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https://www.readbyqxmd.com/read/28428345/proliferation-of-primary-human-hepatocytes-and-prevention-of-hepatitis-b-virus-reinfection-efficiently-deplete-nuclear-cccdna-in-vivo
#1
Lena Allweiss, Tassilo Volz, Katja Giersch, Janine Kah, Giuseppina Raffa, Joerg Petersen, Ansgar W Lohse, Concetta Beninati, Teresa Pollicino, Stephan Urban, Marc Lütgehetmann, Maura Dandri
OBJECTIVE: The stability of the covalently closed circular DNA (cccDNA) in nuclei of non-dividing hepatocytes represents a key determinant of HBV persistence. Contrarily, studies with animal hepadnaviruses indicated that hepatocyte turnover can reduce cccDNA loads but knowledge on the proliferative capacity of HBV-infected primary human hepatocytes (PHHs) in vivo and the fate of cccDNA in dividing PHHs is still lacking. This study aimed to determine the impact of human hepatocyte division on cccDNA stability in vivo...
April 20, 2017: Gut
https://www.readbyqxmd.com/read/28422376/spontaneous-remission-of-hepatitis-b-virus-reactivation-during-direct-acting-antiviral-agent-based-therapy-for-chronic-hepatitis-c
#2
Ken Sato, Takeshi Kobayashi, Yuichi Yamazaki, Satoshi Takakusagi, Norio Horiguchi, Satoru Kakizaki, Motoyasu Kusano, Masanobu Yamada
The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has been reported to cause hepatitis B virus (HBV) reactivation. However, the actual conditions of HBV reactivation and the ideal timing of medical intervention have not been fully evaluated. We reported the cases of two female patients dually infected with HBV and HCV. Both patients were inactive HBV carriers. Although the serum HCV RNA levels promptly decreased after the initiation of DAA-based therapy, the serum HBV DNA levels gradually increased during DAA-based therapy, with the peak serum HBV DNA levels observed at 16 weeks after the initiation of DAA-based therapy in both cases...
April 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28419966/small-nucleolar-rna-aca11-promotes-proliferation-migration-and-invasion-in-hepatocellular-carcinoma-by-targeting-the-pi3k-akt-signaling-pathway
#3
Long Wu, Junying Zheng, Ping Chen, Quanyan Liu, Yufeng Yuan
Emerging evidence suggests that tumorigenesis involves dysregulation of small nucleolar RNAs (snoRNAs). However, the role of small nucleolar RNA ACA11 (ACA11) in the development of hepatocellular carcinoma (HCC) remains unknown. Expression of ACA11 was measured using quantitative RT-PCR in 92 HCC specimens and 7 HCC cell lines. We found that ACA11 expression was significantly upregulated in HCC tissues and hepatoma cell lines. This upregulation of ACA11 in HCC tumors was significantly associated with histological grade, HBV infection, Barcelona Clinic Liver Cancer stage, portal vein tumor thrombus and poorer patient survival...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28408790/hbv-viral-load-and-liver-enzyme-levels-may-be-associated-with-the-wild-mbl2-aa-genotype
#4
Tuane Carolina Ferreira Moura, Ednelza da Silva Graça Amoras, Mauro Sérgio Araújo, Maria Alice Freitas Queiroz, Simone Regina Souza da Silva Conde, Sâmia Demachki, Rosimar Neris Martins-Feitosa, Luiz Fernando Almeida Machado, Izaura Maria Vieira Cayres-Vallinoto, Ricardo Ishak, Antonio Carlos Rosário Vallinoto
The present study investigated the frequencies of rs1800450 (MBL (⁎)B, G>A), rs1800451 (MBL (⁎)C, G>A), and rs5030737 (MBL (⁎)D, C>T) polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n = 92), and a noninfected control group (n = 300) were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28407787/glucose-regulated-protein-78-demonstrates-antiviral-effects-but-is-more-suitable-for-hepatocellular-carcinoma-prevention-in-hepatitis-b
#5
Nai Q Zheng, Zi H Zheng, Hai X Xu, Ming X Huang, Xiao M Peng
BACKGROUND: Hepatitis B virus (HBV) is the leading cause of liver cirrhosis and hepatocellular carcinoma in Asia and Africa. Existing antivirals cannot cure HBV or eliminate risk of hepatocellular carcinoma. Glucose-regulated protein 78 (GRP78) can inhibit HBV replication, but promote virion secretion and hepatocellular cancer cell invasion. For these reasons, the overall effect of GRP78 on HBV production and whether to utilize the HBV replication-inhibitory effect of GRP78 up-regulation or the hepatocellular cancer cell invasion-inhibitory effect of its down-regulation were further investigated in order to improve the efficacy of current antiviral therapy...
