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Gao S.,Shandong University | Sun F.-K.,Shandong University | Fan Y.-C.,Shandong University | Shi C.-H.,Qingdao Infectious Disease Hospital | And 3 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2015

Background Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF). Aim To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis. Methods One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained. Results GSTP1 methylation levels were significantly higher in patients with acute-on-chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67-1.27%; P < 0.01). In acute-on-chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = -0.24, P = 0.01) and model for end-stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1- or 2-month mortality of acute-on-chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut-off points showed significantly poorer survival than those below (P < 0.05). Conclusions Aberrant GSTP1 promoter methylation exists in acute-on-chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure. © 2015 John Wiley & Sons Ltd. Source


Rai D.,Shandong University | Wang L.,Shandong University | Jiang X.,Jinan Infectious Disease Hospital | Zhan P.,Shandong University | And 3 more authors.
Current Medicinal Chemistry | Year: 2015

Current treatment for HCV infections consists of approved direct acting antivirals (DAAs), viz. the protease inhibitors (boceprevir, telaprevir, and simeprevir), NS5B polymerase inhibitors (sofosbuvir) and NS5A inhibitor (ledipasvir) in combination with pegylated interferon α and ribavirin). These treatments have made a great improvement in the treatment of chronic HCV infections in recent years, but their adverse side effects, emergence of resistant mutants, high cost, and increased pill burden have limited their clinical use. Recently, with the increasing knowledge in understanding the HCV life cycle, more targets have been recognized. NS5A protein plays a critical role in assembly of infectious HCV particles and offering potential for HCV therapies. Therefore, discovery and development of novel DAAs targeting NS5A with novel mechanisms of action, are of great necessity to improve the quality of existing HCV treatments. In the present review, we discuss recent advances with NS5A inhibitors with potent anti-HCV activity, and the potential for the development of HCV NS5A inhibitors to combat HCV infections. © 2015 Bentham Science Publishers. Source


Liu N.,Shandong University | Zhao F.,Shandong University | Jia H.,Shandong University | Rai D.,Shandong University | And 3 more authors.
MedChemComm | Year: 2015

Hepatitis B is an infectious inflammatory disease of the liver, which is caused by the hepatitis B virus (HBV). Nowadays, the dramatic development of new HBV inhibitors is focused on discovering diverse non-nucleoside compounds with either novel structures or new mechanisms of action. In this review, we focus on the recent advances in discovery, structural modifications and biological activities studies of several distinct classes of synthetic non-nucleoside small molecular compounds with new mechanisms. This journal is © The Royal Society of Chemistry. Source


Li Z.-H.,Shandong Academy of Sciences | Yue Y.-Y.,Shandong Academy of Sciences | Li P.,Shandong Academy of Sciences | Song N.-N.,Shandong Academy of Sciences | And 5 more authors.
Microbiology and Immunology | Year: 2015

Enterovirus A71 (EV-A71), one of the most important causative agents of hand, foot and mouth disease (HFMD) in children, can lead to severe clinical outcomes, even death. However, the infection spectrum of EV-A71 in different cell lines remains unknown. Therefore, in this study, the biological characteristics of EV-A71 Subgroup C4 in different cell lines were investigated. To this end, the infectivity of EV-A71Jinan1002 isolated from children with severe HFMD was assessed in 18 different host cell lines. It was found that the MA104 cell line displayed biological characteristics suitable for EV-A71 Subgroup C4 strain isolation and proliferation; indeed, it was found that a broad spectrum of cell lines can be infected by EV-A71Jinan1002. Among the screened cells, four cell lines (HEK293, RD, MA104 and Marc145) produced high 50% tissue culture infective dose (TCID50) values calculated in viral proliferations (ranged from 107.6 to 107.8); the TCID50 being negatively associated with the time to appearance of CPE. Proliferation curves demonstrated that EV-A71Jinan1002 amplifies more efficiently in MA104, Hep-2 and RD cells. Remarkably, the virus isolation rate was much higher in MA104 cells than in RD cells. Thus this study, to our knowledge, is for the first to explore the infection spectrum of EV-A71 subgroup C4 in such a large number of different cell lines. Our data provide useful reference data for facilitating further study of EV-A71. © 2015 The Societies and Wiley Publishing Asia Pty Ltd. Source


Zhang Y.,Jinan Infectious Disease Hospital | Kong C.,Dezhou University | Liu Y.,Shandong Academy of Sciences
Asian Journal of Chemistry | Year: 2015

A capillary zone electrophoretic method has been developed to determine ferulic acid, rosemarinic acid and caffeic acid in Rosmarnus officinalis L. The effects of buffer pH and concentration and applied voltage on separation were investigated. The optimum electrophoretic conditions are as follows: 40 mmol L-1 Borax-40 mmol L-1 NaH2PO4 (pH 8.0) as the running buffer and applied voltage of 25 kV. Under the optimized conditions, a good linearity between the peak area and the concentration was found in the ranges of 10-200, 20-400 and 20-400 mg mL-1 for rosemarinic acid, ferulic acid and caffeic acid, respetively. The relative standard deviation in migration time and peak area was 0.68 and 1.37 % for ferulic acid, 0.51 and 1.98 % for rosemarinic acid, 0.76 and 1.86 % for caffeic acid. The detection limits of the three analytes ranged from 3.1 to 5.6 mg mL-1. The recoveries of three analytes ranged between 92.5 and 102.5 %. Source

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