Prosurvival function of the cellular apoptosis susceptibility/importin‐α1 transport cycle is repressed by p53 in liver cancer

Juliane Winkler, Alessandro Ori, Kerstin Holzer, Carsten Sticht, Daniel Dauch, Eva Maria Eiteneuer, Federico Pinna, Robert Geffers, Volker Ehemann, Amparo Andres‐Pons, Kai Breuhahn, Thomas Longerich, Justo Lorenzo Bermejo, Norbert Gretz, Lars Zender, Peter Schirmacher, Martin Beck, Stephan Singer – 6 May 2014 – Proteins of the karyopherin superfamily including importins and exportins represent an essential part of the nucleocytoplasmic transport machinery. However, the functional relevance and regulation of karyopherins in hepatocellular carcinoma (HCC) is poorly understood.

Human drug‐induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump

Michael D. Aleo, Yi Luo, Rachel Swiss, Paul D. Bonin, David M. Potter, Yvonne Will – 6 May 2014 – Drug‐induced liver injury (DILI) accounts for 20‐40% of all instances of clinical hepatic failure and is a common reason for withdrawal of an approved drug or discontinuation of a potentially new drug from clinical/nonclinical development. Numerous individual risk factors contribute to the susceptibility to human DILI and its severity that are either compound‐ and/or patient‐specific.

Elevated sensitivity of macrosteatotic hepatocytes to hypoxia/reoxygenation stress is reversed by a novel defatting protocol

Nir I. Nativ, Gabriel Yarmush, Ashley So, Jeffery Barminko, Timothy J. Maguire, Rene Schloss, Francois Berthiaume, Martin L. Yarmush – 6 May 2014 – Macrosteatotic livers exhibit elevated intrahepatic triglyceride (TG) levels in the form of large lipid droplets (LDs), reduced adenosine triphosphate (ATP) levels, and elevated reactive oxygen species (ROS) levels, and this contributes to their elevated sensitivity to ischemia/reperfusion injury during transplantation. Reducing macrosteatosis in living donors through dieting has been shown to improve transplant outcomes.

Prosurvival function of the cellular apoptosis susceptibility/importin‐α1 transport cycle is repressed by p53 in liver cancer

Juliane Winkler, Alessandro Ori, Kerstin Holzer, Carsten Sticht, Daniel Dauch, Eva Maria Eiteneuer, Federico Pinna, Robert Geffers, Volker Ehemann, Amparo Andres‐Pons, Kai Breuhahn, Thomas Longerich, Justo Lorenzo Bermejo, Norbert Gretz, Lars Zender, Peter Schirmacher, Martin Beck, Stephan Singer – 6 May 2014 – Proteins of the karyopherin superfamily including importins and exportins represent an essential part of the nucleocytoplasmic transport machinery. However, the functional relevance and regulation of karyopherins in hepatocellular carcinoma (HCC) is poorly understood.

Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes

Xiaodan Zhang, William S. Harmsen, Teresa A. Mettler, W. Ray Kim, Rosebud O. Roberts, Terry M. Therneau, Lewis R. Roberts, Roongruedee Chaiteerakij – 3 May 2014 – The risks and benefits of metformin use in patients with cirrhosis with diabetes are debated. Although data on a protective effect of metformin against liver cancer development have been reported, metformin is frequently discontinued once cirrhosis is diagnosed because of concerns about an increased risk of adverse effects of metformin in patients with liver impairment.

Bile acids alter male fertility through G‐protein‐coupled bile acid receptor 1 signaling pathways in mice

Marine Baptissart, Aurélie Vega, Emmanuelle Martinot, Aurélien J. Pommier, Sander M. Houten, Geoffroy Marceau, Angélique de Haze, Silvère Baron, Kristina Schoonjans, Jean‐Marc A. Lobaccaro, David H. Volle – 3 May 2014 – Bile acids (BAs) are signaling molecules that are involved in many physiological functions, such as glucose and energy metabolism. These effects are mediated through activation of the nuclear and membrane receptors, farnesoid X receptor (FXR‐α) and TGR5 (G‐protein‐coupled bile acid receptor 1; GPBAR1).

Modulation of miR‐29 expression by alpha‐fetoprotein is linked to the hepatocellular carcinoma epigenome

Sonya Parpart, Stephanie Roessler, Fei Dong, Vinay Rao, Atsushi Takai, Junfang Ji, Lun‐Xiu Qin, Qing‐Hai Ye, Hu‐Liang Jia, Zhao‐You Tang, Xin Wei Wang – 3 May 2014 – Globally, hepatocellular carcinoma (HCC) accounts for 70%‐85% of primary liver cancers and ranks as the second leading cause of male cancer death. Serum alpha‐fetoprotein (AFP), normally highly expressed in the liver only during fetal development, is reactivated in 60% of HCC tumors and associated with poor patient outcome. We hypothesize that AFP+ and AFP− tumors differ biologically.

Development of hepatitis C virus genotype 3a cell culture system

Sulyi Kim, Tomoko Date, Hiroshi Yokokawa, Tamaki Kono, Hideki Aizaki, Patrick Maurel, Claire Gondeau, Takaji Wakita – 3 May 2014 – Hepatitis C virus (HCV) genotype 3a infection poses a serious health problem worldwide. A significant association has been reported between HCV genotype 3a infections and hepatic steatosis. Nevertheless, virological characterization of genotype 3a HCV is delayed due to the lack of appropriate virus cell culture systems. In the present study, we established the first infectious genotype 3a HCV system by introducing adaptive mutations into the S310 strain.

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