April 13, 2017: Virology Journal
https://www.readbyqxmd.com/read/28403190/prevalence-and-genotype-distribution-of-hepatitis-delta-virus-among-chronic-hepatitis-b-carriers-in-central-vietnam
#6
Hung Minh Nguyen, Bui Tien Sy, Nguyen Thanh Trung, Nghiem Xuan Hoan, Heiner Wedemeyer, Thirumalaisamy P Velavan, C-Thomas Bock
Hepatitis D virus (HDV) infection plays an important role in liver diseases. However, the molecular epidemiology and impact of HDV infection in chronic hepatitis B (CHB) remain uncertain in Vietnam. This cross-sectional study aimed to investigate the prevalence and genotype distribution of HDV among HBsAg-positive patients in Central Vietnam. 250 CHB patients were tested for HDV using newly established HDV-specific RT-PCR techniques. HDV genotypes were determined by direct sequencing. Of the 250 patients 25 (10%) had detectable copies of HDV viral RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28399146/interferon-inducible-ribonuclease-isg20-inhibits-hepatitis-b-virus-replication-through-directly-binding-to-the-epsilon-stem-loop-structure-of-viral-rna
#7
Yuanjie Liu, Hui Nie, Richeng Mao, Bidisha Mitra, Dawei Cai, Ran Yan, Ju-Tao Guo, Timothy M Block, Nadir Mechti, Haitao Guo
Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription of a viral RNA pregenome. We report herein that the interferon (IFN) stimulated exoribonuclease gene of 20 KD (ISG20) inhibits HBV replication through degradation of HBV RNA. ISG20 expression was observed at basal level and was highly upregulated upon IFN treatment in hepatocytes, and knock down of ISG20 resulted in elevation of HBV replication and attenuation of IFN-mediated antiviral effect. The sequence element conferring the susceptibility of HBV RNA to ISG20-mediated RNA degradation was mapped at the HBV RNA terminal redundant region containing epsilon (ε) stem-loop...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28396717/annexin-a2-as-a-biomarker-for-hepatocellular-carcinoma-in-egyptian-patients
#8
Mohamed K Shaker, Hanzada I Abdel Fattah, Ghada S Sabbour, Iman F Montasser, Sara M Abdelhakam, Eman El Hadidy, Rehab Yousry, Ahmed K El Dorry
AIM: To investigate the clinical utility of serum annexin A2 (ANXA2) as a diagnostic marker for early hepatocellular carcinoma (HCC). METHODS: This study was performed in HCC Clinic of Ain Shams University Hospitals, Cairo, Egypt and included: Group 1: Fifty patients with early stage HCC (Barcelona Clinic Liver Cancer stage A); Group 2: Twenty five patients with chronic liver disease; and Control Group: Fifteen healthy, age- and sex-matched subjects who were seronegative for viral hepatitis markers...
March 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28383274/past-current-and-future-developments-of-therapeutic-agents-for-treatment-of-chronic-hepatitis-b-virus-infection
#9
Yameng Pei, Chunting Wang, S Frank Yan, Gang Liu
For decades, treatment of hepatitis B virus (HBV) infection has been relying on interferon (IFN)-based therapies and nucleoside/nucleotide analogues (NAs) that selectively target the viral polymerase reverse transcriptase (RT) domain and thereby disrupt HBV viral DNA synthesis. We have summarized here the key steps in the HBV viral life cycle, which could potentially be targeted by novel anti-HBV therapeutics. A wide range of next-generation direct antiviral agents (DAAs) with distinct mechanisms of actions are discussed, including entry inhibitors, transcription inhibitors, nucleoside/nucleotide analogues, inhibitors of viral ribonuclease H (RNase H), modulators of viral capsid assembly, inhibitors of HBV surface antigen (HBsAg) secretion, RNA interference (RNAi) gene silencers, antisense oligonucleotides (ASOs), and natural products...
