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https://www.readbyqxmd.com/read/29149731/purinergic-drug-targets-for-gastrointestinal-disorders
#1
REVIEW
Geoffrey Burnstock, Kenneth A Jacobson, Fievos L Christofi
Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. Gut inflammation releases ATP that acts on neuronal, glial, epithelial and immune cells. Purinergic signalling in glia and neurons is implicated in enteric neuropathies. Inflammation activates glia to increase ATP release and alter purinergic signalling. ATP release causes neuron death and gut motor dysfunction in colitis via a P2X7-dependent neural-glial pathway and a glial purinergic-connexin-43 pathway...
November 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29148173/metformin-protects-against-intestinal-barrier-dysfunction-via-ampk%C3%AE-1-dependent-inhibition-of-jnk-signalling-activation
#2
Jun Deng, Lishan Zeng, Xueying Lai, Jing Li, Le Liu, Qianyun Lin, Ye Chen
Disruption of the intestinal epithelial barrier, that involves the activation of C-Jun N-terminal kinase (JNK), contributes to initiate and accelerate inflammation in inflammatory bowel disease. Metformin has unexpected beneficial effects other than glucose-lowering effects. Here, we provided evidence that metformin can protect against intestinal barrier dysfunction in colitis. We showed that metformin alleviated dextran sodium sulphate (DSS)-induced decreases in transepithelial electrical resistance, FITC-dextran hyperpermeability, loss of the tight junction (TJ) proteins occludin and ZO-1 and bacterial translocation in Caco-2 cell monolayers or in colitis mice models...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29147967/association-of-inflammatory-bowel-disease-with-arthritis-evidence-from-in-silico-gene-expression-patterns-and-network-topological-analysis
#3
Anukriti Verma, Pallavi Somvanshi, Shafiul Haque, Bhawna Rathi, Shivani Sharda
Inflammatory bowel disease (IBD) is an idiopathic prolonged ailment accountable for inflammatory conditions of the intestine. Moreover, arthritis is responsible for joints' stiffness and painful inflammation. IBD shows certain articular extra-intestinal manifestations associating IBD with arthritis. IBD associated arthritis is found to be linked with ankylosing spondylitis (AS). The present study insights for the potential and putative drug targets and biomarkers of IBD associated with arthritis using in silico approaches...
November 17, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/29146678/cross-organ-sensitisation-between-the-colon-and-bladder-to-pee-or-not-to-pee
#4
Luke Grundy, Stuart M Brierley
Chronic abdominal and pelvic pain are common, debilitating clinical conditions experienced by millions of patients around the globe. The origin of such pain commonly arises from the intestine and bladder, which share common primary roles; the collection, storage and expulsion of waste. These visceral organs are located in close proximity to one another, and also share common innervation from spinal afferent pathways. Chronic abdominal pain, constipation or diarrhoea are primary symptoms for patients with Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD)...
November 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29141885/a-role-for-bacterial-urease-in-gut-dysbiosis-and-crohn-s-disease
#5
Josephine Ni, Ting-Chin David Shen, Eric Z Chen, Kyle Bittinger, Aubrey Bailey, Manuela Roggiani, Alexandra Sirota-Madi, Elliot S Friedman, Lillian Chau, Andrew Lin, Ilana Nissim, Justin Scott, Abigail Lauder, Christopher Hoffmann, Gloriany Rivas, Lindsey Albenberg, Robert N Baldassano, Jonathan Braun, Ramnik J Xavier, Clary B Clish, Marc Yudkoff, Hongzhe Li, Mark Goulian, Frederic D Bushman, James D Lewis, Gary D Wu
Gut dysbiosis during inflammatory bowel disease involves alterations in the gut microbiota associated with inflammation of the host gut. We used a combination of shotgun metagenomic sequencing and metabolomics to analyze fecal samples from pediatric patients with Crohn's disease and found an association between disease severity, gut dysbiosis, and bacterial production of free amino acids. Nitrogen flux studies using (15)N in mice showed that activity of bacterial urease, an enzyme that releases ammonia by hydrolysis of host urea, led to the transfer of murine host-derived nitrogen to the gut microbiota where it was used for amino acid synthesis...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29141575/the-protective-effects-of-extra-virgin-olive-oil-on-immune-mediated-inflammatory-responses
#6
Rosa Casas, Ramon Estruch, Emilio Sacanella
BACKGROUND AND OBJECTIVE: The increasing interest in the Mediterranean diet (MeDiet) hinges on the relevant role it plays in inflammatory diseases. Several clinical, epidemiological and experimental evidences suggest that consumption of the MeDiet reduces the incidence of certain pathologies related to oxidative stress, chronic inflammation and immune system diseases such as cancer, atherosclerosis and cardiovascular disease (CVD). DISCUSSION: These reductions can be partially attributed to extra virgin olive oil (EVOO) consumption which has been described as a key bioactive food because of its high nutritional quality and its particular composition of fatty acids, vitamins and polyphenols...
