Roles of dendritic cells in murine hepatic warm and liver transplantation‐induced cold ischemia/reperfusion injury

Matthew Zhang, Shinya Ueki, Shoko Kimura, Osamu Yoshida, Antonino Castellaneta, Kikumi S. Ozaki, Anthony J. Demetris, Mark Ross, Yoram Vodovotz, Angus W. Thomson, Donna B. Stolz, David A. Geller, Noriko Murase – 26 November 2012 – Dendritic cells (DCs) induce and regulate both innate and adaptive immune responses; however, their in vivo functional importance in hepatic ischemia/reperfusion (IR) injury is perplexing. We hypothesized that liver‐resident DC and locally recruited blood‐borne DC might have distinctive roles in hepatic IR injury.

Defective bile salt biosynthesis and hydroxylation in mice with reduced cytochrome P450 activity

Cindy Kunne, Alexandra Acco, Simon Hohenester, Suzanne Duijst, Dirk R. de Waart, Alaleh Zamanbin, Ronald P.J. Oude Elferink – 26 November 2012 – The difference in bile salt (BS) composition between rodents and humans is mainly caused by formation of muricholate in rodents as well as by efficient rehydroxylation of deoxycholic acid. The aim of this study was to characterize bile formation in a mouse model (Hrn mice) with hepatic disruption of the cytochrome p450 (CYP) oxidoreductase gene, encoding the single electron donor for all CYPs.

Antimitochondrial antibody heterogeneity and the xenobiotic etiology of primary biliary cirrhosis

Richy C.Y. Chen, Phornnop Naiyanetr, Shang‐An Shu, Jinjun Wang, Guo‐Xiang Yang, Thomas P. Kenny, Kathryn C. Guggenheim, Jeffrey D. Butler, Christopher Bowlus, Mi‐Hua Tao, Mark J. Kurth, Aftab A. Ansari, Marshall Kaplan, Ross L. Coppel, Ana Lleo, M. Eric Gershwin, Patrick S.C. Leung – 26 November 2012 – Antimitochondrial antibodies (AMAs) directed against the lipoyl domain of the E2 subunit of pyruvate dehydrogenase (PDC‐E2) are detected in 95% of patients with primary biliary cirrhosis (PBC) and are present before the onset of clinical disease.

Effects of simvastatin administration on rodents with lipopolysaccharide‐induced liver microvascular dysfunction

Vincenzo La Mura, Marcos Pasarín, Cintia Z. Meireles, Rosa Miquel, Aina Rodríguez‐Vilarrupla, Diana Hide, Jorge Gracia‐Sancho, Juan Carlos García‐Pagán, Jaime Bosch, Juan G. Abraldes – 26 November 2012 – Endothelial dysfunction drives vascular derangement and organ failure associated with sepsis. However, the consequences of sepsis on liver sinusoidal endothelial function are largely unknown. Statins might improve microvascular dysfunction in sepsis. The present study explores liver vascular abnormalities and the effects of statins in a rat model of endotoxemia.

Sal‐like protein 4 (SALL4), a stem cell biomarker in liver cancers

Tsunekazu Oikawa, Akihide Kamiya, Mikio Zeniya, Hiromi Chikada, Ahn Dong Hyuck, Yuji Yamazaki, Eliane Wauthier, Hisao Tajiri, Lance D. Miller, Xin Wei Wang, Lola M. Reid, Hiromitsu Nakauchi – 23 November 2012 – Liver cancers, including hepatocellular carcinomas (HCCs), cholangiocarcinomas (CCs), and fibrolamellar HCCs (FL‐HCCs) are among the most common cancers worldwide and are associated with a poor prognosis. Investigations of genes important in liver cancers have focused on Sal‐like protein 4 (SALL4), a member of a family of zinc finger transcription factors.

High susceptibility to liver injury in IL‐27 p28 conditional knockout mice involves intrinsic interferon‐γ dysregulation of CD4+ T cells

Song Zhang, Ruifang Liang, Wei Luo, Chang Liu, Xiaoli Wu, Yanan Gao, Jianlei Hao, Guangchao Cao, Xi Chen, Jun Wei, Siyuan Xia, Zheng Li, Ti Wen, Yunyun Wu, Xinglong Zhou, Puyue Wang, Liqing Zhao, Zhengzhou Wu, Sidong Xiong, Xiaoming Gao, Xiang Gao, Yongyan Chen, Qing Ge, Zhigang Tian, Zhinan Yin – 23 November 2012 – Interleukin (IL)‐27, a newly discovered IL‐12 family cytokine, is composed of p28 and EBI3. In this study, CD11c‐p28f/f conditional knockout mice were generated to delete p28 specifically in dendritic cells (DCs).

Macrophage migration inhibitory factor contributes to ethanol‐induced liver injury by mediating cell injury, steatohepatitis, and steatosis

Mark A. Barnes, Megan R. McMullen, Sanjoy Roychowdhury, Sorana G. Pisano, Xiuli Liu, Abram B. Stavitsky, Richard Bucala, Laura E. Nagy – 23 November 2012 – Macrophage migration inhibitory factor (MIF), a multipotent protein that exhibits both cytokine and chemotactic properties, is expressed by many cell types, including hepatocytes and nonparenchymal cells. We hypothesized that MIF is a key contributor to liver injury after ethanol exposure.

Role of patatin‐like phospholipase domain‐containing 3 on lipid‐induced hepatic steatosis and insulin resistance in rats

Naoki Kumashiro, Toru Yoshimura, Jennifer L. Cantley, Sachin K. Majumdar, Fitsum Guebre‐Egziabher, Romy Kursawe, Daniel F. Vatner, Ioana Fat, Mario Kahn, Derek M. Erion, Xian‐Man Zhang, Dongyan Zhang, Vara Prasad Manchem, Sanjay Bhanot, Glenn S. Gerhard, Kitt F. Petersen, Gary W. Cline, Varman T. Samuel, Gerald I. Shulman – 23 November 2012 – Genome‐wide array studies have associated the patatin‐like phospholipase domain‐containing 3 (PNPLA3) gene polymorphisms with hepatic steatosis.

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