemistry | Year: 2014

A new framework derived from the commercially available diterpenoid alkaloid lappaconitine was evaluated as a Brønsted base catalyst for the enantioselective α-hydroxylation of β-dicarbonyl compounds by using 30% hydrogen peroxide as a green and highly practical source of oxygen. This protocol allows convenient access to the corresponding α-hydroxy-β- oxo esters, α-hydroxy-β-oxo amides and (-)-kjellmanianone with up to 98% yield and 92% ee. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Hu Y.,Zhejiang University | Geng F.,Zhejiang University | Tao L.,Zhejiang University | Hu N.,Zhejiang University | And 3 more authors.
Human Brain Mapping | Year: 2011

Experts of abacus, who have the skills of abacus-based mental calculation (AMC), are able to manipulate numbers via an imagined abacus in mind and demonstrate extraordinary ability in mental calculation. Behavioral studies indicated that abacus experts utilize visual strategy in solving numerical problems, and fMRI studies confirmed the enhanced involvement of visuospatial-related neural resources in AMC. This study aims to explore the possible changes in brain white matter induced by long-term training of AMC. Two matched groups participated: the abacus group consisting of 25 children with over 3-year training in abacus calculation and AMC, the controls including 25 children without any abacus experience. We found that the abacus group showed higher average fractional anisotropy (FA) in whole-brain fiber tracts, and the regions with increased FA were found in corpus callosum, left occipitotemporal junction and right premotor projection. No regions, however, showed decreased FA in the abacus group. Further analysis revealed that the differences in FA values were mainly driven by the alternation of radial rather than axial diffusivities. Furthermore, in forward digit and letter memory span tests, AMC group showed larger digit/letter memory spans. Interestingly, individual differences in white matter tracts were found positively correlated with the memory spans, indicating that the widespread increase of FA in the abacus group result possibly from the AMC training. In conclusion, our findings suggested that long-term AMC training from an early age may improve the memory capacity and enhance the integrity in white matter tracts related to motor and visuospatial processes. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc. Source


Liu H.D.,Harbin Medical University
Sheng li xue bao : [Acta physiologica Sinica] | Year: 2010

The aim of the present study is to investigate the expression of a novel estrogen receptor, G protein-coupled receptor 30 (GPR30) and its correlation with matrix metalloproteinases-9 (MMP-9) in epithelial ovarian cancer (EOC). Ovary tissues were obtained from 39 female patients, including 30 cases of EOC and 9 cases of benign ovarian tumor. Four normal ovary tissues were used as control. Immunohistochemical staining was used to detect the expressions of GPR30 and MMP-9. Chi square test, Fisher's exact test and Spearman's rank correlation analysis were used for statistical analysis. The results showed that GPR30 overexpression rate in EOC cases was significantly higher than those in benign ovarian tumor and normal ovary cases. Whereas MMP-9 overexpression rate in EOC cases was significantly higher than that in normal ovary cases, without any difference to that in benign ovarian tumor cases. To demonstrate the relationship between GPR30 and clinicopathological variables of EOC, we further analyzed the pathology type, FIGO stage and age of patients sampled in our study. The analysis showed there were significant differences of GPR30 overexpression rate among various pathology types and different FIGO stages (P<0.05), and no significant difference of both GPR30 and MMP-9 among three age groups (P>0.05). Moreover, GPR30 expression was positively correlated with MMP-9 (r(s)=1.000, P=0.002). These results suggest that GPR30 may be involved in the invasion and metastasis of EOC, being a potential index of EOC early diagnosis and malignancy grade prediction. Source


Liu J.,Harbin Medical University
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences | Year: 2012

To review the clinical manifestation and laboratory examination of brucellosis. The clinical data of 229 patients with brucellosis admitted from January 2005 to June 2011 were retrospectively analyzed. Compared with the past, the prevalence proportion in rural area, uncertain infectious route and irregular fever type of brucellosis increased. The clinical manifestation became diverse, and standard combination therapy made patients recover more quickly, and get a better prognosis. Compared with the past, the clinical manifestation of brucellosis has changed partly. In order to avoid misdiagnosis and mistreatment, clinical doctors should study the new characteristics of brucellosis and persist in taking the standard antibiotic treatment. Source


Zhang Y.,Harbin Medical University
Clinical & experimental ophthalmology | Year: 2012

The prevalence of blind individuals in the north of China is unknown. The study aimed to investigate the prevalence and causes of blindness and low vision in rural areas in Heilongjiang province of China in 2008-2009. Cross-sectional study. PARTICIPANTS OR SAMPLES: A cluster random sampling method was used to recruit participants of all ages in rural areas of Heilongjiang. Trained professionals performed interviews and clinical examinations to measure visual acuity. The relationships between blindness or low vision and age, gender and education level were analysed. The main outcome measure was prevalence rates of bilateral blindness and bilateral low vision. Of the 11 787 subjects, 10 384 (88.1%) were surveyed. The overall age-adjusted prevalence rates were 0.7% (95% confidence interval: 0.5-0.8%) for bilateral blindness and 1.7% (95% confidence interval: 1.4-1.9%) for bilateral low vision. The prevalence rates of blindness and low vision were higher in the elderly and uneducated population (P < 0.05). The main causes for blindness and low vision were cataracts (44.1 and 46.0%, respectively) and refractive errors (17.7 and 42.5%, respectively). Blindness and low vision are highly prevalent among people with cataracts and refractive errors. Eye care planning must focus on treating the avoidable and curable forms of blindness. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists. Source


Background: Recent studies have suggested that some single nucleotide polymorphisms (SNPs) in the human µ-opioid receptor gene (OPRM1) affect the postoperative analgesic efficacy of opioids and their side effects. In this study, we assessed the association between SNPs in the OPRM1 gene and intraoperative remifentanil consumption as well as perioperative side effects during gynecological hysteroscopic surgery in women from Northern China. Methods: We analyzed 178 women undergoing gynecological hysteroscopic surgery. SNP genotyping was performed using the SNaPshot method. The state anxiety index (SAI) and pressure pain threshold (PPT) of all patients were assessed preoperatively. Monitored anesthesia care was maintained by the intravenous infusion of remifentanil. Intraoperative remifentanil usage and perioperative side effects were recorded. Statistical analyses were performed using SPSS software. Results: Patients carrying one or two copies of the minor allele (G allele) of rs558025 required significantly more intraoperative remifentanil than patients without the minor allele (p = 0.001, corrected p = 0.006). There were no significant associations between the six SNPs and various clinical characteristics. No significant associations between the six SNPs and PPT or SAI were found in our study. Conclusions: SNP rs558025 in the OPRM1 gene was associated with intraoperative remifentanil consumption during gynecological hysteroscopic surgery in our subjects. © 2014 S. Karger AG, Basel Copyright © 2014, S. Karger AG. All rights reserved. Source


Ishibashi O.,Nippon Medical School | Ali Md.M.,Nippon Medical School | Luo S.-S.,Nippon Medical School | Luo S.-S.,Harbin Medical University | And 4 more authors.
Science Signaling | Year: 2011

Short double-stranded RNAs (dsRNAs) induce type I interferon (IFN)-mediated innate immune responses. In functional studies with short interfering RNAs or synthetic mimics of microRNA precursors in vitro, we found that short dsRNAs readily induced apoptosis in cells derived from human granulosa cell tumors, but not in other cell types. Apoptosis was independent of the sequence of the dsRNA, but depended on its length, and was induced by 23- and 24-nucleotide (nt) dsRNAs, but not by shorter dsRNAs (<22 nt) or by the long dsRNA polyinosinic-polycytidylic acid. Microarray analysis revealed that apoptosis was accompanied by the increased expression of IFN-stimulated genes; however, several lines of evidence showed that IFNs did not directly induce apoptosis. Subsequent analyses revealed that the short dsRNAs increased the expression of retinoic acid-inducible gene I (RIG-I) through dsRNA-activated protein kinase (PKR). Although these dsRNAs bore 3′ overhangs and nontriphosphate 5′ termini, which are not thought to be RIG-I-activating structures, the dsRNAs bound to RIG-I and triggered proapoptotic signaling mostly by activating RIG-I, which was followed by activation of the mitogen-activated protein kinase p38. Thus, we suggest that ligand recognition and subsequent signaling by RNA sensors are more complicated than previously believed. In addition, short dsRNAs may serve as pharmacological agents to target specific tumors, such as granulosa cell tumors. Source


Jin A.,University of Toyama | Jin A.,Harbin Medical University | Ozawa T.,University of Toyama | Tajiri K.,University of Toyama | And 3 more authors.
Nature Protocols | Year: 2011

Here we report a new method for isolating antigen-specific antibody-secreting cells (ASCs) using a microwell array chip, which offers a rapid, efficient and high-throughput (up to 234,000 individual cells) system for the detection and retrieval of cells that secrete antibodies of interest on a single-cell basis. We arrayed a large population of lymphoid cells containing ASCs from human peripheral blood on microwell array chips and detected spots with secreted antibodies. This protocol can be completed in less than 7 h, including 3 h of cell culture. The method presented here not only has high sensitivity and specificity comparable with enzyme-linked immunospot (ELISPOT) but it also overcomes the limitations of ELISPOT in recovering ASCs that can be used to produce antigen-specific human monoclonal antibodies. This method can also be used to detect cells secreting molecules other than antibodies, such as cytokines, and it provides a tool for cell analysis and clinical diagnosis. © 2011 Nature America, Inc. All rights reserved. Source


Du M.,The University of Oklahoma Health Sciences Center | Wu M.,The University of Oklahoma Health Sciences Center | Fu D.,The University of Oklahoma Health Sciences Center | Fu D.,Harbin Medical University | And 4 more authors.
Diabetologia | Year: 2013

Aims/hypothesis: Blood-retina barrier leakage in diabetes results in extravasation of plasma lipoproteins. Intra-retinal modified LDLs have been implicated in diabetic retinopathy (DR), but their effects on retinal pigment epithelial (RPE) cells and the added effects of extravasated modified HDLs are unknown. Methods: In human retinas from individuals with and without diabetes and DR, immunohistochemistry was used to detect ApoB, ApoA1 and endoplasmic reticulum (ER) stress markers. In cell culture, human RPE cells were treated with native LDL (N-LDL) or heavily-oxidised glycated LDL (HOG-LDL) with or without pretreatment with native HDL (N-HDL) or heavily-oxidised glycated HDL (HOG-HDL). Cell viability, oxidative stress, ER stress, apoptosis and autophagy were assessed by Cell Counting Kit-8 assay, dichlorofluorescein assay, western blotting, immunofluorescence and TUNEL assay. In separate experiments, RPE cells were treated with lipid oxidation products, 7-ketocholesterol (7-KC, 5-40 μmol/l) or 4-hydroxynonenal (4-HNE, 5-80 μmol/l), with or without pretreatment with N-HDL or HOG-HDL. Results: ApoB, ApoA1 staining and RPE ER stress were increased in the presence of DR. HOG-LDL but not N-LDL significantly decreased RPE cell viability and increased reactive oxygen species generation, ER stress, apoptosis and autophagy. Similarly, 4-HNE and 7-KC decreased viability and induced ER stress. Pretreatment with N-HDL mitigated these effects, whereas HOG-HDL was less effective by most, but not all, measures. Conclusions/interpretation: In DR, extravascular modified LDL may promote RPE injury through oxidative stress, ER stress, autophagy and apoptosis. N-HDL has protective effects, but HOG-HDL is less effective. Extravasation and modification of HDL may modulate the injurious effects of extravasated modified LDL on the retinal pigment epithelium. © 2013 Springer-Verlag Berlin Heidelberg. Source


Liu C.M.,Harbin Medical University
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology | Year: 2010

To investigate the inhibitory effect of transforming growth factor (TGF)-β1 on oral squamous cell carcinoma (OSCC) Tb cell line. Cell counting method was used to examine the inhibitory effect of TGF-β1 on Tb cell and flow cytometry (FCM) assay performed to measure the changes of cell cycle. Superarray was used to screen the changing expression of genes in TGF-β1/Smads signaling pathway.RT-PCR method was used to detect the results of Superarray. TGF-β1 showed significant inhibiting effect on OSCC Tb cell line. TGF-β1 blocked the cell cycle at G1 phase. The expression level of activin receptor-like kinase-1 (ACVRL-1), anti-mullerian hirmine (AMH), cyclim-dependent kinase inhibitor-2B (CDKN-2B) and transforming growth factor-beta-indnced factor (TGIF) was higer in the cells treated with TGF-β1 than in control, while TDGF-1 expression was down-regulated. ACVRL-1 and CDKN-2B gene expression was consistent with the results of Superarray. TGF-β1 can inhibit the growth of OSCC Tb cell line. The mechanism may be related to the regulation of cell cycle and the expression of ACVRL-1 and CDKN-2B in TGF-β1-Smads signaling pathway. Source


Niu Y.,Harbin Medical University
Wei sheng yan jiu = Journal of hygiene research | Year: 2010

To establish a model of evaluating hypolipidemic effect in vitro. Adding cholesterol to the culture medium for HepG2 cells to induce a hypercholesterolemia model. The content of cellular cholesterol and the expression of protein regulating cholesterol metabolism in HepG2 cells were determined. The validation of the model was identified by lovastatin, a widely used cholesterol-lowering drug. Free fatty acid was added to the culture medium for HepG2 cells to induce a hypertriglyceridemia model. The content of cellular triglyceride and the absorption rate of free fatty acid were determined. The validation of the model was identified by fenofibrate, a triglyceride-lowering drug. Cellular cholesterol content was increased and the expression of HMG-CoA redutase, SREBP-2 and LDLR were decreased after adding cholesterol and 25-hydrocholesterol to the culture medium. Cellular cholesterol was decreased and the expression of SREBP-2 and LDLR were up-regulated by Lovastatin. The absorption of oleic acid in cells was up to 40% after adding oleic acid (50 micromol) to the culture medium for 6 h. The absorption of free fatty acid was increased but the content of cellular triglyceride was not increased in cells by Fenofibrate. This model might be an effective method for screening and assessing functional factors for lowing plasma lipids. Source


Kong R.,Harbin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2010

To investigate the effect and mechanism of NF-kappaB P65 gene silencing by small interference RNA on the apoptosis of human pancreatic cancer cells induced by gemcitabine in vitro and in vivo. Human pancreatic cancer cells (BxPC-3 and PANC-1) were cultured and respectively divided into five groups: blank control group, negative control siRNA group, gemcitabine group, NF-kappaB P65 siRNA group and gemcitabine + P65 siRNA group. The ability of cell proliferation was analyzed by MTT; the expression of NF-kappaB P65 and the apoptosis related proteins were examined by Western blot assay; the apoptosis was evaluated by the flow cytometry and laser scanning confocal microscopy analysis stained with Annexin V-FITC/PI; the DNA binding activity of NF-kappaB was examined by electrophoretic mobility shift assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors. The tumor volume was monitored and TUNEL assay was used to assess the apoptosis index in tumor tissue after treatment. At 72 h after transfection, the combination with gemcitabine and p65 siRNA significantly decreased the cell viability index (P < 0.05), and down-regulated the expression of Bcl-2 and procaspase-3 and up-regulated the expression of Bax compared with other groups. The combined treatment significantly increased the rate of apoptosis compared with other groups (P < 0.05). EMSA assay indicated that the DNA binding activity of NF-kappaB significantly decreased in NF-kappaB P65 siRNA group and gemcitabine+P65 siRNA group compared with Control group. The combined therapy inhibited the growth of pancreatic xenograft tumors by apoptosis induction in nude mice (P < 0.01). The effect of gemcitabine inducing cell apoptosis may be potentiated through inhibiting the DNA binding activity of NF-kappaB and regulating the expression of apoptosis related proteins by NF-kappaB P65 siRNA, which can activate the mitochondria apoptosis pathway in pancreatic cancer in vitro and in vivo. Source


Cao M.,Harbin Medical University
Journal of cancer research and clinical oncology | Year: 2014

To determine the interaction between insulin receptor substrate-1 (IRS-1) and miR-23a on the migration and invasion of non-small cell lung cancer (NSCLC) cells, and to examine IRS-1 expression in NSCLC tissues and its correlation with clinicopathologic characteristics. The migration and invasion of A549 cells were measured using transwell assay. miR-23a levels were examined by quantitative reverse transcription-PCR and IRS-1 expression by Western blotting. The interaction between miR-23a and IRS-1 was examined by luciferase reporter assay. IRS-1 expression in 105 NSCLC specimens was determined by immunohistochemistry and its correlation with patient clinicopathologic characteristics was evaluated. Transwell assay revealed that miR-23a significantly promoted the migration and invasion of A549 cells with a 44.0 and 44.6 % increase in the number of migrated and invading cells, respectively. Luciferase assay showed that miR-23a markedly reduced luciferase activities of A549 cells co-transfected with plasmids overexpressing the 3' UTR of IRS-1 mRNA (P < 0.05). Co-transfection of A549 cells with miR-23a and plasmids overexpressing IRS-1 significantly reduced the increase in the number of migrated and invading cells mediated by miR-23a. Immunohistochemistry showed low IRS-1 expression in 26.7 % and high IRS-1 expression in 73.3 % of the NSCLC specimens. Kaplan-Meier analysis revealed that the overall survival and disease-free survival of NSCLC were markedly longer in patients with high IRS-1 expression than those with low IRS-1 expression (P = 0.002). Multivariate Cox regression analysis showed that IRS-1 was an independent prognostic factor for the overall survival of NSCLC patients (RR 0.413 CI 0.238-0.718, P = 0.002). There is an interaction between miR-23a and IRS-1 in the modulation of the migration and invasion of NSCLC cells. IRS-1 is variably expressed in NSCLC patients and correlates with NSCLC patient survival. Source


Fu D.,The University of Oklahoma Health Sciences Center | Fu D.,Harbin Medical University | Wu M.,The University of Oklahoma Health Sciences Center | Zhang J.,The University of Oklahoma Health Sciences Center | And 6 more authors.
Diabetologia | Year: 2012

Aims/hypothesis In previous studies we have shown that extravasated, modified LDL is associated with pericyte loss, an early feature of diabetic retinopathy (DR). Here we sought to determine detailed mechanisms of this LDLinduced pericyte loss. Methods Human retinal capillary pericytes (HRCP) were exposed to 'highly-oxidised glycated' LDL (HOG-LDL) (a model of extravasated and modified LDL) and to 4-hydroxynonenal or 7-ketocholesterol (components of oxidised LDL), or to native LDL for 1 to 24 h with or without 1 h of pretreatment with inhibitors of the following: (1) the scavenger receptor (polyinosinic acid); (2) oxidative stress (N-acetyl cysteine); (3) endoplasmic reticulum (ER) stress (4-phenyl butyric acid); and (4) mitochondrial dysfunction (cyclosporin A). Oxidative stress, ER stress, mitochondrial dysfunction, apoptosis and autophagy were assessed using techniques including western blotting, immunofluorescence, RT-PCR, flow cytometry and TUNEL assay. To assess the relevance of the results in vivo, immunohistochemistry was used to detect the ER stress chaperon, 78 kDa glucose-regulated protein, and the ER sensor, activating transcription factor 6, in retinas from a mouse model of DR that mimics exposure of the retina to elevated glucose and elevated LDL levels, and in retinas from human participants with and without diabetes and DR. Results Compared with native LDL, HOG-LDL activated oxidative and ER stress in HRCP, resulting in mitochondrial dysfunction, apoptosis and autophagy. In a mouse model of diabetes and hyperlipidaemia (vs mouse models of either condition alone), retinal ER stress was enhanced. ER stress was also enhanced in diabetic human retina and correlated with the severity of DR. Conclusions/interpretation Cell culture, animal, and human data suggest that oxidative stress and ER stress are induced by modified LDL, and are implicated in pericyte loss in DR. © Springer-Verlag 2012. Source


Yin J.J.,Harbin Medical University
Autophagy | Year: 2012

In pancreatic β-cells, the endoplasmic reticulum (ER) is the crucial site for insulin biosynthesis, as this is where the protein-folding machinery for secretory proteins is localized. Perturbations to ER function of the β-cell, such as those caused by high levels of free fatty acid and insulin resistance, can lead to an imbalance in protein homeostasis and ER stress, which has been recognized as an important mechanism for type 2 diabetes. Macroautophagy (hereafter referred to as autophagy) is activated as a novel signaling pathway in response to ER stress. In this review, we outline the mechanism of ER stress-mediated β-cell death and focus on the role of autophagy in ameliorating ER stress. The development of drugs to take advantage of the potential protective effect of autophagy in ER stress, such as glucagon like peptide-1, will be a promising avenue of investigation. Source


Zhou C.,Tongji University | Wu Y.-L.,Guangdong Academy of Medical science | Chen G.,Harbin Medical University | Feng J.,Jiangsu Province Cancer Hospital | And 19 more authors.
The Lancet Oncology | Year: 2011

Background: Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC. Methods: We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according to EGFR mutation type, histological subtype (adenocarcinoma vs non-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in patients with confirmed disease who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT00874419, and has completed enrolment; patients are still in follow-up. Findings: 83 patients were randomly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint. Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 [95% CI 10.58-16.53] vs 4.6 [4.21-5.42] months; hazard ratio 0.16, 95% CI 0.10-0.26; p<0.0001). Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib (including neutropenia in 30 [42%] of 72 patients and thrombocytopenia in 29 [40%] patients on chemotherapy vs no patients with either event on erlotinib); the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (three [4%] of 83 patients) and skin rash (two [2%] patients). Chemotherapy was also associated with increased treatment-related serious adverse events (ten [14%] of 72 patients [decreased platelet count, n=8; decreased neutrophil count, n=1; hepatic dysfunction, n=1] vs two [2%] of 83 patients [both hepatic dysfunction]). Interpretation: Compared with standard chemotherapy, erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability. These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC. Funding: F Hoffmann-La Roche Ltd (China); Science and Technology Commission of Shanghai Municipality. © 2011 Elsevier Ltd. Source


Yang W.,China Japan Friendship Hospital | Lu J.,Chinese Peoples Liberation Army | Weng J.,Sun Yat Sen University | Jia W.,Shanghai JiaoTong University | And 16 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults. METHODS: A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report. RESULTS: The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and ≥60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of <18.5, 18.5 to 24.9, 25.0 to 29.9, and ≥30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women). CONCLUSIONS: These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed. Copyright © 2010 Massachusetts Medical Society. All rights reserved. Source


Li L.,Harbin Medical University
Journal of Craniofacial Surgery | Year: 2016

ABSTRACT: Penetrating head and neck trauma could cause significant mortality because of many important structures located in the brain and neck. Although high-velocity penetrating brain injury is often reported, reports of low-velocity, combined head and neck penetrating injury are rare. Hereby, the authors present a case of an old man who had encountered a serious accident, a 29-cm iron fork penetrated into his neck, through the skull base and into brain. After treatment by multidisciplinary team, the patient was in rehabilitation. The multidisciplinary team assists rapid diagnosis and treatment of penetrating neck and head injury is the key to ensure a good outcome. Therefore, as the authors face such patients again, a multidisciplinary team is needed.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0 © 2016 by Mutaz B. Habal, MD. Source


The role of type III transforming growth factor-β receptor (TβRIII) in the pathogenesis of heart diseases remains largely unclear. Here, we investigated the functional role and molecular mechanisms of TβRIII in the development of myocardial hypertrophy. Western blot and quantitative real time-polymerase chain reaction analyses revealed that the expression of TβRIII was significantly elevated in human cardiac hypertrophic samples. Consistently, TβRIII expression was substantially increased in transverse aortic constriction (TAC)– and isoproterenol-induced mouse cardiac hypertrophy in vivo and in isoproterenol-induced cardiomyocyte hypertrophy in vitro. Overexpression of TβRIII resulted in cardiomyocyte hypertrophy, whereas isoproterenol-induced cardiomyocyte hypertrophy was greatly attenuated by knockdown of TβRIII in vitro. Cardiac-specific transgenic expression of TβRIII independently led to cardiac hypertrophy in mice, which was further aggravated by isoproterenol and TAC treatment. Cardiac contractile function of the mice was not altered in TβRIII transgenic mice; however, TAC led to significantly decreased cardiac contractile function in TβRIII transgenic mice compared with control mice. Conversely, isoproterenol- and TAC-induced cardiac hypertrophy and TAC-induced cardiac contractile function impairment were partially reversed by suppression of TβRIII in vivo. Our data suggest that TβRIII mediates stress-induced cardiac hypertrophy through activation of Ca/calmodulin-dependent protein kinase II, which requires a physical interaction of β-arrestin2 with both TβRIII and calmodulin-dependent protein kinase II. Our findings indicate that stress-induced increase in TβRIII expression results in cardiac hypertrophy through β-arrestin2–dependent activation of calmodulin-dependent protein kinase II and that transforming growth factor-β and β-adrenergic receptor signaling are not involved in spontaneous cardiac hypertrophy in cardiac-specific transgenic expression of TβRIII mice. Our findings may provide a novel target for control of myocardial hypertrophy. © 2016 American Heart Association, Inc Source


Jiang Z.,Fudan University | Li C.,Harbin Medical University | Xu Y.,Fudan University | Cai S.,Fudan University
International Journal of Colorectal Disease | Year: 2010

Purpose: Studies on polymorphism of X-ray repair cross-complementing group 1 (XRCC1), group 3 (XRCC3), and colorectal cancer risk are inconclusive. The purpose of this study is to evaluate the role of XRCC1 R399Q, R194W, and XRCC3 T241M genotypes in colorectal cancer susceptibility. Methods: We performed a meta-analysis on all available studies that provided 3,514/4,686 cases/controls for R399Q, 2,767/3,907 cases/controls for R194W and 3,183/3,926 cases/controls for T241M. Results: Overall, no apparent effects of 194 W allele compared to 194R on colorectal cancer risk were found in all subjects and subgroups (Asians and Caucasians). Insignificant effects were also found under other genetic contrasts (homologous contrast, dominant model, and recessive model). The same pattern of results was produced in T241M polymorphism. The 399Q allele compared to 399R showed no significant association with colorectal cancer risk in all subjects and subgroups. However, protective effects of 399QQ genotype were observed under recessive model (QQ/QR + RR) [P=0.02, OR=0.84, 95% CI (0.72, 0.97)] and homozygote contrast (QQ/RR) [P=0.01, OR=0.81; 95% CI (0.69, 0.95)] in all subjects. Conclusion: Results suggested that 399Q allele might act as a recessive allele in its association with colorectal cancer. © 2009 Springer-Verlag. Source


