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https://www.readbyqxmd.com/read/27895587/vitamin-d-signaling-through-induction-of-paneth-cell-defensins-maintains-gut-microbiota-and-improves-metabolic-disorders-and-hepatic-steatosis-in-animal-models
#1
Danmei Su, Yuanyang Nie, Airu Zhu, Zishuo Chen, Pengfei Wu, Li Zhang, Mei Luo, Qun Sun, Linbi Cai, Yuchen Lai, Zhixiong Xiao, Zhongping Duan, Sujun Zheng, Guihui Wu, Richard Hu, Hidekazu Tsukamoto, Aurelia Lugea, Zhenqui Liu, Stephen J Pandol, Yuan-Ping Han
Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD), is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27867006/intercellular-coupling-of-the-cell-cycle-and-circadian-clock-in-adult-stem-cell-culture
#2
Toru Matsu-Ura, Andrey Dovzhenok, Eitaro Aihara, Jill Rood, Hung Le, Yan Ren, Andrew E Rosselot, Tongli Zhang, Choogon Lee, Karl Obrietan, Marshall H Montrose, Sookkyung Lim, Sean R Moore, Christian I Hong
Circadian clock-gated cell division cycles are observed from cyanobacteria to mammals via intracellular molecular connections between these two oscillators. Here we demonstrate WNT-mediated intercellular coupling between the cell cycle and circadian clock in 3D murine intestinal organoids (enteroids). The circadian clock gates a population of cells with heterogeneous cell-cycle times that emerge as 12-hr synchronized cell division cycles. Remarkably, we observe reduced-amplitude oscillations of circadian rhythms in intestinal stem cells and progenitor cells, indicating an intercellular signal arising from differentiated cells governing circadian clock-dependent synchronized cell division cycles...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27866962/distribution-of-muscarinic-acetylcholine-receptor-subtypes-in-the-murine-small-intestine
#3
Eleanor D Muise, Neeru Gandotra, John J Tackett, Michaela C Bamdad, Robert A Cowles
AIMS: Serotonin stimulates enterocyte turnover in the small intestine and studies suggest this is mediated by neuronal signaling via a cholinergic pathway. Distribution of the five known muscarinic receptor subtypes (mAChRs) in the small intestine has not been fully studied, and their role in intestinal growth is unknown. We hypothesized that mAChRs have distinct anatomic distributions within the bowel, and that mAChRs present within intestinal crypts mediate the effects of acetylcholine on the small intestinal mucosa...
November 17, 2016: Life Sciences
https://www.readbyqxmd.com/read/27791005/single-cell-lineage-tracing-reveals-a-role-for-tgf%C3%AE-r2-in-intestinal-stem-cell-dynamics-and-differentiation
#4
Jared M Fischer, Peter P Calabrese, Ashleigh J Miller, Nina M Muñoz, William M Grady, Darryl Shibata, R Michael Liskay
Intestinal stem cells (ISCs) are maintained by a niche mechanism, in which multiple ISCs undergo differential fates where a single ISC clone ultimately occupies the niche. Importantly, mutations continually accumulate within ISCs creating a potential competitive niche environment. Here we use single cell lineage tracing following stochastic transforming growth factor β receptor 2 (TgfβR2) mutation to show cell autonomous effects of TgfβR2 loss on ISC clonal dynamics and differentiation. Specifically, TgfβR2 mutation in ISCs increased clone survival while lengthening times to monoclonality, suggesting that Tgfβ signaling controls both ISC clone extinction and expansion, independent of proliferation...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27788929/circulating-inflammatory-associated-proteins-in-the-first-month-of-life-and-cognitive-impairment-at-age-10-years-in-children-born-extremely-preterm
#5
Karl C K Kuban, Robert M Joseph, Thomas M O'Shea, Timothy Heeren, Raina N Fichorova, Laurie Douglass, Hernan Jara, Jean A Frazier, Deborah Hirtz, Julie Vanier Rollins, Nigel Paneth
OBJECTIVES: To evaluate whether in children born extremely preterm, indicators of sustained systemic inflammation in the first month of life are associated with cognitive impairment at school age. STUDY DESIGN: A total of 873 of 966 eligible children previously enrolled in the multicenter Extremely Low Gestational Age Newborn Study from 2002 to 2004 were evaluated at age 10 years. We analyzed the relationship between elevated blood concentrations of inflammation-associated proteins in the first 2 weeks ("early elevations"; n = 812) and the third and fourth week ("late elevations"; n = 532) of life with neurocognition...
