IL - 22与糖尿病关系的研究进展

目的 本文总结了近年来白细胞介素22 (interleukin 22, IL - 22)与糖尿病(diabetes mellitus，DM)发病关系的研究，希望能为DM的防治及病情评估提供较为可行的策略靶点。方法 本文资料来源于中国知网、PubMed等数据库，以IL - 22、糖尿病、胰岛素、糖异生等关键词进行检索得到。结果 IL - 22可增加胰岛素分泌、促进胰岛素信号转导及维持葡萄糖稳态，参与DM发生、发展及病情演变。结论 IL - 22可通过多个环节参与DM的发病及病情演变，以IL - 22为靶点对于防治DM具有重要参考价值。     

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

荔枝草治疗急性咽炎有效部位筛选＊

目的 筛选荔枝草治疗急性咽炎的有效部位，研究治疗急性咽炎的作用机制，为荔枝草资源的药食两用开发提供理论依据。方法 通过二甲苯致小鼠耳肿胀试验筛选荔枝草抗炎有效部位，采用氨水刺激喉部法建立大鼠急性咽炎模型，通过行为学观察、ELISA双抗夹心检测、病理形态学观察和咽部组织蛋白表达研究乙酸乙酯部位对大鼠急性咽炎的治疗效果。结果 荔枝草乙酸乙酯提取物对二甲苯致小鼠耳肿胀有明显的抑制作用，氨水刺激建立的急性咽炎模型符合急性咽炎动物模型特征，乙酸乙酯部位提取物可显著改善急性咽炎大鼠的咽部病理形态学表现。不同剂量治疗组大鼠血清及咽部组织中IL-1β、IL-6及TNF-α炎性因子数量均下降，高剂量组下降最为明显。荔枝草乙酸乙酯提取物可明显增加大鼠咽部组织IκBα蛋白表达，降低NF-κBp65蛋白表达。结论 荔枝草乙酸乙酯部位提取物对急性咽炎具有治疗作用，可能与抑制咽部炎症病理改变的发生，能调节血液中炎症因子、抑制NF-κB表达和IκBα解离有关。     

IL-37b作用于树突状细胞CD39/ATP轴抑制类风湿性关节炎大鼠炎症反应的作用及机制

目的探讨白细胞介素37b重组蛋白(rmIL-37b)通过调节CD39/ATP轴抑制树突状细胞(DC)诱导类风湿性关节炎(RA)大鼠炎症反应的机制。方法将SD大鼠随机分为空白对照组(CTL)、CIA模型组、rmIL-37b 5μg/kg组、rmIL-37b 10μg/kg组,每组各10只。除了空白对照组外,其余大鼠采用含有卡介苗的完全弗氏佐剂和牛Ⅱ型胶原混合乳液免疫刺激,建立CIA模型。确定建模成功当天(D0),rmIL-37b组分别尾静脉注射5μg/kg、10μg/kg rmIL-37b;CTL组和CIA模型组注射相同体积的(1 ml/kg)生理盐水,连续给药15 d。免疫组化法检测滑膜组织Nod样受体蛋白3(NRPL3)炎症小体的表达,流式细胞术检测DC表型,另外试剂盒检测血清三磷酸腺苷(ATP)和免疫学指标。结果与CIA模型组相比,rmIL-37b 10μg/kg组大鼠足容积、AI值、NLRP3炎症小体表达量、血清ATP、IL-1β、IL-18、肿瘤坏死因子α(TNF-α)、抗Ⅱ型胶原抗体亚型(anti-ColⅡ-IgG、anti-ColⅡ-IgG2a)水平均降低,同时DC表面CD...     