To evaluate the outcome of ST-elevation acute myocardial infarction (STEMI) patients complicated pre-hospital cardiac arrest underwent percutaneous coronary intervention (PCI). From September 2004 to November 2008, 1446 consecutive patients with acute STEMI underwent PCI in our department. 49 out of 1446 patients complicated by pre-hospital cardiac arrest. Clinical outcome including total mortality, adverse cardiac events, stroke and bleeding events during the hospitalization period and within 1 year after discharge was compared between patients with or without pre-hospital cardiac arrest. PCI success rate was similar (85.7% vs. 88.8%, P = 0.497) while the incidence of in-hospital cardiogenic shock 22.4% vs. 3.0%, P < 0.001 and cardiac arrest (44.9% vs. 5.9%, P < 0.001) and in-hospital mortality (36.7% vs. 2.0%, P < 0.001) were significantly higher in patients with pre-hospital cardiac arrest than patients without pre-hospital cardiac arrest. Time from symptom onset to emergency treatment, asystole as initial rhythm, Glasgow coma scale (GCS ≤ 7) and cardiogenic shock on admission were independent risk factors of in-hospital death in patients with pre-hospital cardiac arrest. During follow up, incidences of overall mortality, re-infarction, revascularization and stroke were similar between the two groups. STEMI patients with pre-hospital cardiac arrest undergoing emergency PCI are facing higher risk of cardiogenic shock and cardiac arrest and higher in-hospital mortality compared to those without pre-hospital cardiac arrest. However, the post-hospital discharge outcome was similar between the two groups. Source


Oxidative stress has been linked to endothelial dysfunction in atherosclerosis and hypertension. The present study was designed to investigate the effect of hydrogen peroxide (H2O2) on angiotensin-converting enzyme (ACE), a key regulator of the renin-angiotensin system, and the mechanisms underlying ACE regulation in human umbilical vein endothelial cells (HUVECs). We used Tetrazolium bromide (MTT) assay for cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for cell apoptosis, enzyme-linked immunosorbent assay (ELISA) for cAMP measurement, real-time PCR for mRNA detection, and Western blot for protein analysis in the study. Our results demonstrated that H2O2 (50-1000 μM) decreased HUVECs viability by inducing apoptosis. Notably, H2O2 upregulated ACE expression in a concentration-dependent manner. H2O2 100 μM significantly enhanced cyclic adenosine monophosphate (cAMP) expression by 1.48-fold (P<0.05). Additionally, forskolin 10 μM, a cAMP agonist, was also found to enhance ACE expression by 1.78-fold (P<0.05); in contrast, H-89 10 μM, a protein kinase A (PKA) inhibitor, abolished H2O2-induced ACE expression and prevented the enhancing effect of forskolin-induced ACE expression. Similar effects on ACE mRNA were also observed. cAMP-response element-specific decoy oligodeoxynucleotides (CRE-dODN) containing binding sites for cAMP-response element-binding protein (CREB) inhibited ACE expression at both the mRNA and protein levels. Negative control CRE-dODN had no effect on ACE expression. We conclude that H2O2 upregulates the expression of ACE through the activation of cAMP/PKA/CREB signal pathway in HUVECs, indicating a role of oxidative stress in the pathophysiology of hypertension. Source


Objective: To investigate the correlations of the levels of plasma soluble receptor for advanced glycation end product (sRAGE) with the National Institutes of Health Stroke Scale (NIHSS), grade of white matter lesions, and risk factors for cerebral vascular disease in patients with acute cerebral infarction. Methods: A total of 120 patients with acute cerebral infarction were enrolled retrospectively. They all underwent head MRI. The plasma sRAGE levels of the acute cerebral infarction group and 120 healthy subjects were detected with enzyme-linked immunosorbent assay (ELISA) and were compared. According to the interquartile range (P25 = 540 ng/L, P50 = 1030 ng/L, P75 = 1400 ng/L), the plasma sRAGE levels were divided into 4 quartiles (Ql to Q4). Ql. sRAGE < 540 ng/L (n = 29), Q2 :540 ng/L ≤ sRAGE ≤ 1030 ng/L (n = 31), Q3; 1030 ng/L < sRAGE ≤ 1400 ng/L (n = 30), and Q4: sRAGE > 1400 ng/L (n = 30). The plasma sRAGE levels in the acute cerebral infarction group and the healthy control group were compared using the Wilcoxon rank sum test. Multiple linear regression analysis was used to analyze the correlations of the sRAGE levels with NIHSS scores, grade of cerebral white matter lesions, and cerebrovascular risk factors. Results: (1) The median level of plasma sRAGE was 870 (540.0,1403.8) ng/L in the acute cerebral infarction group,which was lower than 1032 (727.5,1721.5) ng/L in the healthy control group. There was significant difference (P <0.05). (2) Single factor analysis showed that the smoking rate, NIHSS scores, the types of deep white matter hyperintensity (DWMH), and the estimated glomerular filtration rate(eGFR) among Ql,Q2,Q3 and Q4 quartiles were significant different (all P < 0.05). The smoking rate, ratio of patients with high NIHSS score, incidence of severe DWMH and percentage of the patients with normal eGFR in Ql (n =29) were 62.1% (n = 18), 44.8% (n = 13),55.2% (n = 16) and 51.7% (n = 15),respectively,and they had a higher trend than other quartiles. (3) Multiple linear regression analysis showed that the smoking, NIHSS score, eGFR,and severity of DWMH were the influence factors of the levels of plasma sRAGE in patients with acute cerebral infarction.There were significant differences (all P <0.05). Conclusion: The expression levels of the plasma sRAGE in patients with acute cerebral infarction group is significantly lower than those in the healthy subjects, and smoking, neurological defect, eGFR, and severity of DWMH are associated the low level of sRAGE. sRAGE may be used as a reference index for predicting the conditions of acute cerebral infarction. Copyright 2014 by the Chinese Medical Doctor Association. Source


Li Q.,Harbin Medical University
Zhonghua yi xue za zhi | Year: 2010

To study the correlation of real-time continuous monitoring system (RT-CGMS) with venous glucose and capillary glucose values. A total of 33 diabetics received RT-CGMS for 5 days. Fasting venous glucose values were measured at Days 1, 3 and 5 and capillary glucose values recorded 7 times daily. The methods of correlation coefficient, error grid analysis (EGA) and Bland-Altman analysis were employed to assessed the correlation, accuracy and agreement of RT-CGMS with venous glucose and capillary glucose values respectively. The mean amplitude of glucose excursions (MAGE) was calculated during RT-CGMS testing periods. (1) The correlation coefficient of RT-CGMS with vein glucose and capillary glucose values were 0.936, 0.933 (P < 0.01); (2) The analysis results of EGA showed that 98.67%, 98.64% of venous and capillary values fell in the A and B zones and 1.33%, 1.36% fell in the D zone; (3) The agreement analysis showed that RT-CGMS readings were in close agreement with venous glucose and capillary glucose results; (4) The patients at the same MAGE levels had obvious differences in HbA1C. There is a high level of correlation, accuracy and agreement between RT-CGMS and venous glucose and capillary glucose values. Source


Yi R.,Harbin Medical University
African journal of traditional, complementary, and alternative medicines : AJTCAM / African Networks on Ethnomedicines | Year: 2013

The objective of the study was to optimise the LBP extraction technology and to study the anti-aging effect of LBP by establishing D-gal aging mouse model. Orthogonal design was used to study the extraction technology. The experimental aging mouse model was formed by continuous injection of D-gal, and the anti-aging capacity of LBP was tested using measuring MDA, CAT and GSH-px contents and SOD activity in blood and SOD, MDA and Hyp levels in skin. The results showed that the optimum LBP extraction option determined by the orthogonal design is as follows: solid-liquid ratio of 1:30, extraction for 2 times, 90 min each time, and power is 100 kHz. Thus, LBP can increase SOD, CAT and GSH-px levels in blood and reduce MDA level. It can also improve skin SOD activity, reduce skin MDA content, and increase Hyp content. We concluded that the extraction method established in this experiment is easy and feasible, and the yield of LBP is high, apparently showing that LBP has the potential of delaying senility in D-gal induced mice. Source


He P.,Teikyo University | He P.,Harbin Medical University | Takeuchi T.,Teikyo University | Yano E.,Teikyo University
Environmental Health and Preventive Medicine | Year: 2013

Objectives: China is facing a serious public health problem in active and passive smokers. Confronted with this, China has taken some measures to control tobacco. However, this information has not been surveyed at academic level. Our aim is to investigate information relating to tobacco controls in China. Methods: To find information relating to tobacco control, we reviewed and analysed the China National Tobacco Corporation (CNTC) and State Tobacco Monopoly Administration (STMA) mainly by systematic examination of documents made available in the University of California, San Francisco Legacy Tobacco Documents Library and China Tobacco database. Results: Eleven relevant documents met our research purpose, and 18 further relevant documents were found on the CNTC, STMA and Tobacco China database websites. As a result, 29 relevant articles were included in our analysis. We describe the CNTC and STMA's history, structure, and relation to the Chinese Government ministry and to other tobacco companies, and China's tobacco control in detail. Conclusions: The Chinese cigarette market is dominated by a state-owned monopoly, the STMA. Under the protection of the Law of the People's Republic of China on Tobacco Monopoly, the STMA controls all aspects of the tobacco industry. As far as the Chinese tobacco monopoly is concerned, although smoking harms people's health, restraining smoking threatens social stability and government income, which may be more serious problems for any government. China still has a long way to go in creating smoke-free environments. © 2012 The Japanese Society for Hygiene. Source


Feng Y.,Harbin Medical University | Chen H.-L.,Chang Gung University | Chiu C.-H.,Chang Gung University
Genome Biology and Evolution | Year: 2013

Mutation and selection are both thought to impact significantly the nucleotide composition of bacterial genomes. Earlier studies have compared closely related strains to obtain mutation patterns based on the hypothesis that these bacterial strains had diverged so recently that selection will not have had enough time to play its role. In this study, we used a SOLiD autosequencer that was based on a dual-base encoding scheme to sequence the genome of Staphylococcus aureus with a mapping coverage of over 5,000x. Bydirectly counting the variation obtained from these ultradeep sequencing reads, we found that A→G was the predominant single-base substitution and 1 bp deletions were the major small indel. These patterns are completely different from those obtained by comparison of closely related S. aureus strains, where C→T accounted for a larger proportion of mutations and deletions were shown to occur at an almost equal frequency to insertion. These findings suggest that the genomic differences between closely related bacterial strains have already undergone selection and are therefore not representative of spontaneous mutation. © 2013 The Author(s). Source


Han C.,Harbin Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2011

To review the research progress of nucleus pulposus cells phenotypic markers. The domestic and international literature about nucleus pulposus cells phenotypic markers was reviewed extensively and summarized. Due to different biomechanical properties, nucleus pulposus cells and articular chondrocytes have differences in morphology and extracellular components such as the ratio of aggrecan to collagen type II alpha1. Nucleus pulposus cells can be identified by surface marker (CD24), gene markers (hypoxia inducible factor 1alpha, glucose-transporter protein 1, matrix metalloproteinase 2, vascular endothelial growth factor A, etc), and various markers (keratin 19 and glypican 3, paired box 1, forkhead box F1 and integrin-binding sialoprotein, etc). Nucleus pulposus cells and articular chondrocytes have different phenotypic markers, but nucleus pulposus cells are still lack of specific markers. Source


Li M.,Harbin Medical University
Chinese Journal of Contemporary Neurology and Neurosurgery | Year: 2016

Malignant glioma is the most common malignant tumor of central nervous system (CNS). Surgery is the main treatment method, supplemented by radiation and chemotherapy. But the problems of too much trauma, easy recurrence and poor prognosis cannot be avoided. Because of strong anti-tumor specificity, mild adverse reaction and long -term memory etc, immune therapy may be the best auxiliary treatment, and even can replace the surgical treatment. This article focused on the role of engineering cells, including lymphokine-activated killer cell (LAK), natural killer cell (NK), γδ T cell, tumor infiltrating lymphocyte cell (TIL), cytotoxic T lymphocyte cell (CTL) and CD4+ T cell, in the process of treating malignant glioma by adoptive cell therapy (ACT) and reviewed the characteristics, advantage and disadvantages, research trends and progress of these cells. Copyright © 2016 by the Editorial Board of Chinese Journal of Contemporary Neurology and Neurosurgery. Source


Guo S.,Shanghai JiaoTong University | Li X.,Shanghai JiaoTong University | Gao M.,Harbin Medical University | Li Y.,Shanghai JiaoTong University | And 2 more authors.
PLoS ONE | Year: 2013

Background: The prevalence of lung cancer in China will be the world's highest if allowed to proceed uncurbed. To unravel its genetic underpinnings, we sought to investigate the association of three well-characterized nonsynonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) and XRCC3 (Thr241Met) genes with lung cancer risk in northeastern Chinese. Methodology/Principal Findings: This study was hospital-based in design, encompassing 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR (ligase detection reactions) method. Data were analyzed by R language and multifactor dimensionality reduction (MDR) software. Single-locus analysis identified significance in genotype distributions of polymorphism Arg194Trp (P = 0.002) and Arg399Gln (P = 0.017), and in allele distributions of Thr241Met (P = 0.005). Carriers of 399Gln/Gln genotype conferred a 147% increased risk relative to the non-carriers (odds ratio (OR): 2.47; 95% confidence interval (95% CI): 1.48-4.13; P<0.001). For Thr241Met, significance persisted under allelic (OR = 1.63; 95% CI: 1.14-2.33; P = 0.005), additive (OR = 1.64; 95% CI: 1.16-2.32; P = 0.005) and dominant (OR = 1.67; 95% CI: 1.17-2.38; P = 0.004) models. However, common allele combinations were comparable in frequency between patients and controls. In interaction analysis, the overall best MDR model included Arg399Gln and Thr241Met polymorphisms, with a maximal testing accuracy of 63.18% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0175). Conclusions: Our study significantly demonstrated an independent and synergistic contribution of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms to lung cancer susceptibility in northeastern Chinese. © 2013 Guo et al. Source


Li S.,Harbin Medical University
Wei sheng yan jiu = Journal of hygiene research | Year: 2010

To establish a fast and effective model in vitro for screening weight-reducing drugs and taking preliminary evaluation of the model. Mature adipocytes of SD rat induced by oleic acid were used to establish a obesity model in vitro. Isoprel, genistein, caffeine were selected as positive agents and curcumine as negative agent to evaluate the obesity model. Lipolysis of adipocytes was stimulated significantly by isoprel, genistein and caffeine rather than curcumine. This model could be used efficiently for screening weight-losing drugs. Source


Wang C.,Harbin Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2012

To study the effect of anti-tumor peptide of tumstatin on tumor growth of human laryngeal squamous carcinoma in nude mice and the underlying mechanism. Nude mice model bearing laryngocarcinoma were established by using human laryngeal squamous carcinoma cell line (Hep-II). The animals were given tumstatin or PBS for 10 consecutive days. The volumes of the subcutaneous tumor were observed. The microstructure in which the general 2-step immunohistochemical examination was adopted and ultra-micro-structural changes of carcinoma after administration of tumstatin were observed under light and electron microscopes for pathology examination. The differences was statistically significant in the net mice weight, tumor weight, tumor volume and tumor weight/net mice weight between the treatment group and the control group (P<0.01). The restrained percentage of tumor was 51.58%. The necrosis and apoptosis of the tumor cells and the angiogenesis reduction were found under light and electron microscope in the treatment group. MVD of the treatment group was lower than that of the control group (P<0.01). Tumstatin can significantly restrain the development of laryngocarcinoma. Source


Wang Z.,University of Illinois at Chicago | Wang Z.,Harbin Medical University | Yao T.,University of Illinois at Chicago | Song Z.,University of Illinois at Chicago
Alcoholism: Clinical and Experimental Research | Year: 2010

Background: Chronic alcohol consumption causes alcoholic liver disease, which is associated, or initiated, with dysregulated lipid metabolism. Very recent evidence suggested that dysregulated cholesterol metabolism plays an important role in the pathogenesis of alcoholic fatty liver diseases, however, the effects of chronic alcohol exposure on cholesterol homeostasis have not been well studied and underlying mechanisms behind are still elusive. Methods: Male Sprague-Dawley rats weighing 250 ± 5.5 g (mean ± SEM) divided into 2 groups (8 rats per group) and pair-fed with liquid diets containing (in percent of energy intake) 18% protein, 35% fat, 12% carbohydrate, and 35% either ethanol (ethanol diet) or an isocaloric maltose-dextrin mixture (control diet), according to Lieber and De Carli, for 4 weeks. Results: Long-term excessive alcohol feeding to rats caused fatty liver and liver injury, which was associated with disrupted cholesterol homeostasis, characterized by increased hepatic cholesterol levels and hypercholesterolemia. Hepatic cholesterol increases were concomitant with constantly activated sterol regulatory element-binding protein-2 (SREBP-2) in the liver and increased expression of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, a rate-limiting enzyme for cholesterol de novo synthesis, indicating enhanced cholesterol biosynthesis. Alcohol-induced hypercholesterolemia was accompanied by decreased LDL receptor (LDLr) levels in the liver. Further investigations revealed that chronic alcohol exposure increased hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) contents to down-regulate LDLr via a post-translational mechanism. Moreover, alcohol feeding suppressed extracellular signal-regulated kinase (ERK) activation in the liver. In vitro studies showed that inhibition of ERK activation was associated with decreased LDLr expression in HepG2 cells. Conclusions: Our study provides the first evidence that both increased PCSK9 expression and suppressed ERK activation in the liver contributes to alcohol-induced hypercholesterolemia in rats. © 2009 by the Research Society on Alcoholism. Source


Zhu D.,Harbin Medical University | Zhu D.,Biopharmaceutical Key Laboratory of Heilongjiang Province | Ran Y.,Biopharmaceutical Key Laboratory of Heilongjiang Province
Journal of Physiological Sciences | Year: 2012

Pulmonary arterial hypertension (PAH) is a rare disease with a complex aetiology characterized by elevated pulmonary artery resistance, which leads to right heart ventricular afterload and ultimately progressing to right ventricular failure and often death. In addition to other factors, metabolites of arachidonic acid cascade play an important role in the pulmonary vasculature, and disruption of signaling pathways of arachidonic acid plays a central role in the pathogenesis of PAH. 15-Lipoxygenase (15-LO) is upregulated in pulmonary artery endothelial cells and smooth muscle cells of PAH patients, and its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE) in particular seems to play a central role in the contractile machinery, and in the initiation and propagation of cell proliferation via its effects on signal pathways, mitogens, and cell cycle components. Here, we focus on our important research into the role played by 15-LO/15-HETE, which promotes a proliferative, antiapoptotic, and vasoconstrictive physiological milieu leading to hypoxic pulmonary hypertension. © 2012 The Physiological Society of Japan and Springer. Source


Wang Z.,Harbin Institute of Technology | Wu L.,Harbin Medical University | Cai W.,Harbin Institute of Technology | Jiang Z.,Harbin Institute of Technology
Journal of Materials Chemistry | Year: 2012

The poor thermal stability of nanoparticle superlattices heavily inhibits their practical applications. In present research, using stable thiolate-capped Au 11(SCH 2CH 2COO -) 7([CH 3(CH 2) 7] 4N +) 7 nanoclusters as the building blocks, novel luminescent Au 11 nanocluster superlattices with high thermal stability have been fabricated by self-assembly. The nanocluster superlattices have a blade-like morphology and extend on a micrometre length scale with the largest over 50 μm. Under an excitation at 400 nm, the fabricated Au 11 nanocluster superlattices emit a blue luminescence with the emission peak of 473 nm. The native stability of thiolate-capped gold nanoclusters and the steric repulsion induced by the high-density ligands (SCH 2CH 2COO -) 7([CH 3(CH 2) 7] 4N +) 7 endows the fabricated superlattices with high thermal stability. The differential scanning calorimetry and thermogravimetric analysis indicates that the superlattices undergo irreversible endothermic transitions in the range of room temperature to 200 °C, which starts at 124 °C and reaches a peak at 160 °C. When processed with heat treatment below the transition temperature or stored for six months at room temperature, there is no obvious difference detected in the emission intensity of the fabricated Au 11 nanocluster superlattices. Such thermostability gives the fabricated nanocluster superlattices great potential for many applications, especially for optical devices. © 2012 The Royal Society of Chemistry. Source


Liu D.,Harbin Medical University
Cellular and molecular biology (Noisy-le-Grand, France) | Year: 2012

Free fatty acids (FFA) are closely related to insulin resistance in which proteins such as insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3 kinase (PI3K) and glucose transporter type 4 (GLUT4) are involved. Recent researches have shown that G-protein coupled receptor 120 (GPR120) is a receptor for medium and long chain FFA. This study aimed to evaluate the relationship between GPR120 and proteins related to the glucose metabolism. We used siRNA technique to down-regulate the GPR120 expression in 3T3-L1 cells before incubation with palmitic acid (PA), and evaluated the effect of GPR120 expression on the levels of IRS-1, PI3K and GLUT4 after PA induction. RT-PCR and western blot were performed to detect gene and protein levels in differentiated cells. RT-PCR result showed that GPR120 mRNA significantly increased in differentiated cells. GPR120-SiRNA transfection significantly down-regulated GPR120 gene and protein level in differentiated 3T3-L1 cells on day 5 after PA-induced and also decreased lipid droplets accumulated within the cells. SiRNA-mediated decreased of GRP120 was associated with significant reductions in gene and protein levels of IRS-1 and GLUT4. Our results showed that the expression level of GPR120 affected the expression of proteins related to the glucose metabolism, suggesting a contribution of GPR120 in the insulin resistance. Source


Cui J.,Harbin Medical University
The Journal of international medical research | Year: 2012

Expression of the Cacna1c (calcium channel, voltage-dependent, L-type, α1C subunit) gene was studied to investigate the relationship between oxidative stress and L-type calcium channels in the myocardium of selenium-deficient mice. Selenium levels in liver and heart tissue samples from mice fed normal or selenium-deficient diets were evaluated by fluorometry. In the same mice, glutathione peroxidase (GPx) and Cacna1c gene expression were analysed, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured, oxidoreductase gene expression profiles were analysed (by DNA microarray), and myocardial structural changes were studied. In selenium-deficient versus control mice, GPx expression and SOD activity were decreased, and Cacna1c expression and MDA concentration were increased. Selenoprotein oxidoreductase and nonselenoprotein oxidoreductase gene expression differed significantly between selenium-deficient and control mice. In selenium-deficient mice, myocardial fibres were separated by loose collagenous tissue; electron microscopy showed shortened sarcomeres, dilated sarcoplasmic reticulum, scattered myofibril lysis and increased mitochondria with amorphous matrix densities. L-type calcium channels were involved in selenium deficiency-induced cardiomyocyte injury, which was positively related to oxidative stress. Source


Suo C.,Daqing General Hospital Group Oilfield General Hospital | Sun L.,Jilin University | Yang S.,Harbin Medical University
Experimental and Therapeutic Medicine | Year: 2013

Alpinetin is a natural flavonoid that protects cells against fatal injury in ischemia-reperfusion. δ receptor activation protects myocardial cells from trauma; however, the mechanism is unknown. The aim of this study was to explore the function of alpinetin in δ receptor-mediated myocardial apoptosis. The myocardial cells of newly born rats were cultivated and myocardial apoptosis was induced by serum deprivation. The MTT method was used to evaluate cell viability and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining was used to analyze apoptosis. The expression levels of opioid receptor mRNA and protein were tested using reverse transcription-polymerase reaction (RT-PCR) and western blot assays. In addition, an opioid receptor antagonist, as well as protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) inhibitors, were used to determine the inferred signaling pathway. The results showed that that alpinetin reduced the myocardial apoptosis induced by serum deprivation in a concentration-dependent manner. However, the protection conferred to the myocardial cells by alpinetin was blocked by the δ opioid receptor antagonist naltrindole, as well as by PKC and ERK inhibitors (GF109203X and U0126, respectively). In addition, it was shown that alpinetin was able to maintain the stability of the mitochondrial membrane potential, lower the level of intracytoplasmic cytochrome c and reduce Bax displacement from the cytoplasm to the mitochondria. It was concluded that alpinetin was able to activate δ receptors to induce the endogenous protection of myocardial cells via the PKC/ERK signaling pathway. Source


Han S.,Harbin Medical University
Chinese Journal of Endemiology | Year: 2013

Objective: To investigate the prevalence of clonorchiasis among residents of Huachuan Country, Heilongjiang Province and to provide a basis for development of control strategies. Methods: From 2011 to 2012, cluster random sampling was performed to survey the incidence of clonorchiasis in Huachuan Country. Fecal specimens were collected and examined the clonorchis sinensis eggs by Kato-Katz method. A questionnaire survey was conducted to collect related information such as age, gender, occupation and eating habits. The infection characteristic was analyzed. Results: Totally 884 patients with clonorchiasis were found among 2248 residents, and the infection rate was 39.32%. The infection rate in male [47.15%(611/1296)] was significantly higher than females [28.68%(273/952), χ2 = 34.55, P < 0.01]. The infection rate increased with age, which was higher in the 20-69 years old people, with the highest infection rate in the 50-59 years old groups [45.34% (219/483)]. Of the occupational distribution, farmers had the highest infection rate [47.24%(420/889)], followed by cadres and staffs [38.38%(190/495)]. Of residents with fresh fish eating history, the prevalence of clonorchiasis was 53.38% (150/281). Conclusions: The prevalence of clonorchiasis is still high in Huachuan County. To reduce the prevalence of clonorchiasis, comprehensive prevention measures, health education and group chemotherapy should be carried out. Source


