Disease clearance in ulcerative colitis: Is the ultimate therapeutic target?
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ABSTRACT:
SUBMITTER: D'Amico F
PROVIDER: S-EPMC10576599 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Disease clearance in ulcerative colitis: Is the ultimate therapeutic target?
D'Amico Ferdinando F Peyrin-Biroulet Laurent L Danese Silvio S
United European gastroenterology journal 20230703 8
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Project description:BackgroundClinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC.ObjectiveWe aimed to evaluate the impact of disease clearance on long-term outcomes in UC patients.MethodsA multicenter retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Italy) and at the Nancy University Hospital (France) between 2014 and 2021. Disease clearance in UC was defined as simultaneous clinical (partial-Mayo score ≤2), endoscopic (endoscopic-Mayo score = 0), and histological (Nancy index = 0) remission, and patients were monitored over a long-time follow-up (≥12 months), to compare the occurrence of negative outcomes.ResultsA total of 494 patients with UC was included in the study (269, 54.4% males). Disease clearance was present in 109 patients (22.1%) at baseline. Median follow up was 24 months. Patients with disease clearance were associated to a significantly lower risk of UC-related hospitalization compared with the control group (5.5% vs. 23.1%; p < 0.001) at last observation. Similarly, a lower rate of surgeries was detected in patients with disease clearance at baseline compared with those without (1.8% vs. 10.9%; p = 0.003). The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk of hospitalization (log-rank p < 0.0001) and surgery (log-rank p < 0.00095).ConclusionIn UC patients with early disease clearance are at significant lower risk for hospitalization and surgery. Disease clearance should be considered as a new composite outcome.
| S-EPMC9486490 | biostudies-literature
Project description:Ulcerative colitis (UC) is an inflammatory bowel disease, and is characterized by the diffuse inflammation and ulceration in the colon and rectum mucosa, even extending to the caecum. Epigenetic modifications, including DNA methylations, histone modifications and non-coding RNAs, are implicated in the differentiation, maturation, and functional modulation of multiple immune and non-immune cell types, and are influenced and altered in various chronic inflammatory diseases, including UC. Here we review the relevant studies revealing the differential epigenetic features in UC, and summarize the current knowledge about the immunopathogenesis of UC through epigenetic regulation and inflammatory signaling networks, regarding DNA methylation, histone modification, miRNAs and lncRNAs. We also discuss the epigenetic-associated therapeutic strategies for the alleviation and treatment of UC, which will provide insights to intervene in the immunopathological process of UC in view of epigenetic regulation.
| S-EPMC10758477 | biostudies-literature
Project description:In inflammatory bowel disease (IBD), mucosal healing is the primary long-term treatment goal, encompassing both endoscopic and histological outcomes. This paper aims to overview the ability of new treatment options to promote endoscopic and histological healing and to discuss the prognostic significance of endoscopic and histological outcomes. The analysis included randomized-controlled trials (published since 2020) focused on the impact of pharmacological interventions on endoscopic and histological remission in IBD. Even though the Mayo endoscopic subscore is routinely used, the application of validated scoring systems for ulcerative colitis is uncommon. In Crohn's disease (CD), the application of endoscopic scores remains limited to clinical studies. The standardized evaluation of histological features has been performed in several recent ulcerative colitis trials, resorting mostly to the Geboes score and the Nancy histological index. Still, the use of histological scores for CD remains elusive. Current evidence underscores that histological remission conveys the best long-term prognosis, supporting the inclusion of histology as a treatment guide in ulcerative colitis. In CD, data are promising but originated from a few retrospective studies. Further efforts are warranted to: (1) use validated histological indexes for ulcerative colitis, aiming their adoption as treatment targets; (2) promote the validation and utilization of histological scores for CD, at least in clinical studies; (3) confirm the prognostic impact of histological remission in CD; (4) integrate artificial intelligence assets to support grading, particularly in the setting of histology; (5) prospectively define the monitoring frequency of IBD patients who achieved histological remission.