Targeting tissue-resident memory CD8+ T cells in the kidney is a potential therapeutic strategy to ameliorate podocyte injury and glomerulosclerosis

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Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Contributions of the NICHD neonatal research network's generic database to documenting and advancing the outcomes of extremely preterm infants

The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) maintains a database of extremely preterm infants known as the Generic Database (GDB). Begun in 1987, this database now includes more than 91,000 infants, most of whom are extremely preterm (<29 weeks gestation). The GDB has been the backbone of the NRN, providing high quality, prospectively collected data to study the changing epidemiology of extreme prematurity and its outcomes over time. In addition, GDB data have been used to generate hypotheses for prospective studies and to develop new clinical trials by providing information about the numbers and characteristics of available subjects and the expected event rates for conditions and complications to be studied. Since its inception, the GDB has been the basis of more than 200 publications in peer-reviewed journals, many of which have had a significant impact on the field of neonatology.     

核因子κB受体活化因子配体和肿瘤坏死因子α经炎性牙周膜干细胞外泌体促进破骨细胞分化

目的　慢性牙周炎表现的病理性骨吸收非常常见，牙周膜干细胞（PDLSCs）的外泌体（Exo）对骨吸收的作用和影响尚不明确，本研究分析了该Exo蛋白组分对破骨细胞分化的影响。方法　分别从正畸前拔牙患者和慢性牙周炎患者的牙周膜组织中提取PDLSCs，通过流式细胞术检测表面标记物；通过差速离心分别提取2种细胞的Exo，即Exo-WT和Exo-CP，并通过Western blot、透射电子显微镜（TEM）、蛋白浓度检测、纳米粒径追踪检测Exo特征；通过蛋白质谱检测2种Exo的蛋白组分；通过酶联免疫吸附（ELISA）验证了差异表达蛋白肿瘤坏死因子α（TNF-α）、核因子κB受体活化因子配体（RANKL）、白细胞介素（IL）-1α、转化生长因子β（TGF-β）、骨形态发生蛋白2（BMP-2）表达水平；将10、100、1 000 μg·mL^-1的Exo-CP或Exo-WT加入RAW264.7培养基中并于5 d时通过实时荧光定量聚合酶链反应（RT-qPCR）、Western blot、抗酒石酸酸性磷酸酶（TRAP）染色检测破骨分化相关指标表达情况；采用SPSS 24.0软件对实验数据进行统计学分析。结果　Exo-CP富集的差异表达蛋白主要与破骨细胞分化的TNF信号通路、核转录因子κB（NF-κB）信号通路相关；ELISA实验证实了Exo-CP中高表达TNF-α、RANKL、IL-1α，低表达TGF-β1、BMP-2（P<0.05）；Exo-CP作用于RAW264.7，显著提高了细胞的破骨分化相关基因及蛋白的表达水平，TRAP染色可见分化的破骨细胞，且呈现浓度依赖性，100、1 000 μg·mL^-1浓度Exo-CP对破骨细胞分化的促进作用显著高于10 μg·mL^-1浓度组（P<0.05）。结论　慢性牙周炎的病理性骨吸收可能由炎性PDLSCs所分泌的Exo通过促进破骨细胞分化引起，Exo中主要的作用蛋白可能为RANKL和TNF-α，本研究为慢性牙周炎骨吸收的发病机制提供了新视角。     

Cytokine and LL-37 gene expression levels in Bartonella spp. seropositive and seronegative patients of a rheumatology clinic

PurposeThe variation in the immune response to Bartonella spp. infection in humans remains unclear. The present study compares the expression of selected interleukins, cytokines and cathelicidin (LL-37) in rheumatology clinic patients suffering from musculoskeletal symptoms with healthy blood donors. The patients had previously been tested for the presence of Bartonella henselae antibodies.MethodsGene expression of LL-37, interleukin (IL)-2, IL-4, IL-6, IL-12, interferon-(IFN)-γ, and tumor necrosis factor (TNF-α)-α was determined in blood samples using quantitative Polymerase Chain Reaction (qPCR). Statistical analysis was prepared with STATISTICA.ResultsStatistically significant differences in the mRNA levels of the tested cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-12; p<0.0001) were observed between the healthy controls and patients; however, no difference was observed for LL37 mRNA (p ?= ?0.1974). No significant differences in mRNA expression were observed between IgG in anti-Bartonella seropositive and seronegative individuals (p>0.05). The only significant differences between the Bartonella spp. DNA positive and negative patients, indicated by PCR, were observed for TNF-α and IL-12 mRNA (p ?= ?0.0045 and p ?= ?0.0255, respectively).ConclusionA broadly similar immune response to the tested cytokines was observed among the participants irrespective of anti-Bartonella spp. IgG seropositivity. However, the Bartonella DNA-positive participants demonstrated significantly lower expression of IL-12 and TNF-α mRNA; this may indicate that these bacteria have a suppressive influence on the immune system.     