April 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28369997/gene-expression-profile-after-knockdown-of-usp18-in-hepg2-2-15-cells
#10
Lin Li, Qing-Song Lei, Ling-Na Kong, Shu-Jun Zhang, Bo Qin
In our previous work, we found that the expression of ubiquitin-specific protease 18 (USP18), also known as UBP43, is associated with the efficiency of interferon alpha (IFN-α) treatment in patients with chronic hepatitis B (CHB). To elucidate the influence of USP18 on hepatitis B virus (HBV) replication and the mechanism of this activity, we silenced USP18 by introducing short hairpin RNA (shRNA) into Hepg2.2.15 cells. To identify the changed genes and pathways in Hepg2.2.15-shRNA-USP18 cells, we performed a microarray gene expression analysis to compare the Hepg2...
March 31, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28350327/the-envelope-gene-of-hepatitis-b-virus-is-implicated-in-both-differential-virion-secretion-and-genome-replication-capacities-between-genotype-b-and-genotype-c-isolates
#11
Haodi Jia, Yanli Qin, Chaoyang Chen, Fei Zhang, Cheng Li, Li Zong, Yongxiang Wang, Jiming Zhang, Jisu Li, Yumei Wen, Shuping Tong
Chronic infection by hepatitis B virus (HBV) genotype C is associated with a prolonged replicative phase and an increased risk of liver cancer, compared with genotype B infection. We previously found lower replication capacity but more efficient virion secretion by genotype C than genotype B isolates. Virion secretion requires interaction between core particles and ENVELOPE proteins. In the present study, chimeric constructs between genotype B and genotype C clones were generated to identify the structural basis for differential virion secretion...
March 28, 2017: Viruses
https://www.readbyqxmd.com/read/28343069/linc00152-promotes-cancer-progression-in-hepatitis-b-virus-associated-hepatocellular-carcinoma
#12
Xin Deng, Xiao Fang Zhao, Xing Qiu Liang, Ran Chen, Yi Feng Pan, Jian Liang
BACKGROUND: The X protein (HBx) plays as a key role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. The study aimed to figure out the role of Linc00152 in hepatocellular carcinoma (HCC) and the association between the expression levels of Linc00152 and HBx. METHODS: QRT-PCR assays were applied to analyzed the expression levels of Linc00152 and HBx. Kaplan-Meier survival curve was performed to identify the association between LINC00152 and the over survival time (OS) in HCC patients...
March 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28339471/expression-quantitative-trait-loci-for-pax8-contributes-to-the-prognosis-of-hepatocellular-carcinoma
#13
Shijie Ma, Jianshui Yang, Ci Song, Zijun Ge, Jing Zhou, Guoxin Zhang, Zhibin Hu
Paired-box family member PAX8 encodes a transcription factor that has a role in cell differentiation and cell growth and may participate in the prognosis of hepatocellular carcinoma (HCC). By bioinformatics analysis, we identified several single nucleotide polymorphisms (SNPs) within a newly identified long non-coding RNA (lncRNA) AC016683.6 as expression quantitative trait loci (eQTLs) for PAX8. Hence, we hypothesized that PAX8eQTLs in lncRNA AC016683.6 may influence the HCC prognosis. We then performed a case-only study to assess the association between the two SNPs as well as the prognosis of HCC in 331 HBV-positive HCC patients without surgical treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28339072/hepatitis-b-virus-x-protein-increases-microrna%C3%A2-21-expression-and-accelerates-the-development-of-hepatoma-via-the-phosphatase-and-tensin-homolog-phosphoinositide-3%C3%A2-kinase-protein-kinase-b-signaling-pathway
#14
Zhouhua Hou, Jun Quan
Hepatitis B virus (HBV) X protein (HBx) is a key regulatory protein that is involved in HBV infection, replication and carcinogenesis of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the role of HBx in the progression and metastasis of liver cancer cells and to determine the underlying molecular mechanism of HBx in metastatic liver cancer cells. HBx protein expression was detected by western blot analysis, and microRNA (miR)‑21 levels were determined by reverse transcription‑quantitative polymerase chain reaction in the highly metastatic MHCC‑97H low metastatic MHCC‑97L and SMMC‑7721 liver cancer cell lines...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28335554/complete-and-incomplete-hepatitis-b-virus-particles-formation-function-and-application
#15
REVIEW
Jianming Hu, Kuancheng Liu
Hepatitis B virus (HBV) is a para-retrovirus or retroid virus that contains a double-stranded DNA genome and replicates this DNA via reverse transcription of a RNA pregenome. Viral reverse transcription takes place within a capsid upon packaging of the RNA and the viral reverse transcriptase. A major characteristic of HBV replication is the selection of capsids containing the double-stranded DNA, but not those containing the RNA or the single-stranded DNA replication intermediate, for envelopment during virion secretion...
