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inflammatory bowel disease and risk of ophthalmic inflammation-related diseases:a two-sample Mendelian randomization study

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International Journal of Ophthalmology(English edition) 2024年第11期17卷 2100-2108页

作者： Shao-Jie Ren Ting Liu Man-Hong Xu Wei Shi Xiao-Rong Li Tianjin Key Laboratory of Retinal Functions and diseases Tianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Department of Orthopedics Tianjin Medical University General HospitalTianjin 300052China Dingzhou Maternal and Child Health Hospital Dingzhou 073000Hebei ProvinceChina

AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)***:Genetic instruments associated with inflammatory bowel disease(IBD),ulcerative colitis(UC),and Crohn’s disease(CD)were derived from the largest genome-wide association studies(GWAS)published to *** FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis,keratitis,iridocyclitis,chorioretinitis,episcleritis,and optic *** participants were of European *** methods which included inverse variance weighting(IVW),weighted median(WM),and MR-Egger regression were performed to estimate the causal association in this *** took the inverse variance of each study as the weight to calculate the weighted average of effect sizes,to summarize the effect sizes of multiple independent studies,which could provide the most precise estimated *** was used as the primary outcome,while WM and MR-Egger were used to improve the estimation of ***:A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis,keratitis,iridocyclitis,and optic neuritis,but not on chorioretinitis or *** Bonferroni correction,the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis(IVW:OR,1.17;95%CI,1.10-1.24,P=2.54×10^(-7)).CD was significantly associated with conjunctivitis(IVW:OR,1.05;95%CI,1.03-1.08,P=3.20×10^(-5)),keratitis(IVW:OR,1.06;95%CI,1.02-1.09;P=1.13×10^(-3)),and iridocyclitis(IVW:OR,1.09;95%CI,1.04-1.14;P=1.43×10^(-4)).CONCLUSION:IBD causally poses a risk of inflammation of conjunctiva,cornea,Iris-ciliary body complex,and optic *** is more closely associated with the eye inflammation than *** impliy that the relationship of IBD and different parts of the eye structure are different,and provide novel evidence linking based on the association of the gu

关键词： inflammatory bowel disease ulcerative colitis Crohn’s disease ocular inflammation Mendelian randomization

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Biologics in the management of pediatric inflammatory bowel disease:When and what to choose

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World Journal of Clinical Pediatrics 2025年第1期14卷 21-45页

作者： Arghya Samanta Anshu Srivastava Department of Pediatric Gastroenterology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014Uttar PradeshIndia

Pediatric inflammatory bowel disease(PIBD)is a chronic inflammatory disorder of the gastrointestinal tract,with rising global incidence and *** the past two decades,biologics have added to the therapeutic armamentarium and revolutionized the approach to treatment of inflammatory bowel *** available biologics include monoclonal antibodies which target inflammatory cytokines(anti-tumor necrosis factor alpha,anti-interleukin 12/23)or recruitment of leucocytes to the gastrointestinal tract(anti-alpha4beta7 integrin)and small molecules(Janus kinase inhibitors,sphingosine 1-phosphate-inhibitors)which modify the proinflammatory *** their potential disease-modifying ability,recent pediatric guidelines from the West have advocated upfront use of biologics in appropriate clinical scenarios as a top-down approach rather than the conventional step-up *** real-world studies are available regarding the clinical efficacy of biologics in PIBD,there is paucity of long-term outcome and safety data in ***,little information is available about the best approach in the newly industrialized-developing countries where PIBD is rising but at the same time,infections are prevalent and resources are *** this review,we summarize the efficacy and safety profile of biologics and small molecule drugs and discuss the challenges in the management of PIBD,especially in the developing world,and future directions.

