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https://www.readbyqxmd.com/read/28718031/newcomers-in-paediatric-gi-pathology-childhood-enteropathies-including-very-early-onset-monogenic-ibd
#1
Arzu Ensari, Judith Kelsen, Pierre Russo
Childhood enteropathies are a group of diseases causing severe chronic (>2-3 weeks) diarrhoea often starting in the first week of life with the potential for fatal complications for the affected infant. Early identification and accurate classification of childhood enteropathies are, therefore, crucial for making treatment decisions to prevent life-threatening complications. Childhood enteropathies are classified into four groups based on the underlying pathology: (i) conditions related to defective digestion, absorption and transport of nutrients and electrolytes; (ii) disorders related to enterocyte differentiation and polarization; (iii) defects of enteroendocrine cell differentiation; and (iv) disorders associated with defective modulation of intestinal immune response...
July 17, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28704512/a-role-for-the-drosophila-zinc-transporter-zip88e-in-protecting-against-dietary-zinc-toxicity
#2
Christopher D Richards, Coral G Warr, Richard Burke
Zinc absorption in animals is thought to be regulated in a local, cell autonomous manner with intestinal cells responding to dietary zinc content. The Drosophila zinc transporter Zip88E shows strong sequence similarity to Zips 42C.1, 42C.2 and 89B as well as mammalian Zips 1, 2 and 3, suggesting that it may act in concert with the apically-localised Drosophila zinc uptake transporters to facilitate dietary zinc absorption by importing ions into the midgut enterocytes. However, the functional characterisation of Zip88E presented here indicates that Zip88E may instead play a role in detecting and responding to zinc toxicity...
2017: PloS One
https://www.readbyqxmd.com/read/28686870/intestinal-enteroendocrine-lineage-cells-possess-homeostatic-and-injury-inducible-stem-cell-activity
#3
Kelley S Yan, Olivier Gevaert, Grace X Y Zheng, Benedict Anchang, Christopher S Probert, Kathryn A Larkin, Paige S Davies, Zhuan-Fen Cheng, John S Kaddis, Arnold Han, Kelly Roelf, Ruben I Calderon, Esther Cynn, Xiaoyi Hu, Komal Mandleywala, Julie Wilhelmy, Sue M Grimes, David C Corney, Stéphane C Boutet, Jessica M Terry, Phillip Belgrader, Solongo B Ziraldo, Tarjei S Mikkelsen, Fengchao Wang, Richard J von Furstenberg, Nicholas R Smith, Parthasarathy Chandrakesan, Randal May, Mary Ann S Chrissy, Rajan Jain, Christine A Cartwright, Joyce C Niland, Young-Kwon Hong, Jill Carrington, David T Breault, Jonathan Epstein, Courtney W Houchen, John P Lynch, Martin G Martin, Sylvia K Plevritis, Christina Curtis, Hanlee P Ji, Linheng Li, Susan J Henning, Melissa H Wong, Calvin J Kuo
Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5(+) ISCs, the most well-defined ISC pool, but Bmi1-GFP(+) cells were distinct and enriched for enteroendocrine (EE) markers, including Prox1. Prox1-GFP(+) cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1(+) cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28686868/stem-cells-all-that-is-solid-melts-into-air
#4
Maartje van der Heijden, Louis Vermeulen
The intestinal epithelium displays great resilience, as several cell populations can replenish the stem cell pool upon damage. Two studies in Cell Stem Cell extend this capacity to enteroendocrine cells, addressing the molecular basis underlying cellular plasticity observed in the intestine and the identities of putative reserve stem cells.
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28684459/dclk1-expressing-tuft-cells-critical-modulators-of-the-intestinal-niche
#5
Moritz Middelhoff, C Benedikt Westphalen, Yoku Hayakawa, Kelley S Yan, Michael D Gershon, Timothy C Wang, Michael Quante
Dclk1-expressing tuft cells constitute a unique intestinal epithelial lineage that is distinct from enterocytes, Paneth cells, goblet cells, and enteroendocrine cells. Tuft cells express taste-related receptors and distinct transcription factors, and interact closely with the enteric nervous system, suggesting a chemosensory cell lineage. In addition, recent work has shown that tuft cells interact closely with cells of the immune system, with a critical role in the cellular regulatory network governing responses to luminal parasites...
July 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28666112/how-the-gut-feels-smells-and-talks
#6
Joep Beumer, Hans Clevers
Gut-brain signaling plays a central role in a range of homeostatic processes, yet details of this cross-talk remain enigmatic. In this issue of Cell, Bellono and colleagues identify a variety of luminal stimuli acting on serotonin-secreting enteroendocrine cells and, for the first time, demonstrate a functional synaptic interaction with neurons.
