Shanghai Changning Center Hospital
Shanghai Changning Center Hospital
Xu W.-J.,Soochow University of China |
Xie H.-J.,Shanghai Changning Center Hospital |
Cao Q.-R.,Soochow University of China |
Shi L.-L.,Soochow University of China |
And 3 more authors.
Drug Delivery | Year: 2016
This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC0-24 h and Cmax in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL. © 2014 Informa Healthcare USA, Inc.
Zhang X.,Fudan University |
Zhang Z.,Fudan University |
Dai F.,Fudan University |
Shi B.,Fudan University |
And 8 more authors.
PLoS ONE | Year: 2014
Circulating microRNAs have been widely recognized as a novel category of biomarker in a variety of physiological and pathological conditions. Other reports revealed that fragments of organ specific messenger RNAs are also detectable in serum/plasma and can be utilized as sensitive indicators of liver pathology and cancer. In order to assess the sensitivity and reliability of these two class of RNAs as marker of hepatitis B or C induced chronic liver disease, we collected plasma samples from 156 chronic hepatitis B or C patients (HBV active n = 112, HBV carrier n = 19, hepatitis C n = 25) and 22 healthy donors and quantified their circulating mRNA for albumin, HP (haptoglobin), CYP2E1 (cytochrome P450, family 2, subfamily E) and ApoA2 (Apolipoprotein A2) in conjunction with microRNA-122, a well established marker for acute and chronic liver injury. We found that plasma microRNA-122 level is significantly elevated in patients with active HBV but not in HBV carriers. Furthermore, microRNA-122 is not elevated in HCV patients even though their median serum alanine aminotransferase (sALT) was three fold of the healthy donors. Nevertheless, circulating mRNAs, especially albumin mRNA, showed much more sensitivity in distinguishing active hepatitis B, hepatitis B carrier or HCV patientsfrom healthy control. Correlation and multiple linear regression analysis suggested that circulating mRNAs and miRNAs are much more related to HBsAg titre than to sALT. Immunoprecipitation of HBsAg in HBV patients' plasma resulted in enrichment of albumin and HP mRNA suggesting that fragments of liver specific transcripts can be encapsidated into HBsAg particles. Taken together, our results suggest that hepatocyte specific transcripts in plasma like albumin mRNA showed greater sensitivity and specificity in differentiating HBV or HCV induced chronic liver disease than microRNA-122. Circulating mRNA fragments merit more attention in the quest of next generation biomarkers for various maladies. Copyright: © 2014 Zhang et al.
Zhang Q.,Shanghai JiaoTong University |
Yan Zhang R.,Shanghai JiaoTong University |
Qiu J.P.,Shanghai Pudong Gongli Hospital |
Zhang J.F.,Shanghai JiaoTong University |
And 7 more authors.
Circulation: Cardiovascular Quality and Outcomes | Year: 2011
Background: Traditional reperfusion options for patients with acute ST-segment elevation myocardial infarction (STEMI) presenting to non-primary percutaneous coronary intervention (PPCI)-capable hospitals generally include onsite fibrinolytics or emergency transfer for PPCIA third option, involving interventionalist transfer, was examined in the REVERSE-STEMI studyMethods and Results: A total of 334 patients with acute STEMI who presented to 5 referral hospitals with angiographic facilities but without interventionalists qualified for PPCI were randomized to receive PPCI with either an interventionalist- (n=165) or a patient-transfer (n=169) strategyThe primary end point of door-to-balloon (D2B) time and secondary end points of left ventricular ejection fraction and major adverse cardiac events (MACE) at 1-year clinical follow-up were compared between the 2 groupsCompared with the patient-transfer strategy, the interventionalisttransfer strategy resulted in a significantly shortened D2B time (median, 92 minutes versus 141 minutes; P>0.0001), with more patients having first balloon angioplasty within 90 minutes (21.2% versus 7.7%, P>0.001)This treatment strategy also was associated with higher left ventricular ejection fraction (0.60±0.07 versus 0.57±0.09, P>0.001) and improved 1-year MACE-free survival (84.8% versus 74.6%, P=0.019)Multivariate Cox proportional hazards modeling revealed that the interventionalist-transfer strategy was an independent factor for reduced risk of composite MACE (hazard ratio, 0.63; 95% CI, 0.45 to 0.88; P=0.003)Conclusions: The interventionalist-transfer strategy for PPCI may be effective in improving the care of patients with STEMI presenting to a non-PPCI-capable hospital, particularly in a congested cosmopolitan region where patient transfers could be prolonged. © 2011 American Heart Association, Inc.
