Hepatic Cell News Volume 3.30 | Aug 16 2019

TOP STORY

Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis

Investigators performed single-cell RNA sequencing on non-parenchymal cells isolated from healthy and NASH mouse livers. Secretome gene analysis revealed a highly connected network of intrahepatic signaling and disruption of vascular signaling in NASH. [Mol Cell] Full Article | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Praziquantel Ameliorates CCl₄-Induced Liver Fibrosis in Mice by Inhibiting TGF-β/Smad Signaling via Upregulating Smad7 in Hepatic Stellate Cells

Researchers established a mouse model of carbon tetrachloride (CCl₄)-induced liver fibrosis for in vivo studies and used TGF-β1-stimulated human hepatic stellate cell line in addition to other fibroblast-like cell line and fibroblast cell line in vitro. [Br J Pharmacol] Abstract

SOCS5 Inhibition Induces Autophagy to Impair Metastasis in Hepatocellular Carcinoma Cells via the PI3K/Akt/mTOR Pathway

The authors examined the expression levels of suppressor of cytokine signaling (SOCS5) in hepatocellular carcinoma (HCC) using publicly available datasets, and in a patient cohort, using quantitative real-time PCR, western blotting, and immunohistochemistry. The association of SOCS5 expression with clinical pathological data of HCC patients was examined and that with the mTOR pathway was predicted. [Cell Death Dis] Full Article

Role of TGFβ3-Smads-Sp1 Axis in DcR3-Mediated Immune Escape of Hepatocellular Carcinoma

Scientists found that overexpression of decoy receptor 3 (DcR3) in hepatocellular carcinoma (HCC) was mediated by the TGFβ3-Smad-Sp1 signaling pathway, which directly targeted DcR3 promoter regions. Moreover, overexpression of DcR3 in HCC tissues was associated with tumor invasion and metastasis and significantly promoted the differentiation and secretion of Th2 and Treg cells while inhibiting the differentiation and secretion of Th1 cells. [Oncogenesis] Full Article

The TM6SF2 E167K Genetic Variant Induces Lipid Biosynthesis and Reduces Apolipoprotein B Secretion in Human Hepatic 3D Spheroids

Researchers used a human in vitro disease model to understand mechanisms linked to genetic risk variants associated with nonalcoholic fatty liver disease. The model was based on 3D spheroids from primary human hepatocytes from five different donors. [Sci Rep] Full Article

Vitamin D Reverts Resistance to the mTOR Inhibitor Everolimus in Hepatocellular Carcinoma through the Activation of a miR-375/Oncogenes Circuit

The current study evaluated the effect of 1,25(OH)₂Vitamin D (VitD) treatment on everolimus (EVE) sensitivity in established models of hepatocellular carcinoma cell lines resistant to EVE (EveR). DNA content and colony formation assays, which measured the proliferative index, revealed that VitD pre-treatment re-sensitized EveR cells to EVE treatment. [Sci Rep] Full Article

Inducing Differentiation of Human Urine-Derived Stem Cells into Hepatocyte-Like Cells by Co-Culturing with Human Hepatocyte L02 Cells

Human urine-derived stem cells were induced to differentiate into hepatocyte-like cells by co-culturing with human hepatocyte L02 cells, which were confirmed by cellular morphology, messenger RNA expression of albumin, α-fetoprotein and hepatocyte cytochrome P450 analyzed with quantitative reverse transcription polymerase chain reaction and the expression of glycogen detected by glycogen staining kits at 5, 10, and 15 days after co-culturing. [J Cell Biochem] Abstract

Labile Heme Impairs Hepatic Microcirculation and Promotes Hepatic Injury

Investigators provided experimental evidence that heme increased portal pressure via a mechanism that involves hepatic stellate cell-mediated sinusoidal constriction, a hallmark of microcirculatory failure under stress conditions. Moreover, heme exerted direct cytotoxicity in vitro and aggravated tissue damage in a model of polymicrobial sepsis. [Arch Biochem Biophys] Full Article

Netrin-1 Promotes the Collective Cell Migration of Liver Cancer Cells in a 3D Cell Culture Model

