Yaping Li

Caffeic acid phenethyl ester inhibits liver fibrosis in rats

AIM To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester (CAPE) in rats with liver fibrosis. METHODS A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group (n = 10), a vehicle group (n = 10), a model group (n = 15), a vitamin E group (n = 10), and three CAPE groups (CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE (3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin (TBil), aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde (MDA), glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on α-smooth muscle actin (α-SMA), a characteristic hallmark of activated hepatic stellate cells (HSCs), and NF-E2-related factor 2 (Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry. RESULTS Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats (P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group (P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group (P < 0.05). Moreover, CAPE effectively inhibited α-SMA expression while increasing Nrf2 expression compared to the model group (P < 0.01). CONCLUSION The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by inhibiting oxidative stress.

hOGG1 Ser326Cys Polymorphism and Risk of Hepatocellular Carcinoma among East Asians: A Meta-Analysis

Background The hOGG1 gene encodes a DNA glycosylase enzyme responsible for DNA repair. The Ser326Cys polymorphism in this gene may influence its repair ability and thus plays a role in carcinogenesis. Several case-control studies have been conducted on this polymorphism and its relationship with the risk of hepatocellular carcinoma (HCC) among East Asians. However, their results are inconsistent. Methods We performed a meta-analysis of published case-control studies assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. PubMed, EMBASE, SCI, BIOSIS, CNKI and WanFang databases were searched. A random-effect model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses were conducted for additive, dominant and recessive genetic models. Results Eight studies were identified involving 2369 cases and 2442 controls assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. Applying a dominant genetic model, only in the Chinese population, the Cys allele was significantly associated with increased risk of HCC (OR 1.56, 95% CI 1.12–2.17). However, two studies influenced this finding according to sensitivity analysis. Furthermore, considerable heterogeneity and bias existed among Chinese studies. Conclusion There is limited evidence to support that the hOGG1 Ser326Cys polymorphism is associated with HCC risk among East Asians. Well-designed and large-sized studies are required to determine this relationship.

Effects of Saikosaponin-D on syndecan-2, matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 in rats with hepatocellular carcinoma

OBJECTIVE To investigate effects of Saikosaponin D (SSd) on syndecan-2, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in livers of rat with hepatocellular carcinoma (HCC). METHODS Male SD rats were divided into control (n=10), model (n=20) and SSd (n=20) groups, and model and SSd groups given intragastric 0.2% (w/v) N-diethylnitrosamine to induce HCC. SSd group received 0.03% (w/v) SSd in saline. Liver samples were analysed immunohistochemically for syndecan-2, MMP-2, MMP-13 and TIMP-2 at 16 weeks. RESULTS The model group had more malignant nodules than the SSd group; all model-group HCC cells were grade III; SSd-group HCC cells were grades I-II. Controls showed normal hepatic cell phenotypes and no syndecan-2+ staining. Syndecan-2+ staining was greater in the model group (35.2%, P < or = 0.001) than in controls or the SSd group (16.5%, P < or = 0.001). The model group had more intense MMP-2+ staining than controls (0.37 vs 0.27, P< or =0.01) or the SSd group (0.31 vs 0.37, P< or =0.05); and higher MMP-13+ staining (72.55%) than in controls (12.55%, P< or =0.001) and SSd group (20.18%, P< or =0.01). The model group also had more TIMP-2+ staining (57.2%) than controls (20.9%, P< or =0.001) and SSd group (22.7%, P< or=0.001). Controls and SSd group showed no difference in TIMP-2+ rates. CONCLUSION SSd inhibited HCC development, and downregulated expression of syndecan-2, MMP-2, MMP-13 and TIMP-2 in rat HCC liver tissue.

Telaprevir for chronic hepatitis C with genotype 1: a meta-analysis.

