Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets

Vincenzo Cardinale, Yunfang Wang, Guido Carpino, Cai‐Bin Cui, Manuela Gatto, Massimo Rossi, Pasquale Bartolomeo Berloco, Alfredo Cantafora, Eliane Wauthier, Mark E. Furth, Luca Inverardi, Juan Dominguez‐Bendala, Camillo Ricordi, David Gerber, Eugenio Gaudio, Domenico Alvaro, Lola Reid – 2 December 2011 – Multipotent stem/progenitors are present in peribiliary glands of extrahepatic biliary trees from humans of all ages and in high numbers in hepato‐pancreatic common duct, cystic duct, and hilum.

MicroRNA down‐regulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint

Alexandru V. Olaru, Gabriel Ghiaur, Sumitaka Yamanaka, Delgermaa Luvsanjav, Fangmei An, Irinel Popescu, Sorin Alexandrescu, Sarah Allen, Timothy M. Pawlik, Michael Torbenson, Christos Georgiades, Lewis R. Roberts, Gregory J. Gores, Anne Ferguson‐Smith, Maria I. Almeida, George A. Calin, Esteban Mezey, Florin M. Selaru – 2 December 2011 – MicroRNAs (miRs) recently emerged as prominent regulators of cancer processes.

Multiple ascending dose study of BMS‐790052, a nonstructural protein 5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1

Richard E. Nettles, Min Gao, Marc Bifano, Ellen Chung, Anna Persson, Thomas C. Marbury, Ronald Goldwater, Michael P. DeMicco, Maribel Rodriguez‐Torres, Apinya Vutikullird, Ernesto Fuentes, Eric Lawitz, Juan Carlos Lopez‐Talavera, Dennis M. Grasela – 2 December 2011 – The antiviral activity, resistance profile, pharmacokinetics (PK), safety, and tolerability of BMS‐790052, a nonstructural protein 5A (NS5A) replication complex inhibitor, were evaluated in a double‐blind, placebo‐controlled, sequential panel, multiple ascending dose study.

Serum ferritin concentration and transferrin saturation before liver transplantation predict decreased long‐term recipient survival

Tobias J. Weismüller, Gabriele I. Kirchner, Marcus N. Scherer, Ahmed A. Negm, Andreas A. Schnitzbauer, Frank Lehner, Jürgen Klempnauer, Hans J. Schlitt, Michael P. Manns, Christian P. Strassburg – 2 December 2011 – Serum ferritin (SF) concentration is a widely available parameter used to assess iron homeostasis. It has been described as a marker to identify high‐risk patients awaiting liver transplantation (LT) but is also elevated in systemic immune‐mediated diseases, metabolic syndrome, and in hemodialysis where it is associated with an inferior prognosis.

Alteration of hepatic nuclear receptor‐mediated signaling pathways in hepatitis C virus patients with and without a history of alcohol drinking

Chuanghong Wu, Richard Gilroy, Ryan Taylor, Mojtaba Olyaee, Bashar Abdulkarim, Jameson Forster, Maura O'Neil, Ivan Damjanov, Yu‐Jui Yvonne Wan – 2 December 2011 – The current study tests a hypothesis that nuclear receptor signaling is altered in chronic hepatitis C patients and that the altered pattern is specific to alcohol drinking history. The expression of a panel of more than 100 genes encoding nuclear receptors, coregulators, and their direct/indirect targets was studied in human livers.

Phosphatidylcholines as regulators of glucose and lipid homeostasis: Promises and potential risks

Simon Hohenester, Ulrich Beuers – 2 December 2011 – Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH‐1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH‐1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidyl‐choline species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH‐1 agonist ligand in vitro.

Carotid atherosclerosis and chronic hepatitis C: A prospective study of risk associations

Salvatore Petta, Daniele Torres, Giovanni Fazio, Calogero Cammà, Daniela Cabibi, Vito Di Marco, Anna Licata, Giulio Marchesini, Alessandra Mazzola, Gaspare Parrinello, Salvatore Novo, Giuseppe Licata, Antonio Craxì – 2 December 2011 – There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features.

A polymorphism that delays fibrosis in hepatitis C promotes alternative splicing of AZIN1, reducing fibrogenesis

Andrew J. Paris, Zohar Snapir, Cindy D. Christopherson, Shirley Y. Kwok, Ursula E. Lee, Zahra Ghiassi‐Nejad, Peri Kocabayoglu, John J. Sninsky, Josep M. Llovet, Chaim Kahana, Scott L. Friedman – 2 December 2011 – Among several single‐nucleotide polymorphisms (SNPs) that correlate with fibrosis progression in chronic HCV, an SNP in the antizyme inhibitor (AzI) gene is most strongly associated with slow fibrosis progression. Our aim was to identify the mechanism(s) underlying this observation by exploring the impact of the AzI SNP on hepatic stellate cell (HSC) activity.

The green tea polyphenol, epigallocatechin‐3‐gallate, inhibits hepatitis C virus entry

Sandra Ciesek, Thomas von Hahn, Che C. Colpitts, Luis M. Schang, Martina Friesland, Jörg Steinmann, Michael P. Manns, Michael Ott, Heiner Wedemeyer, Philip Meuleman, Thomas Pietschmann, Eike Steinmann – 2 December 2011 – Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Current antiviral therapy fails to clear infection in a substantial proportion of cases. Drug development is focused on nonstructural proteins required for RNA replication. Individuals undergoing orthotopic liver transplantation face rapid, universal reinfection of the graft.

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