Natural antisense transcript stabilizes inducible nitric oxide synthase messenger RNA in rat hepatocytes

Kosuke Matsui, Mikio Nishizawa, Takashi Ozaki, Tominori Kimura, Iwao Hashimoto, Masanori Yamada, Masaki Kaibori, Yasuo Kamiyama, Seiji Ito, Tadayoshi Okumura – 26 January 2008 – During inflammation, inducible nitric oxide synthase (iNOS) is induced to generate the important mediator nitric oxide (NO). Interleukin 1β (IL‐1β) induces iNOS messenger RNA (mRNA), iNOS protein, and NO in rat hepatocytes.

Etiology‐dependent molecular mechanisms in human hepatocarcinogenesis

Christof Schlaeger, Thomas Longerich, Claudia Schiller, Peter Bewerunge, Arianeb Mehrabi, Grischa Toedt, Jörg Kleeff, Volker Ehemann, Roland Eils, Peter Lichter, Peter Schirmacher, Bernhard Radlwimmer – 26 January 2008 – Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is characterized by aggressive tumor behavior coupled with poor prognosis. Various etiologies have been linked to HCC development, most prominently chronic hepatitis B and C virus infections as well as chronic alcohol consumption.

Hepatic parenchymal replacement in mice by transplanted allogeneic hepatocytes is facilitated by bone marrow transplantation and mediated by CD4 cells

Konrad L. Streetz, Regis Doyonnas, Dirk Grimm, D. Denison Jenkins, Sally Fuess, Scott Perryman, Joseph Lin, Christian Trautwein, Judith Shizuru, Helen Blau, Karl G. Sylvester, Mark A. Kay – 26 January 2008 – The lack of adequate donor organs is a major limitation to the successful widespread use of liver transplantation for numerous human hepatic diseases. A desirable alternative therapeutic option is hepatocyte transplantation (HT), but this approach is similarly restricted by a shortage of donor cells and by immunological barriers.

Susceptibility of chimeric mice with livers repopulated by serially subcultured human hepatocytes to hepatitis B virus

Rie Utoh, Chise Tateno, Chihiro Yamasaki, Nobuhiko Hiraga, Miho Kataoka, Takashi Shimada, Kazuaki Chayama, Katsutoshi Yoshizato – 26 January 2008 – We previously identified a small population of replicative hepatocytes in long‐term cultures of human adult parenchymal hepatocytes (PHs) at a frequency of 0.01%‐0.09%. These hepatocytes were able to grow continuously through serial subcultures as colony‐forming parenchymal hepatocytes (CFPHs).

Blocking α2 integrins on rat CC531s colon carcinoma cells prevents operation‐induced augmentation of liver metastases outgrowth

Gerben J. van der Bij, Steven J. Oosterling, Marijn Bögels, Farien Bhoelan, Donna M. Fluitsma, Robert H. J. Beelen, Sybren Meijer, Marjolein van Egmond – 26 January 2008 – Currently, an operation is the only curative option for patients with colorectal cancer. Unfortunately, many patients will develop liver metastases even after successful resection of the primary tumor. Removal of primary colorectal carcinoma may paradoxically increase the risk of metastases development, because accumulating evidence suggests that surgical trauma can stimulate tumor growth.

Diacylglycerol acyltranferase 1 anti‐sense oligonucleotides reduce hepatic fibrosis in mice with nonalcoholic steatohepatitis

Kanji Yamaguchi, Liu Yang, Shannon McCall, Jiawen Huang, Xing Xian Yu, Sanjay K. Pandey, Sanjay Bhanot, Brett P. Monia, Yin‐Xiong Li, Anna Mae Diehl – 26 January 2008 – Retinyl ester (RE) stores decrease during hepatic stellate cell (HSC) activation and liver fibrosis. Although retinol esterification is mostly catalyzed by lecithin:retinol acyltransferase (LRAT), diacylglycerol acyltransferase (DGAT)1 also does this.

Expansion and de novo generation of potentially therapeutic regulatory T cells in patients with autoimmune hepatitis

Maria Serena Longhi, Francesca Meda, Pengyun Wang, Marianne Samyn, Giorgina Mieli‐Vergani, Diego Vergani, Yun Ma – 26 January 2008 – CD4+CD25+ regulatory T cells (T‐regs) are central to the maintenance of immune tolerance and represent an immune intervention candidate in autoimmune hepatitis (AIH), a condition characterized by impaired T‐reg number and function. We investigated whether T‐regs can be expanded from the existing CD4+CD25+ T cell pool and generated de novo from CD4+CD25− T cells in AIH patients and healthy controls.

Liver: An organ with predominant innate immunity

Bin Gao, Won‐Il Jeong, Zhigang Tian – 26 January 2008 – Blood circulating from the intestines to the liver is rich in bacterial products, environmental toxins, and food antigens. To effectively and quickly defend against potentially toxic agents without launching harmful immune responses, the liver relies on its strong innate immune system. This comprises enrichment of innate immune cells (such as macrophages, natural killer, natural killer T, and γδ T cells) and removal of waste molecules and immunologic elimination of microorganisms by liver endothelial cells and Kupffer cells.

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