Z. Eslami, Ommolbanin Younesian, S. J. Mirghani, Wilza Arantes Ferreira Peres, A. Norouzi, Sara Hosseinzadeh, Hosein Naseh, Abdorreza Eghbal Moghanlou, H. Joshaghani, Javad Azari Bideskan
Background: Accumulation of fat in the liver is one of the causes of non-alcoholic fatty liver disease (NAFLD), which affects about 30% of the world's population. Animal models have been useful tools for investigating the mechanisms involved in the etiology of NAFLD and developing new drugs. Objectives: This study aimed to present a new model for the detection of NAFLD in rats. Methods: Forty-eight rats were randomly divided into six experimental groups: (1) control; (2) 45% fructose + 35% olive oil + carbon tetrachloride (FFC1); (3) carbon tetrachloride (1: 4 in olive oil) (C1); (4) carbon tetrachloride (1: 6 in olive oil) (C2); (5) 12.5% fructose + 12.5% olive oil (FF); and (6) 20% fructose + carbon tetrachloride (1: 4 in olive oil) (FC1). Blood samples were taken in three steps, and liver tissue was dissected at the end of the sixth week for histopathological assessments. Results: After six weeks, the alanine transaminase (131.63 ± 1.51), aspartate transaminase (275 ± 1.0), and gamma-glutamyl transferase (4.30 ± 0.1) levels increased significantly in the C1 group (P < 0.05). The serum lipid profile showed significant changes in all groups compared to the controls (P < 0.01). According to the histological results, all experimental groups, except the C2 group, showed symptoms of NAFLD; nevertheless, a higher NAFLD Activity Score (NAS) was found in the C1 group, followed by the FC1 group, compared to the other groups. Conclusions: The present results revealed that injection of 0.1 mL/kg of carbon tetrachloride (C1 group), alone or along with a diet containing 20% fructose (FC1 group), provided useful animal models of NAFLD, although carbon tetrachloride injection alone is the most effective model in inducing NAFLD model that can be used as a new strategy in nutritional and pharmacological studies.
{"title":"An Efficient Model of Non-alcoholic Fatty Liver Disease (NAFLD) Versus Current Experimental Models: Effects of Fructose, Fat, and Carbon Tetrachloride on NAFLD","authors":"Z. Eslami, Ommolbanin Younesian, S. J. Mirghani, Wilza Arantes Ferreira Peres, A. Norouzi, Sara Hosseinzadeh, Hosein Naseh, Abdorreza Eghbal Moghanlou, H. Joshaghani, Javad Azari Bideskan","doi":"10.5812/hepatmon.117696","DOIUrl":"https://doi.org/10.5812/hepatmon.117696","url":null,"abstract":"Background: Accumulation of fat in the liver is one of the causes of non-alcoholic fatty liver disease (NAFLD), which affects about 30% of the world's population. Animal models have been useful tools for investigating the mechanisms involved in the etiology of NAFLD and developing new drugs. Objectives: This study aimed to present a new model for the detection of NAFLD in rats. Methods: Forty-eight rats were randomly divided into six experimental groups: (1) control; (2) 45% fructose + 35% olive oil + carbon tetrachloride (FFC1); (3) carbon tetrachloride (1: 4 in olive oil) (C1); (4) carbon tetrachloride (1: 6 in olive oil) (C2); (5) 12.5% fructose + 12.5% olive oil (FF); and (6) 20% fructose + carbon tetrachloride (1: 4 in olive oil) (FC1). Blood samples were taken in three steps, and liver tissue was dissected at the end of the sixth week for histopathological assessments. Results: After six weeks, the alanine transaminase (131.63 ± 1.51), aspartate transaminase (275 ± 1.0), and gamma-glutamyl transferase (4.30 ± 0.1) levels increased significantly in the C1 group (P < 0.05). The serum lipid profile showed significant changes in all groups compared to the controls (P < 0.01). According to the histological results, all experimental groups, except the C2 group, showed symptoms of NAFLD; nevertheless, a higher NAFLD Activity Score (NAS) was found in the C1 group, followed by the FC1 group, compared to the other groups. Conclusions: The present results revealed that injection of 0.1 mL/kg of carbon tetrachloride (C1 group), alone or along with a diet containing 20% fructose (FC1 group), provided useful animal models of NAFLD, although carbon tetrachloride injection alone is the most effective model in inducing NAFLD model that can be used as a new strategy in nutritional and pharmacological studies.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44207673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Astinchap, A. Monazzami, Khadijeh Fereidoonfara, Z. Rahimi, M. Rahimi
Background: There is limited research on the effects of physical activity with moderate intensity on βklotho (BKL) and fibroblast growth factor-21 (FGF-21) proteins expression in diabetic patients with non-alcoholic fatty liver disease (NAFLD). Objectives: This study was aimed to determine the effects of eight weeks of endurance and resistance training on BKL and FGF-21 proteins expression in diabetic women with NAFLD. Methods: Forty-five diabetic women (age: 51 ± 8 years, height: 158 ± 2 cm, weight: 75 ± 8 kg) with NAFLD participated. The subjects were randomly divided into three groups, including control (n = 15), endurance training (n = 15), and resistance training (n = 15). The enzyme-linked immunosorbent assay (ELISA) was used to measure BKL and FGF-21 proteins. Two-way ANOVA with repeated measures was applied to determine differences at a significant level of P < 0.05. Results: Eight weeks of endurance and resistance training reduced AST, ALT, and FGF-21 (25, 26, 19% and 13, 16, 13%, respectively) and increased BKL (16% and 18, respectively). However, in the variables of HDL, insulin, AST, ALT, FGF-21, and BKL, a significant difference was observed in the control group (P < 0.05). Also, there was a significant difference between the control and training groups in BKL and FGF21 proteins expression (P < 0.05), but no significant difference was observed between the two training groups (P > 0.05). Conclusions: The results suggest that both moderate-intensity endurance and resistance training can modulate the destructive effects of type 2 diabetes and NAFLD on BKL and FGF-21 proteins expression, and there is no difference between the two training methods.