November 13, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29140288/capillary-electrophoresis-hyphenated-with-mass-spectrometry-for-determination-of-inflammatory-bowel-disease-drugs-in-clinical-urine-samples
#7
Katarína Maráková, Juraj Piešťanský, Zuzana Zelinková, Peter Mikuš
Azathioprine is the main thiopurine drug used in the treatment of immune-based inflammations of gastrointestinal tract. For the purpose of therapy control and optimization, effective and reliable analytical methods for a rapid drug monitoring in biological fluids are essential. Here, we developed a separation method based on the capillary electrophoresis (CE) hyphenated with tandem mass spectrometry (MS/MS) for the simultaneous determination of azathioprine and its selected metabolites (6-thioguanine, 6-mercaptopurine, and 6-methylmercaptopurine) as well as other co-medicated drugs (mesalazine, prednisone, and allopurinol)...
November 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29138961/blastocystis-subtypes-isolated-from-irritable-bowel-syndrome-patients-and-co-infection-with-helicobacter-pylori
#8
Ayman A El-Badry, Wegdan M Abd El Wahab, Doaa A Hamdy, Alaa Aboud
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease presenting clinically by abdominal pain with alteration of bowel habits. Although IBS has uncertain etiology, chronic gut inflammation due to persistent exposure to an infectious agent including Blastocystis sp. was proposed. The aim of this study was to detect the prevalence of Blastocystis sp. subtype (ST) isolated from stool of IBS patients and to assess Blastocystis sp. and H. pylori co-infection in IBS patients from Beni-Suef Governorate, Egypt...
November 14, 2017: Parasitology Research
https://www.readbyqxmd.com/read/29137646/the-potential-of-interleukin-37-as-an-effective-therapeutic-agent-in-asthma
#9
REVIEW
Lina Zhang, Jie Zhang, Peng Gao
Interleukin (IL)-37 belongs to the IL-1 cytokine family. It binds to IL-18Rα and recruits the orphan decoy IL-1R8. Emerging evidence shows that IL-37 is a key player in the regulation of inflammation, cellular differentiation, and proliferation. Altered IL-37 expression has been demonstrated in many inflammatory disease conditions, including asthma. In rheumatoid arthritis, IL-37 is involved in the regulation of proliferation, production of inflammatory mediators, and activation of inflammatory cells. Furthermore, this cytokine acts as a negative regulator of inflammation in inflammatory bowel disease...
