The possible mechanisms of Picrasma quassiodes (D. Don) Benn. in the treatment of colitis induced by 2,4,6-trinitrobenzene sulfonic acid in mice

Ethnopharmacological relevance

Picrasma quassiodes (D. Don) Benn.(PQB) is used in folk medicines for the treatment of colds, upper respiratory infection, acute tonsillitis, acute gastroenteritis, bacillary dysentery and a variety of acute infectious diseases in Asia. Although recent reports indicate that PQB has antibacterial, and anti-inflammatory effects, its effects on colitis and its inhibitory mechanisms have not been previously reported.

Aim of the study

To assess the effects and the mode of action of the extract of Picrasma quassiodes (D. Don) Benn.(PQB) on a model of colitis in mice induced by trinitrobenzene sulfonic acid (TNBS).

Materials and methods

We induced mice colitis using TNBS/ethanol, then different doses of Picrasma quassiodes (D. Don) Benn.(PQB) extract (100, 200 and 400 mg/kg/day) and sulfasalazine (500 mg/kg/day) were administered by gavage for 7 days after the induction of colitis. The mice body weight, colonic wet weight, colonic lengths, myeloperoxidase (MPO) activity, macroscopic and histological colon injury were observed. Pro-inflammatory cytokines such as: tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were assayed by enzyme-linked immunoassay. The protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the colons were determined by immunohistochemical analysis.

Results

PQB administration effectively prevented mice diarrhea, decreasing of the body weights, shortening of colon length and increasing of colon wet weight. Macroscopic and histological examinations also indicated that it was protected against colonic edema, ulceration and MPO activity elevation. Furthermore, PQB inhibited the abnormal secretions of pro-inflammatory cytokines, such as TNF-α and IL-8. Additionally, administration of PQB effectively inhibited COX-2 and iNOS protein expression.

Conclusions

These results suggest that PQB has an anti-inflammatory effect on TNBS-induced colitis due to the down-regulations of the productions and expressions of inflammatory mediators, and that it may be a potential inflammatory bowel disease (IBD) drug candidate.     

全氟辛烷磺酸通过NLRP3炎症小体诱导幼年期大鼠肺损伤及格列本脲干预的研究

目的:探讨含NLRP3家族Pyrin域蛋白3(NLRP3)炎症小体参与全氟辛烷磺酸(PFOS)诱导幼年期大鼠肺损伤的可能机制。方法:28只21日龄SD大鼠随机分为对照(C)组、PFOS(P)组、格列本脲(G)组和格列本脲+PFOS(GP)组。将实验动物根据不同分组建立PFOS暴露模型和格列本脲保护模型,留取肺标本进行HE染色,ELISA法检测肺组织中髓过氧化物酶(MPO)含量以及支气管肺泡灌洗液(BALF)中白细胞介素1β(IL-1β)和IL-18含量,高效液相色谱法(HPLC)检测血清中PFOS浓度,Western blot法检测肺组织中NLRP3、caspase-1和含CARD凋亡相关斑点样蛋白(ASC)的蛋白水平。结果:肺组织病理切片HE染色结果显示,与C组相比,P组的气管及肺泡间质可见明显炎症浸润;格列本脲可使炎症反应显著减轻。ELISA结果显示,P组肺组织中MPO含量较C组显著升高(P<0.05),P组BALF中的IL-1β和IL-18含量较C组也明显升高(P<0.05);GP组肺组织MPD含量及BALF中IL-1β和IL-18含量均较P组降低(P<0.05...     

Oral commensal bacterial flora is responsible for peripheral differentiation of neutrophils in the oral mucosa in the steady state

ObjectivesCommensal bacteria in the host body play a fundamental role in the differentiation and maintenance of the immune system. Studies on intestinal immunity have revealed that, under steady-state conditions, microflora have an important role in the maintenance of health. However, the role of oral commensal bacteria on the oral immune system is still unclear. Here, we clarify the interactions between commensal bacteria and the oral mucosal immune system under steady-state conditions.MethodsWe used germ-free mice that had never been exposed to bacteria and conventional mice grown with normal bacterial flora. Oral cells were isolated from the oral mucosa, stained with specific antibodies, and analyzed by flow cytometry. For the detection of myeloperoxidase and intracellular cytokines, oral cells were stimulated with N-formyl-methionine-leucyl-phenylalanine and phorbol 12-myristate 13-acetate/ionomycin, respectively.ResultsWe found that the oral mucosa harbored more neutrophils in germ-free mice than in conventional mice. However, the majority of neutrophils in the germ-free oral mucosa exhibited an immature phenotype. Other immune cells, including macrophages, T cells, and B cells, in the oral mucosa of germ-free mice showed similar differentiation to those in conventional mice. These results indicate that in the steady-state oral mucosa, the normal commensal flora promote the peripheral differentiation of neutrophils.ConclusionsThe presence of commensal flora is critical for the development of adequate immune system in the oral mucosa.     