低氧刺激鼻息肉黏膜上皮细胞炎性因子变化的初探

目的研究低氧刺激慢性鼻窦炎伴鼻息肉(CRSwNP)与正常鼻黏膜上皮细胞炎性因子的变化与异同,探讨其在CRSwNP发病机制中的作用。方法选择2015年6月至2018年1月在吉林大学中日联谊医院就诊的68例CRSwNP患者,其中男性36例,女性32例,年龄(45.2±12.5)岁(xˉ±s,下同),患者的鼻息肉黏膜纳入慢性鼻窦炎鼻息肉组(CRS-NP组),下鼻甲黏膜纳入慢性鼻窦炎下鼻甲组(CRS-IT组),并根据组织病理学结果进一步分成嗜酸粒细胞浸润及非浸润两种类型,即嗜酸粒细胞浸润性鼻息肉组(Eos-NP组,n=34)、非嗜酸粒细胞浸润性鼻息肉组(Non-Eos-NP组,n=34)、嗜酸粒细胞浸润性鼻息肉患者的下鼻甲组(Eos-IT组,n=20)和非嗜酸粒细胞浸润性鼻息肉患者的下鼻甲组(Non-Eos-IT组,n=20);同期25例鼻窦囊肿或鼻中隔偏曲患者的下鼻甲黏膜作为对照组(n=25),其中男性14例,女性11例,年龄(42.8±10.2)岁。免疫组织化学染色分析各组黏膜上皮组织中白细胞介素(IL)17A、干扰素γ(IFN-γ)、肿瘤坏死因子α(TNF-α)与乏氧诱导因子(hypoxia-inducible factor 1α,HIF-1α)的表达情况。酶联免疫吸附试验检测低氧刺激0、24和48 h后各组原代鼻黏膜上皮细胞分泌IL-17A、IFN-γ和TNF-α的差异;免疫荧光、固态光源高内涵与免疫印记实验检测原代鼻黏膜上皮细胞HIF-1α的表达情况。应用SPSS 17.0软件对数据进行统计学分析,采用双向方差分析作为主要统计学方法。结果免疫组织化学染色结果显示,IL-17A和TNF-α在对照组中表达最高(光密度值分别为0.37±0.03、0.53±0.02),IFN-γ和HIF-1α在Eos-IT组中表达最高(光密度值分别为0.47±0.03、0.39±0.02)。未接受低氧刺激时,IL-17A与TNF-α在对照组中水平较低;低氧刺激48 h后,对照组的IL-17A与TNF-α分泌量明显高于其他各组。未接受低氧刺激时,Eos-NP组分泌的IFN-γ明显高于对照组[(13.7±1.3)pg/ml比(11.1±1.6)pg/ml,P<0.05];低氧刺激48 h后,IFN-γ在对照组和Eos-NP组中的分泌量没有显著区别。对照组与CRS-IT组表达的HIF-1α随低氧时间延长而增加,Eos-NP组与Non-Eos-NP组表达的HIF-1α随低氧时间延长而减少。对照组与CRS-IT组HIF-1α主要表达于鼻黏膜上皮细胞的细胞质内,CRS-NP组HIF-1α主要表达于鼻黏膜上皮细胞的细胞核内。结论低氧刺激下,CRSwNP患者的鼻息肉、下鼻甲与正常鼻黏膜上皮细胞中IL-17A、TNF-α、IFN-γ的分泌以及HIF-1α的表达水平存在差异,且呈现不同的亚细胞定位,提示其可能参与了CRSwNP发病相关基因的转录与调控。