AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes and their association with possible transmission routes in the general population of Lahore, as the data exclusively related to this city is limi...AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes and their association with possible transmission routes in the general population of Lahore, as the data exclusively related to this city is limited. METHODS: Complete data regarding patient's history, possible route of infection and biochemical tests was collected from the public hospital for 1364 patients. SPSS version 16 windows software was used for data analysis by univariate and multivariate techniques. RESULTS: Age range ≤ 40 years showed high prevalence of HCV infection. HCV genotype 3a was dominant (55.9%), followed by 1a (23.6%), 4a (12.5%), 3b (3.2%), untypable (2.5%), 4b (1.2%) and mixed type (1.2%). Blood transfusion, dental surgery and barber shops were the main risk factors for HCV transmission. Genotype prevalence was independent of age (P = 0.971) and gender (P = 0.122) while risk factors showed a significant association with age (P = 0.000) and genotypes (P = 0.000). We observed an independent association of risk factors and genotype 3a, while patients with genotype 1 and 4 were mostly infected due to dental surgery blood transfusion and barber shops. Risk factors of intravenous drug use and sexual exposure were exclusively found in ≤ 40 years age group. CONCLUSION: An increase in genotypes 1a and 4a suggest migration of people, possibly from Balochistan and the northern war-zone area. Government should focus on public education regarding infection routes.展开更多
Objective:To evaluate the antiviral activity and phytochemicals of selected plant extracts and their effect on the mitogen-activated protein kinase(MAPK)signaling pathway modulated by hepatitis C virus(HCV)nonstructur...Objective:To evaluate the antiviral activity and phytochemicals of selected plant extracts and their effect on the mitogen-activated protein kinase(MAPK)signaling pathway modulated by hepatitis C virus(HCV)nonstructural protein 5 A(NS5A).Methods:A total of ten plant extracts were initially screened for their toxicities against Hep G2 cells.The non-toxic plants were tested for their inhibitory effect on the expression of HCV NS5A at both m RNA and protein levels using real-time PCR and Western blotting assays,respectively.The differential expression of the genes associated with MAPK pathway in the presence of NS5A gene and plant extract was measured through real-time PCR.Subsequently,the identification of secondary metabolites was carried out by phytochemical and HPLC analysis.Results:The phytochemical profiling of Berberis lyceum revealed the presence of alkaloids,phenols,saponins,tannins,flavonoids,carbohydrates,terpenoids,steroids,and glycosides.Similarly,quercetin,myricetin,gallic acid,caffeic acid,and ferulic acid were identified through HPLC analysis.The methanolic extract of Berberis lyceum strongly inhibited HCV RNA replication with an IC50 of 11.44μg/m L.RT-PCR and Western blotting assays showed that the extract reduced the expression of HCV NS5A in a dosedependent manner.Berberis lyceum extract also attenuated NS5A-induced dysregulation of the MAPK signaling pathway.Conclusions:Our findings suggest that Berberis lyceum extract strongly inhibits HCV propagation by reducing HCV NS5A-induced perturbation of MAPK signaling.展开更多
Chronic Hepatitis C Viral(HCV)infection is a leading health problem worldwide and resulted in fibrotic scar formation,and finally liver-cirrhosis.Although contemporary therapies can partially reverse this destructive ...Chronic Hepatitis C Viral(HCV)infection is a leading health problem worldwide and resulted in fibrotic scar formation,and finally liver-cirrhosis.Although contemporary therapies can partially reverse this destructive process,the rehabilitation is too slow and unsuitable for all chronic infections.The current study elucidates the mechanism of disease progression from early(F1)to moderate(F2,F3),and to severe fibrosis(F4)/cirrhosis in HCV genotype 3a infected patients to find out new candidates as potential disease progression markers and antiviral therapeutic agents.A total of 550 genes were found differentially regulated in the four fibrosis stages and grouped in 22 classes according to their biological functions.Gene set enrichment(GSEA)and Ingenuity pathway analysis(IPA)were used to identify the regulation of crucial biological functions and pathways involved in HCV progression.HCV differentially regulated the expression of genes involved in apoptosis,cell structure,signal transduction,proliferation,metabolism,cytokine signaling,immune response,cell adhesion and maintenance,and post translational modifications by pathway analysis.There was an increasing trend of proliferative and cell growth related genes and shutting down of immune response as the disease progress mild to moderate to advanced stage cirrhosis.The myriad of changes in gene expression showed more chances of developing liver cancer in patients infected with HCV genotype 3a in a systematic manner.The identified gene set can act as disease markers for prediction,whether the fibrosis lead to cirrhosis and its association with end stage liver disease development.展开更多
