Link between gut‐microbiome derived metabolite and shared gene‐effects with hepatic steatosis and fibrosis in NAFLD

Cyrielle Caussy, Cynthia Hsu, Min‐Tzu Lo, Amy Liu, Ricki Bettencourt, Veeral H. Ajmera, Shirin Bassirian, Jonathan Hooker, Ethan Sy, Lisa Richards, Nicholas Schork, Bernd Schnabl, David A. Brenner, Claude B. Sirlin, Chi‐Hua Chen, Rohit Loomba, Genetics of NAFLD in Twins Consortium – 23 March 2018 – Previous studies have shown that gut‐microbiome is associated with nonalcoholic fatty liver disease (NAFLD). We aimed to examine if serum metabolites, especially those derived from the gut‐microbiome, have a shared gene‐effect with hepatic steatosis and fibrosis.

Liver‐enriched transcription factor expression relates to chronic hepatic failure in humans

Jorge Guzman‐Lepe, Eduardo Cervantes‐Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M. Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J. Fox, Kazuki Takeishi, Alejandro Soto‐Gutierrez – 23 March 2018 – The mechanisms by which the liver fails in end‐stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects.

Sphingosine kinase 1 promotes liver fibrosis by preventing miR‐19b‐3p‐mediated inhibition of CCR2

Tian Lan, Changzheng Li, Guizhi Yang, Yue Sun, Lihang Zhuang, Yitao Ou, Hui Li, Genshu Wang, Tatiana Kisseleva, David Brenner, Jiao Guo – 23 March 2018 – Chronic liver disease mediated by activation of hepatic stellate cells (HSCs) and Kupffer cells (KCs) leads to liver fibrosis. Here, we aimed to investigate the molecular mechanism and define the cell type involved in mediating the sphingosine kinase (SphK)1‐dependent effect on liver fibrosis. The levels of expression and activity of SphK1 were significantly increased in fibrotic livers compared with the normal livers in human.

PRDM8 exhibits antitumor activities toward hepatocellular carcinoma by targeting NAP1L1

Zhiqiang Chen, Wen Gao, Liyong Pu, Long Zhang, Guoyong Han, Xueliang Zuo, Yao Zhang, Xiangcheng Li, Hongbing Shen, Jindao Wu, Xuehao Wang – 23 March 2018 – Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. PRDI‐BF1 and RIZ homology domain containing 8 (PRDM8) is a key regulator in neural development and testis steroidogenesis; however, its role in liver carcinogenesis remains to be investigated. In this study, PRDM8 was found to be down‐regulated in HCC, which was linked with shorter recurrence‐free survival.

Anti‐tumoral effects of exercise on hepatocellular carcinoma growth

Uttara Saran, Maria Guarino, Sarai Rodríguez, Cedric Simillion, Matteo Montani, Michelangelo Foti, Bostjan Humar, Marie V. St‐Pierre, Jean‐François Dufour – 22 March 2018 – Regular physical exercise has many beneficial effects, including antitumor properties, and is associated with a reduced risk of developing hepatocellular carcinoma (HCC). Less is known about the impact of exercise on HCC growth and progression.

Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset

Stephanie Barbara Schatz, Christoph Jüngst, Verena Keitel‐Anselmo, Ralf Kubitz, Christina Becker, Patrick Gerner, Eva‐Doreen Pfister, Imeke Goldschmidt, Norman Junge, Daniel Wenning, Stephan Gehring, Stefan Arens, Dirk Bretschneider, Dirk Grothues, Guido Engelmann, Frank Lammert, Ulrich Baumann – 22 March 2018 – Genetic variants in the adenosine triphosphate‐binding cassette subfamily B member 4 (ABCB4) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid‐as

Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset

Stephanie Barbara Schatz, Christoph Jüngst, Verena Keitel‐Anselmo, Ralf Kubitz, Christina Becker, Patrick Gerner, Eva‐Doreen Pfister, Imeke Goldschmidt, Norman Junge, Daniel Wenning, Stephan Gehring, Stefan Arens, Dirk Bretschneider, Dirk Grothues, Guido Engelmann, Frank Lammert, Ulrich Baumann – 22 March 2018 – Genetic variants in the adenosine triphosphate‐binding cassette subfamily B member 4 (ABCB4) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid‐as

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