Our pilot study demonstrated the efficacy of ezetimibe for drug therapy of NASH and may lead to a large-scale clinical trial in the future. “
“MicroRNAs (miRNAs) are small RNAs that posttranscriptionally regulate gene expression. Their aberrant expression is commonly linked with diseased states, including hepatitis C virus (HCV)

infection. Herein, we demonstrate see more that HCV replication induces the expression of miR-27 in cell culture and in vivo HCV infectious models. Overexpression of the HCV proteins core and NS4B independently activates miR-27 expression. Furthermore, we establish that miR-27 overexpression in hepatocytes results in larger and more abundant lipid droplets, as observed by coherent anti-Stokes Raman scattering (CARS) microscopy. This hepatic lipid droplet accumulation coincides with miR-27b’s repression of peroxisome proliferator-activated receptor (PPAR)-α and angiopoietin-like protein 3 (ANGPTL3), known regulators of triglyceride homeostasis. We further demonstrate

that treatment with a PPAR-α agonist, bezafibrate, is able to reverse the miR-27b-induced lipid accumulation in Huh7 cells. This miR-27b-mediated repression of PPAR-α signaling represents a novel mechanism of HCV-induced hepatic steatosis. This link was further demonstrated in vivo through the correlation between miR-27b expression levels and hepatic lipid accumulation in HCV-infected SCID-beige/Alb-uPa mice. Conclusion: Collectively, our results highlight HCV’s up-regulation of miR-27 expression as a novel mechanism contributing to the development MCE公司 of hepatic steatosis. (Hepatology 2014;58:98–108) Sotrastaurin mw Hepatitis C virus (HCV) is a positive sense RNA virus from the Flaviviridae family[1] that currently infects ∼2.35% of the global population.[2] HCV encodes three structural proteins (core, E1, and E2) and seven nonstructural proteins (p7,

NS2, NS3, NS4A, NS4B, NS5A, and NS5B), and relies on host pathways to facilitate its lifecycle.[3] HCV-associated host factors include both coding and noncoding genes, such as microRNAs (miRNAs), which are small RNAs, ∼20-25 nucleotides in length, which posttranscriptionally regulate virtually every cellular pathway.[4] Unlike synthetic silencing RNAs that are designed to target individual genes, miRNAs have evolved to regulate many targets, thereby exerting greater regulatory control. Several viruses modulate the host miRNAs for their pathogenesis.[5] HCV displays interactions with components of the RNA silencing pathway,[6-8] and direct interactions with a liver-abundant miRNA, miR-122.[5, 9] Hepatic miRNAs can influence HCV either through direct interactions with the viral genome or regulation of HCV-associated host pathways.[6] MicroRNA-27 (miR-27) represents a liver-abundant miRNA[10] whose role in HCV pathogenesis is poorly understood. miR-27 regulates lipid metabolism in adipocytes and macrophages and is implicated in atherosclerosis.