BACKGROUND/AIMS The examination of HCV virological clearance through several randomized clinical trials of telaprevir in genotype 1 chronic hepatitis C. METHODOLOGY We analyzed the effect of telaprevir on the end of treatment virological response and the sustained response, and investigated its harmful effect using meta-analysis of 5 randomized controlled trials. RESULTS Overall analysis revealed a significant effect of telaprevir in both naive patients (RR, 1.32; 95% CI, 1.08-1.60) and previously failed treated patients (p<0.0001). Monotherapy and double therapy seemed to show no effect in naive patients. Triple therapy followed with PegIFN-2a plus ribavirin seemed to be effective in both naive patients and previously failed treated patients. Telaprevir was associated with a significantly higher incidence of serious adverse events (RR, 1.45; 95% CI, 1.00-2.10) and with discontinuation (RR, 2.23; 95% CI, 1.40-3.55) because of adverse events. In naive patients, relapsers and non-responders, the regimen of telaprevir/ PegIFN-2a/ribavirin for 12 weeks followed by PegIFN-2a/ribavirin for 12 weeks (T12PR24) was the optimal regimen regarding to efficiency and duration. CONCLUSIONS Telaprevir combined with PegIFN-2a plus ribavirin may improve sustained response in genotype 1 chronic hepatitis C. Regimen T12PR24 may be the best regimen in this respect. New randomized controlled trials are required to confirm this meta-analysis.

Guggulsterone induces apoptosis of human hepatocellular carcinoma cells through intrinsic mitochondrial pathway

AIM To investigate the effects of guggulsterone on the proliferation and apoptosis of human hepatoma HepG2 cells in vitro and relevant mechanisms. METHODS Human hepatocellular carcinoma HepG2 cells and normal human liver L-02 cells were treated with different concentrations of guggulsterone (5-100 μmol/L) for 24-72 h. Cell proliferation was tested by MTT assay. Cell cycle and apoptosis were investigated using flow cytometry (FACS). Bcl-2 and Bax mRNA and protein expression was detected by real-time PCR and Western blot, respectively. TGF-β1, TNF-α, and VEGF contents were determined by ELISA. RESULTS Guggulsterone significantly inhibited HepG2 cell proliferation in a dose- and time-dependent manner. FACS showed that guggulsterone arrested HepG2 cell cycle at G0/G1 phase. Guggulsterone induced apoptosis was also observed in HepG2 cells, with 24.91% ± 2.41% and 53.03% ± 2.28% of apoptotic cells in response to the treatment with 50 μmol/L and 75 μmol/L guggulsterone, respectively. Bax mRNA and protein expression was significantly increased and Bcl-2 mRNA and protein expression was decreased. ELISA analysis showed that the concentrations of TGF-β1 and VEGF were significantly decreased and TNF-α concentration was increased. CONCLUSION Guggulsterone exerts its anticancer effects by inhibiting cell proliferation and inducing apoptosis in HepG2 cells. Guggulsterone induces apoptosis by activation of the intrinsic mitochondrial pathway.

Dominant CD4-dependent RNA-dependent RNA polymerase-specific T-cell responses in children acutely infected with human enterovirus 71 and healthy adult controls

Human enterovirus 71 (EV71) is one of the major causes of hand, foot and mouth disease (HFMD), which leads to significant mortality in infected children. A prophylactic vaccine is urgently needed. However, little is known about the protective T‐cell immunity in individuals infected with the EV71 virus. In this study, we performed a comprehensive ex vivo interferon‐γ ELISPOT analysis in 31 children infected with EV71 as well as in 40 healthy adult controls of the CD4+ and CD8+ T‐cell responses to overlapping peptides spanning the VP1 structural protein and RNA‐dependent RNA polymerase (RdRp) non‐structural protein. EV71‐specific CD4 T‐cell responses were detected in most of the acute patients and were mostly CD4‐dependent RdRp‐specific responses. CD8‐dependent VP1 and RdRp‐specific responses were also detected in a small proportion of recently infected children. There was no significant association between the strength of the T‐cell responses and disease severity observed during the acute EV71 infection phase. Interestingly, an RdRp‐specific, but no VP1‐specific, CD4‐dependent T‐cell response was detected in 30% of the adult controls, and no T‐cell responses were detected in healthy children. In addition, 24 individual peptides containing potential T‐cell epitope regions were identified. The data suggest that CD4‐dependent RdRp‐specific T‐cell responses may play an important role in protective immunity, and the epitopes identified in this study should provide valuable information for future therapeutic and prophylactic vaccine design as well as basic research.

