Graphene-Au nanoparticle based electrochemical immunosensor for fish pathogen Aphanomyces invadans detection

Epizootic ulcerative syndrome (EUS) that is primarily caused by an invasive oomycete fungus Aphanomyces invadans is a devastating fish disease. Rapid diagnosis of EUS is significantly important for the control and treatment of this highly invasive disease. In our study, a label-free immunosensor constructed with G-AuNPs/SAM-Ab-BSA/GCE was proposed for the determination of Aphanomyces invadans. The electrode was prepared by the immobilization of anti-mycelium antibodies on graphene-AuNPs nanocomposite-cysteamine monolayers modified GCE. The optimized parameters were as follows: 90 min as the immersion time of SAM modified electrode in the anti-mycelium solution, 0.20 µg/mL as the concentration of anti-mycelium solution and 10 min as the interaction time of immunoreaction. The immunosensors exhibited low limit detection of 309 ng/mL and good reproducibility.     

Male-Dependent Promotion of Colitis in 129 Rag2−/− Mice Co-Infected with Helicobacter pylori and Helicobacter hepaticus

The prevalence of gastric Helicobacter pylori (Hp) infection is ~50% of the world population. However, how Hp infection influences inflammatory bowel disease in humans is not fully defined. In this study, we examined whether co-infection with Hp influenced Helicobacter hepaticus (Hh)–induced intestinal pathology in Rag2^−/− mice. Rag2^−/− mice of both sexes were infected with Hh, of which a subgroup was followed by infection with Hp two weeks later. Co-infected males, but not females, had significantly higher total colitis index scores in the colon at both 10 and 21 weeks post-Hh infection (WPI) and developed more severe dysplasia at 21 WPI compared with mono-Hh males. There were no significant differences in colonization levels of gastric Hp and colonic Hh between sexes or time-points. In addition, mRNA levels of colonic Il-1β, Ifnγ, Tnfα, Il-17A, Il-17F, Il-18, and Il-23, which play important roles in the development and function of proinflammatory innate lymphoid cell groups 1 and 3, were significantly up-regulated in the dually infected males compared with mono-Hh males at 21 WPI. These data suggest that concomitant Hp infection enhances the inflammatory responses in the colon of-Hh-infected Rag2^−/− males, which results in more severe colitis and dysplasia.     

Profiling of the Bacterial Microbiota along the Murine Alimentary Tract

Here, the spatial distribution of the bacterial flora along the murine alimentary tract was evaluated using high throughput sequencing in wild-type and Tff3-deficient (Tff3^KO) animals. Loss of Tff3 was linked to increased dextran sodium sulfate-induced colitis. This systematic study shows the results of 13 different regions from the esophagus to the rectum. The number of bacterial species (richness) increased from the esophagus to the rectum, from 50 to 200, respectively. Additionally, the bacterial community structure changed continuously; the highest changes were between the upper/middle and lower gastrointestinal compartments when comparing adjacent regions. Lactobacillus was the major colonizer in the upper/middle gastrointestinal tract, especially in the esophagus and stomach. From the caecum, a drastic diminution of Lactobacillus occurred, while members of Lachnospiraceae significantly increased. A significant change occurred in the bacterial community between the ascending and the transverse colon with Bacteroidetes being the major colonizers with relative constant abundance until the rectum. Interestingly, wild-type and Tff3^KO animals did not show significant differences in their bacterial communities, suggesting that Tff3 is not involved in alterations of intraluminal or adhesive microbiota but is obviously important for mucosal protection, e.g., of the sensitive stem cells in the colonic crypts probably by a mucus plume.     

Human Intestinal Dendritic Cells in Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a serious, costly, and persistent health problem with an estimated prevalence in Western countries around 0.5% of the general population; its socioeconomic impact is comparable with that for chronic diseases such as diabetes. Conventional treatment involves escalating drug regimens with concomitant side effects followed, in some cases, by surgical interventions, which are often multiple, mainly in Crohn's disease. The goal of finding a targeted gut‐specific immunotherapy for IBD patients is therefore an important unmet need. However, to achieve this goal we first must understand how dendritic cells (DC), the most potent antigen present cells of the immune system, control the immune tolerance in the gastrointestinal tract and how their properties are altered in those patients suffering from IBD. In this review, we summarize the current available information regarding human intestinal DC subsets composition, phenotype, and function in the human gastrointestinal tract describing how, in the IBD mucosa, DC display pro‐inflammatory properties, which drive disease progression. A better understanding of the mechanisms inducing DC abnormal profile in IBD may provide us with novel tools to perform tissue specific immunomodulation.     

Yogurt starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus ameliorate symptoms and modulate the immune response in a mouse model of dextran sulfate sodium-induced colitis

