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https://www.readbyqxmd.com/read/28934349/the-association-between-acute-graft-versus-host-disease-and-antimicrobial-peptide-expression-in-the-gastrointestinal-tract-after-allogeneic-stem-cell-transplantation
#1
Daniela Weber, Katrin Frauenschläger, Sakhila Ghimire, Katrin Peter, Isabella Panzer, Andreas Hiergeist, Markus Weber, Daniel Kutny, Daniel Wolff, Matthias Grube, Elisabeth Huber, Peter Oefner, Andre Gessner, Thomas Hehlgans, Wolfgang Herr, Ernst Holler
Intestinal microbiota disruption is associated with acute gastrointestinal (GI) Graft-versus-Host Disease (GvHD) and poor outcome after allogeneic stem cell transplantation (ASCT). Here, in a retrospective analysis of 200 patients undergoing ASCT at the Regensburg University Medical Center, we assessed the relative expression of Paneth cell antimicrobial peptides (AMPs), Human Defensins (HD) 5 and 6 and regenerating islet-derived 3α (Reg3α), in 292 human intestinal biopsies as well as Reg3α serum levels in relation to acute GI GvHD...
2017: PloS One
https://www.readbyqxmd.com/read/28911771/measurement-and-prediction-of-chlorine-kinetic-isotope-effects-in-enzymatic-systems
#2
Lukasz Szatkowski, Rabindra Nath Manna, Anna Grzybkowska, Rafał Kamiński, Agnieszka Dybala-Defratyka, Piotr Paneth
Approaches to determine chlorine kinetic isotope effects (Cl-KIEs) on enzymatic dehalogenations are discussed and illustrated by representative examples. Three aspects are considered. First methodology for experimental measurement of Cl-KIEs, with stress being on FAB-IRMS technique developed in our laboratory, is described. Subsequently, we concentrate our discussion on the consequences of reaction complexity in the interpretation of experimental values, a problem especially important in cases of polychlorinated reactants...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28875556/melatonin-alleviates-weanling-stress-in-mice-involvement-of-intestinal-microbiota
#3
Wenkai Ren, Peng Wang, Jiameng Yan, Gang Liu, Benhua Zeng, Tarique Hussain, Can Peng, Jie Yin, Bie Tan, Tiejun Li, Hong Wei, Guoqiang Zhu, Russel J Reiter, Yulong Yin
Melatonin influences intestinal microbiota, and the pathogenesis of various diseases. This study was conducted to explore whether melatonin alleviates weanling stress through intestinal microbiota in a weanling mouse model. Melatonin supplementation in weanling mice (provided in the drinking water at a dosage of 0.2mg/ml for 2 weeks) significantly improved body weight gain (1.4±0.03 g/day in melatonin group vs. 1.2±0.06 g/day in control group) and intestinal morphology [i.e., villus length (258.1±12.2 um in melatonin group vs...
September 5, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28865734/paneth-cell-defects-induce-microbiota-dysbiosis-in-mice-and-promote-visceral-hypersensitivity
#4
Ambre Riba, Maïwenn Olier, Sonia Lacroix-Lamandé, Corinne Lencina, Valérie Bacquié, Cherryl Harkat, Marion Gillet, Marine Baron, Caroline Sommer, Virginie Mallet, Christel Salvador-Cartier, Fabrice Laurent, Vassilia Théodorou, Sandrine Ménard
BACKGROUND & AIMS: Separation of newborn rats from their mothers induces visceral hypersensitivity and impaired epithelial secretory cell lineages when they are adults. Little is known about the mechanisms by which maternal separation causes visceral hypersensitivity or its relationship with defects in epithelial secretory cell lineages. METHODS: We performed studies with C3H/HeN mice separated from their mothers as newborns and mice genetically engineered (Sox9(flox/flox)-vil-cre on C57BL/6 background) to have deficiencies in Paneth cells...
August 30, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28855949/ileal-antimicrobial-peptide-expression-is-dysregulated-in-old-age
#5
Sarah Tremblay, Nathalie Marie Louise Côté, Guillaume Grenier, Gabriella Duclos-Lasnier, Louis-Charles Fortier, Subburaj Ilangumaran, Alfredo Menendez
In an effort to understand the mechanisms underlying the high prevalence of gastrointestinal tract disorders in old age, we investigated the expression of intestinal antimicrobial peptides in the terminal small intestine of aged mice. Our results show that old mice have reduced transcript levels of ileal α-defensins and lysozyme, two important types of intestinal antimicrobial peptides produced by Paneth cells. In contrast, expression of the C-type lectins Reg3b and Reg3g, as well as β-defensin 1, angiogenin 4 and Relmb, which are made by several epithelial cell types, was significantly upregulated in aged animals suggesting an ongoing response to epithelial distress...