An immunohistochemical study showed that certain cells invaded surrounding tissue by collective migration and that Netrin-1 expression in these cells was increased, especially at the invasive front. In the 3D culture model, collective cell migration was clearly observed, as leader cells were followed by cells migrating along a canal. [J Physiol Biochem] Abstract

Expressions of Carbohydrate Response Element Binding Protein and Glucose Transporters in Liver Cancer and Clinical Significance

Researchers investigated the expression patterns of carbohydrate response element binding protein (ChREBP) and glucose transporters (GLUTs) in human hepatocellular carcinoma (HCC) and their association with HCC progression. ChREBP, GLUT2 and GLUT1 immunohistochemistry were performed on liver tissue array containing normal liver tissue, HCC adjacent tissue and cancer tissue of different HCC stages. [Pathol Oncol Res] Full Article

Validation of [¹²⁵I]CPCR_4.3 as an Investigative Tool for the Sensitive and Specific Detection of hCXCR₄ and MmXCR₄ Expression In Vitro and In Vivo

Compared to the reference [⁶⁸Ga] Pentixafor, [¹²⁵I]CPCR_4.3 showed 2.4- to 11-fold increased specific binding to human cancer cell lines with different human CXCR4 expression levels as well as strong and highly specific binding to mCXCR4 expressing cells, which was not detectable for [⁶⁸Ga]Pentixafor. [EJNMMI Res] Full Article

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Current Status in Testing for Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)

Typically, hepatic alterations start with simple steatosis, which easily progresses to more advanced stages such as nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. This course of disease finally leads to end-stage liver disease such as hepatocellular carcinoma, which is associated with increased morbidity and mortality. [Cells] Full Article | Graphical Abstract

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Terns Pharmaceuticals Announces Positive Interim Results from Ongoing Phase I Clinical Trial of TERN-201, a SSAO Inhibitor in Development for NASH

Terns Pharmaceuticals, Inc. announced the interim results of an ongoing Phase I clinical trial of TERN-201, a semicarbazide-sensitive amine oxidase (SSAO) inhibitor, being developed for the treatment of NASH. Interim data from the first-in-human clinical study of TERN-201 demonstrate that single, oral administrations of TERN-201 were well tolerated with no significant safety findings or adverse events observed that led to discontinuation. [Terns Pharmaceuticals, Inc.] Press Release

Prevent Cancer Foundation^® Awards $250,000 in Community Grants

Through its community grants program, the Prevent Cancer Foundation^® is supporting ten projects focused on increasing cancer prevention and early detection in communities across the US, from Honolulu, Hawaii to Baltimore, Maryland. The projects were selected through a highly competitive grants process, and each program will receive a one-year, $25,000 grant. [Prevent Cancer Foundation^®] Press Release

For a Decade, Francis Collins Has Shielded NIH—While Making Waves of His Own

Collins has helped shield the National Institutes of Health (NIH) from threatened budget cuts as well as the upheaval that has shaken many other federal agencies under the Trump administration. [Nature News] Editorial

In Departure for NIH, Cancer Moonshot Requires Grantees to Make Papers Immediately Free

In the United States, federal agencies have stuck to a decade-old policy that allows grantees to publish in journals that keep papers behind a paywall for up to one year. Now, the divide is starting to blur, with one prominent US research program starting to require immediate open access to the peer-reviewed publications it funds. [ScienceMagazine] Editorial

NEW Cancer Evolution and Combinatorial Cancer Therapies: Concepts and Challenges
January 19-23, 2020
Keystone, Colorado, United States

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NEW Postdoctroal Researcher – Human Liver Function and Disease (Karolinska Institutet)

NEW Postdoctoral Fellow – Metabolism and Physiology of Liver Diseases (University of Connecticut)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Multi-Omics Data in the Gut-Liver Axis (Mayo Clinic Health System)

Postdoctoral Researcher – Liver Pathogenesis (Washington University)

Associate Scientist – In Vitro ADME Research (Gilead Sciences)

Postdoctoral Fellow – Hepatitis C Virus (The Research Institute at Nationwide Children’s Hospital)

Project Leader – Chronic Liver Disease Drug Discovery (Inserm Institute for Viral and Liver Disease)

Postdoctoral Position – Human Liver Microphysiology Systems (University of Pittsburgh Drug Discover Institute)

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

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