Hepatic Cell News Volume 3.32 | Aug 30 2019

TOP STORY

LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis

Investigators showed that leukocyte cell-derived chemotaxin 2 (LECT2) was a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupted Tie1/Tie2 heterodimerization, facilitated Tie2/Tie2 homodimerization, activated PPAR signaling, and inhibited the migration and tube formations of EC. [Cell] Abstract | Graphical Abstract

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New High-Throughput Screen Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation

Researchers developed a stringent high-throughput screening platform comprising unmodified SNU-387 and SNU-398 liver cancer cell lines and SNU-387 cell lines engineered to express low and high levels of SALL4. They screened 1597 pharmacologically active small molecules and 21,575 natural product extracts from plant, bacteria, and fungal sources for those that selectively reduced the viability of cells with high levels of SALL4. [Gastroenterology] Abstract

Specific Diacylglycerols Generated by Hepatic Lipogenesis Stimulate the Oncogenic Androgen Receptor Activity in Male Hepatocytes

The effect of hepatic lipogenesis on androgen receptor (AR) was examined by the expression of hydrodynamically injected AR reporter and the endogenous AR target gene; the mechanism was delineated in hepatoma cell lines and validated in male mice. [Int J Obes] Abstract

Targeting PI3K/Akt/mTOR Pathway Identifies Differential Expression and Functional Role of IL-8 in Liver Cancer Stem Cell Enrichment

Sorafenib and DNA intercalators led to the enrichment of liver cancer stem cells (LCSCs) while Rapamycin and DAPT significantly reduced CD133/EpCAM positivity. Sequential treatment with Rapamycin followed by Sorafenib decreased the ratio of LCSCs as well as their sphere formation capacity, as opposed to Sorafenib alone. [Mol Cancer Ther] Abstract

Antifibrotic Effects of Hypocalcemic Vitamin D Analogs in Murine and Human Hepatic Stellate Cells and in the CCl₄ Mouse Model

The authors investigated the antifibrotic potential of clinically available vitamin D analogs compared to that of calcitriol in vitro and in vivo. Murine hepatic stellate cells, Kupffer cells, and human LX-2 cells were treated with vitamin D analogs, and the profibrotic behavior of these cells was studied. [Lab Invest] Abstract

Tomatidine, a Steroidal Alkaloid from Green Tomatoes, Reduces Palmitate-Induced Lipid Accumulation by Activating AMPK via Vitamin D Receptor-Mediated Signaling in Human HepG2 Hepatocytes

Investigators found that tomatidine significantly inhibited palmitate-provoked lipid accumulation and stimulates phosphorylation of AMPK and acetyl-CoA carboxylase 1 in human HepG2 hepatocytes. Results also indicated that tomatidine could enhance triglyceride turnover and decline in lipogenesis by up-regulating adipose triglyceride lipase and down-regulating fatty acid synthase via the AMPK signaling-dependent regulation of transcription factors, element-binding protein-lc and forkhead box protein O1. [Mol Nutr Food Res] Abstract

Quantitative Proteomic and Phosphoproteomic Studies Reveal Novel 5-Fluorouracil Resistant Targets in Hepatocellular Carcinoma

Data indicated that the GnRH signaling pathway was involved in acquiring drug resistance, which has not been well elucidated. The western blotting results confirmed that the expression levels of PLCβ3 and PLCβ3 pS1105 in Bel/5-Fu cells were increased as compared to Bel cells. [J Proteomics] Abstract | Graphical Abstract

A Novel Role of Glutathione S-Transferase A3 in Inhibiting Hepatic Stellate Cell Activation and Rat Hepatic Fibrosis

The accumulation of reactive oxygen species was measured by dichlorodihydrofluorescein fluorescence analysis. The expression of α-smooth muscle actin, fibronectin, and phosphorylation of extracellular signal-regulated kinase1/2, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase and glycogen synthase kinase 3 beta were detected by western blotting. [J Transl Med] Full Article

Augmentation of Glucotoxicity, Oxidative Stress, Apoptosis and Mitochondrial Dysfunction in HepG2 Cells by Palmitic Acid

Scientists used human hepatoma HepG2 cells to investigate the effects of high glucose and high palmitic acid on metabolic-, inflammatory-, and redox-stress-associated alterations in these cells. They showed increased lipid, protein, and DNA damage, leading to caspase-dependent apoptosis and mitochondrial dysfunction. [Nutrients] Abstract

