Intestinal Cell News Volume 4.46 | Nov 30 2018

TOP STORY

An Upstream Protein-Coding Region in Enteroviruses Modulates Virus Infection in Gut Epithelial Cells

In differentiated human intestinal organoids, upstream open reading frame (uORF) protein-knockout echoviruses were attenuated compared to the wild-type at late stages of infection where membrane-associated uORF protein facilitates virus release. Researchers have identified a previously unknown enterovirus protein that facilitated virus growth in gut epithelial cells—the site of initial viral invasion into susceptible hosts. [Nat Microbiol] Abstract | Press Release | Editorial

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Oral Co-Administration of a Bacterial Protease Inhibitor in the Vaccine Formulation Increases Antigen Delivery at the Intestinal Epithelial Barrier

Investigators found that outer membrane protein from Brucella spp. inhibited protease activity from murine intestinal brush-border membranes and cysteine proteases from human intestinal epithelial cells (IECs) promoting co-administered antigen accumulation within lysosomal compartments of IECs. [J Control Release] Full Article

Dclk1 in Tuft Cells Promotes Inflammation-Driven Epithelial Restitution and Mitigates Chronic Colitis

Scientists found 3-4-week-old mucin-type-O-glycan deficient (DKO); lacking intestinal epithelial double cortin-like kinase 1 (Dclk1) mice developed worsened spontaneous colitis characterized by reduced body weight, loose stool, severe colon thickening, epithelial lesions, and inflammatory cell infiltrates compared with DKO mice. The primary defect was an impaired epithelial proliferative response during inflammation. Dclk1 deficiency also reduced inflammation-induced proliferation and growth of colon organoids ex vivo. [Cell Death Differ] Abstract

MALDI-MSI of Immunotherapy: Mapping the EGFR-Targeting Antibody Cetuximab in 3D Colon Cancer Cell Cultures

By performing on-tissue reduction followed by MALDI-MSI analysis, the authors successfully mapped the time-dependent penetration and distribution of cetuximab in spheroids derived from two different colon cancer cell lines. The localization patterns were further confirmed with IF staining of the drug. Changes in other biomolecules following drug treatment were also observed including the elevation of ATP in spheroids. [Anal Chem] Abstract

miR-146a Regulates the Crosstalk between Intestinal Epithelial Cells, Microbial Components and Inflammatory Stimuli

Researchers studied the relationship between bacterial antigens and inflammatory stimuli, and miR-146a expression using intestinal epithelial cell lines and models of colitis. Specific bacterial antigens and cytokines stimulated miR-146a expression, while peptidoglycan, muramyldipeptide and CpG DNA had no effect. [Sci Rep] Full Article

Antrodia cinnamomea Induces Autophagic Cell Death via the CHOP/TRB3/Akt/mTOR Pathway in Colorectal Cancer Cells

A. cinnamomea extracts showed cytotoxicity in HCT116, HT29, SW480, Caco-2 and, Colo205 colorectal cancer cells. Autophagy inhibition but not apoptosis inhibition reversed A. cinnamomea-induced cell death. [Sci Rep] Full Article

PCNA and JNK1‐Stat3 Pathways Respectively Promotes and Inhibits Diabetes‐Associated Centrosome Amplification by Targeting at the ROCK1/14‐3‐3σ Complex in Human Colon Cancer HCT116 Cells

Investigators found that treatment of HCT116 cells with high glucose, insulin, and palmitic acid triggered centrosome amplification and increased the expressions of proliferating cell nuclear antigen (PCNA), nucleophosmin (NPM), and 14‐3‐3σ. Individual knockdown of PCNA, NPM, or 14‐3‐3σ inhibited centrosome amplification. [J Cell Physiol] Full Article

Biogenic Nanoselenium Particles Activate Nrf2‐ARE Pathway by Phosphorylating p38, ERK1/2, and AKT on IPEC‐J2 Cells

The authors demonstrated that treatment of IPEC‐J2 cells with biogenic nanoselenium particles not only elevated the levels of downstream proteins of nuclear factor‐like 2 (Nrf2) such as heme oxygenase‐1 and NQO‐1 in a time‐dependent manner which started to weaken at 12 hours after treatment but also significantly activated Nrf2, mitogen‐activated protein kinase, and the protein kinase B (AKT) pathway in a time‐dependent manner within 24 hours. [J Cell Physiol] Abstract

