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https://www.readbyqxmd.com/read/29787419/a-locus-at-7p14-3-predisposes-to-refractory-celiac-disease-progression-from-celiac-disease
#1
Barbara Hrdlickova, Chris J Mulder, Georgia Malamut, Bertrand Meresse, Mathieu Platteel, Yoichiro Kamatani, Isis Ricaño-Ponce, Roy L J van Wanrooij, Maria M Zorro, Marc Jan Bonder, Javier Gutierrez-Achury, Christophe Cellier, Alexandra Zhernakova, Petula Nijeboer, Pilar Galan, Sebo Withoff, Mark Lathrop, Gerd Bouma, Ramnik J Xavier, Bana Jabri, Nadine C Bensussan, Cisca Wijmenga, Vinod Kumar
BACKGROUND: Approximately 5% of patients with celiac disease (CeD) do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T lymphocytes. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma. It is not known whether genetic variations play a role in severe progression of CeD to RCDII...
May 21, 2018: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29770852/notch-inhibition-counteracts-paneth-cell-death-in-absence-of-caspase-8
#2
M K Jeon, E Kaemmerer, U Schneider, M Schiffer, C Klaus, J Hennings, T Clahsen, T Ackerstaff, M Niggemann, A Schippers, T Longerich, G Sellge, C Trautwein, N Wagner, C Liedtke, N Gassler
Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8∆int ) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity...
May 16, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29743614/healthy-hosts-rule-within-ecological-forces-shaping-the-gut-microbiota
#3
REVIEW
Mariana X Byndloss, Sandy R Pernitzsch, Andreas J Bäumler
A balanced gut microbiota is important for human health, but the mechanisms that maintain homeostasis are incompletely understood. Recent insights suggest the host plays a key role in shaping its gut microbiota to be beneficial. While host control in the small intestine curbs bacterial numbers to avoid competition for simple sugars and amino acids, the host limits oxygen availability in the large intestine to obtain microbial fermentation products from fiber. Epithelial cells are major players in imposing ecological control mechanisms, which involves the release of antimicrobial peptides by small-intestinal Paneth cells and maintenance of luminal anaerobiosis by epithelial hypoxia in the colon...
May 9, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29713315/oral-administration-of-probiotics-increases-paneth-cells-and-intestinal-antimicrobial-activity
#4
Silvia I Cazorla, Carolina Maldonado-Galdeano, Ricardo Weill, Juan De Paula, Gabriela D V Perdigón
The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP) that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431) and L...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29701912/gut-microbiota-as-a-modulator-of-paneth-cells-during-parenteral-nutrition-in-mice
#5
Jiwei Wang, Feng Tian, Peng Wang, Huijun Zheng, Ying Zhang, Hao Tian, Li Zhang, Xuejin Gao, Xinying Wang
BACKGROUND: Parenteral nutrition (PN) leads to decreased production of Paneth cell-derived antimicrobial peptides and is accompanied by dysbiosis of the gut. The role of gut microbiota in regulating Paneth cell function during PN is unknown. METHODS: Male C57BL/6 mice received either an antibiotic cocktail (Abx) or nothing (Normal) in their drinking water for 2 weeks before being fed either standard laboratory chow (Abx-Chow and Normal-Chow) or a continuous infusion of PN solution (Abx-PN and Normal-PN) for 7 days...
April 27, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29701728/synthesis-and-antibacterial-activity-of-new-thiazolidine-2-4-dione-based-chlorophenylthiosemicarbazone-hybrids
#6
Nazar Trotsko, Urszula Kosikowska, Agata Paneth, Tomasz Plech, Anna Malm, Monika Wujec
Series of new thiazolidine-2,4-dione-based chlorophenylthiosemicarbazone hybrids ( 17 ⁻ 40 ) were synthesized by the reaction of condensation chlorophenylthiosemicarbazides with formylphenyl 2-(2,4-dioxothiazolidin-5-yl/ylidene)acetates. New compounds were tested on reference strains of Gram-positive and Gram-negative bacteria. The antibacterial activity of target compounds was determined by broth dilution method. Most active compounds possess minimum inhibitory concentration (MIC) = 3.91 mg/L. These compounds were non-toxic at concentrations close to their antibacterial effect...
