Intestinal Cell News Volume 3.39 | Oct 13 2017

TOP STORY

Esophageal Cancer “Cell of Origin” Identified

Researchers identified cells in the upper digestive tract that can give rise to Barrett’s esophagus, a precursor to esophageal cancer. The discovery of this “cell of origin” promises to accelerate the development of more precise screening tools and therapies for Barrett’s esophagus and esophageal adenocarcinoma, the fastest growing form of cancer in the United States. [Press release from Columbia University discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells from Pediatric Patients with Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate with Outcome

Scientists analyzed DNA methylation patterns and transcriptomes of primary intestinal epithelial cells (IECs) of children newly diagnosed with IBD to learn more about pathogenesis. They found gut segment-specific differences in DNA methylation and transcription profiles of IECs from children with IBD vs controls; some were independent of mucosal inflammation. [Gastroenterology] Abstract

Bioengineering of Functional Human Induced Pluripotent Stem Cell-Derived Intestinal Grafts

Investigators report the engineering of humanized intestinal grafts by repopulating decellularized rat intestinal matrix with human induced pluripotent stem cell (hiPSC)-derived intestinal epithelium and human endothelium. After 28 days of in vitro culture, hiPSC-derived progenitor cells differentiated into a monolayer of polarized intestinal epithelium. [Nat Commun] Full Article | Press Release

Aldose Reductase Inhibitor, Fidarestat Regulates Mitochondrial Biogenesis via Nrf2/HO-1/AMPK Pathway in Colon Cancer Cells

The authors investigated how aldose reductase (AR) inhibition prevents colorectal cancer cell (CRC) growth by regulating the mitochondrial biogenesis via Nrf2/HO-1 pathway. Incubation of CRC cells such as SW-480, HT29, and HCT116 with AR inhibitor, fidarestat that non-covalently binds to the enzyme, increased the expression of Nrf2. [Cancer Lett] Abstract | Graphical Abstract

Subtle Deregulation of the Wnt-Signaling Pathway through Loss of Apc2 Reduces the Fitness of Intestinal Stem Cells

Researchers showed that systemic loss of Apc2 results in an increase in the number of cells displaying nuclear β-catenin at the base of the intestinal crypt. This subsequently impacted the expression levels of several intestinal stem cell (ISC) markers and the fitness of ISCs as assessed by organoid formation efficiency. [Stem Cells] Full Article

Wild-Type and Mutant p53 Differentially Modulate MiR-124/iASPP Feedback following Pohotodynamic Therapy in Human Colon Cancer Cell Line

Scientists found that photodynamic therapy suppressed colorectal cancer cell viability, reduced the tumor size and prolonged the survival time, all of which could be attenuated by p53 mutation or deletion. After p53 mutation or deletion, several miRNA expression levels were downregulated, among which miR-124 was the most strongly downregulated, whereas inhibitor of apoptosis-stimulating protein of p53 (iASPP) expression was upregulated. [Cell Death Dis] Full Article

MicroRNA-378 Protects against Intestinal Ischemia/Reperfusion Injury via a Mechanism Involving the Inhibition of Intestinal Mucosal Cell Apoptosis

Researchers report that miR-378 is one of the markedly decreased miRNAs and found the putative target mRNA that is linked to cell death after applying the TargetScan, miRanda, CLIP-Seq and miRDB prediction algorithms. Their results showed that the overexpression of miR-378 significantly ameliorated intestinal tissue damage in wild-type and transgenic mice and oxygen glucose deprivation/reperfusion-challenged IEC-6 cell injury. [Cell Death Dis] Full Article

Interkinetic Nuclear Migration and Basal Tethering Facilitates Post-Mitotic Daughter Separation in Intestinal Organoids

To determine how position is achieved, scientists followed proliferating cells in intestinal organoids and discovered that behavior of mitotic sisters predicted long-term positioning. They found that normally, 70% of sisters remain neighbors while 30% lose contact and separate after cytokinesis. [J Cell Sci] Abstract

Delta-Toxin from Clostridium perfringens Perturbs Intestinal Epithelial Barrier Function in Caco-2 Cell Monolayers

