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https://www.readbyqxmd.com/read/28808163/a-role-for-fimh-in-extraintestinal-pathogenic-escherichia-coli-invasion-and-translocation-through-the-intestinal-epithelium
#1
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
#2
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
#3
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
#4
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...
July 26, 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
#5
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...
July 21, 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
#6
Shunxing Rong, Jeffrey McDonald, Luke Engelking
Sterol regulatory element-binding protein-2 (SREBP-2) activates transcription of all genes needed for cholesterol biosynthesis. To study SREBP-2 function in 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, they 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...
June 19, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28622386/alpha-defensin-dependent-enhancement-of-enteric-viral-infection
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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...
April 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28361480/human-intestinal-enteroids-new-models-to-study-gastrointestinal-virus-infections
#13
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
#14
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
https://www.readbyqxmd.com/read/28347989/wrn-conditioned-media-is-sufficient-for-in-vitro-propagation-of-intestinal-organoids-from-large-farm-and-small-companion-animals
#15
Robin H Powell, Michael S Behnke
Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN)...
May 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28345602/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
Integration of the intestinal epithelium and the mucosal immune system is critical for gut homeostasis. The intestinal epithelium is a functional barrier that secludes luminal content, senses changes in the gut microenvironment, and releases immune regulators that signal underlying immune cells. However, interactions between epithelial and innate immune cells to maintain barrier integrity and prevent infection are complex and poorly understood. We developed and characterized a primary human macrophage-enteroid co-culture model for in-depth studies of epithelial and macrophage interactions...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288348/a-microengineered-collagen-scaffold-for-generating-a-polarized-crypt-villus-architecture-of-human-small-intestinal-epithelium
#17
Yuli Wang, Dulan B Gunasekara, Mark I Reed, Matthew DiSalvo, Scott J Bultman, Christopher E Sims, Scott T Magness, Nancy L Allbritton
The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available...
June 2017: Biomaterials
https://www.readbyqxmd.com/read/28192061/the-contributions-of-human-mini-intestines-to-the-study-of-intestinal-physiology-and-pathophysiology
#18
Huimin Yu, Nesrin M Hasan, Julie G In, Mary K Estes, Olga Kovbasnjuk, Nicholas C Zachos, Mark Donowitz
The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28159868/using-primary-murine-intestinal-enteroids-to-study-dietary-tag-absorption-lipoprotein-synthesis-and-the-role-of-apoc-iii-in-the-intestine
#19
Javeed Jattan, Cayla Rodia, Diana Li, Adama Diakhate, Hongli Dong, Amy Bataille, Noah F Shroyer, Alison B Kohan
Since its initial report in 2009, the intestinal enteroid culture system has been a powerful tool used to study stem cell biology and development in the gastrointestinal tract. However, a major question is whether enteroids retain intestinal function and physiology. There have been significant contributions describing ion transport physiology of human intestinal organoid cultures, as well as physiology of gastric organoids, but critical studies on dietary fat absorption and chylomicron synthesis in primary intestinal enteroids have not been undertaken...
May 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28148261/dclk1-a-tumor-stem-cell-marker-regulates-pro-survival-signaling-and-self-renewal-of-intestinal-tumor-cells
#20
Parthasarathy Chandrakesan, Jiannan Yao, Dongfeng Qu, Randal May, Nathaniel Weygant, Yang Ge, Naushad Ali, Sripathi M Sureban, Modhi Gude, Kenneth Vega, Eddie Bannerman-Menson, Lijun Xia, Michael Bronze, Guangyu An, Courtney W Houchen
BACKGROUND: More than 80% of intestinal neoplasia is associated with the adenomatous polyposis coli (APC) mutation. Doublecortin-like kinase 1 (Dclk1), a kinase protein, is overexpressed in colorectal cancer and specifically marks tumor stem cells (TSCs) that self-renew and increased the tumor progeny in Apc (Min/+) mice. However, the role of Dclk1 expression and its contribution to regulating pro-survival signaling for tumor progression in Apc mutant cancer is poorly understood. METHODS: We analyzed DCLK1 and pro-survival signaling gene expression datasets of 329 specimens from TCGA Colon Adenocarcinoma Cancer Data...
February 1, 2017: Molecular Cancer
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