Huang J.,Stanford University | Huang J.,CAS Beijing National Laboratory for Molecular | Bu L.,Stanford University | Bu L.,Harbin Medical University | And 6 more authors.
ACS Nano | Year: 2010

The effect of nanoparticle size (30-120 nm) on magnetic resonance imaging (MRI) of hepatic lesions in vivo has been systematically examined using polyvinylpyrrolidone (PVP)-coated iron oxide nanoparticles (PVP-IOs). Such biocompatible PVP-IOs with different sizes were synthesized by a simple one-pot pyrolysis method. These PVP-IOs exhibited good crystallinity and high T 2 relaxivities, and the relaxivity increased with the size of the magnetic nanoparticles. It was found that cellular uptake changed with both size and surface physiochemical properties, and that PVP-IO-37 with a core size of 37 nm and hydrodynamic particle size of 100 nm exhibited higher cellular uptake rate and greater distribution than other PVP-IOs and Feridex. We systematically investigated the effect of nanoparticle size on MRI of normal liver and hepatic lesions in vivo. The physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their ability to accumulate in the liver. The contrast enhancement of PVP-IOs within the liver was highly dependent on the overall size of the nanoparticles, and the 100 nm PVP-IO-37 nanoparticles exhibited the greatest enhancement. These results will have implications in designing engineered nanoparticles that are optimized as MR contrast agents or for use in therapeutics. © 2010 American Chemical Society. Source


Wang R.,University of British Columbia | Wang R.,Harbin Medical University | Zhang M.,University of British Columbia | Zhou W.,University of British Columbia | And 3 more authors.
Journal of Neurochemistry | Year: 2011

Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that plays a regulatory role in targeting proteins for proteasomal degradation. UCH-L1 is highly expressed in neurons and has been demonstrated to promote cell viability and maintain neuronal integrity. Reduced UCH-L1 levels have been observed in various neurodegenerative diseases, and expression of UCH-L1 can rescue synaptic dysfunction and memory deficits in Alzheimer's Disease model mice. However, the mechanisms regulating UCH-L1 expression have not been determined. In this study, we cloned a 1782 bp of the 5′ flanking region of the human UCH-L1 gene and identified a 43 bp fragment containing the transcription start site as the minimal region necessary for promoter activity. Sequence analysis revealed several putative regulatory elements including NF-κB, NFAT, CREB, NRSF, YY1, AP1, and STAT in the UCH-L1 promoter. A functional NF-κB response element was identified in the UCH-L1 promoter region. Expression of NF-κB suppressed UCH-L1 gene transcription. In the RelA knockout system where NF-κB activity is ablated, UCH-L1 expression was significantly increased. Furthermore, activation of NF-κB signaling by the inflammatory stimulator lipopolysaccharide and TNFα resulted in a decrease of UCH-L1 gene expression by inhibiting its transcription. As NF-κB is an important signaling module in inflammatory response, our study suggests a possibility that inflammation might compromise neuronal functions via the interaction of NF-κB and UCH-L1. A better understanding of the NF-κB-regulated UCH-L1 transcription will provide insights to the role of inflammatory responses in Alzheimer's disease and Parkinson's disease. © 2011 International Society for Neurochemistry. Source


Lin C.,Jilin University | Yu Y.,Xian Jiaotong University | Zhao H.-G.,Jilin University | Yang A.,Xian Jiaotong University | And 2 more authors.
Radiotherapy and Oncology | Year: 2012

Purpose: Quercetin (3, 3,′ 4′, 5, 7 - five-flavonoids) is one of the main components of flavonoids, with multifunctions on immune function, anti-oxidation, anti-viral, anti-inflammatory, and cardiovascular protection. We hypothesize that a combination of quercetin with radiation would increase tumor radiosensitivity. To test this hypothesis, we conducted in vitro and in vivo studies. Methods and materials: The in vitro radio-sensitization activity of quercetin was tested in DLD1, HeLa and MCF-7 tumor cell lines by colony formation assays. The in vivo activity was assessed in the DLD-1 human colorectal cancer xenograft model in nude mice. Mechanistic studies were conducted in several cell lines using Western blot analysis and immunofluorescence microscopy. Results: We found that quercetin can significantly increase tumor radiosensitivity both in vitro and in vivo. The in vitro Sensitizing Enhancement Ratios in DLD1, HeLa and MCF-7 cells were 1.87, 1.65, and 1.74, respectively. The mean doubling time of tumor xenografts was significantly increased in irradiated mice treated with quercetin. At the cellular level, exposure to quercetin resulted in prolonged DNA repair. The mechanistic studies demonstrated that quercetin induced radio-sensitization is through inhibiting the ATM kinase, one of the critical DNA damage response proteins. Conclusion: We demonstrate both in vitro and in vivo evidence that combination of quercetin with radiotherapy can enhance tumor radiosensitivity by targeting the ATM-mediated pathway in response to radiation. © 2012 Elsevier Ireland Ltd. All rights reserved. Source


Zhang C.,University of California at San Diego | Zhang C.,Harbin Medical University | Tatham A.J.,University of California at San Diego | Tatham A.J.,University of Edinburgh | And 5 more authors.
Ophthalmology | Year: 2014

Purpose: To investigate the relationship between macular ganglion cell-inner plexiform layer (mGCIPL) thickness and estimated macular retinal ganglion cell (RGC) counts in glaucoma. Design: Observational cohort study. Participants: Cross-sectional study of 77 healthy, 154 glaucoma suspect, and 159 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study. Methods: All eyes underwent 24-2 standard automated perimetry (SAP) and optic nerve and macular imaging using high-definition optical coherence tomography (OCT). The total number of RGCs was estimated using a previously described model that uses SAP and OCT circumpapillary retinal nerve fiber layer (cpRNFL) measurements. The number of macular RGCs was estimated from the temporal cpRNFL and SAP test points within the central 10°. Main Outcome Measures: The correlation between mGCIPL thickness and estimates of macular RGC counts. Results: The average estimated macular RGC count in glaucomatous eyes was 306 010±109 449 cells, which was significantly lower than the estimate of 520 678±106 843 cells in healthy eyes (P < 0.001). Glaucomatous eyes had 41% fewer estimated macular RGCs than healthy eyes and suspects had 21% fewer estimated macular RGCs. There was strong correlation between estimated macular RGC counts and mGCIPL thickness (R2 = 0.67; P < 0.001). Macular RGC counts performed better than average mGCIPL thickness in discriminating healthy and glaucomatous eyes with receiver operating characteristic curve areas of 0.873 and 0.775, respectively (P = 0.015). Conclusions: The strong association between estimated macular RGC counts and mGCIPL thickness and the better diagnostic performance of the macular RGC counts compared with mGCIPL thickness provides further evidence that estimates of RGC number from cpRNFL thickness and SAP sensitivity can be used to assess neural losses in glaucoma. © 2014 American Academy of Ophthalmology. Source


Lu B.,University of Groningen | Lu B.,Harbin Medical University | Tigchelaar W.,University of Groningen | Ruifrok W.P.T.,University of Groningen | And 3 more authors.
European Journal of Heart Failure | Year: 2012

Aims Although cardiac diseases account for the highest mortality and morbidity rates in Western society, there is still a considerable gap in our knowledge of genes that contribute to cardiac (dys)function. Here we screened for gene expression profiles correlated to heart failure. Methods and results By expression profiling we identified a novel gene, termed DHRS7c, which was significantly down-regulated by adrenergic stimulation and in heart failure models. Dhrs7c is a short chain dehydrogenase/reductase (SDR) and is localized to the endo/sarcoplasmic reticulum. Dhrs7c is strongly conserved in vertebrates, and mRNA and protein expression levels were highest in heart and skeletal muscle followed by skin, but were not detectable in other organs. In vitro, both α-and β-adrenergic stimulation repressed Dhrs7c expression in neonatal cardiomyocytes and this could be mimicked by the direct activation of protein kinase C and adenylate cyclase, the respective intracellular targets of these hormones. In contrast, endothelin-1, which also provoked strong hypertrophy development in vitro, did not repress Dhrs7c expression. The latter suggests adrenergic specificity and indicates that down-regulation is not a prerequisite for hypertrophy development. In vivo adrenergic stimulation could also down-regulate Dhrs7c expression. Finally, we confirmed that expression was also down-regulated in two different models of failure and, importantly, also in biopsies from human heart failure patients. Conclusion Our results show that the expression of Dhrs7c, a novel endo/sarcoplasmic reticulum-localized SDR, is inversely correlated with adrenergic stimulation and heart failure development. © 2011 The Author. Source


Wang K.,Harbin Medical University
Wei sheng yan jiu = Journal of hygiene research | Year: 2010

To study the effect of copper deficiency on the nutritional status of iron, the expression of hepcidin mRNA and transferrin receptor mRNA in rats. Forty eight clean male SD rats were randomly divided into four groups according to body weight; and there were 12 rats in each group. The groups are normal iron and copper control group (group I), normal iron and copper deficiency group (group II), normal iron and copper slightly deficient group (group III), both iron and copper slightly deficient group (group IV). Serum, liver and spleen of rats were collected by the end of 8th week. Serum copper, serum iron, hemoglobin, serum transferrin receptor, serum ferritin, liver iron and liver copper, spleen iron and spleen copper were determined. The expression of liver transferring receptor mRNA and hepcidin mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR) method. Compared with the controls, the contents of serum iron and serum ferritin decreased (P < 0.05), but the level of serum transferrin receptor and the content of iron in liver and spleen increased significantly under copper deficiency. The expression of transferrin receptor mRNA in liver increased but the expression of hepcidin mRNA in liver decreased significantly under copper deficiency (P < 0.05). The nutritional status of iron may be affected by copper deficiency through influencing the absorption, storage and transportation of iron. Under the condition of copper deficiency, the expression of hepcidin mRNA in liver was lowered and the expression of transferrin receptor mRNA was enhanced through the way of iron response element-iron regulatory protein (IRE-IRP) to regulate iron metabolism. Source


Liu Q.,University of Pittsburgh | Liu Q.,Harbin Medical University | Turnquist H.R.,University of Pittsburgh
Cytokine | Year: 2013

Interleukin(IL)-33 is a member of the IL-1 cytokine family that has been attributed T helper (Th) type 2 immunity-promoting capacity. However, new studies indicate that IL-33 is a multifunctional protein that acts as transcriptional/signaling repressor, functions as an alarmin alerting the immune system to necrosis, as well as serves as a cytokine that targets cells expressing ST2, the IL-33 receptor. Interestingly, IL-33 is also emerging as a pleiotropic cytokine. Depending on the innate or adaptive immune cells targeted by IL-33, it can not only promote type 2, but also IFN-γ dominated type 1 immunity. In addition, IL-33 expands regulatory T cells. In this review, we assimilate the current knowledge of IL-33 immunobiology and discuss how IL-33 may mediate such diverse roles in the immune response to pathogens and development of immune-mediated pathologies. The function of IL-33 in shaping alloimmune responses to transplanted organs is poorly explored, but a particularly beneficial role of IL-33 in experimental heart transplant models is summarized. Finally, given the implication of IL-33 in pathologies of the lung and intestine, we discuss how IL-33 may contribute to the comparatively poor outcomes following transplantation of these two organs. © 2013 Elsevier Ltd. Source


Chen H.,Harbin Medical University | Yu Y.,Shenyang University | Rong S.,Harbin Maternal and Child Health Care Hospital | Wang H.,Shenyang University
Biomarkers | Year: 2014

Background: An increasing number of methylated genes have been reported as biomarkers for the diagnosis of bladder cancer. However, the results have been inconsistent. We performed a systematic review and meta-analysis to evaluate the feasibility and accuracy of using methylated genes as diagnostic markers for bladder cancer risk. Methods: Studies were systemically searched via the PubMed, ProQuest Health & Medical Complete and Springer Link database up to September 2013. Studies reporting the sensitivity and specificity of methylated biomarkers were extracted and the diagnostic accuracies were assessed by pooled diagnostic odds ratios (DORs) with 95% confidence intervals (CIs). Results: Methylated biomarkers showed accuracy for detecting bladder cancer (urine samples: DOR=36.48, 95% CI=7.12-186.81; tissue samples: DOR=68.71, 95% CI=36.52-129.29). Summary receiver operating characteristic analysis showed that markers in urine had better diagnostic power than those in tissues (area under the curve: 0.89 versus 0.75). Conclusion: The results of this study suggest that methylated biomarkers are suitable for diagnosing cancer risk. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted. Source


Ding Y.,Harvard University | Fu Y.,Harvard University | Fu Y.,Harbin Medical University | Lee J.C.,Harvard University | Hooper D.C.,Harvard University
Journal of Bacteriology | Year: 2012

Staphylococcus aureus readily infects humans, causing infections from mild superficial skin infections to lethal bacteremia and endocarditis. Transporters produced by S. aureus allow the pathogen to adapt to a variety of settings, including survival at sites of infection and in the presence of antibiotics. The native functions of many transporters are unknown, but their potential dual contribution to fitness and antimicrobial resistance highlights their importance in staphylococcal infections. Here, we show that S. aureus NorD, a newly recognized efflux pump of the major facilitator superfamily, contributes to fitness in a murine subcutaneous abscess model. In community-associated methicillin-resistant S. aureus (CA-MRSA) strain MW2, norD was selectively upregulated 36-fold at the infection site relative to growth in vitro, and the norD mutant demonstrated significant fitness impairment in abscesses, with fitness 20- to 40-fold lower than that of the parent MW2 strain. Plasmid-encoded NorD could complement the fitness defect of the MW2 norD mutant. ChromosomalnorD expression is polycistronic with the upstream oligopeptide permease genes (opp1ABCDF), which encode an ABC oligopeptide transporter. Both norD and opp1 were upregulated in abscesses and iron-restricted culture medium and negatively regulated by Fur, but only NorD contributed to fitness in the murine abscess model. © 2012, American Society for Microbiology. Source


Li X.,Nanjing Medical University | Zhang J.,Peking Union Medical College | Huang J.,Nanjing Medical University | Ma A.,Xian Jiaotong University | And 8 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives The purpose of this study was to assess the effects of qili qiangxin capsules in patients with chronic heart failure (CHF). Background Qili qiangxin capsules are a traditional Chinese medicine that has been approved in China for the treatment of CHF, but the evidence supporting its efficacy remains unclear. Methods A total of 512 patients with CHF were enrolled and randomly assigned to receive the placebo or qili qiangxin capsules in addition to their standard medications for the treatment of CHF. The primary endpoint was the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level during 12 weeks of treatment. Results At the 12-week follow-up, a significant reduction in the NT-proBNP level from baseline was observed in both groups, but the qili qiangxin capsule group demonstrated a significantly greater reduction than the placebo group (p = 0.002); 47.95% of patients in the qili qiangxin capsule group demonstrated reductions in NT-proBNP levels of at least 30% compared with 31.98% of patients in the placebo group (p < 0.001). Treatment with qili qiangxin capsules also demonstrated superior performance in comparison to the placebo with respect to New York Heart Association functional classification, left ventricular ejection fraction, 6-min walking distance, and quality of life. Conclusions On a background of standard treatment, qili qiangxin capsules further reduced the levels of NT-proBNP. Together, our data suggest that qili qiangxin capsules could be used in combination therapy for CHF. © 2013 by the American College of Cardiology Foundation Published by Elsevier Inc. Source


Ma G.,Guangdong Medical College | Wang Y.,Guangdong Medical College | Li Y.,Guangdong Medical College | Cui L.,Guangdong Medical College | And 3 more authors.
International Journal of Biological Sciences | Year: 2015

MicroRNAs (miRNAs) have recently emerged as fundamental post-transcriptional regulators inhibit gene expression linked to various biological processes. MiR-206 is one of the most studied and best characterized miRNA to date, which specifically expressed in skeletal muscle. In this review, we summarized the results of studies of miR-206 with emphasis on its function in skeletal muscle development. Importantly, dysregulation of miR-206 has been linked to many disorders in skeletal muscle such as Duchenne muscular dystrophy (DMD) and amyotrophic lateral sclerosis (ALS), and circulating miR-206 has highlighted its potential as a diagnose biomarker. In addition, a mutation in the 3’ untranslated region (3’-UTR) of the myostatin gene in the Texel sheep creating a target site for the miR-206 and miR-1 leads to inhibition of myostatin expression, which likely to cause the muscular hypertrophy phenotype of this breed of sheep. Therefore, miR-206 may become novel target for ameliorating skeletal muscle-related disorders and optimization of muscle quantity of domestic animals. © 2015 Ivyspring International Publisher. Source


Feng Y.,Harbin Medical University | Chien K.-Y.,Chang Gung University | Chen H.-L.,Chang Gung University | Chiu C.-H.,Chang Gung University
Journal of Proteome Research | Year: 2012

Recoding refers to the reprogramming of mRNA translation by nonstandard read-out rules. In this study, we used stable isotope labeling with amino acids in cell culture (SILAC) technology to investigate the proteome of host-adapted Salmonella serovars, which are characteristic of accumulation of pseudogenes. Interestingly, a few annotated pseudogenes were indeed able to express peptides downstream of the inactivation site, suggesting the occurrence of recoding. Two mechanisms of recoding, namely, programmed frameshifting and codon redefinition, were both found. We believe that the phenomena of recoding are not rare in bacteria. More studies are required for a better understanding of bacterial translation and the implication of pseudogene recoding in Salmonella serovars. © 2012 American Chemical Society. Source


Wang B.,Harbin Medical University
Wei sheng yan jiu = Journal of hygiene research | Year: 2011

To explore the influencing factors of establishing diabetes mellitus animal model by the combination of feeding high-fat diet for different periods of time and different dosage of streptozotocin (STZ). Eight-week-aged male Wistar rats were injected (i.p.) with 30 mg/kg STZ after high-fat diet being fed for 0, 4, 6 or 8 weeks respectively, and another 100 male rats were injected (i.p.) with 20 mg/kg, 30 mg/kg and 60 mg/kg STZ respectively after high-fat diet being fed for 4 weeks to establish diabetes mellitus models. Intraperitoneal glucose tolerance test and insulin tolerance test were carried out, and plasma indices were also measured. The type of models was verified by the administration (i.p.) of rosiglitazone. The successful rate of modeling in rats fed with high-fat diet for 4 weeks and received 30 mg/kg STZ injection (i.p.) was the highest (85% & 80%). Their plasma triglyceride and free fatty acid were increased significantly (P < 0.05), but the fasting plasma insulin was not different from the control group, these rats also presented impaired glucose tolerance and insulin resistance. The hyperglycemia and blood lipid disorders of these model rats were recovered by the treatment with rosiglitazone. With increasing age and the duration of high-fat diet, the death rate increased rapidly (50% & 65%). The successful rate of modeling at low dose of STZ (20 mg/kg, i.p.) was only 40%. The highest death rate (75%) was observed in rats treated with high dose of STZ (60 mg/kg, i.p.). The duration of high-fat diet, the dosage of STZ and the age of rats were the most important factors for the successful rate and death rate while establishing diabetic animal model by the combination of high-fat diet and STZ. Source


Kong T.,Harbin Medical University
Wei sheng yan jiu = Journal of hygiene research | Year: 2011

To investigate the effect and mechanism of oleanolic acid (OA)-stimulated lipolysis in primary adipocytes. Adipocytes were isolated from the epididymal fat pads of SD rats. The non-cytotoxic dosage of OA for primary adipocytes was established by MTT test. Adipocytes were divided into four groups: a control group and 3 OA-treated groups (25, 50 and 100 micromol/L). Glycerol released in the culture medium of the control and three OA-treated adipocyte groups was determined after incubation with OA for 4 and 24 hours. The glycerol released in the culture medium of three OA-treated adipocyte groups with protein kinase A inhibitor H-89 (10 micromol/L) was also determined. The expression of native perilipin and hormone-sensitive lipase (HSL) translocation were examined by immunoblotting method. Cytotoxicity was observed when the concentration of OA was 400 micromol/L. After incubation for 4 hours, the release of glycerol in the 50 micromol/L and 100 micromol/L OA groups was increased 12% and 20% (P < 0.05) respectively. After incubation for 24 hours, the release of glycerol was increased 14% (P > 0.05) and 23% (P < 0.05) respectively. There is no change of glycerol release in the three OA- and H-89-treated adipocyte groups. OA may down-regulate the expression of perilipin and promote HSL translocation. OA may stimulate the release of glycerol from primary adipocytes, and the cellular mechanisms of lipolytic action may involve in augmenting perilipin expression and promoting HSL translocation. Source


Wang Z.,University of Queensland | Liu M.,Harbin Medical University
Diabetes Research and Clinical Practice | Year: 2016

Aim Previous estimates of life-years lost to diabetes are highly inconsistent. This study provided the updated estimates of life-years lost to diabetes in the United States. Methods Each of a nationally representative sample of 21,829 adults with diabetes in the U.S. National Health Interview Survey 1997–2009 was individually matched to one without diabetes by age, sex, race, survey year, BMI, smoking status, pre-existing cardiovascular disease and pre-existing cancer. All-cause mortality from original surveys to 31 December 2011 and median survival ages were estimated for those with diabetes and their matched controls. Results Overall median survival age for adults with diabetes was 10.5 years shorter than that for matched controls without diabetes. Estimated life-years lost associated with diabetes decreased with increasing age at diagnosis from 20.0 years for those diagnosed before age 20 years to no difference for those diagnosed after 80 years. Hazard ratios for mortality decreased from 3.03 (95% CI: 2.41, 3.80) for those with diabetes diagnosed before 20 years to 1.04 (95% CI: 0.78, 1.39) for those diagnosed after 80 years. The estimate of life-years lost associated with diabetes was much higher among those with pre-existing cardiovascular disease (20.3 years) than among those without cardiovascular disease (8.5 years). Conclusions The effect of diabetes on survival depends on age at first diagnosis of diabetes and the presence of pre-existing diseases. The life-years lost are higher for those with diabetes diagnosed at younger ages. This study provided the updated estimates of life-years lost associated with diabetes in the United States. © 2016 Elsevier Ireland Ltd Source


Li J.-S.,Wenzhou Medical College | Bi Y.-T.,Wenzhou Medical College | Dong C.,Harbin Medical University | Yang J.-F.,Wenzhou Medical College | Liang W.-D.,Wenzhou Medical College
PLoS ONE | Year: 2011

Streptococcus thermophilus, a gram-positive facultative anaerobe, is one of the most important lactic acid bacteria widely used in the dairy fermentation industry. In this study, we have analyzed the global transcriptional profiling of S. thermophilus upon temperature change. During a temperature shift from 42°C to 50°C, it is found that 196 (10.4%) genes show differential expression with 102 up-regulated and 94 down-regulated at 50°C. In particular, 1) Heat shock genes, such as DnaK, GroESL and clpL, are identified to be elevated at 50°C; 2) Transcriptional regulators, such as HrcA, CtsR, Fur, MarR and MerR family, are differentially expressed, indicating the complex molecular mechanisms of S. thermophilus adapting to heat shock; 3) Genes associated with signal transduction, cell wall genes, iron homeostasis, ABC transporters and restriction-modification system were induced; 4) A large number of the differentially expressed genes are hypothetical genes of unknown function, indicating that much remains to be investigated about the heat shock response of S. thermophilus. Experimental investigation of selected heat shock gene ClpL shows that it plays an important role in the physiology of S. thermophilus at high temperature and meanwhile we confirmed ClpL as a member of the CtsR regulon. Overall, this study has contributed to the underlying adaptive molecular mechanisms of S. thermophilus upon temperature change and provides a basis for future in-depth functional studies. © 2011 Li et al. Source


Guo F.,Harbin Medical University
Wei sheng yan jiu = Journal of hygiene research | Year: 2011

To provide a basis for establishing better animal models with hyperlipidemia by comparing the effects of two different high-fat diets on blood lipids of rats. 30 male Wistar rats were randomly divided into 3 groups (10 rats in each group) , including normal control group (NC), high fat formula diet group I (HFFD I) and high fat formula diet group II (HFFD II). NC group was fed a stock rodent diet, the HFFD I and HFFD II were fed with different high-fat formulae diets. Animals were weighted weekly and blood lipids were determined every two weeks. The experiment lasted for 6 weeks. By the end of the experiment, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in HFFD I group were 1.4 and 2.2 times higher than those of the NC group (P < 0.01). Serum high-density lipoprotein cholesterol (HDL-C) was 22.2% lower than that of NC group. Serum triglyceride (TG) was not significantly different between HFFD I and NC group (P > 0.05). Serum TC and LDL-C of HFFD II group were 11.5 and 5.7 times respectively higher than those of the NC group (P < 0.01). Serum TG and HDL-C were 39.7% and 34.6% respectively lower than those of the NC group. Animal models with hypercholesteremia can be successfully established by the two methods, but the serum TG level of the rats can not be significantly elevated. Source


The origin of Keshan disease (KD), an endemic cardiomyopathy particularly affected children and young women in China, has been a controversial and difficult problem in academics over the past decades. We hypothesize that mycotoxins likely citreoviridin may initiate KD mainly through oxidative stress mechanism by long-term consumption of mouldy cereals due to food shortage lifestyle. Dietary deficiency of selenium, proteins, Vitamin C, E, etc., may act as enhancing factors to exacerbate the pathological damage. This speculation can perfectly explain the features of KD and has received strong supporting evidences. If the hypothesis were to be confirmed, it is of very important value in monitoring and blocking the incidence of KD. Thus, future efforts are needed to investigate specific biomarkers of exposure to citreoviridin in KD cases. © 2009 Elsevier Ltd. Source