Cytokeratin 8 is increased in hepatitis C virus cells and its ectopic expression induces apoptosis of SMMC7721 cells.

AIM To investigate cytokeratin 8 (CK8) overexpression during hepatitis C virus (HCV) infection and its pathogenesis, and the effect of ectopic CK8 expression on hepatoma cell lines. METHODS We successfully established an in vitro HCV cell culture system (HCVcc) to investigate the different expression profiles of CK8 in Huh-7-HCV and Huh-7.5-HCV cells. The expression of CK8 at the mRNA level was determined by real-time polymerase chain reaction (RT-PCR). The expression of CK8 at the protein level was evaluated by Western blotting. We then constructed a eukaryotic expression combination vector containing the coding sequence of human full length CK8 gene. CK8 cDNA was amplified by reverse transcription-PCR and inserted into pEGFP-C1 and the positive clone pEGFP-CK8 was obtained. After confirming the sequence, the recombinant plasmid was transfected into SMMC7721 cells with lipofectamine2000 and CK8 expression was detected using inverted fluorescence microscopy, RT-PCR and Western blotting. Besides, we identified biological function of CK8 on SMMC7721 cells, including cell proliferation, cell cycle and apoptosis detection. RESULTS RT-PCR showed that the expression level of CK8 in Huh-7-HCV and Huh-7.5-HCV cells was 2.88 and 2.95 times higher than in control cells. Western blot showed that CK8 expression in Huh-7-HCV and Huh-7.5-HCV cells was 2.53 and 3.26 times higher than that in control cells, respectively. We found that CK8 at mRNA and protein levels were both significantly increased in HCVcc. CK8 was up-regulated in SMMC7721 cells. CK8 expression at the mRNA level was significantly upregulated in SMMC7721/pEGFP-CK8 cells. CK8 expression in SMMC7721/ pEGFP-CK8 cells was 2.69 times higher than in SMMC7721 cells, and was 2.64 times higher than in SMMC7721/pEGFP-C1 cells. CK8 expression at the protein level in SMMC7721/pEGFP-CK8 cells was 2.46 times higher than in SMMC7721 cells, and was 2.29 times higher than in SMMC7721/pEGFP-C1 cells. Further analysis demonstrated that forced expression of CK8 slowed cell growth and induced apoptosis of SMMC7721 cells. CONCLUSION CK8 up-regulation might have a functional role in HCV infection and pathogenesis, and could be a promising target for the treatment of HCV infection.

Cost-effectiveness of a national enterovirus 71 vaccination program in China

Background and aims Enterovirus 71 (EV71) has caused great morbidity, mortality, and use of health service in children younger than five years in China. Vaccines against EV71 have been proved effective and safe by recent phase 3 trials and are now available in China. The purpose of this study was to evaluate the health impact and cost-effectiveness of a national EV71 vaccination program in China. Methods Using Microsoft Excel, a decision model was built to calculate the net clinical and economic outcomes of EV71 vaccination compared with no EV71 vaccination in a birth cohort of 1,000,000 Chinese children followed for five years. Model parameters came from published epidemiology, clinical and cost data. Results In the base-case, vaccination would annually avert 37,872 cases of hand, foot and mouth disease (HFMD), 2,629 herpangina cases, 72,900 outpatient visits, 6,363 admissions to hospital, 29 deaths, and 945 disability adjusted life years. The break-even price of the vaccine was

Association of gene polymorphisms of pattern-recognition receptor signaling pathway with the risk and severity of hand, foot, and mouth disease caused by enterovirus 71 in Chinese Han population

5.2/dose. When the price was less than

Caffeic acid phenethyl ester up-regulates antioxidant levels in hepatic stellate cell line T6 via an Nrf2-mediated mitogen activated protein kinases pathway

8.3 or