Hepatic Cell News Volume 2.32 | Aug 24 2018

TOP STORY

Inactivation of Caspase 8 in Liver Parenchymal Cells Confers Protection against Murine Obstructive Cholestasis

Twenty-eight days after surgical ligation of the common bile duct, mice with a specific deletion of caspase 8 in liver parenchymal cells showed decreased necrotic foci, serum transaminase levels and apoptosis along with diminished compensatory proliferation and ductular reaction. These results correlated with a decreased inflammatory profile and ameliorated liver fibrogenesis. [J Hepatol] Abstract | Graphical Abstract

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Dual-Targeted Casein Micelles as Green Nanomedicine for Synergistic Phytotherapy of Hepatocellular Carcinoma

Dual-targeted diosmin/berberine-loaded casein micelles demonstrated superior in vivo anti-tumor efficacy in hepatocellular carcinoma bearing mice as revealed by down regulation of cell necrosis markers, inflammatory marker COX2, inhibition of angiogenesis and induction of apoptosis. [J Control Release] Abstract | Graphical Abstract

JMJD6 Promotes Hepatocellular Carcinoma Carcinogenesis by Targeting CDK4

In hepatoma cell lines, researchers demonstrated that knockdown of Jumonji domain-containing protein 6 (JMJD6) inhibited hepatoma cell migration and proliferation. There was a positive correlation between cell cycle regulatory protein CDK4 and JMJD6 level. Inhibiting CDK4 abolished the ability of JMJD6 in enhancing cell proliferation. [Int J Cancer] Abstract

Ghrelin Reduces TNF-α-Induced Human Hepatocyte Apoptosis, Autophagy and Pyroptosis: Role in Obesity-Associated NAFLD

In HepG2 hepatocytes, acylated and desacyl ghrelin treatment reduced TNF-α-induced apoptosis, evidenced by lower caspase-8 and caspase-3 cleavage, and TUNEL-positive cells, and pyroptosis, revealed by decreased caspase-1 activation and lower HMGB1 expression. Acylated ghrelin suppressed TNF-α-activated hepatocyte autophagy, as evidenced by decreased LC3II/I ratio and increased p62 accumulation via AMPK/mTOR. [J Clin Endocrinol Metab] Abstract

MicroRNA-766 Promotes Cancer Progression by Targeting NR3C2 in Hepatocellular Carcinoma

Investigators showed that miR-766 promoted proliferation and metastasis of hepatocellular carcinoma (HCC) cells in vitro and in vivo and that NR3C2 was a direct target of miR-766 and involved in miR-766-mediated proliferation and metastasis of HCC cells. [FASEB J] Abstract

miR-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2

Scientists aimed to explore the effect of miR-382, a member of Dlk1-Dio3 microRNA cluster, during hepatic differentiation from liver progenitor cells. They found that miR-382 increased gradually and was inversely correlated with the potential target, Ezh2, during WB-F344 hepatic differentiation. Functional studies indicated that miR-382 increased the level of hepatocyte-specific genes. [Cell Physiol Biochem] Full Article

Crucial Roles of 5-HT and 5-HT₂ Receptor in Diabetes-Related Lipid Accumulation and Pro-Inflammatory Cytokine Generation in Hepatocytes

The authors revealed the effects of the hepatocellular serotonin (5-HT) system in diabetes-related disorders. In diabetic mice, co-treatment with antagonists of both 5-HT synthesis and 5-HT₂ receptor significantly abolished hepatic steatosis, inflammation, and fibrosis as well as hyperglycemia and dyslipidemia. [Cell Physiol Biochem] Full Article

Deletion of Caveolin-1 Attenuates LPS/GalN-Induced Acute Liver Injury in Mice

“Lipopolysaccharide (LPS)/D-galactosamine (GalN)-treated caveolin-1^-/- mice showed reduced lethality and markedly attenuated liver damage, neutrophil infiltration and hepatocyte apoptosis as compared to wild-type mice. [J Cell Mol Med] Full Article

Emodin Suppresses Activation of Hepatic Stellate Cells through p38 Mitogen-Activated Protein Kinase and Smad Signaling Pathways In Vitro

Researchers demonstrated that emodin suppressed the gene expression of hepatic stellate cell (HSC) activation markers type I collagen, fibronectin, and α-smooth muscle actin, as well as HSC proliferation. Emodin-mediated inhibition of HSC activation could be partially blocked by PD98059 inhibition of p38^MAPK or short hairpin RNA-imposed knockdown of Smad4. [Phytother Res] Abstract

Recapitulation of Hepatitis B Virus-Host Interactions in Liver Organoids from Human Induced Pluripotent Stem Cells

Based on cell-cell interactions, human induced pluripotent stem cell (hiPSC)-derived endodermal, mesenchymal, and endothelial cells cells could organize themselves and gradually differentiate into a functional organoid, which exhibited stronger hepatic functions than hiPSC derived hepatic like cell. [EBioMedicine] Full Article

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Novel Targeted Treatment Options for Advanced Cholangiocarcinoma

The authors summarize the current understanding and future directions of targeted therapeutic options in the management of advanced cholangiocarcinoma. [Expert Opin Investig Drugs] Abstract

Advances in Engineered Human Liver Platforms for Drug Metabolism Studies

Investigators focus on the design features of human liver model platforms and their representative drug metabolism validation datasets, while discussing emerging trends. [Drug Metab Dispos] Abstract | Full Article

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Singapore’s First Clinical Trial Approval for T Cell Engineered (TCR) Immunotherapy for Treatment of Liver Cancer

Lion TCR Pte. Ltd. received approval from the Health Sciences Authority, Singapore, for its Phase I/II multicentre clinical study of its product candidate (LioCyx^™) for the treatment of relapsed liver cancer post-liver transplantation. [Lion TCR Pte. Ltd.] Press Release

European Commission Grants Marketing Authorization for Lenvima^® (Lenvatinib) As First-Line Treatment in Adults with Advanced or Unresectable Hepatocellular Carcinoma

Eisai Co., Ltd. and Merck & Co., Inc. announced that the European Commission has granted a marketing authorization for the oral receptor tyrosine kinase inhibitor LENVIMA^® as a single agent for the first-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma who have received no prior systemic therapy. [Eisai Co., Ltd.] Press Release

Meet Dr. Caroline Lindemans and explore her work using organoids to study intestinal repair. Read the Full Profile

Senate Approves $2B Boost for NIH in $850B+ Spending Bill

For the fourth year in a row, the Senate has approved a significant increase in funding for the National Institutes of Health (NIH). [Fierce Biotech] Editorial

AAAS Insiders Petition to Revoke Honors of Sexual Harassers

Using the hashtag #TimesUpAAAS, 36 researchers recognized by the American Association for the Advancement of Science (AAAS) for their science communication work posted an open letter asking the society not to bestow honors on those “who have engaged in harassment and discrimination.” [The Scientist] Editorial

Former CDC Director Tom Frieden Arrested on Sexual Misconduct Charges

Dr. Thomas Frieden, the former head of the Centers for Disease Control and Prevention (CDC), was arrested and charged with sexual abuse and harassment, according to the New York Police Department. [STAT News] Editorial

NEW Gordon Research Seminar: Vascular Cell Fate, Metabolism and Targeting
January 20-25, 2019
Ventura, California, United States

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