Guo L.Y.,Harbin Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To study the effect of resveratrol bovine serum albumin nanoparticles on SKOV3 cell line and its mechanisms. The morphological changes of the cells exposed to the nanoparticles were observed by apoptotic body/cell nucleus DNA staining under inverted microscope and fluorescence microscope, and the pathway of cell death was determined by phosphatidylserine translocation. Western blotting was performed to detect the activation of cyto.c, caspase-3 and caspase-9. DNA ladder was detected with gel electrophoresis and the cell death was partially inhibited by the pan-caspase inhibitor Z-VAD-FMK. Gel electrophoresis displayed both DNA ladder and smear in RES-BSANP exposed groups, while DNA ladder disappeared in Z-VAD-FMK group and only the smear was left. Cyto.c in the cytoplasm was released at 2 h, while the expression of caspase-9 protein reached the peak level at 4 h and caspase-3 expression was obvious enhanced at 8 h. At 4 h, caspase-9 expression in the cells exposed to 100 μmol/L RES-BSANP was decreased significantly as compared to the cells treated with 50 μmol/L RES-BSANP (P>0.05). RES-BSANP can induce the necrosis and apoptosis of SKOV3 cells via either caspase-dependent or caspase-independent pathways. Source


Zhou J.,Harbin Medical University
Chinese Medical Journal | Year: 2012

Objective To summarize the clinical applications of arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL), as well as non-APL malignancies and to discuss the mechanisms and adverse effects involved in ATO administration. Data sources The data in this article were collected from PubMed and CHKD database with relevant English and Chinese articles published from 1957 to 2011, with key words including acute promyelocytic leukemia, arsenic trioxide, treatment, and mechanism. Study selection Articles including any information about ATO in the treatment of APL were selected. Results APL is a rare subtype of acute myeloid leukemia, with dismal prognosis under treatment with traditional chemotherapy. ATO impressively increases the complete remission rate and prolongs survival of patients with APL, with only mild and transient adverse effects. The advances in the understanding of multiple mechanisms involved in ATO treatment will benefit more cancers in future. Conclusion Deeper understanding of mechanisms involved in ATO treatment may provide rationales for future clinical applications in a number of human malignancies. Source


Shan Z.,Huazhong University of Science and Technology | Bao W.,Huazhong University of Science and Technology | Zhang Y.,Huazhong University of Science and Technology | Rong Y.,Huazhong University of Science and Technology | And 7 more authors.
Diabetes | Year: 2014

Although both SLC30A8 rs13266634 single nucleotide polymorphism and plasma zinc concentrations have been associated with impaired glucose regulation (IGR) and type 2 diabetes (T2D), their interactions for IGR and T2D remain unclear. Therefore, to assess zinc-SLC30A8 interactions, we performed a case-control study in 1,796 participants: 218 newly diagnosed IGR patients, 785 newly diagnosed T2D patients, and 793 individuals with normal glucose tolerance. After adjustment for age, sex, BMI, family history of diabetes, and hypertension, the multivariable odds ratio (OR) of T2D associated with a 10 μg/dL higher plasma zinc level was 0.87 (95% CI 0.85-0.90). Meanwhile, the OR of SLC30A8 rs13266634 homozygous genotypes CC compared with TT was 1.53 (1.11-2.09) for T2D. Similar associations were found in IGR and IGR&T2D groups. Each 10 μg/dL increment of plasma zinc was associated with 22% (OR 0.78 [0.72-0.85]) lower odds of T2D in TT genotype carriers, 17% (0.83 [0.80-0.87]) lower odds in CT genotype carriers, and 7% (0.93 [0.90-0.97]) lower odds in CC genotype carriers (P for interaction = 0.01). Our study suggested that the C allele of rs13266634 was associated with higher odds of T2D, and higher plasma zinc was associated with lower odds. The inverse association of plasma zinc concentrations with T2D was modified by SLC30A8 rs13266634. Further studies are warranted to confirm our findings and clarify the mechanisms underlying the interaction between plasma zinc and the SLC30A8 gene in relation to T2D. © 2014 by the American Diabetes Association. Source


Wang J.J.-Y.,King Abdullah University of Science and Technology | Wang Y.,Ohio State University | Zhao S.,Harbin Medical University | Gao X.,King Abdullah University of Science and Technology
Engineering Applications of Artificial Intelligence | Year: 2015

In this paper, a novel pattern classification approach is proposed by regularizing the classifier learning to maximize mutual information between the classification response and the true class label. We argue that, with the learned classifier, the uncertainty of the true class label of a data sample should be reduced by knowing its classification response as much as possible. The reduced uncertainty is measured by the mutual information between the classification response and the true class label. To this end, when learning a linear classifier, we propose to maximize the mutual information between classification responses and true class labels of training samples, besides minimizing the classification error and reducing the classifier complexity. An objective function is constructed by modeling mutual information with entropy estimation, and it is optimized by a gradient descend method in an iterative algorithm. Experiments on two real world pattern classification problems show the significant improvements achieved by maximum mutual information regularization. © 2014 Elsevier Ltd. Source


Li B.,Harvard University | Li B.,Harbin Medical University | Castano A.P.,Harvard University | Hudson T.E.,Harvard University | And 5 more authors.
FASEB Journal | Year: 2010

Kidney damage due to injury rarely resolves completely, and there are currently no therapies capable of promoting repair. In addition to understanding mechanisms by which tissues are damaged, illuminating mechanisms of repair and regeneration is also of great importance. Here we show that the melanoma-associated, transmembrane glycoprotein, Gpnmb, is up-regulated 15-fold following ischemic damage in kidney tissue and by more than 10-fold in macrophages and 3-fold in surviving epithelial cells. Gpnmb-expressing macrophages and epithelial cells were found to contain apoptotic bodies at 3 times the rate of nonexpressing cells. Either mutation of Gpnmb or ablation of inflammatory macrophages prevents normal repair of the kidney. Significantly, the kidneys from postischemic Gpnmb mutant mice exhibited a 5-fold increase in apoptotic cellular debris compared to wild-type mice. These mice also experienced an 85% increase in mortality following bilateral ischemic kidney. Finally, we demonstrate that Gpnmb is a phagocytic protein that is necessary for recruitment of the autophagy protein LC3 to the phagosome where these proteins are colocalized and for lysosomal fusion with the phagosome and hence bulk degradation of their content. Therefore, Gpnmb is a novel prorepair gene that is necessary for crosstalk between the macroautophagic degradation pathway and phagocytosis. © FASEB. Source


Luo X.,Montreal Heart Institute | Yang B.,Harbin Medical University | Nattel S.,Montreal Heart Institute
Nature Reviews Cardiology | Year: 2015

Atrial fibrillation (AF), the most common sustained arrhythmia in clinical practice, is an important contributor to cardiac morbidity and mortality. Pharmacological approaches currently available to treat patients with AF lack sufficient efficacy and are associated with potential adverse effects. Even though ablation is generally more effective than pharmacotherapy, this invasive procedure has considerable potential complications and is limited by long-term recurrences. Novel therapies based on the underlying molecular mechanisms of AF can provide useful alternatives to current treatments. MicroRNAs (miRNAs), endogenous short RNA sequences that regulate gene expression, have been implicated in the control of AF, providing novel insights into the molecular basis of the pathogenesis of AF and suggesting miRNA targeting as a potential approach for the management of this common arrhythmia. In this Review, we provide a comprehensive analysis of the current experimental evidence supporting miRNAs as important factors in AF and discuss their therapeutic implications. We first provide background information on the pathophysiology of AF and the biological determinants of miRNA synthesis and action, followed by experimental evidence for miRNA-mediated regulation of AF, and finally provide a comprehensive overview of miRNAs as potential novel therapeutic targets for AF. © 2015 Macmillan Publishers Limited. All rights reserved. Source


Objective: To investigate the present prevalence state of children's Kaschin-Beck disease (KBD) in Xinghai county of Qinghai province, a relative active KBD area in 2009, and to investigate their nutritional selenium level of local children and the T-2 toxin contamination level in their staple food. Methods: Right hand X-ray photographs of children aged 7-12 in Shang, Zhong and Xia villages of Tangnaihai countryside in Xinghai county were taken. X-ray diagnosis was carried out according to the "Diagnostic Criteria of Kashin Beck Disease" (GB 16003-1995). Selected samples (children's hair, drinking water and their staple food) were collected according to X-ray film taken. Selenium contents in hair, drinking water and staple food samples were measured by 2, 3-diaminonaphthalene fluorescence, and T-2 toxin in staple food sample was detected with enzyme-linked immunosorbent assay(ELISA) kits. Results: Total X-ray detection rate of children KBD was 12.20%(31/254) and KBD positive rate of children in Xia village was up to 14.97% (22/147), Shang village was up to 9.52% (6/63), and Zhong village was up to 6.82%(3/44). The selenium level in children's body and outer environment was very low, namely, the selenium content in hair, drinking water, wheat and flour was (0.250 ± 0.136)mg/kg, (0.156 ± 0.046)μg/L, (0.0045 ± 0.0030)mg/kg, and (0.0067 ± 0.0116)mg/kg, respectively. The T-2 toxin level was relatively high in children's staple food, which was (78.91 ± 46.17)μg/kg in wheat and (47.47 ± 46.47) μg/kg in flour. Conclusions: In relative active KBD areas of Xinghai county of Qinghai province, the children's selenium nutritional level is low, and the T-2 toxin' contamination level in their staple food is relatively high, which is consistent with the distribution of local children's KBD. Source


Liu X.,Harbin Medical University
Wei sheng yan jiu = Journal of hygiene research | Year: 2011

To evaluate the differences of oxidative stress level between obesity-prone rats and obesity-resistant rats. Male Wistar rats were divided into control group (10 rats) fed with basal diet and high fat group (30 rats) fed with high-fat diet for 6 weeks. Ten rats in obesity-prone (OP) group and obesity-resistant (OR) group were selected from the high-fat diet group according to the gain of body weight. All rats were killed by the end of 13th week. Serum SOD, MDA, GSH-Px, blood lipids and fatty acids were detected by standard methods. SOD was lower in OP rats than that in OR rats and control rats. GSH-Px was lower in OP rats than that in OR rats. MDA was higher in OP rats than that in control rats. The energy intake, body fat content, FBG, serum lipids, serum insulin, ISI and free fatty acids in OP rats were significantly different from those in OR rats, but there were no differences between OR and control rats. Compared with OR rats, the oxidative stress responses were increased and the antioxidant capacities were decreased in OP rats after 13 weeks of experiment. Source


Wang Z.,University of Illinois at Chicago | Wang Z.,Harbin Medical University | Yao T.,University of Illinois at Chicago | Song Z.,University of Illinois at Chicago
Journal of Lipid Research | Year: 2010

The mechanisms involved in the development of alcoholic liver disease (ALD) are not well established. We investigated the involvement of acyl-CoA: diacylglycerol acyltransferase 2 (DGAT2) upregulation in mediating hepatic fat accumulation induced by chronic alcohol consumption. Chronic alcohol feeding caused fatty liver and increased hepatic DGAT2 gene and protein expression, concomitant with a significant suppression of hepatic MAPK/ERK kinase/extracellular regulated kinase 1/2 (MEK/ERK1/2) activation. In vitro studies demonstrated that specific inhibitors of the MEK/ERK1/2 pathway increased DGAT2 gene expression and triglyceride (TG) contents in HepG2 cells, whereas epidermal growth factor, a strong ERK1/2 activator, had the opposite effect. Moreover, chronic alcohol feeding decreased hepatic S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio, an indicator of disrupted transmethylation reactions. Mechanistic investigations revealed that N-acetyl-S-farnesyl-L-cysteine, a potent inhibitor of isoprenylcysteine carboxyl methyltransferase, suppressed ERK1/2 activation, followed by an enhanced DGAT2 expression and an elevated TG content in HepG2 cells. Lastly, we demonstrated that the beneficial effects of betaine supplementation in ALD were associated with improved SAM/SAH ratio, alleviated ERK1/2 inhibition, and attenuated DGAT2 upregulation. In conclusion, our data suggest that upregulation of DGAT2 plays an important role in the pathogenesis of ALD, and that abnormal methionine metabolism contributes, at least partially, to DGAT2 upregulation via suppression of MEK/ERK1/2 activation. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc. Source


Li Y.-H.,University of Electronic Science and Technology of China | Li Y.-H.,China National Institute of Biological Sciences | Dong M.-Q.,China National Institute of Biological Sciences | Guo Z.,University of Electronic Science and Technology of China | Guo Z.,Harbin Medical University
Mechanisms of Ageing and Development | Year: 2010

An important task of aging research is to find genes that regulate lifespan. However, identification of genes related to longevity (referred to as longevity genes hereafter) through web-lab experiments such as genetic screens is a tedious and labor-intensive activity. Developing an algorithm to predict longevity genes should facilitate aging research. In this paper, we systematically analyzed properties of longevity genes in Caenorhabditis elegans and found that, when compared to genes not yet known to be involved in longevity, known longevity genes display the following features: (i) longer genomic sequences and protein sequences, (ii) a stronger tendency to co-express with other genes during a transition from dauer state (an extremely long lifespan) to non-dauer state (a normal lifespan), (iii) significant enrichment in certain functions and RNAi phenotypes, (iv) higher sequence conservation, and (v) higher in several network topological features such as degrees in a functional interaction network. Based on these features, we developed an algorithm to predict longevity genes in C. elegans and obtained 243 novel longevity genes with a precision rate of 0.85. Some of the predicted genes have been validated by published articles or wet lab experiments. The contribution of each feature to the predicted results was also evaluated. © 2010 Elsevier Ireland Ltd. Source


Zhao W.,Harbin Medical University
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2010

To investigate the effect and mechanism of Zuoguiyin (ZGY, a Chinese medical remedy for regulating qi and nourishing yin) on expression of ovarian follicle-stimulating hormone receptor (FSHR) in rats during peri-menopausal period (PMP). PMP rats were administered with low (13.78 g/kg), middle (20.67 g/kg) and high (31.00 g/kg) dose ZGY respectively by gastrogavage for eight weeks. FSHR mRNA and protein expressions were detected by RT-PCR and immunohistochemistry respectively. Besides, granulosa cells, collected from pregnant mare serum treated nonage rats, were incubated, and the level of FSHR mRNA expression in the cultured cells were detected after various disposals. (1) Ovarian levels of FSHR mRNA and protein expressions in PMP rats were significantly lower than those in young rats (P<0.01), but were up-regulated significantly by ZGY treatment (P<0.01). (2) As compared with the control, FSHR mRNA expression increased in cultured granulosa cells after treated by ZGY extract; the increasing effect of ZGY was enhanced by combined treatment with Forskolin and attenuated by Genistein (a tyrosine protein kinase inhibitor). ZGY could improve the ovarian functions during PMP by up-regulating the expression of FSHR and raise the ovarian responsibility to FSH, which may be possibly realized by activating cAMP-protein kinase and tyrosine protein kinase signal pathway. Source


Kang K.,Harbin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2010

To study the protective function and pathophysiology of cystathionine gamma-lyase (CSE)/hydrogen sulfide (H(2)S) system in hepatic ischemia-reperfusion injury (HIRI) in rats. Wistar rats were randomly distributed into sham group (n = 18), ischemia-reperfusion (IR) group (n = 18), IR + NaHS group (n = 18) and IR + DL-propargylglycine (PAG) group (n = 18). The hepatic IR model was established by Pringle's hepatic vascular occlusion. At each of the indicated time points (1, 3 and 6 hours after IR), the serum levels of H(2)S and the hepatic CSE activity were measured. The serum levels of inflammatory factors, including TNF-α, IL-10 were determined by ELISA methods. The expression of apoptotic protein, TNF-α, in liver tissue was tested by Western blot assay, cell apoptosis was examined by TUNEL and the histological changes were examined in each group. The serum levels of H(2)S and CSE activity were significantly increased in group IR compared with group sham at all indicated time points (P < 0.05). The serum level of inflammatory factors (P < 0.01) and the hepatic expression of TNF-α protein (P < 0.05) were elevated obviously in group IR than that in group sham. Administration of NaHS could reduce the production of inflammatory factors in serum (P < 0.01), inhibit hepatic protein expression of TNF-α (P < 0.05) and attenuate the liver histological scores of IR injury (P < 0.05), whereas PAG aggravated them. The endogenous CSE/H(2)S system maybe involved in the pathogenesis of hepatic IR injury, which suggests that CSE/H(2)S system can protect liver from IR injury in rats by intervening in inflammatory reaction, attenuating the injury severity and inhibiting expression of apoptotic protein TNF-α. Source


Wang S.J.,Harbin Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2010

To investigate the anti-tumor activity of combined gemcitabine with dihydroartemisinin, and the mechanism of the anti-tumor effect of gemcitabine enhanced by dihydroartemisinin on pancreatic cancer. For cultured cells, cell growth was determined by the MTT assay and apoptosis was evaluated by flow cytometry analysis and confocal laser scanning microscope stained with Annexin V-FITC/PI. The nuclear extract for determining NF-kappaB DNA-binding activity was analyzed by EMSA, while nuclear P65 and its downstream gene expression was determined by Western blot assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors and the tumor volume was monitored after exposure to agents. TUNEL assay was used to assess tumor cell apoptosis in tumor tissue. After combination of gemcitabine and dihydroartemisinin treatment, the proliferative inhibition rates of pancreatic cancer cells BxPC-3 and Panc-1 reached up to (81.1 +/- 3.9)% and (76.5 +/- 3.3)%, and the apoptosis rates were up to (53.6 +/- 3.8)% and (48.3 +/- 4.3)%, the differences were significantly (P < 0.01) compared with gemcitabine [(24.8 +/- 2.9)% and (21.8 +/- 3.5)%]. All the treatment groups inhibited the growth of pancreatic xenograft tumors in nude mice. The tumor volume and apoptosis index were (262 +/- 37) mm(3) and (50 +/- 4)% respectively in the combined treatment, compared to those of [(384 +/- 56) mm(3) and (25 +/- 3)%] in gemcitabine, the differences were significantly (P < 0.05). EMSA showed that gemcitabine alone obviously enhanced its DNA-binding activity compared to control. However, dihydroartemisinin significantly reduced its DNA-binding activity, so that abrogated the inducing effect of gemcitabine on NF-kappaB activation. Western blot assay indicated that dihydroartemisinin downregulated expression of nuclear P65, and combined treatment not only downregulated the expression of Cyclin D1, Bcl-xL and Bcl-2 while upregulated Bax, thus reduced the Bcl-2/Bax ratio, but also increased the caspase-3 activation, all of which increased apoptosis in both BxPC-3 and Panc-1 cells. Dihydroartemisinin significantly abrogated the inducing effect of gemcitabine on NF-kappaB activation and downregulated the expression of NF-kappaB targeted gene products, which may be one possible mechanism by which dihydroartemisinin augments the anti-tumor effect of gemcitabine on pancreatic cancer. Source


Testes-specific protease 50 (TSP50) is a potential cancer-associated gene that may be involved in human laryngocarcinoma. The present study aimed to investigate suppressive effects on the HEp2 human laryngocarcinoma cell line by transfection with TSP50-specific short hairpin RNA (shRNA). Western blot analysis was used to detect the expression levels of TSP50. MTT assay was used to evaluate cell proliferation. Wound healing was used in cell migration and invasion assays to evaluate the cell exercise capacity. Nuclear staining assay was used to evaluate cell apoptosis after knockdown of TSP50. Expression levels of TSP50 protein in the shRNA group were downregulated successfully by transfection, and the knockdown of endogenous TSP50 in HEp2 cells greatly inhibited nuclear factor κB (NF-κB) activity. MTT results showed that the cell proliferation in the shRNA group was significantly more depressed than that in the blank (P < 0.05) and negative control groups (P < 0.05). Additionally, a decreased number of migrated cells in the shRNA group was observed (P < 0.05) using a cell migration and invasion assay. Moreover, knockdown of endogenous TSP50 expression can induce apoptosis in HEp2 Cells. These data indicated that knockdown of TSP50 may cause inhibition of proliferation, migration, and invasion of HEp2 cells. This study provides a new perspective in understanding the molecular mechanisms underlying the progression of laryngocarcinoma and offers a potential therapeutic target for laryngocarcinoma. © 2014, International Society of Oncology and BioMarkers (ISOBM). Source


Wang J.,University of Electronic Science and Technology of China | Zhou X.,University of Electronic Science and Technology of China | Zhu J.,University of Electronic Science and Technology of China | Zhou C.,University of Electronic Science and Technology of China | And 2 more authors.
BMC Bioinformatics | Year: 2010

Background: Semantic similarity scores for protein pairs are widely applied in functional genomic researches for finding functional clusters of proteins, predicting protein functions and protein-protein interactions, and for identifying putative disease genes. However, because some proteins, such as those related to diseases, tend to be studied more intensively, annotations are likely to be biased, which may affect applications based on semantic similarity measures. Thus, it is necessary to evaluate the effects of the bias on semantic similarity scores between proteins and then find a method to avoid them.Results: First, we evaluated 14 commonly used semantic similarity scores for protein pairs and demonstrated that they significantly correlated with the numbers of annotation terms for the proteins (also known as the protein annotation length). These results suggested that current applications of the semantic similarity scores between proteins might be unreliable. Then, to reduce this annotation bias effect, we proposed normalizing the semantic similarity scores between proteins using the power transformation of the scores. We provide evidence that this improves performance in some applications.Conclusions: Current semantic similarity measures for protein pairs are highly dependent on protein annotation lengths, which are subject to biological research bias. This affects applications that are based on these semantic similarity scores, especially in clustering studies that rely on score magnitudes. The normalized scores proposed in this paper can reduce the effects of this bias to some extent. © 2010 Wang et al; licensee BioMed Central Ltd. Source


To investigate the effects of biological characters of the human ovarian cell line (OVCAR) by stable transfection short hairpin RNA into the target HMGA1 gene. Experiments were divided into two groups: transfected the OVCAR cells with pSilence4.1-CMV-Hs plasmid as group A, while transfected OVCAR cells with pSilence4.1-CMV-Hn plasmid as group B, in which stably transfected cells were gained by antibiotic screening. The comparative expressions of HMGA1 were detected by RT-PCR and western blot. Methyl thiazolyl tetrazolium (MTT) method was applied to measure cell proliferation and at the same time, the cell growth curve was also be mapped. Vitro invasion assay was used to observe the invasion ability of the cancer cells, and the tumor growth of the nude mice inoculated of tumor cells were compared with before and after transfection. In group A, the expression level of mRNA and protein HMGA1 gene in OVCAR cells were remarkably reduced before and after the stable transfected with HMGA1 siRNA, in which the percents of mRNA expression were [(86.3 ± 2.7)% vs. (35.8 ± 3.1)%, P < 0.05], the expression of protein were [(68.6 ± 2.8)% vs. (22.3 ± 4.2)%, P < 0.05)]. The OVCAR cell growth in stable transfection status was more significantly decreased than that in non-transfection status (P < 0.05). In group B, there were no statistical difference in the expression of HMGA1 siRNA, protein and the cell growth between before and after transfection states (P > 0.05). The invasion cell numbers were reduced from before to after transfection state in group A [(53 ± 6) vs. (21 ± 6), P < 0.05], while there was no significant difference in group B [(51 ± 6) vs. (47 ± 8), P > 0.05]. After inoculated transfected cells into nude mice, it took (6.0 ± 0.9) days to grow the planed tumors in group A, which was much shorter than that (12.3 ± 3.9) days in group B (P < 0.05). After 5 weeks, the tumor weight and volume in group A was were significantly lower than those in group B [(0.8 ± 0.3) g vs. (2.1 ± 0.4) g, (205 ± 34) mm(3) vs. (987 ± 82) mm(3), all P < 0.05]. HMGA1 siRNA could remarkably reduce the expression of HMGA1 gene in ovarian cell and also inhabit the ovarian cell growth. Source


Wang H.,Harbin Medical University | Wang X.,Daqing Oilfield General Hospital
Therapeutics and Clinical Risk Management | Year: 2016

Objective: This study was designed to investigate the efficacy and safety outcomes of ticagrelor in comparison with clopidogrel on a background of aspirin in elderly Chinese patients with acute coronary syndrome (ACS). Patients and methods: A double-blinded, randomized controlled study was conducted, and 200 patients older than 65 years with the diagnosis of ACS were assigned 1:1 to take ticagrelor or clopidogrel. The course of treatment was required to continue for 12 months. Results: The median age of the whole cohort was 79 years (range: 65-93 years), and females accounted for 32.5% (65 patients). Baseline characteristics and clinical diagnosis had no significant difference between patients taking ticagrelor and clopidogrel; they were also balanced with respect to other treatments (P>0.05 for all). The risk of cardiovascular death was significantly lower in patients taking ticagrelor compared with clopidogrel, as was the risk of myocardial infarction (P<0.05 for all); there was no difference in the risk of stroke (P>0.05). Ticagrelor was more effective than clopidogrel in decreasing the primary efficacy end point (cardiovascular death, myocardial infarction, and stroke, P<0.05). The all-cause mortality was not significantly different between patients taking ticagrelor and clopidogrel (P>0.05). The difference in the risk of bleeding, platelet inhibition and patient outcomes major bleeding (life-threatening bleeding and others), and platelet inhibition and patient outcomes minor bleeding was not evident between patients taking ticagrelor and clopidogrel (P>0.05 for all). Conclusion: The current study in elderly Chinese patients with ACS demonstrated that ticagrelor reduced the primary efficacy end point at no expense of increased bleeding risk compared with clopidogrel, suggesting that ticagrelor is a suitable alternative for use in elderly Chinese patients with ACS. © 2016 Wang and Wang. Source


Geng S.,Harvard University | Zhou S.,Harvard University | Glowacki J.,Harvard University | Glowacki J.,Harbin Medical University | Glowacki J.,Brigham and Womens Hospital
Journal of Bone and Mineral Research | Year: 2011