2017: Immunity & Ageing: I & A
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/28835755/intestinal-stem-cell-niche-the-extracellular-matrix-and-cellular-components
#7
REVIEW
Laween Meran, Anna Baulies, Vivian S W Li
The intestinal epithelium comprises a monolayer of polarised columnar cells organised along the crypt-villus axis. Intestinal stem cells reside at the base of crypts and are constantly nourished by their surrounding niche for maintenance, self-renewal, and differentiation. The cellular microenvironment including the adjacent Paneth cells, stromal cells, smooth muscle cells, and neural cells as well as the extracellular matrix together constitute the intestinal stem cell niche. A dynamic regulatory network exists among the epithelium, stromal cells, and the matrix via complex signal transduction to maintain tissue homeostasis...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28817680/human-alpha-defensin-5-is-a-candidate-biomarker-to-delineate-inflammatory-bowel-disease
#8
Amanda D Williams, Olga Y Korolkova, Amos M Sakwe, Timothy M Geiger, Samuel D James, Roberta L Muldoon, Alan J Herline, J Shawn Goodwin, Michael G Izban, Mary K Washington, Duane T Smoot, Billy R Ballard, Maria Gazouli, Amosy E M'Koma
Inability to distinguish Crohn's colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately...
2017: PloS One
https://www.readbyqxmd.com/read/28813414/a-randomized-synbiotic-trial-to-prevent-sepsis-among-infants-in-rural-india
#9
Pinaki Panigrahi, Sailajanandan Parida, Nimai C Nanda, Radhanath Satpathy, Lingaraj Pradhan, Dinesh S Chandel, Lorena Baccaglini, Arjit Mohapatra, Subhranshu S Mohapatra, Pravas R Misra, Rama Chaudhry, Hegang H Chen, Judith A Johnson, J Glenn Morris, Nigel Paneth, Ira H Gewolb
Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. No efficient means of prevention is currently available. Here we report on a randomized, double-blind, placebo-controlled trial of an oral synbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) in rural Indian newborns. We enrolled 4,556 infants that were at least 2,000 g at birth, at least 35 weeks of gestation, and with no signs of sepsis or other morbidity, and monitored them for 60 days...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28806085/resolving-discrepancy-between-theory-and-experiment-in-4-nitrotoluene-oxidation
#10
Kamila Klajman, Grzegorz Ciepielowski, Rafał Kamiński, Paweł Adamczyk, Piotr Paneth
We have performed calculations of possible oxidation pathways of 4-nitrotoluene (4NT) by permanganate anion and evaluated relative contributions of oxidation of the methyl group and aromatic ring. Although a few theory levels matched the experimental results obtained by compound specific isotope analysis (CSIA) for 4NT, they failed in reproducing results for other nitrotoluene derivatives studied previously [Wijker, R.S.; Adamczyk, P.; Bolotin, J.; Paneth, P.; Hofstetter, T.B. Environ. Sci. Technol., 2013, 47, 13459-13468]...
August 28, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28801754/expression-profiling-of-tas2r-genes-reveals-a-complex-pattern-along-the-mouse-gi-tract-and-the-presence-of-tas2r131-in-a-subset-of-intestinal-paneth-cells
#11
Simone Prandi, Anja Voigt, Wolfgang Meyerhof, Maik Behrens
The chemical variability of the intestinal lumen requires the presence of molecular receptors detecting the various substances naturally occurring in the diet and as a result of the activity of the microbiota. Despite their early discovery, intestinal bitter taste receptors (Tas2r) have not yet been assigned an unambiguous physiological function. Recently, using a CRE-recombinant approach we showed that the Tas2r131 gene is expressed in a subset of mucin-producing goblet cells in the colon of mice. Moreover, we also demonstrated that the expression of the Tas2r131 locus is not restricted to this region...
August 11, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28770667/autophagy-counters-lps-mediated-suppression-of-lysozyme
#12
Sudha B Singh, Henry C Lin
Impaired Paneth cell expression of antimicrobial protein (AMP) lysozyme is found in patients with Crohn's disease with the autophagy gene ATG16L1 risk allele, in mice with mutations in autophagy genes Atg16L1, Atg5 and Atg7, and in Irgm1 knockout mice. Defective autophagy is also associated with expansion of resident Gram-negative bacteria in the intestinal lumen. These findings suggest that autophagy may control extracellular resident microbes by governing expression of lysozyme. To test the hypothesis that autophagy may have a defensive role in host response to resident extracellular microbes, we investigated the relationship between gut microbes, autophagy, and lysozyme...
