关键词： Cell biology   Diseases  

摘要： Inflammatory bowel disease (IBD) is one of the most common diseases in the gastrointestinal tract related to aberrant inflammation. Pyroptosis, which is characterized by inflammasome formation, the activation of caspase-1, and the separation of the N- and C-terminals of GSDMD, might be related to IBD pathogenesis. NEK7 is an important component of the NLRP3 inflammasome in macrophages. We attempted to investigate the mechanism of NEK7 interacting with NLRP3 to modulate the pyroptosis in IBD. NEK7 mRNA and protein expression and pyroptosis-associated factors, including Caspase-1 (p45, p20), NLRP3, and GSDMD, were upregulated in IBD tissues. NEK7 knockdown abolish ATP + LPS-induced pyroptosis in vitro and improved DSS-induced chronic colitis in vivo. NEK7 interacted with NLRP3, as revealed by Co-IP and GST pull-down assays, to exert its effects. Moreover, short-term LPS treatment alone induced no significant changes in NEK7 protein level. TLR4/NF-kappa B signaling in MODE-K cells could be activated by LPS treatment. LPS-induced NEK7 upregulation could be significantly reversed by JSH-23, an inhibitor of p65. Furthermore, LUC and ChIP assays revealed that RELA might activate the transcription of NEK7 via targeting its promoter region. LPS-induced TLR4/NF-kappa B activation causes an increase in NEK7 expression by RELA binding NEK7 promoter region. In conclusion, NEK7 interacts with NLRP3 to modulate NLRP3 inflammasome activation, therefore modulating the pyroptosis in MODE-K cells and DSS-induced chronic colitis in mice. We provide a novel mechanism of NEK7-NLRP3 interaction affecting IBD via pyroptosis.

关键词： Patient experience   colonoscopy   IBD   anxiety   pain and discomfort   chronic disease  

摘要： Background: Patients with Inflammatory Bowel Disease (IBD) undergo repeated colonoscopies to monitor their lifelong disease. Objective: To describe experiences from repeated colonoscopies in patients with IBD. Methods: Within a qualitative design 33 patients with IBD who had undergone at least three colonoscopies were interviewed by telephone. Hermeneutic interpretation served as the framework of the analysis. Results: The colonoscopy procedure was explained as strenuous to undergo and interfered with daily life. It reminded patients of a lifelong disease, but the necessity of the colonoscopy, being life-saving, was highlighted. The colonoscopies entailed several unpredictable aspects - no control over pain, potential blame and unpredictable care. Shame, inferiority and uncertainty enhanced the feeling of being exposed and vulnerable. Conclusion: Repeated colonoscopies can be perceived as both an assurance of life and a reminder of a lifelong illness. Healthcare professionals need to provide support in terms of awareness of patients' vulnerability, despite extensive experience of the colonoscopy procedure. For example, person-centred care and continuity in care are potential interventions based on the results of this study. Another important aspect of care is to minimise interference in everyday life to prevent feelings of loss of the healthy self, for example by self-administrated outpatient booking systems. Summarize the established knowledge on this subject. center dot Previous research in quality related to colonoscopy has mainly focused on technical and medical aspects. center dot Knowledge based on the patients' perspective is rare and the few existing studies included mainly persons included in screening programs. What are the significant and/or new findings of this study? center dot Patients with IBD undergoing repeated colonoscopies express specific needs in several aspects related to the colonoscopy procedure: center dot Continuity and a person-centered ap

摘要： Macrophages drive the pathological process of inflammatory bowel diseases (IBD) mostly by secreting proinflammatory cytokines, such as Tnf-alpha. Recent studies have indicated the association between epigenetic modifications and macrophage functions. However, epigenetic mechanisms regulating macrophages' functional involvement in IBD remain unknown. In this study, we investigated whether the epigenetic regulator Uhrf1 plays a role in innate immunity by functionally regulating macrophages in intestines. We employed two transgenic strains of mice (one with Uhrf1 deficiency in macrophages [Uhrf1(fl/fl)Lyz2-Cre mice] and the other with the two mutations at Uhrf1's DNA methylation regulatory site [Uhrf1(YP187/188AA) mice]) to assess their susceptibility to dextran sodium sulfate-induced colitis. We examined the cytokines derived from Uhrf1(fl/fl)Lyz2-Cre and Uhrf1(YP187/188AA) macrophages in response to LPS stimulation. We also analyzed the effects of proinflammatory cytokines on Uhrf1 expression in macrophages. The data demonstrated that Uhrf1 deficiency and Uhrf1(YP187/188AA )mutation resulted in severe colitis in the dextran sodium sulfate-treated mice. In vitro analysis revealed the hypomethylation of Tnf-alpha promoter and the increased Tnf-alpha expression in Uhrf1(fl/fl)Lyz2-Cre and Uhrf1(YP187/188AA )macrophages in response to LPS stimulation, and anti-Tnf-alpha therapy implied the key role of Tnf-alpha to the aggravated colitis in Uhrf1-deficient mice. Exogenous Tnf-alpha destabilized Uhrf1 protein through ubiquitination-mediated protein degradation, triggering macrophage activation. In conclusion, we identified that Uhrf1-mediated DNA methylation controls Tnf-alpha expression of macrophages in the experimental colitis resembling IBD. The epigenetic mechanisms that activate macrophages may provide new therapeutic targets for IBD treatment.

