Mammalian target of rapamycin regulates vascular endothelial growth factor–dependent liver cyst growth in polycystin‐2–defective mice

Carlo Spirli, Stefano Okolicsanyi, Romina Fiorotto, Luca Fabris, Massimiliano Cadamuro, Silvia Lecchi, Xin Tian, Stefan Somlo, Mario Strazzabosco – 22 April 2010 – Polycystic liver disease may complicate autosomal dominant polycystic kidney disease (ADPKD), a disease caused by mutations in polycystins, which are proteins that regulate signaling, morphogenesis, and differentiation in epithelial cells. The cystic biliary epithelium [liver cystic epithelium (LCE)] secretes vascular endothelial growth factor (VEGF), which promotes liver cyst growth via autocrine and paracrine mechanisms.

Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development

Thomas Touboul, Nicholas R. F. Hannan, Sébastien Corbineau, Amélie Martinez, Clémence Martinet, Sophie Branchereau, Sylvie Mainot, Hélène Strick‐Marchand, Roger Pedersen, James Di Santo, Anne Weber, Ludovic Vallier – 22 April 2010 – Generation of hepatocytes from human embryonic stem cells (hESCs) could represent an advantageous source of cells for cell therapy approaches as an alternative to orthotopic liver transplantation. However, the generation of differentiated hepatocytes from hESCs remains a major challenge, especially using a method compatible with clinical applications.

Deletion of CD39 on natural killer cells attenuates hepatic ischemia/reperfusion injury in mice

Guido Beldi, Yara Banz, Alexander Kroemer, Xiaofeng Sun, Yan Wu, Nadine Graubardt, Alyssa Rellstab, Martina Nowak, Keiichi Enjyoji, Xian Li, Wolfgang G. Junger, Daniel Candinas, Simon C. Robson – 22 April 2010 – Natural killer (NK) cells play crucial roles in innate immunity and express CD39 (Ecto‐nucleoside triphosphate diphosphohydrolase 1 [E‐NTPD1]), a rate‐limiting ectonucleotidase in the phosphohydrolysis of extracellular nucleotides to adenosine.

miR‐17‐5p Promotes migration of human hepatocellular carcinoma cells through the p38 mitogen‐activated protein kinase‐heat shock protein 27 pathway

Fu Yang, Yixuan Yin, Fang Wang, Yuqi Wang, Ling Zhang, Ying Tang, Shuhan Sun – 22 April 2010 – miR‐17‐5p is overexpressed in hepatocellular carcinoma (HCC), but the specific regulatory mechanisms of miR‐17‐5p in HCC remain unknown. We investigated the molecular basis of miR‐17‐5p as an oncogene in human HCC cell lines. Our in vivo and in vitro data indicate that miR‐17‐5p up‐regulates the migration and proliferation of HCC cells.

Glucagon‐like peptide‐1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway

Nitika Arora Gupta, Jamie Mells, Richard M. Dunham, Arash Grakoui, Jeffrey Handy, Neeraj Kumar Saxena, Frank A. Anania – 22 April 2010 – Glucagon‐like peptide 1 (GLP‐1) is a naturally occurring peptide secreted by the L cells of the small intestine. GLP‐1 functions as an incretin and stimulates glucose‐mediated insulin production by pancreatic β cells. In this study, we demonstrate that exendin‐4/GLP‐1 has a cognate receptor on human hepatocytes and that exendin‐4 has a direct effect on the reduction of hepatic steatosis in the absence of insulin.

Estimation of the healthy upper limits for serum alanine aminotransferase in Asian populations with normal liver histology

Jae Keun Lee, Ju Hyun Shim, Han Chu Lee, Sae Hwan Lee, Kang Mo Kim, Young‐Suk Lim, Young‐Hwa Chung, Yung Sang Lee, Dong Jin Suh – 22 April 2010 – A recent study in young Italian subjects suggested that the healthy thresholds for serum alanine aminotransferase (ALT) levels should be adjusted to 30 IU/L for men and 19 IU/L for women when assessing risk factors for nonalcoholic fatty liver disease. Our aim was to assess serum ALT concentrations in healthy Korean individuals and to determine the factors affecting ALT levels in these populations.

MicroRNAs control hepatocyte proliferation during liver regeneration

Guisheng Song, Amar Deep Sharma, Garrett R. Roll, Raymond Ng, Andrew Y. Lee, Robert H. Blelloch, Niels M. Frandsen, Holger Willenbring – 22 April 2010 – MicroRNAs (miRNAs) constitute a new class of regulators of gene expression. Among other actions, miRNAs have been shown to control cell proliferation in development and cancer. However, whether miRNAs regulate hepatocyte proliferation during liver regeneration is unknown.

Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease

Kausik Das, Kshaunish Das, Partha S. Mukherjee, Alip Ghosh, Sumantra Ghosh, Asit R. Mridha, Tapan Dhibar, Bhaskar Bhattacharya, Dilip Bhattacharya, Byomkesh Manna, Gopal K. Dhali, Amal Santra, Abhijit Chowdhury – 22 April 2010 – There is a paucity of community‐based epidemiological data on nonalcoholic fatty liver (NAFL) among nonaffluent populations in developing countries. Available studies are radiological and/or biochemical and lack histological assessment, limiting their strength.

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