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28659730/acute-selective-bioactivity-of-grape-seed-proanthocyanidins-on-enteroendocrine-secretions-in-the-gastrointestinal-tract
#7
Àngela Casanova-Martí, Joan Serrano, M Teresa Blay, Ximena Terra, Anna Ardévol, Montserrat Pinent
Background: Enteroendocrine cells respond to food components by secreting an array of hormones that regulate several functions. We have previously shown that grape seed proanthocyanidins (GSPE) modulate GLP-1 levels. Objective: To deepen on the knowledge of the mechanisms used by GSPE to increase GLP-1, and extend it to its role at modulation of other enterohormones. Design: We used an ex vivo system to test direct modulation of enterohormones; STC-1 cells to test pure phenolic compounds; and rats to test the effects at different gastrointestinal segments...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28648363/dynamic-reorganization-of-chromatin-accessibility-signatures-during-dedifferentiation-of-secretory-precursors-into-lgr5-intestinal-stem-cells
#8
Unmesh Jadhav, Madhurima Saxena, Nicholas K O'Neill, Assieh Saadatpour, Guo-Cheng Yuan, Zachary Herbert, Kazutaka Murata, Ramesh A Shivdasani
Replicating Lgr5(+) stem cells and quiescent Bmi1(+) cells behave as intestinal stem cells (ISCs) in vivo. Disrupting Lgr5(+) ISCs triggers epithelial renewal from Bmi1(+) cells, from secretory or absorptive progenitors, and from Paneth cell precursors, revealing a high degree of plasticity within intestinal crypts. Here, we show that GFP(+) cells from Bmi1(GFP) mice are preterminal enteroendocrine cells and we identify CD69(+)CD274(+) cells as related goblet cell precursors. Upon loss of native Lgr5(+) ISCs, both populations revert toward an Lgr5(+) cell identity...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28637464/kaiso-differentially-regulates-components-of-the-notch-signaling-pathway-in-intestinal-cells
#9
Shaiya C Robinson, Kristina Klobucar, Christina C Pierre, Amna Ansari, Svetlana Zhenilo, Egor Prokhortchouk, Juliet M Daniel
BACKGROUND: In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso (Tg) ) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut...
June 21, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28636167/berberine-ameliorates-collagen-induced-arthritis-in-rats-by-suppressing-th17-cell-responses-via-inducing-cortistatin-in-the-gut
#10
Mengfan Yue, Yufeng Xia, Can Shi, Chunge Guan, Yunfan Li, Rui Liu, Zhifeng Wei, Yue Dai
Berberine, an isoquinoline alkaloid, has been reported to ameliorate various autoimmune diseases including rheumatoid arthritis by oral administration. However, its mechanism remains mysterious due to an extremely low bioavailability. The fact that berberine is easy to accumulate in gut, the largest endocrine organ in the body, attracts us to explore its anti-arthritic mechanism in view of the induction of intestinal immunosuppressive neuropeptides. In this study, berberine (200 mg/kg, i.g.) was shown to ameliorate collagen-induced arthritis in rats, which was manifested by the reduction of clinical signs and joint destruction, as well as marked down-regulation of Th17 cell frequency and IL-17 level in blood...
June 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28625150/update-on-the-molecular-mechanisms-underlying-the-effect-of-cholecystokinin-and-cholecystokinin-1-receptor-on-the-formation-of-cholesterol-gallstones
#11
Helen H Wang, Piero Portincasa, David Q-H Wang
Cholecystokinin (CCK) is an important neuro-intestinal peptide hormone produced by the enteroendocrine I-cells in the upper part of small intestine. Protein- and fat-enriched food plays an important role in triggering CCK secretion from the intestine. Carbohydrates stimulate only small amounts of CCK release. The CCK-1 receptor (CCK-1R) is largely localized in the gallbladder, sphincter of Oddi, pancreas, small intestine, gastric mucosa, and pyloric sphincter, where it is responsible for CCK to regulate multiple digestive processes including gallbladder contraction, pancreatic secretion, small intestinal transit, and gastric emptying...
June 19, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28614796/%C3%AE-synuclein-in-gut-endocrine-cells-and-its-implications-for-parkinson-s-disease
#12
Rashmi Chandra, Annie Hiniker, Yien-Ming Kuo, Robert L Nussbaum, Rodger A Liddle
Parkinson's disease (PD) is a progressive neurodegenerative disease with devastating clinical manifestations. In PD, neuronal death is associated with intracellular aggregates of the neuronal protein α-synuclein known as Lewy bodies. Although the cause of sporadic PD is not well understood, abundant clinical and pathological evidence show that misfolded α-synuclein is found in enteric nerves before it appears in the brain. This suggests a model in which PD pathology originates in the gut and spreads to the central nervous system via cell-to-cell prion-like propagation, such that transfer of misfolded α-synuclein initiates misfolding of native α-synuclein in recipient cells...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28608155/pathophysiology-of-gastric-nets-role-of-gastrin-and-menin
#13
REVIEW
Sinju Sundaresan, Anthony J Kang, Juanita L Merchant
PURPOSE OF REVIEW: Neuroendocrine tumors (NETs) were initially identified as a separate entity in the early 1900s as a unique malignancy that secretes bioactive amines. GI-NETs are the most frequent type and represent a unique subset of NETs, because at least 75% of these tumors represent gastrin stimulation of the enterochromaffin-like cell located in the body of the stomach. The purpose of this review is to understand the specific role of gastrin in the generation of Gastric NETs (G-NETs)...
