Programmed cell death-1 (PD-1) is involved in hepatitis B virus (HBV) infection, the leading cause of hepatocellular carcinoma (HCC) worldwide. Single-nucleotide polymorphism, rs10204525, located in the PD1 3′ untranslated regions (UTR), is associated with chronic HBV infection. MicroRNAs (miRNAs) regulate gene expression via specific binding to the target 3′UTR of mRNA. In this study, three miRNAs were predicted to putatively interact with PD1 rs10204525 polymorphic site of allele G. One of them, miRNA-4717, was demonstrated to allele-specifically affect luciferase activity in a dose-dependent manner in cells transfected with vectors containing different rs10204525 alleles. In lymphocytes from chronic HBV patients withrs10204525 genotype GG, miR-4717 mimics significantly decreased PD-1 expression and increased (TNF)-α and interferon (IFN)-γ production. miR-4717 inhibitor significantly increased PD-1 expression and decreased TNF-α and IFN-γ production although not significantly. In lymphocytes from chronic HBV patients with rs10204525 genotype AA, no similar effects were observed. miR-4717 levels in peripheral lymphocytes from patients with HBV-related chronic hepatitis, cirrhosis and HCC were significantly decreased. In conclusion, miR-4717 may allele-specifically regulate PD-1 expression through interaction with the 3′ UTR of PD1 mRNA, leading to the alteration of immune regulation and affecting the susceptibility and disease course of chronic HBV infection.
Based on transcriptomic data from four experimental settings with drought-resistant and drought-sensitive cultivars under drought and well-watered conditions, statistical analysis revealed three categories encompassing 169 highly differentially expressed genes (DEGs) in response to drought in Brassica napus L., including 37 drought-resistant cultivar-related genes, 35 drought-sensitive cultivar-related genes and 97 cultivar non-specific ones. We provide evidence that the identified DEGs were fairly uniformly distributed on different chromosomes and their expression patterns are variety specific. Except commonly enriched in response to various stimuli or stresses, different categories of DEGs show specific enrichment in certain biological processes or pathways, which indicated the possibility of functional differences among the three categories. Network analysis revealed relationships among the 169 DEGs, annotated biological processes and pathways. The 169 DEGs can be classified into different functional categories via preferred pathways or biological processes. Some pathways might simultaneously involve a large number of shared DEGs, and these pathways are likely to cross-talk and have overlapping biological functions. Several members of the identified DEGs fit to drought stress signal transduction pathway in Arabidopsis thaliana. Finally, quantitative real-time PCR validations confirmed the reproducibility of the RNA-seq data. These investigations are profitable for the improvement of crop varieties through transgenic engineering.
Background: Sodium taurocholate cotransporting polypeptide (NTCP) plays an important role in the enterohepatic circulation of bile acids and hepatocyte function and was recently proposed to be a functional receptor for hepatitis B virus (HBV). Objective: This study investigated the association of the functional polymorphism c.800C > T (p.S267F) (rs2296651) of the NTCP gene with HBV infection. Methods: The study included 244 patients with chronic HBV infection, 76 HBV infection resolvers, and 113 healthy controls. The polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The distribution of the genotype and allele frequency of rs2296651 polymorphism was significantly different among the HBV patients, HBV infection resolvers, and healthy controls ( p = 0.034 and p = 0.039, respectively). The frequency of genotype CT in HBV patients was significantly higher than that in healthy controls (11.9% vs. 4.4%, p = 0.026, odds ratios [OR] = 2.913, 95% confidence intervals [95% CI] = 1.097-7.738). The frequency of allele T in HBV patients was also significantly higher than that in healthy controls (5.9% vs. 2.2%, p = 0.029, OR = 2.793, 95% CI = 1.067-7.312). The frequency of genotype CT and allele T in HBV patients was higher than that in HBV infection resolvers although the difference was not significant. The genotype and allele frequency between infection resolvers and healthy controls and between HBV patients with different clinical diseases had no significant difference. Conclusion: These findings suggest that the rs2296651 polymorphism may predispose the susceptibility to and chronicity of HBV infection.
BackgroundHepatocellular carcinoma (HCC) is among the most common and lethal cancers worldwide, especially in China.MethodsWe retrospectively analyzed data from patients who were diagnosed and treated HCC between 2002 and 2011 in a large hospital in northwest China and compared the data between periods 2002–2006 (P1) and 2007–2011 (P2).Results2045 patients were included in analysis. The HCC stages at diagnosis according to the Barcelona clinic liver cancer staging system had no significant change. Treatment options of liver transplantation, transcatheter arterial chemoembolization and other therapy decreased while percutaneous local ablation and supportive care increased from P1 to P2. Options of surgical resection and systematic therapy had no significant change. Patient survival rates at 1, 3 and 5 years significantly improved from P1 to P2. The treatments with increasing option trend had a higher magnitude of survival increase and vise versa.ConclusionOver the last 10 years, the patient survival had a significant increase which was mainly a result of the optimal therapeutic selections according to disease stages in this center. However, the proportion of patients diagnosed at early stages of HCC remained low and did not increase, a result calling for implementing surveillance system for at risk patients.
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