Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology

Teresa I. Ng, Hongmei Mo, Tami Pilot‐Matias, Yupeng He, Gennadiy Koev, Preethi Krishnan, Rubina Mondal, Ron Pithawalla, Wenping He, Tanya Dekhtyar, Jeremy Packer, Mark Schurdak, Akhteruzzaman Molla – 29 May 2007 – Hepatitis C virus (HCV) replication is highly dependent on host cell factors. Identification of these host factors not only facilitates understanding of the biology of HCV infection but also enables the discovery of novel targets for anti‐HCV therapy.

The mannose receptor on murine liver sinusoidal endothelial cells is the main denatured collagen clearance receptor

Ivana Malovic, Karen K. Sørensen, Kjetil H. Elvevold, Geir Ivar Nedredal, Steinar Paulsen, Alexander V. Erofeev, Bård H. Smedsrød, Peter A. G. McCourt – 29 May 2007 – The purpose of this study was to identify the receptor responsible for endocytosis of denatured collagen from blood. The major site of clearance of this material (at least 0.5 g/day in humans) is a receptor on liver sinusoidal endothelial cells (LSECs). We have now identified an 180‐kDa endocytic receptor on LSECs, peptide mass fingerprinting of which revealed it to be the mannose receptor.

Th2 and regulatory immune reactions are increased in immunoglobin G4‐related sclerosing pancreatitis and cholangitis

Yoh Zen, Takahiko Fujii, Kenichi Harada, Mitsuhiro Kawano, Kazunori Yamada, Masayuki Takahira, Yasuni Nakanuma – 29 May 2007 – Immunoglobin G (IgG) 4‐related sclerosing pancreatitis and cholangitis (autoimmune pancreato‐cholangitis [AIPC]) are recently recognized disease entities characterized by high serum IgG4 concentrations and sclerosing inflammation with numerous IgG4‐positive plasma cells, although the underlining immune mechanism remains only speculative.

Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis

Kanji Yamaguchi, Liu Yang, Shannon McCall, Jiawen Huang, Xing Xian Yu, Sanjay K. Pandey, Sanjay Bhanot, Brett P. Monia, Yin‐Xiong Li, Anna Mae Diehl – 29 May 2007 – In the early stages of nonalcoholic fatty liver disease (NAFLD), triglycerides accumulate in hepatocytes. Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step in hepatocyte triglyceride biosynthesis. DGAT2 antisense oligonucleotide (ASO) treatment improved hepatic steatosis dramatically in a previous study of obese mice.

Hepatic stellate cell protrusions couple platelet‐derived growth factor‐BB to chemotaxis

Andrew C. Melton, Hal F. Yee – 29 May 2007 – Hepatic stellate cells play an essential role in the liver's injury response. Although stellate cells are defined by the presence of cytoplasmic protrusions, the function of these characteristic structures has been obscure. We hypothesized that stellate cell protrusions act by coupling injury‐associated stimuli to chemotaxis.

Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis

Akira Hirose, Masafumi Ono, Toshiji Saibara, Yasuko Nozaki, Kosei Masuda, Akemi Yoshioka, Masaya Takahashi, Naoaki Akisawa, Shinji Iwasaki, Jude A. Oben, Saburo Onishi – 29 May 2007 – Nonalcoholic steatohepatitis (NASH) is now the most frequent cause of chronic liver impairment in developed countries and is a suggested causative factor in the development of cryptogenic cirrhosis and hepatocellular carcinoma. At present there is no effective and accepted therapy for NASH.

The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids

Alexandre Louvet, Sylvie Naveau, Marcelle Abdelnour, Marie‐José Ramond, Emmanuel Diaz, Laetitia Fartoux, Sébastien Dharancy, Frédéric Texier, Antoine Hollebecque, Lawrence Serfaty, Emmanuel Boleslawski, Pierre Deltenre, Valérie Canva, François‐René Pruvot, Philippe Mathurin – 29 May 2007 – Early identification of patients with severe (discriminant function ≥ 32) alcoholic hepatitis (AH) not responding to corticosteroids is crucial. We generated a specific prognostic model (Lille model) to identify candidates early on for alternative therapies.

Cell cycle effects resulting from inhibition of hepatocyte growth factor and its receptor c‐Met in regenerating rat livers by RNA interference

Shirish Paranjpe, William C. Bowen, Aaron W. Bell, Kari Nejak‐Bowen, Jian‐Hua Luo, George K. Michalopoulos – 29 May 2007 – Hepatocyte growth factor (HGF) and its receptor c‐Met are involved in liver regeneration. The role of HGF and c‐Met in liver regeneration in rat following two‐thirds partial hepatectomy (PHx) was investigated using RNA interference to silence HGF and c‐Met in separate experiments. A mixture of 2 c‐Met‐specific short hairpin RNA (ShRNA) sequences, ShM1 and ShM2, and 3 HGF‐specific ShRNA, ShH1, ShH3, and ShH4, were complexed with linear polyethylenimine.

Endotoxemia produces coma and brain swelling in bile duct ligated rats

Gavin Wright, Nathan A. Davies, Debbie L. Shawcross, Stephen J. Hodges, Claudia Zwingmann, Heather F. Brooks, Ali R. Mani, David Harry, Vanessa Stadlbauer, Zheng Zou, Roger Williams, Ceri Davies, Kevin P. Moore, Rajiv Jalan – 29 May 2007 – This study explores the hypothesis that the inflammatory response induced by administration of lipopolysaccharide (LPS) exacerbates brain edema in cirrhotic rats; and if so whether this is associated with altered brain metabolism of ammonia or anatomical disturbance of the blood‐brain barrier.

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