关键词： asthma   atopic dermatitis   barrier   chronic rhinosinusitis   eosinophilic esophagitis   inflammatory bowel diseases   tight junction  

摘要： This review focuses on recent developments related to asthma, chronic rhinosinusitis, atopic dermatitis (AD), eosinophilic esophagitis, and inflammatory bowel diseases (IBD), with a particular focus on tight junctions (TJs) and their role in the pathogenetic mechanisms of these diseases. Lung, skin, and intestinal surfaces are lined by epithelial cells that interact with environmental factors and immune cells. Therefore, together with the cellular immune system, the epithelium performs a pivotal role as the first line physical barrier against external antigens. Paracellular space is almost exclusively sealed by TJs and is maintained by complex protein-protein interactions. Thus, TJ dysfunction increases paracellular permeability, resulting in enhanced flux across TJs. Epithelial TJ dysfunction also causes immune cell activation and contributes to the pathogenesis of chronic lung, skin, and intestinal inflammation. Characterization of TJ protein alteration is one of the key factors for enhancing our understanding of allergic diseases as well as IBDs. Furthermore, TJ-based epithelial disturbance can promote immune cell behaviors, such as those in dendritic cells, Th2 cells, Th17 cells, and innate lymphoid cells (ILCs), thereby offering new insights into TJ-based targets. The purpose of this review is to illustrate how TJ dysfunction can lead to the disruption of the immune homeostasis in barrier tissues and subsequent inflammation. This review also highlights the various TJ barrier dysfunctions across different organ sites, which would help to develop future drugs to target allergic diseases and IBD.

关键词： Stomas   depression   anxiety   inflammatory bowel disease  

摘要： Aim Patients with inflammatory bowel disease (IBD) are diagnosed with anxiety/depression at higher rates than the general population. We aimed to determine the frequency of anxiety/depression among IBD patients and the temporal association with abdominal surgery and stoma formation. Method We conducted a retrospective cohort study in adult patients with IBD using difference-in-difference methodology and a large commercial claims database (2003-2016). Outcomes were anxiety/depression diagnoses before and after major abdominal surgery or stoma formation. Results We identified 10 481 IBD patients who underwent major abdominal surgery, 18.8% of whom underwent stoma formation, and 41 924 nonsurgical age- and sex-matched IBD controls who were assigned random index dates. Rates of anxiety and depression increased among all cohorts (P < 0.001). Surgical patients had higher odds of anxiety [one surgery, adjusted OR 6.90 (95% CI 6.11-7.79), P < 0.001;two or more surgeries, 7.53 (5.99-9.46), P < 0.001] and depression [one surgery, 6.15 (5.57-6.80), P < 0.001;two or more surgeries, 6.88 (5.66-8.36), P < 0.001] than nonsurgical controls. Undergoing multiple surgeries was associated with a significant increase in depression from 'pre' to 'post' time periods [1.43 (1.18-1.73), P < 0.001]. Amongst surgical patients, stoma formation was independently associated with anxiety [1.40 (1.17-1.68), P < 0.001] and depression [1.23 (1.05-1.45), P = 0.01]. New ostomates experienced a greater increase in postoperative anxiety [1.24 (1.05-1.47), P = 0.01] and depression [1.19 (1.03-1.45), P = 0.01] than other surgical patients. Conclusion IBD patients who undergo surgery have higher rates of anxiety and depression than nonsurgical patients. Rates of anxiety and depression increase following surgery. Stoma formation represents an additional risk factor. These findings suggest the need for perioperative psychosocial support services.

关键词： Vedolizumab   Personalised Medicine   Precision Medicine   Endoscopic Remisison   IBD  

摘要： BACKGROUND & AIMS: We aimed to identify biomarkers that might be used to predict responses of patients with inflammatory bowel diseases (IBD) to vedolizumab therapy. METHODS: We obtained biopsies from inflamed colon of patients with IBD who began treatment with vedolizumab (n = 31) or tumor necrosis factor (TNF) antagonists (n = 20) and performed RNA-sequencing analyses. We compared gene expression patterns between patients who did and did not enter endoscopic remission (absence of ulcerations at month 6 for patients with Crohn's disease or Mayo endoscopic subscore <= 1at week 14 for patients with ulcerative colitis) and performed pathway analysis and cell deconvolution for training (n = 20) and validation (n = 11) datasets. Colon biopsies were also analyzed by immunohistochemistry. We validated a baseline gene expression pattern associated with endoscopic remission after vedolizumab therapy using 3 independent datasets (n = 66). RESULTS: We identified significant differences in expression levels of 44 genes between patients who entered remission after vedolizumab and those who did not;we found significant increases in leukocyte migration in colon tissues from patients who did not enter remission (P < .006). Deconvolution methods identified a significant enrichment of monocytes (P = .005), M1-macrophages (P = .05), and CD4+ T cells (P = .008) in colon tissues from patients who did not enter remission, whereas colon tissues from patients in remission had higher numbers of naive B cells before treatment (P = .05). Baseline expression levels of PIWIL1, MAATS1, RGS13, and DCHS2 identified patients who did vs did not enter remission with 80% accuracy in the training set and 100% accuracy in validation dataset 1. We validated these findings in the 3 independent datasets by microarray, RNA sequencing and quantitative PCR analysis (P = .003). Expression levels of these 4 genes did not associate with response to anti-TNF agents. We confirmed the presence of proteins encoded