基金Supported by Prime Minister Program for Prevention and Control of Hepatitis in Pakistan (2005-2010)Grant # 863 by Higher Education Commission
文摘AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes and their association with possible transmission routes in the general population of Lahore, as the data exclusively related to this city is limited. METHODS: Complete data regarding patient's history, possible route of infection and biochemical tests was collected from the public hospital for 1364 patients. SPSS version 16 windows software was used for data analysis by univariate and multivariate techniques. RESULTS: Age range ≤ 40 years showed high prevalence of HCV infection. HCV genotype 3a was dominant (55.9%), followed by 1a (23.6%), 4a (12.5%), 3b (3.2%), untypable (2.5%), 4b (1.2%) and mixed type (1.2%). Blood transfusion, dental surgery and barber shops were the main risk factors for HCV transmission. Genotype prevalence was independent of age (P = 0.971) and gender (P = 0.122) while risk factors showed a significant association with age (P = 0.000) and genotypes (P = 0.000). We observed an independent association of risk factors and genotype 3a, while patients with genotype 1 and 4 were mostly infected due to dental surgery blood transfusion and barber shops. Risk factors of intravenous drug use and sexual exposure were exclusively found in ≤ 40 years age group. CONCLUSION: An increase in genotypes 1a and 4a suggest migration of people, possibly from Balochistan and the northern war-zone area. Government should focus on public education regarding infection routes.
基金supported by the CEMB-TWAS Postgraduate Fellowship(FR number 3240286682,2015)granted to Mr.Koloko Brice Landry
文摘Objective:To evaluate the antiviral activity and phytochemicals of selected plant extracts and their effect on the mitogen-activated protein kinase(MAPK)signaling pathway modulated by hepatitis C virus(HCV)nonstructural protein 5 A(NS5A).Methods:A total of ten plant extracts were initially screened for their toxicities against Hep G2 cells.The non-toxic plants were tested for their inhibitory effect on the expression of HCV NS5A at both m RNA and protein levels using real-time PCR and Western blotting assays,respectively.The differential expression of the genes associated with MAPK pathway in the presence of NS5A gene and plant extract was measured through real-time PCR.Subsequently,the identification of secondary metabolites was carried out by phytochemical and HPLC analysis.Results:The phytochemical profiling of Berberis lyceum revealed the presence of alkaloids,phenols,saponins,tannins,flavonoids,carbohydrates,terpenoids,steroids,and glycosides.Similarly,quercetin,myricetin,gallic acid,caffeic acid,and ferulic acid were identified through HPLC analysis.The methanolic extract of Berberis lyceum strongly inhibited HCV RNA replication with an IC50 of 11.44μg/m L.RT-PCR and Western blotting assays showed that the extract reduced the expression of HCV NS5A in a dosedependent manner.Berberis lyceum extract also attenuated NS5A-induced dysregulation of the MAPK signaling pathway.Conclusions:Our findings suggest that Berberis lyceum extract strongly inhibits HCV propagation by reducing HCV NS5A-induced perturbation of MAPK signaling.
文摘Chronic Hepatitis C Viral(HCV)infection is a leading health problem worldwide and resulted in fibrotic scar formation,and finally liver-cirrhosis.Although contemporary therapies can partially reverse this destructive process,the rehabilitation is too slow and unsuitable for all chronic infections.The current study elucidates the mechanism of disease progression from early(F1)to moderate(F2,F3),and to severe fibrosis(F4)/cirrhosis in HCV genotype 3a infected patients to find out new candidates as potential disease progression markers and antiviral therapeutic agents.A total of 550 genes were found differentially regulated in the four fibrosis stages and grouped in 22 classes according to their biological functions.Gene set enrichment(GSEA)and Ingenuity pathway analysis(IPA)were used to identify the regulation of crucial biological functions and pathways involved in HCV progression.HCV differentially regulated the expression of genes involved in apoptosis,cell structure,signal transduction,proliferation,metabolism,cytokine signaling,immune response,cell adhesion and maintenance,and post translational modifications by pathway analysis.There was an increasing trend of proliferative and cell growth related genes and shutting down of immune response as the disease progress mild to moderate to advanced stage cirrhosis.The myriad of changes in gene expression showed more chances of developing liver cancer in patients infected with HCV genotype 3a in a systematic manner.The identified gene set can act as disease markers for prediction,whether the fibrosis lead to cirrhosis and its association with end stage liver disease development.