Ying‐Hong Shi, Wen‐Xing Ding, Jian Zhou, Jun‐Yi He, Yang Xu, Andrea A. Gambotto, Hannah Rabinowich, Jia Fan, Xiao‐Ming Yin – 2 May 2008 – Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Despite significantly improved diagnosis and treatment in recent years, the long‐term therapeutic effect is compromised by the frequent recurrence and metastasis, of which the molecular mechanisms are not fully understood.

Qiang You, Linling Cheng, Ross M. Kedl, Cynthia Ju – 2 May 2008 – The liver is known to favor the induction of immunological tolerance rather than immunity. Although Kupffer cells (KC) have been indicated to play a role in liver tolerance to allografts and soluble antigens, the mechanisms involved remain unclear. We hypothesized that KCs could promote immune tolerance by acting as incompetent antigen‐presenting cells (APC), as well as actively suppressing T cell activation induced by other potent APCs.

Guido Beldi, Yan Wu, Yara Banz, Michael Nowak, Lindsay Miller, Keiichi Enjyoji, Arvand Haschemi, Gennady G. Yegutkin, Daniel Candinas, Mark Exley, Simon C. Robson – 2 May 2008 – Concanavalin A (Con A)–induced injury is an established natural killer T (NKT) cell–mediated model of inflammation that has been used in studies of immune liver disease. Extracellular nucleotides, such as adenosine triphosphate, are released by Con A–stimulated cells and bind to specific purinergic type 2 receptors to modulate immune activation responses.

Jacquelyn J. Maher, Pablo Leon, James C. Ryan – 2 May 2008 – Obesity is an inflammatory disorder characterized by heightened activity of the innate immune system. Innate immune activation is central to the development of obesity‐related insulin resistance; it also plays an important role in obesity‐related tissue damage, such as that seen in atherosclerosis. Recent research has implicated the innate immune system in the pathophysiology of obesity‐related liver disease.

Ian Homer Y. Cua, Jason M. Hui, James G. Kench, Jacob George – 2 May 2008 – The interaction between insulin resistance (IR), steatosis and genotype to fibrosis in chronic hepatitis C virus (HCV) infection has not been comprehensively assessed. We hypothesized that IR is a key mediator for the development of both steatosis and fibrosis in 346 untreated, nondiabetic patients solely infected with either genotype 1 or 3. We examined for genotype‐specific interactions between IR, steatosis and fibrosis by performing subgroup analyses.

Sang Seop Lee, Eun‐Young Cha, Hyun‐Ju Jung, Ji‐Hong Shon, Eun‐Young Kim, Chang‐Woo Yeo, Jae‐Gook Shin – 2 May 2008 – Hepatocyte nuclear factor‐4 alpha (HNF4A) is an essential transcriptional regulator for many genes that are expressed preferentially in the liver. Among the important functions of the liver is drug metabolism in response to xenobiotic exposure. Recent studies have suggested that HNF4A regulates the expression of cytochrome P450 (CYP), including CYP2D6 and CYP3A4, which show large individual variations in their activities.

Mary Jane Masson, Leah D. Carpenter, Mary L. Graf, Lance R. Pohl – 2 May 2008 – Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. Although DMSO is generally thought of as being relatively inert, it can induce biological effects that are often overlooked.

Takashi Nitta, Jae‐Sung Kim, Dagmara Mohuczy, Kevin E. Behrns – 2 May 2008 – Hepatocytes that reside in a chronically‐injured liver have altered growth responses compared to hepatocytes in normal liver. Transforming growth factor beta (TGFβ) is upregulated in the cirrhotic liver, and cirrhotic hepatocytes, unlike normal hepatocytes exposed to this cytokine, exhibit decreased apoptosis. In fetal hepatocytes, TGFβ also induces epithelial‐mesenchymal transition (EMT) and signaling changes in cell survival pathways.

Silke Marhenke, Jutta Lamlé, Laura Elisa Buitrago‐Molina, José Manuel Fernández Cañón, Robert Geffers, Milton Finegold, Michael Sporn, Masayuki Yamamoto, Michael P. Manns, Markus Grompe, Arndt Vogel – 2 May 2008 – In tyrosinemia type 1 (HT1), accumulation of toxic metabolites results in oxidative stress and DNA damage, leading to a high incidence of hepatocellular carcinomas. Nuclear factor erythroid‐2 related factor 2 (Nrf2) is a key transcription factor important for cellular protection against oxidative stress and chemical induced liver damage.

Stevan A. Gonzalez, Emmet B. Keeffe – 25 April 2008