Augmented Antitumor Activity of 5‐FU by Double Knockdown of MDM4 and MDM2 in Colon and Gastric Cancer Cells

Murine double minute homolog 4 (MDM4)/MDM2 double knockdown with siRNAs enhanced 5‐FU‐induced p53 activation, arrested cell cycle at the Gap 1 phase, and potentiated the antitumor effect of 5‐FU in wild‐type TP53/high MDM4 human colon and gastric cancer cells. [Cancer Sci] Abstract

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Modeling Human Digestive Diseases with CRISPR-Cas9-Modified Organoids

Researchers review the derivation of organoids from human gastrointestinal tissues and how CRISPR-Cas9 technology can be used to study these organoids. [Gastroenterology] Abstract

2D- and 3D-Based Intestinal Stem Cell Cultures for Personalized Medicine

The authors provide an overview of the different types of 2D- and 3D-based intestinal stem cell cultures, their potential benefits, and the drawbacks in personalized medicine in treatment of the intestinal disorders. [Cells] Full Article

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Innovent Announces Global Collaboration with Hutchison MediPharma to Evaluate Combination of Sintilimab and Fruquintinib in Solid Tumors

Innovent Biologics, Inc. announced that it has entered into a global collaboration agreement with Hutchison China MediTech Limited, through its Innovation Platform subsidiary Hutchison MediPharma Limited, to evaluate the safety and tolerability of Innovent’s sintilimab in combination with Hutchison MediPharma’s fruquintinib in patients with advanced solid tumors. [Innovent Biologics, Inc.] Press Release

Celyad Doses First mCRC Patient in the Phase I alloSHRINK Trial Evaluating Non-Gene Edited Allogeneic CAR-T Candidate, CYAD-101

Celyad announced the injection of the first patient in the Phase I alloSHRINK trial evaluating the company’s non-gene edited allogeneic CAR-T therapy, CYAD-101, administered concurrently with FOLFOX chemotherapy in the treatment of patients with unresectable metastatic colorectal cancer (mCRC). [Celyad] Press Release

OSE Immunotherapeutics Receives Belgian Authorization for a Phase I Clinical Trial to Evaluate Anti-IL-7 Receptor Antagonist OSE-127

OSE Immunotherapeutics SA announced authorization by Federal Agency for Medicines and Health Products and Belgian Ethics Committee to initiate a Phase I clinical trial of OSE-127, a monoclonal antibody targeting the IL-7 receptor with a novel mechanism of action. [OSE Immunotherapeutics SA (Business Wire, Inc.)] Press Release

Learn the basics of culturing mouse intestinal organoids with an instructional video series. Watch the Video Now

NIH Director Says There’s Work to Do on Regulating Genome Editing Globally

The apparent birth this month of the first genetically modified babies is “a lesson in the potential for human hubris to overtake us,” Dr. Francis Collins, the director of the National Institutes of Health (NIH), told STAT, but he said there is little U.S. officials can do to influence how China sanctions the rogue scientist who claims to have led the ethically dubious scientific breakthrough. [STAT News] Editorial

Some Research May Be Encouraging Ineffective Prescriptions, Says New Study

A new paper published by McGill University researchers in JAMA Internal Medicine suggests that some clinical trials may promote the use of ineffective and costly treatments. That’s the opposite of what clinical trials are aimed at, namely preventing ineffective and costly treatments from being taken up by physicians and patients. [McGill University] Editorial

NEW Keystone Symposia: Lipidomics and Functional Metabolic Pathways in Disease
March 31-April 4, 2019
Steamboat Springs, Colorado, United States

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NEW PhD Scholarship – Biophysical Nanomedicine (Technical University of Denmark)

NEW Postdoctoral Scientist – Intestinal Immunology (University of Oxford)

Postdoctoral Research Fellowship – Mucosal Immunology (University of Oslo)

PhD Scholarship – 3D Printed Microenvironments for Mini-Organ Culture (Technical University of Denmark)

Postdoctoral Researcher – Pesticide Exposure and Effects on Colorectal Cancer (Luxembourg Institute of Health)

Postdoctoral Fellow – Organoid Modeling of Bacterial Infections (Uppsala University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Fellow – Intestinal & Colonic Stem Cell Research (Albert Einstein College of Medicine of Yeshiva University)

PhD Studentship – Gastrointestinal Adenocarcinomas (University of Cambridge)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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