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https://www.readbyqxmd.com/read/29030247/inhibition-of-intestinal-ascorbic-acid-uptake-by-lipopolysaccharide-is-mediated-via-transcriptional-mechanism-s
#1
Veedamali S Subramanian, Subrata Sabui, Hamid Moradi, Jonathan S Marchant, Hamid M Said
Ascorbic acid (AA) accumulation in intestinal epithelial cells is an active transport process mainly mediated by two sodium-dependent vitamin C transporters (SVCT-1 and SVCT-2). To date, little is known about the effect of gut microbiota generated lipopolysaccharide (LPS) on intestinal absorption of water-soluble vitamins. Therefore, the objective of this study was to investigate the effects of bacterially-derived LPS on AA homeostasis in enterocytes using Caco-2 cells, mouse intestine and intestinal enteroids models...
October 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28958857/the-function-of-atpase-copper-transporter-atp7b-in-intestine
#2
Hannah Pierson, Abigael Muchenditsi, Byung-Eun Kim, Martina Ralle, Nicholas Zachos, Dominik Huster, Svetlana Lutsenko
BACKGROUND & AIMS: Wilson disease is a disorder of copper (Cu) misbalance caused by mutations in the ATPase copper transporting beta gene (ATP7B). ATP7B is highly expressed in the liver-the major site of Cu accumulation in patients with Wilson disease. The intestine also expresses ATP7B, but little is known about the contribution of intestinal ATP7B to normal intestinal homeostasis or to Wilson disease manifestations. We characterized the role of ATP7B in mouse intestinal organoids and tissues...
September 25, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28934294/immunopathology-of-childhood-celiac-disease-key-role-of-intestinal-epithelial-cells
#3
Grzegorz Pietz, Rituparna De, Maria Hedberg, Veronika Sjöberg, Olof Sandström, Olle Hernell, Sten Hammarström, Marie-Louise Hammarström
BACKGROUND & AIMS: Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria. METHODS: Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels...
2017: PloS One
https://www.readbyqxmd.com/read/28929461/the-isolation-culture-and-propagation-of-murine-intestinal-enteroids-for-the-study-of-dietary-lipid-metabolism
#4
Diana Li, Hongli Dong, Alison B Kohan
Since the initial report in 2009 by Sato and Clevers, primary enteroids have been of major interest in the fields of stem cell biology and gastrointestinal (GI) tract biology. More recently, we and others have made major inroads into the physiological relevance of these enteroid models and have shown that enteroids derived from the stomach, intestine, or colon recapitulate major functions of these tissues, namely, gastric acid secretion, lipid absorption and lipoprotein secretion, and ion transport. Here, we detail the isolation of stem cells from the small intestine and the culture and propagation of those stem cells into mature three-dimensional enteroids...
September 20, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28912250/role-of-microrna-423-5p-in-post-transcriptional-regulation-of-the-intestinal-riboflavin-transporter-3
#5
Ram Lakhan, Veedamali S Subramanian, Hamid M Said
Riboflavin (RF) is essential for normal cellular functions and health. Humans obtain RF from exogenous sources via intestinal absorption that involves a highly specific carrier-mediated process. We have recently established that the riboflavin transporter-3 (RFVT3) is vital for the normal intestinal RF uptake process, and have characterized certain aspects of its transcriptional regulation. Little is known, however, about how this transporter is regulated at the post-transcriptional level. We address this issue focusing on the role of microRNAs...
September 14, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28854151/aging-effects-on-intestinal-homeostasis-associated-with-expansion-and-dysfunction-of-intestinal-epithelial-stem-cells
#6
Emily C Moorefield, Sarah F Andres, R Eric Blue, Laurianne Van Landeghem, Amanda T Mah, M Agostina Santoro, Shengli Ding
Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFP(Low)), activatable reserve IESC and enteroendocrine cells (Sox9-EGFP(High)), Sox9-EGFP(Sublow) progenitors, and Sox9-EGFP(Negative) differentiated lineages. Crypt-villus morphology, cellular composition and apoptosis were measured by histology...
August 29, 2017: Aging
https://www.readbyqxmd.com/read/28808163/a-role-for-fimh-in-extraintestinal-pathogenic-escherichia-coli-invasion-and-translocation-through-the-intestinal-epithelium
#7
Nina M Poole, Sabrina I Green, Anubama Rajan, Luz E Vela, Xi-Lei Zeng, Mary K Estes, Anthony W Maresso
The translocation of bacteria across the intestinal epithelium of immunocompromised patients can lead to bacteremia and life-threatening sepsis. Extraintestinal Pathogenic Escherichia coli (ExPEC), so named because this pathotype infects tissues distal to the intestinal tract, is a frequent cause of such infections, is often multidrug resistant, and chronically colonizes a sizable portion of the healthy population. Although several virulence factors and their roles in pathogenesis are well described for ExPEC that cause urinary tract infections and meningitis, they have not been linked to translocation through intestinal barriers, a fundamentally distant yet important clinical phenomenon...
