Hepatic Cell News Volume 3.38 | Oct 11 2019

TOP STORY

Loss of Xanthine Oxidoreductase Potentiates Propagation of Hepatocellular Carcinoma Stem Cells

Researchers identified that xanthine oxidoreductase (XOR), which was expressed at low levels in human hepatic carcinoma (HCC) samples and liver cancer stem cells (CSCs), restrained HCC formation and chemoresistance by attenuating liver CSCs propagation. Mechanistically, XOR physically interacted with USP15, thereby promoting deubiquitination of Kelch Like ECH Associated Protein 1 to stabilize its expression, which led to degradation of Nrf2 via ubiquitination and subsequently reactive oxygen species accumulation in liver CSCs. [Hepatology] Abstract

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Bmi1 Drives Hepatocarcinogenesis by Repressing the TGFβ2/SMAD Signaling Axis

In Bmi1-knockout mouse livers and hepatocellular carcinoma (HCC) cell lines, TGFβ2/SMAD cascade proteins were upregulated. TGFβ2 expression was inversely correlated with Bmi1 expression in human and mouse HCC tissues. [Oncogene] Abstract

The Contrary Intracellular and Extracellular Functions of PEDF in HCC Development

Investigators demonstrated that the intracellular pigment epithelium-derived factor (PEDF) led to the accumulation of free fatty acids (FFAs) and eventually promoted hepatocellular carcinoma (HCC) cell growth by inhibiting the activation of AMPK via ubiquitin-proteasome-mediated degradation, which causes increased de novo fatty acid synthesis and decreased FFA oxidation. [Cell Death Dis] Full Article

Progranulin Attenuates Liver Fibrosis by Downregulating the Inflammatory Response

The authors examined the effect of progranulin (PGRN) in two different models of chronic liver disease, methionine-choline-deficient diet-induced non-alcoholic steatohepatitis and carbon tetrachloride-induced liver fibrosis. To induce long-term expression of PGRN, PGRN-expressing adenovirus was delivered via injection into the tibialis anterior. [Cell Death Dis] Full Article

Au(III)-Proline Derivatives Exhibiting Selective Antiproliferative Activity against HepG2/SB3 Apoptosis-Resistant Cancer Cells

Researchers focused on the demonstration of a peculiar behavior of Au(III)-dithiocarbamato species in solution. The complexes were screened for their anti-proliferative activity against two human cancer cell lines, namely HepG2 and HepG2/SB3, taken as models of hepatocellular carcinoma. [Dalton Trans] Abstract | Graphical Abstract

c-Myc Transactivates GP73 and Promotes Metastasis of Hepatocellular Carcinoma Cells through GP73-Mediated MMP-7 Trafficking in a Mildly Hypoxic Microenvironment

It was discovered that c-Myc transactivated GP73 in a mildly hypoxic microenvironment and that the activation of c-Myc upregulated the expression of matrix metalloproteinase-7 (MMP-7). Moreover, it was shown that GP73 interacted with intracellular MMP-7 in the region of the cytoplasmic domain and facilitated the trafficking and secretion of MMP-7, resulting in cell metastasis. [Oncogenesis] Full Article

A Novel Form of Deleted in Breast Cancer 1 (DBC1) Lacking the N-Terminal Domain Does Not Bind SIRT1 and Is Dynamically Regulated In Vivo

Scientists showed that in quiescent cells DBC1 was proteolytically cleaved, producing a protein (DN-DBC1) that missed the S1-like domain and no longer bound to SIRT1. DN-DBC1 was also found in vivo in mouse and human tissues. [Sci Rep] Full Article

Hepatospecific Ablation of p38α MAPK Governs Liver Regeneration through Modulation of Inflammatory Response to CCl₄-Induced Acute Injury

Mechanistically, researchers provided strong evidence that Ccl2/Ccl5 chemokines were crucial for a proper hepatoprotective response observed secondary to p38α ablation. Indeed, antibody blockade of Ccl2/Ccl5 was sufficient to abrogate hepatoprotection through a concomitant decrease of both inflammatory cells recruitment and antioxidative response that resulted ultimately in higher liver damages. [Sci Rep] Full Article