October 24, 2016: Journal of Pediatrics
https://www.readbyqxmd.com/read/27753990/ed-05-2-interaction-of-gut-dysbiosis-and-innate-immune-dysfunction-in-the-development-of-metabolic-syndrome
#6
Myung-Shik Lee
Low-grade systemic inflammation in adipose tissues or liver, is an important etiologic factor in insulin resistance. LPS is an important element causing such metabolic inflammation, and intestinal flora is considered a major source of systemic LPS. We studied changes of intestinal microbiota associated with high-fat diet (HFD) that causes insulin resistance and metabolic stress. 16S rRNA gene sequencing showed that HFD significantly decreased the abundance of a mucin-degrading bacterium Akkermansia muciniphila compared to control diet...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27736879/zinc-transporter-slc39a7-zip7-promotes-intestinal-epithelial-self-renewal-by-resolving-er-stress
#7
Wakana Ohashi, Shunsuke Kimura, Toshihiko Iwanaga, Yukihiro Furusawa, Tarou Irié, Hironori Izumi, Takashi Watanabe, Atsushi Hijikata, Takafumi Hara, Osamu Ohara, Haruhiko Koseki, Toshiro Sato, Sylvie Robine, Hisashi Mori, Yuichi Hattori, Hiroshi Watarai, Kenji Mishima, Hiroshi Ohno, Koji Hase, Toshiyuki Fukada
Zinc transporters play a critical role in spatiotemporal regulation of zinc homeostasis. Although disruption of zinc homeostasis has been implicated in disorders such as intestinal inflammation and aberrant epithelial morphology, it is largely unknown which zinc transporters are responsible for the intestinal epithelial homeostasis. Here, we show that Zrt-Irt-like protein (ZIP) transporter ZIP7, which is highly expressed in the intestinal crypt, is essential for intestinal epithelial proliferation. Mice lacking Zip7 in intestinal epithelium triggered endoplasmic reticulum (ER) stress in proliferative progenitor cells, leading to significant cell death of progenitor cells...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27732932/the-first-investigation-of-wilms-tumour-atomic-structure-nitrogen-and-carbon-isotopic-composition-as-a-novel-biomarker-for-the-most-individual-approach-in-cancer-disease
#8
Katarzyna Taran, Tomasz FrÄ Czek, Anita Sikora-Szubert, Anna Sitkiewicz, Wojciech Må Ynarski, Józef Kobos, Piotr Paneth
The paper describes a novel approach to investigating Wilms' tumour (nephroblastoma) biology at the atomic level. Isotope Ratio Mass Spectrometry (IRMS) was used to directly assess the isotope ratios of nitrogen and carbon in 84 Wilms' tumour tissue samples from 28 cases representing the histological spectrum of nephroblastoma. Marked differences in nitrogen and carbon isotope ratios were found between nephroblastoma histological types and along the course of cancer disease, with a breakout in isotope ratio of the examined elements in tumour tissue found between stages 2 and 3...
October 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27729212/paneth-cell-alterations-in-the-development-and-phenotype-of-crohn-s-disease
#9
Thaddeus S Stappenbeck, Dermot P B McGovern
Pathogenesis of Crohn's disease (CD) involves immune and microbial dysregulation, induced by environmental factors in genetically susceptible individuals. There are believed to be multiple subtypes of CD, which contributes to its observed clinical heterogeneity. This concept has been reinforced by recognition of the complexity of the genetic, microbial, immune, and environmental factors that affect risk for CD. Paneth cells mediate immunity in and maintain the small intestinal epithelium; defects in activities of these cells have been observed in high proportions of patients with CD, and associated with more aggressive CD phenotype...
