Autophagy is a highly-regulated,conserved cellular process for the degradation of intracellular components in lysosomes to maintain the energetic balance of the *** is a pro-survival mechanism that plays an important ...
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Autophagy is a highly-regulated,conserved cellular process for the degradation of intracellular components in lysosomes to maintain the energetic balance of the *** is a pro-survival mechanism that plays an important role during development,differentiation,apoptosis,ageing and innate and adaptive immune ***,autophagy has been described to be involved in the development of various human diseases,e.g.,chronic liver diseases and the development of hepatocellular *** hepatitis c virus(HcV) is a major cause of chronic liver *** has recently been described that HcV,like other RNA viruses,hijacks the autophagic machinery to improve its ***,the mechanisms underlying its activation are *** replication and assembly occurs at the so-called membranous web that consists of lipid droplets and rearranged endoplasmic reticulum-derived membranes including single-,doubleand multi-membrane *** double-membrane vesicles have been identified to contain NS3,NS5 A,viral RNA and the autophagosomal marker microtubuleassociated protein 1 light chain 3,corroborating the involvement of the autophagic pathway in the HcV *** this review,we will highlight the crosstalk of the autophagosomal compartment with different steps of the HcV life-cycle and address its implications on favoring the survival of infected hepatocytes.
In 1926, c. G. Jung visited Taos Pueblo in northern New Mexico, whose chief said, "How can there be another god? Nothing can be without the sun." Nineteen years later and some sixty miles away, on land appro...
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In 1926, c. G. Jung visited Taos Pueblo in northern New Mexico, whose chief said, "How can there be another god? Nothing can be without the sun." Nineteen years later and some sixty miles away, on land appropriated by the US government from the Ildefonso Pueblo, the Los Alamos National Laboratory was built. Here the first atomic bombs were designed and constructed. Then, in the summer of 1945, the first nuclear device was tested in the desert of southern New Mexico, lighting "a thousand suns." In The Nuclear Borderlands: The Manhattan Project in Post-cold War New Mexico, Joseph Masco, an anthropologist at the University of chicago, offers a unique ethnographic analysis of the people and land that was appropriated for the birthplace and continued research and development of nuclear weapons that have prompted, along with global warming, the so-called Doomsday clock to be set at two minutes to oblivion.
AIM: To describe our experience using a low-acceleratingdose regimen(LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis c virus(HcV) recurrence. METHODS: From 2003, a protocolized LADR st...
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AIM: To describe our experience using a low-acceleratingdose regimen(LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis c virus(HcV) recurrence. METHODS: From 2003, a protocolized LADR strategy was employed to treat liver transplant(LT) recipients with recurrent HcV at our institution. Medical records of 182 adult patients with recurrent HcV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28 B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B(rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include(1) patient and graft survival;(2) effect of anti-viral therapy on liver histology(fibrosis and inflammation);(3) incidence of on-treatment development of AcR, cDR, or PcH;(4) association of recipient and donor IL28 B genotype with SVR; and(5) incidence of antiviral therapy-associated adverse events(anemia, leukopenia, thrombocytopenia, depression) and hepatic ***: The overall SVR rate was 38%(29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HcV Gt(P < 0.0001), donor age(P = 0.003), cytomegalovirus mismatch(P = 0.001), baseline serum bilirubin(P = 0.002), and baseline viral load(P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-cc/donor-non cc pairs(P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR(97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L(P = 0.01), total bilirubin ≥ 1.5 mg/d L(P = 0.001) and creatinine ≥ 2 mg/d L(P = 0.001) were independently associated
AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis c virus(HcV) core protein in Hep G2 ***: HcV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cho...
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AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis c virus(HcV) core protein in Hep G2 ***: HcV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGcR) was measured by quantitative real-time PcR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi ***: HcV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGcR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HcV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HcV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HcV core protein. cONcLUSION: HcV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein.
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