Rat hepatocyte spheroids formed by rocked technique maintain differentiated hepatocyte gene expression and function

Colleen M. Brophy, Jennifer L. Luebke‐Wheeler, Bruce P. Amiot, Harris Khan, Rory P. Remmel, Piero Rinaldo, Scott L. Nyberg – 28 January 2009 – The culture of primary hepatocytes as spheroids creates an efficient three‐dimensional tissue construct for hepatic studies in vitro. Spheroids possess structural polarity and functional bile canaliculi with normal differentiated function. Thus, hepatocyte spheroids have been proposed as the cell source in a variety of diagnostic, discovery, and therapeutic applications, such as a bioartificial liver.

Hepatic steatosis in response to acute alcohol exposure in zebrafish requires sterol regulatory element binding protein activation

Michael J. Passeri, Ayca Cinaroglu, Chuan Gao, Kirsten C. Sadler – 28 January 2009 – Steatosis is the most common consequence of acute alcohol abuse and may predispose to more severe hepatic disease. Increased lipogenesis driven by the sterol response element binding protein (SREBP) transcription factors is essential for steatosis associated with chronic alcohol ingestion, but the mechanisms underlying steatosis following acute alcohol exposure are unknown.

Reduction of glycosphingolipid biosynthesis stimulates biliary lipid secretion in mice

Nora Bijl, Cindy P. A. A. van Roomen, Vassilis Triantis, Milka Sokolovic, Roelof Ottenhoff, Saskia Scheij, Marco van Eijk, Rolf G. Boot, Johannes M. Aerts, Albert K. Groen – 28 January 2009 – Recent reports indicate that glycosphingolipids play an important role in regulation of carbohydrate metabolism. We have shown that the iminosugar N‐(5′‐adamantane‐1′‐yl‐methoxy)‐pentyl‐1‐deoxynojirimycin (AMP‐DNM), an inhibitor of the enzyme glucosylceramide synthase, is a potent enhancer of insulin signaling in rodent models for insulin resistance and type 2 diabetes.

Blocking the hedgehog pathway inhibits hepatoblastoma growth

Melanie Eichenmüller, Ivonne Gruner, Beate Hagl, Beate Häberle, Josef Müller‐Höcker, Dietrich von Schweinitz, Roland Kappler – 28 January 2009 – Recent evidence has indicated that Hedgehog (Hh) signaling significantly contributes to liver development and regeneration and that activation of the pathway may contribute to growth of hepatocellular carcinoma (HCC) in adults. However, the role of Hh signaling in pediatric liver tumors remains to be elucidated.

Role of overexpression of CD151 and/or c‐Met in predicting prognosis of hepatocellular carcinoma

Ai‐Wu Ke, Guo‐Ming Shi, Jian Zhou, Fei‐Zhen Wu, Zhen‐Bin Ding, Mei‐Yu Hu, Yang Xu, Zheng‐Ji Song, Zhi‐Jun Wang, Jin‐Cai Wu, Dou‐Sheng Bai, Jia‐chu Li, Kang‐Da Liu, Jia Fan – 28 January 2009 – It has been reported that tetraspanin CD151 acts as a promoter of metastasis in several tumors and plays an important role in c‐Met/hepatocyte growth factor signaling. However, the role of CD151 alone and coexpression of CD151/c‐Met in hepatocellular carcinoma (HCC) remains unclear.

Early hepatitis B virus DNA reduction in hepatitis B e antigen–positive patients with chronic hepatitis B: A randomized international study of entecavir versus adefovir

Nancy Leung, Cheng‐Yuan Peng, Hie‐Won Hann, Jose Sollano, Judy Lao‐Tan, Chao‐Wei Hsu, Laurentius Lesmana, Man‐Fung Yuen, Lennox Jeffers, Morris Sherman, Albert Min, Kimberly Mencarini, Ulysses Diva, Anne Cross, Richard Wilber, Juan Lopez‐Talavera – 28 December 2008 – This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir (ETV) versus adefovir (ADV) in hepatitis B e antigen positive nucleoside‐naïve adults with chronic hepatitis B (CHB).

Insulin resistance is a risk factor for esophageal varices in hepatitis C virus cirrhosis

Calogero Cammà, Salvatore Petta, Vito Di Marco, Fabrizio Bronte, Stefania Ciminnisi, Giusalba Licata, Sergio Peralta, Fabio Simone, Giulio Marchesini, Antonio Craxì – 28 December 2008 – Indirect methods to predict the presence of esophageal varices (EV) in patients with cirrhosis are not sensitive enough to be used as a surrogate for endoscopy. We tested the effectiveness of liver stiffness measurement (LSM) by transient elastography and the presence of insulin resistance (IR), a marker associated with fibrosis progression, in the noninvasive prediction of portal hypertension.

The cAMP effectors Epac and protein kinase a (PKA) are involved in the hepatic cystogenesis of an animal model of autosomal recessive polycystic kidney disease (ARPKD)

Jesús M. Banales, Tatyana V. Masyuk, Sergio A. Gradilone, Anatoliy I. Masyuk, Juan F. Medina, Nicholas F. LaRusso – 28 December 2008 – PCK rats, an animal model of autosomal recessive polycystic kidney disease (ARPKD), develop cholangiocyte‐derived liver cysts associated with increased intracellular adenosine 3′,5′‐cyclic adenosine monophosphate (cAMP), the inhibition of which suppresses cyst growth.

Hepatocyte‐specific deletion of Cdc42 results in delayed liver regeneration after partial hepatectomy in mice

Haixin Yuan, Hong Zhang, Xunwei Wu, Zhe Zhang, Dan Du, Wenchao Zhou, Shuhua Zhou, Cord Brakebusch, Zhengjun Chen – 28 December 2008 – Cdc42, a member of the Rho guanosine triphosphatase (GTPase) family, plays important roles in the regulation of the cytoskeleton, cell proliferation, cell polarity, and cellular transport, but little is known about its specific function in mammalian liver. We investigated the function of Cdc42 in regulating liver regeneration. Using a mouse model with liver‐specific knockout of Cdc42 (Cdc42LK), we studied liver regeneration after partial hepatectomy.

Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management

Raj Vuppalanchi, Naga Chalasani – 28 December 2008 – Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease in the western world. It is now recognized that these patients have myriad of important co‐morbidities (e.g., diabetes, hypothyroidism and metabolic syndrome). The workup of patients with suspected NAFLD should consist of excluding competing etiologies and systemic evaluation of metabolic comorbidities. NAFLD is histologically categorized into steatosis and steatohepatitis, two states with fairly dichotomous natural history.

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