July 2017: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/28607910/exploiting-induced-senescence-in-intestinal-organoids-to-drive-enteroendocrine-cell-expansion
#14
EDITORIAL
Robert G Ramsay, Helen E Abud
No abstract text is available yet for this article.
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28591806/quantitative-proteomics-of-intestinal-mucosa-from-male-mice-lacking-intestinal-epithelial-insulin-receptors
#15
Stina Rikke Jensen, Erwin M Schoof, Sarah E Wheeler, Henning Hvid, Jonas Ahnfelt-Rønne, Bo Falck Hansen, Erica Nishimura, Grith Skytte Olsen, Thomas Kislinger, Patricia L Brubaker
The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was applied to jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon...
June 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28580281/glucagon-like-peptide-2-promotes-gallbladder-refilling-via-a-tgr5-independent-glp-2r-dependent-pathway
#16
Bernardo Yusta, Dianne Matthews, Grace B Flock, John R Ussher, Brigitte Lavoie, Gary M Mawe, Daniel J Drucker
OBJECTIVE: Glucagon-like peptides (GLPs) are secreted from enteroendocrine cells in response to nutrients and bile acids and control metabolism via actions on structurally-related yet distinct G protein coupled receptors. GLP-1 regulates gut motility, appetite, islet function, and glucose homeostasis, whereas GLP-2 enhances intestinal nutrient absorption. GLP-1R agonists are used to treat diabetes and obesity, and a GLP-2R agonist is approved to treat short bowel syndrome. Unexpectedly, reports of gallbladder disease have been associated with the use of both GLP-1R and GLP-2R agonists and after bariatric surgery, although the mechanisms remain unknown...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28533434/lysophosphatidylinositol-induced-activation-of-the-cation-channel-trpv2-triggers-glucagon-like-peptide-1-secretion-in-enteroendocrine-l-cells
#17
Kazuki Harada, Tetsuya Kitaguchi, Taichi Kamiya, Kyaw Htet Aung, Kazuaki Nakamura, Kunihiro Ohta, Takashi Tsuboi
The lysophosphatidylinositol (LPI) has crucial roles in multiple physiological processes, including insulin exocytosis from pancreatic islets. However, the role of LPI in secretion of glucagon-like peptide-1 (GLP-1), a hormone that enhances glucose-induced insulin secretion, is unclear. Here, we used the murine enteroendocrine L cell line GLUTag and primary murine small intestinal cells to elucidate the mechanism of LPI-induced GLP-1 secretion. Exogenous LPI addition increased intracellular Ca(2+) concentrations ([Ca(2+)] i ) in GLUTag cells and induced GLP-1 secretion from both GLUTag and acutely prepared primary intestinal cells...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533229/intrinsic-regulation-of-enteroendocrine-fate-by-numb
#18
Jérémy Sallé, Louis Gervais, Benjamin Boumard, Marine Stefanutti, Katarzyna Siudeja, Allison J Bardin
How terminal cell fates are specified in dynamically renewing adult tissues is not well understood. Here we explore terminal cell fate establishment during homeostasis using the enteroendocrine cells (EEs) of the adult Drosophila midgut as a paradigm. Our data argue against the existence of local feedback signals, and we identify Numb as an intrinsic regulator of EE fate. Our data further indicate that Numb, with alpha-adaptin, acts upstream or in parallel of known regulators of EE fate to limit Notch signaling, thereby facilitating EE fate acquisition...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28523577/ffa3-activation-stimulates-duodenal-bicarbonate-secretion-and-prevents-nsaid-induced-enteropathy-via-the-glp-2-pathway-in-rats
#19
Hyder Said, Yasutada Akiba, Kazuyuki Narimatsu, Koji Maruta, Ayaka Kuri, Ken-Ichi Iwamoto, Atsukazu Kuwahara, Jonathan D Kaunitz
BACKGROUND: Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO3(-) secretion...
August 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28523111/discovery-of-orally-efficacious-tetrahydrobenzimidazoles-as-tgr5-agonists-for-type-2-diabetes
#20
Xuqing Zhang, Mark Wall, Zhihua Sui, Jack Kauffman, Cuifen Hou, Cailin Chen, Fuyong Du, Thomas Kirchner, Yin Liang, Dana L Johnson, William V Murray, Keith Demarest
We have discovered a novel series of tetrahydrobenzimidazoles 3 as TGR5 agonists. Initial structure-activity relationship studies with an assay that measured cAMP levels in murine enteroendocrine cells (STC-1 cells) led to the discovery of potent agonists with submicromolar EC50 values for mTGR5. Subsequent optimization through methylation of the 7-position of the core tetrahydrobenzimidazole ring resulted in the identification of potent agonists for both mTGR5 and hTGR5 (human enteroendocrine NCI-H716 cells)...
May 11, 2017: ACS Medicinal Chemistry Letters
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