关键词： inflammatory bowel disease   resveratrol   mechanism   bioavailability   metabolites  

摘要： Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, comprising ulcerative colitis (UC) and Crohn's disease (CD). Progression of IBD leads to long-term impairment of intestinal structure and function. The pathogenesis of IBD is complex, involving environmental, immunological, genetic, microbial, and psychological factors. The conventional therapies and many existing biopharmaceuticals for IBD have limited efficacy or adverse effects. As a promising safe and effective therapy for IBD, resveratrol has been studied widely, as it has shown anti-inflammatory and antioxidant activity. Resveratrol's mechanism of action involves multiple immune responses and signaling pathways;it is absorbed quickly and metabolized into various derivatives. However, the poor water solubility and low bioavailability of resveratrol limit its clinical applications. Further research should attempt to improve the stability and oral bioavailability of resveratrol by modification and various delivery systems.

关键词： Microbial diversity   16S rDNA   Inflammatory bowel disease (IBD)   Statistical analysis  

摘要： Inflammatory bowel disease (IBD) is a multifactorial disease including both genetic and environmental factors. We compared the diversity of intestinal microbesamong a cohort of IBD patients to study the microbial ecological effects on IBD. Fecal samples from patients were sequenced with next generation sequence technology at 16S rDNA region. With statistical tools, microbial community was investigated at different level. The gut microbial diversity of Crohn's disease (CD) patients and colonic polyp (CP) patients significantly different from each other. However, the character of ulcerative colitis (UC) patients has of both CD and CP features. The microbial community from IBD patients can be very different (CD patient) or somewhat similar (UC patients) to non-IBD patients. Microbial diversity can be an important etiological factor for IBD clinical phenotype.

关键词： SEROTONIN   INFLAMMATORY bowel disease treatment   NEUROENDOCRINE system   GASTROINTESTINAL hormones   MUCOUS membrane  

摘要： Background: Serotonin (5-hydroxytryptamine, 5-HT) is an important mediator of every major gut-related function. Recent investigations also suggest that 5-HT can influence the development and severity of inflammation within the gut, particularly in the setting of inflammatory bowel disease (IBD). Aim: To review the roles that the intestinal serotonin signalling system plays in gut function, with a specific focus on IBD. Methods: We reviewed manuscripts from 1952 to 2017 that investigated and discussed roles for 5-HT signalling in gastrointestinal function and IBD, as well as the influence of inflammation on 5-HT signalling elements within the gut. Results: Inflammation appears to affect every major element of intestinal 5-HT signalling, including 5-HT synthesis, release, receptor expression and reuptake capacity. Importantly, many studies (most utilising animal models) also demonstrate that modulation of selective serotonergic receptors (via agonism of 5-HT4R and antagonism of 5-HT3R) or 5-HT signal termination (via serotonin reuptake inhibitors) can alter the likelihood and severity of intestinal inflammation and/or its complicating symptoms. However, there are few human studies that have studied these relationships in a targeted manner. Conclusions: Insights discussed in this review have strong potential to lead to new diagnostic and therapeutic tools to improve the management of IBD and other related disorders. Specifically, strategies that focus on modifying the activity of selective serotonin receptors and reuptake transporters in the gut could be effective for controlling disease activity and/or its associated symptoms. Further studies in humans are required, however, to more completely understand the pathophysiological mechanisms underlying the roles of 5-HT in this setting.

关键词： Crohn's Disease   Biologics   Pharmacokinetics   Serum Drug Level  

摘要： BACKGROUND & AIMS: It is not clear whether combination therapy with immunomodulators affects the immunogenicity of tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel disease. We performed a meta-analysis to quantify the effects of combined immunomodulator therapy on the presence of antibodies against TNF antagonists (antidrug antibodies [ADAs]) and trough levels of anti-TNF agents. METHODS: We systematically searched publication databases for studies that reported prevalence of ADAs in patients who received anti-TNF agents. Raw data from studies that met the inclusion criteria were pooled to determine effect estimates. We performed subgroup and metaregression analyses to determine the level of heterogeneity among study outcomes. RESULTS: We analyzed findings from 35 studies that met inclusion criteria (results reported from 6790 patients with inflammatory bowel disease). The pooled risk ratio for formation of ADAs in patients receiving combined therapy with immunomodulators, versus that of patients receiving anti-TNF monotherapy, was 0.49 (95% confidence interval, 0.41-0.59;P < .001). However, the pooled analysis did not demonstrate a significant difference in trough levels of anti-TNF agents between patients with versus without concurrent use of immunomodulators (standardized mean difference, 0.11;95% confidence interval, 0.19-0.41;P = .47). Subgroup analyses of patients treated with different TNF antagonists revealed no difference in the formation of ADAs (P = .50 for interaction);the protective effect of immunomodulators did not differ with type of drug patients were given (methotrexate vs thiopurines), or assay for ADA. We observed heterogeneity only among studies of patients with ulcerative colitis (I-2 = 76%). Funnel plot and Egger test analyses indicated publication bias in the studies (P = .001). CONCLUSIONS: In a meta-analysis of published studies, we associated combined treatment with immunomodulators with reduced risk of formation