October 8, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27703457/nod2-a-critical-regulator-of-ileal-microbiota-and-crohn-s-disease
#10
Tabasum Sidiq, Sayuri Yoshihama, Isaac Downs, Koichi S Kobayashi
The human intestinal tract harbors large bacterial community consisting of commensal, symbiotic, and pathogenic strains, which are constantly interacting with the intestinal immune system. This interaction elicits a non-pathological basal level of immune responses and contributes to shaping both the intestinal immune system and bacterial community. Recent studies on human microbiota are revealing the critical role of intestinal bacterial community in the pathogenesis of both systemic and intestinal diseases, including Crohn's disease (CD)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27699268/paneth-cell-defects-in-crohn-s-disease-patients-promote-dysbiosis
#11
Ta-Chiang Liu, Bhaskar Gurram, Megan T Baldridge, Richard Head, Vy Lam, Chengwei Luo, Yumei Cao, Pippa Simpson, Michael Hayward, Mary L Holtz, Pavlos Bousounis, Joshua Noe, Diana Lerner, Jose Cabrera, Vincent Biank, Michael Stephens, Curtis Huttenhower, Dermot P B McGovern, Ramnik J Xavier, Thaddeus S Stappenbeck, Nita H Salzman
BACKGROUND: Paneth cell dysfunction has been implicated in a subset of Crohn's disease (CD) patients. We previously stratified clinical outcomes of CD patients by using Paneth cell phenotypes, which we defined by the intracellular distribution of antimicrobial proteins. Animal studies suggest that Paneth cells shape the intestinal microbiome. However, it is unclear whether Paneth cell phenotypes alter the microbiome complexity in CD subjects. Therefore, we analyzed the correlation of Paneth cell phenotypes with mucosal microbiome composition and ileal RNA expression in pediatric CD and noninflammatory bowel disease (non-IBD) patients...
June 2, 2016: JCI Insight
https://www.readbyqxmd.com/read/27685631/mesenchymal-stem-cells-stimulate-intestinal-stem-cells-to-repair-radiation-induced-intestinal-injury
#12
Wei Gong, Mengzheng Guo, Zhibo Han, Yan Wang, Ping Yang, Chang Xu, Qin Wang, Liqing Du, Qian Li, Hui Zhao, Feiyue Fan, Qiang Liu
The loss of stem cells residing in the base of the intestinal crypt has a key role in radiation-induced intestinal injury. In particular, Lgr5(+) intestinal stem cells (ISCs) are indispensable for intestinal regeneration following exposure to radiation. Mesenchymal stem cells (MSCs) have previously been shown to improve intestinal epithelial repair in a mouse model of radiation injury, and, therefore, it was hypothesized that this protective effect is related to Lgr5(+) ISCs. In this study, it was found that, following exposure to radiation, transplantation of MSCs improved the survival of the mice, ameliorated intestinal injury and increased the number of regenerating crypts...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27642901/ed-05-2-interaction-of-gut-dysbiosis-and-innate-immune-dysfunction-in-the-development-of-metabolic-syndrome
#13
Myung-Shik Lee
Low-grade systemic inflammation in adipose tissues or liver, is an important etiologic factor in insulin resistance. LPS is an important element causing such metabolic inflammation, and intestinal flora is considered a major source of systemic LPS. We studied changes of intestinal microbiota associated with high-fat diet (HFD) that causes insulin resistance and metabolic stress. 16S rRNA gene sequencing showed that HFD significantly decreased the abundance of a mucin-degrading bacterium Akkermansia muciniphila compared to control diet...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27636409/bifidobacterium-infantis-nls-super-strain-reduces-the-expression-of-%C3%AE-defensin-5-a-marker-of-innate-immunity-in-the-mucosa-of-active-celiac-disease-patients
#14
Maria I Pinto-Sánchez, Edgardo C Smecuol, Maria P Temprano, Emilia Sugai, Andrea González, María L Moreno, Xianxi Huang, Premysl Bercik, Ana Cabanne, Horacio Vázquez, Sonia Niveloni, Roberto Mazure, Eduardo Mauriño, Elena F Verdú, Julio C Bai
BACKGROUND: We have previously shown a reduction of gastrointestinal symptoms after the oral administration of Bifidobacterium infantis Natren Life Start super strain (NLS-SS) in untreated celiac disease (CD) patients. The symptomatic improvement was not associated with changes in intestinal permeability or serum levels of cytokines, chemokines, or growth factors. Therefore, we hypothesized that the beneficial symptomatic effect observed previously in patients with CD treated with B. infantis may be related to the modulation of innate immunity...
September 15, 2016: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/27589719/expression-distribution-and-role-of-aquaporin-water-channels-in-human-and-animal-stomach-and-intestines
#15
REVIEW
Cui Zhu, Zhuang Chen, Zongyong Jiang
Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs) represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1-11) have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes), goblet cells and Paneth cells...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27581119/donkey-milk-consumption-exerts-anti-inflammatory-properties-by-normalizing-antimicrobial-peptides-levels-in-paneth-s-cells-in-a-model-of-ileitis-in-mice
#16
Sophie Yvon, Maïwenn Olier, Mathilde Leveque, Gwenaëlle Jard, Helene Tormo, Djamila Ali Haimoud-Lekhal, Magali Peter, Hélène Eutamène
PURPOSE: In this study, we showed the beneficial effects of donkey milk (DM) on inflammatory damages, endogenous antimicrobial peptides levels and fecal microbiota profile in a mice model of Crohn's disease. Nowadays, new strategies of microbiome manipulations are on the light involving specific diets to induce and/or to maintain clinical remission. Interest of DM is explained by its high levels of antimicrobial peptides which confer it anti-inflammatory properties. METHODS: C57BL/6 mice were orally administered with or without indomethacin for 5 days and co-treated with vehicle, DM or heated DM during 7 days...