{"title":"Modulation of Fibroblast Growth Factor-21 and βklotho Proteins Expression in Type 2 Diabetic Women with Non-alcoholic Fatty Liver Disease Following Endurance and Strength Training","authors":"A. Astinchap, A. Monazzami, Khadijeh Fereidoonfara, Z. Rahimi, M. Rahimi","doi":"10.5812/hepatmon.116513","DOIUrl":"https://doi.org/10.5812/hepatmon.116513","url":null,"abstract":"Background: There is limited research on the effects of physical activity with moderate intensity on βklotho (BKL) and fibroblast growth factor-21 (FGF-21) proteins expression in diabetic patients with non-alcoholic fatty liver disease (NAFLD). Objectives: This study was aimed to determine the effects of eight weeks of endurance and resistance training on BKL and FGF-21 proteins expression in diabetic women with NAFLD. Methods: Forty-five diabetic women (age: 51 ± 8 years, height: 158 ± 2 cm, weight: 75 ± 8 kg) with NAFLD participated. The subjects were randomly divided into three groups, including control (n = 15), endurance training (n = 15), and resistance training (n = 15). The enzyme-linked immunosorbent assay (ELISA) was used to measure BKL and FGF-21 proteins. Two-way ANOVA with repeated measures was applied to determine differences at a significant level of P < 0.05. Results: Eight weeks of endurance and resistance training reduced AST, ALT, and FGF-21 (25, 26, 19% and 13, 16, 13%, respectively) and increased BKL (16% and 18, respectively). However, in the variables of HDL, insulin, AST, ALT, FGF-21, and BKL, a significant difference was observed in the control group (P < 0.05). Also, there was a significant difference between the control and training groups in BKL and FGF21 proteins expression (P < 0.05), but no significant difference was observed between the two training groups (P > 0.05). Conclusions: The results suggest that both moderate-intensity endurance and resistance training can modulate the destructive effects of type 2 diabetes and NAFLD on BKL and FGF-21 proteins expression, and there is no difference between the two training methods.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44451193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Cheng, Zhe Zhu, Shuyuan Ye, Junfeng Chen, Xunjun Dong, Guosheng Gao
Background: Secreted frizzled-related protein 4 (sFRP4) is elevated in hepatocellular carcinoma (HCC) patients, suggesting that it can be served as a candidate marker for diagnosing HCC. However, little is known about its role in the different stages of chronic hepatitis B virus (HBV) infection. Objectives: This study was conducted to explore the clinical value of plasma sFRP4 in the different stages of chronic HBV infection. Methods: A total of 303 patients with chronic HBV infection were enrolled in this cross-sectional study. They were classified into the chronic hepatitis B (CHB), liver cirrhosis (LC), HCC, and acute-on-chronic liver failure (ACLF) groups on admission. Additionally, 30 healthy subjects were included in the healthy control (HC) group. The clinical value of plasma sFRP4 in the different stages of chronic HBV infection was analyzed. Results: There were 54, 85, 105, 59, and 30 cases in the CHB, LC, HCC, ACLF, and HC groups, respectively. ACLF group had the highest plasma sFRP4 levels compared to the CHB, LC, and HCC groups (all P < 0.001), followed by the HCC and LC groups. LC and HCC groups were found with up-regulated sFRP4 than the CHB group (all P < 0.05). High levels of plasma sFRP4 were recognized as an independent risk factor for distinguishing patients with ACLF from patients with CHB and LC [adjusted odds ratio (OR):1.005, 95% confidence interval (CI): 1.000 - 1.010, P = 0.043], with the area under the receiver operating characteristic curve (AUC) of 0.790 (95% CI: 0.726 - 0.844, P < 0.001). However, in patients with ACLF, plasma sFRP4 levels in the deteriorated group were higher than in the improved group, with a marginally significant difference (P = 0.071). The AUC for predicting the 90 days prognosis in patients with ACLF was 0.640 (P = 0.064). Conclusions: Plasma sFRP4 might be a biomarker to reflect the progression of chronic HBV infection. However, it was not significantly related to the prognosis in patients with ACLF; we did not find this, which may be due to the small sample size.
