摘要： LINKED CONTENT This article is linked to McCurdy et al and McCurdy papers. To view these articles, visit and .

关键词： Arthritis   Inflammatory bowel disease   PPI interactions   Pathway analysis   Microarray analysis   Topology analysis  

摘要： 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. Microarray data analysis of datasets involving IBD affected and AS affected vs controls were done to explore the differentially expressed genes (DEGs). In majority of the datasets, the common DEGs found were sterile alpha motif domain containing 9 like (SAMD9L), inhibin beta A subunit (INHBA), transmembrane protein 45A (TMEM45A) and transmembrane and tetratricopeptide repeat containing 1 (TMTC1). The common functions and pathways found between the DEGs were control of macromolecule metabolism process, control of metabolic process, control of primary metabolic process, and control of protein metabolic process, cell differentiation, organ development, single-organism development process, multicellular organism development process, development of system, single-multicellular organism development process, developmental process, development of anatomical structure, multicellular organismal development process, control of biological process, cell proliferation, hematopoietic progenitor cell differentiation and immune system process. TMTC1 and INBHA were found to be more biologically significant genes according to the topological properties of the network. This study also suggests that TMTC1, INBHA, TMEM45A and SAMD9L DEGs and their accompanying pathways might have the potential to be exploited as drug targets and biomarkers in the diagnosis and/or treatment of IBD linked arthritis and warrants for further experimental validation.

关键词： enrichment analysis   gene expression profiling   inflammatory bowel disease   integrative analysis   transcriptome-wide association study  

摘要： Inflammatory bowel disease (IBD) is a complex disease, resulting from abnormal immune response to intestinal tract microbiota in genetically susceptible individuals. Crohn's disease and ulcerative colitis (UC) are the two major types of IBD. Transcriptome-wide association study (TWAS) of IBD was first performed using a large-scale genome-wide association study summary data sets of IBD. The FUSION software was applied for TWAS, considering various tissues and cells. The genes identified by TWAS were then validated by the gene expression profiling data sets of IBD. The functional annotation and potential pathways of common differentially expressed genes were further subjected to gene ontology (GO) and pathway enrichment analysis. Integrative analysis of TWAS and messenger RNA (mRNA) expression data detected several tissues related common genes for UC, such as HLA-DRB1 (P-TWAS = 0.024;mRNA expression ratio = 1.700) and TAP2 in colon (P (TWAS) = 0.047;mRNA expression ratio = 2.170). Further comparing the GO enrichment analysis results of TWAS and mRNA expression data, we identified 11 common GO terms for UC, such as plasma membrane (P value = 5.08 x 10(-10)) in intestinal tissues and immune response (P = 0.001) in peripheral blood. We also detected several common pathways for UC, including cell adhesion molecules (P = 0.003) in intestinal tissues, IBD (P = 0.049) in whole blood and phagosome (P = 0.0003) in peripheral blood. Our study results provide novel clues for understanding the genetic mechanism of IBD.

关键词： Education   inflammatory bowel disease   primary healthcare   referral  

摘要： Background/Aims: Inflammatory bowel disease (IBD) is a chronic inflammatory condition that requires early diagnosis and proper management. Patients with early symptoms of IBD are typically evaluated first by primary healthcare (PHC) physicians, who in turn refer patients with suspected IBD to specialists. Therefore, we aimed to assess the knowledge and attitude of PHC physicians toward IBD. Materials and Methods: We conducted a comparative cross-sectional survey of PHC physicians practicing at the Ministry of Health PHC centers in Jeddah, KSA. Demographics and data on the knowledge and practices of physicians were collected through a predefined and tested questionnaire that included three domains (Eaden, Leong, and Sign/Symptom Awareness). A subgroup of the cohort was educated about IBD referral criteria (group A, n = 65) prior to study initiation and their responses were compared with those from the remaining group (group B, n = 135). Regression analysis was used to test associations with the significance threshold set at 5%. Results: A total of 211 PHC physicians were surveyed with a response rate of 95%. Female physicians comprised 66.5% of the cohort and the mean age was 32.26 +/- 6.6 years. About 91% of physicians were Saudi nationals, and 75.5% were MBBS degree holders. The majority of the respondents (93%) reported seeing zero to five patients with 1BD per month, and almost half of the physicians preferred to always refer patients to specialists (49.5%). Most of the respondents were uncomfortable (3.27 +/- 1.4 to 4.35 +/- 1.2) with initiating or managing specific medical therapies (maintenance therapy, therapy for acute flare, corticosteroids, immunomodulators, and biologics) for patients with IBD. With regard to knowledge, group A had higher scores in all three domains especially in the Sign/Symptom Awareness domain (mean score 6.17 +/- 1.1 vs. 3.5 +/- 1.01, P < 0.001). According to multivariate analyses, both groups' knowledge showed no significant relation

