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https://www.readbyqxmd.com/read/28603092/crosstalk-of-liver-immune-cells-and-cell-death-mechanisms-in-different-murine-models-of-liver-injury-and-its-clinical-relevance
#1
Hilal Ahmad Khan, Muhammad Zishan Ahmad, Junaid Ali Khan, Muhammad Imran Arshad
BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions...
June 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28595015/2-chloro-2-fluoro-ribonucleotide-prodrugs-with-potent-pan-genotypic-activity-against-hepatitis-c-virus-replication-in-culture
#2
Shaoman Zhou, Sawsan Mahmoud, Peng Liu, Longhu Zhou, Maryam Ehteshami, Leda Bassit, Sijia Tao, Robert A Domaoal, Ozkan Sari, Coralie De Schutter, Sheida Amiralaei, Ahmed Khalil, Olivia Ollinger Russell, Tamara R McBrayer, Tony Whitaker, Nageh Abou-Taleb, Franck Amblard, Steven J Coats, Raymond Felix Schinazi
Pan-genotypic nucleoside HCV inhibitors display a high genetic barrier to drug resistance and are the preferred direct acting agents to achieve complete sustained virologic response in humans. Herein, we report, the discovery of a -D-2'-Cl,2'-F-uridine phosphoramidate nucleotide 16, as a non-toxic pan-genotypic anti-HCV agent. Phosphoramidate 16 in its 5'-triphosphate form specifically inhibited HCV NS5B polymerase with no marked inhibition of human polymerases and cellular mitochondrial RNA polymerase. Studies on the intracellular half-life of phosphoramidate 16-TP in live cells demonstrated favorable half-life of 11...
June 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28570836/the-influence-of-hepatitis-c-virus-therapy-on-the-dna-base-excision-repair-system-of-peripheral-blood-mononuclear-cells
#3
Piotr Czarny, Anna Merecz-Sadowska, Kinga Majchrzak, Maciej Jabłkowski, Janusz Szemraj, Tomasz Śliwiński, Bolesław Karwowski
Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage...
June 1, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28559253/nucleotide-substrate-specificity-of-hepatitis-c-analogs-for-human-mitochondrial-rna-polymerase
#4
Maryam Ehteshami, Longhu Zhou, Sheida Amiralaei, Jadd R Shelton, Jong Hyun Cho, Hongwang Zhang, Hao Li, Xiao Lu, Tugba Ozturk, Richard Stanton, Franck Amblard, Tamara R McBrayer, Steven J Coats, Raymond F Schinazi
Nucleoside analog inhibitors (NAI) are an important class of antiviral agents. Although highly effective, some NAI with anti-hepatitis C virus (HCV) activity can cause toxicity presumably due to off-target inhibition of host mitochondrial RNA polymerase (POLRMT). The in vitro nucleotide substrate specificity of POLRMT enzyme was studied in order to explore structure-activity relationships that can facilitate the identification of non-toxic NAI. These finding have important implications for all anti-RNA virus NAI development...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28558073/hepatitis-e-virus-persists-in-the-presence-of-a-type-iii-interferon-response
#5
Xin Yin, Xinlei Li, Charuta Ambardekar, Zhimin Hu, Sébastien Lhomme, Zongdi Feng
The RIG-I-like RNA helicase (RLR)-mediated interferon (IFN) response plays a pivotal role in the hepatic antiviral immunity. The hepatitis A virus (HAV) and the hepatitis C virus (HCV) counter this response by encoding a viral protease that cleaves the mitochondria antiviral signaling protein (MAVS), a common signaling adaptor for RLRs. However, a third hepatotropic RNA virus, the hepatitis E virus (HEV), does not appear to encode a functional protease yet persists in infected cells. We investigated HEV-induced IFN responses in human hepatoma cells and primary human hepatocytes...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28483922/quantitative-micro-spectroscopic-imaging-reveals-viral-and-cellular-rna-helicase-interactions-in-live-cells
#6
M J Corby, Michael R Stoneman, Gabriel Biener, Joel D Paprocki, Rajesh Kolli, Valerica Raicu, David N Frick
Human cells detect RNA viruses through a set of helicases called RIG-I like receptors (RLRs) that initiate the interferon response via a mitochondrial signaling complex. Many RNA viruses also encode helicases, which sometimes are covalently linked to proteases that cleave signaling proteins. One unresolved question is how RLRs interact with each other and with viral proteins in cells. This study examined the interactions among the hepatitis C virus (HCV) helicase and RLR helicases in live cells with quantitative micro-spectroscopic imaging (Q-MSI), a technique that determines Forster Resonance Energy Transfer (FRET) efficiency and sub-cellular donor and acceptor concentrations...