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] has many noncalcemic actions that rest on inhibition of proliferation and promotion of differentiation in malignant and normal cell types. 1,25(OH) 2D3 stimulates osteoblast differentiation of human marrow stromal cells (hMSCs), but little is known about the effects of 25-hydroxyvitamin D3 [25(OH)D3] on these cells. Recent evidence shows that hMSCs participate in vitamin D metabolism and can activate 25(OH)D3 by CYP27B1/1α-hydroxylase. These studies test the hypothesis that antiproliferative and prodifferentiation effects of 25(OH)D 3 in hMSCs depend on CYP27B1. We studied hMSCs that constitutively express high (hMSCshi-1α) or low (hMSCslo-1α) levels of CYP27B1 with equivalent expression of CYP24A1 and vitamin D receptor. In hMSCshi-1α, 25(OH)D3 reduced proliferation, downregulated proliferating cell nuclear antigen (PCNA), upregulated p21 Waf1/Cip1, and decreased cyclin D1. Unlike 1,25(OH)2D 3, the antiapoptotic effects of 25(OH)D3 on Bax and Bcl-2 were blocked by the P450 inhibitor ketoconazole. The antiproliferative effects of 25(OH)D3 in hMSCshi-1α and of 1,25(OH) 2D3 in both samples of hMSCs were explained by cell cycle arrest, not by increased apoptosis. Stimulation of osteoblast differentiation in hMSCshi-1α by 25(OH)D3 was prevented by ketoconazole and upon transfection with CYP27B1 siRNA. These data indicate that CYP27B1 is required for 25(OH)D3's action in hMSCs. Three lines of evidence indicate that CYP27B1 is required for the antiproliferative and prodifferentiation effects of 25(OH)D3 on hMSCs: Those effects were not seen (1) in hMSCs with low constitutive expression of CYP27B1, (2) in hMSCs treated with ketoconazole, and (3) in hMSCs in which CYP27B1 expression was silenced. Osteoblast differentiation and skeletal homeostasis may be regulated by autocrine/paracrine actions of 25(OH)D3 in hMSCs. © 2011 American Society for Bone and Mineral Research. Source


Zhang W.,Capital Medical University | Zhang J.,CAS Beijing Institute of Genomics | Yan W.,Capital Medical University | You G.,Capital Medical University | And 9 more authors.
Cancer | Year: 2013

Background: More reliable clinical outcome prediction is required to better guide more personalized treatment for patients with primary glioblastoma multiforme (GBM). The objective of this study was to identify a microRNA expression signature to improve outcome prediction for patients with primary GBM. METHODS: A cohort of Chinese patients with primary GBM (n = 82) was analyzed using whole-genome microRNA expression profiling with patients divided into a training set and a testing set. Cox regression and risk-score analyses were used to develop a 5-microRNA signature using 41 training samples. The signature was validated in 41 other test samples, in an independent cohort of 35 patients with GBM, and in the Cancer Genome Atlas data set. RESULTS: Patients who had high risk scores according to the 5-microRNA signature had poor overall survival and progression-free survival compared with patients who had low risk scores. Multivariate Cox analysis indicated that the 5-microRNA signature was an independent prognostic biomarker after adjusting for other clinicopathologic and genetic factors, such as extent of resection, temozolomide chemotherapy, preoperative Karnofsky performance status score, isocitrate dehydrogenase 1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. CONCLUSIONS: The 5-microRNA signature was identified as an independent risk predictor that identified patients who had a high risk of unfavorable outcome, demonstrating its potential for personalizing cancer management. The authors concluded that this signature should be evaluated in further prospective studies. © 2012 American Cancer Society. Source


Li F.F.,Harbin Medical University
Journal of molecular neuroscience : MN | Year: 2012

Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant disorder characterized by periodic attacks of muscle weakness associated with a decrease in the serum potassium level. Several mutations in the skeletal muscle calcium channel α-subunit gene CACNA1S have been documented to be causative for HypoPP, but mutations in other genes have also been implicated in HypoPP. To further reveal the genetic causes of HypoPP, we genotyped members of a five-generational Chinese family with HypoPP patients and identified a novel His916Gln mutation in all male HypoPP patients of the family. Clinical analysis demonstrated that the penetrance of the mutation was complete in male carriers, but we did not find evident clinical features in female carriers. This study expanded the spectrum of CACNA1S mutations associated with HypoPP and demonstrated a gender difference in the penetrance of the disease. Source


Liu H.,Stanford University | Liu S.,Stanford University | Miao Z.,Stanford University | Deng Z.,Wuhan University | And 3 more authors.
Journal of Medicinal Chemistry | Year: 2013

Melanoma is an aggressive skin cancer with worldwide increasing incidence. Development of positron emission tomography (PET) probes for early detection of melanoma is critical for improving the survival rate of melanoma patients. In this research, 18F-picolinamide-based PET probes were prepared by direct radiofluorination of the bromopicolinamide precursors using no-carrier-added 18F-fluoride. The resulting probes, 18F-1, 18F-2 and 18F-3, were then evaluated in vivo by small animal PET imaging and biodistribution studies in C57BL/6 mice bearing B16F10 murine melanoma tumors. Noninvasive small animal PET studies demonstrated excellent tumor imaging contrasts for all probes, while 18F-2 showed higher tumor to muscle ratios than 18F-1 and 18F-3. Furthermore, 18F-2 demonstrated good in vivo stability as evidenced by the low bone uptake in biodistribution studies. Collectively, these findings suggest 18F-2 as a highly promising PET probe for translation into clinical detection of melanoma. © 2013 American Chemical Society. Source


Chen Y.G.,Harbin Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2011

To evaluate the differences in oncologic outcomes between inflammatory adhesion and malignant adhesion in patients with stage IIC colorectal cancer after multivisceral resection(MVR). A retrospective review was undertaken of 287 patients who underwent MVR for stage IIC CRC, 120 patients for stage IIB, and 140 patients for IIIA. Patients were divided into two groups: inflammatory adhesion(IA) and malignant invasion(MI). There were 153 patients with colon cancer and 135 patients with rectal cancer in the stage IIC group. The overall survival was significantly lower in the MI group at 5 years(38.5% vs. 59.4%, P<0.05). Stage IIC patients with IA had similar survival rate to the patients with stage IIB CRC. Compared to the MA group, patients with stage IIIA CRC showed significant differences in 5 years overall survival rate. Univariate analysis showed that differentiation, adhesion pattern, and complication were significant prognostic factors for patients with colon cancer, while pathological characteristics, adhesion pattern, and differentiation were significant for rectal cancer. MI is an adverse prognostic factor for patients with stage IIC CRC. T4 should be further classified according to the adhesion pattern. Source


Ding J.,Harbin Institute of Technology | Cheng H.,Harbin Institute of Technology | Cheng H.,Utah State University | Ning C.,Harbin Medical University | And 2 more authors.
Journal of Ultrasound in Medicine | Year: 2011

Objectives-The purpose of this study was to evaluate color thyroid elastograms quantitatively and objectively and select more effective features to differentiate benign from malignant thyroid nodules. Methods-The study was approved by the Ethics Committee of Harbin Medical University. A total of 125 cases (56 malignant and 69 benign) were analyzed in this retrospective study. The original color thyroid elastograms were transferred from the red-green-blue color space to the hue-saturation-value color space. The elasticity information was represented by the hue component of color elastograms. The lesion regions were delineated by radiologists, and statistical and textural features were extracted. Then the most effective and reliable features among them were selected by using a minimum redundancy-maximum relevance algorithm. The selected features were input to a support vector machine to differentiate benign from malignant thyroid nodules. Results-The classification accuracy was 93.6% when the hard area ratio and textural feature (energy) of the lesion region were used. The area under the receiver operating characteristic curve for the hard area ratio was higher than that for the strain ratio (0.97 versus 0.87; P< .01), and the area under the curve for the hard area ratio was also higher than that for the color score (0.97 versus 0.80; P < .001). The results also showed that the features were robust for lesion region delineation. Conclusions-The hard area ratio is an important and quantitative metric for elastograms. Quantitative analysis of elastograms using computer-aided diagnostic techniques can improve diagnostic accuracy. © 2011 by the American Institute of Ultrasound in Medicine. Source


Wang C.,Harbin Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2011

To study the incentives of laryngeal cancer in Heilongjiang province. A 1:One matched case control study was used to study the risk factors of laryngeal cancer in Heilongjiang province, distributing all tested staff by the same gender, age, urban and rural. Logistic regression models were used to analysis the relationship. In single Logistic regression models, such habit as high levels of education, frequently consumption of sauerkraut, BBQ food, processed meats, the less physical activity, a relatively short time, smoking, irascible, and other factors would increase the risk of suffering from laryngeal cancer. But regular consumption of fresh vegetables, coarse grains, eggs, milk, and regular physical activity would reduce the risk of suffering from laryngeal cancer. The odds ratios (OR) were calculated using multiple Logistic regression models, ORs for the highest versus the lowest quintile of intake were 15.502 0 for high levels of education. 8.012 0 for smoking frequently. 7. 2680 for eating sauerkraut. 2.904 0 for eating BBQ food. 0.408 0 for exercise in protective factors. Potential risk factors for laryngeal cancer were eating sauerkraut. BBQ food and smoking frequently, but proper exercise may reduce the risk of laryngeal cancer. Source


Kim M.H.,Dong - A University | Jin E.,Harbin Medical University | Zhang H.-Z.,Dong - A University | Kim S.-W.,Dong - A University
International Journal of Cardiology | Year: 2013

Background: Recently, we showed the angio-vasculogenic potential of uncultured human peripheral blood (hPB)-derived CD31+ cells. However, thus far, the angiogenic property of the cultured hPB-derived CD31+ (C-31+) cells is unknown. Thus, this study aimed to assess the angiogenic potency of C-31+ cells on experimental ischemia. Methods: CD31+ and CD31- cells were isolated by magnetic bead separation technique, and cultured in EBM-2 complete medium for 6 days. The expression of multiple angiogenic genes in these cells was measured using qRT-PCR. In addition, endothelial progenitor cell culture and matrigel network formation assays were performed. A mouse model of hindlimb ischemia induced by surgical resection of the right femoral artery was used, and the C-31 + cells were intramuscularly transplanted into the ischemic area. Immunohistochemical analysis was also performed. Results: C-31+ cells exclusively showed higher colony-forming activity, and gave rise to EPCs. C-31+ cells also induced higher endothelial network formation, and exhibited higher pro-angiogenic and lower inflammatory gene expression. In our ischemic hindlimb model, transplantation of C-31+ cells induced increased blood perfusion (0.652±0.03 vs. 0.47±0.04; P<0.01) and increased capillary density (85±5.5 vs. 57±4.1; P<0.01) as compared to C-31- cells. In addition, angiogenic factors were markedly upregulated after the transplantation of C-31+ cells, indicating that C-31+ cells contributed to the neovascularization. Conclusions: The high angiogenic and therapeutic potential of C-31+ cells observed in our ischemic animal model suggests a novel role of hPB-derived cultured CD31+ cells in the treatment of ischemic cardiovascular diseases. © 2011 Elsevier Ireland Ltd. All rights reserved. Source


Yang L.,New York Medical College | Yang L.,Harbin Medical University | Edvinsson J.,New York Medical College | Palmer L.G.,New York Medical College
Journal of General Physiology | Year: 2012

We investigated the effects of changing extracellular K+ concentrations on block of the weak inward-rectifier K+ channel Kir1.1b (ROMK2) by the three intracellular cations Mg2+, Na+, and TEA+. Single-channel currents were monitored in inside-out patches made from Xenopus laevis oocytes expressing the channels. With 110 mM K+ in the inside (cytoplasmic) solution and 11 mM K+ in the outside (extracellular) solution, these three cations blocked K+ currents with a range of apparent affinities (Ki (0) = 1.6 mM for Mg2+, 160 mM for Na+, and 1.8 mM for TEA+) but with similar voltage dependence (zδ = 0.58 for Mg2+, 0.71 for Na+, and 0.61 for TEA+) despite having different valences. When external K+ was increased to 110 mM, the apparent affinity of all three blockers was decreased approximately threefold with no significant change in the voltage dependence of block. The possibility that the transmembrane cavity is the site of block was explored by making mutations at the N152 residue, a position previously shown to affect rectification in Kir channels. N152D increased the affinity for block by Mg2+ but not for Na+ or TEA+. In contrast, the N152Y mutation increased the affinity for block by TEA+ but not for Na+ or Mg2+. Replacing the C terminus of the channel with that of the strong inward-rectifier Kir2.1 increased the affinity of block by Mg2+ but had a small effect on that by Na+. TEA+ block was enhanced and had a larger voltage dependence. We used an eight-state kinetic model to simulate these results. The effects of voltage and external K+ could be explained by a model in which the blockers occupy a site, presumably in the transmembrane cavity, at a position that is largely unaffected by changes in the electric field. The effects of voltage and extracellular K+ are explained by shifts in the occupancy of sites within the selectivity filter by K+ ions. © 2012 Yang et al. Source


Zhao W.,Harbin Medical University
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology | Year: 2010

To investigate the expression changes and regulation of pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA in corpus luteum during pregnancy. Pregnant rats' ovaries were collected at different time points. The techniques of RT-PCR and in situ hybridization were used to observe expression changes of PACAP mRNA in rat ovaries during pregnancy. To further explore the regulation mechanism of PACAP mRNA expression in corpus luteum, luteal cells were cultured in vitro. Immature (25 - 28 days old) female Sprague-Dawley rats were injected subcutaneously with 50IU pregnant mare serum gonadotrophin (PMSG), and 25IU human chorionic gonadotrophin (hCG) 48 h later, to induce follicular development and luteum formation. On day 6 after hCG administration (the day of hCG administration was the first day), the rats were killed by guillotine and the ovarian luteal cells were collected. After incubation for 24 h, luteal cells were administration with various factors for 24 h. And then expression changes of PACAP mRNA in luteal cells after administration with different factors were detected by RT-PCR, and radioimmunoassay was used to analyze progesterone levels. With the development of pregnancy, the expression of PACAP mRNA increased gradually, reached the peak at pregnancy 19 d, and then decreased. Compared with control group, platelet activating factor (PAF), forskolin and PMA could obviously stimulate PACAP mRNA expression in luteal cells which were cultured with corresponding factors for 24 h. At the same time, progesterone levels in culture media were also elevated. PACAP, acting as a local ovary regulator, was closely related to the maintenance of medium-term and late pregnancy. PAF could directly stimulate PACAP mRNA expression in luteal cells, and protein kinase C (PKC) and protein kinase A (PKA) signal pathways could both participate in this process. Source


Pan S.,Peking University | Pan S.,Harbin Medical University | Dong Q.,Peking University | Sun L.-S.,Peking University | Li T.-J.,Peking University
Clinical Cancer Research | Year: 2010

Purpose: PTCH1 has been identified as the gene responsible for nevoid basal cell carcinoma syndrome (NBCCS). Keratocystic odontogenic tumors (KCOT) are aggressive jaw lesions that may occur in isolation or in association with NBCCS. The aim of this study was to investigate the genetic and/or epigenetic mechanisms of inactivation of the PTCH1 gene in patients with NBCCS and related sporadic KCOTs. Experimental Design: Loss of heterozygosity was analyzed in 44 patients (15 NBCCS-related and 29 sporadic KCOTs), all of whom were previously analyzed for PTCH1 mutations. Allelic location was established in tumors carrying two coincident mutations. PTCH1 mRNA expression and promoter methylation status were analyzed in a panel of KCOTs to define the possible role of epigenetic effects on PTCH1 inactivation. Results: Although mutations and loss of heterozygosity of PTCH1 were frequently detected in both syndromic and nonsyndromic cases, hypermethylation of the PTCH1 promoter was not identified in the present series. Of all the 44 cases examined, 13 were identified to fit the two-hit model, 14 to conform to a one-hit model, and the remaining 17 cases showing no alteration in PTCH1. The distribution of twohit, one-hit, and non-hit cases was significantly different between syndrome and nonsyndrome patients (P < 0.02). Conclusions: This study indicates that PTCH1 gene alternation may play a significant role in the pathogenesis of NBCCS and the related sporadic tumors. Not only the standard two-hit model, but also haploinsufficiency or dominant-negative isoforms may be implicated in the inactivation of the PTCH1 gene. ©2010 AACR. Source


Cai Z.,Texas A&M University | Cai Z.,Guangdong Medical College | Zhao Y.,Harbin Medical University | Zhao B.,Guangdong Medical College
Current Alzheimer Research | Year: 2012

Evidence from basic molecular biology has noted a critical role of GSK-3 in Alzheimer's disease (AD) pathogenesis such as beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangle (NFT), and neuronal degeneration. Aβ generation and deposition represents a key feature and is generated from APP by the sequential actions of two proteolytic enzymes: β-secretase and γ-secretase. GSK-3 could play a critical role in Aβ production via enhancing β-secretase activity. GSK-3 not only modulates APP processing in the process of Aβ generation, but regulates Aβ production by interfering with APP cleavage at the γ-secretase complex step since the APP and PS1 (a component of γ- secretase complex) are substrates of GSK-3 as well. GSK-3 may downregulate α-secretase through inhibiting PKC and ADAMs activity which are the substrates of GSK-3 contributing to Aβ production. Meanwhile, Aβ accumulation can induce GSK-3 activation through Aβ-mediated neuroinflammation and oxidative stress. Considering that active GSK-3 and some common GSK-3-shared factors induce the hyperphosphorylation of tau and neurofibrillary lesions, GSK-3 is a possible linking between amyloid plaques and NFT pathology. Additionally, GSK-3 could disrupt acetylcholine activity, and accelerate axon degeneration and failures in axonal transport, and lead to cognitive impairment in AD. Preclinical and clinical studies have supported that GSK-3β inhibitors could be useful in the treatment of AD. Consequently, an effective measure to inhibit GSK-3 activity may be a very attractive drug target in AD. © 2012 Bentham Science Publishers. Source


Tian M.J.,Harbin Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2013

Study the effects of β-glucan in highland barley on blood glucose and serum lipid in high fat diet induced C57 mouse. Using table of random number, 40 male C57BL/6 mice were randomly divided into 4 groups (10 mice in each group) by weight: high dosage group (4% β-glucan and high fat diet), low dosage group (2% β-glucan and high fat diet), high fat diet group and normal control group. Food-intake and body weight of C57 mouse were observed. Glucose tolerance tests and examinations of fasting blood glucose were performed at the end of 11 weeks of intervention. Mice were sacrificed after 12 wk of treatment, and serum specimens were obtained to test relevant biochemical indicators. After 12 weeks raise, among high dosage group, low dosage group, high fat diet group and normal control group, the weight was (32.8 ± 1.5), (40.4 ± 1.9), (40.7 ± 2.1) and (33.5 ± 1.3) g, respectively (F = 55.26, P < 0.05); average food intake was (3.48 ± 0.56), (3.69 ± 0.76), (3.66 ± 0.81) and (3.54 ± 0.61) g/d respectively (F = 0.26, P > 0.05); fasting blood-glucose was (5.29 ± 1.59), (6.13 ± 1.75), (7.63 ± 1.09) and (4.24 ± 0.98) mmol/L respectively (F = 9.54, P < 0.01); serum insulin level was (1.97 ± 0.10), (2.44 ± 0.24), (3.02 ± 0.36) and (1.48 ± 0.28) ng/ml respectively (F = 47.58, P < 0.01); the area under blood glucose concentration curve was (25.81 ± 1.44), (30.42 ± 2.01), (35.17 ± 1.20) and (21.03 ± 1.24) mmol×L(-1)×h(-1), respectively (F = 64.98, P < 0.05); insulin resistance index was (9.84 ± 3.78), (13.69 ± 4.48), (21.54 ± 3.27) and (5.81 ± 1.59) respectively (F = 30.18, P < 0.01); serum total cholesterol (TC) level was (4.05 ± 0.88), (4.30 ± 0.48), (4.73 ± 0.66) and (3.37 ± 0.40) mmol/L respectively (F = 6.70, P < 0.01); serum triglyceride (TG) level was (0.90 ± 0.09), (0.98 ± 0.09), (1.05 ± 0.06) and (0.76 ± 0.26) mmol/L respectively (F = 6.75, P < 0.01); serum high-density lipoprotein cholesterol (HDL-C) level was (2.91 ± 0.59), (3.34 ± 0.46), (4.89 ± 0.42) and (3.24 ± 0.37) mmol/L respectively (F = 31.73, P < 0.01); serum low-density lipoprotein cholesterol (LDL-C) level was (0.25 ± 0.15), (0.42 ± 0.19), (0.72 ± 0.12) and (0.32 ± 0.11) mmol/L, respectively (F = 17.27, P < 0.01); free fatty acids (FFA) level was (1.06 ± 0.03), (1.05 ± 0.05), (1.18 ± 0.32) and (1.04 ± 0.02) mmol/L, respectively (F = 1.36, P > 0.05); HDL-C/LDL-C was (13.77 ± 5.51), (9.11 ± 3.53), (7.04 ± 1.65) and (11.21 ± 3.31), respectively (F = 5.24, P < 0.01). The β-glucan in highland barley reduced the serum glucose and serum lipid, as well as insulin resistance and the risk of arterial sclerosis in high-fat induced C57 mouse. Source


Hu D.,Peking University | Liu L.,Chinese Academy of Sciences | Li W.,Harbin Medical University
Advances in Therapy | Year: 2014

Introduction: Single-pill combination (SPC) therapy of two drugs is recommended by international guidelines, including the Chinese guidelines (2010), for the treatment of hypertension in high-risk patients who require marked blood pressure (BP) reductions. Real-world data on the efficacy and safety of valsartan/amlodipine (Val/Aml) SPC are scarce. The present study is the first observational study in China to evaluate the efficacy (primary endpoint) and safety of Val/Aml (80/5 mg) SPC in Chinese patients with hypertension whose BP was not adequately controlled by monotherapy in a real-world setting. Methods: This prospective, multicenter, open-label, post-marketing observational study included 11,422 Chinese adults (≥18 years) with essential hypertension from 238 sites of 29 provinces who were prescribed once-daily Val/Aml (80/5 mg) SPC. Patients were treated for 8 weeks. The primary efficacy variable of the study included changes in mean sitting systolic BP (MSSBP) and mean diastolic BP (MSDBP) from baseline to week 8 (end point). The secondary efficacy variable of the study included BP control rate and response rate at week 4 and 8. Safety assessments included recording and measurement of all adverse events (AEs) and vital signs in the safety population. Results: A significant reduction of 27.1 mmHg in MSSBP (159.6 vs. 132.5 mmHg; P < 0.0001) and 15.2 mmHg in MSDBP (95.6 vs. 80.4 mmHg; P < 0.0001) from baseline was observed at week 8. The BP-lowering efficacy of Val/Aml SPC was independent of age and comorbidities. BP control of <140/90 mmHg was achieved in 76.8% (n = 8,692) of the patients. The most frequently reported AEs were dizziness (0.2%), headache (0.2%), upper respiratory tract infection (0.2%), and edema (0.2%). Only three serious AEs were reported and they were not drug-related. Conclusion: This is the first evidence-based real-world data in Chinese hypertensive patients which demonstrate the efficacy and safety of Val/Aml (80/5 mg) SPC. © 2014 The Author(s). Source


Yang M.-M.,Chinese University of Hong Kong | Yang M.-M.,Harbin Medical University | Lai T.Y.Y.,Chinese University of Hong Kong | Luk F.O.J.,Chinese University of Hong Kong | Pang C.-P.,Chinese University of Hong Kong
Retina | Year: 2014

Background: Uveitis is a diverse group of intraocular inflammatory disease and is a significant cause of visual loss worldwide. Recent studies have identified various endogenous immune mechanisms and genetic factors that are involved in the pathogenesis of uveitis. This review provides an overview on the role of genetics in the development and clinical course of uveitis. Methods: PUBMED was used for literature search, and articles published from 1970 to 2012 that evaluated the genetic associations and mechanisms involved in the development and clinical features of uveitis were included. Results: Studies have demonstrated associations between various genetic factors and the development and clinical course of intraocular inflammatory conditions. Genes involved included genes expressing interleukins, chemokines, chemokine receptors, and tumor necrosis factor and genes involved in complement system, oxidation, and other intracellular molecular pathways. Conclusion: Multiple genetic factors play important roles in the pathogenesis of uveitis and may influence the clinical course of uveitis. Further studies to investigate the genetic mechanisms of uveitis might identify additional genetic associations and might have the potential for identifying novel therapeutic targets in the treatment of intraocular inflammation. Copyright © 2014 by Ophthalmic Communications Society, Inc. Source


Xia Y.,Harbin Medical University | Zhang B.,Shanxi Institute of Coal CAS Chemistry | Wang Y.,Harbin Institute of Technology | Qian M.,Harbin Institute of Technology | Geng L.,Harbin Institute of Technology
Materials Science and Engineering C | Year: 2012

In this paper, the in-vitro cytotoxicity and the in-vivo compatibility of Mg-4.0Zn-0.2Ca alloy are studied. The cytotoxicity of Mg-4.0Zn-0.2Ca alloy is examined by MTT method on osteoblast cells. The in-vivo behavior of Mg-4.0Zn-0.2Ca alloy is investigated on rabbits. It has been found that Mg-4.0Zn-0.2Ca alloy extract has no cytotoxicity on osteoblast cells. Three months after in-vivo experiment, about 35-38% magnesium alloy implant has been degraded and a degradation layer which is composed of Ca, P, O and Mg has been formed on the magnesium alloy implants. Histological analysis showed that new bone is observed around magnesium implant without inflammation reaction. In-vitro and in-vivo test indicated that the Mg-4.0Zn-0.2Ca alloy has good biocompatibility. © 2012 Elsevier B.V. All rights reserved. Source


Liu M.-L.,Jinan University | Duan Y.-H.,Jinan University | Hou Y.-L.,Harbin Medical University | Li C.,Shenyang Pharmaceutical University | And 4 more authors.
Organic Letters | Year: 2013

Nardoaristolones A and B, two novel terpenoids derived from the aristolane-type sesquiterpenoid, were isolated from the underground parts of Nardostachys chinensis Batal. Nardoaristolone A is the first reported aristolane-chalcone derivative, while nardoaristolone B possesses a nor-aristolane sesquiterpenoid skeleton with an unusual 3/5/6 tricyclic ring system. Their structures were elucidated by spectroscopic measurements, and the absolute configurations were established by single-crystal X-ray diffraction experiments. © 2013 American Chemical Society. Source


