31 Notably, miR-21, a microRNA mediating PTEN down-regulation in NAFLD,10 was not increased in HCV core 3a–expressing cells (data not shown); this suggests that other, hitherto unknown PTEN-targeting microRNAs are involved in this process. Steatosis in patients with chronic hepatitis

C www.selleckchem.com/products/chir-99021-ct99021-hcl.html is clinically relevant because it influences both the progression of liver disease and the response to antivirals. Whether the clinical impact of steatosis depends on its pathogenesis (i.e., viral versus metabolic) remains a matter of debate.22 In this respect, alterations of PTEN expression/activity induced by HCV not only may lead to a deregulated lipid metabolism and potentially impaired insulin sensitivity but also may contribute to the progression of liver disease toward cirrhosis and HCC. Indeed, PTEN is a well-established tumor suppressor that is frequently mutated/deleted or down-regulated in human cancers, including HCC.11, 12 In addition, liver-specific PTEN knockout mice develop steatohepatitis, fibrosis, and HCC6, 7; this supports a role for PTEN in liver

fibrosis and carcinogenesis. Fulvestrant cell line Finally, an analysis of cirrhotic and HCC tissues from HCV-infected patients has shown that PTEN is often down-regulated in tumors, and higher PTEN expression levels are a factor predicting prolonged survival.32 Further molecular, clinical, and epidemiological studies are now warranted for determining in greater detail the mechanisms by which an HCV genotype 3a infection alters the function of PTEN in the liver and the role of these PTEN alterations in the pathogenesis of hepatitis C. Furthermore, it

remains to be established whether PTEN represents a therapeutic target for preventing the progression of liver disease toward its most ominous complications, learn more cirrhosis and HCC. The authors thank the Genomics Platform of the National Centers of Competence in Research (Geneva, Switzerland) for the RT-PCR analyses and S. Conzelmann, M. Fournier, C. Maeder, and S. Startchik for their invaluable help. Additional Supporting Information may be found in the online version of this article. “
“In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups.