Hepatic Cell News Volume 4.12 | Apr 3 2020

TOP STORY

Low-Dose Silver Nanoparticle Surface Chemistry and Temporal Effects on Gene Expression in Human Liver Cells

Researchers evaluated cellular responses to low-dose silver nanoparticles (AgNPs) exposure across time. Human liver cells were exposed to AgNPs with three different surface charges and complete gene expression was monitored across a 24 hour period. [Small] Abstract

(Ranked by impact factor of the journal)

Atorvastatin-Induced Senescence of Hepatocellular Carcinoma Is Mediated by Downregulation of hTERT through the Suppression of the IL-6/STAT3 Pathway

The authors examined the effects of atorvastatin-induced senescence in both hepatocellular carcinoma (HCC) cells and mouse xenograft models. The phenomenon and mechanism of senescence was examined by cell cycle analysis, senescence-associated β-galactosidase staining and western blotting in HCC cells, and HCC tissues from mice were analyzed by immunohistochemical staining. [Cell Death Discov] Full Article

Alamandine Attenuates Hepatic Fibrosis by Regulating Autophagy Induced by NOX4-Dependent ROS

Investigators explored the effect of alamandine on hepatic fibrosis via regulation of autophagy by redox balance modulation. In vivo, alamandine reduced ccl4-induced hepatic fibrosis, H₂O₂ content, protein levels of NOX4 and autophagy impairment. In vitro, angiotensin II (Ang II) treatment elevated NOX4 protein expression and ROS production along with upregulation of the ACE/Ang II/AT1R axis. [Clin Sci (Lond)] Abstract | Full Article

Inhibitors of Na⁺/K⁺ ATPase Exhibit Antitumor Effects on Multicellular Tumor Spheroids of Hepatocellular Carcinoma

Researchers showed that the multicellular tumor spheroid (MCTS) model provided a new paradigm for high-throughput drug screening and will significantly improve the efficiency of identifying new drugs for hepatocellular carcinoma (HCC) treatment. Through utilization of MCTS models, they found that inhibitors of Na⁺/K⁺-ATPase may be feasible as a novel target to sensitize HCC cells. [Sci Rep] Abstract

The In Vitro Effects of Phospholipase D1-mTOR Axis in Liver Fibrogenesis

Investigators documented significant increase of phospholipase D (PLD)1, not PLD2 in CCl4-induced cirrhotic compared to normal liver tissues. Suppression of PLD1 activities by PLD inhibitors or down-regulation of PLD1 expression in HSC-T6 could significantly restrain TGFβ1-induced fibrogenesis, as reflected by decreased cell proliferation and reduced expression of pro-fibrogenic markers. [Life Sci] Abstract | Graphical Abstract

Igf2bp1 Is Required for Hepatic Outgrowth During Early Liver Development in Zebrafish

Through whole-mount in situ hybridization, researchers showed that igf2bp1 was constantly and stably expressed at early stages of embryo development in zebrafish. Both the morpholino-induced knockdown and CRISPR/Cas9-mediated knockout of igf2bp1 led to a reduced-size liver phenotype. Further analysis revealed that igf2bp1 was required for hepatic outgrowth, but not for hepatoblast specification and budding. [Gene] Abstract

Triflumuron Induces Cytotoxic Effects on Hepatic and Renal Human Cell Lines

The authors showed, according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, that triflumuron reduced significantly the cell viability and increased the reactive oxygen species generation, malondialdehyde levels, and mitochondrial membrane potential in both human renal embryonic cells and hepatocytes. [J Biochem Mol Toxicol] Abstract

Programmable Synthetic Protein Circuits for the Identification and Suppression of Hepatocellular Carcinoma

To demonstrate the utility of synthetic-promoter-free gene circuits possessing two control layers, the circuit was engineered to sense AFP expression and the PPI between YAP and 14-3-3σ, the matching profile of HCC. Gene circuit loaded cells distinguished HCC from other cells and released therapeutic antibodies, exhibiting in vitro and in vivo therapeutic effects. [Mol Ther Oncolytics] Abstract | Graphical Abstract