Yue H.Y.,Sungkyunkwan University | Yue H.Y.,Harbin University of Science and Technology | Huang S.,Harbin Medical University | Chang J.,Sungkyunkwan University | And 12 more authors.
ACS Nano | Year: 2014

We report that vertically aligned ZnO nanowire arrays (ZnO NWAs) were fabricated on 3D graphene foam (GF) and used to selectively detect uric acid (UA), dopamine (DA), and ascorbic acid (AA) by a differential pulse voltammetry method. The optimized ZnO NWA/GF electrode provided a high surface area and high selectivity with a detection limit of 1 nM for UA and DA. The high selectivity in the oxidation potential was explained by the gap difference between the lowest unoccupied and highest occupied molecular orbitals of a biomolecule for a set of given electrodes. This method was further used to detect UA levels in the serum of patients with Parkinson's disease (PD). The UA level was 25% lower in PD patients than in healthy individuals. This finding strongly implies that UA can be used as a biomarker for PD. © 2014 American Chemical Society. Source


Goldstein I.J.,University of Groningen | Van Veldhuisen D.J.,University of Groningen | Bank R.A.,Harbin Medical University | De Boer R.A.,University of Michigan | De Boer R.A.,University of Groningen
Circulation: Heart Failure | Year: 2013

Background-Galectin-3 has been implicated in the development of organ fibrosis. It is unknown whether it is a relevant therapeutic target in cardiac remodeling and heart failure. Methods and Results-Galectin-3 knock-out and wild-type mice were subjected to angiotensin II infusion (2.5 μg/kg for 14 days) or transverse aortic constriction for 28 days to provoke cardiac remodeling. The efficacy of the galectin-3 inhibitor N-acetyllactosamine was evaluated in TGR(mREN2)27 (REN2) rats and in wild-type mice with the aim of reversing established cardiac remodeling after transverse aortic constriction. In wild-type mice, angiotensin II and transverse aortic constriction perturbations caused left-ventricular (LV) hypertrophy, decreased fractional shortening, and increased LV end-diastolic pressure and fibrosis (P<0.05 versus control wild type). Galectin-3 knock-out mice also developed LV hypertrophy but without LV dysfunction and fibrosis (P=NS). In REN2 rats, pharmacological inhibition of galectin-3 attenuated LV dysfunction and fibrosis. To elucidate the beneficial effects of galectin-3 inhibition on myocardial fibrogenesis, cultured fibroblasts were treated with galectin-3 in the absence or presence of galectin-3 inhibitor. Inhibition of galectin-3 was associated with a downregulation in collagen production (collagen I and III), collagen processing, cleavage, cross-linking, and deposition. Similar results were observed in REN2 rats. Inhibition of galectin-3 also attenuated the progression of cardiac remodeling in a long-term transverse aortic constriction mouse model. Conclusions-Genetic disruption and pharmacological inhibition of galectin-3 attenuates cardiac fibrosis, LV dysfunction, and subsequent heart failure development. Drugs binding to galectin-3 may be potential therapeutic candidates for the prevention or reversal of heart failure with extensive fibrosis. © 2013 American Heart Association, Inc. Source


Wang D.,Shenyang Pharmaceutical University | Tang J.,Harbin Medical University | Wang Y.,Shenyang Pharmaceutical University | Ramishetti S.,University of North Carolina at Chapel Hill | And 3 more authors.
Molecular Pharmaceutics | Year: 2013

Multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Tocopheryl polyethylene glycol 1000 succinate (TPGS) has been extensively explored for the treatment of MDR in cancer because of its ability to inhibit P-glycoprotein. Here, we have established multifunctional nanoparticles (MFNPs) using a single-molecule modification of TPGS, which can deliver a hydrophobic drug, paclitaxel (PTX), and a hydrophilic drug, fluorouracil (5-FU), and overcome MDR in cancer. Our data indicated that, when delivered into a PTX-resistant cell line using MFNPs, the combination of PTX and 5-FU was more cytotoxic than each agent individually. © 2013 American Chemical Society. Source


Liu W.,Harbin Medical University | Moussawi M.,University of Vermont | Roberts B.,University of Vermont | Boyson J.E.,University of Vermont | Huber S.A.,University of Vermont
American Journal of Pathology | Year: 2013

Coxsackievirus B3 (CVB3) variants H3 and H310A1 differ by a single nonconserved amino acid in the VP2 capsid region. C57Bl/6 mice infected with the H3 virus develop myocarditis correlating with activation of T cells expressing the Vγ4 T cell receptor chain. Infecting mice with H310A1 activates natural killer T (NKT; mCD1d-tetramer+ TCRβ+) cells, but not Vγ4 T cells, and fails to induce myocarditis. H310A1 infection preferentially activates M2 alternatively activated macrophage and CD4 +FoxP3 (T regulatory) cells, whereas CD4+Th1 (IFN-γ+) cells are suppressed. By contrast, H3 virus infection activates M1 proinflammatory and CD4+Th1 cells, but not T regulatory cells. The M1 macrophage show significantly increased CD1d expression compared to M2 macrophage. The ability of NKT cells to suppress myocarditis was shown by adoptive transfer of purified NKT cells into H3-infected NKT knockout (Jα18 knockout) mice, which inhibited cardiac inflammation and increased T regulatory cell response. Cardiac virus titers were equivalent in all mouse strains indicating that neither Vγ4 nor NKT cells participate in control of virus infection. These data show that NKT and Vγ4 cells cross-regulate T regulatory cell responses during CVB3 infections and are the primary factor determining viral pathogenesis in this mouse model. © 2013 American Society for Investigative Pathology. Source


Jia S.S.,Harbin Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2010

To evaluate the feasibility of routine inclusion of levels II and III in neck dissection to treat the occult neck metastasis as elective treatment for supraglottic cancer with clinically node negative (cN0). The results of 52 cN0 patients with supraglottic cancer treated in Tumor Hospital, Harbin Medical University from October 2002 to March 2006 were reviewed retrospectively. Of the 52 patients with supraglottic cancer and cN0 neck, 32 cases received ipsilateral SND (levels II and III) and 20 cases with bilateral SND (levels II and III). Fifteen (28.9%) of 52 patients were found to have occult regional metastasis on pathological examination. Three patients without metastasis in dissected side at pathologic examination showed metastasis in the contralateral undissected neck later on therefore the total occult metastasis rate was 34.6% (18 of 52). The unilateral and bilateral neck occult metastases were determined in 15 cases (28.9%) and 3 cases (5.8%) respectively. A total of 1190 lymph nodes were harvested in 72 specimens, with 30 positive nodes. The distributions of the 30 positive nodes were as follows: level IIA 83.3% (25 nodes), level III 16.7% (5 nodes). Three-year regional recurrence rate was 5.8%. The 3-year survival rate was 84.6% according to Kaplan-Meier in all cN0 patients (n = 52). Patients with positive neck metastasis and patients with extracapsular spread had higher regional recurrence rates (P = 0.021 and 0.002, respectively). The results support the use of SND (levels II and III) in cN0 supraglottic cancer. This procedure will reduce both operating time and morbidity, without compromising the oncologic result. Source


Wang X.,Harbin Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2010

To detect the expression and distribution of surfactant A (SP-A) in nasal polyps and to probe into its significance in the pathology of nasal polyps. Immunohistochemical staining and RT-PCR (reverse transcription polymerase chain reaction) were explored to detect SP-A in nasal polyps and controls. In nasal polyp tissues, SP-A expressed not only in the cytoplasm of the epithelium but also in the cytoplasm of the plasma cells. Moreover it expressed in the serous glands but not in the mucous glands. The expression of SP-A was distributed in the same location of turbinates. But the expression of SP-A between nasal polyps and turbinates differed significantly (P < 0.05). SP-A mRNA was detected in the nasal polyps and controls. The expression potency ratio of SP-A/beta-actin in nasal polyps was stronger than in turbinates (P < 0.05). Both nasal polyps and nasal mucosa expressed SP-A mRNA and protein, but the expression was stronger in nasal polyps. The role of SP-A in the innate immunity may contribute to the pathogenesis of nasal polyps. SP-A may become the new target in the therapy of chronic rhinosinusitis. Source


Matta B.M.,University of Pittsburgh | Lott J.M.,University of Pittsburgh | Mathews L.R.,University of Pittsburgh | Liu Q.,University of Pittsburgh | And 4 more authors.
Journal of Immunology | Year: 2014

IL-33 is a recently characterized IL-1 family member that is proposed to function as an alarmin, or endogenous signal of cellular damage, as well as act as a pleiotropic cytokine. The ability of IL-33 to potentiate both Th1 and Th2 immunity supports its role in pathogen clearance and disease immunopathology. Yet, IL-33 restrains experimental colitis and transplant rejection by expanding regulatory T cells (Treg) via an undefined mechanism. We sought to determine the influence of IL-33 on hematopoietic cells that drives Treg expansion and underlies the therapeutic benefit of IL-33 administration. In this study, we identify a feedback loop in which conventional mouse CD11c+ dendritic cells (DC) stimulated by IL-33 secrete IL-2 to selectively expand IL-33R(ST2+)-suppressive CD4+Foxp3+ Treg. Interestingly, this occurs in the absence of classical DC maturation, and DC-derived (innate) IL-2 increases ST2 expression on both DC and interacting Treg. ST2+ Treg represent an activated subset of Foxp3+ cells, demonstrated to be ICOShighCD44high compared with their ST2- counterparts. Furthermore, although studies have shown that IL-33-exposed DC promote Th2 responses, we reveal that ST2+ DC are required for IL-33-mediated in vitro and in vivo Treg expansion. Thus, we have uncovered a relationship between IL-33 and innate IL-2 that promotes the selective expansion of ST2+ Treg over non-Treg. These findings identify a novel regulatory pathway driven by IL-33 in immune cells that may be harnessed for therapeutic benefit or for robust expansion of Treg in vitro and in vivo. Copyright © 2014 by The American Association of Immunologists, Inc. Source


Gu X.,Guangdong Medical College | Yao L.,Guangdong Medical College | Ma G.,Guangdong Medical College | Cui L.,Guangdong Medical College | And 4 more authors.
Neuro-Oncology | Year: 2014

BackgroundThe translationally controlled tumor protein (TCTP) is a multifunctional protein that plays important roles in immune responses, cell proliferation, tumorigenicity and cell apoptosis. Here, we examined the clinical value of TCTP in glioma patient survival and investigated the functional roles and mechanism of TCTP in glioma development.MethodsTCTP expression was determined through immunohistochemical staining, immunoblotting, and quantitative real-time PCR (qRT-PCR). TCTP or TCF-4 expression was silenced using short hairpin (sh) RNA. In vitro cell proliferation was detected using MTT, BrdU and colony formation assays, and in vivo tumor growth was performed using the xenograft model. TCTP/TCF-4/β-catenin association was detected using a co-immunoprecipitation (co-IP) assay. TCF-4 transcription activity was detected using a TOPflash/FOPflash report gene assay. Wnt/β-catenin- targeted gene expression was detected through Western blotting.ResultsTCTP protein levels were significantly elevated in high-grade gliomas compared with low-grade gliomas and normal brain tissues. Importantly, the expression of TCTP was significantly associated with poorer overall survival and disease-free survival, and TCTP also reduced the survival rate after treatment with radiotherapy and temozolomide (RT-TMZ) for glioma patients. The ectopic expression of TCTP enhanced glioma cell proliferation both in vitro and in vivo, whereas the knockdown of TCTP inhibited this effect. Similarly, the overexpression of TCTP increased β-catenin binding to TCF-4, TOPflash report gene transcription activity, and the expression of Wnt/β-catenin signaling target genes including c-Myc and cyclin D1; notably, the knockdown of TCTP reduced these effects. The knockdown of TCF-4 using shRNA rescued the enhanced cell proliferation induced by the overexpression of TCTP.ConclusionTCTP is associated with reduced survival of glioma patients and induces glioma tumor growth through enhanced Wnt/β-catenin signaling. © 2013 © The Author(s) 2013. Source


Moguillansky D.,University of Pittsburgh | Leng X.,Harbin Medical University | Carson A.,University of Pittsburgh | Lavery L.,University of Pittsburgh | And 3 more authors.
European Heart Journal | Year: 2011

Aims The density of vasa vasorum within atherosclerotic plaque correlates with histologic features of plaque vulnerability in post-mortem studies. Imaging methods to non-invasively detect vasa vasorum are limited. We hypothesized that contrast ultrasound (CUS) can quantify vasa vasorum during atherosclerosis progression. Methods and results New Zealand white rabbits received a high-fat diet for 3 weeks, and bilateral femoral artery stenosis was induced by balloon injury. Contrast ultrasound femoral imaging was performed at baseline and 2, 4, and 6 weeks post injury to quantify adventitial videointensity. At each imaging time point 10 vessels were sectioned and stained with haematoxylin and eosin and von-Willebrand factor. Adventitial vasa vasorum density was quantified by counting the number of stained microvessels and their total cross-sectional area. Plaque size (per cent lumen area) progressed over time (P < 0.001), as did adventitial vasa vasorum density (P < 0.001). Plateau peak videointensity also progressed, demonstrating a strong linear correlation with histologic vasa vasorum density (P < 0.001). Receiver operating characteristic analysis indicated that a three-fold increase in median adventitial videointensity had a sensitivity of 100 and specificity of 88 for predicting abnormal neovascularization. Conclusion We have histologically validated that CUS quantifies the development of adventitial vasa vasorum associated with atherosclerosis progression. This imaging technique has the potential for characterizing prognostically significant plaque features. © 2010 The Author. Source


Wang Z.D.,Harbin Medical University
Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji | Year: 2011

In this study, we generated embryonic stem cells from parthenogenetic embryos (PESCs), and induced them to differentiate to motor neurons, which could be an alternative source of histocompatible cells for replacement of therapy and theoretical foundation for studying the relationship of genome imprint and neural differentiation. The parthenogenetic activation rate of B6D2F1 mouse oocytes was 93.26%. We established eight parthenogenetic embryonic stem cell lines and the establishment rate from parthenogenetic embryos was 23.53%. The pluripotency marker Oct4, the cell surface marker SSEA-1, and alkaline phosphatase exhibited in PESCs. Karyotype analysis showed normal 40 chromosomes when examined at passages 10 and 30, which was in accordance with their oocyte origins. Three germinal layers were differentiated in vivo and in vitro. Mouse PESCs, which were treated by tretinoin and sonic hedgehog with extracellular matrix, could generate motor neurons that expressed the specific markers such as HB9 and Olig2. Source


Li B.-Y.,Indiana University - Purdue University Indianapolis | Li B.-Y.,Harbin Medical University | Glazebrook P.,Case Western Reserve University | Kunze D.L.,Case Western Reserve University | Schild J.H.,Indiana University - Purdue University Indianapolis
American Journal of Physiology - Cell Physiology | Year: 2011

High conductance calcium-activated potassium (BKCa) channels can modulate cell excitability and neurotransmitter release at synaptic and afferent terminals. BKCa channels are present in primary afferents of most, if not, all internal organs and are an intriguing target for pharmacological manipulation of visceral sensation. Our laboratory has a long-standing interest in the neurophysiological differences between myelinated and unmyelinated visceral afferent function. Here, we seek to determine whether there is a differential distribution of BKCa channels in myelinated and unmyelinated vagal afferents. Immunocytochemistry studies with double staining for the BK-type KCa1.1 channel protein and isolectin B4 (IB4), a reliable marker of unmyelinated peripheral afferents, reveal a pattern of IB4 labeling that strongly correlates with the expression of the KCa1.1 channel protein. Measures of cell size and immunostaining intensity for KCa1.1 and IB4 cluster into two statistically distinct (P < 0.05) populations of cells. Smaller diameter neurons most often presented with strong IB4 labeling and are presumed to be unmyelinated (n = 1,390) vagal afferents. Larger diameter neurons most often lacked or exhibited a very weak IB4 labeling and are presumed to be myelinated (n = 58) vagal afferents. Complimentary electrophysiological studies reveal that the BKCa channel blockers charybdotoxin (ChTX) and iberiotoxin (IbTX) bring about a comparable elevation in excitability and action potential widening in unmyelinated neurons but had no effect on the excitability of myelinated vagal afferents. This study is the first to demonstrate using combined immunohistochemical and electrophysiological techniques that KCa1.1 channels are uniquely expressed in unmyelinated C-type vagal afferents and do not contribute to the dynamic discharge characteristics of myelinated A-type vagal afferents. This unique functional distribution of BK-type KCa channels may provide an opportunity for afferent selective pharmacological intervention across a wide range of visceral pathophysiologies, particularly those with a reflexogenic etiology and pain. © 2011 the American Physiological Society. Source


Zhang Z.-Y.,Heilongjiang University | Zhang Z.-Y.,Harbin Medical University | Deng Z.-P.,Heilongjiang University | Huo L.-H.,Heilongjiang University | And 2 more authors.
Inorganic Chemistry | Year: 2013

In this Article, self-assembly of AgX (X = NO3 - and ClO4 -) salts and four flexible unsymmetrical bis(pyridyl) ligands, namely, N-(pyridin-2-ylmethyl)pyridin-3-amine (L1), N-(pyridin-3-ylmethyl)pyridin-2-amine (L2), N-(pyridin-4-ylmethyl)pyridin-2- amine (L3), and N-(pyridin-4-ylmethyl)pyridin-3-amine (L4), results in the formation of eight helical silver(I) coordination polymers, [Ag(L)(NO 3)]n [L = L1 (1), L2 (2), L3 (3), L4 (4)] and [Ag(L)(ClO4)]n [L = L1 (5), L2 (6), L3 (7), L4 (8)], which have been characterized by elemental analysis, IR, TG, PL, and powder and single-crystal X-ray diffraction. The alternating one-dimensional (1-D) left- and right-handed helical chains are included in achiral complexes 1-3 and 5-8. By contrast, the ligand L4 only alternately bridges Ag(I) cation to form the 1-D right-handed helical chain in complex 4. The pitches of these helical chains locate in the range 5.694(5)-17.016(6) Å. Meanwhile, the present four unsymmetrical bis(pyridyl) ligands in the eight complexes present diverse cis-trans and trans-trans conformation and facilitate the construction of helical structures. Moreover, the solid-state luminescent emission intensities of the perchlorate-containing complexes are stronger than those of nitrate-containing complexes at room temperature. © 2013 American Chemical Society. Source


Sun X.,Harbin Medical University
Wei sheng yan jiu = Journal of hygiene research | Year: 2010

To investigate the relationship between Alzheimer' s disease(AD) and insulin resistance and blood lipids. Serum samples collected from 45 AD patients and 44 healthy controls were analyzed by automatic biochemical analyzer to detect the levels of blood glucose, insulin, blood lipids. The variables were evaluated statistically by SPSS 11.0. Serum total cholesterol (TC), insulin (INS), insulin sensitivity index (IAI) and body mass index (BMI) from AD patients were significantly higher than those from health controls (P < 0.05), whereas the insulin resistance index (IR) and insulin secretion index (IS) from AD patients were significantly lower than those from healthy controls (P < 0.05). The abnormality of blood lipids and insulin might have potentially harmful effects on central nervous system, of which especially the neurotoxic effect on amyloid (Abeta) neurotoxicity and tau protein phosphorylation might result in memory impairment. These suggested that high blood lipids and insulin resistance were probable risk factors of Alzheimer's disease. Source


Yamamoto M.,Hokkaido University | Hosoda M.,Hokkaido University | Nakano K.,Hokkaido University | Jia S.,Hokkaido University | And 6 more authors.
Cancer Science | Year: 2014

Aromatase inhibitors have played a central role in endocrine therapy for estrogen receptor (ER)-positive breast cancer in postmenopausal women. However, factors predictive of the efficacy of aromatase inhibitors, and prognostic factors, both for early and late recurrence in women treated with adjuvant aromatase inhibitors have not been identified. Whole genome analysis identified that a TP53 gene mutation exists in ER-positive breast cancers, although the frequency of TP53 gene mutation in luminal tumors is lower compared with basal-like or human epidermal growth factor receptor type 2 (HER2)-positive breast cancers. We examined expression of p53, as well as ER, progesterone receptor, HER2 and Ki-67 using immunohistochemistry in postmenopausal ER-positive breast cancer patients who were treated with aromatase inhibitors as adjuvant endocrine therapy. There were 53 (21%) tumors that contained 10% or more p53-positive cells. High p53 expression was positively correlated with tumor grade, HER2 score and Ki-67 expression. Significant association was observed between disease-free survival and high p53 expression in multivariate analysis (P < 0.0001). Compared with women without recurrence, women with early recurrence had significantly higher p53 expression (P < 0.0001), as did women with late recurrence (P = 0.037). The present study demonstrates that p53 accumulation is a strong predictor of both early and late recurrence in ER-positive breast cancer patients treated with aromatase inhibitors as adjuvant endocrine therapy. TP53 gene alteration might be a key biological characteristic of ER-positive breast cancer. © 2013 The Authors. Source


Li J.,Harbin Medical University
Canadian journal of physiology and pharmacology | Year: 2013

Geraniin has previously been reported to possess extensive biological activity. In this study, we reported that geraniin is an inhibitor of tumor activity in vitro and in vivo. Geraniin suppressed the proliferation of A549 cells in a dose- and time-dependent manner. Geraniin arrested the cell cycle in the S phase and induced a significant accumulation of reactive oxygen species (ROS), as well as an increased percentage of cells with mitochondrial membrane potential (MMP) disruption. Western blot analysis showed that geraniin inhibited Bcl-2 expression and induced Bax expression to disintegrate the outer mitochondrial membrane and cause cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascades. Additionally, geraniin resulted in tumor growth inhibition in A549 xenografts. Our results indicate cytotoxic activity of geraniin towards cancer cells in vitro and in vivo. Source


Li Y.,Harbin Medical University | Guo L.,Dong - A University | Ahn H.S.,Ilsin Christian Hospital | Kim M.H.,Dong - A University | And 2 more authors.
Journal of Cellular and Molecular Medicine | Year: 2014

Recently, we reported that human amniotic membrane-derived mesenchymal stem cells (AMMs) possess great angiogenic potential. In this study, we determined whether local injection of AMMs ameliorates peripheral neuropathy. AMMs were transplanted into injured sciatic nerves. AMM injection promoted significant recovery of motor nerve conduction velocity and voltage amplitude compared to human adipose-derived mesenchymal stem cells. AMM implantation also augmented blood perfusion and increased intraneural vascularity. Whole-mount fluorescent imaging analysis demonstrated that AMMs exhibited higher engraftment and endothelial incorporation abilities in the sciatic nerve. In addition, the higher expression of pro-angiogenic factors was detected in AMMs injected into the peripheral nerve. Therefore, these data provide novel therapeutic and mechanistic insights into stem cell biology, and AMM transplantation may represent an alternative therapeutic option for treating peripheral neuropathy. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. Source


Yan W.,Capital Medical University | Zhang W.,Capital Medical University | You G.,Capital Medical University | Zhang J.,Nanjing Medical University | And 8 more authors.
Neuro-Oncology | Year: 2012

Defining glioma subtypes based on objective genetic and molecular signatures may allow for a more rational, patient-specific approach to molecularly targeted therapy. However, prior studies attempting to classify glioma subtypes have given conflicting results. We aim to complement and validate the existing molecular classification system on a large number of samples from an East Asian population. A total of 225 samples from Chinese patients was selected for whole genome gene expression profiling. Consensus clustering was applied. Three major groups of gliomas were identified (referred to as G1, G2, and G3). The G1 subgroup correlates with a good clinical outcome, young age, and extremely high frequency of IDH1 mutations. Relative to the G1 subgroup, the G3 subgroup is correlated with a poorer clinical outcome, older age, and a very low rate of mutations in the IDH1 gene. Correlations of the G2 subgroup with respect to clinical outcome, age, and IDH1 mutation fall between the G1 and G3 subgroups. In addition, the G2 subtype was associated with a higher percentage of loss of 1p/19q when compared with G1 and G3 subtypes. Furthermore, our classification scheme was validated on 2 independent datasets derived from the cancer genome atlas (TCGA) and Rembrandt. With use of the TCGA classification system, proneural, neural, and mesenchymal, but not classical subtype, associated gene signatures were clearly defined. In summary, our results reveal that 3 main subtypes stably exist in Chinese patients with glioma. Our classification scheme may reflect the clinical and genetic alterations more clearly. Classical subtype-associated gene signature was not found in our dataset. © 2012 The Author(s). Source


Chen G.,Peking Union Medical College | Pan S.-Q.,Harbin Medical University | Shen C.,Peking Union Medical College | Pan S.-F.,Capital Medical University | And 2 more authors.
Acta Pharmacologica Sinica | Year: 2014

Aim: To investigate the effects of puerarin (Pue), an isoflavone derived from Kudzu roots, on angiotensin II (Ang II)-induced hypertrophy of cardiomyocytes in vivo and in vitro.Methods:C57BL/6J mice were infused with Ang II and treated with Pue (100 mg·kg -1·d -1, po) for 15 d. After the treatment, systolic blood pressure (SBP) and left ventricular wall thickness were assessed. The ratios of heart weight to body weight (HW/BW) and left ventricular weight to body weight (LVW/BW) were determined, and heart morphometry was assessed. Expression of fetal-type genes (ANP, BNP and β-MHC) in left ventricles was measured using semi-quantitative RT-PCR. Mouse primary cardiomyocytes were treated with Pue (50, 100, 200 μmol/L), then exposed to Ang II (1 μmol/L). ROS level was examined with flow cytometry, the binding activity of NF-κB was determined using EMSA. Western blot was used to measure the levels of ERK1/2, p38 and NF-κB pathway proteins. [ 3 H]leucine incorporation was used to measure the rate of protein synthesis. Results: Oral administration of Pue significantly suppressed Ang II-induced increases in the myocyte surface area, HW/BW, LVW/BW, SBP and left ventricular wall thickness. Furthermore, Pue significantly suppressed Ang II-induced increases in ANP, BNP and β-MHC expression in the left ventricles in vivo. Treatment of cardiomyocytes with Pue (50-500 μmol/L) did not affect the viability of cardiomyocytes in vitro. Pretreatment of cardiomyocytes with Pue dose-dependently inhibited Ang II-induced increases in ROS production, NF-κB binding activity, protein synthesis and cell breadth. Furthermore, pretreatment with Pue significantly suppressed Ang II-induced activation of ERK1/2, p38 and the NF-κB pathway proteins and the expression of ANP and β-MHC in cardiomyocytes. The positive drug valsartan exerted similar effects on Ang II-induced cardiac hypertrophy in vivo and in vitro. Conclusion: Pue attenuates Ang II-induced cardiac hypertrophy by inhibiting activation of the redox-sensitive ERK1/2, p38 and the NF-κB pathways. © 2014 CPS and SIMM. Source