November 14, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29136128/the-proton-activated-receptor-gpr4-modulates-intestinal-inflammation
#10
Yu Wang, Cheryl de Vallière, Pedro H Imenez Silva, Irina Leonardi, Sven Gruber, Alexandra Gerstgrasser, Hassan Melham, Achim Weber, Katharina Leucht, Lutz Wolfram, Martin Hausmann, Carsten Krieg, Koray Thomasson, Onur Boyman, Isabelle Frey-Wagner, Gerhard Rogler, Carsten A Wagner
BACKGROUND AND AIMS: During active inflammation tissue intraluminal intestinal pH is decreased in patients with inflammatory bowel disease (IBD). Acidic pH may play a role in IBD pathophysiology. Recently, proton sensing G-protein coupled receptors were identified, including GPR4, OGR1 (GPR68), and TDAG8 (GPR65). We investigated whether GPR4 is involved in intestinal inflammation. METHODS: The role of GPR4 was assessed in murine colitis models: chronic dextran sulphate sodium (DSS) administration and by crossbreeding into an IL-10 deficient background for development of spontaneous colitis...
November 9, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29134616/zonulin-inflammation-and-iron-status-in-patients-with-early-stages-of-chronic-kidney-disease
#11
Ewelina Lukaszyk, Mateusz Lukaszyk, Ewa Koc-Zorawska, Anna Bodzenta-Lukaszyk, Jolanta Malyszko
BACKGROUND/AIMS: Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. METHODS: Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study...
November 13, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29133078/enteric-delivery-of-regenerating-family-member-3-alpha-alters-the-intestinal-microbiota-and-controls-inflammation-in-mice-with-colitis
#12
Marion Darnaud, Alexandre Dos Santos, Patrick Gonzalez, Sandrine Augui, Claire Lacoste, Christophe Desterke, Gert De Hertogh, Emma Valentino, Emilie Braun, Jinzi Zheng, Raphael Boisgard, Christel Neut, Laurent Dubuquoy, Franck Chiappini, Didier Samuel, Patricia Lepage, Francesca Guerrieri, Joel Doré, Christian Bréchot, Nicolas Moniaux, Jamila Faivre
BACKGROUND & AIMS: Paneth cell dysfunction causes deficiencies in intestinal C-type lectins and antimicrobial peptides, which leads to dysbiosis of the intestinal microbiota, alters the mucosal barrier, and promotes development of inflammatory bowel diseases. We investigated whether transgenic expression of the human regenerating family member 3 alpha gene (REG3A) alters the fecal microbiota and affects development of colitis in mice. METHODS: We performed studies with C57BL/6 mice that express human regenerating family member 3 alpha (hREG3A) in hepatocytes, via the albumin gene promoter...
November 10, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29129972/inflammation-and-colorectal-cancer
#13
Apple G Long, Emma T Lundsmith, Kathryn E Hamilton
Colorectal cancer (CRC) is the fourth most common cancer in both men and women in the United States, resulting in over 55,000 deaths annually. Environmental and genetic factors influence the development of CRC, and inflammation is a critical hallmark of cancer that may arise from a variety of factors. Purpose of review: While patients with inflammatory bowel disease (IBD) have a higher risk of developing CRC, sporadic CRCs may engender or be potentiated by inflammation as well. In this review, we focus on recent advances in basic and translational research utilizing murine models to understand the contribution of inflammatory signaling pathways to CRC...
August 2017: Current Colorectal Cancer Reports
https://www.readbyqxmd.com/read/29129670/microalgae-derived-oxylipins-decrease-inflammatory-mediators-by-regulating-the-subcellular-location-of-nf%C3%AE%C2%BAb-and-ppar-%C3%AE
#14
Javier Ávila-Román, Elena Talero, Carolina de Los Reyes, Sofía García-Mauriño, Virginia Motilva
Oxylipins (OXLs) are bioactive molecules generated by the oxidation of fatty acids that promote the resolution of acute inflammation and prevent chronic inflammatory processes through molecular mechanisms that are not well known. We have previously reported the anti-inflammatory activity of microalgae-derived OXLs and OXL-containing biomass in two inflammatory bowel disease (IBD) models: 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis and TNBS-induced recurrent colitis. In this study, we examined the in vitro anti-inflammatory mechanism of action of the most abundant OXLs isolated from Chlamydomonas debaryana (13S-HOTE and 13S-HODE) and Nannochloropsis gaditana (15S-HEPE)...
