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Infectious Disease: Hepatitis

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Total 297 results found since Jan 2013.

Hepatitis B virus X protein induces expression of alpha-fetoprotein and activates PI3K/mTOR signaling pathway in liver cells.
In this study, we investigated the regulatory impact of AFP expression on HBx-mediated malignant transformation of human hepatocytes. We found that HBV induced the expression of AFP before that of oncogenes, e.g., Src, Ras and chemokine (C-X-C motif) receptor 4 (CXCR4), and AFP activated protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in HBV-related HCC tissues and in human liver cells transfected with HBx. Cytoplasmic AFP interacted with and inhibited phosphatase and tensin homolog deleted on chromosome 10 (PTEN), activating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway and promoting mTOR-...
Source: Oncotarget - February 18, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Antiviral and Immunoregulatory Effects of Indoleamine-2,3-Dioxygenase in Hepatitis C Virus Infection
In patients with hepatitis C virus (HCV) infection, enhanced activity of indoleamine-2,3-dioxygenase 1 (IDO) has been reported. IDO - a tryptophan-catabolizing enzyme - has been considered as both an innate defence mechanism and an important regulator of the immune response. The molecular mechanism of IDO induction in HCV infection and its role in the antiviral immune response remain unknown. Using primary human hepatocytes, we show that HCV infection stimulates IDO expression. IDO gene induction was transient and coincided with the expression of types I and III interferons (IFNs) and IFN-stimulated genes in HCV-infected h...
Source: Journal of Innate Immunity - March 19, 2015 Category: Allergy & Immunology Source Type: research

HDVDB: a data warehouse for hepatitis delta virus.
Abstract Hepatitis Delta Virus (HDV) is an RNA virus and causes delta hepatitis in humans. Although a lot of data is available for HDV, but retrieval of information is a complicated task. Current web database 'HDVDB' provides a comprehensive web-resource for HDV. The database is basically concerned with basic information about HDV and disease caused by this virus, genome structure, pathogenesis, epidemiology, symptoms and prevention, etc. Database also supplies sequence data and bibliographic information about HDV. A tool 'siHDV Predict' to design the effective siRNA molecule to control the activity of HDV, is als...
Source: International Journal of Bioinformatics Research and Applications - March 21, 2015 Category: Bioinformatics Authors: Singh S, Gupta SK, Nischal A, Pant KK, Seth PK Tags: Int J Bioinform Res Appl Source Type: research

Novel Robust in Vitro Hepatitis B Virus Infection Model Using Fresh Human Hepatocytes Isolated from Humanized Mice.
Abstract The molecular mechanisms underlying the hepatitis B virus (HBV) life cycle are poorly understood because of the lack of appropriate in vitro infection models. Herein, we report a highly effective in vitro HBV infection system using fresh human hepatocytes (HHs) isolated from chimeric mice with humanized livers. After the inoculation of sera collected from HBV-infected chimeric mice or patients to HHs, we measured levels of HBV DNA, mRNA, covalently closed circular DNA, and viral protein expression in HHs. We investigated the neutralization activity of hepatitis B immune globulin and the effects of siRNA...
Source: The American Journal of Pathology - March 17, 2015 Category: Pathology Authors: Ishida Y, Yamasaki C, Yanagi A, Yoshizane Y, Fujikawa K, Watashi K, Abe H, Wakita T, Hayes CN, Chayama K, Tateno C Tags: Am J Pathol Source Type: research

Lipopolysaccharide (LPS)-Induced Biliary Epithelial Cell NRas Activation Requires Epidermal Growth Factor Receptor (EGFR)
by Christy E. Trussoni, James H. Tabibian, Patrick L. Splinter, Steven P. O’Hara Cholangiocytes (biliary epithelial cells) actively participate in microbe-induced proinflammatory responses in the liver and contribute to inflammatory and infectious cholangiopathies. We previously demonstrated that cholangiocyte TLR-dependent NRas activation contributes to proinflammatory/ proliferative responses. We test the hypothesis that LPS-induced activation of NRas requires the EGFR. SV40-transformed human cholangiocytes (H69 cells), or low passage normal human cholangiocytes (NHC), were treated with LPS in the presence or absence ...
Source: PLoS One - April 27, 2015 Category: Biomedical Science Authors: Christy E. Trussoni et al. Source Type: research