May 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28480979/down-regulation-of-trif-tlr3-and-mavs-in-hcv-infected-liver-correlates-with-the-outcome-of-infection
#7
Premashis Kar, Deepak Kumar, Phani Kumar Gumma, Soumya Jyoti Chowdhury, Vijay Kumar Karra
AIMS: In virus-infected cells, pattern recognition receptors (PRRs) recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS), TIR-domain-containing adapter-inducing interferon-β (TRIF) and TNF receptor associated factor (TRAF6) which induces interferon. Toll-like receptor 3 (TLR3) induces activation of the NF-kappa B (NF-κB) for interferon production. The study has been designed to assess the correlation of TLR3, MAVS, TRIF and TRAF6 outcome of HCV infection...
May 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28471941/basic-science-and-pathogenesis-of-ageing-with-hiv-potential-mechanisms-and-biomarkers
#8
Claire Lagathu, Andrea Cossarizza, Véronique Béréziat, Milena Nasi, Jacqueline Capeau, Marcello Pinti
: The increased prevalence of age-related comorbidities and mortality is worrisome in ageing HIV-infected patients. Here, we aim to analyse the different ageing mechanisms with regard to HIV infection. Ageing results from the time-dependent accumulation of random cellular damage. Epigenetic modifications and mitochondrial DNA haplogroups modulate ageing. In antiretroviral treatment-controlled patients, epigenetic clock appears to be advanced, and some haplogroups are associated with HIV infection severity. Telomere shortening is enhanced in HIV-infected patients because of HIV and some nucleoside analogue reverse transcriptase inhibitors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28394926/gp73-represses-host-innate-immune-response-to-promote-virus-replication-by-facilitating-mavs-and-traf6-degradation
#9
Xuewu Zhang, Chengliang Zhu, Tianci Wang, Hui Jiang, Yahui Ren, Qi Zhang, Kailang Wu, Fang Liu, Yingle Liu, Jianguo Wu
Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients' serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28329914/ginsenoside-rg3-restores-hepatitis-c-virus-induced-aberrant-mitochondrial-dynamics-and-inhibits-virus-propagation
#10
Seong-Jun Kim, Jae Young Jang, Eun-Jung Kim, Eun Kyung Cho, Dae Gyun Ahn, Chonsaeng Kim, Han Seul Park, Soung Won Jeong, Sae Hwan Lee, Sang Gyune Kim, Young Seok Kim, Hong Soo Kim, Boo Sung Kim, Ji-Hyung Lee, Aleem Siddiqui
Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their treatment of patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine and other conditions, which may be linked to mitochondrial dysfunction. Here we show that clinically prescribed DAAs, including Sofosbuvir, affect mitochondrial dynamics...
March 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28304119/serum-markers-for-mitochondrial-dysfunction-and-cell-death-are-possible-predictive-indicators-for-drug-induced-liver-injury-by-direct-acting-antivirals
#11
Keisuke Kakisaka, Yuichi Yoshida, Yuji Suzuki, Takuro Sato, Hidekatsu Kuroda, Akio Miyasaka, Yasuhiro Takikawa
AIM: We prospectively screened patients treated with direct-acting antivirals (DAA) in order to detect and analyze serum markers that are present prior to the development of drug-induced liver injury (DILI). METHODS: The levels of various serum markers among DILI, non-DILI and control groups were compared. The DILI group consisted of eight patients whose alanine aminotransferase (ALT) levels exceeded 32 IU/L during the DAA treatment. Eight patients without DILI were selected for the non-DILI group via a matched-group design based on age, sex and disease severity...
March 17, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28228506/low-plasma-zinc-is-associated-with-higher-mitochondrial-oxidative-stress-and-faster-liver-fibrosis-development-in-the-miami-adult-studies-in-hiv-cohort
#12
Sabrina S Martinez, Adriana Campa, Yinghui Li, Christina Fleetwood, Tiffanie Stewart, Venkataraghavan Ramamoorthy, Marianna K Baum
Background: Oxidative stress and reduced antioxidants may be a trigger for liver fibrogenesis. Reducing oxidative stress through higher antioxidant concentration may be a potential antifibrotic target.Objective: We aimed to investigate longitudinally whether plasma zinc, an antioxidant, is related to mitochondrial oxidative stress and the progression of liver fibrosis in the Miami Adult Studies in HIV (MASH) cohort.Methods: A prospective observational cohort study was conducted in 487 predominantly African American HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected adults with a mean ± SD age of 47...
