Activation of chemokine and inflammatory cytokine response in hepatitis C virus–infected hepatocytes depends on toll‐like receptor 3 sensing of hepatitis C virus double‐stranded RNA intermediates

Kui Li, Nan L. Li, Dahai Wei, Susan R. Pfeffer, Meiyun Fan, Lawrence M. Pfeffer – 26 October 2011 – Chemokines and inflammatory cytokines are key regulators of immunity and inflammation during viral infections. Hepatitis C virus (HCV) is a hepatotropic RNA virus frequently associated with chronic liver inflammation and hepatocellular carcinoma. Intrahepatic levels of chemokines and cytokines are elevated in chronic HCV infections, but the underlying mechanisms remain unclear.

Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation

Marc Lütgehetmann, Lida V. Mancke, Tassilo Volz, Martina Helbig, Lena Allweiss, Till Bornscheuer, Joerg M. Pollok, Ansgar W. Lohse, J. Petersen, Stephan Urban, Maura Dandri – 26 October 2011 – No specific drugs are currently available against hepatitis delta virus (HDV), a defective virus leading to the most severe form of chronic viral hepatitis in man. The lack of convenient HDV infection models has hampered the development of effective therapeutics.

β‐Catenin is essential for ethanol metabolism and protection against alcohol‐mediated liver steatosis in mice

Shiguang Liu, Tzu‐Hsuan Yeh, Vijay P. Singh, Sruti Shiva, Lindsay Krauland, Huanan Li, Pili Zhang, Kusum Kharbanda, Vladimir Ritov, Satdarshan P.S. Monga, Donald K. Scott, Patricia K. Eagon, Jaideep Behari – 26 October 2011 – The liver plays a central role in ethanol metabolism, and oxidative stress is implicated in alcohol‐mediated liver injury. β‐Catenin regulates hepatic metabolic zonation and adaptive response to oxidative stress. We hypothesized that β‐catenin regulates the hepatic response to ethanol ingestion.

Stem cells in liver diseases and cancer: Recent advances on the path to new therapies

C. Bart Rountree, Lopa Mishra, Holger Willenbring – 26 October 2011 – Stem cells have potential for therapy of liver diseases, but may also be involved in the formation of liver cancer. Recently, the American Association for the Study of Liver Diseases Henry M. and Lillian Stratton Basic Research Single Topic Conference “Stem Cells in Liver Diseases and Cancer: Discovery and Promise” brought together a diverse group of investigators to define the status of research on stem cells and cancer stem cells in the liver and identify problems and solutions on the path to clinical translation.

Receptor activator of nuclear factor‐κB ligand (RANKL) protects against hepatic ischemia/reperfusion injury in mice

Nozomu Sakai, Heather L. Van Sweringen, Rebecca Schuster, John Blanchard, Justin M. Burns, Amit D. Tevar, Michael J. Edwards, Alex B. Lentsch – 26 October 2011 – The transcription factor nuclear factor kappaB (NF‐κB) plays diverse roles in the acute injury response to hepatic ischemia/reperfusion (I/R). Activation of NF‐κB in Kupffer cells promotes inflammation through cytokine expression, whereas activation in hepatocytes may be cell protective.

Hepatic macrophage migration and differentiation critical for liver fibrosis is mediated by the chemokine receptor C‐C motif chemokine receptor 8 in mice

Felix Heymann, Linda Hammerich, Dunja Storch, Matthias Bartneck, Sebastian Huss, Vanessa Rüsseler, Nikolaus Gassler, Sergio A. Lira, Tom Luedde, Christian Trautwein, Frank Tacke – 26 October 2011 – Chemokines critically control the infiltration of immune cells upon liver injury, thereby promoting hepatic inflammation and fibrosis. The chemokine receptor CCR8 can affect trafficking of monocytes/macrophages, monocyte‐derived dendritic cells (DCs) and T‐helper cell (Th) subsets, but its role in liver diseases is currently unknown.

Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers

Lucia Russo, Jorge Gracia‐Sancho, Héctor García‐Calderó, Giusi Marrone, Juan Carlos García‐Pagán, Guillermo García‐Cardeña, Jaime Bosch – 26 October 2011 – Pathophysiological alterations in the endothelial phenotype result in endothelial dysfunction. Flow cessation, occurring during organ procurement for transplantation, triggers the endothelial dysfunction characteristic of ischemia/reperfusion injury, partly due to a reduction in the expression of the vasoprotective transcription factor Kruppel‐like Factor 2 (KLF2).

Plasma cells and the chronic nonsuppurative destructive cholangitis of primary biliary cirrhosis

Toru Takahashi, Tomofumi Miura, Junichiro Nakamura, Satoshi Yamada, Tsutomu Miura, Masahiko Yanagi, Yasunobu Matsuda, Hiroyuki Usuda, Iwao Emura, Koichi Tsuneyama, Xiao‐Song He, M. Eric Gershwin – 26 October 2011 – There has been increased interest in the role of B cells in the pathogenesis of primary biliary cirrhosis (PBC). Although the vast majority of patients with this disease have anti‐mitochondrial antibodies, there is no correlation of anti‐mitochondrial antibody titer and/or presence with disease severity.

Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: Results from the hepatitis C antiviral long‐term treatment against cirrhosis trial

Gregory T. Everson, Mitchell L. Shiffman, John C. Hoefs, Timothy R. Morgan, Richard K. Sterling, David A. Wagner, Shannon Lauriski, Teresa M. Curto, Anne Stoddard, Elizabeth C. Wright, the HALT‐C Trial Group – 26 October 2011 – Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome.

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