Kao Y.C.J.,University of North Carolina at Chapel Hill | Li W.,University of North Carolina at Chapel Hill | Li W.,Harbin Medical University | Lai H.-Y.,University of North Carolina at Chapel Hill | And 3 more authors.
Neurobiology of Disease | Year: 2014

Cortical spreading depolarization (CSD) is known to exacerbate ischemic damage, as the number of CSDs correlates with the final infarct volumes and suppressing CSDs improves functional outcomes. To investigate the role of CSD in ischemic damage, we developed a novel rat model of photothrombotic ischemia using a miniature implantable optic fiber that allows lesion induction inside the magnetic resonance imaging (MRI) scanner. We were able to precisely control the location and the size of the ischemic lesion, and continuously monitor dynamic perfusion and diffusion MRI signal changes at high temporal resolution before, during and after the onset of focal ischemia. Our model showed that apparent diffusion coefficient (ADC) and cerebral blood flow (CBF) in the ischemic core dropped immediately after lesion onset by 20. ±. 6 and 41. ±. 23%, respectively, and continually declined over the next 5. h. Meanwhile, CSDs were observed in all animals (n. =. 36) and displayed either a transient decrease of ADC by 17. ±. 3% or an increase of CBF by 104. ±. 15%. All CSDs were initiated from the rim of the ischemic core, propagated outward, and confined to the ipsilesional cortex. Additionally, we demonstrated that by controlling the size of perfusion-diffusion mismatch (which approximates the penumbra) in our model, the number of CSDs correlated with the mismatch area rather than the final infarct volume. This study introduces a novel platform to study CSDs in real-time with high reproducibility using MRI. © 2014 Elsevier Inc. Source


Xia Y.H.,Harbin Medical University | Zhang B.P.,Shanxi Institute of Coal CAS Chemistry | Lu C.X.,Shanxi Institute of Coal CAS Chemistry | Geng L.,Harbin Institute of Technology
Materials Science and Engineering C | Year: 2013

In this paper, corrosion resistance of the Mg-4.0Zn-0.2Ca alloy was modified by micro-arc oxidation (MAO) process. The microstructure and phase constituents of MAO layer were characterized by SEM, XRD and X-ray photoelectron spectroscopy (XPS). The corrosion resistance of MAO treated Mg-4.0Zn-0.2Ca alloy in the simulated body fluid were characterized by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The microstructure results indicated that a kind of ceramic film was composed byMgO and MgF2 was formed on the surface of Mg-4.0Zn-0.2Ca alloy after MAO treatment. The electrochemical test reveals that the corrosion resistance ofMAO treated samples increase 1 order of magnitude. Themechanical intensity test showed that the MAO treated samples has suitable mechanical properties. © 2013 Elsevier B.V. All rights reserved. Source


Sun Y.,Harbin Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2013

To express and purify the human papillomavirus type 16 (HPV16) E2 protein in prokaryotic bacteria and prepare the antiserum of HPV16 E2. After amplified by PCR, HPV16 E2 was inserted into pET21b vector. The recombinant pET21b-HPV16E2 vector was transfected into E.coli BL21 (DE3). Expression product was identified after induction. Through purification, denaturation and renaturation, soluble protein was obtained. With the HPV16 E2 protein, we immunized BALB/c mice and examined mouse IFN-γ, CD4(+); T cells, CD8(+); T cells, CD4/CD8 ratio and antiserum titer. Restriction digestion and DNA sequencing showed pET21b-HPV16E2 was constructed successfully. Relative molecular mass (Mr;) of HPV16 E2 was 42 000 in SDS-PAGE and the specificity of the protein was confirmed with Western blotting. The antiserum could specifically bind with HPV16 E2 protein. In the immunized BALB/c mice, antiserum titre, CD4(+); T cell count and CD4/CD8 ratio increased, while mouse IFN-γ did not change obviously. Soluble HPV16 E2 protein was obtained successfully. The antiserum of high titer against HPV16 E2 was prepared in mice. Source


Sun W.,Baylor College of Medicine | Sun W.,Harbin Medical University | Yang J.,Baylor College of Medicine
Cellular Signalling | Year: 2010

PKC, β-arrestin 2, CARMA3, BCL10, MALT1, TRAF6 and MEKK3 are signaling proteins that have a key role in G protein-coupled receptor (GPCR)-mediated activation of nuclear factor-κB (NF-κB) pathway in nonhematopoietic cells in response to lysophosphatidic acid (LPA) stimulation. The PKC, β-arrestin 2, CARMA3-BCL10-MALT1-TRAF6 signalosome, and MEKK3 functions as a link between GPCR signaling and IKK-NF-κB activation. Here we briefly summarize recent progress in the understanding of the molecular and biological functions of these proteins in GPCR-mediated NF-κB activation in nonhematopoietic cells. © 2010 Elsevier Inc. Source


Wang C.,Jiangsu Diabetes Research Center | Wang C.,Nanjing University | Bian Z.,Jiangsu Diabetes Research Center | Wei D.,Jiangsu Cancer Hospital | Zhang J.-G.,Harbin Medical University
Molecular and Cellular Biochemistry | Year: 2011

microRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by targeting mRNAs, inhibiting the expression of the associated proteins. Although a role for aberrant miRNA expression in cancer has been postulated, the pathophysiologic role and relevance of aberrantly expressed miRNAs in tumor biology has not been established. We evaluated the expression pattern of miRNAs in human breast cancer cells by qPCR, finding out an up-regulated miRNA miR-29b and studying its biological effect by migration assay. We defined a target gene PTEN by bioinformatics approach and western blot. In breast cancer cell line MDA-MB-231 cell, which migrate faster than MCF-7, we observed that miR-29b was highly over-expressed. Inhibition of miR-29b in cultured cells increased the expression of the phosphatase and tensin homolog (PTEN) tumor suppressor, promoting apoptosis, decreasing migration, and decreasing invasion. In contrast, enhanced miR-29b expression by transfection with pre-miR-29b decreased the expression of PTEN and impaired apoptosis, increasing tumor cell migration and invasion. Moreover, PTEN was shown to be a direct target of miR-29b and was also shown to contribute to the miR-29b-mediated effects on cell invasion. Modulation of miR-29b altered the role of PTEN involved in cell migration and invasion. Aberrant expression of miR-29b, which modulates PTEN expression, can contribute to migration, invasion, and anti-apoptosis. © 2011 Springer Science+Business Media, LLC. Source


Sun X.,University of Auckland | Sun X.,Harbin Medical University | Jiang R.,University of Auckland | Przepiorski A.,University of Auckland | And 3 more authors.
BMC Cancer | Year: 2012

Background: Tamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers.Methods: In a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5 mg/Kg) were fed an Fe-Lf supplemented diet (5 g/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon γ (IFN-γ) were analyzed.Results: Tamoxifen weakly (IC50 ~ 8 μM) inhibited the proliferation of 4T1 cells at pharmacological concentrations in vitro. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all P < 0.001), respectively, compared to untreated controls. The combination therapy was significantly (all P < 0.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-γ, and intestinal cells expressing IL-18 and IFN-γ. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors.Conclusions: The results indicate that Fe-Lf is a potent natural adjuvant capable of augmenting the chemotherapeutic activity of tamoxifen. It could have application in delaying relapse in tamoxifen-treated breast cancer patients who are at risk of developing ER-negative tumors. © 2012 Sun et al.; licensee BioMed Central Ltd. Source


Ma H.-P.,Jining No. 1 Peoples Hospital | Li W.,Jining No. 1 Peoples Hospital | Liu X.-M.,Harbin Medical University
Experimental and Therapeutic Medicine | Year: 2014

Previous studies have revealed the role of matrix metalloproteinase 9 (MMP9) in asthma and chronic obstructive pulmonary disease (COPD). However, its role in airway inflammation in cough variant asthma (CVA) remains unknown. In the present study, variations in the levels of MMP9 and interleukin (IL)-5 in the induced sputum of patients with CVA prior to and following therapy with inhaled corticosteroid and long-acting β2-agonist (ICS/LABA), were detected. The levels of IL-5 and percentage of eosinophils (EOS) in the induced sputum from patients with CVA were significantly higher than those in the control group of healthy individuals. The levels of MMP9 in the induced sputum from patients with CVA were also significantly higher than those in the control group. Following treatment with ICS/LABA for 6-9 months, the levels of MMP9 and IL-5, as well as the percentage of EOS, in the induced sputum from patients with CVA had significantly decreased. Thus, MMP9 may be an important biomarker in the airway inflammation of CVA. Source


Guo X.M.,Harbin Institute of Technology | Guo B.,Harbin Institute of Technology | Zhang Q.,Harbin Medical University | Sun X.,Harbin Institute of Technology
Dalton Transactions | Year: 2011

In this paper, the structural and zeta potential properties of 10-hydroxycamptothecin (HCPT) were investigated by FT-IR and zeta potential analyzer under different pH. The anticancer drug HCPT as a model drug was used to prepare a high-performance and relatively easy-to-fabricate system on Fe 3O4 magnetite nanoparticles by using a polystyrene sulfonate (PSS) and HCPT interlayer self-assembly method. The results obtained from FT-IR and XRD confirmed that HCPT was molecularly dispersed into the nanoparticles. The method holds not only environment-friendly characteristics and the ability to mimic the self-organization process in biological systems but also greatly decreases adjuvant polymers. In addition, the system has an ideal drug payload for the delivery of insoluble HCPTs. © The Royal Society of Chemistry 2011. Source


Feng P.,University of Sichuan | Zhou X.-H.,Harbin Medical University | Zhou X.-H.,University of Washington | Zhou X.-H.,Peking University | And 3 more authors.
Statistics in Medicine | Year: 2012

The propensity score method is widely used in clinical studies to estimate the effect of a treatment with two levels on patient's outcomes. However, due to the complexity of many diseases, an effective treatment often involves multiple components. For example, in the practice of Traditional Chinese Medicine (TCM), an effective treatment may include multiple components, e.g. Chinese herbs, acupuncture, and massage therapy. In clinical trials involving TCM, patients could be randomly assigned to either the treatment or control group, but they or their doctors may make different choices about which treatment component to use. As a result, treatment components are not randomly assigned. Rosenbaum and Rubin proposed the propensity score method for binary treatments, and Imbens extended their work to multiple treatments. These authors defined the generalized propensity score as the conditional probability of receiving a particular level of the treatment given the pre-treatment variables. In the present work, we adopted this approach and developed a statistical methodology based on the generalized propensity score in order to estimate treatment effects in the case of multiple treatments. Two methods were discussed and compared: propensity score regression adjustment and propensity score weighting. We used these methods to assess the relative effectiveness of individual treatments in the multiple-treatment IMPACT clinical trial. The results reveal that both methods perform well when the sample size is moderate or large. © 2011 John Wiley & Sons, Ltd. Source


Wang X.,Texas A&M University | Wang S.,Texas A&M University | Li C.,Texas A&M University | Li C.,Harbin Medical University | And 12 more authors.
PLoS Genetics | Year: 2012

Family with sequence similarity 20,-member C (FAM20C) is highly expressed in the mineralized tissues of mammals. Genetic studies showed that the loss-of-function mutations in FAM20C were associated with human lethal osteosclerotic bone dysplasia (Raine Syndrome), implying an inhibitory role of this molecule in bone formation. However, in vitro gain- and loss-of-function studies suggested that FAM20C promotes the differentiation and mineralization of mouse mesenchymal cells and odontoblasts. Recently, we generated Fam20c conditional knockout (cKO) mice in which Fam20c was globally inactivated (by crossbreeding with Sox2-Cre mice) or inactivated specifically in the mineralized tissues (by crossbreeding with 3.6 kb Col 1a1-Cre mice). Fam20c transgenic mice were also generated and crossbred with Fam20c cKO mice to introduce the transgene in the knockout background. In vitro gain- and loss-of-function were examined by adding recombinant FAM20C to MC3T3-E1 cells and by lentiviral shRNA-mediated knockdown of FAM20C in human and mouse osteogenic cell lines. Surprisingly, both the global and mineralized tissue-specific cKO mice developed hypophosphatemic rickets (but not osteosclerosis), along with a significant downregulation of osteoblast differentiation markers and a dramatic elevation of fibroblast growth factor 23 (FGF23) in the serum and bone. The mice expressing the Fam20c transgene in the wild-type background showed no abnormalities, while the expression of the Fam20c transgene fully rescued the skeletal defects in the cKO mice. Recombinant FAM20C promoted the differentiation and mineralization of MC3T3-E1 cells. Knockdown of FAM20C led to a remarkable downregulation of DMP1, along with a significant upregulation of FGF23 in both human and mouse osteogenic cell lines. These results indicate that FAM20C is a bone formation "promoter" but not an "inhibitor" in mouse osteogenesis. We conclude that FAM20C may regulate osteogenesis through its direct role in facilitating osteoblast differentiation and its systemic regulation of phosphate homeostasis via the mediation of FGF23. © 2012 Wang et al. Source


Ni X.,Harbin Medical University | Ni X.,University of Illinois at Chicago | Zhang W.,University of Illinois at Chicago | Huang R.S.,University of Chicago
Wiley Interdisciplinary Reviews: Systems Biology and Medicine | Year: 2013

Clinical response to therapeutic treatments often varies among individual patients, ranging from beneficial effect to even fatal adverse reaction. Pharmacogenomics holds the promise of personalized medicine through elucidating genetic determinants responsible for pharmacological outcomes (e.g., cytotoxicities to anticancer drugs) and therefore guide the prescription decision prior to drug treatment. Besides traditional candidate gene-based approaches, technical advances have begun to allow application of whole-genome approaches to pharmacogenomic discovery. In particular, comprehensive understanding of human genetic variation provides the basis for applying GWAS (genome-wide association studies) in pharmacogenomic research to identify genomic loci associated with pharmacological phenotypes (e.g., individual dose requirement for warfarin). We therefore briefly reviewed the background for pharmacogenetic/pharmacogenomic research with statins and warfarin as examples for the GWAS discovery and their clinical implementation. In conclusion, with some challenges, whole-genome approaches such as GWAS have allowed unprecedented progress in identifying genetic variants associated with pharmacological phenotypes, as well as provided foundation for the next wave of pharmacogenomic discovery utilizing sequencing-based approaches. Furthermore, investigation of the complex interactions among genetic and epigenetic factors on the whole-genome scale will become the post-GWAS research focus for pharmacologic complex traits. © 2012 Wiley Periodicals, Inc. Source


Zuo Y.-C.,Inner Mongolia University | Peng Y.,Inner Mongolia University of Technology | Liu L.,Inner Mongolia University of Technology | Chen W.,Hebei United University | And 2 more authors.
Analytical Biochemistry | Year: 2014

Peroxidases as universal enzymes are essential for the regulation of reactive oxygen species levels and play major roles in both disease prevention and human pathologies. Automated prediction of functional protein localization is rarely reported and also is important for designing new drugs and drug targets. In this study, we first propose a support vector machine (SVM)-based method to predict peroxidase subcellular localization. Various Chou' pseudo amino acid descriptors and gene ontology (GO)-homology patterns were selected as input features to multiclass SVM. Prediction results showed that the smoothed PSSM encoding pattern performed better than the other approaches. The best overall prediction accuracy was 87.0% in a jackknife test using a PSSM profile of pattern with width = 5. We also demonstrate that the present GO annotation is far from complete or deep enough for annotating proteins with a specific function. © 2014 Elsevier Inc. All rights reserved. Source


OBJECTIVES: In this study, we identified the protein kinases that play the most distinct roles in the occurrence of acute pancreatitis (AP).METHODS: Gene expression profile data were downloaded from Gene Expression Omnibus database (GSE3644). The sample was from caerulein-induced AP mice. The intersection of the differentially expressed genes in AP mice taken from a protein kinase database was obtained for screening of the protein kinase encoded genes that were differentially expressed. Database for annotation, visualization, and integrated discovery was used for the functional enrichment analysis. Kinase inhibitors that regulated these kinases were retrieved from PubMed through text mining.RESULTS: Twenty-nine differentially expressed kinase encoded genes were identified through screening. The functional enrichment analysis demonstrated that the functions of these genes were primarily enriched in “mitogen-activated protein kinase signaling pathway,” followed by “extracellular regulated protein kinases pathway,” “neurotrophin signaling pathway,” “adherens junction,” and “gap junction.” SRC and epidermal growth factor receptor (EGFR) were related to extracellular regulated protein kinases pathway and also related to adherens junction as well as gap junction. On the basis of the regulated kinases, the kinase inhibitors reported in the literature were classified into multiple groups.CONCLUSIONS: EGFR and SRC may be coexpressed in AP. The kinase inhibitors working together in SRC and EGFR may play better efficacy in the treatment of AP. © 2014 by Lippincott Williams & Wilkins. Source


Zhao J.,Peking Union Medical College | Ellwein L.B.,U.S. National Institutes of Health | Cui H.,Harbin Medical University | Ge J.,Sun Yat Sen University | And 7 more authors.
Ophthalmology | Year: 2010

Purpose: Describe the prevalence of visual impairment/blindness among older adults in rural populations in China. Design: Population-based, cross-sectional study. Participants: We evaluated 45 747 adults ≥50 years of age. Methods: Geographically defined cluster sampling was used in randomly selecting a cross-section of residents from a representative rural county within each of 9 provinces in mainland China. Participants were enumerated through village registers followed by door-to-door household visits. Eligible persons were invited to local examination sites for visual acuity (VA) testing and eye examination. Main Outcome Measures: Presenting and best-corrected distance VA. Results: Of 50 395 enumerated eligible persons, 45 747 (90.8%) were examined and tested for VA. The prevalence of presenting visual impairment <20/63 to ≥20/400 in the better eye was 10.8% and blindness (<20/400) was 2.29%. Across the 9 provinces, presenting visual impairment ranged from 6.89% to 15.8%, and blindness from 1.27% to 5.40%. With best-corrected VA, the prevalence of visual impairment was 5.30%, and 1.93% for blindness. The ranges across the 9 provinces were 3.13% to 9.51% for visual impairment and 0.74% to 4.95% for blindness. Visual impairment and blindness were associated with older age, female gender, lack of education, and geographic area (province) with both presenting and best-corrected VA. Conclusions: Visual impairment and blindness are important public health problems in rural China, with significant regional variations in prevalence. Blindness prevention programs targeting the rural elderly should be expanded, particularly in areas with limited access and affordability of eye care services. Special emphasis should be given to reaching women and those without education. Greater attention should also be given to correction of refractive error. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. © 2010 American Academy of Ophthalmology. Source


Wang L.,Harbin Medical University | Wang L.,New York Medical College | Zhang C.,New York Medical College | Zhang C.,Xuzhou Medical College | And 3 more authors.
Journal of the American Society of Nephrology | Year: 2015

Kcnj10 encodes the inwardly rectifying K+ channel Kir4.1 in the basolateral membrane of the distal convoluted tubule (DCT) and is activated by c-Src. However, the regulation and function of this K+ channel are incompletely characterized. Here, patch-clamp experiments in Kcnj10-transfected HEK293 cells demonstrated that c-Src-induced stimulation of Kcnj10 requires coexpression of caveolin-1 (cav-1), and immunostainingshowed expression of cav-1 in the basolateralmembrane of parvalbumin-positive DCT. Patch-clamp experiments detected a 40-pS inwardly rectifying K+ channel, a heterotetramer of Kir4.1/Kir5.1, in the basolateral membrane of the early DCT (DCT1) in both wild-type (WT) and cav-1- knockout (KO) mice. However, the activity of this basolateral 40-pS K+ channel was lower in KO mice than inWTmice.Moreover, the K+ reversal potential (an indication ofmembrane potential) was less negative in the DCT1 of KO mice than in the DCT1 of WT mice. Western blot analysis demonstrated that cav-1 deficiency decreased the expression of the Na+/Cl- cotransporter and Ste20-proline-alanine-rich kinase (SPAK) but increased the expression of epithelial Na+ channel-α. Furthermore, the urinary excretion of Mg2+ and K+ was significantly higher in KO mice than in WT mice, and KO mice developed hypomagnesemia, hypocalcemia, and hypokalemia. We conclude that disruption of cav-1 decreases basolateral K+ channel activity and depolarizes the cell membrane potential in the DCT1 at least in part by suppressing the stimulatory effect of c-Src on Kcnj10. Furthermore, the decrease in Kcnj10 and Na+/Cl- cotransporter expression induced by cav-1 deficiency may underlie the compromised renal transport of Mg2+, Ca2+, and K+. Copyright © 2015 by the American Society of Nephrology. Source


Ma L.,Jilin University | Cai Y.-J.,Jilin University | Yu L.,Harbin Medical University | Feng J.-Y.,Jilin University | And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013

Chronic infection with hepatitis B virus (HBV) is associated with impairment of T and NK cell immunity. This study was aimed at investigating the impact of treatment with telbivudine (LDT) on T and NK cell immunity in patients with chronic hepatitis B (CHB). A total of 54 CHB patients and 30 healthy controls (HC) were recruited. Individual patients were treated orally with 600 mg LDT daily for 13 months. The serum HBV DNA loads, the levels of the HBV-related biomarkers alanine aminotransferase (ALT) and aspartate transaminase (AST), and the numbers of different subsets of peripheral T and NK cells in subjects were measured before and longitudinally after LDT treatment. Following treatment with LDT, the serum HBV DNA loads and the percentages of HBsAg- or HBeAg-seropositive cases were gradually reduced, accompanied by decreased levels of serum ALT and AST. In comparison with the HC, fewer CD3- CD56+ and CD244+ NK cells and CD3+ CD8 + T cells, lower frequencies of cytokine + CD4+ T cells, and more CD3+ CD4+, CD4+ CD25 + Foxp3+, CD4+ CD25+ CD127 low, and CD8+ PD-1+ T cells were detected in CHB patients. Treatment with LDT increased the numbers of NK and CD8+ cells and the frequencies of cytokine+ CD4+ T cells but reduced the numbers of CD4+ CD25+ Foxp3+, CD4+ CD25+ CD127low, and CD8+ PD-1+ T cells in CHB patients. The frequencies of cytokine + CD4+ T cells were negatively associated with the levels of serum HBV DNA, ALT, and AST. Thus, treatment with LDT inhibits HBV replication, modulates T and NK cell immunity, and improves liver function in Chinese patients with CHB. Copyright © 2013, American Society for Microbiology. Source


Hurvitz S.A.,University of California at Los Angeles | Andre F.,University Paris - Sud | Jiang Z.,Beijing 307 Hospital of PLA | Shao Z.,Fudan University | And 16 more authors.
The Lancet Oncology | Year: 2015

Background: mTOR inhibition reverses trastuzumab resistance via the hyperactivated PIK/AKT/mTOR pathway due to PTEN loss, by sensitising PTEN-deficient tumours to trastuzumab. The BOLERO-1 study assessed the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer. Methods: In this phase 3, randomised, double-blind trial, patients were enrolled across 141 sites in 28 countries. Eligible patients were aged 18 years or older, with locally assessed HER2-positive advanced breast cancer, with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, who had not received previous trastuzumab or chemotherapy for advanced breast cancer within 12 months of randomisation, had measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) or bone lesions in the absence of measurable disease, without previous systemic treatment for advanced disease except endocrine therapy. Patients were randomly assigned (2:1) with an interactive voice and web response system to receive either 10 mg everolimus once a day orally or placebo plus weekly trastuzumab intravenously at 4 mg/kg loading dose on day 1 with subsequent weekly doses of 2 mg/kg of each 4 week cycle plus paclitaxel intravenously at a dose of 80 mg/m2 on days 1, 8, and 15 of each 4 week cycle. Randomisation was stratified according to previous use of trastuzumab and visceral metastasis. Patients and investigators were masked to the assigned treatments. Identity of experimental treatments was concealed by use of everolimus and placebo that were identical in packaging, labelling, appearance, and administration schedule. The two primary objectives were investigator-assessed progression-free survival in the full study population and in the subset of patients with hormone receptor-negative breast cancer at baseline; the latter was added during the course of the study, before unmasking based on new clinical and biological findings from other studies. All efficacy analyses were based on the intention-to-treat population. Enrolment for this trial is closed and results of the final progression-free survival analyses are presented here. This trial is registered with ClinicalTrials.gov, number NCT00876395. Findings: Between Sept 10, 2009, and Dec 16, 2012, 719 patients were randomly assigned to receive everolimus (n=480) or placebo (n=239). Median follow-up was 41·3 months (IQR 35·4-46·6). In the full population, median progression-free survival was 14·95 months (95% CI 14·55-17·91) with everolimus versus 14·49 months (12·29-17·08) with placebo (hazard ratio 0·89, 95% CI 0·73-1·08; p=0·1166). In the HR-negative subpopulation (n=311), median progression-free survival with everolimus was 20·27 months (95% CI 14·95-24·08) versus 13·08 months (10·05-16·56) with placebo (hazard ratio 0·66, 95% CI 0·48-0·91; p=0·0049); however, the protocol-specified significance threshold (p=0·0044) was not crossed. The most common adverse events with everolimus were stomatitis (314 [67%] of 472 patients in the everolimus group vs 77 [32%] of 238 patients in the placebo group), diarrhoea (267 [57%] vs 111 [47%] patients), and alopecia (221 [47%] vs 125 [53%]). The most frequently reported grade 3 or 4 adverse events in the everolimus group versus the placebo group were neutropenia (117 [25%] vs 35 [15%]), stomatitis (59 [13%] vs three [1%]), anaemia (46 [10%] vs six [3%]) and diarrhoea (43 [9%] vs 10 [4%]) On-treatment adverse event-related deaths were reported in 17 (4%) patients in the everolimus group and none in the placebo group. Interpretation: Although progression-free survival was not significantly different between groups in the full analysis population, the 7·2 months prolongation we noted with the addition of everolimus in the HR-negative, HER2-positive population warrants further investigation, even if it did not meet prespecified criteria for significance. The safety profile was generally consistent with what was previously reported in BOLERO-3. Proactive monitoring and early management of adverse events in patients given everolimus and chemotherapy is crucial. Funding: Novartis Pharmaceuticals. © 2015 Elsevier Ltd. Source