关键词： inflammatory   bowel   neonatal  

摘要： To the Editor:The incidence of inflammatory bowel disease(IBD)has been increasing in recent years;nevertheless,neonatal IBD with IL10-RA gene mutations are rare with great therapeutic ***,we reported a case of very early onset inflammatory bowel disease(VEO-IBD)with an IL-10RA gene mutation which was effectively treated by adalimumab.

关键词： Toxicity  

摘要： Purpose: Inflammatory bowel disease (IBD) is a known risk factor for rectal cancer, and RT is often an important part of therapy for these patients. Previously published studies have raised concerns for increased rates of RT toxicity in patients with IBD. We performed a matched case-control analysis to assess RT-related toxicity in a large sample of U.S. veterans afflicted with IBD and rectal cancer. Methods and Materials: We identified 186 veterans with rectal cancer (71 Patients with IBD treated with RT, 71 matched controls without IBD treated with RT, and 44 nonmatched controls with IBD treated without RT) diagnosed between 2000 and 2015. We analyzed short- and long-term toxicity and mortality in multivariable logistic regression, Fine-Gray, and frailty models, adjusting for potential confounders. Results: When comparing patients with and without IBD treated with RT there were no differences in RT breaks (adjusted odds ratio [aOR], 1.70;95% confidence interval [CI], 0.38-4.76;P = .49) or the need for antidiarrheal medication during RT (aOR, 1.53;95% CI, 0.70-3.35;P = .29). There was a trend toward higher risk of hospital admission during RT for RT thorn patients with IBD (aOR, 2.69;95% CI, 0.88-8.22;P = .08). There were higher rates of small bowel obstruction (OR, 15;95% CI, 1.9-115;P = .009) and a trend toward higher rates of abdominopelvic adhesions (OR, 3.6;95% CI, 0.98-13;P = .05) in the RT + IBD cohort. However, compared with a nonmatched cohort of patients with IBD treated without RT there were no differences in long-term complications. No differences were found in other acute or long-term toxicities. Rectal cancer-specific mortality appeared similar across all cohorts. Conclusions: RT does not appear to increase the rates of acute or long-term toxicity in patients with IBD and should be considered a standard part of therapy when otherwise indicated. (C) 2019 Elsevier Inc. All rights reserved.

摘要： Background Spondyloarthritis is the most frequent extra-intestinal manifestation of IBD. Aim To present simple strategies to identify and differentiate inflammatory joint pain in IBD patients. Methods A panel of Belgian gastroenterologists and rheumatologists developed seven algorithms for IBD patients with joint symptoms based on a Delphi exercise conducted between April and December 2016. Here, we focus on referral strategies for patients with chronic back pain (evidence-based strategy), large joint monoarthritis, oligo- or polyarticular arthritis or arthralgia (based on expert opinion). We also present management tools for IBD patients with acute back pain and small joint monoarthritis (Supplementary file). Results The reported algorithm for IBD patients with chronic back pain uses basic clinical criteria to identify which patients should be referred to the emergency room (spondylodiscitis), physical medicine and rehabilitation (mechanical back pain) or rheumatologist (spondyloarthritis). IBD patients with large joint monoarthritis should be referred to emergency room if septic arthritis is suspected;in other patients, blood analyses and referral to a rheumatologist for articular puncture with evacuation of synovial fluid are recommended. The analysis of synovial fluid allows for identification of non-inflammatory (e.g., osteoarthritis) and inflammatory (e.g., [pseudo]-gout, peripheral spondyloarthritis and Borrelia burgdorferi arthritis) conditions. In patients with inflammatory oligoarticular or polyarticular arthralgia, erythrocyte sedimentation rate, concomitant therapies, anti-nuclear factor and anti-double-stranded DNA antibody levels should be evaluated;in anti-tumour necrosis factor-treated patients, a drug-induced lupus-like syndrome should be considered. Conclusions We propose straightforward strategies for IBD patients with joint symptoms, which are specific enough to select initial treatment and referral pattern.