F127 Poloxamer Effect on Cytotoxicity Induction of Tumor Cell Cultures Treated with Doxorubicin

PLC/PRF/5 and SKHep1 cells were exposed to Pluronic^® F127 at several concentrations. The effect of F127 on breast cancer resistant protein expression, mitochondrial transmembrane potential and cell hypodiploidy was assessed. Finally, the effect of this copolymer on cytotoxicity of doxorubicin in both hepatoma cell lines was investigated, as expressed by its reverse resistance index. [J Pharm Pharmacol] Abstract

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Biology and Significance of Alpha-Fetoprotein in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a complex disease with multiple pathogenic mechanisms caused by a variety of risk factors, making it difficult to characterize with a single biomarker. In fact, numerous biomarkers have been studied in HCC, but alpha-fetoprotein remains the most widely used and accepted serum marker since its discovery over 60 years ago. [Liver Int] Abstract

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Saint Joseph Mercy Gets $19.3 Million Grant for Cancer Treatment

Saint Joseph Mercy Health System has received a $19.3-million grant to improve care and participate in advanced cancer treatment trials. The Michigan Cancer Research Consortium, led by St. Joseph Mercy, was one of 34 grant recipients in the National Cancer Institute’s Community Oncology Research Program, a national network focused on community-based cancer care, according to a release from the health system. [Saint Joseph Mercy Health System] Press Release

ICRF Announces $4.3M. in Cancer Research Grants

The US-based Israel Cancer Research Fund (ICRF announced on the 28^th of August 69 grants worth $4.3m. to researchers at ten different institutions including include Ariel University, Bar-Ilan University, Ben-Gurion University of the Negev, Carmel Medical Center, Chaim Sheba Medical Center, Hebrew University of Jerusalem, Rambam Health Care Campus, Technion, Tel Aviv University and the Weizmann Institute of Science. [ICFR (The Jerusalem Post)] Press Release

Foreign Interference under the Spotlight at Australian Universities

The Australian government says it will establish an expert committee to detect and respond to cyberattacks, intellectual-property theft and other strikes against universities by foreign governments or groups. The move comes amid growing concerns from some politicians and academics about foreign influence at Australian campuses. [Nature News] Editorial

University of Illinois Protected Harassers: Investigation

Multiple professors at the University of Illinois Urbana-Champaign (UIUC) who were credibly accused of sexual harassment have been put on paid administrative leave, allowed to leave the institution quietly, or both, ProPublica Illinois and NPR Illinois jointly reported August 27. Among them was Valarmathi Thiruvanamalai, a comparative biosciences faculty member who went on to a position at the University of Alabama at Birmingham after his resignation from UIUC. [The Scientist] Editorial

Younger Scientists Need Better Support

Letters from research funders to university leaders rarely raise eyebrows. But a letter sent this month by the heads of the United Kingdom’s three largest medical-research funders did just that. [Nature News] Editorial

FDA Warns Testing Companies: Don’t Tell Patients How Their DNA Influences Response to Specific Drugs

Amid a boom in genetic testing that aims to predict a person’s response to medication, the FDA has been quietly pressuring a handful of companies to stop reporting results to patients about how their genes may interact with specific drugs. [STAT News] Editorial

NEW NF-kB, JAK-STAT & MAPK in Health, Disease & Therapy
October 7-11, 2019
Suzhou, China

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NEW Postdoctoral Researcher – Liver Disease (Albert Einstein College of Medicine)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Research Technologist – Intestinal Stem Cell Biology (STEMCELL Technologies Inc.)

Senior Researcher – Inflammatory Diseases (Genentech, Inc.)

Research Assistant – Pathophysiology of Enteroviruses (University of Cambridge)

Postdoctoral Researcher – Microbiome in IBD (GIGA-Medical Genomics Unit)

Postdoctoral Fellow – Quantifying Intra-tumour Heteregeneity with Multi-Omics Data (The Institute of Cancer Research)

Postdoctoral Fellow – Designer Probiotics (Massacheusetts General Hospital)

Postdoctoral Fellow – Multi-Omics in Intra-Tumor Heteregenity (The Institute of Cancer Research)

Postdoctoral Researchers – Microbiota in Neonatal Immunity and Imprinting (Institut Pasteur)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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