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Infectious Disease: Hepatitis

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Total 297 results found since Jan 2013.

Safety, Tolerability, and Pharmacokinetics of ARC ‐520 Injection, an RNA Interference‐Based Therapeutic for the Treatment of Chronic Hepatitis B Virus Infection, in Healthy Volunteers
Abstract ARC‐520 Injection, an RNA interference drug for the treatment of hepatitis B that targets cccDNA‐derived viral mRNA transcripts with high specificity, effectively reduces the production of viral proteins and HBV DNA. In this phase 1 randomized, double‐blind, placebo‐controlled study, 54 healthy volunteers (half male, half female) received a single, intravenous dose of 0.01–4.0 mg/kg ARC‐520 Injection (n = 36) or placebo (n = 18). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (cytokines and complement). Pharmacokinetics of the siRNA and peptide excipient components co...
Source: Clinical Pharmacology in Drug Development - December 11, 2016 Category: Drugs & Pharmacology Authors: Thomas Schluep, Jason Lickliter, James Hamilton, David L. Lewis, Ching ‐Lung Lai, Johnson YN Lau, Stephen A. Locarnini, Robert G. Gish, Bruce D. Given Tags: Original Article Source Type: research

Crosstalk between different family members: IL27 recapitulates IFN γ responses in HCC cells, but is inhibited by IL6-type cytokines
In this study, we show that IL27 induces STAT1 and STAT3 phosphorylation in 5 HCC lines and 3 different types of non-transformed liver cells. We were especially interested in the relevance of the IL27-induced STAT3 activation in liver cells. Thus, we compared the IL27 responses with those induced by IFNγ (STAT1-dominated response) or IL6-type cytokines (IL6, hyper-IL6 (hy-IL6) or OSM) (STAT3-dominated response) by microarray analysis and find that in HCC cells, IL27 induces an IFNγ-like, STAT1-dependent transcriptional response, but we do not find an effective STAT3-dependent response. Validation experiments corroborate ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - December 9, 2016 Category: Molecular Biology Source Type: research

HBx drives alpha fetoprotein expression to promote initiation of liver cancer stem cells through activating PI3K/AKT signal pathway
This article is protected by copyright. All rights reserved.
Source: International Journal of Cancer - December 7, 2016 Category: Cancer & Oncology Authors: Mingyue Zhu, Wei Li, Yan Lu, Xu Dong, Bo Lin, Chen Yi, Xueer Zhang, Junli Guo, Mengsen Li Tags: Research Article Source Type: research

Hepatic stellate cells secrete WFA+ ‐M2BP; its role in biological interactions with Kupffer cells
ConclusionsWFA+‐M2BP from HSCs induces Mac‐2 expression in KCs, which in turn activates HSCs to be fibrogenic.
Source: Journal of Gastroenterology and Hepatology - November 30, 2016 Category: Gastroenterology Authors: Yuki Bekki, Tomoharu Yoshizumi, Shinji Shimoda, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Atsushi Kuno, Hisashi Narimatsu, Ken Shirabe, Yoshihiko Maehara Tags: Original Article ‐ Hepatology (Experimental) Source Type: research

Inhibition of hepatitis C virus using siRNA targeted to the virus and Hsp90.
Abstract Hepatitis C (HCV) is a viral disease affecting millions of people worldwide, and persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma. During treatment for hepatitis C, the occurrence of viral resistance is common. To reduce the occurrence of resistance, new viral treatments should target both viral and cellular factors. Many interactions occur between viral and host proteins during the HCV replication cycle and might be used for the development of new therapies against hepatitis C. Heat shock protein 90 (Hsp90) plays a role in...
Source: Cell Stress and Chaperones - November 16, 2016 Category: Cytology Authors: Braga AC, Carneiro BM, Batista MN, Akinaga MM, Rahal P Tags: Cell Stress Chaperones Source Type: research

Host factor PRPF31 is involved in cccDNA production in HBV-replicating cells.
In this study, we identified pre-mRNA processing factor 31 (PRPF31) by siRNA screening as a factor associated with cccDNA. PRPF31 knockdown by siRNA decreased cccDNA formation without serious cytotoxicity. In rescue experiments, expression of siRNA-resistant PRPF31 recovered cccDNA formation. PRPF31 knockdown did not affect HBV core protein and HBV core DNA levels in HBV-replicating cells. Chromatin immunoprecipitation and immunoprecipitation assays revealed an association between PRPF31 and cccDNA. Furthermore, co-overexpression of PRPF31 and HBx enhanced cccDNA formation in HepAD38 cells. Taken together, the present fin...
Source: Biochemical and Biophysical Research communications - November 14, 2016 Category: Biochemistry Authors: Kinoshita W, Ogura N, Watashi K, Wakita T Tags: Biochem Biophys Res Commun Source Type: research

Acetaldehyde Disrupts Interferon Alpha Signaling in Hepatitis C Virus ‐Infected Liver Cells by Up‐Regulating USP18
ConclusionsWe conclude that Ach disrupts IFNα‐induced STAT1 phosphorylation by the up‐regulation of USP18 to block the innate immunity protection in HCV‐infected liver cells, thereby contributing to HCV‐alcohol pathogenesis. This, in part, may explain the mechanism of HCV‐infection exacerbation/progression in alcohol‐abusing patients. IFNα is an important innate immunity factor, which controls HCV replication and spread via the JAK‐STAT1 pathway activation. Here, we investigated the mechanisms which major ethanol metabolite, acetaldehyde, uses to enhance HCV RNA by decreasing IFNα‐induced STAT1 phosphor...
Source: Alcoholism: Clinical and Experimental Research - September 25, 2016 Category: Addiction Authors: Murali Ganesan, Larisa Y. Poluektova, Dean J. Tuma, Kusum K. Kharbanda, Natalia A. Osna Tags: Original Article Source Type: research

HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12.
This study aimed to investigate the role of HBx-induced miR-21 in the apoptosis of HCC cells. In the study, interleukin-12 (IL-12) was demonstrated as a direct target of miR-21 by dual‑luciferase report assay, and miR-21 was highly expressed in HCC cells (HepG2 and HepG2 2.2.15) compared to L02 cells, but IL-12 was weakly expressed as detected by real-time quantitative PCR (RT-qPCR). Furthermore, miR-21 mimics, inhibitor, HBx-targeted siRNA, and the HBx overexpression vector (pHBx) were used to observe the regulatory effects of HBx-induced miR-21 via IL-12, and cell apoptosis was assessed. The results showed that over...
Source: Oncology Reports - September 1, 2016 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Hepatic Stellate Cells in Liver Fibrosis and siRNA-Based Therapy.
Abstract Hepatic fibrosis is a reversible wound-healing response to either acute or chronic liver injury caused by hepatitis B or C, alcohol, and toxic agents. Hepatic fibrosis is characterized by excessive accumulation and reduced degradation of extracellular matrix (ECM). Excessive accumulation of ECM alters the hepatic architecture leading to liver fibrosis and cirrhosis. Cirrhosis results in failure of common functions of the liver. Hepatic stellate cells (HSC) play a major role in the development of liver fibrosis as HSC are the main source of the excessive production of ECM in an injured liver. RNA interfere...
Source: Pharmacological Reviews - August 17, 2016 Category: Drugs & Pharmacology Authors: Omar R, Yang J, Liu H, Davies NM, Gong Y Tags: Rev Physiol Biochem Pharmacol Source Type: research

Assembly and release of infectious hepatitis C virus involving unusual organization of the secretory pathway.
CONCLUSION: Prior activity of the WNV subgenomic replicon in BHK-21 cells promoted re-wiring of host factors for the assembly and release of infectious HCV in a caspase-1-dependent mechanism. PMID: 27429716 [PubMed]
Source: World Journal of Hepatology - July 21, 2016 Category: Gastroenterology Tags: World J Hepatol Source Type: research

Gene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue.
In conclusion, this study shows that gene regulatory network alterations of cultivated hepatocytes resemble those of inflammatory liver diseases and should therefore be considered and exploited as disease models. PMID: 27339419 [PubMed - as supplied by publisher]
Source: Archives of Toxicology - June 22, 2016 Category: Toxicology Authors: Godoy P, Widera A, Schmidt-Heck W, Campos G, Meyer C, Cadenas C, Reif R, Stöber R, Hammad S, Pütter L, Gianmoena K, Marchan R, Ghallab A, Edlund K, Nüssler A, Thasler WE, Damm G, Seehofer D, Weiss TS, Dirsch O, Dahmen U, Gebhardt R, Chaudhari U, Megana Tags: Arch Toxicol Source Type: research

Hepatitis B Virus X Protein Driven Alpha Fetoprotein Expression to Promote Malignant Behaviors of Normal Liver Cells and Hepatoma Cells
Conclusions: HBx through stimulating expression of AFP to promote malignant behaviors of human normal liver cells and HCC cells; AFP maybe used as a novel biotarget for therapeutics of HCC patients.
Source: Journal of Cancer - June 5, 2016 Category: Cancer & Oncology Authors: Mingyue Zhu, Yan Lu, Wei Li, Junli Guo, Xu Dong, Bo Lin, Yi Chen, Xieju Xie, Mengsen Li Tags: Research Paper Source Type: research

Asialoglycoprotein receptor facilitates infection of PLC/PRF/5 cells by HEV through interaction with ORF2
This article is protected by copyright. All rights reserved
Source: Journal of Medical Virology - May 8, 2016 Category: Virology Authors: Li Zhang, Yabin Tian, Zhiheng Wen, Feng Zhang, Ying Qi, Weijin Huang, Heqiu Zhang, Youchun Wang Tags: Research Article Source Type: research

Suppression of duck hepatitis A virus Type 1 replication by lentivirus-mediated RNA-dependent RNA polymerase (RdRp) gene-specific siRNA
To explore the application of RNAi technology for the control of duck hepatitis A virus type 1 (DHAV-1). The RNA-dependent RNA polymerase (RdRp) gene was amplified by PCR. pEGFP-RdRp was constructed for fusion expression of EGFP-RdRp protein. According to the sequence of RdRp, three gene-specific siRNAs were designed and the corresponding shRNA was inserted into pmiRZip to construct pRdRp-sh...
Source: African Journal of Microbiology Research - May 6, 2016 Category: Microbiology Source Type: research

Inhibitory effect of miR-125b on hepatitis C virus core protein-induced TLR2/MyD88 signaling in THP-1 cells.
CONCLUSION: The inverse correlation between miR-125b and cytokine expression after HCV core challenge suggests that miR-125b may negatively regulate HCV-induced immune responses by targeting TLR2/MyD88 signaling in monocytes. PMID: 27158204 [PubMed - in process]
Source: World Journal of Gastroenterology : WJG - May 6, 2016 Category: Gastroenterology Authors: Peng C, Wang H, Zhang WJ, Jie SH, Tong QX, Lu MJ, Yang DL Tags: World J Gastroenterol Source Type: research