ulcerative colitis (UC)

溃疡性结肠炎 (UC)
  • 文章类型: Journal Article
    溃疡性结肠炎(UC)的胃肠道慢性发炎,病因复杂,涉及免疫学,环境,和遗传因素。UC典型的炎症反应通过活化B细胞的核因子κ-轻链增强剂(NF-κB)信号通路显着调节。最新研究表明,NF-κB信号传导受三种主要类型的非编码RNA(ncRNAs)控制:环状RNA(circularRNAs,circRNAs)。长链非编码RNA(lncRNA),和microRNAs(miRNAs)。这些ncRNAs可以通过充当分子海绵来改变NF-κB途径中关键基因的表达,转录调节因子,和表观遗传修饰剂。这篇综述综合了关于ncRNAs在UC中调节NF-κB信号传导的功能的最新知识,讨论了它们作为疾病预后和诊断的生物标志物的潜力,探索他们的治疗潜力。了解ncRNAs和NF-κB信号之间复杂的相互作用可能为UC发病机制和靶向治疗策略提供新的见解。
    The gastrointestinal tract is chronically inflamed in ulcerative colitis (UC), which has a complicated etiology involving immunological, environmental, and genetic factors. The inflammatory response that is typical of UC is significantly regulated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Latest research has displayed that NF-κB signaling is controlled by three main types of non-coding RNAs (ncRNAs): circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs). These ncRNAs can change the expression of key genes within the NF-κB pathway by acting as molecular sponges, transcriptional regulators, and epigenetic modifiers. This review synthesizes current knowledge on the functions by which ncRNAs modulate NF-κB signaling in UC, discusses their potential as biomarkers for disease prognosis and diagnosis, and explores their therapeutic potential. Understanding the intricate interactions between ncRNAs and NF-κB signaling may provide novel insights into UC pathogenesis and targeted therapeutic strategies.
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  • 文章类型: Journal Article
    背景炎症性肠病(IBD),包括克罗恩病(CD)和溃疡性结肠炎(UC),提出了重大挑战,特别是儿科患者。维生素D缺乏与IBD有关,但其在疾病活动和缓解中的作用尚不清楚。这项研究调查了血清维生素D水平与IBD标志物之间的关系,包括小儿克罗恩病活动指数(PCDAI),小儿溃疡性结肠炎活动指数(PUCAI),粪便钙卫蛋白水平,和内窥镜检查结果。它还探讨了这些关系中的种族和民族差异。方法对来自Nemours儿童健康EMR系统的51例IBD患儿进行回顾性研究。纳入标准要求在诊断和治疗后记录血清维生素D水平,和至少一项PUCAI/PCDAI的治疗后评估,钙卫蛋白,或内窥镜检查。该研究采用Spearman和Pearson相关性检验来分析维生素D水平与IBD标志物之间的关联。使用t检验和卡方检验对种族和种族进行分析。结果血清维生素D水平的变化与IBD标志物之间无统计学意义的相关性(内窥镜检查结果,钙卫蛋白水平,UC和CD的PUCAI/PCDAI评分)。种族和种族差异的分析显示,与非西班牙裔相比,西班牙裔患者的治疗后钙卫蛋白水平明显更高,尽管其他标记没有显着差异。维生素D水平在种族或族裔之间没有显着差异。结论本研究发现儿科患者血清维生素D水平与IBD活性标志物之间无显著相关性。尽管有最初的假设,维生素D水平似乎对评估IBD缓解或疾病状态没有帮助.观察到IBD严重程度的种族和种族差异,但需要进一步研究更大的样本量和更一致的数据收集才能得出更明确的结论。
    Background Inflammatory bowel disease (IBD), including Crohn\'s disease (CD) and ulcerative colitis (UC), presents significant challenges, particularly in pediatric patients. Vitamin D deficiency has been associated with IBD, but its role in disease activity and remission remains unclear. This study investigates the relationship between serum vitamin D levels and IBD markers, including Pediatric Crohn\'s Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), fecal calprotectin levels, and endoscopy findings. It also explores racial and ethnic disparities in these relationships. Methodology A retrospective study was conducted involving 51 pediatric patients with IBD from the Nemours Children\'s Health EMR system. Inclusion criteria required documented serum vitamin D levels at diagnosis and post-treatment, and at least one post-treatment assessment of PUCAI/PCDAI, calprotectin, or endoscopy. The study employed Spearman and Pearson correlation tests to analyze the associations between vitamin D levels and IBD markers. Ethnicity and race were analyzed using t-tests and chi-square tests. Results No statistically significant correlations were found between changes in serum vitamin D levels and IBD markers (endoscopy results, calprotectin levels, PUCAI/PCDAI scores) for both UC and CD. Analysis of racial and ethnic disparities revealed that Hispanic patients had significantly higher post-treatment calprotectin levels compared to non-Hispanics, although other markers showed no significant differences. Vitamin D levels did not significantly differ between racial or ethnic groups. Conclusions This study found no significant correlation between serum vitamin D levels and IBD activity markers in pediatric patients. Despite initial hypotheses, vitamin D levels do not appear to be useful in assessing IBD remission or disease state. Racial and ethnic disparities in IBD severity were observed, but further research with larger sample sizes and more consistent data collection is needed to draw more definitive conclusions.
