Functional alterations of liver innate immunity of mice with aging in response to CpG‐oligodeoxynucleotide

Toshinobu Kawabata, Manabu Kinoshita, Akihito Inatsu, Yoshiko Habu, Hiroyuki Nakashima, Nariyoshi Shinomiya, Shuhji Seki – 28 October 2008 – Immune functions of liver natural killer T (NKT) cells induced by the synthetic ligand α‐galactosylceramide enhanced age‐dependently; hepatic injury and multiorgan dysfunction syndrome (MODS) induced by ligand‐activated NKT cells were also enhanced. This study investigated how aging affects liver innate immunity after common bacteria DNA stimulation.

Heme oxygenase‐1 suppresses hepatitis C virus replication and increases resistance of hepatocytes to oxidant injury

Zhaowen Zhu, Anne T. Wilson, M. Meleah Mathahs, Feng Wen, Kyle E. Brown, Bruce A. Luxon, Warren N. Schmidt – 28 October 2008 – Oxidative injury to hepatocytes occurs as a result of hepatitis C virus (HCV) infection and replication. Modulation of host cell antioxidant enzymes such as heme oxygenase‐1 (HO‐1) may be useful therapeutically to minimize cellular injury, reduce viral replication, and attenuate liver disease. In this report, we evaluated the effects of HO‐1 overexpression on HCV replication and hepatocellular injury.

Evaluation of previously nonscreened hereditary hemorrhagic telangiectasia patients shows frequent liver involvement and early cardiac consequences

Rodica Gincul, Gaetan Lesca, Bénédicte Gelas‐Dore, Nathalie Rollin, Martine Barthelet, Sophie Dupuis‐Girod, Franck Pilleul, Sophie Giraud, Henri Plauchu, Jean‐Christophe Saurin – 28 October 2008 – Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by cutaneous, mucosal, and sometimes visceral arteriovenous malformations. Severe hepatic manifestations have been characterized in a subgroup of patients, but few data are available in previously nonscreened patients. We prospectively evaluated liver involvement and its cardiac consequences in such patients.

Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen–negative chronic hepatitis B virus infection?

George V. Papatheodoridis, Emanuel K. Manesis, Spilios Manolakopoulos, Ioannis S. Elefsiniotis, John Goulis, John Giannousis, Antonios Bilalis, Georgia Kafiri, Dimitrios Tzourmakliotis, Athanasios J. Archimandritis – 28 October 2008 – The diagnosis of hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA ≥2,000 IU/mL.

The angiogenic makeup of human hepatocellular carcinoma does not favor vascular endothelial growth factor/angiopoietin‐driven sprouting neovascularization

Wenjiao Zeng, Annette S.H. Gouw, Marius C. van den Heuvel, Peter J. Zwiers, Pieter E. Zondervan, Sibrand Poppema, Nong Zhang, Inge Platteel, Koert P. de Jong, Grietje Molema – 28 October 2008 – Quantitative data on the expression of multiple factors that control angiogenesis in hepatocellular carcinoma (HCC) are limited. A better understanding of the mechanisms underlying angiogenesis in HCC will improve the rational choice of anti‐angiogenic treatment.

Rab4 facilitates cyclic adenosine monophosphate–stimulated bile acid uptake and Na+‐taurocholate cotransporting polypeptide translocation

Christopher M. Schonhoff, Krishna Thankey, Cynthia R.L. Webster, Yoshiyuki Wakabayashi, Allan W. Wolkoff, M. Sawkat Anwer – 28 October 2008 – Cyclic adenosine monophosphate (cAMP) stimulates hepatic bile acid uptake by translocating sodium‐taurocholate (TC) cotransporting polypeptide (Ntcp) from an endosomal compartment to the plasma membrane. Rab4 is associated with early endosomes and involved in vesicular trafficking. This study was designed to determine the role of Rab4 in cAMP‐induced TC uptake and Ntcp translocation.

Translocation of iron from lysosomes into mitochondria is a key event during oxidative stress‐induced hepatocellular injury

Akira Uchiyama, Jae‐Sung Kim, Kazuyoshi Kon, Hartmut Jaeschke, Kenichi Ikejima, Sumio Watanabe, John J. Lemasters – 28 October 2008 – Iron overload exacerbates various liver diseases. In hepatocytes, a portion of non‐heme iron is sequestered in lysosomes and endosomes. The precise mechanisms by which lysosomal iron participates in hepatocellular injury remain uncertain. Here, our aim was to determine the role of intracellular movement of chelatable iron in oxidative stress‐induced killing to cultured hepatocytes from C3Heb mice and Sprague‐Dawley rats.

Alpha‐lipoic acid decreases hepatic lipogenesis through adenosine monophosphate‐activated protein kinase (AMPK)‐dependent and AMPK‐independent pathways

Keun‐Gyu Park, Ae‐Kyung Min, Eun Hee Koh, Hyoun Sik Kim, Mi‐Ok Kim, Hye‐Sun Park, Yong‐Deuk Kim, Tae‐Seung Yoon, Byoung Kuk Jang, Jae Seok Hwang, Jae Bum Kim, Hueng‐Sik Choi, Joong‐Yeol Park, In‐Kyu Lee, Ki‐Up Lee – 28 October 2008 – Fatty liver is common in obese subjects with insulin resistance. Hepatic expression of sterol regulatory element binding protein‐1c (SREBP‐1c), which plays a major role in hepatic steatosis, is regulated by multiple factors, including insulin, adenosine monophosphate–activated protein kinase (AMPK), liver X receptors (LXRs), and specificity protein 1.

Intrahepatic levels of CXCR3‐associated chemokines correlate with liver inflammation and fibrosis in chronic hepatitis C

Marija Zeremski, Lydia M. Petrovic, Luis Chiriboga, Queenie B. Brown, Herman T. Yee, Milan Kinkhabwala, Ira M. Jacobson, Rositsa Dimova, Marianthi Markatou, Andrew H. Talal – 28 October 2008 – Chemokines, chemotactic cytokines, may promote hepatic inflammation in chronic hepatitis C virus (HCV) infection through the recruitment of lymphocytes to the liver parenchyma.

Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor‐4α gene

Chuan Yin, Yong Lin, Xin Zhang, Yue‐Xiang Chen, Xin Zeng, Hai‐Yan Yue, Jun‐Liang Hou, Xing Deng, Jun‐Ping Zhang, Ze‐Guang Han, Wei‐Fen Xie – 28 October 2008 – Previous studies have shown that hepatocyte nuclear factor‐4α (HNF4α) is a central regulator of differentiated hepatocyte phenotype and forced expression of HNF4α could promote reversion of tumors toward a less invasive phenotype. However, the effect of HNF4α on cancer stem cells (CSCs) and the treatment of hepatocellular carcinoma (HCC) with HNF4α have not been reported.

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