DNA methylation-associated colonic mucosal immune and defense responses in treatment-na?ve pediatric ulcerative colitis

Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn’s disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P < 0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.     

Modifications of mesenteric adipose tissue during moderate experimental colitis in mice

Aims

Adipose tissue secretes various proteins referred to as adipokines, being involved in inflammation. It was recognized that mesenteric adipose tissue (MAT) is altered by inflammation, and pathologies such as inflammatory bowel disease (IBD). The aim of this study was to investigate the alterations of the mesenteric adipose tissue in two experimental colitis models in mice adapted to obtain moderate colonic inflammation.

Main methods

Colonic inflammation was obtained using two models, either DSS dissolved in drinking water or intra-colonic instillation of DNBS. The expression of adipokines (leptin and adiponectin) and inflammatory markers (IL-6, MCP-1, F4/80) was studied by qRT-PCR in the MAT of treated and control mice.

Key findings

Observations of the colon and IL-6 plasma level determination demonstrated that DNBS treatment led to stronger inflammation. Colitis induced a decrease of mRNA encoding to leptin and adiponectin in MAT. In contrast, colonic inflammation led to an increase of mRNA encoding to IL-6, MCP-1 and F4/80, a specific marker of macrophages.

Significance

The mesenteric adipose tissue, in two models of moderate colitis, shows a loss of adipose profile and a strong increase of inflammatory pattern, close to the observations made in MAT of IBD patients. These data suggest that these pro-inflammatory modifications of MAT have to be taken into account in the pathophysiology of IBD.     

乳杆菌对急性溃疡性结肠炎模型小鼠的疗效观察

目的观察植物乳杆菌YXCC-1和嗜酸乳杆菌YXCC-2对小鼠急性溃疡性结肠炎(UC)的疗效。方法对这两株菌进行体外模拟胃肠环境抗性研究,并进行动物实验。采用DSS诱导的小鼠急性UC模型,将60只小鼠随机分为4组,分别为空白对照组、DSS模型组、YXCC-1组和YXCC-2组,每组15只,观察小鼠治疗前后一般情况,计算小鼠组织学损伤评分以及观察组织学病理改变。结果菌株YXCC-1、YXCC-2有一定的耐酸、耐胆盐能力,在人工肠液环境下能较好存活;灌胃菌株发酵液可显著降低UC小鼠DAI水平,明显改善结肠组织损伤。结论植物乳杆菌YXCC-1、嗜酸乳杆菌YXCC-2发酵液对小鼠溃疡性结肠炎有治疗作用,且两者疗效相当。     

水罐疗法联合白头翁汤灌肠对溃疡性结肠炎患者Th1/Th2免疫平衡及肠黏膜屏障功能的影响

摘要 目的：探讨水罐疗法联合白头翁汤灌肠对溃疡性结肠炎（UC）患者Th1/Th2免疫平衡及肠黏膜屏障功能的影响。方法：选取2020年2月~2022年5月期间湖南中医药大学第一附属医院收治的UC患者100例。根据随机数字表法分为对照组（n=50）和研究组（n=50）。对照组患者接受白头翁汤灌肠,研究组在此基础上接受水罐疗法。对比两组疗效、中医证候评分、Th1/Th2免疫平衡及肠黏膜屏障功能变化情况。结果：研究组的总有效率明显高于对照组（P<0.05）。治疗后,两组里急后重、身热不扬、腹泻黏液脓血便、小便短赤、肛门灼热、腹痛、口干口苦等症状评分均降低,且研究组低于对照组同期（P<0.05）。治疗后,两组Th1/Th2相关指标白介素（IL）-2、γ-干扰素（IFN-γ）均降低,且研究组较对照组低;IL-4、IL-10均升高,且研究组较对照组高（P<0.05）。治疗后,两组肠黏膜屏障功能指标二胺氧化酶（DAO）、D-乳酸（D-LA）均降低,且研究组低于对照组同期（P<0.05）。结论：水罐疗法联合白头翁汤灌肠治疗UC患者,总有效率高,可缓解中医证候,疗效显著,对调节患者的Th1/Th2免疫平衡及肠黏膜屏障功能具有重要作用。     

Mesenchymal stem cell expression of interleukin-35 protects against ulcerative colitis by suppressing mucosal immune responses

Background

Interleukin-35 (IL-35) has recently been identified as an immunosuppressive cytokine that has been used as a potential therapy for chronic inflammatory and autoimmune diseases. However, there remains a paucity of data regarding its potential benefits after integration into mesenchymal stem cells (MSCs).