关键词： Biologics Children inflammatory bowel disease Therapeutic drug monitoring Dual biologic

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Procyanidin C1 Modulates the Microbiome to Increase FOXO1 Signaling and Valeric Acid Levels to Protect the Mucosal Barrier in inflammatory bowel disease

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Engineering 2024年第11期42卷 108-120页

作者： Xifan Wang Pengjie Wang Yixuan Li Huiyuan Guo Ran Wang Siyuan Liu Ju Qiu Xiaoyu Wang Yanling Hao Yunyi Zhao Haiping Liao Zhongju Zou Josephine Thinwa Rong Liu Department of Obstetrics and Gynecology Columbia UniversityNew YorkNY 10032USA Food Laboratory of Zhongyuan Luohe 462000China Department of Internal Medicine Department of MicrobiologyUT Southwestern Medical CenterDallas 75390-9030USA

inflammatory bowel disease(IBD)refers to a pair of prevalent conditions(Crohn’s disease and ulcerative colitis)distinguished by persistent inflammation of the large *** C1(PCC1)is a natu-rally occurring substance derived from grape seeds that has demonstrated notable anti-inflammatory *** study examines the potential utility of PCC1 as a treatment for IBD and subsequently examines the host-cell-and microbiome-related mechanisms underlying the detected therapeutic *** with a classic dextran sodium sulfate(DSS)-induced mouse IBD model,we show that PCC1 protects the mucosal barrier and thereby confers strong protective effects against ***1 pretreatment resulted in anti-inflammatory effects and protection against multiple pathological phenotypes in the IBD model mice,including reduced weight loss,lower disease activity index(DAI)totals,and enhanced colon size,as well as obviously beneficial effects on the mucosal barrier(e.g.,barrier thickness and activity of mucus-degrading enzymes).We also analyzed the autophagy marker microtubule-associated protein1 light chain 3(LC3)and found that the level of LC3 was significantly elevated in the intestinal epithelial cell samples of the PCC1-pretreatment group as compared with the non-model mice ***1 altered the fecal microbiome composition,which included elevating the abundance of Akkermansia muci-niphila and Christensenella *** microbiome transplant(FMT)experiments showed that deliver-ing a microbiome from PCC1-treated animals into PCC1-naïve animals conferred *** profiling revealed that both the PCC1-pretreatment and PCC1 FMT groups had elevated levels of the microbiota-derived metabolite valeric acid,and supplementation with this short-chain fatty acid(SCFA)also conferred strong protection against ***,inhibitor experiments confirmed that the beneficial effects of valeric acid on the mucus layer are mediated by FOXO1 signaling in the goble

关键词： inflammatory bowel disease Mucosal Barrier Autophagy

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Double-layer probiotic encapsulation for enhanced bacteriotherapy against inflammatory bowel disease

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Nano Research 2024年第10期17卷 9103-9110页

作者： Yixin Wang Jun Liu Sichen Yuan Yawen You Quanyin Hu Pharmaceutical Sciences Division School of PharmacyUniversity of Wisconsin-MadisonMadisonWI 53705USA Carbone Cancer Center School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonWI 53705USA Wisconsin Center for NanoBioSystems School of PharmacyUniversity of Wisconsin-MadisonMadisonWI 53705USA

inflammatory bowel disease(IBD)is inflammatory intestinal disorders associated with dysregulated gut *** that leverages bacteria as therapeutics has shown tremendous promise in resolving gut dysbiosis and reducing inflammatory mediators to treat *** delivered probiotics,such as Escherichia coli Nissle 1917(EcN),can produce beneficial ingredients,competitively inhibit the proliferation of pathogens,and promote the restoration of gut microbiome ***,environmental stresses(such as gastric acids)in the gastrointestinal(GI)tract pose an enormous challenge to the probiotics following oral administration,leading to decreases in viability and activity of ***,the inferior mucoadhesive capability of probiotics results in low colonization efficacy,further compromising their therapeutic *** probiotics with functional biomaterials may protect them from elimination and prolong their retention in the GI ***,we developed a facile double-layer electrostatic assembly technique to encapsulate EcN bacteria in protective layers of mucoadhesive chitosan(CS)and immunomodulatory hyaluronic acid(HA)to generate *** biomaterials confer the coated EcN resistance to environmental assault and enhanced mucoadhesion in the GI *** probiotics equipped with the multifunctional shield can thus suppress inflammation and reshape the intestinal microenvironment to enhance therapeutic efficacy for the prevention and treatment of ***,this study presents a novel probiotic coating strategy to augment the outcome of bacteriotherapy to combat IBD.