Sun D.,Harvard University | Sun D.,Harbin Medical University | Nakao S.,Harvard University | Xie F.,Harvard University | And 3 more authors.
FASEB Journal | Year: 2010

The need remains great for early diagnosis of diseases. The special structure of the eye provides a unique opportunity for noninvasive light-based imaging of fundus vasculature. To detect endothelial injury at the early and reversible stage of adhesion molecule up-regulation, we generated novel imaging agents that target two distinct types of endothelial molecules, a mediator of rolling, P-selectin, and one that mediates firm adhesion, ICAM-1. Interactions of these double-conjugated fluorescent microspheres (MSs) in retinal or choroidal microvasculature were visualized in live animals by scanning laser ophthalmoscopy. The new imaging agents showed significantly higher sensitivity for detection of endothelial injury than singly conjugated MSs (rPSGL-1- or α-ICAM-1-conjugated), both in terms of rolling (P<0.01) and firm adhesion (P<0.01). The rolling flux of α-ICAM-1-conjugated MSs did not differ in EIU animals, whereas double-conjugated MSs showed significantly higher rolling flux (P<0.01), revealing that ICAM-1 in vivo supports rolling, once MS interaction with the endothelium is initiated. Double-conjugated MSs specifically detected firmly adhering leukocytes (P<0.01), allowing in vivo quantification of immune response. Antiinflammatory treatment with dexamethasone led to reduced leukocyte accumulation (P<0.01) as well as MS interaction (P<0.01), which suggests that treatment success and resolution of inflammation is quantitatively reflected with this molecular imaging approach. This work introduces novel imaging agents for noninvasive detection of endothelial injury in vivo. Our approach may be developed further to diagnose human disease at a much earlier stage than currently possible. © FASEB. Source


Wang Y.,Beijing Tiantan Hospital | Li S.,Capital Medical University | Chen L.,Harbin Medical University | You G.,Beijing Tiantan Hospital | And 8 more authors.
Neuro-Oncology | Year: 2012

Glioblastomas (GBMs) containing foci that resemble oligodendroglioma are dened as GBM with oligodendroglioma component (GBMO). However, whether GBMO is a distinct clinicopathological variant of GBM or merely represents a divergent pattern of differentiation remains controversial. We investigated 219 consecutive primary GBMs, of which 40 (18.3) were confirmed as GBMOs. The clinical features and genetic proles of the GBMOs were analyzed and compared with the conventional GBMs. The GBMO group showed more frequent tumor-related seizures (P=. 027), higher frequency of IDH1 mutation (31 vs. <5, P. 015), lower MGMT expression (P=. 016), and longer survival (19.0 vs. 13.2 months; P=. 022). In multivariate Cox regression analyses, presence of an oligodendroglioma component was predictive of longer survival (P=. 001), but the extent of the oligodendroglial component appeared not to be linked to prognosis (P=. 664). The codeletions of 1p/19q, somewhat surprisingly, were infrequent (<5) in both GBMO and conventional GBM. In addition, the response to aggressive therapy differed: the GBMO group had no survival advantage associated with aggressive treatment protocols, whereas a clear treatment effect was observed in the conventional GBM group. Collectively, the clinical behavior and genetic alterations of GBMO thus differs from those of conventional GBM. Presence of an oligodendroglial component may therefore be a useful classification and stratification variable in therapeutic trials of GBMs. © 2012 The Author(s). Source


Zhang Q.-Y.,Liaoning Medical University | Zhang Q.-Y.,Harbin Medical University | Fu J.-H.,Liaoning Medical University | Xue X.-D.,Liaoning Medical University
Experimental and Therapeutic Medicine | Year: 2014

The aim of the present study was to investigate water transport dysfunction in alveolar epithelial type II cells (AECII), which were exposed to hyperoxia, and to investigate the mechanism of pulmonary edema resulting from hyperoxic lung injury. The lung cells of newborn rats were isolated for primary cell culture and divided into control and experimental groups. The control and experimental group cells were placed into a normoxic incubator (oxygen volume fraction, 0.21) or hyperoxic incubator (oxygen volume fraction, 0.9), respectively. Twenty-four, 48 and 72 h after cell attachment, the gene transcription and protein expression levels of aquaporin-1 (AQP1) were detected via quantitative polymerase chain reaction and western blot analysis. Flow cytometry was conducted to detect the volume of the cells in the experimental and control groups. In the present study, it was identified that AQP1 expression and cell volume were greater in the experimental group when compared with the control group. Thus, hyperoxia may disturb the gene expression regulation of AQP1 in AECII, resulting in water transport dysfunction. This may be one of the mechanisms underlying pulmonary edema caused by hyperoxic lung injury. Source


Colorectal cancer is a kind of malignancies with high incidence in the worldwide, that is seriously harmed human health. So far the pathogenesis of the disease is not fully understood, this causing many difficulties to the diagnosis and treatment of the disease, and resulting in the cure rates of disease is not ideal. With the development of molecular genetics and molecular biology, many oncogenes and tumor suppressor genes have been found to be associated with the disease, and this made it is possible to reveal the pathogenesis of colorectal cancer at the molecular level. However, it is a complex and multi-step process from normal colorectal epithelial cells transformed to colorectal cancer cells, and it is the results of polygenic and multifactorial interactions. Now it is thought that the Wnt, TGF-beta, PI3K/Akt, MAPK and p53 signaling pathways are closely associated with pathogenesis of colorectal cancer. Based on the five kinds of signaling pathways as the main line, this article reviewed the roles of different signaling pathways and their related genes in the pathogenesis of colorectal cancer. Source


Li C.,Northeast Agricultural University | Li Y.,Northeast Agricultural University | Cheng X.,Harbin Medical University | Feng L.,Northeast Agricultural University | And 2 more authors.
Bioresource Technology | Year: 2013

In this study, a unique biofilm consisting of three bacterial strains with high biofilm-forming capability (Bacillus subtilis E2, E3, and N4) and an acetonitrile-degrading bacterium (Rhodococcus rhodochrous BX2) was established for acetonitrile-containing wastewater treatment. The results indicated that this biofilm exhibited strong resistance to acetonitrile loading shock and displayed a typical spatial and structural heterogeneity and completely depleted the initial concentration of acetonitrile (800mgL-1) within 24h in a moving-bed-biofilm reactor (MBBR) after operation for 30days. The immobilization of BX2 cells in the biofilm was confirmed by PCR-DGGE. It has been demonstrated that biofilm-forming bacteria can promote the immobilization of contaminant-degrading bacteria in the biofilms and can subsequently improve the degradation of contaminants in wastewater. This approach offers a novel strategy for enhancing biological oxidation of toxic pollutants in wastewater. © 2012 Elsevier Ltd. Source


To evaluate the effects of valsartan and carnitine on cardiomyocyte Calpain-1 and Bcl-xl expressions of dogs with chronic alcohol intake-induced cardiomyopathy. Dogs were randomly assigned into 4 groups (n = 7 each): (1) alcohol fed (free access to 5%, 1(st) week; 10% 2(nd) week; 500 ml 25% bolus plus free access to 5% from 3 to 24 weeks, A); (2) alcohol + valsartan (5 mg×kg(-1)×d(-1), B); (3) alcohol + carnitine (300 mg×kg(-1)×d(-1), C); (4) Control (D). After six months, all animals were assessed for left ventricular (LV) function by echocardiography. The Bad and Bcl-xl protein expressions were evaluated by immunohistochemistry. The expression of Calpain-1 protein was determined with Western blot. Myocardial morphology was quantified on HE stained slices and under electron microscopy. The terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) was performed for apoptosis analysis. Compared with group D, LVEDD and LVESD were significantly increased while EF and FS significantly decreased in group A. In alcohol fed group, expressions of Bad and Calpain-1 protein were significantly increased while Bcl-xl protein expression was downregulated, all changes could be significantly attenuated by intervention with valsartan and carnitine (all P < 0.05). These data suggest that alcohol could promote cardiac myocyte apoptosis, reduce cardiac function and aggravate myocardial remodeling which valsartan and carnitine could reduce alcoholic cardiomyopathy by downregulating Calpain-1 and Bad protein expression and upregulating expression of Bcl-xl protein. Source


Kanwar J.R.,Deakin University | Sun X.,Harbin Medical University | Sun X.,University of Auckland | Punj V.,University of Southern California | And 5 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2012

The incidence of neurological diseases of unknown etiology is increasing, including well-studied diseases such as Alzhiemer's, Parkinson's, and multiple sclerosis. The blood-brain barrier provides protection for the brain but also hinders the treatment and diagnosis of these neurological diseases, because the drugs must cross the blood-brain barrier to reach the lesions. Thus, attention has turned to developing novel and effective delivery systems that are capable of carrying drug and that provide good bioavailability in the brain. Nanoneurotechnology, particularly application of nanoparticles in drug delivery, has provided promising answers to some of these issues in recent years. Here we review the recent advances in the understanding of several common forms of neurological diseases and particularly the applications of nanoparticles to treat and diagnose them. In addition, we discuss the integration of bioinformatics and modern genomic approaches in the development of nanoparticles. From the Clinical Editor: In this review paper, applications of nanotechnology-based diagnostic methods and therapeutic modalities are discussed addressing a variety of neurological disorders, with special attention to blood-brain barrier delivery methods. These novel nanomedicine approaches are expected to revolutionize several aspects of clinical neurology. © 2012 Elsevier Inc. Source


Lv W.,Harbin University | Yang T.,Harbin Medical University
Clinical Biochemistry | Year: 2012

Objectives: The aim was to investigate the free fatty acid (FFA) metabolic profiles and to identify biomarkers that can be used to distinguish patients with breast cancer (BC) from benign (BE) patients or healthy controls. Design and methods: A total of 114 subjects were divided into the following three groups: BC patients, BE patients and controls. The FFA profiles in three groups were studied by gas chromatography-mass spectrometry coupled with multivariate statistical analysis. Results: Three saturated fatty acids (C14:0, C16:0 and C18:0) and three unsaturated fatty acids (C18:2, C18:3 and C20:5) in BC were significantly different than controls. Palmitic acid, stearic acid, linoleic acid and total FFA were identified as potential biomarkers distinguished BC from the other groups. Conclusion: The alterations of FFA could reflect underlying metabolic changes in BC patients, and this study has demonstrated that FFA biomarkers might be helpful for prevention and characterization of BC patients. © 2011 The Canadian Society of Clinical Chemists. Source


Tang J.,Harbin Medical University | Wang Y.,Shenyang Pharmaceutical University | Wang D.,Shenyang Pharmaceutical University | Wang Y.,University of North Carolina at Chapel Hill | And 3 more authors.
Biomacromolecules | Year: 2013

Multidrug resistance (MDR) is a major barrier to the chemotherapy treatment of many cancers. However, some nonionic surfactants, for example, Brij, have been shown to restore the sensitivity of MDR cells to such drugs. The aim of this study was to explore the reversal effect of Brij on MDR tumor cells and elucidate its potential mechanism. Our data indicate that the structure of Brij surfactants plays an important role in overcoming MDR in cancer, that is, modified hydrophilic-lipophilic balance (MHLB, the ratio of the number (n) of hydrophilic repeating units of ethylene oxide (EO) to the number (m) of carbons in the hydrophobic tail (CH2)). Cell viability of cells treated with paclitaxel (PTX) nanocrystals (NCs) formulated with Brij showed positive correlations with MHLB (R2 = 0.8195); the higher the ratio of Brij to PTX in NCs, the higher cytotoxicity induced by the PTX NCs. Significant increases in intracellular accumulation of 3H-PTX (P-gp substrate) were observed in an MDR cell line (H460/taxR cells) treated with Brij 78 (MHLB = 1.11) and Brij 97 (MHLB = 0.6). After treatments with Brij 78 and Brij 97, the levels of intracellular ATP were decreased and verapamil-induced ATPase activities of P-gp were inhibited in multidrug resistant cells. The responses of the cells to Brij 78 and Brij 97 in ATP depletion studies correlated with the cell viability induced by PTX/Brij NCs and intracellular accumulation of 3H-PTX. Brij 78 and Brij 97 could not alter the levels of P-gp expression detected by Western blotting. These findings may provide some insight into the likelihood of further development of more potent P-gp inhibitors for the treatment of MDR in cancer. © 2013 American Chemical Society. Source


Wang Z.,University of Illinois at Chicago | Wang Z.,Harbin Medical University | Dou X.,University of Illinois at Chicago | Dou X.,Zhejiang Chinese Medical University | And 5 more authors.
Hepatology | Year: 2014

Chronic alcohol consumption leads to hypertriglyceridemia, which is positively associated with alcoholic liver disease (ALD). However, whether and how it contributes to the development of fatty liver and liver injury are largely unknown. In this study we demonstrate that chronic alcohol exposure differently regulates the expression of very-low-density lipoprotein receptor (VLDLR) in adipose tissue and the liver. Whereas adipose tissue VLDLR is significantly down-regulated, its hepatic expression is dramatically increased after chronic alcohol feeding. While HepG2 cells stably overexpressing VLDLR manifests increased intracellular triglyceride accumulation, VLDLR-deficient mice are protective against fatty liver and liver injury after chronic alcohol exposure. Mechanistic investigations using both in vitro and in vivo systems reveal that oxidative stress-induced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation plays a critical role in alcohol-induced VLDLR up-regulation in hepatocytes, but not in adipocytes. Oxidative stress enhances VLDLR gene expression and protein abundance in primary hepatocytes, concomitant with the Nrf2 activation. Conversely, Nrf2 gene silencing abrogates oxidative stress-induced VLDLR up-regulation in the liver, but not in adipose tissue. In mice, alcohol exposure induces hepatic oxidative stress and Nrf2 activation. Supplementation of N-acetylcysteine alleviates fatty liver and liver injury induced by chronic alcohol exposure, which is associated with suppressed Nrf2 activation and attenuated VLDLR increase in the liver. Furthermore, in comparison to wild-type counterparts, Nrf2-deficient mice demonstrate attenuated hepatic VLDLR expression increase in response to chronic alcohol exposure. Conclusion: Chronic alcohol consumption differently alters VLDLR expression in adipose tissue and the liver. Oxidative stress-induced Nrf2 activation is mechanistically involved in VLDLR overexpression in hepatocytes in response to chronic alcohol consumption. Hepatic VLDLR overexpression plays an important role in the pathogenesis of ALD. © 2014 by the American Association for the Study of Liver Diseases. Source


Zhu J.,University of Pittsburgh | Li Y.,University of Pittsburgh | Lu A.,University of Pittsburgh | Gharaibeh B.,University of Pittsburgh | And 5 more authors.
American Journal of Pathology | Year: 2011

Recovery from skeletal muscle injury is often incomplete because of the formation of fibrosis and inadequate myofiber regeneration; therefore, injured muscle could benefit significantly from therapies that both stimulate muscle regeneration and inhibit fibrosis. To this end, we focused on blocking myostatin, a member of the transforming growth factorβ superfamily and a negative regulator of muscle regeneration, with the myostatin antagonist follistatin. In vivo, follistatin-overexpressing transgenic mice underwent significantly greater myofiber regeneration and had less fibrosis formation compared with wild-type mice after skeletal muscle injury. Follistatin's mode of action is likely due to its ability to block myostatin and enhance neovacularization. Furthermore, muscle progenitor cells isolated from follistatin-overexpressing mice were significantly superior to muscle progenitors isolated from wild-type mice at regenerating dystrophin-positive myofibers when transplanted into the skeletal muscle of dystrophic mdx/severe combined immunodeficiency mice. In vitro, follistatin stimulated myoblasts to express MyoD, Myf5, and myogenin, which are myogenic transcription factors that promote myogenic differentiation. Moreover, follistatin's ability to enhance muscle differentiation is at least partially due to its ability to block myostatin, activin A, and transforming growth factorβ1, all of which are negative regulators of muscle cell differentiation. The findings of this study suggest that follistatin is a promising agent for improving skeletal muscle healing after injury and muscle diseases, such as the muscular dystrophies. © 2011 American Society for Investigative Pathology. Source


Wu H.,Johns Hopkins University | Wu H.,Harbin Medical University | Wu T.,Johns Hopkins University | Wu T.,Shanghai University | And 2 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2011

Intracerebral hemorrhage (ICH) is a devastating form of stroke. In this study, we examined the efficacy of deferoxamine (DFX), an iron chelator, after collagenase-induced ICH in 12-month-old mice. Intracerebral hemorrhage was induced by intrastriatal injection of collagenase. Deferoxamine (200 mg/kg, intraperitoneal) or vehicle was administrated 6 hours after ICH and then every 12 hours for up to 3 days. Neurologic deficits were examined on days 1 and 3 after ICH. Mice were killed after 1 or 3 days of DFX treatment for examination of iron deposition, neuronal death, oxidative stress, microglia/astrocyte activation, neutrophil infiltration, brain injury volume, and brain edema and swelling. Collagenase-induced ICH resulted in iron overload in the perihematomal region on day 3. Systemic administration of DFX decreased iron accumulation and neuronal death, attenuated production of reactive oxygen species, and reduced microglial activation and neutrophil infiltration without affecting astrocytes. Although DFX did not reduce brain injury volume, edema, or swelling, it improved neurologic function. Results of our study indicate that iron toxicity contributes to collagenase-induced hemorrhagic brain injury and that reducing iron accumulation can reduce neuronal death and modestly improve functional outcome after ICH in mice. © 2011 ISCBFM All rights reserved. Source


Akino T.,Harvard University | Han X.,Harvard University | Han X.,Harbin Medical University | Nakayama H.,Harvard University | And 5 more authors.
Cancer Research | Year: 2014

Invasion and dissemination of medulloblastoma within the central nervous system is the principal factor predicting medulloblastoma treatment failure and death. Netrin-1 is an axon guidance factor implicated in tumor and vascular biology, including in invasive behaviors. We found that exogenous netrin-1 stimulated invasion of human medulloblastoma cells and endothelial cells in contrast to VEGF-A, which promoted invasion of endothelial cells but not medulloblastoma cells. Furthermore, medulloblastoma cells expressed endogenous netrin-1 along with its receptors, neogenin and UNC5B. Blockades in endogenous netrin-1, neogenin, or UNC5B reduced medulloblastoma invasiveness. Neogenin blockade inhibited netrin-1-induced endothelial cells tube formation and recruitment of endothelial cells into Matrigel plugs, two hallmarks of angiogenesis. In patients with pediatric medulloblastoma, netrin-1 mRNA levels were increased 1.7-fold in medulloblastoma tumor specimens compared with control specimens from the same patient. Immunohistochemical analyses showed that netrin-1 was elevated in medulloblastoma tumors versus cerebellum controls. Notably, urinary levels of netrin-1 were 9-fold higher in patients with medulloblastoma compared with control individuals. Moreover, urinary netrin-1 levels were higher in patients with invasive medulloblastoma compared with patients with noninvasive medulloblastoma. Finally, we noted that urinary netrin-1 levels diminished after medulloblastoma resection in patients. Our results suggest netrin-1 is a candidate biomarker capable of detecting an invasive, disseminated phenotype in patients with medulloblastoma and predicting their disease status. ©2014 AACR. Source


Wang Y.,Harbin Medical University
African journal of traditional, complementary, and alternative medicines : AJTCAM / African Networks on Ethnomedicines | Year: 2013

The objective of this paper was to study the anti-Ehrlich ascites carcinoma effect of purified toad venom extract and its mechanism. Mouse model of Ehrlich ascites carcinoma was established with cisplatin as the control to observe the inhibitory effect of purified toad venom extract on malignant peritoneal effusion in mice. The results showed that compared with the control group, ascites volume, number of tumour cells and tumour cell viability decreased and ascites inhibition rate reached over 50% in each treatment group, and with the increase of the dose, incidence of ascites showed a downward trend. The number of tumour cells in ascites and tumour cell viability in the purified toad venom high-dose group were lower than those of the cisplatin group. Compared with the model group, survival time was prolonged in varying degrees in the purified toad venom groups and cisplatin group. The study concluded that purified extract of toad venom has an anti-Ehrlich ascites carcinoma effect. Source


Ren Y.,Harbin Engineering University | Li N.,Harbin Engineering University | Feng J.,Harbin Engineering University | Luan T.,Harbin Medical University | And 3 more authors.
Journal of Colloid and Interface Science | Year: 2012

The adsorption of Pb(II) and Cu(II) from aqueous solution on magnetic porous ferrospinel MnFe 2O 4 prepared by a sol-gel process was investigated. Single batch experiment was employed to test pH effect, sorption kinetics, and isotherm. The interaction mechanism and the regeneration were also explored. The results showed that Pb(II) and Cu(II) removal was strongly pH-dependent with an optimum pH value of 6.0, and the equilibrium time was 3.0h. The adsorption process could be described by a pseudo-second-order model, and the initial sorption rates were 526.3 and 2631.5μmolg -1min -1 for Pb(II) and Cu(II) ions, respectively. The equilibrium data were corresponded well with Langmuir isotherm, and the maximum adsorption capacities were 333.3 and 952.4μmolg -1 for Pb(II) and Cu(II) ions, respectively. The adsorbed Pb(II) and Cu(II) ions were in the form of the complex with oxygen in carboxyl and hydroxyl groups binding on the surface of magnetic porous MnFe 2O 4. The sorbent could be reused for five times with high removal efficiency. © 2011 Elsevier Inc. Source


Liu W.,Harbin Medical University | Huber S.A.,University of Vermont
Virology Journal | Year: 2011

CD1d is a non-classical major histocompatibility class 1-like molecule which primarily presents either microbial or endogenous glycolipid antigens to T cells involved in innate immunity. Natural killer T (NKT) cells and a subpopulation of T cells expressing the V4 T cell receptor (TCR) recognize CD1d. NKT and V4 T cells function in the innate immune response via rapid activation subsequent to infection and secrete large quantities of cytokines that both help control infection and modulate the developing adaptive immune response. T regulatory cells represent one cell population impacted by both NKT and V4 T cells. This review discusses the evidence that NKT cells promote T regulatory cell activation both through direct interaction of NKT cell and dendritic cells and through NKT cell secretion of large amounts of TGF, IL-10 and IL-2. Recent studies have shown that CD1d-restricted V4 T cells, in contrast to NKT cells, selectively kill T regulatory cells through a caspase-dependent mechanism. V4 T cell elimination of the T regulatory cell population allows activation of autoimmune CD8+ effector cells leading to severe cardiac injury in a coxsackievirus B3 (CVB3) myocarditis model in mice. CD1d-restricted immunity can therefore lead to either immunosuppression or autoimmunity depending upon the type of innate effector dominating during the infection. © 2011 Liu and Huber; licensee BioMed Central Ltd. Source


Wei G.C.,Harbin Medical University
Bing du xue bao = Chinese journal of virology / [bian ji, Bing du xue bao bian ji wei yuan hui] | Year: 2012

In this study, we constructed the plasmid of Sendai virus (SeV) BB1 strain minigenome with Gaussia luciferase (Gluc) as reporter and compared the rescue efficiency of SeV minigenome mediated by T7 promoter with that by CMV promoter. Firstly, the sequence was designed and synthesized which contained hammerhead ribozyme, sequence composed of the trailer, untranslated region of L gene, untranslated region of N gene, and the leader from SeV, and mutant hepatitis delta virus ribozyme sequence. Then, the synthesized sequence was inserted into pVAX1 containing CMV and T7 promoters and the general vector for SeV minigenome pVAX-miniSeV was obtained. Furthermore, pVAX-miniSeV-Gluc (+) and pVAX-miniSeV-Gluc(-) were obtained by inserting Gluc gene into pVAX-miniSeV. From the supernatant of BHK-21 cell transfected with pVAX-miniSeV-Gluc(+), high level of Gluc expression was detection indicating the normal transcription function of CMV promoter. pVAX-SeV-miniGluc(-) and plasmids expressing N,P and L protein of SeV were co-transfected into BST T7/5 cell which derived from BHK-21 and expressed T7 RNA polymerase stably. And high expression of Gluc was found, which indicated that SeV minigenome was efficiently rescued. However, we failed to repeat the result on BHK-21 cell, implying that T7 promoter and CMV promoter may have different effects on the rescue efficiency of SeV minigenome. Therefore, we further constructed SeV minigenome vectors pT7-miniSeV-Gluc (-) and pCMV-miniSeV-Gluc(-) with single promoter of T7 or CMV. Then, these vectors were transfected into BSR T7/ 5 cells respectively accompanied with the N, P, and L protein expression vectors. The result demonstrated that high expression of Gluc was found in the group of pT7-miniSeV-Gluc(-), which failed in the group of pCMV-miniSeV-Gluc(-). It indicated that T7 promoter significantly increased the rescue efficiency of SeV minigenome. We successfully constructed a SeV minigenome vector with secreted luciferase gene as report er and proved T7 promoter can enhance the rescue efficiency of SeV minigenome, which provides basis for construction of infectious clone containing SeV full-length genome. Source