April 26, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29701691/paneth-cells-during-viral-infection-and-pathogenesis
#7
REVIEW
Mayumi K Holly, Jason G Smith
Paneth cells are major secretory cells located in the crypts of Lieberkühn in the small intestine. Our understanding of the diverse roles that Paneth cells play in homeostasis and disease has grown substantially since their discovery over a hundred years ago. Classically, Paneth cells have been characterized as a significant source of antimicrobial peptides and proteins important in host defense and shaping the composition of the commensal microbiota. More recently, Paneth cells have been shown to supply key developmental and homeostatic signals to intestinal stem cells in the crypt base...
April 26, 2018: Viruses
https://www.readbyqxmd.com/read/29698056/the-muc2-mucin-coats-murine-paneth-cell-granules-and-facilitates-their-content-release-and-dispersion
#8
Martin Stahl, Sarah Tremblay, Marinieve Montero, Wayne Vogl, Lijun Xia, Kevan Jacobson, Alfredo Menendez, Bruce A Vallance
Paneth cells are a key subset of secretory epithelial cells found at the base of small intestinal crypts. Unlike intestinal goblet cells, which secrete the mucin Muc2, Paneth cells are best known for producing an array of antimicrobial factors. We unexpectedly identified Muc2 staining localized around Paneth cell granules. Electron microscopy (EM) confirmed an electron lucent halo around these granules, which was lost in Paneth cells from Muc2 deficient (-/- ) mice. EM as well as immunostaining for lysozyme revealed that Muc2-/- Paneth cells contained larger, more densely packed granules within their cytoplasm and we detected defects in the transcription of key antimicrobial genes in the ileal tissues of Muc2-/- mice...
April 26, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29685982/-entamoeba-histolytica-alters-ileal-paneth-cell-functions-in-intact-and-muc2-mucin-deficiency
#9
Eduardo R Cobo, Ravi Holani, France Moreau, Kiminori Nakamura, Tokiyoshi Ayabe, Jennifer R Mastroianni, Andre Ouellette, Kris Chadee
Enteric α-defensins, termed cryptdins (Crps) in mice, and lysozymes secreted by Paneth cells contribute to innate host defense in the ileum. Antimicrobial factors including lysozymes and β-defensins are often embedded in luminal glycosylated colonic Muc2 mucin secreted by goblet cells that form the protective mucus layer critical in gut homeostasis and pathogen invasion. In this study we investigated ileal innate immunity against Entamoeba histolytica (Eh ), the causative agent of intestinal amebiasis, by inoculating parasites in closed ileal loops in Muc2+/+ and Muc2-/- littermates and quantifying Paneth cell localization (lysozyme expression) and function (Crps secretion)...
April 23, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29675450/engineered-human-gastrointestinal-cultures-to-study-the-microbiome-and-infectious-diseases
#10
REVIEW
Sarah E Blutt, Sue E Crawford, Sasirekha Ramani, Winnie Y Zou, Mary K Estes
New models to study the intestine are key to understanding intestinal diseases and developing novel treatments. Intestinal organ-like culture systems (organoids and enteroids) have substantially advanced the study of the human gastrointestinal tract. Stem cell-derived cultures produce self-organizing structures that contain the multiple differentiated intestinal epithelial cell types including enterocytes, goblet, Paneth, and enteroendocrine cells. Understanding host-microbial interactions is one area in which these cultures are expediting major advancements...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29675025/impact-of-paneth-cell-autophagy-on-inflammatory-bowel-disease
#11
REVIEW
Shu-Ling Wang, Bo-Zong Shao, Sheng-Bing Zhao, Jun Fang, Lun Gu, Chao-Yu Miao, Zhao-Shen Li, Yu Bai
Intestinal mucosal barrier, mainly consisting of the mucus layer and epithelium, functions in absorbing nutrition as well as prevention of the invasion of pathogenic microorganisms. Paneth cell, an important component of mucosal barrier, plays a vital role in maintaining the intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Current evidence shows that the dysfunction of intestinal mucosal barrier, especially Paneth cell, participates in the onset and progression of inflammatory bowel disease (IBD)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29672847/loss-of-n-wasp-drives-early-progression-in-an-apc-model-of-intestinal-tumourigenesis
#12
Hayley T Morris, Loic Fort, Heather J Spence, Rachana Patel, David F Vincent, James H Park, Scott B Snapper, Francis A Carey, Owen J Sansom, Laura M Machesky
N-WASP (WASL) is a widely expressed cytoskeletal signalling and scaffold protein also implicated in regulation of Wnt signalling and homeostatic maintenance of skin epithelial architecture. N-WASP mediates invasion of cancer cells in vitro and its depletion reduces invasion and metastatic dissemination of breast cancer. Given this role in cancer invasion and universal expression in the gastrointestinal tract, we explored a role for N-WASP in the initiation and progression of colorectal cancer. While deletion of N-wasp is not detectably harmful in the murine intestinal tract, numbers of Paneth cells increased, indicating potential changes in the stem cell niche and migration up the crypt-villus axis was enhanced...