摘要： There continues to be a major need for more effective inflammatory bowel disease (IBD) therapies. IL-13R alpha 2 is a decoy receptor that binds the cytokine IL-13 with high affinity and diminishes its STAT6-mediated effector functions. Previously, we found that IL-13R alpha 2 was necessary for IBD in mice deficient in the anti-inflammatory cytokine IL-10. Here, we tested for the first time a therapeutic antibody specifically targeting IL-13R alpha 2. We also used the antibody and Il3r alpha 2(-/-) mice to dissect the role of IL-13R alpha 2 in IBD pathogenesis and recovery. Il13r alpha 2(-/-) mice were modestly protected from induction of dextran sodium sulfate (DSS)-induced colitis. Following a 7-day recovery period, Il13r alpha 2(-/-) mice or wild-type mice administered the IL-13R alpha 2-neutralizing antibody had significantly improved colon health compared to control mice. Neutralizing IL-13R alpha 2 to increase IL-13 bioavailability promoted resolution of IBD even if neutralization occurred only during recovery. To link our observations in mice to a large human cohort, we conducted a phenome-wide association study of a more active variant of IL-13 (R130Q) that has reduced affinity for IL-13R alpha 2. Human subjects carrying R130Q reported a lower risk for Crohn's disease. Our findings endorse moving anti-IL-13R alpha 2 into preclinical drug development with the goal of accelerating recovery and maintaining remission in Crohn's disease patients.

关键词： Physical activity   Exergaming   Inflammatory bowel disease   Pediatrics   Inflammation  

摘要： Background Evidence is growing that both short- and long-term physical exercise have the potential to positively impact on the physiological system related to inflammatory indices, though, such patterns are unknown for pediatric patients with Inflammatory Bowel Disease (IBD). The aim of the present intervention study was to investigate the influence of a single bout and chronic moderate-intensity exercise on IBD-related inflammatory indices and exercise capacity among pediatric individuals with IBD and healthy controls. Method Twenty-one pediatric patients with IBD, split into a "remission-group" (IBD-RE;n = 14) and an "active disease group" (IBD-AD;n = 7), were compared to 23 age matched healthy controls (HC). All participants completed a single bout of exercise at baseline and an 8-week exercise intervention. Before and after the single bout of exercise IBD-related inflammatory indices (erythrocyte sedimentation rate (ESR), albumin, C-reactive protein (CRP), cortisol, hemoglobin, hematocrit, thrombocytes and leukocytes) were assessed. Results At baseline, after a single bout of exercise, inflammation (albumin, hemoglobin, erythrocytes, hematocrit and leukocytes) increased in all three groups IBD-AD, IBD-RE and HC. CRP and thrombocytes were only elevated in IBD-AD and IBD-RE, compared to HC. After a longer-term exercise intervention, ESR, CRP and thrombocytes significantly decreased in all groups. The longer-term exercise intervention did not decrease acute immunopathologic responses after a single bout of exercise, compared to baseline. Conclusion Whereas a single bout of exercise increases albumin, erythrocytes and leukocytes, longer-term moderate-intensity exercise reduced inflammatory markers in pediatric patients with IBD. Children and teenagers with IBD should be encouraged to engage in regular moderate-intensity exercise activities, as such activities may contribute to inflammation suppression and improved disease management.