August 14, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28792626/advanced-three-dimensional-culture-of-equine-intestinal-epithelial-stem-cells
#8
A Stieler Stewart, J M Freund, L M Gonzalez
BACKGROUND: Intestinal epithelial stem cells are critical to epithelial repair following gastrointestinal injury. The culture of intestinal stem cells has quickly become a cornerstone of a vast number of new research endeavours that range from determining tissue viability to testing drug efficacy for humans. This study aims to describe the methods of equine stem cell culture and highlights the future benefits of these techniques for the advancement of equine medicine. OBJECTIVES: To describe the isolation and culture of small intestinal stem cells into three-dimensional (3D) enteroids in horses without clinical gastrointestinal abnormalities...
August 9, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28751424/a-simple-cost-effective-method-for-generating-murine-colonic-3d-enteroids-and-2d-monolayers-for-studies-of-primary-epithelial-cell-function
#9
Elizabeth H Fernando, Michael Dicay, Martin Stahl, Marilyn H Gordon, Andrew Vegso, Cristiane Baggio, Laurie Alston, Fernando Lopes, Kristi Baker, Simon Andrew Hirota, Derek M McKay, Bruce A Vallance, Wallace K MacNaughton
Cancer cell lines have been the mainstay of intestinal epithelial experimentation for decades, due primarily to their immortality and ease of culture. However, because of the inherent biological abnormalities of cancer cell lines, many cellular biologists are currently transitioning away from these models, and toward more representative primary cells. This has been particularly challenging, but recent advances in the generation of intestinal organoids have brought the routine use of primary cells within reach of most epithelial biologists...
July 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28747340/epithelial-tnf-receptor-signaling-promotes-mucosal-repair-in-inflammatory-bowel-disease
#10
Emily M Bradford, Stacy H Ryu, Ajay Pal Singh, Goo Lee, Tatiana Goretsky, Preetika Sinh, David B Williams, Amber L Cloud, Elias Gounaris, Vihang Patel, Olivia F Lamping, Evan B Lynch, Mary Pat Moyer, Isabelle G De Plaen, David J Shealy, Guang-Yu Yang, Terrence A Barrett
TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/β-catenin-mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models. We hypothesized that TNF exerts beneficial effects on intestinal epithelial cell (IEC) responses to injury...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28739253/key-differences-between-apoc-iii-regulation-and-expression-in-intestine-and-liver
#11
COMPARATIVE STUDY
Gabrielle West, Cayla Rodia, Diana Li, Zania Johnson, Hongli Dong, Alison B Kohan
ApoC-III is a critical cardiovascular risk factor, and humans expressing null mutations in apoC-III are robustly protected from cardiovascular disease. Because of its critical role in elevating plasma lipids and CVD risk, hepatic apoC-III regulation has been studied at length. Considerably less is known about the factors that regulate intestinal apoC-III. In this work, we use primary murine enteroids, Caco-2 cells, and dietary studies in wild-type mice to show that intestinal apoC-III expression does not change in response to fatty acids, glucose, or insulin administration, in contrast to hepatic apoC-III...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28630260/cholesterol-auxotrophy-and-intolerance-to-ezetimibe-in-mice-with-srebp-2-deficiency-in-the-intestine
#12
Shunxing Rong, Jeffrey G McDonald, Luke J Engelking
SREBP-2 activates transcription of all genes needed for cholesterol biosynthesis. To study SREBP-2 function in the intestine, we generated a mouse model (Vil-BP2(-/-) ) in which Cre recombinase ablates SREBP-2 in intestinal epithelia. Intestines of Vil-BP2(-/-) mice had reduced expression of genes required for sterol synthesis, in vivo sterol synthesis rates, and epithelial cholesterol contents. On a cholesterol-free diet, the mice displayed chronic enteropathy with histological abnormalities of both villi and crypts, growth restriction, and reduced survival that was prevented by supplementation of cholesterol in the diet...