参苓白术散联合针刺对溃疡性结肠炎大鼠内质网应激、炎症反应的作用机制

摘要 目的：探讨参苓白术散联合针刺对溃疡性结肠炎大鼠内质网应激、炎症反应的作用机制。方法：采用三硝基苯磺酸的方法构建溃疡性结肠炎大鼠模型。给予大鼠参苓白术散联合针刺干预。采用ELISA法检测大鼠病变结肠的炎症反应和氧化应激水平;采用肉眼观察各组结肠组织形态学评分;采用Western blot 检测大鼠内质网应激相关蛋白的表达。结果：与空白组相比,模型组、针刺组、参苓白术散、参苓白术散组联合针刺组大鼠体质量更低（P＜0.05）;与模型组相比,针刺组、参苓白术散、参苓白术散组联合针刺组溃疡指数评分和大鼠体质量更低（P＜0.05）,且参苓白术散组联合针刺组明显低于针刺组和参苓白术散组;与空白组相比,模型组、针刺组、参苓白术散、参苓白术散组联合针刺组ROS、GSH-Px、MDA更高（P＜0.05）;与模型组相比,针刺组、参苓白术散、参苓白术散组联合针刺组ROS、GSH-Px、MDA更低（P＜0.05）,且参苓白术散组联合针刺组明显低于针刺组和参苓白术散组;与空白组相比,模型组、针刺组、参苓白术散、参苓白术散组联合针刺组TNF-α、IL-1β、IL-18更高（P＜0.05）;与模型组相比,针刺组、参苓白术散、参苓白术散组联合针刺组TNF-α、IL-1β、IL-18更低（P＜0.05）,且参苓白术散组联合针刺组低于针刺组和参苓白术散组;与空白组相比,模型组、针刺组、参苓白术散、参苓白术散组联合针刺组GRP78、p-PERK、p-eIF2α更高（P＜0.05）;与模型组相比,针刺组、参苓白术散、参苓白术散组联合针刺组GRP78、p-PERK、p-eIF2α更低（P＜0.05）,且参苓白术散组联合针刺组明显低于针刺组和参苓白术散组。结论：参苓白术散组联合针刺可有效抑制溃疡性结肠炎大鼠内质网应激,进而抑制炎症反应和氧化应激反应,并促进溃疡性结肠炎大鼠病变病情转归。     

Picroside III,an Active Ingredient of Picrorhiza scrophulariiflora,Ameliorates Experimental Colitis by Protecting Intestinal Barrier Integrity

This study aims to explore the protective effects of Picroside III, an active ingredient of Picrorhiza scrophulariiflora, on the intestinal epithelial barrier in tumor necrosis factor-α (TNF-α) induced Caco-2 cells and dextran sulfate sodium (DSS) induced colitis in mice. Results show that Picroside III significantly alleviated clinical signs of colitis including body weight loss, disease activity index increase, colon shortening, and colon tissue damage. It also increased claudin-3, ZO-1 and occludin expressions and decreased claudin-2 expression in the colon tissues of mice with colitis. In vitro, Picroside III also significantly promoted wound healing, decreased the permeability of cell monolayer, upregulated the expressions of claudin-3, ZO-1 and occludin and downregulated the expression of claudin-2 in TNF-α treated Caco-2 cells. Mechanism studies show that Picroside III significantly promoted AMP-activated protein kinase (AMPK) phosphorylation in vitro and in vivo, and blockade with AMPK could significantly attenuate the upregulation of Picroside III in ZO-1 and occludin expressions and the downregulation of claudin-2 expression in TNF-α treated Caco-2 cells. In conclusion, this study demonstrates that Picroside III attenuated DSS-induced colitis by promoting colonic mucosal wound healing and epithelial barrier function recovery via the activation of AMPK.