关键词： Phytochemicals   Intestinal permeability   Inflammation   Colitis   Oxidative stress   Gut microbiota  

摘要： Gastrointestinal tract is the second largest organ in the body that mainly functions in nutrients and minerals intake through the intestinal barrier. Intestinal permeability maintains the circulation of minerals and nutrients from digested foods. Life and all the metabolic processes depend either directly or indirectly on proper functioning of GI tract. Compromised intestinal permeability and related disorders are common among all the patients with inflammatory bowel disease (IBD), which is a collective term of inflammatory diseases including Crohn's disease and ulcerative colitis. Many synthetic drugs are currently in use to treat IBD such as 5-aminosalicylic acid corticosteroids. However, they all have some drawbacks as long-term use result in many complications. These problems encourage us to look out for alternative medicine. Numerous in vitro and in vivo experiments showed that the plant-derived secondary metabolites including phenolic compounds, glucosinolates, alkaloids, terpenoids, oligosaccharides, and quinones could reduce permeability, ameliorate-related dysfunctions with promising results. In addition, many of them could modulate enzymatic activity, suppress the inflammatory transcriptional factors, ease oxidative stress, and reduce pro-inflammatory cytokines secretion. In this review, we summarized the phytochemicals, which were proven potent in treating increased intestinal permeability and related complication along with their mechanism of action.

关键词： Hypoxia   Inflammatory bowel disease   Preclinical imaging  

摘要： Accurate and sensitive imaging of hypoxia associated with inflammatory bowel disease (IBD) is significant for the precise diagnosis and treatment of this disease, but it remains a challenge for traditional hypoxia-activatable fluorescence probes because of a more moderate hypoxic state during IBD than under other pathological conditions. To address this issue, herein, we designed a hypoxia-activatable and cytoplasmic protein-powered fluorescence cascade amplifier, named HCFA, to image hypoxia associated with IBD in vivo. In our design, a 4-aminobenzoic acid (azo)-modified mesoporous silica nanoparticle (MSN) was used as a container to load black hole quencher 2 (BHQ2) and cytoplasmic protein-binding squarylium dye (SQ);then, the beta-cyclodextrin polymer (beta-CDP) combined with azo through a host-guest interaction to form HCFA. Upon passive stagnation in the inflamed tissue of IBD, the azo band would be cleaved under a hypoxic microenvironment, and SQwas released to activate the fluorescence of HCFA. Moreover, the unconstrained SQ can bind with cytoplasmic protein to exhibit drastic fluorescence intensity enhancement, realizing the fluorescence signal amplification for imaging of hypoxia. When one takes advantage of the large load capacity of MSN and the unique property of SQ HCFA can sense oxygen levels in the range of 0% to 10%. Meanwhile, the fluorescence imaging results demonstrate that HCFA can sensitively distinguish different levels of cellular hypoxia and monitor the variations of hypoxia in vivo, highlighting HCFA as a promising tool for the detection of hypoxia associated with IBD.

关键词： Inflammatory bowel diseases   Disability   Quality of life   IBD disk   IBD-disability index   Patient-reported outcomes  

摘要： Background Inflammatory Bowel Diseases (IBD) affect psychological, family, social and professional dimensions of patients' life, leading to disability which is essential to quantify as part of Patient-Reported Outcomes (PROs) newly included in the targets to reach in IBD patients. Up to now, the IBD-Disability Index (IBD-DI) was the only validated tool to assess disability, but it is not appropriate for use in clinical practice. The IBD Disk was developed, a shortened and self-administered tool, adapted from the IBD-DI, in order to give immediate representation of patient-reported disability. However, the IBD Disk has not been validated yet in clinical practice. The aims of the VALIDate study are to validate this tool in a large population of IBD patients and to compare it to the already validated IBD-DI. Methods The VALIDate study is an ongoing multicentric prospective cohort study launched in April 2018 in 3 French University Hospitals (Nantes, Rennes, Angers), with an objective to reach a sample of 400 patients over a period inclusion of 6 months. Each patient will fill in the two questionnaires IBD Disk and IBD-DI at baseline, then between 3 and 12 months later, during a follow-up visit. Clinical and socio-demographic data will also be collected. During these two consultations, gastroenterologists and patients will evaluate disease activity thanks to a semi-quantitative 4-grade scale, named respectively PGA (Physician Global Assessment) and PtGA (Patient Global Assessment). This cohort will allow to evaluate the validity of the IBD Disk with respect to the IBD-DI in order to generalize its use for clinical practice. Other psychometric criteria of the IBD Disk will also be analysed as its reliability or its discriminant capacity. Close attention will nonetheless be needed to minimize the number of lost to follow-up patients between baseline and follow-up. Discussion The VALIDate study is the study designed to validate the IBD Disk, a visual tool easily useable in

