Intestinal Cell News Volume 5.12 | Apr 5 2019

TOP STORY

Oncogenic Potential of Truncated RXRα during Colitis-Associated Colorectal Tumorigenesis by Promoting Il-6-STAT3 Signaling

Mechanistic studies revealed an extensive interaction between truncated retinoid X receptor-alpha (tRXRα) and TRAF6 in the cytoplasm of macrophages, leading to TRAF6 ubiquitination and subsequent activation of the NF-κB inflammatory pathway. K-80003, a tRXRα modulator derived from nonsteroidal anti-inflammatory drug sulindac, suppressed the growth of tRXRα-mediated colorectal tumor by inhibiting the NF-κB-IL-6-STAT3 signaling cascade. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Colonic CD90⁺ Crypt Fibroblasts Secrete Semaphorins to Support Epithelial Growth

Using a number of established stromal cell markers, researchers phenotypically and functionally examined fibroblast populations in the colon. CD90⁺ fibroblasts located in close proximity to stem cells in vivo supported organoid growth in vitro and expressed crucial stem cell growth factors, such as Grem1, Wnt2b, and R-spondin3. [Cell Rep] Full Article | Graphical Abstract

Deficiency in Intestinal Epithelial Reg4 Ameliorates Intestinal Inflammation and Alters the Colonic Bacterial Composition

Regenerating islet-derived family member (Reg4) mice altered the colonic bacterial composition and reduced the bacterial adherence to the colonic epithelium. In vitro, Reg4 was shown to promote the growth of colonic organoids, and that this occurred through a mechanism involving activation of signal transducer and activator of transcription 3. [Mucosal Immunol] Full Article

Targeting β-Catenin Overcomes Mek Inhibition Resistance in Colon Cancer with KRAS and PIK3CA Mutations

Scientists investigated a biomarker of response for mitogen-activated protein kinase (MEK) inhibition in KRAS mutant colon cancers by LC-MS/MS analysis. They tested the MEK inhibitor in PIK3CA wild and mutant colon cancer cells. In addition, they tested the combinational effects of MEK and TNKS inhibitor in vitro and in vivo. [Br J Cancer] Abstract

Cancer Testis Antigen 55 Deficiency Attenuates Colitis-Associated Colorectal Cancer by Inhibiting Nf-κB Signaling

Mechanistically, cancer testis antigen 55 (CT55) acted as an accelerator of tumor necrosis factor (TNF)-α-induced nuclear factor-κB signaling. Upon stimulation with TNF-α, CT55 interacted with the IκB kinase (IKK) complex, which increased the phosphorylation of IKKα/β and activates IKK-p65 signaling, while knockout of CT55 blocked IKK–p65 signaling. [Cell Death Dis] Full Article

Side-Directed Transfer and Presystemic Metabolism of Selenoneine in a Human Intestinal Barrier Model

Selenoneine and the reference species Se-methylselenocysteine (MeSeCys) and selenite were applied to the Caco-2 intestinal barrier model. Selenoneine was transferred in higher amounts, but with similar kinetics as selenite, while MeSeCys showed the highest permeability. [Mol Nutr Food Res] Abstract

Chiral Phenoxyacetic Acid Analogues Inhibit Colon Cancer Cell Proliferation Acting as PPARγ Partial Agonists

Researchers analyzed a series of chiral phenoxyacetic acid analogues for their ability to inhibit colorectal cancer cells growth by binding PPARγ as partial agonists as assessed in transactivation assays of a PPARG-reporter gene. They further investigated compounds (R,S)-3, (S)-3 and (R,S)-7 because they combined the best antiproliferative activity and a limited transactivation potential and found that they induced cell cycle arrest mainly via upregulation of p21^waf1/cip1. [Sci Rep] Full Article

The Potential Probiotic Lactobacillus rhamnosus Cncm I-3690 Strain Protects the Intestinal Barrier by Stimulating Both Mucus Production and Cytoprotective Response

Results showed that L. rhamnosus CNCM I-3690 could physically maintain modulated goblet cells and the mucus layer and counteract changes in local and systemic lymphocytes. Furthermore, mice colonic transcriptome analysis revealed that CNCM I-3690 enhanced the expression of genes related to healthy gut permeability: motility and absorption, cell proliferation; and protective functions by inhibiting endogenous proteases. [Sci Rep] Full Article

mTORC1 Signaling Activation Increases Intestinal Stem Cell Activity and Promotes Epithelial Cell Proliferation

