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https://www.readbyqxmd.com/read/28806085/resolving-discrepancy-between-theory-and-experiment-in-4-nitrotoluene-oxidation
#1
Kamila Klajman, Grzegorz Ciepielowski, Rafal Kaminski, 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 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 14, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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