Conjugation is essential for the anticholestatic effect of NorUrsodeoxycholic acid in taurolithocholic acid–induced cholestasis in rat liver

Gerald U. Denk, Silvia Maitz, Ralf Wimmer, Christian Rust, Pietro Invernizzi, Sacha Ferdinandusse, Wim Kulik, Andrea Fuchsbichler, Peter Fickert, Michael Trauner, Alan F. Hofmann, Ulrich Beuers – 20 August 2010 – NorUDCA (24‐norursodeoxycholic acid), the C23‐homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic Mdr2 (Abcb4) (multidrug resistance protein 2/ATP‐binding cassette b4) knockout mice with sclerosing/fibrosing cholangitis.

Disruption of the 12/15‐lipoxygenase gene (Alox15) protects hyperlipidemic mice from nonalcoholic fatty liver disease

Marcos Martínez‐Clemente, Natàlia Ferré, Esther Titos, Raquel Horrillo, Ana González‐Périz, Eva Morán‐Salvador, Cristina López‐Vicario, Rosa Miquel, Vicente Arroyo, Colin D. Funk, Joan Clària – 20 August 2010 – We have shown that Alox15, the gene encoding for 12/15‐lipoxygenase (12/15‐LO), is markedly up‐regulated in livers from apolipoprotein E‐deficient (ApoE−/−) mice, which spontaneously develop nonalcoholic fatty liver disease secondary to hyperlipidemia.

Growth arrest–specific protein 6 is hepatoprotective against murine ischemia/reperfusion injury

Laura Llacuna, Cristina Bárcena, Lola Bellido‐Martín, Laura Fernández, Milica Stefanovic, Montserrat Marí, Carmen García‐Ruiz, José C. Fernández‐Checa, Pablo García de Frutos, Albert Morales – 20 August 2010 – Growth arrest–specific gene 6 (GAS6) promotes growth and cell survival during tissue repair and development in different organs, including the liver. However, the specific role of GAS6 in liver ischemia/reperfusion (I/R) injury has not been previously addressed. Here we report an early increase in serum GAS6 levels after I/R exposure.

Re‐evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease

Emanuele Nicastro, Giusy Ranucci, Pietro Vajro, Angela Vegnente, Raffaele Iorio – 20 August 2010 – The diagnosis of Wilson disease (WD) is challenging, especially in children. Early detection is desirable in order to avoid dramatic disease progression. The aim of our study was to re‐evaluate in WD children with mild liver disease the conventional diagnostic criteria and the WD scoring system proposed by an international consensus in 2001.

Bacterial DNA translocation is associated with systemic circulatory abnormalities and intrahepatic endothelial dysfunction in patients with cirrhosis

Pablo Bellot, Juan Carlos García‐Pagán, Rubén Francés, Juan G. Abraldes, Miguel Navasa, Miguel Pérez‐Mateo, José Such, Jaime Bosch – 20 August 2010 – Presence of bacterial DNA in noninfected patients with cirrhosis and ascites is associated with a marked inflammatory response including activation of the inducible form of nitric oxide synthase and release of nitric oxide, similar to that observed in patients with spontaneous bacterial peritonitis. Although presence of bacterial DNA is associated with an impaired prognosis, no information is available regarding its hemodynamic consequences.

IL28B genotype is associated with differential expression of intrahepatic interferon‐stimulated genes in patients with chronic hepatitis C

Thomas J. Urban, Alexander J. Thompson, Shelton S. Bradrick, Jacques Fellay, Detlef Schuppan, Kenneth D. Cronin, Linda Hong, Alexander McKenzie, Keyur Patel, Kevin V. Shianna, John G. McHutchison, David B. Goldstein, Nezam Afdhal – 20 August 2010 – Genetic variation in the IL28B (interleukin 28B; interferon lambda 3) region has been associated with sustained virological response (SVR) rates in patients with chronic hepatitis C (CHC) who were treated with peginterferon‐α and ribavirin.

Liver‐specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice

Kwang Suk Ko, Maria Lauda Tomasi, Ainhoa Iglesias‐Ara, Barbara A. French, Samuel W. French, Komal Ramani, Juan José Lozano, Pilsoo Oh, Lina He, Bangyan L Stiles, Tony W.H Li, Heping Yang, M. Luz Martínez‐Chantar, José M. Mato, Shelly C. Lu – 20 August 2010 – Prohibitin 1 (PHB1) is a highly conserved, ubiquitously expressed protein that participates in diverse processes including mitochondrial chaperone, growth and apoptosis. The role of PHB1 in vivo is unclear and whether it is a tumor suppressor is controversial.

Biliverdin inhibits hepatitis C virus nonstructural 3/4A protease activity: Mechanism for the antiviral effects of heme oxygenase?

Zhaowen Zhu, Anne T. Wilson, Bruce A. Luxon, Kyle E. Brown, M. Meleah Mathahs, Sarmistha Bandyopadhyay, Anton P. McCaffrey, Warren N. Schmidt – 20 August 2010 – Induction of heme oxygenase‐1 (HO‐1) inhibits hepatitis C virus (HCV) replication. Of the products of the reaction catalyzed by HO‐1, iron has been shown to inhibit HCV ribonucleic acid (RNA) polymerase, but little is known about the antiviral activity of biliverdin (BV).

Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: Impact of liver methylation of the peroxisome proliferator–activated receptor γ coactivator 1α promoter

Silvia Sookoian, Maria Soledad Rosselli, Carolina Gemma, Adriana L. Burgueño, Tomas Fernández Gianotti, Gustavo O. Castaño, Carlos J. Pirola – 20 August 2010 – Insulin resistance (IR) and mitochondrial dysfunction play a central role in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). We hypothesized that genetic factors and epigenetic modifications occurring in the liver contribute to the IR phenotype.

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