关键词： inflammatory bowel disease   dual-functionalized mesenchymal stem cells   CX3CR1   IL-25  

摘要： Mesenchymal stem cells (MSCs) have shown great promise in inflammatory bowel disease (IBD) treatment, owing to their immunosuppressive capabilities, but their therapeutic effectiveness is sometimes thwarted by their low efficiency in entering the inflamed colon and variable immunomodulatory ability in vivo. Here, we demonstrated a new methodology to manipulate MSCs to express CX3C chemokine receptor 1 (CX3CR1) and interleukin-25 (IL-25) to promote their delivery to the inflamed colon and enhance their immunosuppressive capability. Compared to MSCs without treatment, MSCs infected with a lentivirus (LV) encoding CX3CR1 and IL-25 (CX3CR1&IL-25-LV-MSCs) exhibited enhanced targeting to the inflamed colon and could further move into extravascular space of the colon tissues via trans-endothelial migration in dextran sodium sulfate (DSS)-challenged mice after MSC intravenous injection. The administration of the CX3CR1&IL-25LV-MSCs achieved a better therapeutic effect than that of the untreated MSCs, as indicated by pathological indices and inflammatory markers. Antibody-blocking studies indicated that the enhanced therapeutic effects of dual-functionalized MSCs were dependent on CX3CR1 and IL-25 function. Overall, this strategy, which is based on enhancing the homing and immunosuppressive abilities of MSCs, represents a promising therapeutic approach that may be valuable in IBD therapy.

关键词： Th17   Memory T cell   Therapeutic response  

摘要： The effect of TNF-blockers on T-lymphocyte subsets is largely unknown in inflammatory bowel diseases (IBDs). The aim of the present study was to analyze the prevalence of T-cell subtypes and their correlation to therapeutic response. Sixty-eight patients with Crohn's disease (CD), 46 with ulcerative colitis (UC) were enrolled. (1) The clinical course was followed after the initiation of TNF-blockers (prospective study). (2) The immunophenotype was also compared between long-term anti-TNF treated-responders and non-responders (cross-sectional study). The results were compared with those of therapy-naive patients with active disease and those in remission with non-biological immunosuppressive therapy, and with healthy controls. Fourteen subtypes of peripheral blood T cells were measured with flow cytometry. The prevalence of Th2 and Th17 cells, of HLA-DR- and CD69-positive CD4 and CD8 cells, was higher, whereas the percentage of CD45RA-positive CD4 and CD8 cells was lower in both IBDs than in controls. CD8CD69 cell frequency was lower in remission, and decreased during anti-TNF therapy in CD responders. CD8CD45RO memory cells had higher prevalence in UC non-responders than in those starting anti-TNF. CD4CD45RO percentage < 49.05 at the initiation of TNF-blockers was predictive of a subsequent therapeutic response in CD, and Th2 and Th17 prevalence correlated with the duration of remission on TNF-blockers in UC. This study provided a detailed description of the T-cell composition in IBDs. CD8CD69 prevalence may be an activity marker in CD, and CD4CD45RO, Th2 and Th17 levels could be predictive for a therapeutic response to anti-TNF.

关键词： Nutrigenetics   nutrigenomics   transcriptomics   proteomics   metabolomics   genome   epi-genome   microbiome   inflammatory bowel disease  

摘要： Inflammatory bowel disease is the umbrella term for a group of diseases whose incidence has been increasing over the past century. Although initial literature analyses had suggested a small number of genes, perhaps between 10 and 20, responsible for disease susceptibility, subsequent national and international collaborations have significantly modified those estimations to greater than 240, with more expected as the technologies continue to advance. As well as direct effects on the genome providing possible targets for therapy or functional foods, it is clear that the immune system, the epi-genome and the gut microbiome also play an important role in disease development and progression. While certain foods accelerate disease development in individuals carrying specific genotypes, the same foods appear beneficial to other genetic groups. Gene-nutrient-microbiota interactions also become important, and tissue culture or animal models are available to initially test hypotheses. However, genomic technologies are necessary to reveal all major effects, whether beneficial or otherwise, in animal or human studies. These technologies include transcriptomics, proteomics and metabolomics, which reveal details of what has happened in a gene-diet or gene-drug interaction. At an international level, the field originally called nutrigenomics, has now been divided into two complementary fields: nutrigenetics and nutrigenomics.

关键词： Intestinal   micro-environment   dysbiosis   Inflammatory   bowel   disease   Multi-omics   Probiotics   Fecal   microbiota   transplantation  

摘要： The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes,the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease(IBD).In the past few years,with the advances in the understanding of microbiome,its metabolites and further application of next generation sequencing,analysis of dynamic alteration of gut micro-environment was realized,which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis *** subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential *** this review,we will summarize the recent knowledge about multi-dimensional dysbiosis,the inter-action between fungus and bacteria under inflamed mucosa,and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.