April 19, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29643147/-ex-vivo-gut-culture-for-studying-differentiation-and-migration-of-small-intestinal-epithelial-cells
#13
Xiaofei Sun, Xing Fu, Min Du, Mei-Jun Zhu
Epithelial cultures are commonly used for studying gut health. However, due to the absence of mesenchymal cells and gut structure, epithelial culture systems including recently developed three-dimensional organoid culture cannot accurately represent in vivo gut development, which requires intense cross-regulation of the epithelial layer with the underlying mesenchymal tissue. In addition, organoid culture is costly. To overcome this, a new culture system was developed using mouse embryonic small intestine. Cultured intestine showed spontaneous peristalsis, indicating the maintenance of the normal gut physiological structure...
April 2018: Open Biology
https://www.readbyqxmd.com/read/29629872/radical-and-lunatic-fringes-modulate-notch-ligands-to-support-mammalian-intestinal-homeostasis
#14
Preetish Kadur Lakshminarasimha Murthy, Tara Srinivasan, Matthew S Bochter, Rui Xi, Anastasia Kristine Varanko, Kuei-Ling Tung, Fatih Semerci, Keli Xu, Mirjana Maletic-Savatic, Susan E Cole, Xiling Shen
Notch signalling maintains stem cell regeneration at the mouse intestinal crypt base and balances the absorptive and secretory lineages in the upper crypt and villus. Here we report the role of Fringe family of glycosyltransferases in modulating Notch activity in the two compartments. At the crypt base, RFNG is enriched in the Paneth cells and increases cell surface expression of DLL1 and DLL4. This promotes Notch activity in the neighbouring Lgr5 + stem cells assisting their self-renewal. Expressed by various secretory cells in the upper crypt and villus, LFNG promotes DLL surface expression and suppresses the secretory lineage ...
April 9, 2018: ELife
https://www.readbyqxmd.com/read/29618461/lessons-from-the-crypt-hmga1-amping-up-wnt-for-stem-cells-and-tumor-progression
#15
REVIEW
Linda Resar, Lionel Chia, Lingling Xian
High mobility group A1 (HMGA1) chromatin remodeling proteins are enriched in aggressive cancers and stem cells, although their common function in these settings has remained elusive until now. Recent work in murine intestinal stem cells (ISC) revealed a novel role for Hmga1 in enhancing self-renewal by amplifying Wnt signaling, both by inducing genes expressing Wnt agonist receptors and Wnt effectors. Surprisingly, Hmga1 also "builds" a stem cell niche by upregulating Sox9 , a factor required for differentiation to Paneth cells; these cells constitute an epithelial niche by secreting Wnt and other factors to support ISCs...
