Assessing the effect of EWDP on vegetation restoration by remote sensing in the lower reaches of Tarim River

In this study, effect of ecological water diversion on vegetation restoration in the lower reaches of Tarim River is assessed by coupling remote sensing techniques and a field-based survey. Land use/cover and fractional vegetation coverage (Fvc) maps derived from remote sensing images, ground validation data, and hydrological observation data are adopted to analyze the responses of Ecological Water Diversion Project (EWDP). The results indicate that, the EWDP has showed a positive effect on vegetation restoration in the lower part of Tarim Basin. During 2001 to 2013, transformation from unused land to nature vegetation (i.e. forest land, grassland and scrubland) was the major process of land use/cover change; the area of natural vegetation showed a 4.7% increase, and the area of unused land reduced by 6.8%. Landscape patch size was decreased, the degree of fragmentation and diversity of landscape was increased, and landscape structure in the study area became more complex. Moreover, vegetation coverage promoted from 2001 to 2013; average Fvc in 2013 was 1.5 times greater than that in 2001. The results can provide not only an accurate assessment for the EWDP, but also a visual insight for the water resources management practices in the study area, such that the sustainability for local ecosystem can be facilitated.     

Crystal structure of the passenger domain of the Escherichia coli autotransporter EspP

Autotransporters represent a large superfamily of known and putative virulence factors produced by Gram-negative bacteria. They consist of an N-terminal “passenger domain” responsible for the specific effector functions of the molecule and a C-terminal “β-domain” responsible for translocation of the passenger across the bacterial outer membrane. Here, we present the 2.5-Å crystal structure of the passenger domain of the extracellular serine protease EspP, produced by the pathogen Escherichia coli O157:H7 and a member of the serine protease autotransporters of Enterobacteriaceae (SPATEs). Like the previously structurally characterized SPATE passenger domains, the EspP passenger domain contains an extended right-handed parallel β-helix preceded by an N-terminal globular domain housing the catalytic function of the protease. Of note, however, is the absence of a second globular domain protruding from this β-helix. We describe the structure of the EspP passenger domain in the context of previous results and provide an alternative hypothesis for the function of the β-helix within SPATEs.     

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.     

双歧杆菌三联活菌胶囊对溃疡性结肠炎患者血清白介素-6、8和10水平的影响及疗效观察

目的探讨双歧杆菌三联活菌胶囊对溃疡性结肠炎（UC）患者血清白介素（IL）-6、8和10水平的影响及疗效观察。方法选取88例UC患者,随机分为观察组和对照组。两组患者均酌情予以柳氮磺胺吡啶、5-氨基水杨酸和糖皮质激素等常规治疗。观察组患者在此基础上加用口服双歧杆菌三联活菌胶囊420mg/次,3次/d,连用8周。对照组患者除不使用双歧杆菌三联活菌胶囊外余治疗同观察组。观察两组患者治疗前后血清IL-6、8和10水平变化,并比较其临床疗效及不良反应。结果治疗8周后,两组患者血清IL-6、8水平明显下降,IL-10水平明显上升（P〈0.05或P〈0.01）,且观察组下降值或上升值大于对照组（P〈0.05）;观察组患者总有效率明显高于对照组（χ2=4.42,P〈0.05）;治疗中对照组出现不良反应3例,观察组出现5例,症状均较轻,两组患者不良反应发生率比较差异无统计学意义（χ2=0.14,P〉0.05）。结论双歧杆菌三联活菌胶囊治疗UC的疗效确切,安全性较好,作用与其能降低血清IL-6、8水平,提高血清IL-10水平,减轻肠黏膜局部炎症反应密切相关。     

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.     

Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome

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Exploring the Potential Mechanism of Guchang Zhixie Wan for Treating Ulcerative Colitis by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation as Well as Cell Experiments

Guchang Zhixie Wan (GZW) is a commonly used Chinese medicine for the treatment of ulcerative colitis (UC). This research explored the potential pharmacological mechanism of GZW in UC. The active ingredients, potential targets, and UC-related genes of GZW were retrieved from public databases. The pharmacological mechanisms including key components, potential targets and signal pathways were determined through bioinformatics analysis. The results of this study were verified through virtual molecular docking and cell experiments. Network analysis revealed that 26 active GZW compounds and 148 potential GZW target proteins were associated with UC. Quercetin, kaempferol and β-sitosterol were identified as the core active ingredients of GZW. IFNG, IL-1A, IL-1B, JUN, RELA, and STAT1 were indicated as key targets of GZW. These key targets have a strong affinity for quercetin, kaempferol, and β-sitosterol. GO and KEGG enrichment analysis showed that GZW target proteins are highly enriched in inflammatory, immune, and oxidative stress-related pathways. This study confirmed the therapeutic effect and revealed potential molecular mechanism of GZW on UC. And the protective effects of GZW on inflammatory bowel disease pathway were also revealed through STAT3/NF-κB/IL-6 pathway. The findings of this study enhanced our understanding of GZW in the treatment of UC and provided a feasible method for discovering potential drugs from traditional Chinese medicine formulations.     

Transgenic overexpression of ITGB6 in intestinal epithelial cells exacerbates dextran sulfate sodium-induced colitis in mice

Integrins, as a large family of cell adhesion molecules, play a crucial role in maintaining intestinal homeostasis. In inflammatory bowel disease (IBD), homeostasis is disrupted. Integrin αvβ6, which is mainly regulated by the integrin β6 subunit gene (ITGB6), is a cell adhesion molecule that mediates cell-cell and cell-matrix interactions. However, the role of ITGB6 in the pathogenesis of IBD remains elusive. In this study, we found that ITGB6 was markedly upregulated in inflamed intestinal tissues from patients with IBD. Then, we generated an intestinal epithelial cell-specific ITGB6 transgenic mouse model. Conditional ITGB6 transgene expression exacerbated experimental colitis in mouse models of acute and chronic dextran sulphate sodium (DSS)-induced colitis. Survival analyses revealed that ITGB6 transgene expression correlated with poor prognosis in DSS-induced colitis. Furthermore, our data indicated that ITGB6 transgene expression increased macrophages infiltration, pro-inflammatory cytokines secretion, integrin ligands expression and Stat1 signalling pathway activation. Collectively, our findings revealed a previously unknown role of ITGB6 in IBD and highlighted the possibility of ITGB6 as a diagnostic marker and therapeutic target for IBD.