关键词： Proteomics   Inflammatory bowel disease   Biomarkers   Animal models of colitis, inflammation  

摘要： Recently, proteomics studies have provided important information on the role of proteins in health and disease. In the domain of inflammatory bowel disease, proteomics has shed important light on the pathogenesis and pathophysiology of inflammation and has contributed to the discovery of some putative clinical biomarkers of disease activity. By being able to obtain a large number of specimens from multiple sites and control for confounding environmental, genetic, and metabolic factors, proteomics studies using animal models of colitis offered an alternative approach to human studies. Our aim is to review the information and lessons acquired so far from the use of proteomics in animal models of colitis. These studies helped understand the importance of different proteins at different stages of the disease and unraveled the different pathways that are activated or inhibited during the inflammatory process. Expressed proteins related to inflammation, cellular structure, endoplasmic reticulum stress, and energy depletion advanced the knowledge about the reaction of intestinal cells to inflammation and repair. The role of mesenteric lymphocytes, exosomes, and the intestinal mucosal barrier was emphasized in the inflammatory process. In addition, studies in animal models revealed mechanisms of the beneficial effects of some therapeutic interventions and foods or food components on intestinal inflammation by monitoring changes in protein expression and paved the way for some new possible inflammatory pathways to target in the future. Advances in proteomics technology will further clarify the interaction between intestinal microbiota and IBD pathogenesis and investigate the gene-environmental axis of IBD etiology.

关键词： IBD   Crohn's disease   Ulcerative colitis   NLRP3 inflammasome   ATG16L1  

摘要： NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1 beta to IL-1 beta. To investigate NLRP3 inflammasome activation in inflammatory bowel disease. Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1 beta, IL-6, and TNF alpha were measured in cell supernatants and concentration of pro-IL-1 beta was measured in cell lysates. NLRP3 activation was defined as more than 30% increase in IL-1 beta production after MSU addition. In separate experiments, PBMCs were lysed for RNA isolation transcripts of IL-1 beta, TNF alpha, NLRP3, and CASP1 were measured by RT-PCR. DNA was isolated from CD patients for ATG16L1 gene genotyping. NLRP3 inflammasome was activated in 60% of CD patients compared to 28.6% of controls (p = 0.042);no significant difference was detected between UC and controls. Among UC patients, NLRP3 activation was associated (p = 0.008) with long-standing disease (> 1.5 years). IL-1 beta levels were significantly higher in CD patents in comparison with controls (p = 0.032). No difference was detected in the levels of IL-6, TNF alpha, pro-IL-1 beta and in the numbers IL-1 beta, TNF alpha, NLRP3, and CASP1 transcripts among groups. IL-1 beta production was similar between carriers of wild-type and of SNP alleles of the rs2241880. NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease.

关键词： Incisional hernia   Mesh repair   Hernia recurrence   Crohn's disease   Ulcerative colitis   Enterocutaneous fistula  

摘要： Background: Incisional Hernia (IH) repair in patients with Inflammatory Bowel Disease (IBD) has not been well studied. Methods: Outcomes of 170 patients with IBD who underwent IH repair were included in the study. Results: The incidence of recurrence after IH repair in IBD is 27%. Patients with Crohn's disease (CD) had larger defects at the time of repair, higher proportion of bowel resection and a longer postoperative stay when compared to Ulcerative colitis (UC). The only significant predictor of recurrence after IH repair was the number of previous bowel resections prior to hernia repair (HR 1.59, p < 0.01). Three cases (10%) of late onset enterocutaneous fistulas were identified in patients who underwent IH repair with synthetic mesh inlay. Conclusion: Surgical repair results in a recurrence of IH in 27% of patients with IBD. The number of previous bowel resections is the only factor that correlates with development of recurrent IH in IBD. Published by Elsevier Inc.