Li C.,Shanghai JiaoTong University |
Bai Y.,Shanghai JiaoTong University |
Liu H.,Shanghai JiaoTong University |
Zuo X.,Shanghai Changning Center Hospital |
And 3 more authors.
Acta Biochimica et Biophysica Sinica | Year: 2013
Keloids are tumor-like skin scars that grow as a result of the aberrant healing of skin injuries, with no effective treatment. The molecular mechanism underlying keloid pathogenesis is still largely unknown. In this study, we compared microRNA (miRNA) expression profiles between keloid-derived fibroblasts and normal fibroblasts (including fetal and adult dermal fibroblasts) by miRNA microarray analysis. We found that the miRNA profiles in keloid-derived fibroblasts are different with those in normal fibroblasts. Nine miRNAs were differentially expressed, six of which were significantly up-regulated in keloid fibroblasts (KFs), including miR-152, miR-23b-3p, miR-31-5p, miR-320c, miR-30a-5p, and hsv1-miR-H7, and three of which were significantly down-regulated, including miR-4328, miR-145-5p, and miR-143-3p. Functional annotations of differentially expressed miRNA targets revealed that they were enriched in several signaling pathways important for scar wound healing. In conclusion, we demonstrate that the miRNA expression profile is altered in KFs compared with in fetal and adult dermal fibroblasts, and the expression profile may provide a useful clue for exploring the pathogenesis of keloids. miRNAs might partially contribute to the etiology of keloids by affecting several signaling pathways relevant to scar wound healing. © 2013 The Author.
Wang G.,Shanghai Public Health Clinical Center |
Shen Z.,Shanghai Public Health Clinical Center |
Qian F.,Shanghai Changning Center Hospital |
Li Y.,Shanghai Dongfang Hospital |
And 2 more authors.
Journal of Clinical Virology | Year: 2014
Background: Sapovirus has been accepted as a major cause of acute gastroenteritis worldwide. It can affect all age groups, ranging from young adults to the elderly, while little is known about the epidemiological patterns and genetic characteristics of sapovirus infections in China. Objectives: To investigate the prevalence of sapovirus infections among adult outpatients suffering from acute gastroenteritis in Shanghai, China. Study design: From April 2011 to March 2013, fecal specimens from 1125 adult outpatients (≥16 years of age) with acute gastroenteritis were collected. Reverse transcription polymerase chain reaction (RT-PCR) was employed for detection of sapovirus, and 5' end of capsid gene were sequenced for genotyping and phylogenetic analysis. Results: The overall occurrence of sapovirus infection in adult outpatients was 3.73% (42 in 1125) through the two-year surveillance period, and sapovirus diarrhea is more common in spring and winter. The highest sapovirus positive rate was observed in adults of ≥56 years old, and statistically significant relationship was observed when compared with other age groups (p<. 0.05). Only three genotypes were detected, whereas GI.2 was proved to be the predominant strain, occupying 78.57% (33 in 42) of all strains, followed by GIV, GI.1 and GII.3. Conclusions: Sapovirus was commonly found in adults with acute gastroenteritis in Shanghai, China, while no specific seasonal variation of sapovirus diarrhea could be distinguished. GI.2 strains established themselves in a short time span as the predominant genotype in Shanghai, China. © 2014 Elsevier B.V.