November 9, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29126504/medical-management-of-pediatric-inflammatory-bowel-disease
#15
Katherine R Baldwin, Jess L Kaplan
Inflammatory bowel diseases (IBD) are chronic autoimmune conditions of the gut affecting both pediatric and adult patients. Medical therapy is often successful at inducing and maintaining remission and preventing disease complications. The mainstays of treatment are medications and other therapies that reduce inflammation and suppress the overactive immune system. Here we review current medical therapies for pediatric IBD, discuss future therapeutics, and present current treatment goals and approaches.
December 2017: Seminars in Pediatric Surgery
https://www.readbyqxmd.com/read/29122501/psychoneuroimmunological-approach-to-gastrointestinal-related-pain
#16
REVIEW
Karlo Toljan, Bruce Vrooman
BACKGROUND AND PURPOSE (AIMS): Psychoneuroimmunology is both a theoretical and practical field of medicine in which human biology and psychology are considered an interconnected unity. Through such a framework it is possible to elucidate complex syndromes in gastrointestinal related pain, particularly chronic non-malignant. The aim is to provide insight into pathophysiological mechanisms and suggest treatment modalities according to a comprehensive paradigm. The article also presents novel findings that may guide clinicians to recognize new targets or scientists to find new research topics...
November 6, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29121519/iguratimod-ameliorates-inflammatory-responses-by-modulating-the-th17-treg-paradigm-in-dextran-sulphate-sodium-induced-murine-colitis
#17
Xue-Pei Jiang, Xie-Lin Huang, Zao-Peng Yang, Shun-Cai Wang, Wei Xie, Lei Miao, Li Tang, Zhi-Ming Huang
Inflammatory bowel disease (IBD) is an autoimmune disease with an abnormal and persistent immune response. Iguratimod, a novel anti-rheumatic drug, exhibits anti-inflammatory effects and regulates immune response. The role of iguratimod in intestinal mucosal inflammation and immunity has not been examined. The aim of this study was to investigate whether iguratimod ameliorates dextran sulphate sodium (DSS)-induced murine colitis and its potential regulatory mechanism. Murine colitis was induced by administering 2...
November 6, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29120406/regulation-and-sensing-of-inflammasomes-and-their-impact-on-intestinal-health
#18
REVIEW
Nicole Ranson, Dale Kunde, Rajaraman Eri
Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and hematopoitic interferon-inducible nuclear protein (HIN) domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated, some of these receptors oligomerize to form the structural backbone of a signalling platform known as an inflammasome. Inflammasomes promote the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18...
November 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29118756/th17-cell-and-epithelial-cell-crosstalk-during-inflammatory-bowel-disease-and-carcinogenesis
#19
REVIEW
Jan Kempski, Leonie Brockmann, Nicola Gagliani, Samuel Huber
The intestine is colonized by hundreds of different species of commensal bacteria, viruses, and fungi. Therefore, the intestinal immune system is constantly being challenged by foreign antigens. The immune system, the commensal microbiota, and the intestinal epithelial surface have to maintain a tight balance to guarantee defense against potential pathogens and to prevent chronic inflammatory conditions at the same time. Failure of these mechanisms can lead to a vicious cycle in which a perpetual tissue damage/repair process results in a pathological reorganization of the normal mucosal surface...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29118468/the-intricate-link-among-gut-immunological-niche-microbiota-and-xenobiotics-in-intestinal-pathology
#20
REVIEW
Danilo Pagliari, Giovanni Gambassi, Ciriaco A Piccirillo, Rossella Cianci
Inflammatory bowel diseases (IBDs) are diseases characterized by various degrees of inflammation involving the gastrointestinal tract. Ulcerative colitis and Crohn's disease are characterized by a dysregulated immune response leading to structural gut alterations in genetically predisposed individuals. Diverticular disease is characterized by abnormal immune response to normal gut microbiota. IBDs are linked to a lack of physiological tolerance of the mucosal immune system to resident gut microbiota and pathogens...
2017: Mediators of Inflammation
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