关键词： neutrophils   immunomodulation   inflammatory bowel diseases   CD177  

摘要： Inflammatory bowel diseases (IBD), comprising of ulcerative colitis and Crohn's disease, are inflammatory disorders of the gastrointestinal tract characterized by chronically relapsing mucosal inflammation. Neutrophils, as the effector cells of acute inflammation, have long been reported to play a role in the maintenance of intestinal homeostasis and pathogenesis of IBD. At the early stage of mucosal inflammation in patients with IBD, neutrophils flood into intestinal mucosa, phagocytose pathogenic microbes, and promote mucosal healing and resolution of inflammation. However, large numbers of neutrophils infiltrating in the inflamed mucosa and accumulating in the epithelia cause damage of mucosal architecture, compromised epithelial barrier and production of inflammatory mediators. In this review we discuss the critical roles of neutrophils in modulating innate and adaptive immune responses in intestinal mucosa, and, importantly, clarify the potential roles of neutrophils related to their production of inflammatory mediators, transenthothelial and transepithelial migration into intestinal mucosa, and the underlying mechanisms in regulating mucosal inflammation of IBD. Moreover, we also describe a new subset of neutrophils (i.e., CD177(+) neutrophils) and illustrate its protective role in modulating intestinal mucosal immune responses in IBD.

关键词： ileal diversion   inflammatory bowel disease-unclassified   ostomy  

摘要： Objectives: Diverting ileostomy is used as a temporizing therapy in patients with perianal Crohn disease;however, little data exist regarding its use for colonic disease. The primary aim of the present study was to determine the role of diversion in severe refractory colonic inflammatory bowel disease (IBD) in a pediatric population. Methods: Retrospective study of patients who underwent diverting ileostomy at The Children's Hospital of Philadelphia from 2000 to 2014 for the management of severe, refractory colonic IBD. Clinical variables were compared in the 1 year before ileostomy and 1 year after diversion. Surgical and disease outcomes including changes in diagnosis were reviewed through 2015. Results: Twenty-four patients underwent diverting ileostomy for refractory colonic disease. Initial diagnoses were Crohn disease in 10 (42%), ulcerative colitis in 1 (4%), and IBD-unclassified in 13 patients (54%). Comparing data before and after surgery, there were statistically significant improvements in height and weight velocities, height velocity z score, blood transfusion requirement, hemoglobin, and hospitalization rates. Chronic steroid use decreased from 71% to 22%. At the conclusion of the study, 10 patients had undergone subsequent colectomy, 7 had successful bowel reanastomosis, and 7 remain diverted. Seven patients (29%) had a change in diagnosis. There were 13 surgical complications in 7 subjects, including prolapse reduction, stoma revision, and resection of ischemic bowel. Conclusions: In pediatric patients with refractory colonic IBD, diverting ileostomy can be a successful intervention to induce clinical stability. Importantly, diversion is a steroid-sparing therapy and allows additional time to clarify the diagnosis.

关键词： hypercoagulability   inflammatory bowel disease   low-molecular-weight heparins   thrombophilia   thrombosis   thrombosis prophylaxis  

摘要： The close relationship between inflammation and thrombosis affects the progression and severity of inflammatory bowel disease (IBD). The prevalence of venous thromboembolism (VTE) varies between 1% and 7% among patients with IBD. The VTE risk in patients with IBD is at least 3 times higher than that in the normal general population. The absolute risk is very high during hospitalization, active disease, and surgery. The IBD-related VTE occurs at younger ages and recurs more frequently. The development of thrombosis in IBD is due to the interaction of many hereditary and acquired risk factors. Each patient diagnosed with IBD should be evaluated for a personal and family history of thrombosis and for prothrombotic drug use. Although procoagulant factors are increased during the natural course of inflammation, natural anticoagulants and fibrinolytic activity are decreased. Although IBD is accepted as a prothrombotic condition, there is no treatment that can remove this risk from daily practice. Patient training is required to control important factors, such as long-term immobilization and smoking. Oral contraceptives and hormone replacement therapy should be avoided. Inducing permanent disease remission must be the key approach for the prevention of thrombosis. Low-molecular-weight heparin (LMWH) is the basis of prophylactic treatment, which reduces the thrombosis risk by 50%. Prophylaxis with LMWH should be administered to all patients with IBD hospitalized due to disease attack or surgery. Long-term or even life-long anticoagulation therapy should be planned if there is insufficient disease control, recurrent VTE attacks, positive thrombophilia tests, or thrombosis in vital veins.