PubMed | Chinese PLA General Hospital, Shanghai Changning Center Hospital, Tongji University and Beijing Jiaotong University
Type: | Journal: Stem cells international | Year: 2015
The poor survival rate of transplanted stem cells in ischemic myocardium has limited their therapeutic efficacy. Curcumin has potent antioxidant property. This study investigates whether prior curcumin treatment protects stem cells from oxidative stress injury and improves myocardial recovery following cells transplantation. Autologous Sprague-Dawley rat adipose derived mesenchymal stem cells (ADSCs) were pretreated with or without curcumin. The hydrogen peroxide/serum deprivation (H2O2/SD) medium was used to mimic the ischemic condition in vitro. Cytoprotective effects of curcumin on ADSCs were evaluated. Curcumin pretreatment significantly increased cell viability and VEGF secretion, and decreased cell injury and apoptosis via regulation of PTEN/Akt/p53 and HO-1 signal proteins expression. The therapeutic potential of ADSCs implantation was investigated in myocardial ischemia-reperfusion injury (IRI) model. Transplantation of curcumin pretreated ADSCs not only resulted in better heart function, higher cells retention, and smaller infarct size, but also decreased myocardial apoptosis, promoted neovascularization, and increased VEGF level in ischemic myocardium. Together, priming of ADSCs with curcumin improved tolerance to oxidative stress injury and resulted in enhancement of their therapeutic potential of ADSCs for myocardial repair. Curcumin pretreatment is a promising adjuvant strategy for stem cells transplantation in myocardial restoration.
Lu J.-H.,Shanghai Changning Center Hospital |
Shi Z.-F.,Fudan University |
Xu H.,Shanghai Changning Center Hospital
Molecular and Cellular Biochemistry | Year: 2014
Doxorubicin has displayed significant cytotoxic effects against the lung cancer cells; however, the underlying mechanisms remain inconclusive. In the current study, we provided evidence to show that mitochondrial p53 and cyclophilin D (Cyp-D) complexation is required for doxorubicin-induced death of lung cancer A549 cells. Doxorubicin induced both apoptotic and non-apoptotic death of A549 cells. Cyclosporine A (CsA), the Cyp-D inhibitor, and Cyp-D silencing were prevented doxorubicin-induced non-apoptotic death of A549 cells, while cells overexpressing Cyp-D were hyper-sensitive to doxorubicin. In A549 cells, doxorubicin-activated p53, the latter translocated to mitochondria and physically interacted with Cyp-D. The p53/Cyp-D mitochondrial complexation was prevented by CsA or Cyp-D silencing, or by p53 inhibitor pifithrin-α. Significantly, doxorubicin-induced anti-tumor ability in vivo was also compromised by CsA, or when Cyp-D was silenced. Together, these data suggested that Dox-induced non-apoptotic death of A549 cells requires mitochondrial Cyp-D-p53 complexation. © 2013 Springer Science+Business Media.
Kai S.,Shanghai Changning Center Hospital |
Lu J.-H.,Shanghai Changning Center Hospital |
Hui P.-P.,Shanghai Changning Center Hospital |
Zhao H.,Shanghai Changning Center Hospital
Biochemical and Biophysical Research Communications | Year: 2014
Lung cancer is a major cause of cancer-related mortality in the United States and around the world. Due to the pre-existing or acquired chemo-resistance, the current standard chemotherapy regimens only show moderate activity against lung cancer. In the current study, we explored the potential anti-lung cancer activity of cinobufotalin in vivo and in vitro, and studied the underlying mechanisms. We demonstrated that cinobufotalin displayed considerable cytotoxicity against lung cancer cells (A549, H460 and HTB-58 lines) without inducing significant cell apoptosis. Our data suggest that mitochondrial protein cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates cinobufotalin-induced non-apoptotic death of lung cancer cells. The Cyp-D inhibitor cyclosporine A (CsA), the mPTP blocker sanglifehrin A (SfA), and Cyp-D shRNA-silencing significantly inhibited cinobufotalin-induced mitochondrial membrane potential (MMP) reduction and A549 cell death (but not apoptosis). Using a mice xenograft model, we found that cinobufotalin inhibited A549 lung cancer cell growth in vivo. Thus, cinobufotalin mainly induces Cyp-D-dependent non-apoptotic death in cultured lung cancer cells. The results of this study suggest that cinobufotalin might be further investigated as a novel anti-lung cancer agent. © 2014 Elsevier Inc. All rights reserved.
