S‐adenosylhomocysteine sensitizes to TNF‐α hepatotoxicity in mice and liver cells: A possible etiological factor in alcoholic liver disease

Zhenyuan Song, Zhanxiang Zhou, Silvia Uriarte, Lipeng Wang, Y. James Kang, Theresa Chen, Shirish Barve, Craig J. McClain – 23 February 2009 – In alcoholic liver disease, tumor necrosis factor‐α (TNFα) is a critical effector molecule, and abnormal methionine metabolism is a fundamental acquired metabolic abnormality. Although hepatocytes are resistant to TNFα‐induced killing under normal circumstances, previous studies have shown that primary hepatocytes from rats chronically fed alcohol have increased TNFα cytotoxicity.

Induction or expansion of T‐cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers

Maryline Mancini‐Bourgine, Hélène Fontaine, Daniel Scott‐Algara, Stanislas Pol, Christian Bréchot, Marie‐Louise Michel – 23 February 2009 – Despite the availability of effective hepatitis B vaccines for many years, over 370 million people remain persistently infected with hepatitis B virus (HBV). Viral persistence is thought to be related to poor HBV‐specific T‐cell responses. A phase I clinical trial was performed in chronic HBV carriers to investigate whether HBV DNA vaccination could restore T‐cell responsiveness.

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.

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.

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.

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.

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.

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George V. Papatheodoridis, Emanuel K. Manesis, Spilios Manolakopoulos, Ioannis S. Elefsiniotis, John Goulis, Athanasios J. Archimandritis – 28 January 2009

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