关键词： probiotics biomaterial coating inflammatory bowel disease mucoadhesion oral administration

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Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease

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Nano Research 2024年第3期17卷 1748-1759页

作者： Zhenxing Zhu Dongtao Zhou Yi Yin Zhun Li Zhen Guo Yongchun Pan Yanfeng Gao Jingjing Yang Weiming Zhu Yujun Song Yi Li Department of General Surgery Affiliated Jinling HospitalMedical SchoolNanjing UniversityNanjing 210093China College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China Department of General Surgery Affiliated Drum Tower HospitalMedical SchoolNanjing UniversityNanjing 210008China Department of Biochemistry and Molecular Biology School of Medicine&Holistic Integrative MedicineJiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationNanjing University of Chinese MedicineNanjing 210023China

inflammatory bowel disease(IBD)is an autoimmune gastrointestinal disease characterized by chronic relapsing inflammation of the *** pyroptosis that exists in the inflamed intestine can activate damage signals and aggravate local inflammation in ***,we designed an oral pyroptosis nanoinhibitor,DXMS@CuM@PPADT@PSS(DCMP),which can target intestinal lesions,and respond to reactive oxygen species(ROS)to release active sites and drugs at the *** can inhibit the activation of the nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3(NLRP3)inflammasomes by scavenging ROS,resulting in the down-regulation of gasdermin D(GSDMD)cleavage thus inhibiting *** also improved intestinal barrier function,decreased inflammatory cytokine levels,and increased the diversity of gut microbiota in mice with *** work is believed to expand the biomedical application of nanomaterials for innate immunity modulation.

关键词： inflammatory bowel disease nanoinhibitors pyroptosis synergistic therapy antioxidant

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Extraluminal factors contributing to inflammatory bowel disease

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World Journal of Gastroenterology 2011年第5期17卷 572-577页

作者： Arvind Batra Thorsten Stroh Britta Siegmund Charité Universittsmedizin Berlin Campus Benjamin FranklinMedical Department I(Gastroenterology/Rheumatology/Infectious Diseases)Hindenburgdamm 3012200 BerlinGermany

Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease(IBD).The genome-wide association studies clearly support the earlier developed concept that IBD occurs in genetically predisposed individuals who are exposed to distinct environmental factors,which together result in dysregulation of the mucosal immune ***,the majority of previous studies have focused on the immune response within the intestinal *** present review aims to emphasize the contribution of three extraluminal structures to this inflammatory process,namely the mesenteric fat tissue,the lymphatics and the *** our view across the intestinal wall will not only facilitate our understanding of the disease,but will also us to identify future therapeutic targets.

关键词： inflammatory bowel disease Extraluminalstructures Mesenteric fat tissue Lymphatics Microvas-culature

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Maintenance of remission with infliximab in inflammatory bowel disease: Effi cacy and safety long-term follow-up

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World Journal of Gastroenterology 2007年第39期13卷 5238-5244页

作者： Renato Caviglia Mentore Ribolsi Marina Rizzi Sara Emerenziani Maria Laura Annunziata Michele Cicala Department of Digestive diseases Campus Bio-Medico University Rome Italy

AIM: To evaluate the safety and efficacy of a long- term therapy with infliximab in Crohn’s disease (CD) and ulcerative colitis (UC) patients retrospectively. METHODS: The medical charts of 50 patients (40 CD and 10 UC), who received after a loading dose of 3 infl iximab infusions scheduled re-treatments every 8 wk as a maintenance protocol, were reviewed. RESULTS: Median (range) duration of treatment was 27 (4-64) mo in CD patients and 24.5 (6-46) mo in UC patients. Overall, 32 (80%) CD and 9 (90%) UC patients showed a sustained clinical response or remission throughout the maintenance period. Three CD patients shortened the interval between infusions. Eight (20%) CD patients and 1 UC patient underwent surgery for flare up of disease. Nine out of 29 CD and 4 out of 9 UC patients, who discontinued infliximab scheduled treatment, are still relapse-free after a median of 16 (5-30) and 6.5 (4-16) mo following the last infusion, respectively. Ten CD patients (25%) and 1 UC patient required concomitant steroid therapy during maintenance period, compared to 30 (75%) and 9 (90%) patients at enrolment. Of the 50 patients, 16 (32%) experienced at least 1 adverse event and 3 patients (6%) were diagnosed with cancer during maintenance treatment. CONCLUSION: Scheduled infl iximab strategy is effective in maintaining long-term clinical remission both in CD and UC and determines a marked steroid sparing effect. Long-lasting remission was observed following infliximab withdrawal.

