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https://www.readbyqxmd.com/read/28719255/patient-reported-adverse-effects-associated-with-combination-antiretroviral-therapy-and-coadministered-enzyme-inducing-antiepileptic-drugs
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28637464/kaiso-differentially-regulates-components-of-the-notch-signaling-pathway-in-intestinal-cells
#6
Shaiya C Robinson, Kristina Klobucar, Christina C Pierre, Amna Ansari, Svetlana Zhenilo, Egor Prokhortchouk, Juliet M Daniel
BACKGROUND: In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso (Tg) ) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut...
June 21, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28606477/n-3-polyunsaturated-fatty-acid-enriched-lipid-emulsion-improves-paneth-cell-function-via-the-il-22-stat3-pathway-in-a-mouse-model-of-total-parenteral-nutrition
#7
Jiwei Wang, Feng Tian, Huijun Zheng, Hao Tian, Peng Wang, Li Zhang, Xuejin Gao, Xinying Wang
Total parenteral nutrition (TPN) is a life-saving therapy for patients with gastrointestinal dysfunction or failure. Long-term TPN impairs gut barrier function and contributes to infections and poor clinical outcomes. However, the underlying mechanisms of TPN-related gut barrier damage have not been fully elucidated, and effective measures are still rare. Here, we compared the effects of a predominantly n-6 polyunsaturated fatty acids emulsion (PUFAs; Intralipid) and a lipid emulsion containing n-3 PUFAs (Intralipid plus Omegaven) on antimicrobial peptides produced by Paneth cells...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28597514/macrophage-migration-inhibitory-factor-induces-inflammation-and-predicts-spinal-progression-in-ankylosing-spondylitis
#8
Vidya Ranganathan, Francesco Ciccia, Fanxing Zeng, Ismail Sari, Guiliana Guggino, Janogini Muralitharan, Eric Gracey, Nigil Haroon
OBJECTIVES: To understand the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of Ankylosing Spondylitis (AS). METHODS: AS patients satisfying the modified New York criteria were recruited for the study. Healthy volunteers, rheumatoid arthritis and osteoarthritis patients were included as controls. Based on the annual rate of increase in mSASSS scores, AS patients were classified as progressors or non-progressors. MIF levels were quantitated by ELISA in the serum and synovial fluid...
June 8, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28594381/lipophilicity-studies-on-thiosemicarbazide-derivatives
#9
Agata Paneth, Anna Hawrył, Tomasz Plech, Mirosław Hawrył, Ryszard Świeboda, Dominika Janowska, Monika Wujec, Piotr Paneth
The lipophilicity of two series of thiosemicarbazide derivatives was assessed by the RP-HPLC method with the RP-18 chromatographic column and the methanol-water mixture as the mobile phase. Distribution coefficients logPHPLC were compared to calculated values generated by commonly used AClogP software and quantum chemical calculations. The reliability of the predictions was evaluated using the correlation matrix and PCA. For 4-benzoylthiosemicarbazides, a high correlation between theoretical and experimental logP parameters was obtained using the XlogP3 algorithm, while for 4-aryl/(cyclohexyl)thiosemicarbazides, the XlogP2 parameter was strongly correlated with the experimentally obtained logP...
June 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28591806/quantitative-proteomics-of-intestinal-mucosa-from-male-mice-lacking-intestinal-epithelial-insulin-receptors
#10
Stina Rikke Jensen, Erwin M Schoof, Sarah E Wheeler, Henning Hvid, Jonas Ahnfelt-Rønne, Bo Falck Hansen, Erica Nishimura, Grith Skytte Olsen, Thomas Kislinger, Patricia L Brubaker
The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was applied to jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon...
June 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28561063/selective-analysis-of-cancer-cell-intrinsic-transcriptional-traits-defines-novel-clinically-relevant-subtypes-of-colorectal-cancer
#11
Claudio Isella, Francesco Brundu, Sara E Bellomo, Francesco Galimi, Eugenia Zanella, Roberta Porporato, Consalvo Petti, Alessandro Fiori, Francesca Orzan, Rebecca Senetta, Carla Boccaccio, Elisa Ficarra, Luigi Marchionni, Livio Trusolino, Enzo Medico, Andrea Bertotti
Stromal content heavily impacts the transcriptional classification of colorectal cancer (CRC), with clinical and biological implications. Lineage-dependent stromal transcriptional components could therefore dominate over more subtle expression traits inherent to cancer cells. Since in patient-derived xenografts (PDXs) stromal cells of the human tumour are substituted by murine counterparts, here we deploy human-specific expression profiling of CRC PDXs to assess cancer-cell intrinsic transcriptional features...
May 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28559141/establishment-of-a-refined-culture-method-for-rat-colon-organoids
#12
Hiroyuki Isshiki, Yoshiaki Arimura, Kanna Nagaishi, Kentaro Kawakami, Kei Onodera, Kentaro Yamashita, Yasuyoshi Naishiro, Mineko Fujimiya, Kohzoh Imai, Yasuhisa Shinomura
BACKGROUND: Methods for the artificial three-dimensional (3D) culture of mouse and human small-intestinal and large-intestinal stem cells have been established with CD24(+) or Paneth cell niches. In contrast, no studies have established stable 3D culture for rat colon stem cells. In this study, we established an advanced method for efficient rat colonic stem cell culture. METHODS: Using various tissue homogenates, we investigated the colonic organoid forming capacity under the TMDU protocol immediately adjacent to Ootani's 3D culture assembly in the same culture dish...
