The β2 integrin CD11b attenuates polyinosinic:Polycytidylic acid–induced hepatitis by negatively regulating natural killer cell functions

Minggang Zhang, Yanmei Han, Chaofeng Han, Sheng Xu, Yan Bao, Zhubo Chen, Yan Gu, Dajing Xia, Xuetao Cao – 29 October 2009 – The β2 integrins play a key role in inflammation and immune responses. The β2 integrin CD11b has been shown recently to be important in the maintenance of tolerance; however, the underlying mechanisms remain to be fully understood. Natural killer (NK) cells are an important effector of innate immunity but are also a regulator of adaptive immune response.

Identification of androgen response elements in the enhancer I of hepatitis B virus: A mechanism for sex disparity in chronic hepatitis B

Sheng‐Han Wang, Shiou‐Hwei Yeh, Wei‐Hsiang Lin, Hurng‐Yi Wang, Ding‐Shinn Chen, Pei‐Jer Chen – 29 October 2009 – Hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) occurs more often in men than in women. Male HBV carriers usually have higher viral loads, which is a well‐known risk factor for HCC. Whether and how the male androgen axis regulates HBV transcription and replication is investigated here. We used HBV transgenic mice to evaluate any sex disparity of serum hepatitis B surface antigen and HBV titers as well as the castration effect on this disparity.

Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma

Muh‐Hwa Yang, Chih‐Li Chen, Gar‐Yang Chau, Shih‐Hwa Chiou, Chien‐Wei Su, Teh‐Ying Chou, Wei‐Li Peng, Jaw‐Ching Wu – 29 October 2009 – The epithelial‐mesenchymal transition (EMT) is critical for induction of invasiveness and metastasis of human cancers. In this study we investigated the expression profiles of the EMT markers, the relationship between EMT markers and patient/tumor/viral factors, and the interplay between major EMT regulators in human hepatocellular carcinoma (HCC).

Inhibition of extracellular signal‐regulated kinase 1 by adenovirus mediated small interfering RNA attenuates hepatic fibrosis in rats

Wei Zhong, Wei‐Feng Shen, Bei‐Fang Ning, Ping‐Fang Hu, Yong Lin, Hai‐Yan Yue, Chuan Yin, Jun‐Liang Hou, Yue‐Xiang Chen, Jun‐Ping Zhang, Xin Zhang, Wei‐Fen Xie – 29 October 2009 – Extracellular signal‐regulated kinase 1 (ERK1) is a critical part of the mitogen‐activated protein kinase signal transduction pathway, which is involved in hepatic fibrosis. However, the effect of down‐regulation of ERK1 on hepatic fibrosis has not been reported. Here, we induced hepatic fibrosis in rats with dimethylnitrosamine administration or bile duct ligation.

Long‐term exclusive zinc monotherapy in symptomatic Wilson disease: Experience in 17 patients

Francisca H. H. Linn, Roderick H. J. Houwen, Jan van Hattum, Stefan van der Kleij, Karel J. van Erpecum – 29 October 2009 – Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13–26) with approximately half presenting as adolescents. Presentation was exclusively hepatic, exclusively neurologic, and combined in seven, five, and five patients, respectively. The median follow‐up was 14 years (range 2–30).

Pan‐caspase inhibitor VX‐166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis

Rafal P. Witek, W. Carl Stone, F. Gamze Karaca, Wing‐Kin Syn, Thiago A. Pereira, Kolade M. Agboola, Alessia Omenetti, Youngmi Jung, Vanessa Teaberry, Steve S. Choi, Cynthia D. Guy, John Pollard, Peter Charlton, Anna Mae Diehl – 29 October 2009 – Nonalcoholic fatty liver disease (NAFLD) is a potentially progressive liver disease that culminates in cirrhosis. Cirrhosis occurs more often in individuals with nonalcoholic steatohepatitis (NASH) than in those with steatosis (nonalcoholic fatty liver [NAFL]).

Impact of pegylated interferon and ribavirin on morbidity and mortality in patients with chronic hepatitis C and normal aminotransferases in France

Sylvie Deuffic‐Burban, Gérard Babany, Isabelle Lonjon‐Domanec, Pierre Deltenre, Valérie Canva‐Delcambre, Sébastien Dharancy, Alexandre Louvet, Françoise Roudot‐Thoraval, Philippe Mathurin – 29 October 2009 – Clinicians continue to raise questions concerning the necessity of treating chronic hepatitis C virus (HCV)‐infected patients with normal alanine aminotransferase (N‐ALT), in light of their slower progression to cirrhosis than patients with elevated alanine aminotraferase (E‐ALT).

Pharmacological inhibition of integrin αvβ3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis

Eleonora Patsenker, Yury Popov, Felix Stickel, Vreni Schneider, Monika Ledermann, Hans Sägesser, Gerald Niedobitek, Simon L. Goodman, Detlef Schuppan – 29 October 2009 – The vitronectin receptor integrin αvβ3 promotes angiogenesis by mediating migration and proliferation of endothelial cells, but also drives fibrogenic activation of hepatic stellate cells (HSCs) in vitro. Expecting antifibrotic synergism, we studied the effect of αvβ3 inhibition in two in vivo models of liver fibrogenesis.

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