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  • 文章类型: Journal Article
    据报道,外胚层间充质干细胞来源的条件培养基(EMSC-CM)可预防小鼠溃疡性结肠炎(UC)。但其缓解UC的潜在机制需要进一步阐明。这里,据报道,EMSC-CM可以减轻LPS诱导的IEC-6细胞的促炎反应,并在体外调节巨噬细胞向抗炎类型的极化。此外,通过双乳法制备的PLGA微球构建用于口服递送EMSCs-CM(EMSCs-CM-PLGA),这有利于EMSC-CM对受损结肠粘膜的结肠靶向粘附。结果表明,口服EMSC-CM-PLGA微球可减轻炎症细胞浸润,维持肠粘膜屏障。进一步研究发现,EMSCs-CM-PLGA微球处理逐渐抑制NF-κB通路的激活,从而调节结肠组织巨噬细胞M1/M2极化平衡,从而减轻DSS诱导的UC。本研究结果将为EMSCs-CM在UC修复中的临床应用提供理论依据。
    Ectodermal mesenchymal stem cells-derived conditioned medium (EMSCs-CM) has been reported to protect against ulcerative colitis (UC) in mice, but its underlying mechanism in alleviating UC need to be further elucidated. Here, it is reported that EMSCs-CM could attenuate pro-inflammatory response of LPS-induced IEC-6 cells and regulate the polarization of macrophages towards anti-inflammatory type in vitro. Furthermore, PLGA microspheres prepared by the double emulsion method were constructed for oral delivery of EMSCs-CM (EMSCs-CM-PLGA), which are beneficial for colon-targeted adhesion of EMSCs-CM to the damaged colon mucosa. The results showed that orally-administered of EMSCs-CM-PLGA microspheres reduced inflammatory cells infiltration and maintained the intestinal mucosal barrier. Further investigation found that EMSCs-CM-PLGA microspheres treatment gradually inhibited the activation of NF-κB pathway to regulate M1/M2 polarization balance in colon tissue macrophages, thereby alleviating DSS-induced UC. These results of this study will provide a theoretical basis for clinical application of EMSCs-CM in UC repair.
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  • 文章类型: Journal Article
    溃疡性结肠炎(UC)是一种慢性结肠炎症性疾病,其发病机制尚不清楚。多胺代谢酶在UC中起着至关重要的作用。在这项研究中,我们旨在鉴定关键的多胺相关基因(PRGs),并探讨PRGs与UC的疾病状态和治疗反应之间的潜在机制.我们分析了来自GEO数据库的UC患者的mRNA测序数据和临床信息,并确定了NNMT,使用差异表达分析和加权基因共表达网络分析(WCGNA),PTGS2、TRIM22、TGM2和PPARG作为与活动性UC相关的关键PRG。受试者工作特征曲线(ROC)分析证实了这些关键基因在UC和结肠炎相关性结肠癌(CAC)诊断中的准确性,我们在外部验证集中验证了它们与治疗反应的关系。此外,单细胞分析显示,关键PRG对某些免疫细胞类型具有特异性,强调肠组织干细胞在活动性UC中的重要作用。结果在体外和体内实验中得到验证,包括结肠炎小鼠模型和CAC小鼠模型。总之,这些关键PRG可有效预测UC患者的进展,并可作为UC治疗反应的新药理学生物标志物.
    Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon, and its pathogenesis remains unclear. Polyamine metabolic enzymes play a crucial role in UC. In this study, we aimed to identify pivotal polyamine-related genes (PRGs) and explore the underlying mechanism between PRGs and the disease status and therapeutic response of UC. We analyzed mRNA-sequencing data and clinical information of UC patients from the GEO database and identified NNMT, PTGS2, TRIM22, TGM2, and PPARG as key PRGs associated with active UC using differential expression analysis and weighted gene co-expression network analysis (WCGNA). Receiver operator characteristic curve (ROC) analysis confirmed the accuracy of these key genes in UC and colitis-associated colon cancer (CAC) diagnosis, and we validated their relationship with therapeutic response in external verification sets. Additionally, single-cell analysis revealed that the key PRGs were specific to certain immune cell types, emphasizing the vital role of intestinal tissue stem cells in active UC. The results were validated in vitro and in vivo experiments, including the colitis mice model and CAC mice model. In conclusion, these key PRGs effectively predict the progression of UC patients and could serve as new pharmacological biomarkers for the therapeutic response of UC.
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  • 文章类型: Journal Article
    目前,没有已知的溃疡性结肠炎(UC)的原因,一种难以治疗的炎症性肠病。本试验旨在研究铁皮石斛多糖(DOP)对葡聚糖硫酸钠(DSS)诱导的小鼠急性UC的保护作用及其机制。我们发现DOP可以改善减肥效果,降低疾病活动指数(DAI),并调节白细胞介素2(IL-2)的释放,DSS诱导的急性UC小鼠中的IL-4、IL-6和IL-10。此外,DOP通过增加杯状细胞密度和维持紧密连接保持UC小鼠肠屏障的完整性。DOP显著提高了总抗氧化能力(T-AOC),和还原型谷胱甘肽(GSH),一氧化氮(NO),和丙二醛(MDA)在血液中的水平。在血清生物化学方面,DOP显著升高胆红素(BIL)水平,碱性磷酸酶(ALP),总胆汁酸(TBA),肌酐(Crea),和创造性激酶同工酶(CKMB)。此外,DOP增加了乳杆菌的相对丰度。DOP还通过调节嘌呤的代谢来改善肠道健康并刺激有效的抗炎和抗病毒物质的合成,前列腺素,和白三烯.因此,DOP可以被认为是治疗UC的功能性膳食补充剂,因为它改善了DSS诱导的UC小鼠的状况。
    Currently, there is no known cause for ulcerative colitis (UC), an inflammatory bowel disease that is difficult to treat. This assay aimed to investigate the protective effects and mechanisms of Dendrobium officinale polysaccharide (DOP) in mice with acute UC induced by dextran sulphate sodium (DSS). We found that DOP could improve weight loss, decrease the disease activity index (DAI), and regulate the release of interleukin 2 (IL-2), IL-4, IL-6, and IL-10 in DSS-induced acute UC mice. Additionally, DOP preserved the integrity of the intestinal barrier in UC mice by increasing goblet cell density and maintaining tight junctions. DOP significantly enhanced total antioxidant capacity (T-AOC), and reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels in the bloodstream. In terms of serum biochemistry, DOP markedly elevated levels of bilirubin (BIL), alkaline phosphatase (ALP), total bile acid (TBA), creatinine (Crea), and creative kinase isoenzyme (CKMB). Furthermore, DOP increased the relative abundance of Lactobacillales. DOP also improved intestinal health and stimulated the synthesis of potent anti-inflammatory and antiviral substances by regulating the metabolism of purines, prostaglandins, and leukotrienes. Therefore, DOP can be considered a functional dietary supplement for the treatment of UC, as it improves the condition of DSS-induced UC mice.
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  • 文章类型: Case Reports
    原发性硬化性胆管炎(PSC)是一种罕见的慢性炎症性疾病,其中多灶性胆管纤维化最终导致狭窄甚至阻塞,形成交替扩张的多焦点狭窄。这里,我们报道了一例极为罕见的与溃疡性结肠炎(UC)相关并与胆管癌并存的PSC病例,该病例是一名33岁男性,表现为右上腹疼痛和深色尿液.肝功能测试混乱,和ERCP发现串珠状的胆管造影外观,原因是多灶性胆管狭窄与肝总管和肝内胆管的正常和扩张段交替出现。我们旨在记录与UC相关并与胆管癌共存的PSC典型病例,以添加有关这些罕见病理的现有数据。
    Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory disease in which multifocal fibrosis of bile ducts causes eventually narrowing and even blocking, forming multifocal strictures alternated to dilatations. Here, we reported an extremely rare case of PSC associated with ulcerative colitis (UC) and coexisting with cholangiocarcinoma in a 33-year-old male presented with right upper quadrant pain and dark urine. Liver function tests were deranged, and ERCP found a beaded cholangiography appearance due to multifocal bile duct strictures alternating with normal and dilated segments of the common hepatic duct and the intrahepatic bile ducts. We aim to document this typical case of PSC associated with UC and coexisted with cholangiocarcinoma to add the existing data on these rare pathologies.