May 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28552621/intestinal-epithelial-sirtuin-1-regulates-intestinal-inflammation-during-aging-in-mice-by-altering-the-intestinal-microbiota
#13
Alicia S Wellman, Mallikarjuna R Metukuri, Nevzat Kazgan, Xiaojiang Xu, Qing Xu, Natalie S X Ren, Agnieszka Czopik, Michael T Shanahan, Ashley Kang, Willa Chen, M Andrea Azcarate-Peril, Ajay S Gulati, David C Fargo, Leonard Guarente, Xiaoling Li
BACKGROUND & AIMS: Intestinal epithelial homeostasis is maintained by complex interactions among epithelial cells, commensal gut microorganisms, and immune cells. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD), but the mechanisms of this process are not clear. We investigated how Sirtuin 1 (SIRT1), a conserved mammalian NAD(+)-dependent protein deacetylase, senses environmental stress to alter intestinal integrity. METHODS: We performed studies of mice with disruption of Sirt1 specifically in the intestinal epithelium (SIRT1 iKO, villin-Cre+, Sirt1(flox/flox) mice) and control mice (villin-Cre-, Sirt1(flox/flox)) on a C57BL/6 background...
May 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28550196/il-6-signaling-regulates-small-intestinal-crypt-homeostasis
#14
Victoria Jeffery, Andrew J Goldson, Jack R Dainty, Marcello Chieppa, Anastasia Sobolewski
Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28547368/erratum-to-synergistic-effect-of-aluminum-and-ionizing-radiation-upon-ultrastructure-oxidative-stress-and-apoptotic-alterations-in-paneth-cells-of-rat-intestine
#15
N A Eltahawy, S M Elsonbaty, S Abunour, W E Zahran
No abstract text is available yet for this article.
May 25, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28536321/-disruption-of-gut-immune-system-caused-by-damage-of-intestinal-stem-cells-and-their-niche-in-graft-versus-host-disease-after-allogeneic-hematopoietic-stem-cell-transplantation
#16
Eiko Hayase, Takanori Teshima
Allogeneic hematopoietic stem cell transplantation(allo-SCT)is curative therapy for various hematological diseases. Graft-versus-host disease(GVHD)and infection remain the main problems in allo-SCT. Gastrointestinal tract is targeted by GVHD. In intestinal GVHD, intestinal stem cells and Paneth cells reside at the base of crypts are damaged by donor T cells. These damage leads to disruption of intestinal mucosal barrier and intestinal dysbiosis, resulting in more exaggerated GVHD. Recently, we and others have reported that R-Spondin1 and interleukin-22 as factors regenerated intestinal tissue homeostasis in murine model of bone marrow transplantation...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28522995/dysbiosis-of-intestinal-microbiota-and-decreased-antimicrobial-peptide-level-in-paneth-cells-during-hypertriglyceridemia-related-acute-necrotizing-pancreatitis-in-rats
#17
Chunlan Huang, Jing Chen, Jingjing Wang, Hui Zhou, Yingying Lu, Lihong Lou, Junyuan Zheng, Ling Tian, Xingpeng Wang, Zhongwei Cao, Yue Zeng
Hypertriglyceridemia (HTG) aggravates the course of acute pancreatitis (AP). Intestinal barrier dysfunction is implicated in the pathogenesis of AP during which dysbiosis of intestinal microbiota contributes to the dysfunction in intestinal barrier. However, few studies focus on the changes in intestine during HTG-related acute necrotizing pancreatitis (ANP). Here, we investigated the changes in intestinal microbiota and Paneth cell antimicrobial peptides (AMPs) in HTG-related ANP (HANP) in rats. Rats fed a high-fat diet to induce HTG and ANP was induced by retrograde injection of 3...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28483523/effect-of-essential-amino-acids-on-enteroids-methionine-deprivation-suppresses-proliferation-and-affects-differentiation-in-enteroid-stem-cells
#18
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/28469609/guardians-of-the-gut-enteric-defensins
#19
REVIEW
Sumathi Sankaran-Walters, Ronald Hart, Chantelle Dills
Enteric defensins likely play a key role in the management of the human microbiome throughout development. The functional and mechanistic diversity of defensins is much greater than was initially thought. Defensin expression and overall Paneth cell physiology likely plays a key role in the development of colitis and other inflammatory or dysbiotic diseases of the gut. As our understanding of enteric defensins grows, their potential as tools of clinical intervention becomes more apparent. In this review, we focus on the function and activity of Paneth Cell defensins and highlight their role in disease...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28467944/metabolic-teamwork-in-the-stem-cell-niche
#20
Jatin Roper, Ömer H Yilmaz
Nearby cells can support stem cell differentiation, but the metabolic activities in stem cell niches are unknown. A recent study (Rodríguez-Colman et al., 2017) reveals a metabolic partnership in the intestinal stem cell niche: glycolysis in niche Paneth cells provides lactate to drive mitochondrial oxidative phosphorylation in intestinal stem cells.
May 2, 2017: Cell Metabolism
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