Among biomarkers of neutrophil activity,matrix metalloproteinases 8 independently predicts remission of metabolic syndrome

Background and aimsInflammation due to the excess of nutrient intake plays an important role in the pathophysiology of metabolic syndrome (MetS). Here, the potential influence of neutrophils and their degranulation markers on MetS improvement upon dietary and behavioral counselling, has been investigated. Specifically, we aimed at investigating their role as potential predictors of metabolic syndrome improvements.Methods and Resultspatients with MetS (n = 127) received behavioral and dietary recommendations before follow-up at 6 months. Serum levels of matrix metalloproteinases (MMP)8, MMP9, myeloperoxidase (MPO), tissue inhibitor of MMP (TIMP)-1, TIMP-2, TIMP-3 and resistin were tested at baseline. In the whole cohort, baseline levels of proinflammatory MMP8, MMP9 and MPO increased together with the number of MetS criteria. Seventy-three (57%) patients experienced a reduction in MetS-defining criteria at follow-up. With respect to those with no improvement, such individuals showed lower weight and waist circumference at enrolment, less frequent smoking habits, higher levels of triglycerides and lower circulating MMP8. At logistic regression analysis, baseline MMP8 showed negative predictive ability (odds ratio (OR) 0.979 [0.961–0.997]; p = 0.025) against MetS improvement. Such findings hold true even when included in the backward stepwise logistic regression model confirming MMP8 as an independent predictor (OR 0.970 [0.949–0.993]; p = 0.009). Receiver operating characteristic (ROC) curve confirmed the predictive ability of MMP8 combined in a model including baseline MetS criteria and waist circumference. Bootstrap resampling analysis internally validated our findings.ConclusionImprovement of MetS is independently associated with baseline low MMP-8 levels, suggesting a pivotal role for inflammation in metabolic alteration.     

A diagnostic score for eosinophilic granulomatosis with polyangiitis among eosinophilic disorders

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a form of systemic vasculitis with eosinophilic inflammation. However, existing classification criteria are all designed to classify EGPA among vasculitis and there is no established method distinguishing EGPA from other eosinophilic disorders. The aim of the present study was to propose a scoring system to differentiate EGPA among eosinophilic disorders.MethodsNon-supervised hierarchical clustering using Ward's method and principal component analysis (PCA) were performed for 19 clinical parameters of 58 patients with eosinophilia-related diseases at a tertiary university hospital. The newly proposed scoring system was externally validated in 40 patients at another tertiary institution.ResultsTwo distinct clusters were identified, and clinical features including peripheral neuropathy, asthma, skin involvement, lung involvement, rheumatoid factor (RF) positivity, myeloperoxidase (MPO)–anti-neutrophil cytoplasmic antibody (ANCA) positivity, IgE elevation, C-reactive protein (CRP) elevation, and vasculitis pathological findings were predominantly observed in one of these clusters (p < 0.05). Ten features defining the cluster with a high rate of vasculitis were weighted by PCA to create the E-CASE (EGPA classification among systemic eosinophilia) scoring system, on a 16-point scale. Based on the distribution of scores in the primary cohort, we defined an E-CASE score ≥12 as positive, ≤ 8 as negative, and 9–11 as undeterminable. The sensitivity and specificity of the E-CASE score in the validation cohort were 93.3% and 100%, respectively.ConclusionsWe developed and verified a novel scoring system for differentiating EGPA from other types of eosinophilic disorders.     

髓过氧化物酶在冠心病中的诊断应用

大量研究证实,炎症促进了动脉粥样硬化的形成及发展,表现为粥样硬化斑块的形成.动脉硬化引起的危重心血管事件,如心肌梗死或缺血性脑卒中,为易损斑块破裂所导致[1].血制品中的蛋白或酶类通常作为生物标记物,反映疾病状态,并提供诊断及预后价值[2].     

Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors

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非糖尿病维持性血液透析患者髓过氧化物酶与颈动脉硬化的相关性

目的探讨非糖尿病维持性血液透析患者髓过氧化物酶与颈动脉硬化相关指标的关系。方法酶联免疫吸附法测定非糖尿病维持性血液透析患者同一次透析前后血浆髓过氧化物酶和血清弹性蛋白酶水平变化,同时B超测定两侧颈总动脉内膜中膜厚度、斑块数量及面积,并对各项指标做相关性分析。结果血液透析后血浆髓过氧化物酶水平明显高于血液透析前(P<0.01),血清弹性蛋白酶水平透析前后无明显变化。年龄、血液透析前髓过氧化物酶水平与颈总动脉内膜中膜厚度明显正相关(P<0.01),血液透析后髓过氧化物酶水平与血液透析前后弹性蛋白酶水平无相关,与各项颈动脉硬化指标也无相关。结论年龄及血液透析前髓过氧化物酶水平与动脉硬化有关,而特定血液透析条件时血液透析后血浆髓过氧化物酶水平的升高与中性粒细胞脱颗粒及动脉硬化程度无关,可能是肝素诱发的动脉壁髓过氧化物酶释放,这种释放对维持性血液透析患者动脉硬化的意义有待进一步研究。     

髓过氧化物酶与急性冠状动脉综合征的关系

炎症在动脉粥样硬化的发生、发展中占有重要的地位，髓过氧化物酶是由活化的中性粒细胞、单核细胞和部分巨噬细胞分泌的，是中性粒细胞活化的标志物。髓过氧化物酶及其氧化产物具有促进动脉粥样硬化的作用，并参与斑块的不稳定，与急性冠状动脉综合征的发生密切相关。髓过氧化物酶可作为急性冠状动脉综合征的早期预测因子，并可预测其不良事件的发生情况。