{"title":"Clinical Value of Plasma Secreted Frizzled-Related Protein 4 in the Chronic Hepatitis B Virus Infection: A Cross-sectional Study","authors":"M. Cheng, Zhe Zhu, Shuyuan Ye, Junfeng Chen, Xunjun Dong, Guosheng Gao","doi":"10.5812/hepatmon.116525","DOIUrl":"https://doi.org/10.5812/hepatmon.116525","url":null,"abstract":"Background: Secreted frizzled-related protein 4 (sFRP4) is elevated in hepatocellular carcinoma (HCC) patients, suggesting that it can be served as a candidate marker for diagnosing HCC. However, little is known about its role in the different stages of chronic hepatitis B virus (HBV) infection. Objectives: This study was conducted to explore the clinical value of plasma sFRP4 in the different stages of chronic HBV infection. Methods: A total of 303 patients with chronic HBV infection were enrolled in this cross-sectional study. They were classified into the chronic hepatitis B (CHB), liver cirrhosis (LC), HCC, and acute-on-chronic liver failure (ACLF) groups on admission. Additionally, 30 healthy subjects were included in the healthy control (HC) group. The clinical value of plasma sFRP4 in the different stages of chronic HBV infection was analyzed. Results: There were 54, 85, 105, 59, and 30 cases in the CHB, LC, HCC, ACLF, and HC groups, respectively. ACLF group had the highest plasma sFRP4 levels compared to the CHB, LC, and HCC groups (all P < 0.001), followed by the HCC and LC groups. LC and HCC groups were found with up-regulated sFRP4 than the CHB group (all P < 0.05). High levels of plasma sFRP4 were recognized as an independent risk factor for distinguishing patients with ACLF from patients with CHB and LC [adjusted odds ratio (OR):1.005, 95% confidence interval (CI): 1.000 - 1.010, P = 0.043], with the area under the receiver operating characteristic curve (AUC) of 0.790 (95% CI: 0.726 - 0.844, P < 0.001). However, in patients with ACLF, plasma sFRP4 levels in the deteriorated group were higher than in the improved group, with a marginally significant difference (P = 0.071). The AUC for predicting the 90 days prognosis in patients with ACLF was 0.640 (P = 0.064). Conclusions: Plasma sFRP4 might be a biomarker to reflect the progression of chronic HBV infection. However, it was not significantly related to the prognosis in patients with ACLF; we did not find this, which may be due to the small sample size.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45897104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Hepatitis C virus (HCV) may remain asymptomatic or cause liver fibrosis and cirrhosis. Objectives: We aimed to assess the relationship between serum peptidyl-prolyl cis-trans isomerase NIMA-interacted 1 (Pin1) levels and liver fibrosis due to HCV. Methods: Serum samples of successive patients with HCV genotype 1b and healthy volunteers were collected, and Pin1 levels were measured using ELISA kits. Liver fibrosis stages were calculated by the Ishak Scoring System and subdivided into two groups; stage < 3 (mild fibrosis) and ≥ 3 (advanced fibrosis). Correlation and area under receiver operating characteristics (AUROC) analysis were used to investigate the relationship between Pin1 and clinical and histopathological properties of HCV infection. Results: Ninety-four patients with HCV and 47 age- and sex-matched volunteers were included. The median age of the participants was 52, and 55% of whom were females. The mean (SD) of Pin1 serum level was significantly higher in the HCV group compared with healthy volunteers (33.94 (21.15) vs. 26.82 (8.85) pg/mL, respectively, P = 0.007). Seventy-seven (82%) and 17 (18%) of the participants showed mild and advanced fibrosis, respectively. Pin1 serum levels were significantly lower in the mild compared with advanced fibrosis group (29 (17.88) vs. 43.59 (7.98) pg/mL, respectively, P < 0.001). We found a significantly positive correlation between Pin1 serum level and liver fibrosis stage (r = 0.71, P < 0.001). The cut off of 33.04 pg/mL of Pin1 serum level showed the best sensitivity (100%) and specificity (68.4%) (AUROC = 0.81 [95% confidence interval: 0.72 - 0.90], P < 0.001) for distinguishing advanced from mild liver fibrosis. Conclusions: Serum Pin1 level may be a relevant marker for predicting liver fibrosis in HCV infected patients.