Du G.,Shanghai University of Traditional Chinese Medicine |
Song Z.,Shanghai Changning Center Hospital |
Zhang Q.,Shanghai Changning Center Hospital
Preventive Medicine | Year: 2013
Objective: The purpose of the present study was to investigate whether gamma-glutamyltransferase (GGT) is an independent predictor for future cardiovascular (CV) and all-cause mortality with prospective observational studies by meta-analysis. Methods: Electronic literature databases (Cochrane Library, Medline, and Embase) were searched for relevant prospective observational studies on the association between baseline GGT and CV and all-cause mortality published prior to June 2012. Pooled adjust relative risk (RR) and corresponding 95% confidence intervals(CI) were calculated separately for categorical risk estimates(highest vs. lowest GGT quartile) and continuous risk estimates (per unit-log GGT increment). Results: Seven studies with 273,141 participants were identified and analyzed. The pooled RR of CV mortality for highest vs. lowest GGT quartile was 1.52 (95% CI 1.36-1.70). The pooled RR of CV mortality for per unit-log (GGT) increment was 1.76 (95% CI 1.60-1.94). The pooled RR for all-cause mortality for highest vs. low GGT quartile was 1.56 (95% CI 1.34-1.83). Subgroup analyses based on region, gender, follow-up duration, and sample size showed that the positive association between GGT and risk of CV mortality was consistently observed in each subgroup except for the Asia subgroup (RR =1.59, 95% CI 0.76-3.30). Conclusions: GGT is an independent predictor for future CV mortality and all-cause mortality, and might be independent of alcohol intake. •Inconsistent findings regarding the association between elevated plasma GGT levels and cardiovascular and all-cause mortality risk•We performed a meta-analysis on plasma GGT levels and cardiovascular and all-cause mortality risk.•Elevated plasma GGT significantly increased the risk of cardiovascular and all-cause mortality, and the increase was an independent predictor.•Routine GGT assays will be helpful in identifying mortality risk. © 2013 Elsevier Inc..
Huang B.,Tongji University |
Wu Q.,Shanghai Changning Center Hospital |
Ge Y.,Tongji University |
Zhang J.,Tongji University |
And 5 more authors.
International Journal of Oncology | Year: 2014
N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins and the dysfunction of which is a common feature of various carcinomas. Nevertheless, the role of GnT-V remains controversial. Therefore, the clinical implication of GnT-V expression may differ in each cancer type. The implication of GnT-V status in patients with gastric cancer has not been studied extensively. In the present study, we examined GnT-V expression in gastric cancer specimen both at protein and mRNA levels. We compared GnT-V expression with clinical and pathologic variables. Kaplan-Meier survival curves were generated to show the cause-specific survival. Furthermore, the small interfering RNA was devised to downregulate the GnT-V mRNA expression in SGC7901 and BGC 823 cells. We characterized the function implication of GnT-V by cell proliferation and invasiveness analysis. Analysis in gastric cancer specimen revealed that GnT-V expression correlated with tumor grade and stage. The overall survival time of positive GnT-V expression in gastric cancer was significantly shorter than that of negative GnT-V expression. Moreover, the downregulation of GnT-V expression by small interfering RNA resulted in a decrease of cell proliferation and invasiveness in SGC7901 and BGC 823 cells accompanied by morphological change. This supports that GnT-V correlates with metastasis and prognosis in gastric cancer. These results contribute to new insight into the underlying molecular mechanisms of GnT-V regulation in gastric cancer with potential translational clinical applications.