In the process of heat exposure, the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway was significantly inhibited in both IPEC-J2 cells and enteroids. Correspondingly, treatment of IPEC-J2 and enteroids with the mTORC1 agonist MHY1485 at 41°C significantly attenuated the inhibition of proliferation and protein synthesis, increased intestinal stem cell activity, and promoted expansion and budding of enteroid. [J Cell Physiol] Abstract

Enhanced Transepithelial Permeation of Gallic Acid and (−)-Epigallocatechin Gallate across Human Intestinal Caco-2 Cells Using Electrospun Xanthan Nanofibers

Electrospun xanthan polysaccharide X-gallic acid (X-GA) and X-(−)-epigallocatechin gallate (X-EGCG) nanofibers were incubated with Caco-2 cells, and the cell viability, transepithelial transport, and permeability properties across cell monolayers were investigated. An increase of GA and EGCG permeability was observed when the polyphenols were loaded into xanthan nanofibers, compared to the free compounds. [Pharmaceutics] Full Article

Spirulina Crude Protein Promotes the Migration and Proliferation in Iec-6 Cells by Activating Egfr/Mapk Signaling Pathway

The authors investigated the proliferative effects of spirulina crude protein (SPCP) on rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. The results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. [Mar Drugs] Full Article

Subscribe to one of our other 19 science newsletters such as Pulmonary Cell News & ESC & iPSC News.

Pharmacological Autophagy Regulators as Therapeutic Agents for Inflammatory Bowel Diseases

The authors summarize the drugs administered to IBD patients and describe recently emerged therapeutic agents. They compile evidence on the contribution of autophagy to IBD pathogenesis, give an overview of pharmacological autophagy regulators in animal models of colitis, and propose novel therapeutic avenues based on autophagy components. [Trends Mol Med] Abstract

Stem Cells in Homeostasis and Cancer of the Gut

Investigators present an overview of the current knowledge on intestinal stem cells in homeostasis and their role in malignant transformation. Also, they discuss the existence of stem cells in intestinal adenomas and colorectal cancer and how these cells contribute to (pre-)malignant growth. [Mol Cancer] Full Article

Harnessing the Innate Immune System and Local Immunological Microenvironment to Treat Colorectal Cancer

Several important factors, including cytokines, chemotherapeutics and the microbiome, influence the plasticity and functionality of innate (myeloid) cells in the microenvironment, and this complexity of regulation has limited translation into successful trials so far. Current concepts of the immunobiology of the innate arm in the tumor microenvironment are presented in the context of clinical translation. [Br J Cancer] Full Article

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

European Medicines Agency Accepts Takeda’s Marketing Authorization Application for a Subcutaneous Formulation of Vedolizumab for Maintenance Therapy in Moderately to Severely Active Ulcerative Colitis and Crohn’s Disease

Takeda Pharmaceutical Company Limited announced that the European Medicines Agency has accepted a Marketing Authorization Line Extension Application for a subcutaneous formulation of the gut-selective biologic vedolizumab for maintenance therapy in adults with moderately to severely active ulcerative colitis or Crohn’s disease. [Takeda Pharmaceutical Company Limited] Press Release

Palatin Technologies Announces Positive Top Line Results of Oral Clinical Study of Pl-8177 for Ulcerative Colitis and Other Inflammatory Bowel Diseases

Palatin Technologies, Inc. announced positive results of a micro-dose study of radiolabeled PL-8177 using an oral, delayed-release, polymer formulation. [Palatin Technologies, Inc. (iR Direct)] Press Release

Enteromed Conducts New Clinical Research into Irritable Bowel Syndrome That Can Offer Real Hope and Drug Free Relief to Patients

A large clinical trial “RELIEVE-IBS-D” for patients with diarrhoea predominant IBS included in the National Institute for Health Research portfolio has started recruitment in England. The trial is using some of the latest research technologies to collect data and new information about IBS-D. [Enteromed Ltd. (PR Newswire)] Press Release

FDA Approves the Reintroduction of Zelnorm™ (Tegaserod) for Irritable Bowel Syndrome with Constipation (IBS-C) in Women under 65