August 31, 2016: European Journal of Nutrition
https://www.readbyqxmd.com/read/27573849/reg4-deep-crypt-secretory-cells-function-as-epithelial-niche-for-lgr5-stem-cells-in-colon
#17
Nobuo Sasaki, Norman Sachs, Kay Wiebrands, Saskia I J Ellenbroek, Arianna Fumagalli, Anna Lyubimova, Harry Begthel, Maaike van den Born, Johan H van Es, Wouter R Karthaus, Vivian S W Li, Carmen López-Iglesias, Peter J Peters, Jacco van Rheenen, Alexander van Oudenaarden, Hans Clevers
Leucine-rich repeat-containing G-protein coupled receptor 5-positive (Lgr5(+)) stem cells reside at crypt bottoms of the small and large intestine. Small intestinal Paneth cells supply Wnt3, EGF, and Notch signals to neighboring Lgr5(+) stem cells. Whereas the colon lacks Paneth cells, deep crypt secretory (DCS) cells are intermingled with Lgr5(+) stem cells at crypt bottoms. Here, we report regenerating islet-derived family member 4 (Reg4) as a marker of DCS cells. To investigate a niche function, we eliminated DCS cells by using the diphtheria-toxin receptor gene knocked into the murine Reg4 locus...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27573241/branched-fatty-acid-esters-of-hydroxy-fatty-acids-fahfas-protect-against-colitis-by-regulating-gut-innate-and-adaptive-immune-responses
#18
Jennifer Lee, Pedro M Moraes-Vieira, Angela Castoldi, Pratik Aryal, Eric U Yee, Christopher Vickers, Oren Parnas, Cynthia J Donaldson, Alan Saghatelian, Barbara B Kahn
We recently discovered a structurally novel class of endogenous lipids, branched palmitic acid esters of hydroxy stearic acids (PAHSAs), with beneficial metabolic and anti-inflammatory effects. We tested whether PAHSAs protect against colitis, which is a chronic inflammatory disease driven predominantly by defects in the innate mucosal barrier and adaptive immune system. There is an unmet clinical need for safe and well tolerated oral therapeutics with direct anti-inflammatory effects. Wild-type mice were pretreated orally with vehicle or 5-PAHSA (10 mg/kg) and 9-PAHSA (5 mg/kg) once daily for 3 days, followed by 10 days of either 0% or 2% dextran sulfate sodium water with continued vehicle or PAHSA treatment...
October 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27572949/association-of-bactericidal-dysfunction-of-paneth-cells-in-streptozocin-induced-diabetic-mice-with-insulin-deficiency
#19
Tao Yu, Hong-Sheng Yang, Xi-Ji Lu, Zhong-Sheng Xia, Hui Ouyang, Ti-Dong Shan, Can-Ze Huang, Qi-Kui Chen
BACKGROUND Type 1 diabetes mellitus (T1DM) is associated with increased risks of enteric infection. Paneth cells constitute the first line of the gut defense. Little is known about the impact of T1DM on the bactericidal function of intestinal Paneth cells. MATERIAL AND METHODS A T1DM mouse model was induced by intraperitoneal injection of streptozocin. The analysis of intestinal microbiota and the mucosal bactericidal assay were conducted to evaluate intestinal innate defense. Numbers of Paneth cells and their expression of related antimicrobial peptides were analyzed...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27570798/immunofluorescent-staining-of-mouse-intestinal-stem-cells
#20
Kevin P O'Rourke, Lukas E Dow, Scott W Lowe
Immunofluorescent staining of organoids can be performed to visualize molecular markers of cell behavior. For example, cell proliferation marked by incorporation of nucleotide (EdU), or to observe markers of intestinal differentiation including paneth cells, goblet cells, or enterocytes (see Figure 1). In this protocol we detail a method to fix, permeabilize, stain and mount intestinal organoids for analysis by immunofluorescent confocal microscopy.
February 20, 2016: Bio-protocol
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