October 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28622386/alpha-defensin-dependent-enhancement-of-enteric-viral-infection
#13
Sarah S Wilson, Beth A Bromme, Mayumi K Holly, Mayim E Wiens, Anshu P Gounder, Youngmee Sul, Jason G Smith
The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric α-defensins. Although they most commonly function as potent antivirals in cell culture, enteric α-defensins have also been shown to enhance some viral infections in vitro. Efforts to determine the physiologic relevance of enhanced infection have been limited by the absence of a suitable cell culture system. To address this issue, here we use primary stem cell-derived small intestinal enteroids to examine the impact of naturally secreted α-defensins on infection by the enteric mouse pathogen, mouse adenovirus 2 (MAdV-2)...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28534432/gastrointestinal-microphysiological-systems
#14
Sarah E Blutt, James R Broughman, Winnie Zou, Xi-Lei Zeng, Umesh C Karandikar, Julie In, Nicholas C Zachos, Olga Kovbasnjuk, Mark Donowitz, Mary K Estes
Gastrointestinal diseases are a significant health care and economic burden. Prevention and treatment of these diseases have been limited by the available human biologic models. Microphysiological systems comprise organ-specific human cultures that recapitulate many structural, biological, and functional properties of the organ in smaller scale including aspects of flow, shear stress and chemical gradients. The development of intestinal microphysiological system platforms represents a critical component in improving our understanding, prevention, and treatment of gastrointestinal diseases...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28483523/effect-of-essential-amino-acids-on-enteroids-methionine-deprivation-suppresses-proliferation-and-affects-differentiation-in-enteroid-stem-cells
#15
Yuki Saito, Ken Iwatsuki, Hikaru Hanyu, Natsuki Maruyama, Eitaro Aihara, Miki Tadaishi, Makoto Shimizu, Kazuo Kobayashi-Hattori
We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28467395/erratum-a-primary-human-macrophage-enteroid-co-culture-model-to-investigate-mucosal-gut-physiology-and-host-pathogen-interactions
#16
Gaelle Noel, Nicholas W Baetz, Janet F Staab, Mark Donowitz, Olga Kovbasnjuk, Marcela F Pasetti, Nicholas C Zachos
No abstract text is available yet for this article.
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28462380/cell-adhesion-molecule-cd166-alcam-functions-within-the-crypt-to-orchestrate-murine-intestinal-stem-cell-homeostasis
#17
Nicholas R Smith, Paige S Davies, Trevor G Levin, Alexandra C Gallagher, Douglas R Keene, Sidharth K Sengupta, Nikki Wieghard, Edward El Rassi, Melissa H Wong
BACKGROUND & AIMS: Intestinal epithelial homeostasis is maintained by active-cycling and slow-cycling stem cells confined within an instructive crypt-based niche. Exquisite regulating of these stem cell populations along the proliferation-to-differentiation axis maintains a homeostatic balance to prevent hyperproliferation and cancer. Although recent studies focus on how secreted ligands from mesenchymal and epithelial populations regulate intestinal stem cells (ISCs), it remains unclear what role cell adhesion plays in shaping the regulatory niche...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28390865/spdef-induces-quiescence-of-colorectal-cancer-cells-by%C3%A2-changing-the-transcriptional-targets-of-%C3%AE-catenin
#18
Yuan-Hung Lo, Taeko K Noah, Min-Shan Chen, Winnie Zou, Ester Borras, Eduardo Vilar, Noah F Shroyer
BACKGROUND & AIMS: The canonical Wnt signaling pathway activates the transcriptional activity of β-catenin. This pathway is often activated in colorectal cancer cells, but strategies to block it in tumors have not been effective. The SAM pointed domain containing ETS transcription factor (SPDEF) suppresses formation of colon tumors by unclear mechanisms. We investigated these mechanisms and the effects of SPDEF on β-catenin activity in mouse models of colorectal cancer (CRC), CRC cell lines, and mouse and human normal and cancer colonoids...
July 2017: Gastroenterology
https://www.readbyqxmd.com/read/28361480/human-intestinal-enteroids-new-models-to-study-gastrointestinal-virus-infections
#19
Winnie Y Zou, Sarah E Blutt, Sue E Crawford, Khalil Ettayebi, Xi-Lei Zeng, Kapil Saxena, Sasirekha Ramani, Umesh C Karandikar, Nicholas C Zachos, Mary K Estes
Human rotavirus (HRV) and human norovirus (HuNoV) infections are recognized as the most common causes of epidemic and sporadic cases of gastroenteritis worldwide. The study of these two human gastrointestinal viruses is important for understanding basic virus-host interactions and mechanisms of pathogenesis and to establish models to evaluate vaccines and treatments. Despite the introduction of live-attenuated vaccines to prevent life-threatening HRV-induced disease, the burden of HRV illness remains significant in low-income and less-industrialized countries, and small animal models or ex vivo models to study HRV infections efficiently are lacking...
March 31, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28359759/a-vesicle-trafficking-protein-%C3%AE-snap-regulates-paneth-cell-differentiation-in%C3%A2-vivo
#20
Susana Lechuga, Nayden G Naydenov, Alex Feygin, Antonio J Jimenez, Andrei I Ivanov
A soluble N-ethylmaleimide-sensitive factor-attachment protein alpha (αSNAP) is a multifunctional scaffolding protein that regulates intracellular vesicle trafficking and signaling. In cultured intestinal epithelial cells, αSNAP has been shown to be essential for cell survival, motility, and adhesion; however, its physiologic functions in the intestinal mucosa remain unknown. In the present study, we used a mouse with a spontaneous hydrocephalus with hop gait (hyh) mutation of αSNAP to examine the roles of this trafficking protein in regulating intestinal epithelial homeostasis in vivo...
May 13, 2017: Biochemical and Biophysical Research Communications
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