April 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29616040/cholinergic-activation-enhances-resistance-to-oral-salmonella-infection-by-modulating-innate-immune-defense-mechanisms-at-the-intestinal-barrier
#16
Ray M Al-Barazie, Ghada Hassan Bashir, Mohammed M Qureshi, Yassir A Mohamed, Ashraf Al-Sbiei, Saeed Tariq, Wim J Lammers, Basel K Al-Ramadi, Maria J Fernandez-Cabezudo
Inflammation is a crucial defense mechanism that protects the body from the devastating effects of invading pathogens. However, an unrestrained inflammatory reaction may result in systemic manifestations with dire consequences to the host. The extent of activation of the inflammatory response is tightly regulated through immunological and neural pathways. Previously, we demonstrated that cholinergic stimulation confers enhanced protection in experimental animals orally infected with virulent Salmonella enterica serovar Typhimurium...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29615438/generation-of-intestinal-organoids-suitable-for-pharmacokinetic-studies-from-human-induced-pluripotent-stem-cells
#17
Daichi Onozato, Misaki Yamashita, Anna Nakanishi, Takumi Akagawa, Yuriko Kida, Isamu Ogawa, Tadahiro Hashita, Takahiro Iwao, Tamihide Matsunaga
Intestinal organoids morphologically resemble intestinal tissues, and are expected to be used in both regenerative medicine and drug development studies, including pharmacokinetic studies. However, the pharmacokinetic properties of these organoids remain poorly characterized. In this study, we aimed to generate pharmacokinetically functional intestinal organoids from human induced pluripotent stem (iPS) cells. Human iPS cells were induced to differentiate into the hindgut and then seeded on EZSPHERE plates to generate uniform spheroids, and the floating spheroids were subsequently differentiated into intestinal organoids by using small-molecule compounds...
April 3, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29605266/gastrointestinal-mucosal-development-and-injury-in-premature-lambs-supported-by-the-artificial-placenta
#18
Jennifer S McLeod, Joseph T Church, Prathusha Yerramilli, Megan A Coughlin, Elena M Perkins, Raja Rabah, Robert H Bartlett, Alvaro Rojas-Pena, Joel K Greenson, Erin E Perrone, George B Mychaliska
BACKGROUND: An Artificial Placenta (AP) utilizing extracorporeal life support (ECLS) could revolutionize care of extremely premature newborns, but its effects on gastrointestinal morphology and injury need investigation. METHODS: Lambs (116-121days GA, term=145; n=5) were delivered by C-section, cannulated for ECLS, had total parenteral nutrition (TPN) provided, and were supported for 7days before euthanasia. Early and Late Tissue Controls (ETC, n=5 and LTC, n=5) delivered at 115-121days and 125-131days, respectively, were immediately sacrificed...
March 8, 2018: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29593242/the-role-of-csf1r-dependent-macrophages-in-control-of-the-intestinal-stem-cell-niche
#19
Anuj Sehgal, David S Donaldson, Clare Pridans, Kristin A Sauter, David A Hume, Neil A Mabbott
Colony-stimulating factor 1 (CSF1) controls the growth and differentiation of macrophages.CSF1R signaling has been implicated in the maintenance of the intestinal stem cell niche and differentiation of Paneth cells, but evidence of expression of CSF1R within the crypt is equivocal. Here we show that CSF1R-dependent macrophages influence intestinal epithelial differentiation and homeostasis. In the intestinal lamina propria CSF1R mRNA expression is restricted to macrophages which are intimately associated with the crypt epithelium, and is undetectable in Paneth cells...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29589539/paneth-cells-and-their-antimicrobials-in-intestinal-immunity
#20
Timon E Adolph, Lisa Mayr, Felix Grabherr, Herbert Tilg
Since the initial description of granular-rich small-intestinal crypt-based epithelial cells in 1872, today referred to as Paneth cells, a plethora of recent studies underlined their function in intestinal homeostasis. Paneth cells are evolutionary conserved highly secretory cells that produce antimicrobials to control gut microbial communities. Moreover, Paneth cells emerged as stem cell regulators that translate environmental cues into intestinal epithelial responses. Paneth cell disturbances may instigate intestinal inflammation and provide susceptibility to infection...
March 27, 2018: Current Pharmaceutical Design
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