背景:丙型肝炎病毒(HCV)可能保持无症状或引起肝纤维化和肝硬化。目的:我们旨在评估血清肽酰脯氨酸顺式反式异构酶1 (nima -相互作用1)水平与丙型肝炎肝纤维化之间的关系。方法:连续收集HCV基因型1b患者和健康志愿者的血清样本，采用ELISA试剂盒检测Pin1水平。采用Ishak评分系统计算肝纤维化分期，并细分为两组;分期< 3(轻度纤维化)和≥3(晚期纤维化)。采用相关性分析和AUROC (area under receiver operating characteristic)分析Pin1与HCV感染临床和组织病理学特征的关系。结果:纳入94例HCV患者和47名年龄和性别匹配的志愿者。参与者的年龄中位数为52岁，其中55%为女性。HCV组血清Pin1水平均值(SD)显著高于健康志愿者(33.94 (21.15)vs. 26.82 (8.85) pg/mL, P = 0.007)。77名(82%)和17名(18%)的参与者分别表现为轻度和晚期纤维化。与晚期纤维化组相比，轻度纤维化组血清Pin1水平显著降低(分别为29(17.88)比43.59 (7.98)pg/mL, P < 0.001)。我们发现血清Pin1水平与肝纤维化分期呈正相关(r = 0.71, P < 0.001)。血清Pin1水平以33.04 pg/mL为临界值，是区分晚期和轻度肝纤维化的最佳敏感性(100%)和特异性(68.4%)(AUROC = 0.81[95%可信区间:0.72 ~ 0.90]，P < 0.001)。结论:血清Pin1水平可能是预测HCV感染患者肝纤维化的相关指标。
{"title":"Serum Peptidyl-prolyl Cis-trans Isomerase NIMA-interacted 1 (Pin1) as a Non-invasive Marker for Liver Fibrosis due to Chronic Hepatitis C Virus.","authors":"M. Cengiz, S. Ozenirler","doi":"10.5812/hepatmon.116687","DOIUrl":"https://doi.org/10.5812/hepatmon.116687","url":null,"abstract":"Background: Hepatitis C virus (HCV) may remain asymptomatic or cause liver fibrosis and cirrhosis. Objectives: We aimed to assess the relationship between serum peptidyl-prolyl cis-trans isomerase NIMA-interacted 1 (Pin1) levels and liver fibrosis due to HCV. Methods: Serum samples of successive patients with HCV genotype 1b and healthy volunteers were collected, and Pin1 levels were measured using ELISA kits. Liver fibrosis stages were calculated by the Ishak Scoring System and subdivided into two groups; stage < 3 (mild fibrosis) and ≥ 3 (advanced fibrosis). Correlation and area under receiver operating characteristics (AUROC) analysis were used to investigate the relationship between Pin1 and clinical and histopathological properties of HCV infection. Results: Ninety-four patients with HCV and 47 age- and sex-matched volunteers were included. The median age of the participants was 52, and 55% of whom were females. The mean (SD) of Pin1 serum level was significantly higher in the HCV group compared with healthy volunteers (33.94 (21.15) vs. 26.82 (8.85) pg/mL, respectively, P = 0.007). Seventy-seven (82%) and 17 (18%) of the participants showed mild and advanced fibrosis, respectively. Pin1 serum levels were significantly lower in the mild compared with advanced fibrosis group (29 (17.88) vs. 43.59 (7.98) pg/mL, respectively, P < 0.001). We found a significantly positive correlation between Pin1 serum level and liver fibrosis stage (r = 0.71, P < 0.001). The cut off of 33.04 pg/mL of Pin1 serum level showed the best sensitivity (100%) and specificity (68.4%) (AUROC = 0.81 [95% confidence interval: 0.72 - 0.90], P < 0.001) for distinguishing advanced from mild liver fibrosis. Conclusions: Serum Pin1 level may be a relevant marker for predicting liver fibrosis in HCV infected patients.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41934437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hossein Ghaderi-Zefrehi, Mohammad Gholami-Fesharaki, Amir Ghorbanzadeh, Farzin Sadeghi
Context: Hepatitis C Virus (HCV) infection is a major cause of chronic cirrhosis and hepatocellular carcinoma. Approximately 30% of infected persons with HCV spontaneously clear the viral infection; but, some of the remaining patients develop chronic HCV. Studies show that HLA molecules play an important role in the outcome of HCV infection by influencing the efficiency of the antiviral immune response to HCV infection. It is now known that polymorphisms in HLA loci are associated with HCV susceptibility or clearance. The purpose of the present study was to systematically review the studies that reported the association of HLA class II alleles (HLA-DQ and HLA-DR) with the outcome of HCV infection. Evidence Acquisition: Studies were identified by searching electronic databases, including PubMed and Scopus. A total of 12,265 relevant studies were identified by the electronic search, of which a total of 19 eligible papers were identified that were meta-analyzed for the association between HLA class II alleles and the outcome of HCV infection. Results: Subjects carrying HLA-DQB1*0301, HLA-DQB1*0501, HLA-DRB1*1303, HLA-DRB1*1201, HLA-DRB1*0401, HLA-DRB1*0101, and HLA-DRB1*1101 alleles were significantly associated with higher spontaneous clearance of HCV infection. Conclusions: The data from the current study confirm that several polymorphisms in HLA-DQ and HLA-DR loci are correlated with the clearance of HCV infection. Identifying these polymorphisms may contribute to a better understanding of immune mechanisms of HCV clearance or persistence.
