Introduction: Hepatic diseases comprise inflammations of the liver, which can originate from drug-induced, toxic, autoimmune sources and particularly hepatitis B and C virus infection. The outcome of the disease is li...Introduction: Hepatic diseases comprise inflammations of the liver, which can originate from drug-induced, toxic, autoimmune sources and particularly hepatitis B and C virus infection. The outcome of the disease is linked to interactions between the immune system and the virus, and also depends on the age and immune status of the patient. The aim of this study was to evaluate the association of a MAP3K14 (rs2074292), CD40 (rs1883832) polymorphism and chronic hepatitis B virus carriage in a population from Burkina Faso. Methods: In this case-control analysis, 223 and 173 samples, consisting of 90 and 53 controls and 133 and 120 cases, were examined for MAP3K14 and CD40 respectively. The cases included patients with Chronic Hepatitis B (CHB), cirrhosis or hepatocellular carcinoma (HCC). Genomic DNA extraction was executed using INVITROGEN and FAVORGEN kits. Genotyping of MAP3K14 (rs2074292) and CD40 (rs1883832) gene polymorphisms was accomplished via real-time PCR on the QuantStudioTM 5 Real-Time instrument, followed by allelic discrimination using TaqMan Genotyper Software. Data was interpreted using SPSS version 20 and Epi info version 7.5.2.0. Odds ratios (OR), confidence intervals (CI), and p-values were derived for risk and significance evaluation. Results: This study showed that the heterozygous CT genotype and the mutated T allele of the CD40 (rs1883832) gene are involved in the progression of chronic hepatitis to cirrhosis and hepatocellular carcinoma in HBV-infected patients. However, no association was found between polymorphisms in the MAP3K14 gene (rs2074292) and the progression of HBV infection. By combining the two polymorphisms, we observed either high risk or protection, depending on the genotypes of the MAP3K14 and CD40 genes simultaneously carried by the patient. Conclusion: Polymorphisms of the MAP3K14 and CD40 genes are associated with the evolution of HBV infection.展开更多
Cells need to coordinate gene expression with their metabolic states to maintain cell homeostasis and growth.However,how cells transduce nutrient availability to appropriate gene expression response via histone modifi...Cells need to coordinate gene expression with their metabolic states to maintain cell homeostasis and growth.However,how cells transduce nutrient availability to appropriate gene expression response via histone modifications remains largely unknown.Here,we report that glucose specifically induces histone H3K4 trimethylation(H3K4me3),an evolutionarily conserved histone covalent modification associated with active gene transcription,and that glycolytic enzymes and metabolites are required for this in?duction.Although glycolysis supplies S-adenosylmethionine for histone methyltransferase Setl to catalyze H3K4me3,glucose induces H3K4me3 primarily by inhibiting histone demethylase Jhd2-catalyzed H3K4 demethylation.Glycolysis provides acetyl-CoA to stimulate histone acetyltransferase Gcn5 to acetylate H3K14,which then inhibits the binding of Jhd2 to chromatin to increase H3K4me3.By repressing Jhd2-mediated H3K4 demethylation,glycolytic enzymes regulate gene expression and cell survival during chronological aging.Thus,our results elucidate how cells reprogram their gene expression programs in response to glucose availability via histone modifications.展开更多
Objective:Anti-high-mobility group box 1(HMGB1)is involved in the pathogenesis of many inflammatory and autoimmune diseases,including psoriasis.The present study aimed to investigate the therapeutic effects of HMGB1 m...Objective:Anti-high-mobility group box 1(HMGB1)is involved in the pathogenesis of many inflammatory and autoimmune diseases,including psoriasis.The present study aimed to investigate the therapeutic effects of HMGB1 monoclonal antibody(mAb)in keratin 14(K14)-vascular endothelial growth factor(VEGF)transgenic homozygous mice.Methods:Twelve VEGF transgenic mice were randomly divided into two groups of six mice each:the anti-HMGB1 mAb group and the immune complex(IC)mAb group.The mice underwent intraperitoneal injection