Abstract 814: Truncated HBx-dependent silencing of growth arrest-specific 2 promotes hepatocarcinogenesis through inhibition of p53-mediated apoptosis
In conclusion, our integrated study uncovered a novel viral mechanism in hepatocarcinogenesis, wherein HBxΔ35 ablates p53-driven apoptosis via direct silencing of GAS2, and thereby provides survival advantage for pre-neoplastic hepatocytes to facilitate cancer development.Citation Format: Alfred S. L. Cheng, Ranxu Zhu, Myth T.S. Mok, Wai Kang, Ka-Fai To, Joseph J.Y. Sung, Henry L.Y. Chan. Truncated HBx-dependent silencing of growth arrest-specific 2 promotes hepatocarcinogenesis through inhibition of p53-mediated apoptosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Rese...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Cheng, A. S. L., Zhu, R., Mok, M. T. S., Kang, W., To, K.-F., Sung, J. J. Y., Chan, H. L. Y. Tags: Carcinogenesis Source Type: research

Potential Use of Thioalkylated Mannose-Modified Dendrimer (G3)/α-Cyclodextrin Conjugate as an NF-κB siRNA Carrier for the Treatment of Fulminant Hepatitis
Molecular PharmaceuticsDOI: 10.1021/mp500814f
Source: Molecular Pharmaceutics - August 20, 2015 Category: Drugs & Pharmacology Authors: Keiichi Motoyama, Ryosuke Mitsuyasu, Chiho Akao, Irhan Ibrahim Abu Hashim, Nana Sato, Takahiro Tanaka, Taishi Higashi and Hidetoshi Arima Source Type: research

New and Emerging Agents for the Treatment of Hemophilia: Focus on Extended Half-Life Recombinant Clotting Proteins
Abstract Hemophilia A and B are X-linked disorders caused by deficient or defective clotting factor VIII (FVIII) or IX factor (FIX) proteins, and characterized by spontaneous or traumatic bleeding into joints and muscles. Previous use of plasma and plasma-derived clotting factors that lacked appropriate viral inactivation steps in manufacturing led to significant morbidity associated with transfusion-transmitted HIV and hepatitis C virus (HCV). The development of recombinant proteins revolutionized their treatment, and, with no new HIV or HCV infection via clotting proteins for nearly 30 years, greatly improved t...
Source: Drugs - August 27, 2015 Category: Drugs & Pharmacology Source Type: research

Heterogeneous ribonucleoprotein K (hnRNP K) binds miR-122, a mature liver-specific microRNA required for hepatitis C virus replication.
Abstract Heterogeneous ribonucleoprotein K (hnRNP K) binds to the 5' untranslated region of the hepatitis C virus (HCV) and is required for HCV RNA replication. The hnRNP K binding site on HCV RNA overlaps with the sequence recognized by the liver-specific microRNA, miR-122. A proteome chip containing ~17,000 unique human proteins probed with miR-122 identified hnRNP K as one of the strong binding proteins. In vitro kinetic study showed hnRNP K binds miR-122 with a nanomolar dissociation constant, in which the short pyrimidine-rich residues in the central and 3' portion of the miR-122 were required for hnRNP K bin...
Source: Molecular and Cellular Proteomics : MCP - September 1, 2015 Category: Molecular Biology Authors: Fan B, Sutandy FX, Syu GD, Middleton S, Yi G, Lu KY, Chen CS, Kao CC Tags: Mol Cell Proteomics Source Type: research

SUMO1 depletion prevents lipid droplet accumulation and HCV replication
Abstract Infection by hepatitis C virus (HCV) is a major public-health problem. Chronic infection often leads to cirrhosis, steatosis, and hepatocellular carcinoma. The life cycle of HCV depends on the host cell machinery and involves intimate interaction between viral and host proteins. However, the role of host proteins in the life cycle of HCV remains poorly understood. Here, we identify the small ubiquitin-related modifier (SUMO1) as a key host factor required for HCV replication. We performed a series of cell biology and biochemistry experiments using the HCV JFH-1 (Japanese fulminate hepatitis 1) genotype 2a...
Source: Archives of Virology - October 8, 2015 Category: Virology Source Type: research

