Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways

Publication date: 14 November 2019Source: Cell, Volume 179, Issue 5Author(s): Bing Huang, Zhanghua Chen, Lanlan Geng, Jun Wang, Huiying Liang, Yujie Cao, Huan Chen, Wanming Huang, Meiling Su, Hanqing Wang, Yanhui Xu, Yukun Liu, Bingtai Lu, Huifang Xian, Huiwen Li, Huilin Li, Lu Ren, Jing Xie, Liping Ye, Hongli WangSummaryPediatric-onset colitis and inflammatory bowel disease (IBD) have significant effects on the growth of infants and children, but the etiopathogenesis underlying disease subtypes remains incompletely understood. Here, we report single-cell clustering, immune phenotyping, and risk gene analysis for children with undifferentiated colitis, Crohn’s disease, and ulcerative colitis. We demonstrate disease-specific characteristics, as well as common pathogenesis marked by impaired cyclic AMP (cAMP)-response signaling. Specifically, infiltration of PDE4B- and TNF-expressing macrophages, decreased abundance of CD39-expressing intraepithelial T cells, and platelet aggregation and release of 5-hydroxytryptamine at the colonic mucosae were common in colitis and IBD patients. Targeting these pathways by using the phosphodiesterase inhibitor dipyridamole restored immune homeostasis and improved colitis symptoms in a pilot study. In summary, comprehensive analysis of the colonic mucosae has uncovered common pathogenesis and therapeutic targets for children with colitis and IBD.Graphical Abstract
Source: Cell - Category: Cytology Source Type: research

Related Links:

CONCLUSION: Our findings indicated that AS II could alleviate inflammatory response in LPS-induced CCD-18Co cells and in DSS-induced UC in mice. In conclusion, AS II may serve as a potential agent for the treatment of UC. PMID: 31814910 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
AbstractOsteopenia and osteoporosis are common features in inflammatory bowel disease (IBD), comprising both Crohn ’s disease and ulcerative colitis. Moreover, Crohn’s disease is associated with increased fracture risk. The etiology of bone loss in IBD is multifactorial. It includes insufficient intake or absorption of calcium, vitamin D, and potassium; smoking; a low peak bone mass; a low body mass index; a nd decreased physical activity. In several studies, it has been shown that elevated concentrations of systemic and local pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), inte...
Source: Osteoporosis International - Category: Orthopaedics Source Type: research
In conclusion, vitexin possess hepatoprotective activities against colitis-induced liver injury, it has potential application prospects in the treatment of liver injury induced by ulcerative colitis. PMID: 31810123 [PubMed - in process]
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
In conclusion, we proved that HLJDD-NBA fraction is an effective fraction of HLJDD in treating UC in mice, and it can maintain the intestinal flora homeostasis of UC mice, which increases our understanding of the mechanism of HLJDD in treating UC and lays a foundation for the development of new anti-ulcer drugs. PMID: 31810136 [PubMed - in process]
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
There is no time more joyous and stressful as the end of year holidays. As we fast approach the holidays this year it’s time to start thinking about how you’ll navigate family parties and other familial obligations. In this episode, we give our best tips for making holiday parties less stressful and how to decide if not going is the best option for you.  It’s rough out there, but we care about you and we wish you a happy, healthy holiday season. (Transcript Available Below) SUBSCRIBE &REVIEW About The Not Crazy Podcast Hosts Gabe Howard is an award-winning writer and speaker who lives with bi...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Anxiety and Panic Depression Family General Holiday Coping Not Crazy Podcast Source Type: blogs
Authors: Liu Z, Xie W, Li M, Liu J, Liang X, Li T Abstract Polaprezinc (PZ), a chelate of zinc and L-carnosine, has been widely used in the treatment of gastric ulcers since 1994. In recent years, researchers have found PZ to have a beneficial effect on various experimentally induced models of colitis in mice. In the present study, 6% dextran sodium sulfate (DSS) was used to induce a model of ulcerative colitis (UC) in Institute of Cancer Research mice. The therapeutic effect and mechanism of PZ action in a model of UC was studied in order to provide an experimental basis for the clinical application of PZ in UC tr...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
AbstractBackgroundMediterranean diet (MED) is associated with health benefits, yet scarce data exist regarding the role of MED in inflammatory bowel diseases (IBD). Herein, we aimed to evaluate the association between MED and inflammatory markers in patients with IBD after pouch surgery.MethodsConsecutive patients after pouch surgery due to ulcerative colitis (UC) were recruited at a comprehensive pouch clinic. Adherence to MED was calculated according to MED score, ranging from 0 (low adherence) to 9 (high adherence), based on food-frequency questionnaires. Pouch behavior was defined as normal pouch (NP) or pouchitis base...
Source: European Journal of Nutrition - Category: Nutrition Source Type: research
ConclusionsApheresis was well tolerated as maintenance therapy for UC although the cumulative clinical remission rate at 12  months was comparable between the apheresis and control groups.
Source: Journal of Gastroenterology - Category: Gastroenterology Source Type: research
The efficacy of antibody-based therapeutics depends on their pharmacokinetics. The pharmacokinetic and exposure response profiles of ustekinumab, a monoclonal antibody against interleukin 12/interleukin 23, are known in patients with Crohn ’s disease, yet there are few data from patients with ulcerative colitis. We characterized ustekinumab’s pharmacokinetics, exposure response, and optimal serum concentrations in patients with ulcerative colitis.
Source: Clinical Gastroenterology and Hepatology - Category: Gastroenterology Authors: Source Type: research
Abstract The skin is the largest human organ, comprising the epidermis that is composed of epithelial tissue, the dermis composed of connective tissue, and the innermost subcutaneous tissue. Generally, skin conditions are due to aging and the influence of the external environment, but empirically patients with gastrointestinal diseases are more prone to pruritus and inflammation caused by dry skin. A decrease in the skin barrier function, involving immunocompetent mast cells and oxidative stress, was noted in indomethacin-induced small intestine inflammation, dextran sodium sulfate (DSS)-induced ulcerative colitis...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research
More News: Children | Cytology | Genetics | Inflammatory Bowel Disease | Pediatrics | Study | Ulcerative Colitis