of anti-HMGB1 mAb or IC mAb once every 2 days for a total of three treatments.Compare the lesions on the ears of the mice and evaluate the severity of the lesions using the baseline and clinical scores on the last day of treatment.The changes in psoriasis-like lesions,cellular infiltration of T cells,dendritic cells,and neutrophils were detected by hematoxylin-eosin staining and immunohistochemistry.The mRNA expression of the inflammatory cytokines,including interleukin(IL)-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the lesions were assessed by real-time quantitative polymerase chain reaction.The number ofγδT cells in the lesions of two groups were detected by flow cytometry.Thet test was used to compare their differences.Results:The anti-HMGB1 mAb effectively ameliorated the clinical skin lesions.The clinical scores in the anti-HMGB1 mAb group were lower than those in the IC mAb group(6.00±0.52vs.10.83±0.48,P<0.001).Histopathologic changes and improvements in the K14-VEGF transgenic homozygous mice were evident after three treatments.The scores of mice in the anti-HMGB1 mAb group were significantly lower than those in the IC mAb group(3.25±0.71vs.6.95±0.83,P=0.0033).The average epidermal thickness in the anti-HMGB1 mAb group was reduced by about 45%when compared with that in the IC mAb group(32.15±7.08vs.64.69±7.93,P=0.0054).Moreover,anti-HMGB1 mAb also decreased the number of infiltrating CD3+T cells,myeloperoxidase-positive neutrophils,and CD11c+dendritic cells.The ratio of ear skinγδT cells was reduced in anti-HMGB1 mAb treated group.The mRNA expression of IL-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the anti-HMGB1 mAb group were significantly reduced when compared with IC mAb group(0.36±0.070vs.1.98±0.62,P=0.0148;6.43±1.37vs.13.80±1.33,P=0.0006;2.62±0.83vs.7.77±1.32,P=0.0026;4.69±1.13vs.11.41±1.92,P=0.0054).Conclusion:HMGB1 blockade(anti-HMGB1 mAb)reduced leukocyte infiltration and suppressed inflammatory cytokine expression in this K14-VEGF transgenic mouse model,markedly reducing the severity of the psoriasis-like lesions.HMGB1 blockade might serve as a potential target for the treatment of psoriasis.展开更多
文摘Introduction: Hepatic diseases comprise inflammations of the liver, which can originate from drug-induced, toxic, autoimmune sources and particularly hepatitis B and C virus infection. The outcome of the disease is linked to interactions between the immune system and the virus, and also depends on the age and immune status of the patient. The aim of this study was to evaluate the association of a MAP3K14 (rs2074292), CD40 (rs1883832) polymorphism and chronic hepatitis B virus carriage in a population from Burkina Faso. Methods: In this case-control analysis, 223 and 173 samples, consisting of 90 and 53 controls and 133 and 120 cases, were examined for MAP3K14 and CD40 respectively. The cases included patients with Chronic Hepatitis B (CHB), cirrhosis or hepatocellular carcinoma (HCC). Genomic DNA extraction was executed using INVITROGEN and FAVORGEN kits. Genotyping of MAP3K14 (rs2074292) and CD40 (rs1883832) gene polymorphisms was accomplished via real-time PCR on the QuantStudioTM 5 Real-Time instrument, followed by allelic discrimination using TaqMan Genotyper Software. Data was interpreted using SPSS version 20 and Epi info version 7.5.2.0. Odds ratios (OR), confidence intervals (CI), and p-values were derived for risk and significance evaluation. Results: This study showed that the heterozygous CT genotype and the mutated T allele of the CD40 (rs1883832) gene are involved in the progression of chronic hepatitis to cirrhosis and hepatocellular carcinoma in HBV-infected patients. However, no association was found between polymorphisms in the MAP3K14 gene (rs2074292) and the progression of HBV infection. By combining the two polymorphisms, we observed either high risk or protection, depending on the genotypes of the MAP3K14 and CD40 genes simultaneously carried by the patient. Conclusion: Polymorphisms of the MAP3K14 and CD40 genes are associated with the evolution of HBV infection.
基金supported by grants from the National Natural Science Foundation of China(31970578,31872812,31671335,and 31600046)the Natural Science Foundation of Hubei Province(2017CFA066).