We investigated the yogurt starter cultures of Lactobacillus bulgaricus 151 and Streptococcus thermophilus MK-10 for their effect on the severity of experimental colitis, lymphocyte profile, and regulatory T-cell response. Colitis was induced in BALB/c mice via the administration of 3.5% dextran sulfate sodium salt (DSS) in drinking water for 6 d. Next, the mice were gavaged intragastrically with an active yogurt cultures (YC) mixture (～5 × 10⁹ cfu/mouse per day) or saline (vehicle) for 8 d. Mice receiving DSS or saline alone served as positive and negative controls, respectively. The length of the colon, disease activity index, histological scores, myeloperoxidase activity, epithelium-associated microbes, short-chain fatty acid profile, total IgA antibody-forming cells, CD3⁺CD8⁺, CD3⁺CD4⁺, CD3⁺CD4⁺CD25⁺, CD3⁺CD4⁺CD25⁺Foxp3⁺ T-cell subsets, and cytokine profiles (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and tumor necrosis factor) were examined after termination of the mice. Feeding mice with YC mixture reduced disease symptoms and modified intestinal microbiota and host inflammatory responsiveness to DSS. We observed limited weight loss and a decreased disease activity index score, lowered myeloperoxidase activity, and somewhat reduced damage of the intestine. The YC mixture upregulated the colon length, increased the amount and diversity of mucosa-associated microbes (enterobacteria, enterococci, and yeast), and decreased the concentration of putrefactive short-chain fatty acids in the cecal contents. It downregulated the input of cytotoxic CD3⁺CD8⁺ T cells and CD3⁺CD4⁺CD25⁺FoxP3⁺ regulatory T cells in Peyer's patches and enhanced CD3⁺CD4⁺CD25⁺ T cells in spleens and CD3⁺CD4⁺CD25⁺FoxP3⁺ cells in peripheral blood mononuclear cells. Simultaneously, IgA antibody-forming cells were downregulated in mesenteric lymph nodes (MLN) and enhanced in spleens (SPL). The cultures mostly enhanced the production of cytokines tested in MLN and SPL, except for IL-6, which was downregulated in MLN. Interleukin-2 and IL-4 were the most upregulated in MLN, whereas IL-10, IL-4, IL-2, IFN-γ, and tumor necrosis factor were most upregulated in SPL. In serum, the YC mixture downregulated IFN-γ and clearly increased IL-2. Based on these results, we recognize the high anti-inflammatory and immunomodulatory potential of the L. bulgaricus 151 and S. thermophilus MK-10 set. The strains possess the ability to modulate the intestinal mucosal and systemic immune system toward both IgA production and induction of regulatory T cells, shifting Th1/Th2 balance.     

谷维素抑制DSS诱导的小鼠结肠炎症及其分子机理研究

谷维素(oryzanol)是米糠中重要的活性物质之一。C57BL/6小鼠连续饮用1.0%葡聚糖硫酸钠(dextran sulphate sodium,DSS)12 d,用以建立溃疡性结肠炎模型,评估谷维素的抗炎作用及其分子机理研究。结果发现:谷维素组小鼠能明显缓解DSS诱导的结肠炎症,小鼠肠壁厚度、结肠长度、结肠重量、炎症细胞浸润、疾病活动指数(disease active index,DAI)等病理指标明显改变;谷维素也能明显改善结肠组织中炎症损伤重要生化指标如髓过氧化物酶(myeloperoxidase,MPO)和丙二醛(malondialdehyde,MDA)的含量,同时减少血浆中亚硝酸盐的含量;RT-q PCR技术分析发现结肠组织炎症因子TNF-α、IFN-γ、IL-1和IL-6等m RNA表达水平受到明显抑制,Western blotting分析进一步证实了谷维素能抑制炎症因子的蛋白表达水平。结论:谷维素对DSS诱导的小鼠结肠炎具有抑制作用,其作用的分子机理可能与下调炎症因子的表达相关。     

巴柳氮的合成改进

以对-硝基苯甲酰氯为起始原料,经缩合、还原、重氮化、偶合4步反应制得巴柳氮,总收率73. 9%。利用TLC ,IR ,1HNMR对产品进行了表征。     

慢性结肠炎中药保留灌肠的护理对策

目的探讨结肠透析机清洗结肠后,进行中药汤剂保留灌肠治疗慢性结肠炎的护理对策。方法随机将慢性结肠炎病人192例分成2组,治疗组98例,对照组94例,治疗组先采用透析机对结肠进行充分清洗。对照组采用传统手工清洁浣肠后用同样的中药汁200～250mL进行保留灌肠。结果治疗组82例症状完全缓解,随访半年无复发,14例临床症状部分缓解,1例症状未缓解。对照组56例症状完全缓解,半年以后无复发,28例症状部分缓解,10例症状未缓解,2组均无并发症。结论结肠透析机清洗结肠配合中药汤剂保留灌肠治疗慢性结肠炎,疗效明显好于传统的中药汤剂灌肠,且复发率大为降低,经济安全。     

Novel Role of Ghrelin Receptor in Gut Dysbiosis and Experimental Colitis in Aging

Chronic low-grade inflammation is a hallmark of aging, which is now coined as inflamm-aging. Inflamm-aging contributes to many age-associated diseases such as obesity, type 2 diabetes, cardiovascular disease, and inflammatory bowel disease (IBD). We have shown that gut hormone ghrelin, via its receptor growth hormone secretagogue receptor (GHS-R), regulates energy metabolism and inflammation in aging. Emerging evidence suggests that gut microbiome has a critical role in intestinal immunity of the host. To determine whether microbiome is an integral driving force of GHS-R mediated immune-metabolic homeostasis in aging, we assessed the gut microbiome profiles of young and old GHS-R global knockout (KO) mice. While young GHS-R KO mice showed marginal changes in Bacteroidetes and Firmicutes, aged GHS-R KO mice exhibited reduced Bacteroidetes and increased Firmicutes, featuring a disease-susceptible microbiome profile. To further study the role of GHS-R in intestinal inflammation in aging, we induced acute colitis in young and aged GHS-R KO mice using dextran sulfate sodium (DSS). The GHS-R KO mice showed more severe disease activity scores, higher proinflammatory cytokine expression, and decreased expression of tight junction markers. These results suggest that GHS-R plays an important role in microbiome homeostasis and gut inflammation during aging; GHS-R suppression exacerbates intestinal inflammation in aging and increases vulnerability to colitis. Collectively, our finding reveals for the first time that GHS-R is an important regulator of intestinal health in aging; targeting GHS-R may present a novel therapeutic strategy for prevention/treatment of aging leaky gut and inflammatory bowel disease.