US WorldMeds has announced that Sloan Pharma, S.a.r.l. has received approval from FDA for the reintroduction of Zelnorm™, a twice-daily oral treatment for irritable bowel syndrome with constipation in women under 65. [US WorldMeds Holdings, LLC (PR Newswire)] Press Release

Evoke Pharma Receives Complete Response Letter and Recommendations to Address Deficiencies from FDA for Gimoti™ NDA

Evoke Pharma, Inc. announced that it has received a Complete Response Letter from the FDA for its 505(b)(2) New Drug Application for Gimoti™ for the relief of symptoms associated with acute and recurrent diabetic gastroparesis. [Evoke Pharma, Inc.] Press Release

Drug-Device Glitches Prompt FDA to Turn Back Evoke Pharma’s Gimoti Nasal Spray

The FDA has rebuffed Evoke Pharma’s nasal spray Gimoti, a version of the decades-old oral drug metoclopramide, on worries the spray device isn’t delivering “reproducible” dosing, a company executive said Tuesday. [Questex LLC.] Press Release

CDISC to Develop Data Standards for Crohn’s Disease with Support from the Helmsley Charitable Trust

CDISC will develop the first global, non-proprietary clinical data standards for Crohn’s disease with a grant award of $1 million from The Leona M. and Harry B. Helmsley Charitable Trust. CDISC Standards specify how to structure data to expedite approval of new therapeutics and enable data sharing, cross-study comparisons, and meta-analyses. [Clinical Data Interchange Standards Consortium] Press Release

Stand Up to Cancer Grants First Peggy Prescott Award in Colorectal Cancer Research

Stand Up To Cancer announced the recipient of its inaugural Stand Up To Cancer Peggy Prescott Early Career Scientist Award in Colorectal Cancer Research, which was funded by Dallas Cowboys QB and SU2C Ambassador Dak Prescott in memory of his mother who passed away from the disease in 2013. The fellowship provides $50,000 in research funding over a two-year term to a rising star in the colorectal cancer field. [Stand Up To Cancer] Press Release

Novartis Ponies Up $310M for IFM Therapeutics’ Inflammation-Focused Unit

Novartis is handing over $310 million up front to acquire IFM Therapeutics’ inflammation-centered subsidiary, IFM Tre. The deal includes up to $1.265 billion in milestones and gives Novartis access to one clinical and two preclinical NLRP3 antagonist programs from IFM Tre. [Questex LLC.] Press Release

Dr. Caroline Lindemans explains her work on intestinal repair following injury in graft versus host disease. Listen Now

NIH Police Yank Iranian Graduate Student from Lab as Agency Clamps Down on Security

The National Institutes of Health is requiring all visitors — including patients — to disclose their citizenship as a condition of entry, a policy that has unnerved staff scientists and led to recent disputes with at least two Iranian scientists invited to make presentations, only to be blocked from campus. [The Washington Post] Editorial

Bioethicists Concerned over Japan’s Chimera Embryo Regulations

Japanese regulators have effectively given the green light to research involving human-animal chimera embryos, which are created by implanting human pluripotent stem cells into animals in early development. The revised guidelines, issued in early March, lift a previous requirement to terminate such embryos after 14 days. [The Scientist] Editorial

NEW Digestive Disease Week 2019
May 18-21, 2019
San Diego, California, United States

NEW American Society of Colon and Rectal Surgeons 2019 Annual Meeting
June 1-5, 2019
Cleaveland, Ohio, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral – IBS and Autoimmune Disease (National Research Council of Canada)

Postdoctoral Position – Animal Genomics & IBD (University of Liège)

Graduate Student Position – Breast & Colorectal Cancer Research (Dalhousie University)

Postdoctoral Fellow – Inflammatory Bowel Disease Research (University of Toronto)

Postdoctoral Fellow – Functional Genomics & IBD (Wellcome Sanger Institute)

Research Group Leader – Intestinal Epithelial Barrier in Autoimmune Diseases (BioMed X Innovation Center)

Postdoctoral & Research Associate Positions – Biology of Intestinal & Colon Stem Cells & Gastrointestinal Cancer (Johns Hopkins University)

Postdoctoral Researcher Positions – Intestinal Epithelial Barrier in Autoimmune Diseases (BioMed X Innovation Center)

Faculty Position- General Gastroenterology (Oregon Health and Science University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Intestinal Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.