April 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28218651/proteome-characteristics-of-non-alcoholic-steatohepatitis-liver-tissue-and-associated-hepatocellular-carcinomas
#13
Anna Kakehashi, Vasily E Stefanov, Naomi Ishii, Takahiro Okuno, Hideki Fujii, Kazuaki Kawai, Norifumi Kawada, Hideki Wanibuchi
To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV⁺ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28182609/genetic-polymorphisms-associated-with-liver-disease-progression-in-hiv-hcv-coinfected-patients
#14
REVIEW
Luz M Medrano, María A Jiménez-Sousa, Amanda Fernández-Rodríguez, Salvador Resino
The pathogenic mechanisms of the accelerated progression of liver injury in HIV/HCV coinfection are incompletely understood. The progression of liver disease is variable between individuals having similar risk factors, suggesting that genetic background is an important contributor. The aim of this review is to give a summary of all single nucleotide polymorphisms associated with the severity of liver disease in patients coinfected with HIV and HCV reported in the literature. Therefore, a systematic search for articles published was made, 17 of which were selected for this review...
January 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28174739/increased-mitochondrial-genetic-diversity-in-persons-infected-with-hepatitis-c-virus
#15
David S Campo, Ha-Jung Roh, Brian L Pearlman, Daniel S Fierer, Sumathi Ramachandran, Gilberto Vaughan, Andrew Hinds, Zoya Dimitrova, Pavel Skums, Yury Khudyakov
BACKGROUND & AIMS: The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression. METHODS: We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28125040/silymarin-silybin-and-chronic-liver-disease-a-marriage-of-many-years
#16
REVIEW
Alessandro Federico, Marcello Dallio, Carmelina Loguercio
Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation...
January 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28077274/the-role-and-regulation-of-the-peroxisome-proliferator-activated-receptor-alpha-in-human-liver
#17
REVIEW
Sander Kersten, Rinke Stienstra
The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice have shown that PPARα serves as the master regulator of hepatic lipid metabolism during fasting. In addition, PPARα suppresses inflammation and the acute phase response. Comparatively little is known about PPARα in human liver...
May 2017: Biochimie
https://www.readbyqxmd.com/read/27807226/subcellular-localizations-of-rig-i-trim25-and-mavs-complexes
#18
M T Sánchez-Aparicio, J Ayllón, A Leo-Macias, T Wolff, A García-Sastre
The retinoic acid-inducible gene 1 (RIG-I) signaling pathway is essential for the recognition of viruses and the initiation of host interferon (IFN)-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds mitochondrial antiviral signaling protein (MAVS), leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway through the use of bimolecular fluorescence complementation (BiFC) and super-resolution microscopy...
January 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27670736/the-prevalence-of-autoantibody-and-its-relationship-with-genotypes-of-hepatitis-c-virus-in-patients-with-chronic-hepatitis-c-virus-infection
#19
Sevİn Kirdar, Asli Gamze Sener, Merve Cengİz, Nerİman Aydin
The prevalence of autoantibody in the patients with chronic hepatitis C infection, and the relationship between the autoantibodies and HCV genotypes were investigated in this study. One hundred and eight anti-HCV positive and 86 anti-HCV negative patients were included in the study. Anti-HCV were studied by enzyme immunassay (EIA). HCV RNA was determined by real time polymerase chain reaction (PCR) and HCV genotypes were determined by a reverse-line blot hybridization. Anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), Anti-mitochondrial antibodies (AMA), liver kidney microsomal antibodies (LKM) were detected by indirect immunofluorescence assay...
November 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/27646677/improving-icsi-a-review-from-the-spermatozoon-perspective
#20
REVIEW
Mara Simopoulou, Laertis Gkoles, Panagiotis Bakas, Polina Giannelou, Theodoros Kalampokas, Konstantinos Pantos, Michael Koutsilieris
Intracytoplasmic sperm injection (ICSI) is the most frequently applied method for fertilization making the process of identifying the perfect spermatozoon fundamental. Herein we offer a critical and thorough presentation on the techniques reported regarding (i) handling and preparing semen samples, (ii) identifying and 'fishing' spermatozoa, and (iii) improving key factors, such as motility for a successful ICSI practice. These approaches are suggested to make the process easier and more effective especially in atypical and challenging circumstances...
December 2016: Systems Biology in Reproductive Medicine
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