Silencing Transcription Factor FOXM1 Represses Proliferation, Migration, and Invasion While Inducing Apoptosis of Liver Cancer Stem Cells by Regulating the Expression of ALDH2

CD133⁺CD24⁺ liver cancer stem cells (LCSCs) were sorted and identified. A series of experiments were carried out to determine the proliferation, colony formation rate, migration, invasion, and apoptosis of LCSCs after interfering with FOXM1. [IUBMB Life] Abstract

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Mesenchymal Stem Cells for the Treatment of Liver Disease: Present and Perspectives

The safety and therapeutic effects of mesenchymal stem cells in patients with chronic liver disease have been observed in many clinical studies. The authors discuss several strategies targeted at improving viable cell engraftment and the potential challenges in the use of extracellular vesicle-based therapies for liver disease in the future. [Gut Liver] Abstract | Download Full Article

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Akcea and Pfizer Inc. Announce Licensing Agreement for Investigative Antisense Therapy AKCEA-ANGPTL3-L(Rx)

Akcea Therapeutics, Inc. and Pfizer Inc. announced that the companies have entered into a worldwide exclusive licensing agreement for AKCEA-ANGPTL3-LRx, an investigational antisense therapy being developed to treat patients with certain cardiovascular and metabolic diseases. [Akcea Therapeutics, Inc.] Press Release

DURECT Announces Completion of Enrollment in Its Phase IIa Clinical Trial of DUR-928 in Psoriasis and 50% Enrollment in Its Phase Ib DUR-928 Clinical Trial in NASH

DURECT Corporation announced that it has completed enrollment in its Phase IIa clinical trial of topical DUR-928 in patients with mild to moderate plaque psoriasis. The company also announced that it has now enrolled 30 of the planned 60 patients in its ongoing Phase Ib trial with oral DUR-928 in patients with non-alcoholic steatohepatitis (NASH). [DURECT Corporation] Press Release

NGM Bio Announces Positive Interim Results from Ongoing 24-Week Phase II Study Evaluating Aldafermin (NGM282) in Patients with NASH

NGM Biopharmaceuticals, Inc. announced positive preliminary results from a pre-specified interim analysis of the aldafermin 1 mg 24-week Cohort 4, which is the final cohort of an adaptive Phase II study evaluating the efficacy, safety and tolerability of aldafermin in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH). [NGM Biopharmaceuticals, Inc.] Press Release

In Bid to Boost Transparency, bioRxiv Begins Posting Peer Reviews Next to Preprints

BioRxiv, the server for life sciences preprints, has begun an experiment that allows select journals and independent peer-review services to publicly post evaluations of its papers should the authors make the request. [ScienceInsider] Editorial

‘There’s No Hope for The Rest of Us.’ Uyghur Scientists Swept Up in China’s Massive Detentions

No one outside the Chinese government knows where Tashpolat Tiyip is. No one knows exactly what charges have been filed against him. The only thing that anyone really knows is that in April 2017, as the geographer and former president of Xinjiang University in Ürümqi prepared to fly from Beijing to Berlin for a scientific conference and the launch of a research center, he disappeared without even a phone call to colleagues or family. [ScienceInsider] Editorial

NEW Liver Cancer Summit 2020
February 6-8, 2020
Prague, Czech Republic

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NEW Postdoctoral Associates – Organogenesis of Liver, Heart and Pancreas (The University of Manchester)

NEW Assistant Professor – Liver Research (The University of Hong Kong)

NEW Research Associate – Pluripotent Stem Cells in Liver Development (The Wellcome Institute)

Postdoctoral Researcher – Gene Regulation in Liver Cancer (Umeå University)

Chief Editor – Nature Ageing (Nature Research)

Research Scientist – Fibrosis (Gilead Sciences, Inc.)

Postdoctoral Researchers – Liver Diseases (Albert Einstein College of Medicine)

Postdoctoral Researcher – Liver Cell-Cell Interactions (Flanders Institute for Biotechnology)

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

Senior Researcher – Inflammatory Diseases (Genentech, Inc.)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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