关键词： inflammatory bowel disease Crohn's disease Ulcerative colitis Infliximab therapy Steroidsparing

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Treatment of inflammatory bowel disease:A review of medical therapy

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World Journal of Gastroenterology 2008年第3期14卷 354-377页

作者： Patricia L Kozuch Stephen B Hanauer Division of Gastroenterology and Hepatology Department of Medicine Thomas Jefferson University Hospital Philadelphia PA United States University of Chicago Hospitals Department of Medicine Section of Gastroenterology and Nutrition Chicago IL 60637 United States

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission. With the recent advent of therapies that inhibit tumor necrosis factor (TNF) alpha the overlap in medical therapies for UC and CD has become greater. Although 5-ASA agents have been a mainstay in the treatment of both CD and UC, the data for their efficacy in patients with CD, particularly as maintenance therapy, are equivocal. Antibiotics may have a limited role in the treatment of colonic CD. Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; non- systemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-moderate disease. 6-mercaptopurine (6-MP) and its prodrug azathioprine are steroid-sparing immunomodulators effective in the maintenance of remission of both CD and UC, while methotrexate may be used in both induction and maintenance of CD. Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC.

关键词： inflammatory bowel disease Crohn's disease Ulcerative colitis Medical therapy

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How expensive is inflammatory bowel disease? A critical analysis

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World Journal of Gastroenterology 2008年第43期14卷 6641-6647页

作者： Selwyn Odes inflammatory Bowcl diseases Unit Department of Gastroenterology and HcpatologySoroka Medical Center and Ben Gurion University of the NcgevPO Box 151Beer Sheva 84101Israel

Economic analysis of chronic diseases is required for proper allocation of resources and understanding costeffectiveness studies of new therapies. Studies on health care cost of ulcerative colitis （UC） and Crohn＇s disease （CD） are reviewed here. These studies were carried out in various countries with disparate health care systems. In the United States, data were often modeled or retrieved from large insurance schemes. Surgery and in-patient hospitalization accounted for over half the outlay on UC and CD. Fistulous disease in CD and parenteral nutrition were very costly. In Canada, overall charges were lower than in the United States, but there too, surgical costs were relatively high. In European studies, economic data were abstracted directly from patients＇ files. One pan-European study examined the outlay on UC and CD in a community-based prospective inception cohort followed for 10 years. Overall costs in Europe were lower than in the United States. Surgery, hospitalization, year of follow-up, disease phenotype in CD and ASCA-positivity impacted significantly on costs. In all studies, the cost data were right skewed, aminosalicylates were expensive drugs, and biological agents the most expensive; moreover indirect costs were not calculated. Infliximab raised costs considerably in CD, but there were no long-term followup studies, so that the cost-benefit of biological agents remains unknown. In conclusion, costs of managing UC and CD vary by country, surgery, genotype and several other factors. The most important question for further research is whether the biological therapies are cost-effective in the long-term.

关键词： inflammatory bowel disease Ulcerative colitis Crohn's disease Cost-analysis Medical economics

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Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

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Journal of Pharmaceutical Analysis 2024年第2期14卷 177-195页

作者： Haochen Hui Zhuoya Wang Xuerong Zhao Lina Xu Lianhong Yin Feifei Wang Liping Qu Jinyong Peng Department of Pharmaceutical Analysis College of PharmacyDalian Medical UniversityDalianLiaoning116044China Innovation Materials Research and Development Center Botanee Research InstituteYunnan Botanee Bio-technology Group Co.Ltd.Kunming650106China Department of Traditional Chinese Medicine Pharmacology School of PharmacyAnhui University of Chinese MedicineHefei230012China

inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is *** acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and *** results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism *** transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model *** conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against *** is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

关键词： Gut microbiota inflammatory bowel disease Polysaccharide Selaginella uncinata(Desv.)Spring Thiamine metabolism

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