Endoplasmic reticulum stress induces hepatic steatosis via increased expression of the hepatic very low‐density lipoprotein receptor

Hyunsun Jo, Sung Sik Choe, Kyung Cheul Shin, Hagoon Jang, Jae Ho Lee, Je Kyung Seong, Sung Hoon Back, Jae Bum Kim – 13 November 2012 – Recent evidence suggests that obese animals exhibit increased endoplasmic reticulum (ER) stress in the liver and adipose tissue. Although ER stress is closely associated with lipid homeostasis, it is largely unknown how ER stress contributes to hepatic steatosis. In this study, we demonstrate that the induction of ER stress stimulates hepatic steatosis through increased expression of the hepatic very low‐density lipoprotein receptor (VLDLR).

Preexisting epithelial diversity in normal human livers: A tissue‐tethered cytometric analysis in portal/periportal epithelial cells

Kumiko Isse, Andrew Lesniak, Kedar Grama, John Maier, Susan Specht, Marcela Castillo‐Rama, John Lunz, Badrinath Roysam, George Michalopoulos, Anthony J. Demetris – 13 November 2012 – Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs). Considerable epithelial diversity, however, arises during disease states when a variety of hepatocyte‐BEC hybrid cells appear.

Hepatitis C virus promotes t‐helper (Th)17 responses through thymic stromal lymphopoietin production by infected hepatocytes

Hai‐Chon Lee, Sung‐Sang J. Sung, Peter D. Krueger, Yoon‐Ah Jo, Hugo R. Rosen, Steven F. Ziegler, Young S. Hahn – 13 November 2012 – Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Here we report that infection of hepatic cells by HCV stimulates nuclear factor kappa B (NFκB)‐dependent production of thymic stromal lymphopoietin (TSLP). Hepatocyte‐derived TSLP in turn conditions dendritic cells (DCs) to drive T‐helper (Th)17 differentiation.

Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine

Elodie Beaumont, Romuald Patient, Christophe Hourioux, Isabelle Dimier‐Poisson, Philippe Roingeard – 13 November 2012 – The development of a prophylactic vaccine against hepatitis C virus (HCV) has become an important medical priority, because 3‐4 million new HCV infections are thought to occur each year worldwide. Hepatitis B virus (HBV) is another major human pathogen, but infections with this virus can be prevented with a safe, efficient vaccine, based on the remarkable ability of the envelope protein (S) of this virus to self‐assemble into highly immunogenic subviral particles.

Increased susceptibility of natural killer T‐cell‐deficient mice to acetaminophen‐induced liver injury

Brittany V. Martin‐Murphy, Douglas J. Kominsky, David J. Orlicky, Terrence M. Donohue, Cynthia Ju – 13 November 2012 – Acetaminophen (APAP) overdose causes severe, fulminant liver injury. The underlying mechanism of APAP‐induced liver injury (AILI), studied by a murine model, displays similar characteristics of injury as those observed in patients. Previous studies suggest that aside from APAP‐induced direct damage to hepatocytes, the hepatic innate immune system is activated and may contribute to the overall pathogenesis of AILI.

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

Xijun Wang, Aihua Zhang, Hui Sun – 13 November 2012 – Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy and the third most common cause of cancer‐related death worldwide. Incidence remains highest in the developing world and is steadily increasing across the developed world. Current diagnostic modalities, of ultrasound and α‐fetoprotein, are expensive and lack sensitivity in tumor detection. Because of its asymptomatic nature, HCC is usually diagnosed at late and advanced stages, for which there are no effective therapies.

Contrast‐enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: Clinical and biological significance

Kota Sato, Shinji Tanaka, Yusuke Mitsunori, Kaoru Mogushi, Mahmut Yasen, Arihiro Aihara, Daisuke Ban, Takanori Ochiai, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Hiroshi Tanaka, Shigeki Arii – 13 November 2012 – Abnormal tumor vascularity is one of the typical features of hepatocellular carcinoma (HCC). In this study, the significance of contrast‐enhanced intraoperative ultrasonography (CEIOUS) images of HCC vasculature was evaluated by clinicopathological and gene expression analyses. We enrolled 82 patients who underwent curative hepatic resection for HCC with CEIOUS.

Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis

Chiung‐Kuei Huang, Soo Ok Lee, Kuo‐Pao Lai, Wen‐Lung Ma, Tzu‐Hua Lin, Meng‐Yin Tsai, Jie Luo, Chawnshang Chang – 13 November 2012 – Transplantation of bone marrow mesenchymal stem cells (BM‐MSCs) has been considered as an alternative therapy, replacing liver transplantation in clinical trials, to treat liver cirrhosis, an irreversible disease that may eventually lead to liver cancer development. However, low survival rate of the BM‐MSCs leading to unsatisfactory efficacy remains a major concern.

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