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Condition: Crohn's Disease

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Total 54 results found since Jan 2013.

A Genome-Wide siRNA Screen Reveals Positive and Negative Regulators of the NOD2 and NF-κB Signaling Pathways.
Abstract The cytoplasmic receptor NOD2 (nucleotide-binding oligomerization domain 2) senses peptidoglycan fragments and triggers host defense pathways, including activation of nuclear factor κB (NF-κB) signaling, which lead to inflammatory immune responses. Dysregulation of NOD2 signaling is associated with inflammatory diseases, such as Crohn's disease and Blau syndrome. We used a genome-wide small interfering RNA screen to identify regulators of the NOD2 signaling pathway. Several genes associated with Crohn's disease risk were identified in the screen. A comparison of candidates from this screen with other "o...
Source: Science Signaling - January 23, 2013 Category: Biomedical Science Authors: Warner N, Burberry A, Franchi L, Kim YG, McDonald C, Sartor MA, Núñez G Tags: Sci Signal Source Type: research

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters
Conclusion In summary, this study is the first to combine metabolomics, transcriptomics, and genome-wide association studies in a porcine model. Our results improve understanding of the genetic regulation of metabolites which link to transcripts and finally biochemical-clinical parameters. Further, high-performance profiling of metabolites as intermediate phenotypes is a potentially powerful approach to uncover how genetic variation affects metabolic and health status. Our results advance knowledge in areas of biomedical and agricultural interest and identify potential correlates of biomarkers, SNPs-metabolites, SNPs-tran...
Source: Frontiers in Genetics - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Oligonucleotides —A Novel Promising Therapeutic Option for IBD
Conclusions In this review, we focused on recent and past approaches to test the therapeutic efficacy of oligonucleotide based therapies in IBD. The combining mechanistic mode of oligonucleotide based therapeutics is a targeted action on specific pro-inflammatory molecules, which are over activated in IBD patients and contribute significantly to disease pathogenesis. The proposed high selectivity of the agents is derived from its mode of action, that aims to specifically block certain inflammatory molecular patterns, without a general systemic effect on other molecular targets. It would be important for each oligonucleot...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

NOD2 and TLR2 Signal via TBK1 and PI31 to Direct Cross-Presentation and CD8 T Cell Responses
The objective of this study was to explore the role of NOD2 and TLR2 in cross-presentation in human dendritic cells undertaking an unbiased screen. We have used a quantitative phosphoproteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by a computational analysis to identify the proteins as differentially abundant in response to NOD2 and TLR2 sensing. Validation of the phosphoproteomic analysis was performed by the detection of proteins in phosphoenriched lysates and detected by western blot. Techniques for the modulation of gene expression (shRNA and siRNA) were used to confirm the resu...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Chromosome region maintenance-1 (CRM1) regulates apoptosis of intestinal epithelial cells via p27kip1 in Crohn's disease
Conclusions Up-regulated CRM1 may facilitate IEC apoptosis possibly through p27kip1 in CD, indicating an important role of CRM1 in the pathophysiology of CD.
Source: Clinics and Research in Hepatology and Gastroenterology - March 9, 2017 Category: Gastroenterology Source Type: research

Transforming growth factor β1-induced collagen production in myofibroblasts is mediated by reactive oxygen species derived from NADPH oxidase 4.
In this study, we examined the role of NOX4 in collagen production by intestinal myofibroblasts stimulated with transforming growth factor (TGF)-β1. Using LmcMF cells, an intestinal subepithelial myofibroblast (ISEMF) line, we first examined the induction of collagen production by TGF-β1. Subsequently, we investigated the role of NOX4 in TGF-β1-induced collagen I production in these cells using SB525334 (an SMAD2/3 inhibitor), diphenyleneiodonium (an NOX inhibitor), and Nox4 small interfering RNA (siRNA). Production of collagen was assessed with Sirius red staining, and Nox4 expression was measured by quantitative real-...
Source: Biochemical and Biophysical Research communications - October 23, 2018 Category: Biochemistry Authors: Hotta Y, Uchiyama K, Takagi T, Kashiwagi S, Nakano T, Mukai R, Toyokawa Y, Yasuda T, Ueda T, Suyama Y, Murakami T, Tanaka M, Majima A, Doi T, Hirai Y, Mizushima K, Morita M, Higashimura Y, Inoue K, Fukui A, Okayama T, Katada K, Kamada K, Handa O, Ishikawa Tags: Biochem Biophys Res Commun Source Type: research

Research Resource A Genome-Wide siRNA Screen Reveals Positive and Negative Regulators of the NOD2 and NF-{kappa}B Signaling Pathways
A small interfering RNA screen provides insight into the mechanisms of Crohn's disease pathogenesis.
Source: Signal Transduction Knowledge Environment - January 16, 2013 Category: Science Authors: Neil Warner, Aaron Burberry, Luigi Franchi, Yun-Gi Kim, Christine McDonald, Maureen A. Sartor, Gabriel Nunez Source Type: news