文摘Cells need to coordinate gene expression with their metabolic states to maintain cell homeostasis and growth.However,how cells transduce nutrient availability to appropriate gene expression response via histone modifications remains largely unknown.Here,we report that glucose specifically induces histone H3K4 trimethylation(H3K4me3),an evolutionarily conserved histone covalent modification associated with active gene transcription,and that glycolytic enzymes and metabolites are required for this in?duction.Although glycolysis supplies S-adenosylmethionine for histone methyltransferase Setl to catalyze H3K4me3,glucose induces H3K4me3 primarily by inhibiting histone demethylase Jhd2-catalyzed H3K4 demethylation.Glycolysis provides acetyl-CoA to stimulate histone acetyltransferase Gcn5 to acetylate H3K14,which then inhibits the binding of Jhd2 to chromatin to increase H3K4me3.By repressing Jhd2-mediated H3K4 demethylation,glycolytic enzymes regulate gene expression and cell survival during chronological aging.Thus,our results elucidate how cells reprogram their gene expression programs in response to glucose availability via histone modifications.
基金supported in part by the Natural Science Foundation of China(No.81470143)research grants from the Health and Family Planning Commission of Sichuan Province(Nos.150005 and 16PJ035)。
文摘Objective:Anti-high-mobility group box 1(HMGB1)is involved in the pathogenesis of many inflammatory and autoimmune diseases,including psoriasis.The present study aimed to investigate the therapeutic effects of HMGB1 monoclonal antibody(mAb)in keratin 14(K14)-vascular endothelial growth factor(VEGF)transgenic homozygous mice.Methods:Twelve VEGF transgenic mice were randomly divided into two groups of six mice each:the anti-HMGB1 mAb group and the immune complex(IC)mAb group.The mice underwent intraperitoneal injection of anti-HMGB1 mAb or IC mAb once every 2 days for a total of three treatments.Compare the lesions on the ears of the mice and evaluate the severity of the lesions using the baseline and clinical scores on the last day of treatment.The changes in psoriasis-like lesions,cellular infiltration of T cells,dendritic cells,and neutrophils were detected by hematoxylin-eosin staining and immunohistochemistry.The mRNA expression of the inflammatory cytokines,including interleukin(IL)-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the lesions were assessed by real-time quantitative polymerase chain reaction.The number ofγδT cells in the lesions of two groups were detected by flow cytometry.Thet test was used to compare their differences.Results:The anti-HMGB1 mAb effectively ameliorated the clinical skin lesions.The clinical scores in the anti-HMGB1 mAb group were lower than those in the IC mAb group(6.00±0.52vs.10.83±0.48,P<0.001).Histopathologic changes and improvements in the K14-VEGF transgenic homozygous mice were evident after three treatments.The scores of mice in the anti-HMGB1 mAb group were significantly lower than those in the IC mAb group(3.25±0.71vs.6.95±0.83,P=0.0033).The average epidermal thickness in the anti-HMGB1 mAb group was reduced by about 45%when compared with that in the IC mAb group(32.15±7.08vs.64.69±7.93,P=0.0054).Moreover,anti-HMGB1 mAb also decreased the number of infiltrating CD3+T cells,myeloperoxidase-positive neutrophils,and CD11c+dendritic cells.The ratio of ear skinγδT cells was reduced in anti-HMGB1 mAb treated group.The mRNA expression of IL-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the anti-HMGB1 mAb group were significantly reduced when compared with IC mAb group(0.36±0.070vs.1.98±0.62,P=0.0148;6.43±1.37vs.13.80±1.33,P=0.0006;2.62±0.83vs.7.77±1.32,P=0.0026;4.69±1.13vs.11.41±1.92,P=0.0054).Conclusion:HMGB1 blockade(anti-HMGB1 mAb)reduced leukocyte infiltration and suppressed inflammatory cytokine expression in this K14-VEGF transgenic mouse model,markedly reducing the severity of the psoriasis-like lesions.HMGB1 blockade might serve as a potential target for the treatment of psoriasis.