{"title":"Association of HLA Class II Alleles with Outcome of Hepatitis C Virus Infection: A Systematic Review and Meta-analysis","authors":"Hossein Ghaderi-Zefrehi, Mohammad Gholami-Fesharaki, Amir Ghorbanzadeh, Farzin Sadeghi","doi":"10.5812/hepatmon.109493","DOIUrl":"https://doi.org/10.5812/hepatmon.109493","url":null,"abstract":"Context: Hepatitis C Virus (HCV) infection is a major cause of chronic cirrhosis and hepatocellular carcinoma. Approximately 30% of infected persons with HCV spontaneously clear the viral infection; but, some of the remaining patients develop chronic HCV. Studies show that HLA molecules play an important role in the outcome of HCV infection by influencing the efficiency of the antiviral immune response to HCV infection. It is now known that polymorphisms in HLA loci are associated with HCV susceptibility or clearance. The purpose of the present study was to systematically review the studies that reported the association of HLA class II alleles (HLA-DQ and HLA-DR) with the outcome of HCV infection. Evidence Acquisition: Studies were identified by searching electronic databases, including PubMed and Scopus. A total of 12,265 relevant studies were identified by the electronic search, of which a total of 19 eligible papers were identified that were meta-analyzed for the association between HLA class II alleles and the outcome of HCV infection. Results: Subjects carrying HLA-DQB1*0301, HLA-DQB1*0501, HLA-DRB1*1303, HLA-DRB1*1201, HLA-DRB1*0401, HLA-DRB1*0101, and HLA-DRB1*1101 alleles were significantly associated with higher spontaneous clearance of HCV infection. Conclusions: The data from the current study confirm that several polymorphisms in HLA-DQ and HLA-DR loci are correlated with the clearance of HCV infection. Identifying these polymorphisms may contribute to a better understanding of immune mechanisms of HCV clearance or persistence.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47318514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junwang Zhang, Xumei Kang, Ling Zhang, Hui-min Wang, Z. Deng
Background: Non-alcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma, but the understanding of the regulatory mechanisms driving NASH is not comprehensive. Objectives: We aimed to identify the potential markers of NASH and explore their relationship with immune cell populations. Methods: Five gene expression datasets for NASH were downloaded from the Gene Expression Omnibus and European Bioinformatics Institute (EBI) Array Express databases. Differentially expressed genes (DEGs) between NASH and controls were screened. Gene Ontology-Biological Process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for functional enrichment analysis of DEGs. Among the candidate genes selected from the protein-protein interaction (PPI) network and module analysis, DEG signatures were further identified using least absolute shrinkage and selection operator (LASSO) regression analysis. The Spearman correlation coefficient was calculated to assess the correlation between DEG signatures and immune cell abundance based on the CIBERSORT algorithm. Results: We screened 403 upregulated, and 158 downregulated DEGs for NASH, and they were mainly enriched in GO-BP, including the inflammatory response, innate immune response, signal transduction, and KEGG pathways, such as the pathways involved in cancer (e.g., the PI3K-Akt signaling pathway), and focal adhesion. We then screened 73 candidate genes from the PPI network and module analysis and finally identified 17 DEG signatures. By evaluating their relationship with immune cell populations, 12 DEG signatures were found to correlate with activated dendritic cells, resting dendritic cells, M2 macrophages, monocytes, neutrophils, and resting memory CD4 T cells, which were significantly different between the NASH and control tissues. Conclusions: We identified a 17-DEG-signature as a candidate biomarker for NASH and analyzed its relationship with immune infiltration in NASH.