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  • 文章类型: Journal Article
    炎症性肠病(IBD)在胃肠病学领域提出了持续的挑战,需要不断探索创新的治疗策略。与现有治疗方式相关的有限疗效和潜在副作用强调了对IBD治疗新方法的迫切需要。对该疾病复杂发病机制的理解的最新进展揭示了有希望的治疗靶点,关注肠道微生物组,免疫失调,和遗传倾向。本摘要深入探讨了对IBD治疗新途径的迫切需求,检查潜在的治疗目标,例如,磷酸二酯酶4(PDE4)抑制剂,免疫系统,酪氨酸激酶受体(TYK),Toll样受体(TLRs),肠道微生物群的调节,干细胞疗法,纤维化管理,白细胞介素(IL)调节和氧化应激,并提供了对近期突破的见解,这些突破预示着IBD治疗领域的变革时代。精准医学的进展,生物制剂,小分子抑制剂,微生物组调节技术的探索是关键的里程碑,为提高疗效提供了新的希望,减少副作用,并改善IBD治疗的患者预后。
    UNASSIGNED: Inflammatory Bowel Disease (IBD) poses a persistent challenge in the realm of gastroenterology, necessitating continual exploration of innovative treatment strategies. The limited efficacy and potential side effects associated with existing therapeutic modalities underscore the urgent need for novel approaches in IBD management. This study aims to examine potential therapeutic targets and recent advancements in understanding the disease\'s intricate pathogenesis, with a spotlight on the gut microbiome, immune dysregulation, and genetic predispositions.
    UNASSIGNED: A comprehensive review was conducted to delve into the pressing demand for new avenues in IBD treatment. The study examined potential therapeutic targets such as phosphodiesterase 4 (PDE4) inhibitors, immune system modulators, Tyrosine kinase receptors (TYK), Toll-like receptors (TLRs), modulation of the gut microbiota, stem cell therapy, fibrosis management, interleukins (ILs) regulation, and oxidative stress mitigation. Additionally, advances in precision medicine, biologics, small molecule inhibitors, and microbiome modulation techniques were explored.
    UNASSIGNED: The investigation unveiled promising therapeutic targets and provided insights into recent breakthroughs that herald a transformative era in the therapeutic landscape for IBD. Advances in precision medicine, biologics, small molecule inhibitors, and the exploration of microbiome modulation techniques stood out as pivotal milestones in the field of gastroenterology.
    UNASSIGNED: The findings offer renewed hope for enhanced efficacy, reduced side effects, and improved patient outcomes in the treatment of IBD. These innovative approaches necessitate continual exploration and underscore the urgent need for novel strategies in IBD management, potentially revolutionizing the realm of gastroenterology.
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  • 文章类型: Case Reports
    一名26岁男性,无明显病史,表现为便血,被诊断为溃疡性结肠炎(UC)并伴有免疫性血小板减少症(ITP),是UC的肠外表现(EIM)。本病例报告深入探讨了UC之间罕见的重叠,炎症性肠病的一种亚型,主要影响结肠和直肠,和ITP,导致血小板破坏的自身免疫性疾病。患者的非典型表现和随后对针对UC和ITP的治疗方案的积极反应强调了对UC患者采取全面和多方面的诊断方法的必要性。尤其是面对非胃肠道症状如无法解释的血小板减少症。这项研究的发现加强了对UC的不同表现的理解,并突出了其与其他自身免疫性疾病的潜在交集。倡导在管理这些复杂的临床病例时采用综合护理策略。
    A 26-year-old male with no significant medical history presented with hematochezia and was diagnosed with ulcerative colitis (UC) accompanied by immune thrombocytopenia (ITP) as an extraintestinal manifestation (EIM) of UC. This case report delves into the uncommon overlap between UC, a subtype of inflammatory bowel disease primarily affecting the colon and rectum, and ITP, an autoimmune condition leading to platelet destruction. The patient\'s atypical presentation and subsequent positive response to a treatment regimen targeting both UC and ITP underscores the necessity for a thorough and multifaceted diagnostic approach in individuals with UC, especially when faced with non-gastrointestinal symptoms like unexplained thrombocytopenia. The findings from this study enhance the understanding of UC\'s diverse manifestations and highlight its potential intersection with other autoimmune diseases, advocating for integrated care strategies in managing such intricate clinical cases.