关键词： Pediatric IBD   Illness uncertainty   Illness intrusiveness   Depressive symptoms  

摘要： Youth with inflammatory bowel disease (IBD) and their parents are at increased risk for psychological adjustment difficulties, potentially due to the uncertain and intrusive nature of IBD. However, empirical investigations have yet to assess the contribution of these unique disease features to adjustment outcomes. Our aim was to examine: 1) the influence of youth and parent perceptions of illness uncertainty and illness intrusiveness on youth adjustment;and 2) examine the influence of youth and parent perceived uncertainty and intrusiveness on parent adjustment. Youth with IBD (N = 107) and their primary caregiver completed measures of illness uncertainty, illness intrusiveness, and psychological adjustment. Results revealed that youth illness uncertainty was more closely associated with youth depressive symptoms than was youth perceived intrusiveness. Further, youth illness perceptions were more closely associated with youth depressive symptoms compared to parent perceptions;however, results also suggested that parent illness perceptions may indirectly impact youth adjustment through their influence on youth illness perceptions. Finally, parent illness intrusiveness demonstrated a more robust association with parent adjustment compared to parent illness uncertainty, and both youth and parent illness intrusiveness were independently related to parent adjustment. Findings highlighted the transactional nature of adjustment in pediatric IBD and the importance of examining clinically relevant youth and parent subjective illness perceptions, like uncertainty and intrusiveness, in investigations of youth and parent adjustment outcomes in this population.

关键词： anti-TNF agents   inflammatory bowel disease   switching therapy   vedolizumab  

摘要： Background and Aim Vedolizumab (VDZ) has been used in inflammatory bowel disease (IBD) patients who failed anti-tumor necrosis factor (TNF) therapy. This study was to examine long-term outcome of IBD patients switching to VDZ from anti-TNF agents for reasons other than failure of therapy. Methods Inflammatory bowel disease patients at the University of Chicago IBD center who were in clinical remission with anti-TNF therapy and then electively changed to VDZ due to reasons other than loss of response were retrospectively analyzed. The primary outcome was the durability of clinical remission maintained by VDZ as assessed by Kaplan-Meier survival analysis. The proportion of patients in clinical and endoscopic remission at 6-12 months after switching to VDZ therapy was analyzed. Results A total of 41 patients (36 with Crohn's disease and 5 with ulcerative colitis) met the inclusion criteria and were in clinical remission at the time of switch. The majority of patients switched therapy due to adverse effects (56.1%) or infections (14.6%). During a median duration of 30 months (range 7-52) of VDZ therapy, 34 (82.9%) were in VDZ-maintained clinical remission. One (2.4%) and four (9.8%) patients discontinued VDZ due to flare and adverse effects, respectively. Endoscopic remission was present in 25 of 30 patients (83.3%) who had a follow-up colonoscopy. Conclusions Vedolizumab was effective and safe in maintaining remission in IBD patients who switched from anti-TNF agents due to reasons other than failure of therapy. Our results suggest that switching anti-TNF remitters to VDZ treatment is a safe practice in specific patient populations.

关键词： lives with children   Mother   life   Administration of BCG vaccine   Attenuated Vaccines   Vaccines   abandoned children   Child  

摘要： Background Children born to mothers with IBD may be exposed to anti-TNF alpha agents antenatally. Current European guidelines recommend postponing live vaccines until after 6 months of life in this population. Data on the safety of live vaccines administration in the first year of life of these children are sparse with one reported fatality following bacillus Calmette-Guerin (BCG) administration. Aims To describe the use and safety of vaccines administered in children born to mothers with IBD and exposed antenatally to anti-TNF alpha agents Methods Data from children born to mothers with IBD between 2013 and 2014 were collected retrospectively from the French Health Insurance Database. Vaccines recommended before or at 1 year of age were considered. Results Among 4741 children, 670 (14.1%) were exposed to anti-TNF alpha agents antenatally, with concomitant thiopurines in 16.0% (n = 107) and steroids in 19.3% (n = 214). Among these 670 children, 315 (47%) were exposed up to delivery. Exposed children were less likely than non-exposed to receive BCG (88/670, 13.1% vs 780/4071, 19.2% respectively, P < .05) and received it later in life (months, mean +/- SD, 4.3 +/- 3.9 and 2.4 +/- 2.9 respectively, P < .001). In exposed children, 64/88 (73%) received BCG vaccination before 6 months of age, but with no BCG-related severe adverse event observed during the first year. Uptake of other vaccines recommended before 6 months was above 85% in both groups. Conclusion In children exposed antenatally to anti-TNF alpha agents, vaccinations are often not postponed in keeping with the recommendations, but no BCG-related severe adverse events were reported in children vaccinated before 6 months of life.