MACROD2 Deficiency Promotes Hepatocellular Carcinoma Growth and Metastasis by Activating GSK-3β/β-Catenin Signaling

Through whole-genome sequencing, scientists identified MACROD2 as the gene most frequently affected by structural variations, which were associated with low MACROD2 expression levels. Low MACROD2 expression was predictive of tumor recurrence and poor overall survival. [npj Genomic Med] Abstract

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The Epigenetic Drug Discovery Landscape for Metabolic-Associated Fatty Liver Disease

The authors review recent advances in the understanding of epigenetic regulation and programming during metabolic-associated fatty liver disease (MAFLD), including DNA methylation, histone modifications, chromatin remodelling, transcriptional control, and noncoding RNAs. They also discuss the potential translational implications and challenges of epigenetics in the context of MAFLD. [Trends Genet] Abstract

Cancer Stemness in Hepatocellular Carcinoma: Mechanisms and Translational Potential

Investigators review the potential interaction between cancer stem cells and their microenvironment, providing insight into the regulation of the tumour-initiating ability as well as the cellular plasticity of liver cancer stem cells. Potential specific therapeutic targeting of liver cancer stemness is also discussed. [Br J Cancer] Abstract

Regulation and Function Of Capicua In Mammals

The scientist provides a broad overview of the current understanding of the regulation and functions of capicua in mammals and discusses future research directions. [Exp Mol Med] Abstract

Visit our reviews page to see a complete list of reviews in the hepatic cell research field.

OliX Pharmaceuticals and AM Chemicals Announce Exclusive Licensing and Supply Agreement for GalNAc-Conjugation Technology for Liver Targeting

OliX Pharmaceuticals, Inc. have announced that the company has signed an exclusive worldwide licensing agreement with AM Chemicals for the rights to patents and know-how encompassing the technology to conjugate N-acetylgalactosamine to OliX’ asymmetric small interfering RNA molecules for liver targeting. [OliX Pharmaceuticals, Inc.] Press Release

All AKR-001 Dose Groups Met Week 12 Efficacy Endpoints in NASH Phase IIa BALANCED Study

Akero Therapeutics, Inc. announced that all three AKR-001 dose groups in the BALANCED study met the primary endpoint of absolute change from baseline in liver fat as measured by magnetic resonance imaging – proton density fat fraction – at week 12. [Akero Therapeutics, Inc.] Press Release

Female Scientists Allege Discrimination, Neglect of Research on Women at NIH’s Child Health Institute

In November 2014, nine senior female scientists at the National Institute of Child Health and Human Development requested a meeting with their director. Their concern: that the careers of women at the institute’s Division of Intramural Research were being stymied by its powerful scientific director, Constantine Stratakis. [ScienceInsider] Editorial

Americans Are Underestimating How Long Coronavirus Disruptions Will Last, Health Experts Say

Public health experts are increasingly worried that Americans are underestimating how long the coronavirus pandemic will disrupt everyday life in the country, warning that the Trump administration’s timelines are offering many a false sense of comfort. [STAT News] Editorial

Coronavirus Will Transform UK Work and Travel, Says AA

The aftermath of the Covid-19 crisis will transform the way we live, work and travel in the UK, the AA says. It predicts a permanent reduction in the demand for travel because people have learned during the crisis to use home-working technology. The implications are profound for commuters and for government finances. [BBC News] Editorial

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NEW Postdoctoral Position – Gut-Liver Axis (University of California, Davis)

Staff Scientist – Therapeutics for Gastrointestinal Cancers (City of Hope)

Postdoctoral Position – Metabolic Diseases (University of Southern Denmark)

Postdoctoral Position – Liver Pathogenesis (Washington University in St.Louis)

Therapuetic Specialist – Inflammation (Gilead Sciences Inc.)

Postdoctoral Fellow – The Microbiome in Liver Disease (University of Oslo)

Postdoctoral Researcher – Liver Pathogenesis (Washington University in St. Louis)

Senior Postdoctoral Research Assistant – Liver Research (University of Dundee)

Postdoctoral Fellow – Fatty Liver Dieases (University of Kansas Medical Center)

Team Leader – Cholangiocytes (Miromatrix Medical)

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