August 2017: Innate Immunity
https://www.readbyqxmd.com/read/28768191/intrinsic-autophagy-is-required-for-the-maintenance-of-intestinal-stem-cells-and-for-irradiation-induced-intestinal-regeneration
#13
Jumpei Asano, Taku Sato, Shizuko Ichinose, Mihoko Kajita, Nobuyuki Onai, Shigeomi Shimizu, Toshiaki Ohteki
Autophagy is a lysosomal degradation pathway with important roles in physiological homeostasis and disease. However, the role of autophagy in intestinal stem cells (ISCs) is unclear. Here, we show that intrinsic autophagy in ISCs is important for ISC homeostasis. Mice lacking autophagy protein 5 (ATG5) in intestinal epithelial cells (iECs) (Villin-Cre: Atg5(fl/fl), hereafter Atg5(ΔIEC) mice) or in all iECs except Paneth cells (Ah-Cre: Atg5(fl/fl) mice) had significantly fewer ISCs than did control mice and showed impaired ISC-dependent intestinal recovery after irradiation...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28758961/nrf2-knockout-protects-from-intestinal-injuries-in-c57bl-6j-mice-following-abdominal-irradiation-with-%C3%AE-rays
#14
Wenyan Yang, Zhijuan Sun, Bing Yang, Qin Wang
Radiation-induced intestinal injuries (RIII) commonly occur in patients who suffer from pelvic or abdominal cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant, and the radioprotective role of Nrf2 is found in bone marrow, lung, and intestine, etc. Here, we investigated the effect of Nrf2 knockout on radiation-induced intestinal injuries using Nrf2 knockout (Nrf2(-/-)) mice and wild-type (Nrf2(+/+)) C57BL/6J mice following 13 Gy abdominal irradiation (ABI)...
July 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28751470/paneth-cells-secrete-lysozyme-via-secretory-autophagy-during-bacterial-infection-of-the-intestine
#15
Shai Bel, Mihir Pendse, Yuhao Wang, Yun Li, Kelly A Ruhn, Brian Hassell, Tess Leal, Sebastian E Winter, Ramnik J Xavier, Lora V Hooper
Intestinal Paneth cells limit bacterial invasion by secreting antimicrobial proteins including lysozyme. However, invasive pathogens can disrupt the Golgi apparatus, interfering with secretion and compromising intestinal antimicrobial defense. Here we show that during bacterial infection, lysozyme is rerouted through secretory autophagy, an autophagy-based alternative secretion pathway. Secretory autophagy was triggered in Paneth cells by bacteria-induced endoplasmic reticulum (ER) stress, required extrinsic signals from innate lymphoid cells, and limited bacterial dissemination...
July 27, 2017: Science
https://www.readbyqxmd.com/read/28719255/patient-reported-adverse-effects-associated-with-combination-antiretroviral-therapy-and-coadministered-enzyme-inducing-antiepileptic-drugs
#16
Melissa A Elafros, Gretchen L Birbeck, Joseph C Gardiner, Omar K Siddiqi, Izukanji Sikazwe, Nigel Paneth, Christopher M Bositis, Jason F Okulicz
AbstractConcurrent treatment with combination antiretroviral therapy (cART) and an enzyme-inducing antiepileptic drug (EI-AED) is common in resource-limited settings; however, the incidence and impact of adverse effects in cotreated patients is largely unknown. Symptoms of adverse effects were assessed by both spontaneous report and checklist for 145 human immunodeficiency virus (HIV)-infected Zambian adults initiating various treatment combinations, such as cART with an EI-AED (N = 20), cART only (N = 43), or neither drug (untreated; N = 82)...
June 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28686579/synergy-between-prkdc-and-trp53-regulates-stem-cell-proliferation-and-gi-ars-after-irradiation
#17
Kay E Gurley, Amanda K Ashley, Russell D Moser, Christopher J Kemp
Ionizing radiation (IR) is one of the most widely used treatments for cancer. However, acute damage to the gastrointestinal tract or gastrointestinal acute radiation syndrome (GI-ARS) is a major dose-limiting side effect, and the mechanisms that underlie this remain unclear. Here we use mouse models to explore the relative roles of DNA repair, apoptosis, and cell cycle arrest in radiation response. IR induces DNA double strand breaks and DNA-PK mutant Prkdc(scid/scid) mice are sensitive to GI-ARS due to an inability to repair these breaks...
July 7, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28684459/dclk1-expressing-tuft-cells-critical-modulators-of-the-intestinal-niche
#18
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/28652797/flll32-a-curcumin-analog-ameliorates-intestinal-injury-in-necrotizing-enterocolitis
#19
Jeffrey Eckert, Brian Scott, Shelley M Lawrence, Michael Ihnat, Hala Chaaban
BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease that primarily affects premature infants. It is characterized by inflammation and leukocyte infiltration that can progress to intestinal necrosis, perforation, systemic inflammatory response, and death. In this study, we examined the effect of FLLL32, a curcumin analog, on an NEC-like neonatal intestinal injury model. METHODS: NEC was induced in CD-1 mice pups using the Paneth cell ablation and Klebsiella infection model...
2017: Journal of Inflammation Research
https://www.readbyqxmd.com/read/28648363/dynamic-reorganization-of-chromatin-accessibility-signatures-during-dedifferentiation-of-secretory-precursors-into-lgr5-intestinal-stem-cells
#20
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
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