Impaired autophagy leads to abnormal dendritic cell–epithelial cell interactions
Conclusions: In intestinal DC–epithelial cell interactions, autophagy deficiency leads to decreased antigen sampling, increased DC maturation and a more pro-inflammatory type of DC.
Source: Journal of Critical Care - September 17, 2012 Category: Gastroenterology Authors: Caterina Strisciuglio, Marjolijn Duijvestein, Auke P. Verhaar, Anne Christine W. Vos, Gijs R. van den Brink, Daniel W. Hommes, Manon E. Wildenberg Tags: Regular papers Source Type: research

Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients.
This article is protected by copyright. All rights reserved. PMID: 24943399 [PubMed - as supplied by publisher]
Source: Immunology - June 18, 2014 Category: Allergy & Immunology Authors: Smith A, Sewell G, Levine A, Chew T, Dunne J, O'Shea N, Smith P, Harrison P, Macdonald C, Bloom S, Segal A Tags: Immunology Source Type: research

Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway
Abstract: Isorhamnetin is an O-methylated flavonol present in fruit and vegetables. We recently reported the identification of isorhamnetin as an activator of the human pregnane X receptor (PXR), a known target for abrogating inflammation in inflammatory bowel disease (IBD). The current study investigated the role of isorhamnetin as a putative mouse PXR activator in ameliorating chemically induced IBD. Using two different models (ulcerative colitis like and Crohn's disease like) of experimental IBD in mice, we demonstrated that isorhamnetin abrogated inflammation through inhibiting the activity of myeloperoxidase, the leve...
Source: The Journal of Nutritional Biochemistry - May 9, 2014 Category: Biochemistry Authors: Wei Dou, Jingjing Zhang, Hao Li, Sandhya Kortagere, Katherine Sun, Lili Ding, Gaiyan Ren, Zhengtao Wang, Sridhar Mani Tags: Research Articles Source Type: research

Regulators of NOD2-induced IL-8 Secretion Signal Transduction
NOD2 encodes an intracellular multidomain pattern recognition receptor that is the strongest known genetic risk factor in the pathogenesis of Crohn disease (CD), a chronic relapsing inflammatory disorder of the intestinal tract. NOD2 functions as a sensor for bacterial cell wall components and activates proinflammatory and antimicrobial signaling pathways. Here, using a genome-wide small interfering RNA (siRNA) screen, we identify numerous genes that regulate secretion of the proinflammatory cytokine IL-8 in response to NOD2 activation. Moreover, many of the identified IL-8 regulators are linked by protein-protein interact...
Source: Journal of Biological Chemistry - October 9, 2014 Category: Chemistry Authors: Warner, N., Burberry, A., Pliakas, M., McDonald, C., Nunez, G. Tags: Immunology Source Type: research

Vacuolar protein sorting 4B regulates apoptosis of intestinal epithelial cells via p38 MAPK in Crohn's disease.
In this study, we reported for the first time that VPS4B was over-expressed in intestinal epithelial cell (IECs) of patients with CD. In TNBS-induced mouse colitis models, we observed the up-regulation of VPS4B was accompanied with the elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and phosphorylated p38 in colitis IECs. Co-localization of VPS4B and active caspase-3 in IECs of the TNBS group further indicated the possible involvement of VPS4B in IEC apoptosis. Employing the TNF-α-treated HT29 cells as an in vitro IEC apoptosis model, we confirmed the positive correlation of VPS4B with caspase...
Source: Experimental and Molecular Pathology - December 20, 2014 Category: Pathology Authors: Zhang D, Wang L, Yan L, Miao X, Gong C, Xiao M, Ni R, Tang Q Tags: Exp Mol Pathol Source Type: research

Ex vivo immunosuppressive effects of mesenchymal stem cells on Crohn’s disease mucosal T cells are largely dependent on indoleamine 2,3-dioxygenase activity and cell-cell contact
Conclusion: MSCs exert potent immunomodulant effects on antigen-specific T cells in CD through a complex paracrine and cell-cell contact-mediated action, which may be exploited for widespread therapeutic use.
Source: Stem Cell Research and Therapy - July 24, 2015 Category: Stem Cells Authors: Rachele CiccocioppoGiuseppina CangemiPeter KruzliakAlessandra GalliaElena BettiCarla BadulliMiryam MartinettiMarila CervioAlessandro PecciValeria BozziPaolo DionigiLivia VisaiAntonella GurradoCostanza AlvisiCristina PiconeManuela MontiMaria BernardoPaolo Source Type: research

Increased IGF-IEc Expression and Mechano-Growth Factor Production in Intestinal Muscle of Fibrostenotic Crohn's Disease and Smooth Muscle Hypertrophy.
Abstract The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression, IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. MGF derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were i...
Source: Am J Physiol Gastroi... - October 1, 2015 Category: Gastroenterology Authors: Li C, Vu K, Hazelgrove K, Kuemmerle JF Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy
The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF p...
Source: AJP: Gastrointestinal and Liver Physiology - December 1, 2015 Category: Gastroenterology Authors: Li, C., Vu, K., Hazelgrove, K., Kuemmerle, J. F. Tags: HORMONES, NEUROTRANSMITTERS, GROWTH FACTORS, RECEPTORS, AND SIGNALING Source Type: research