RNA Interference as a Therapeutic Strategy for the Treatment of Liver Diseases.
Abstract RNA interference has emerged as an innovative technology for gene silencing that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs (siRNAs). Its therapeutic application has important advantages over small-molecule drugs since offers the possibility of targeting virtually all genes and allows selective silencing of one or several genes. So far, a relative small proportion of cellular proteins can bind and respond to chemical drugs. Based on that, RNA interference-mediated gene silencing is widely considered as a crucial breakthrough in molecular biology with a...
Source: Current Pharmaceutical Design - October 23, 2015 Category: Drugs & Pharmacology Authors: Gonzalez-Rodriguez A, Valverde AM Tags: Curr Pharm Des Source Type: research

Novel pH-sensitive multifunctional envelope-type nanodevice for siRNA-based treatments for chronic HBV infection
Antiviral agents including entecavir (ETV) suppress replication of the Hepatitis B virus (HBV) genome in human hepatocytes, but they do not reduce the abundance of viral proteins. The present study focused on effectively reducing viral proteins levels.
Source: Journal of Hepatology - October 23, 2015 Category: Gastroenterology Authors: Naoki Yamamoto, Yusuke Sato, Tsubasa Munakata, Masakazu Kakuni, Chise Tateno, Takahiro Sanada, Yuichi Hirata, Shuko Murakami, Yasuhito Tanaka, Kazuaki Chayama, Hiroto Hatakeyama, Mamoru Hyodo, Hideyoshi Harashima, Michinori Kohara Source Type: research

Inhibition of hepatitis B virus replication in vivo using lipoplexes containing altritol-modified antiviral siRNAs.
Authors: Hean J, Crowther C, Ely A, Ul Islam R, Barichievy S, Bloom K, Weinberg MS, van Otterlo WA, de Koning CB, Salazar F, Marion P, Roesch EB, Lemaitre M, Herdewijn P, Arbuthnot P Abstract Chronic infection with the hepatitis B virus (HBV) occurs in approximately 6% of the world's population and carriers of the virus are at risk for complicating hepatocellular carcinoma. Current treatment options have limited efficacy and chronic HBV infection is likely to remain a significant global medical problem for many years to come. Silencing HBV gene expression by harnessing RNA interference (RNAi) presents an attractive...
Source: Artificial DNA: PNA and XNA - November 19, 2015 Category: Genetics & Stem Cells Tags: Artif DNA PNA XNA Source Type: research

Upregulating the Expression of Survivin-HBXIP Complex Contributes to the Protective Role of IMM-H004 in Transient Global Cerebral Ischemia/Reperfusion
Abstract IMM-H004, a 3-piperazinylcoumarin compound derived from coumarin, has been proved effective against CA1 cell loss and spatial learning impairments resulting from transient global ischemia/reperfusion (TGCI/R), while the mechanism is still largely unknown. Here, we confirmed that treatment of rats with IMM-H004 immediately after TGCI/R ameliorated delayed neuronal death (DND) in the CA1 of hippocampus and cortex. Further study suggested that IMM-H004 contributed to the expression of antiapoptotic protein survivin through the activation of PI3K-dependent protein kinase B (PKB/Akt), which led to the phosphor...
Source: Molecular Neurobiology - January 7, 2016 Category: Neurology Source Type: research

HCV-activated NLRP3 Inflammasome Regulates Lipid Metabolism Molecular Bases of Disease
In this study, we elucidate the potential link between chronic hepatitis C-associated inflammation and alteration of lipid homeostasis in infected cells. Our results reveal that the HCV-activated NLRP3 inflammasome is required for the up-regulation of lipogenic genes such as 3-hydroxy-3-methylglutaryl-coenzyme A synthase, fatty acid synthase, and stearoyl-CoA desaturase. Using pharmacological inhibitors and siRNA against the inflammasome components (NLRP3, apoptosis-associated speck-like protein containing a CARD, and caspase-1), we further show that the activation of the NLRP3 inflammasome plays a critical role in lipid d...
Source: Journal of Biological Chemistry - February 12, 2016 Category: Chemistry Authors: McRae, S., Iqbal, J., Sarkar-Dutta, M., Lane, S., Nagaraj, A., Ali, N., Waris, G. Tags: Microbiology Source Type: research