Delta-toxin led to a reduction in transepithelial electrical resistance and increased the permeability of fluorescence isothiocyanate-conjugated dextran in human intestinal epithelial Caco-2 cells without changing the tight junction proteins, such as zonula occludens-1, occludin, and claudin-1. [Biochim Biophys Acta] Abstract | Graphical Abstract

The Loss of P2X7 Receptor Expression Leads to Increase Intestinal Glucose Transit and Hepatic Steatosis

The authors used P2rx7^−/− mice to decipher P2X7 functions in intestinal glucose transport and evaluated the impacts on metabolism. Immunohistochemistry analyses revealed the presence of GLUT2 at the apical domain of P2rx7^−/− jejunum enterocytes. [Sci Rep] Full Article

Alcohol Feeding in Mice Promotes Colonic Hyperpermeability and Changes in Colonic Organoid Stem Cell Fate

Investigators tested the hypothesis that alcohol affects intestinal stem cells using an in vivo model and ex vivo organoids generated from jejunum and colon from mice fed chronic alcohol. Alcohol-fed mice exhibited colonic (but not small intestinal) hyperpermeability, steatohepatitis and decreased butyrate/total short chain fatty acid ratio in stool. [Alcohol Clin Exp Res] Abstract

The Role of Intestinal Stem Cells in Epithelial Regeneration Following Radiation-Induced Gut Injury

Intestinal epithelial cells show remarkable plasticity in regenerating the epithelium following radiation injury. The authors explore the regenerative capacity and mechanisms of various populations of intestinal stem cells in response to ionizing radiation. [Curr Stem Cell Rep] Abstract

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Synergy Pharmaceuticals to Highlight New Data for TRULANCE^™ (Plecanatide)

Synergy Pharmaceuticals Inc. announced that the company will present two abstracts, including Phase III studies evaluating TRULANCE^™ for the treatment of adults with irritable bowel syndrome with constipation. [Press release from Synergy Pharmaceuticals Inc. discussing research to be presented at the 2017 World Congress of Gastroenterology (WCOG) at American College of Gastroenterology (ACG), Orlando] Press Release

FDA Awards 15 Grants for Clinical Trials to Stimulate Product Development for Rare Diseases

The FDA announced that it has awarded 15 new clinical trial research grants totaling more than $22 million over the next four years to boost the development of products for patients with rare diseases. [U.S. Food and Drug Administration] Press Release

Ardelyx’s Pivotal Phase III Study of Tenapanor for IBS-C Hits Primary and All Secondary Endpoints to Support NDA Submission in 2018

Ardelyx, Inc. reported positive results from T3MPO-2, its second Phase III study of tenapanor for irritable bowel syndrome with constipation (IBS-C). The study hit statistical significance for the primary endpoint and all secondary endpoints evaluated for the topline results and demonstrated the ability to normalize bowel movements. [Ardelyx, Inc.] Press Release

MabVax Therapeutics Initiates Patient Enrollment in a Phase I Trial for MVT-1075, a New Radioimmunotherapy Treatment for Advanced Pancreatic, Colon and Lung Cancers

MabVax Therapeutics Holdings, Inc. announced the initiation of patient enrollment at a second site, Memorial Sloan Kettering Cancer Center, in a Phase I clinical trial evaluating a new radioimmunotherapy product for patients with locally advanced or metastatic adenocarcinoma of the pancreas or other CA19-9 positive malignancies including colon and lung cancers. [MabVax Therapeutics Holdings, Inc.] Press Release

NSF Drops Preproposals, Deadlines for Biologists Seeking Funding

The National Science Foundation (NSF) will no longer require biologists applying for grants to submit preproposals and to adhere to an annual deadline for submissions. The changes pull the plug on a five-year pilot project in two NSF divisions—and mark the agency’s latest attempt to reduce the burden of the grant review system on its staff and outside researchers without lowering its standards. [ScienceInsider] Editorial

South African Researchers Bemoan Slashed Funds

Academics in South Africa are in uproar after a government research agency announced plans to cut the budget of a prestigious grant program that rewards the country’s best researchers. [Nature News] Editorial

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