However, in all models that we generated using this technique, transfected cells were fully differentiated hepatocytes located in zone 3 and, thus, preneoplastic lesions developed always in zone 3 vein proximity.[7] The morphological demonstration, showing that affected single cells in AKT/Notch1 mice

were never located in zone 1 but always in zone 3 (Fig. 1D-I) is a proof of the physiologic principle of the method,[6] in line with all our models,[7] and in absolute contradiction to the progenitor-cell hypothesis. Furthermore, electron microscopy showed the presence of tight junctions between transfected and normal hepatocytes (supporting Fig. 10),[2] thus indicating their hepatocellular nature. Matthias Evert, M.D.1Frank Dombrowski, M.D.1Biao

Fan, M.D., Ph.D.2Silvia Ribback, M.D.1Xin Chen, Ph.D.2Diego F. Calvisi, M.D.1 “
“T cells play a crucial role for viral clearance or persistence; however, the precise mechanisms Belnacasan cost that control their responses during viral infection remain incompletely understood. microRNAs (miR) have been implicated as key regulators controlling diverse biological processes through posttranscriptional repression. Here, we demonstrate that hepatitis C virus (HCV)-mediated decline of miR-181a expression impairs CD4+ T cell responses via over-expression of dual specific phosphatase 6 (DUSP6). Specifically, a significant decline of miR-181a expression along with over-expression of DUSP6 were observed in CD4+ T cells from chronically HCV-infected individuals compared buy GSK2118436 to healthy subjects, and the levels of miR-181a loss were found to be negatively associated with the levels of DUSP6 over-expression MCE in these cells. Importantly, reconstitution of miR-181a or blockade of DUSP6 expression

in CD4+ T cells led to improved T cell responses including enhanced CD25 and CD69 expressions, increased IL-2 expression, and improved proliferation of CD4+ T cells derived from chronically HCV-infected individuals. Since a decline of miR-181a concomitant with DUSP6 over-expression are the signature markers for age-associated T cell senescence, these findings provide novel mechanistic insights into HCV-mediated premature T cell aging via miR-181a-regulated DUSP6 signaling, and reveal new targets for therapeutic rejuvenation of impaired T cell responses during chronic viral infection. This article is protected by copyright. All rights reserved. “
“In a recent issue of Hepatology, Herrera et al.[1] reported that human bone-marrow derived mesenchymal stem cells (hMSCs) provided protection from death from fulminant liver failure (FLF) induced by intraperitoneal injection of D-galactosamine/lipopolysaccharide (GalN/LPS) in severe combined immune deficiency (SCID) mice. SCID mice lack functional T and B cells and have been used extensively in xenotransplantation. However, the mice still possess normal natural killer (NK) cells.