{"title":"Identification of a 17-gene-signature in Non-alcoholic Steatohepatitis and Its Relationship with Immune Cell Infiltration","authors":"Junwang Zhang, Xumei Kang, Ling Zhang, Hui-min Wang, Z. Deng","doi":"10.5812/HEPATMON.116366","DOIUrl":"https://doi.org/10.5812/HEPATMON.116366","url":null,"abstract":"Background: Non-alcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma, but the understanding of the regulatory mechanisms driving NASH is not comprehensive. Objectives: We aimed to identify the potential markers of NASH and explore their relationship with immune cell populations. Methods: Five gene expression datasets for NASH were downloaded from the Gene Expression Omnibus and European Bioinformatics Institute (EBI) Array Express databases. Differentially expressed genes (DEGs) between NASH and controls were screened. Gene Ontology-Biological Process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for functional enrichment analysis of DEGs. Among the candidate genes selected from the protein-protein interaction (PPI) network and module analysis, DEG signatures were further identified using least absolute shrinkage and selection operator (LASSO) regression analysis. The Spearman correlation coefficient was calculated to assess the correlation between DEG signatures and immune cell abundance based on the CIBERSORT algorithm. Results: We screened 403 upregulated, and 158 downregulated DEGs for NASH, and they were mainly enriched in GO-BP, including the inflammatory response, innate immune response, signal transduction, and KEGG pathways, such as the pathways involved in cancer (e.g., the PI3K-Akt signaling pathway), and focal adhesion. We then screened 73 candidate genes from the PPI network and module analysis and finally identified 17 DEG signatures. By evaluating their relationship with immune cell populations, 12 DEG signatures were found to correlate with activated dendritic cells, resting dendritic cells, M2 macrophages, monocytes, neutrophils, and resting memory CD4 T cells, which were significantly different between the NASH and control tissues. Conclusions: We identified a 17-DEG-signature as a candidate biomarker for NASH and analyzed its relationship with immune infiltration in NASH.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44733800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Hepatic stellate cells (HSCs) play a primary role in liver fibrogenesis. NOXs are the main origin of reactive oxygen species (ROS) in the liver. Among them, NOX1, NOX2, and NOX4 are expressed more in HSCs and are involved in the development of liver fibrosis. Quercetin, an abundant citrus flavonoid, is known to have beneficial effects on liver injury and hepatic fibrosis. Objectives: In this study, the effect of quercetin on NOX1, NOX2, and NOX4 expression and Smad3 phosphorylation induced by TGF-β in the human hepatic LX2 cell line was investigated. Methods: The cytotoxic effects of quercetin on the cells were determined by MTT assay. The cells were activated with 2 ng/mL of TGF-β for 24 h and then treated with different concentrations of Quercetin. The mRNA expression rates of NOX1, NOX2, NOX4, and phosphorylated Smad 3C (p-Smad3C) were analyzed using real-time polymerase chain reaction (PCR) and western blot assays. Results: TGF-β increased the mRNA expression of NOX1, NOX2, and NOX4 and the protein level of p-Smad3C in the LX2 cell line. Quercetin significantly decreased the mRNA expression of NOX1, NOX2, and NOX4 in the LX-2 cells. Moreover, quercetin significantly diminished the p-Smad3C level in the LX-2 cell line activated with TGF-β. Conclusions: Quercetin may be effective in improving hepatic fibrosis via the reduction of NOX1, NOX2, and NOX4 expression in activated HSCs. The main mechanism through which quercetin reduces the expression of these target genes may be related to the reduction of the p-Smad3C level.
{"title":"Effect of Quercetin on the Expression of NOXs and P-Smad3C in TGF-Β-Activated Hepatic Stellate Cell Line LX-2","authors":"Narges Mohammadtaghvaei, Reza Afarin, Fatemeh Mavalizadeh, Elham Shakerian, Samaneh Salehipour Bavarsad, G. Mohammadzadeh","doi":"10.5812/hepatmon.116875","DOIUrl":"https://doi.org/10.5812/hepatmon.116875","url":null,"abstract":"Background: Hepatic stellate cells (HSCs) play a primary role in liver fibrogenesis. NOXs are the main origin of reactive oxygen species (ROS) in the liver. Among them, NOX1, NOX2, and NOX4 are expressed more in HSCs and are involved in the development of liver fibrosis. Quercetin, an abundant citrus flavonoid, is known to have beneficial effects on liver injury and hepatic fibrosis. Objectives: In this study, the effect of quercetin on NOX1, NOX2, and NOX4 expression and Smad3 phosphorylation induced by TGF-β in the human hepatic LX2 cell line was investigated. Methods: The cytotoxic effects of quercetin on the cells were determined by MTT assay. The cells were activated with 2 ng/mL of TGF-β for 24 h and then treated with different concentrations of Quercetin. The mRNA expression rates of NOX1, NOX2, NOX4, and phosphorylated Smad 3C (p-Smad3C) were analyzed using real-time polymerase chain reaction (PCR) and western blot assays. Results: TGF-β increased the mRNA expression of NOX1, NOX2, and NOX4 and the protein level of p-Smad3C in the LX2 cell line. Quercetin significantly decreased the mRNA expression of NOX1, NOX2, and NOX4 in the LX-2 cells. Moreover, quercetin significantly diminished the p-Smad3C level in the LX-2 cell line activated with TGF-β. Conclusions: Quercetin may be effective in improving hepatic fibrosis via the reduction of NOX1, NOX2, and NOX4 expression in activated HSCs. The main mechanism through which quercetin reduces the expression of these target genes may be related to the reduction of the p-Smad3C level.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43909727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shaomei Zhu, Bochao Liu, Yuxia Xu, Ling Zhang, Z. Xia, Jihong Liu, Xiaoming Zhou, Yongshui Fu, J. Allain, Chengyao Li, Tingting Li
Background: The traditional ultracentrifugation purification method of hepatitis C virus (HCV) particles requires special equipment, limiting its wide application. Therefore, more effective and convenient methods for HCV are needed. Objectives: The present study aimed to establish simple and effective purification methods for HCV. Methods: The infectious clone of the HCV genome (JFH-1) was transfected to the human hepatoma cell line (Huh7.5.1) and cultured in Dulbecco’s modified eagle medium/nutrient mixture F-12. The infectivity of JFH-1 culture was determined by reverse transcription-quantitative polymerase chain reaction and immunofluorescence. After concentration by centrifugal filter devices, HCV particles were purified by heparin-affinity chromatography and magnetic separation technique. The purified viruses were detected by the western blot and immune-electron microscopy. Results: The infectious titer of JFH-1 transfected Huh7.5.1 in the serum-free culture medium was 4.5 × 104 FFU/mL, and HCV ribonucleic acid load was 3.946 × 106 IU/mL in 30 days of cell culture post-transfection. After purification by heparin-affinity chromatography or magnetic separation method, viral particles were visualized with spherical morphology and an average diameter of 55 nm assessed by electron microscopy. The viruses were confirmed by the western blot and immune-electron microscopy with specific antibodies to HCV. Conclusions: The heparin-affinity chromatography and magnetic separation methods were established for the purification of HCV, which were simple and efficient methods for the stable purification of HCV particles on a large scale.
{"title":"Two New Purification Methods of Hepatitis C Virus Particles from Serum-Free Culture System","authors":"Shaomei Zhu, Bochao Liu, Yuxia Xu, Ling Zhang, Z. Xia, Jihong Liu, Xiaoming Zhou, Yongshui Fu, J. Allain, Chengyao Li, Tingting Li","doi":"10.5812/hepatmon.115727","DOIUrl":"https://doi.org/10.5812/hepatmon.115727","url":null,"abstract":"Background: The traditional ultracentrifugation purification method of hepatitis C virus (HCV) particles requires special equipment, limiting its wide application. Therefore, more effective and convenient methods for HCV are needed. Objectives: The present study aimed to establish simple and effective purification methods for HCV. Methods: The infectious clone of the HCV genome (JFH-1) was transfected to the human hepatoma cell line (Huh7.5.1) and cultured in Dulbecco’s modified eagle medium/nutrient mixture F-12. The infectivity of JFH-1 culture was determined by reverse transcription-quantitative polymerase chain reaction and immunofluorescence. After concentration by centrifugal filter devices, HCV particles were purified by heparin-affinity chromatography and magnetic separation technique. The purified viruses were detected by the western blot and immune-electron microscopy. Results: The infectious titer of JFH-1 transfected Huh7.5.1 in the serum-free culture medium was 4.5 × 104 FFU/mL, and HCV ribonucleic acid load was 3.946 × 106 IU/mL in 30 days of cell culture post-transfection. After purification by heparin-affinity chromatography or magnetic separation method, viral particles were visualized with spherical morphology and an average diameter of 55 nm assessed by electron microscopy. The viruses were confirmed by the western blot and immune-electron microscopy with specific antibodies to HCV. Conclusions: The heparin-affinity chromatography and magnetic separation methods were established for the purification of HCV, which were simple and efficient methods for the stable purification of HCV particles on a large scale.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43647576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sibel Altunışık Toplu, A. Kose, S. Karakas, Y. Bayindir, B. Otlu, S. Yılmaz
Background: Cytomegalovirus (CMV) is one of the leading viral agents that can pave the way for serious complications and organ damage in solid organ transplant (SOT) recipients after transplantation. Strategies have been developed to protect at-risk patients from CMV infection following transplantation. Since more than 90% of adults in Turkey were positive for CMV IgG, universal CMV prophylaxis was applied, and the results were evaluated. Objectives: This study aimed to evaluate the results of universal CMV prophylaxis after liver transplantation in the long term. Methods: A total of 1,090 liver transplant patients were evaluated in terms of CMV infection in the Organ Transplantation Institute of Inonu University, Malatya, Turkey, from October 2014 to December 2019. In order to identify the CMV infections, quantitative nucleic acid amplification (QNAT) was used to detect potential CMV DNA. The cut-off value of CMV DNA was determined to be 1000 copies/mL after transplantation. Results: According to the clinical and laboratory assessments, 33 (3%) patients were diagnosed with CMV infection, and 25 (2.3%) patients were evaluated as possibly having CMV syndrome. Also, eight of the 33 patients were assessed as having end-organ CMV disease and 25 as probable CMV syndrome. In the late period following prophylaxis, CMV infection was observed in 10 (0.9%) cases. The infection rate after prophylaxis (0.9%) was lower than the infection rate (2.1%) seen during prophylaxis. Conclusions: Close clinical follow-up with CMV prophylaxis and strict monitoring of CMV DNA by determining a specific cut-off point are important in the follow-up of liver transplant patients.
