Elevated hepatic multidrug resistance‐associated protein 3/ATP‐binding cassette subfamily C 3 expression in human obstructive cholestasis is mediated through tumor necrosis factor alpha and c‐Jun NH2‐terminal kinase/stress‐activated protein kinase–signali

Jin Chai, Yu He, Shi‐Ying Cai, Zhongyong Jiang, Huaizhi Wang, Qiong Li, Lei Chen, Zhihong Peng, Xiaochong He, Xiaoping Wu, Tianli Xiao, Rongquan Wang, James L. Boyer, Wensheng Chen – 22 November 2011 – Multidrug resistance‐associated protein 3 (MRP3, ABC subfamily C [ABCC]3) plays an important role in protecting hepatocytes and other tissues by excreting an array of toxic organic anion conjugates, including bile salts. MRP3/ABCC3 expression is increased in the liver of some cholestatic patients, but the molecular mechanism of this up‐regulation remains elusive.

(−)‐Epigallocatechin‐3‐gallate is a new inhibitor of hepatitis C virus entry

Noémie Calland, Anna Albecka, Sandrine Belouzard, Czeslaw Wychowski, Gilles Duverlie, Véronique Descamps, Didier Hober, Jean Dubuisson, Yves Rouillé, Karin Séron – 22 November 2011 – Here, we identify (−)‐epigallocatechin‐3‐gallate (EGCG) as a new inhibitor of hepatitis C virus (HCV) entry. EGCG is a flavonoid present in green tea extract belonging to the subclass of catechins, which has many properties. Particularly, EGCG possesses antiviral activity and impairs cellular lipid metabolism.

International cross‐cultural field validation of an European Organization for Research and Treatment of Cancer questionnaire module for patients with primary liver cancer, the European Organization for Research and Treatment of Cancer quality‐of‐life ques

Wei‐Chu Chie, Jane M. Blazeby, Chin‐Fu Hsiao, Herng‐Chia Chiu, Ronnie T. Poon, Naoko Mikoshiba, Gillian Al‐Kadhimi, Nigel Heaton, Jozer Calara, Peter Collins, Katharine Caddick, Anna Costantini, Valerie Vilgrain, Ludovic Trinquart, Chieh Chiang, On behalf of the EORTC Quality of Life Group – 22 November 2011 – This international field validation study examined the psychometric properties and clinical validity of the European Organization for Research and Treatment of Cancer (EORTC) questionnaire module for hepatocellular carcinoma (HCC), the EORTC quality‐of‐life questionnaire (QLQ)‐HCC18.

Cytomegalovirus‐specific T‐cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells

Stephen M. Brindley, Allison M. Lanham, Frederick M. Karrer, Rebecca M. Tucker, Andrew P. Fontenot, Cara L. Mack – 22 November 2011 – Biliary atresia (BA) is a progressive, inflammatory cholangiopathy that culminates in fibrosis of extrahepatic and intrahepatic bile ducts. A leading theory on the pathogenesis of BA is that the bile duct damage is initiated by a virus infection, followed by a bile duct‐targeted autoimmune response. One mechanism of autoimmunity entails a diminished number or function of regulatory T cells (Tregs).

Genetic variants in human leukocyte antigen/DP‐DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development

Lingmin Hu, Xiangjun Zhai, Jibin Liu, Minjie Chu, Shandong Pan, Jie Jiang, Yixin Zhang, Hua Wang, Jianguo Chen, Hongbing Shen, Zhibin Hu – 22 November 2011 – Recent genome‐wide association studies showed that four single‐nucleotide polymorphisms (SNPs) in human leukocyte antigen (HLA)‐DP (rs3077and rs9277535) and HLA‐DQ (rs2856718 and rs7453920) were associated with chronic hepatitis B virus (HBV) infection in Japanese populations. More than 75% of hepatocellular carcinoma (HCC) patients are attributable to persistent infection of hepatitis B virus (HBV), especially in China.

Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents

Nicola Santoro, Clarence K. Zhang, Hongyu Zhao, Andrew J. Pakstis, Grace Kim, Romy Kursawe, Daniel J. Dykas, Allen E. Bale, Cosimo Giannini, Bridget Pierpont, Melissa M. Shaw, Leif Groop, Sonia Caprio – 22 November 2011 – Recently, the single nucleotide polymorphism (SNP) identified as rs1260326, in the glucokinase regulatory protein (GCKR), was associated with hypertriglyceridemia in adults.

Interleukin‐30: A novel antiinflammatory cytokine candidate for prevention and treatment of inflammatory cytokine‐induced liver injury

Denada Dibra, Jeffry Cutrera, Xueqing Xia, Bhaskar Kallakury, Lopa Mishra, Shulin Li – 22 November 2011 – The liver is the major metabolic organ and is subjected to constant attacks from chronic viral infection, uptake of therapeutic drugs, life behavior (alcoholic), and environmental contaminants, all of which result in chronic inflammation, fibrosis, and, ultimately, cancer. Therefore, there is an urgent need to discover effective therapeutic agents for the prevention and treatment of liver injury, the ideal drug being a naturally occurring biological inhibitor.

Thrombospondin‐1 is a novel negative regulator of liver regeneration after partial hepatectomy through transforming growth factor‐beta1 activation in mice

Hiromitsu Hayashi, Keiko Sakai, Hideo Baba, Takao Sakai – 22 November 2011 – The matricellular protein, thrombospondin‐1 (TSP‐1), is prominently expressed during tissue repair. TSP‐1 binds to matrix components, proteases, cytokines, and growth factors and activates intracellular signals through its multiple domains. TSP‐1 converts latent transforming growth factor‐beta1 (TGF‐β1) complexes into their biologically active form. TGF‐β plays significant roles in cell‐cycle regulation, modulation of differentiation, and induction of apoptosis.

Caveolin‐1 orchestrates the balance between glucose and lipid‐dependent energy metabolism: Implications for liver regeneration

Manuel Alejandro Fernández‐Rojo, Christina Restall, Charles Ferguson, Nick Martel, Sally Martin, Marta Bosch, Adam Kassan, Gary M. Leong, Sheree D. Martin, Sean L. McGee, George E.O. Muscat, Robin L. Anderson, Carlos Enrich, Albert Pol, Robert G. Parton – 22 November 2011 – Caveolin‐1 (CAV1) is a structural protein of caveolae involved in lipid homeostasis and endocytosis.

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