Type 2 inositol 1,4,5‐trisphosphate receptor modulates bile salt export pump activity in rat hepatocytes

Emma A. Kruglov, Samir Gautam, Mateus T. Guerra, Michael H. Nathanson – 11 July 2011 – Bile salt secretion is mediated primarily by the bile salt export pump (Bsep), a transporter on the canalicular membrane of the hepatocyte. However, little is known about the short‐term regulation of Bsep activity. Ca2+ regulates targeting and insertion of transporters in many cell systems, and Ca2+ release near the canalicular membrane is mediated by the type II inositol 1,4,5‐trisphosphate receptor (InsP3R2), so we investigated the possible role of InsP3R2 in modulating Bsep activity.

Nuclear factor high‐mobility group box1 mediating the activation of toll‐like receptor 4 signaling in hepatocytes in the early stage of nonalcoholic fatty liver disease in mice

Liang Li, Lei Chen, Liang Hu, Yuan Liu, Han‐Yong Sun, Jing Tang, Yu‐Jie Hou, Yan‐Xin Chang, Qian‐Qian Tu, Gen‐Sheng Feng, Feng Shen, Meng‐Chao Wu, Hong‐Yang Wang – 11 July 2011 – One of the challenges surrounding nonalcoholic fatty liver disease (NAFLD) is to discover the mechanisms that underlie the initiation of it. The aim of the present study was to elucidate the effects of Toll‐like receptor 4 (TLR4) signaling in liver parenchymal cells during the early stage of NAFLD.

Dual farnesoid X receptor/TGR5 agonist INT‐767 reduces liver injury in the Mdr2−/− (Abcb4−/−) mouse cholangiopathy model by promoting biliary HCO output

Anna Baghdasaryan, Thierry Claudel, Judith Gumhold, Dagmar Silbert, Luciano Adorini, Aldo Roda, Stefania Vecchiotti, Frank J. Gonzalez, Kristina Schoonjans, Mario Strazzabosco, Peter Fickert, Michael Trauner – 11 July 2011 – Chronic cholangiopathies have limited therapeutic options and represent an important indication for liver transplantation. The nuclear farnesoid X receptor (FXR) and the membrane G protein‐coupled receptor, TGR5, regulate bile acid (BA) homeostasis and inflammation.

Circulating microRNAs as potential markers of human drug‐induced liver injury

Philip J. Starkey Lewis, James Dear, Vivien Platt, Kenneth J. Simpson, Darren G.N. Craig, Daniel J. Antoine, Neil S. French, Neeraj Dhaun, David J. Webb, Eithne M. Costello, John P. Neoptolemos, Jonathan Moggs, Chris E. Goldring, B. Kevin Park – 11 July 2011 – New biomarkers of liver injury are required in the clinic and in preclinical pharmaceutical evaluation. Previous studies demonstrate that two liver‐enriched microRNAs (miR‐122 and miR‐192) are promising biomarkers of acetaminophen‐induced acute liver injury (APAP‐ALI) in mice.

Dysregulation of the unfolded protein response in db/db mice with diet‐induced steatohepatitis

Mary E. Rinella, M. Shaddab Siddiqui, Konstantina Gardikiotes, Jeanne Gottstein, Marc Elias, Richard M. Green – 11 July 2011 – In humans with nonalcoholic fatty liver, diabetes is associated with more advanced disease. We have previously shown that diabetic db/db mice are highly susceptible to methionine choline‐deficient diet (MCD)‐induced hepatic injury.

Epimorphin promotes human hepatocellular carcinoma invasion and metastasis through activation of focal adhesion kinase/extracellular signal‐regulated kinase/matrix metalloproteinase‐9 axis

Ya‐Li Jia, Lei Shi, Jun‐Nian Zhou, Chun‐Jiang Fu, Lin Chen, Hong‐Feng Yuan, Yun‐Fang Wang, Xin‐Long Yan, Ying‐Chen Xu, Quan Zeng, Wen Yue, Xue‐Tao Pei – 11 July 2011 – The high incidence rate of hepatocellular carcinoma (HCC) is mainly the result of frequent metastasis and tumor recurrence. Unfortunately, the underlying molecular mechanisms driving HCC metastasis are still not fully understood. It has been demonstrated that tumor stroma cells contribute to primary tumor growth and metastasis.

Shorter durations and lower doses of peginterferon alfa‐2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C

Y.‐F. Liaw, J.‐D. Jia, H.L.Y. Chan, K.H. Han, T. Tanwandee, W.L. Chuang, D.M. Tan, X.Y. Chen, E. Gane, T. Piratvisuth, L. Chen, Q. Xie, J.J.Y. Sung, C. Wat, C. Bernaards, Y. Cui, P. Marcellin – 11 July 2011 – As there is currently a lack of consensus on the most appropriate dose and duration of peginterferon alfa‐2a (PEG‐IFNα‐2a) therapy in hepatitis B e antigen (HBeAg)‐positive patients, the efficacy and safety of either 24 or 48 weeks' duration and 90 μg/week or 180 μg/week doses were compared.

Comparison of the 2‐step tuberculin skin test and the quantiFERON‐TB gold in‐tube test for the screening of tuberculosis infection before liver transplantation

Susana Casas, Laura Muñoz, Raquel Moure, Jose Castellote, Maria R. Guerra, Lucia Gonzalez, Ana Andreu, Antoni G. Rafecas, Fernando Alcaide, Miguel Santin – 11 July 2011 – The ability of interferon‐γ release assays (IGRAs) to detect latent tuberculosis (TB) infection before liver transplantation (LT) is not well established.

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