{"title":"Evaluation of Cytomegalovirus Infections in Liver Transplant Recipients Under Universal Prophylaxis: A Single Centre Experience","authors":"Sibel Altunışık Toplu, A. Kose, S. Karakas, Y. Bayindir, B. Otlu, S. Yılmaz","doi":"10.5812/HEPATMON.115370","DOIUrl":"https://doi.org/10.5812/HEPATMON.115370","url":null,"abstract":"Background: Cytomegalovirus (CMV) is one of the leading viral agents that can pave the way for serious complications and organ damage in solid organ transplant (SOT) recipients after transplantation. Strategies have been developed to protect at-risk patients from CMV infection following transplantation. Since more than 90% of adults in Turkey were positive for CMV IgG, universal CMV prophylaxis was applied, and the results were evaluated. Objectives: This study aimed to evaluate the results of universal CMV prophylaxis after liver transplantation in the long term. Methods: A total of 1,090 liver transplant patients were evaluated in terms of CMV infection in the Organ Transplantation Institute of Inonu University, Malatya, Turkey, from October 2014 to December 2019. In order to identify the CMV infections, quantitative nucleic acid amplification (QNAT) was used to detect potential CMV DNA. The cut-off value of CMV DNA was determined to be 1000 copies/mL after transplantation. Results: According to the clinical and laboratory assessments, 33 (3%) patients were diagnosed with CMV infection, and 25 (2.3%) patients were evaluated as possibly having CMV syndrome. Also, eight of the 33 patients were assessed as having end-organ CMV disease and 25 as probable CMV syndrome. In the late period following prophylaxis, CMV infection was observed in 10 (0.9%) cases. The infection rate after prophylaxis (0.9%) was lower than the infection rate (2.1%) seen during prophylaxis. Conclusions: Close clinical follow-up with CMV prophylaxis and strict monitoring of CMV DNA by determining a specific cut-off point are important in the follow-up of liver transplant patients.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44673932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guo Zhou, Jiaxin Bei, Tianyang Li, K. Zhu, Zhengkun Tu
Background: Activation of hepatic stellate cells (HSCs) is an important driver of liver fibrosis, which is a health problem of global concern, and there is no effective solution for it at the present. Senescent activated HSCs are preferentially killed by natural killer cells (NK cells) to promote the regression of hepatic fibrosis. Objectives: The purpose of this study was to investigate the effect of polyinosinic-polycytidylic acid (poly I:C) on HSCs’ senescence, a trigger for NK cell-induced cytotoxicity. Methods: The senescence of HSCs was assessed by western blot, qRT-PCR, and flow cytometry, and NK cell cytotoxicity was assessed in a co-culture of NK cells with poly I:C-treated HSCs by measuring CD107a expression. Results: The expression of p16, p21, SA-β-gal, MICA/MICB, and ULBP2 increased in poly I:C-treated HSCs, rendering them significantly susceptible to NK cell cytotoxicity. Conclusions: Poly I:C induces cellular senescence in HSCs and triggers NK cell immunosurveillance, suggesting that the role of poly I:C in HSC senescence may promote fibrosis regression.
{"title":"TLR3 Mediates Senescence and Immunosurveillance of Hepatic Stellate Cells","authors":"Guo Zhou, Jiaxin Bei, Tianyang Li, K. Zhu, Zhengkun Tu","doi":"10.5812/HEPATMON.114381","DOIUrl":"https://doi.org/10.5812/HEPATMON.114381","url":null,"abstract":"Background: Activation of hepatic stellate cells (HSCs) is an important driver of liver fibrosis, which is a health problem of global concern, and there is no effective solution for it at the present. Senescent activated HSCs are preferentially killed by natural killer cells (NK cells) to promote the regression of hepatic fibrosis. Objectives: The purpose of this study was to investigate the effect of polyinosinic-polycytidylic acid (poly I:C) on HSCs’ senescence, a trigger for NK cell-induced cytotoxicity. Methods: The senescence of HSCs was assessed by western blot, qRT-PCR, and flow cytometry, and NK cell cytotoxicity was assessed in a co-culture of NK cells with poly I:C-treated HSCs by measuring CD107a expression. Results: The expression of p16, p21, SA-β-gal, MICA/MICB, and ULBP2 increased in poly I:C-treated HSCs, rendering them significantly susceptible to NK cell cytotoxicity. Conclusions: Poly I:C induces cellular senescence in HSCs and triggers NK cell immunosurveillance, suggesting that the role of poly I:C in HSC senescence may promote fibrosis regression.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47934287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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