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  • 文章类型: Journal Article
    背景:已提出维多珠单抗与新发脊柱关节炎(SpA)的时间关系。
    目的:我们通过系列临床评估和磁共振成像(MRI)评估了炎症性肠病(IBD)患者中vedolizumab起始和新发SpA之间的关系。
    方法:一项针对24例IBD患者的单中心前瞻性观察性研究。如果患者患有活动性溃疡性结肠炎或克罗恩病(CD),则符合资格。正在启动维多珠单抗,既往无关节炎或SpA病史,适合进行系列MRI检查。风湿病学家在第一次给药之前以及第8周和第24周进行临床评估。轴向MRI由盲化的中央阅读器进行评估,并在基线8和24周进行。
    结果:9名肿瘤坏死因子(TNF)抑制剂初治患者(4名男性;平均年龄53.2岁;6名UC;3个CD)和8名TNF抑制剂患者(7名男性;平均年龄48岁;3个UC;5个CD)完成了所有评估。没有患者出现轴性关节炎的新特征或外周SpA的特征(炎性寡关节炎,附着性炎,牙龈炎,或牛皮癣(指甲,身体,或头皮))。两组均表现出良好的肠道反应。
    结论:Vedolizumab开始治疗24周后,在有TNF抑制剂的IBD患者或未使用TNF抑制剂的IBD患者中,未诱导轴性或外周性SpA的新特征。
    BACKGROUND: A temporal relationship between vedolizumab and new-onset spondyloarthritis (SpA) has been suggested.
    OBJECTIVE: We evaluated the relationship between vedolizumab initiation and development of new-onset SpA in patients with inflammatory bowel disease (IBD) through serial clinical evaluation and magnetic resonance imaging (MRI).
    METHODS: A single-centre prospective observational study of 24 patients with IBD. Patients were eligible if they had active ulcerative colitis or Crohn\'s disease (CD), were initiating vedolizumab, had no prior history of arthritis or SpA and were suitable for serial MRI. A rheumatologist performed clinical evaluation prior to the first dose and 8 and 24 weeks. Axial MRI was evaluated by a blinded central reader and performed at baseline 8 and 24 weeks.
    RESULTS: Nine tumor necrosis factor (TNF) inhibitor-naïve patients (4 male; mean age 53.2 years; 6 UC; 3 CD) and eight TNF inhibitor-experienced patients (7 male; mean age 48 years; 3 UC; 5 CD) completed all assessments. No patients developed new features of axial arthritis or features of peripheral SpA (inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp)). Both groups demonstrated a good intestinal response.
    CONCLUSIONS: Vedolizumab initiation did not induce new features of axial or peripheral SpA after 24 weeks of treatment in TNF inhibitor-experienced or TNF inhibitor-naive patients with IBD.
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  • 文章类型: Journal Article
    研究一种称为“Ferment”的新型饮料在溃疡性结肠炎(UC)病例中的疗效及其对肠道微生物群的影响。
    在这项研究中,我们开发了一种混合果汁和乳酸菌的复合物,称为Ferment。给小鼠喂食发酵剂35天,在用硫酸葡聚糖钠盐诱导UC之前。我们随后使用16SrRNA测序研究了肠道微生物组组成。
    发酵处理后,小鼠体重增加,动物表现出更少的腹泻,减少血便的频率,减少结肠炎症.有益菌属的细菌,Akkermansia,发酵治疗后,普雷沃乐在肠道中富集,而有害生物包括丹毒病菌,Dubosiella,和Alistipes减少了。
    这些数据将Ferment作为增强免疫力和预防UC的有希望的饮食候选物。
    UNASSIGNED: To investigate the therapeutic efficiency of a novel drink termed \"Ferment\" in cases of ulcerative colitis (UC) and its influence on the gut microbiota.
    UNASSIGNED: In this study, we developed a complex of mixed fruit juice and lactic acid bacteria referred to as Ferment. Ferment was fed to mice for 35 days, before inducing UC with Dextran Sulfate Sodium Salt. We subsequently investigated the gut microbiome composition using 16S rRNA sequencing.
    UNASSIGNED: After Ferment treatment, mouse body weight increased, and animals displayed less diarrhea, reduced frequency of bloody stools, and reduced inflammation in the colon. Beneficial bacteria belonging to Ileibacterium, Akkermansia, and Prevotellacea were enriched in the gut after Ferment treatment, while detrimental organisms including Erysipelatoclostridium, Dubosiella, and Alistipes were reduced.
    UNASSIGNED: These data place Ferment as a promising dietary candidate for enhancing immunity and protecting against UC.
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