Histone deacetylase (HDAC) inhibitors show clinical promise for the treatment of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the effect of HDAC inhibitor treatment on hepatitis C ...Histone deacetylase (HDAC) inhibitors show clinical promise for the treatment of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the effect of HDAC inhibitor treatment on hepatitis C virus (HCV)replication in Huh7 human liver cells and in a mouse model of HCV infection. Viral replication was markedly suppressed by the HDAC3 inhibitor at concentrations below 1 mmol/L, with no cellular toxicity. This was accompanied by upregulation of liver-expressed antimicrobial peptide 1 (LEAP-1) and downregulation of apolipoprotein-A1 (Apo-A1), as determined by microarray and quantitative RT-PCR analyses. Moreover, HDAC3 was found to modulate the binding of CCAAT-enhancer-binding protein a (C/EBPa), hypoxia-inducible factor 1 a (HIF1 a), and signal transducer and activator of transcription 3 (STAT3) to the LEAP-1 promoter. HDAC3 inhibitor treatment also blocked HCV replication in a mouse model of HCV infection. These results indicate that epigenetic therapy with HDAC3 inhibitor may be a potential treatment for diseases associated with HCV infection such as HCC.展开更多
Objective To investigate the relationship among -75 bp/+83 bp polymorphism in apolipoprotein A1 (apo A1) gene, lipids levels and the occurrence of coronary atherosclerosis disease (CAD).Methods We determined distri...Objective To investigate the relationship among -75 bp/+83 bp polymorphism in apolipoprotein A1 (apo A1) gene, lipids levels and the occurrence of coronary atherosclerosis disease (CAD).Methods We determined distributions of two MspI polymorphisms of the apo A1 gene at -75 bp and +83 bp, and blood lipids levels among 137 Chinese patients (92 with CAD and 45 in the control group) in relation to circulating lipids and coronary angiography. Results The demographic information for 137 subjects showed that subjects with CAD tended to have more unfavorable lipoprotein variables. Genotype distributions at both sites were different between the CAD and control groups. Furthermore, the control group had higher M1-/M2- frequencies than the CAD group (M1: P<0.005; M2: P<0.05) and the “M1-”(A) and “M2-” alleles were associated with increased high-density lipoprotein cholesterol (HDL-C) (M1-: P<0.0001; M2-: P<0.05) and apo A1 (M1-: P<0.0001; M2-: P<0.05) levels. “M1-” and “M2-” were significantly negatively correlated with CAD (P<0.01 and P<0.05, respectively).Conclusions Our results suggest that changes from G to A at the -75 bp site and from C to T or G to A at the +83 bp site do increase circulating levels of apo A1 and HDL-C. And those individuals with these changes are likely to have a lower risk of developing CAD.展开更多
基金supported by the National Key Research and Development Program of China to YZ(2018YFA0507202)the Program for Youth Innovation Promotion Association in Chinese Academy of Science to JC
文摘Histone deacetylase (HDAC) inhibitors show clinical promise for the treatment of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the effect of HDAC inhibitor treatment on hepatitis C virus (HCV)replication in Huh7 human liver cells and in a mouse model of HCV infection. Viral replication was markedly suppressed by the HDAC3 inhibitor at concentrations below 1 mmol/L, with no cellular toxicity. This was accompanied by upregulation of liver-expressed antimicrobial peptide 1 (LEAP-1) and downregulation of apolipoprotein-A1 (Apo-A1), as determined by microarray and quantitative RT-PCR analyses. Moreover, HDAC3 was found to modulate the binding of CCAAT-enhancer-binding protein a (C/EBPa), hypoxia-inducible factor 1 a (HIF1 a), and signal transducer and activator of transcription 3 (STAT3) to the LEAP-1 promoter. HDAC3 inhibitor treatment also blocked HCV replication in a mouse model of HCV infection. These results indicate that epigenetic therapy with HDAC3 inhibitor may be a potential treatment for diseases associated with HCV infection such as HCC.
文摘Objective To investigate the relationship among -75 bp/+83 bp polymorphism in apolipoprotein A1 (apo A1) gene, lipids levels and the occurrence of coronary atherosclerosis disease (CAD).Methods We determined distributions of two MspI polymorphisms of the apo A1 gene at -75 bp and +83 bp, and blood lipids levels among 137 Chinese patients (92 with CAD and 45 in the control group) in relation to circulating lipids and coronary angiography. Results The demographic information for 137 subjects showed that subjects with CAD tended to have more unfavorable lipoprotein variables. Genotype distributions at both sites were different between the CAD and control groups. Furthermore, the control group had higher M1-/M2- frequencies than the CAD group (M1: P<0.005; M2: P<0.05) and the “M1-”(A) and “M2-” alleles were associated with increased high-density lipoprotein cholesterol (HDL-C) (M1-: P<0.0001; M2-: P<0.05) and apo A1 (M1-: P<0.0001; M2-: P<0.05) levels. “M1-” and “M2-” were significantly negatively correlated with CAD (P<0.01 and P<0.05, respectively).Conclusions Our results suggest that changes from G to A at the -75 bp site and from C to T or G to A at the +83 bp site do increase circulating levels of apo A1 and HDL-C. And those individuals with these changes are likely to have a lower risk of developing CAD.