| S-EPMC10836991 | biostudies-literature
Project description:Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Several conventional treatments for UC such as corticosteroids, immunosuppressive agents, tumor necrosis factor antagonist, integrin blockers, and interleukin antagonist, and salicylates are available but are associated with the various limitations and side-effects. None of the above treatments helps to achieve the ultimate goal of the therapy, i.e., maintenance of remission in the long-term. Natural remedies for the treatment of UC show comparatively less side effects as compared to conventional approaches, and affordable. The current review presents details on the role of herbal drugs in the treatment and cure of UC. Google, PubMed, Web of Science, and Scopus portals have been searched for potentially relevant literature to get the latest developments and updated information related to use of natural drugs in the treatment of UC. Natural products have been used over centuries to treat UC. Some of the essential herbal constituents exhibiting antiulcerogenic activity include gymnemic acid (Gymnema sylvestre), shagoal (Zingiber officinale), catechin (Camellia sinensis), curcumin (Curcuma longa), arctigenin (Arctium lappa), and boswellic acid (Boswellia serrata). Although many plant-derived products have been recommended for UC, further research to understand the exact molecular mechanism is still warranted to establish their usefulness clinically.
| S-EPMC8948151 | biostudies-literature
Project description:Ulcerative colitis (UC) is a chronic relapsing and remitting gastrointestinal disorder of uncertain aetiology. The last two decades have seen an expansion in the therapeutic arsenal used to treat UC. This has resulted in improved clinical remission and response rates. Nonetheless, staples in our current medical management originate from trials conducted in the early 20th century. In this review article, we aim to outline the key milestones in the history of the medical management of UC in addition to highlighting promising therapeutic developments for the future.
| S-EPMC9720837 | biostudies-literature
Project description:In this study, we examined the therapeutic effects of an immune-stimulating peptide, WKYMVm, in ulcerative colitis. The administration of WKYMVm to dextran sodium sulfate (DSS)-treated mice reversed decreases in body weight, bleeding score and stool score in addition to reversing DSS-induced mucosa destruction and shortened colon. The WKYMVm-induced therapeutic effect against ulcerative colitis was strongly inhibited by a formyl peptide receptor (FPR) 2 antagonist, WRWWWW, indicating the crucial role of FPR2 in this effect. Mechanistically, WKYMVm effectively decreases intestinal permeability by stimulating colon epithelial cell proliferation. WKYMVm also strongly decreases interleukin-23 and transforming growth factor-β production in the colon of DSS-treated mice. We suggest that the potent immune-modulating peptide WKYMVm and its receptor FPR2 may be useful in the development of efficient therapeutic agents against chronic intestinal inflammatory diseases.
| S-EPMC3789265 | biostudies-other
Project description:Huangqin decoction (HQD) is a Traditional Chinese Medicine formula for ulcerative colitis. However, the pharmacology and molecular mechanism of HQD on ulcerative colitis is still unclear. Combined microarray analysis, network pharmacology, and molecular docking for revealing the therapeutic targets and molecular mechanism of HQD against ulcerative colitis. TCMSP, DrugBank, Swiss Target Prediction were utilized to search the active components and effective targets of HQD. Ulcerative colitis effective targets were obtained by microarray data from the GEO database (GSE107499). Co-targets between HQD and ulcerative colitis are obtained by Draw Venn Diagram. PPI (Protein-protein interaction) network was constructed by the STRING database. To obtain the core target, topological analysis is exploited by Cytoscape 3.7.2. GO and KEGG enrichment pathway analysis was performed to Metascape platform, and molecular docking through Autodock Vina 1.1.2 finished. 161 active components with 486 effective targets of HQD were screened. 1542 ulcerative colitis effective targets were obtained with |Log2FC|> 1 and adjusted P-value < 0.05. The Venn analysis was contained 79 co-targets. Enrichment analysis showed that HQD played a role in TNF signaling pathway, IL-17 signaling pathway, Th17 cell differentiation, etc. IL6, TNF, IL1B, PTGS2, ESR1, and PPARG with the highest degree from PPI network were successfully docked with 19 core components of HQD, respectively. According to ZINC15 database, quercetin (ZINC4175638), baicalein (ZINC3871633), and wogonin (ZINC899093) recognized as key compounds of HQD on ulcerative colitis. PTGS2, ESR1, and PPARG are potential therapeutic targets of HQD. HQD can act on multiple targets through multi-pathway, to carry out its therapeutic role in ulcerative colitis.
| S-EPMC8741777 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2012-12-19 | E-GEOD-32149 | biostudies-arrayexpress
Project description:Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend continuously to proximal segments of the colon. Ulcerative colitis usually presents with bloody diarrhoea and is diagnosed by colonoscopy and histological findings. The aim of management is to induce and then maintain remission, defined as resolution of symptoms and endoscopic healing. Treatments for ulcerative colitis include 5-aminosalicylic acid drugs, steroids, and immunosuppressants. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. The therapeutic armamentarium for ulcerative colitis is expanding, and the number of drugs with new targets will rapidly increase in coming years.
| S-EPMC6487890 | biostudies-literature