摘要： The current understanding of inflammatory bowel disease (IBD) pathogenesis implicates a complex interaction between host genetics, host immunity, microbiome, and environmental exposures. Mechanisms gleaned from genetics and molecular pathogenesis offer clues to the critical triggers of mucosal inflammation and guide the development of therapeutic interventions. A complex network of interactions between host genetic factors, microbes, and microbial metabolites governs intestinal homeostasis, making classification and mechanistic dissection of involved pathways challenging. In this Review, we discuss these challenges, areas of active translation, and opportunities for development of next-generation therapies.

关键词： Inflammatory bowel disease   cutaneous manifestations   probiotics  

摘要： Background: Inflammatory bowel diseases (IBDs) are associated with extraintestinal manifestations including skin lesions. The intestinal microflora plays a key role in the development and course of IBD. Aim: To examine the efficacy of probiotics and the occurrence of skin lesions in patients with IBD. Methods: The occurrence of cutaneous lesions in IBD patients from Northern Sardinia was analyzed according to demographic, anthropometrics, clinical features, treatments, and probiotic use expressed as the ratio of disease duration under probiotic treatment and the total disease duration. Results: In 170 IBD patients (59.4% women;UC: 61.2%) at least one skin lesion was present (8.2%) at diagnosis and in 30.6% developed during the follow-up. Psoriasis, erythema nodosum, and pyoderma gangrenosum were the most frequent. An inverse trend was observed between probiotics use and skin lesions occurrence after adjusting for confounders, including conventional treatment for IBD. The risk of developing at least one skin lesion was 1.40 for probiotic use between 5-19% of disease duration and 0.3 for probiotic use > 50%. Body mass index, Crohn phenotype, marriage, and potency of IBD-treatment were significant predictors for developing skin lesions. Conclusion: These findings suggest that probiotics may be an additional tool in the treatment of IBD.

关键词： Inflammatory bowel disease   Non-coding RNA   Intestinal barrier  

摘要： Aims: The role of long non-coding RNA's (lncRNA) in the biology of ulcerative colitis (UC) is not well understood. We have previously detected changes in lncRNA's associated with UC. This study aims to characterize one specific lncRNA, CDKN2B-AS1 whose expression was downregulated in UC patients. Main methods: UC biopsies were used to determine the levels of linear and circular CDKN2B-AS1 relative to healthy controls. In situ hybridization was used to determine the localization of CKDN2B-AS1 in the colon. The intestinal epithelial cell line, Caco-2, was used to study the effects of shRNA mediated loss of CDKN2B-AS1. Transepithelial electrical resistance was used to measure barrier function. An RT-PCR array, immunoblots and immunohistochemistry were used to determine tight junction proteins that CDKN2B-AS1 regulates. Key findings: CDKN2B-AS1 is transcribed into not only linear transcripts but also as circular RNA through back-splicing and both forms are decreased in IBD. CDKN2B-AS1 is expressed mainly in colonic epithelial cells. Cells with down-regulated CDKN2B-AS1 exhibited increased proliferation and no alterations in apoptosis. Targeting both the linear and circular transcripts of CDKN2B-AS1 with short hairpin RNAs enhanced barrier function. We subsequently determined that Claudin-2, a "leaky Claudin" known to decrease barrier function, was decreased in CDKN2B-AS1 knockdown cells. Significance: This study identifies a novel lncRNA with both linear and circular transcripts affecting UC biology.

关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Small-molecule  

摘要： Inflammatory bowel disease (IBD) is a chronic, debilitating condition with a significant impact on quality of life. In spite of recent advances with antibody therapies, there remains a significant unmet medical need in IBD. Ongoing research and development efforts aim to identify new therapies that will increase remission rates beyond those achieved with current standard-of-care, while maintaining a high safety margin. This review will provide an overview of the small-molecule agents that are being explored in this regard.