March 21, 2017: Viruses
https://www.readbyqxmd.com/read/28335522/extracellular-vesicles-deliver-host-and-virus-rna-and-regulate-innate-immune-response
#16
REVIEW
Takahisa Kouwaki, Masaaki Okamoto, Hirotake Tsukamoto, Yoshimi Fukushima, Hiroyuki Oshiumi
The innate immune system plays a crucial role in controlling viral infection. Pattern recognition receptors (PRRs), such as Toll-like receptors and RIG-I-like receptors, sense viral components called pathogen-associated molecular patterns (PAMPs) and trigger signals to induce innate immune responses. Extracellular vesicles (EVs), including exosomes and microvesicles, deliver functional RNA and mediate intercellular communications. Recent studies have revealed that EVs released from virus-infected cells deliver viral RNA to dendritic cells and macrophages, thereby activating PRRs in recipient cells, which results in the expression of type I interferon and pro-inflammatory cytokines...
March 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28303593/sb-9200-a-novel-agonist-of-innate-immunity-shows-potent-antiviral-activity-against-resistant-hcv-variants
#17
Meleri Jones, Morven E Cunningham, Peter Wing, Sampath DeSilva, Rupa Challa, Anjaneyulu Sheri, Seetharamaiyer Padmanabhan, Radhakrishnan P Iyer, Brent E Korba, Nezam Afdhal, Graham R Foster
SB 9200 is a novel, first-in-class oral modulator of innate immunity that is believed to act via the activation of the RIG-I and NOD2 pathways. SB 9200 has broad-spectrum antiviral activity against RNA viruses including hepatitis C virus (HCV), norovirus, respiratory syncytial virus and influenza and has demonstrated activity against hepatitis B virus (HBV) in vitro and in vivo. In phase I clinical trials in chronically infected HCV patients, SB 9200 has been shown to reduce HCV RNA by up to 1.9 log10 . Here, we demonstrate the antiviral activity of SB 9200 against a HCV replicon system and patient derived virus...
March 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28297795/-the-potential-use-of-serum-hbv-rna-to-guide-the-functional-cure-of-chronic-hepatitis-b
#18
F M Lu, J Wang, X M Chen, J N Jiang, W H Zhang, J M Zhao, H Ren, J L Hou, N S Xia
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in infected hepatocytes is the main cause of off-therapy viral rebound. The half-life of cccDNA is only 33-50 days, so the conversion of newly synthesized rcDNA to cccDNA in the nucleus is essential for the maintenance of cccDNA pool in infected hepatocytes. Though not directly targeting the existing cccDNA, current nucleos(t)ide analogues (NAs) may exhaust the cccDNA reservoir by blocking the rcDNA formation. Indeed, a prolonged consolidation therapy post loss of serum HBV DNA can achieve sustained remission and thus safe drug discontinuation in a small proportion of chronic hepatitis B (CHB) patients...
February 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28285979/the-added-value-of-hepatitis-e-diagnostics-in-determining-causes-of-hepatitis-in-routine-diagnostic-settings-in-the-netherlands
#19
Meintje Doting, Jan Weel, H Niesters, A Riezebos-Brilman, Afke Brandenburg
OBJECTIVES: Hepatitis E virus (HEV) genotype 3 is endemic in Europe and an underdiagnosed and emerging (public) health issue. In recent years commercial enzyme immunoassays (EIAs) that detect antibodies to HEV more adequately, became available. We investigated the added value of this HEV serology in the diagnostic work flow to detect viral causes of recent hepatitis. METHODS: During a two year period (May 2013 - May 2015), HEV serology was added to the hepatitis work flow, consisting of serological detection of hepatitis A-B-C virus (HAV, HBV, HCV), Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV)...
March 7, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28267418/microrna-125b-5p-mediates-post-transcriptional-regulation-of-hepatitis-b-virus-replication-via-the-lin28b-let-7-axis
#20
Wanyu Deng, Xiaoyong Zhang, Zhiyong Ma, Yong Lin, Mengji Lu
MicroRNAs (miRNAs) are able to modulate hepatitis B virus (HBV) replication and play an important role in the pathogenesis of HBV infection. Recently, we have identified that serum miR-125b-5p level correlated with HBV DNA levels and liver necroinflammation. In the present study, we addressed how miR-125b-5p regulated HBV replication at the different steps, inclduing viral transcription, assembly, and virion production and investigated the underlying mechanisms. We found that miR-125b-5p overexpression increased HBV replication without altering HBV transcription...
March 7, 2017: RNA Biology
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