外泌体在病毒感染中的研究进展

外泌体（exosomes）是由细胞释放至胞外的膜性囊泡,直径40~100nm。外泌体可介导细胞间信息传递和物质交换,在疾病的发生发展中发挥着重要作用。在病毒感染过程中,外泌体既可传递病毒核酸、RNA和蛋白质,又可传递抗病毒分子引起免疫应答。通过对外泌体的深入研究,可在病毒感染临床治疗中提供新前景。     

外泌体miRNAs在器官纤维化中作用的研究进展

外泌体是由多种细胞主动分泌产生的可携带蛋白质、脂质、miRNAs等生物分子的微小囊泡。外泌体微小RNAs(miRNAs)稳定的存在于体液循环中,参与器官多项病理过程。在器官纤维化疾病中,外泌体miRNAs的含量与正常组织相比呈现出明显的差异性表达,通过调控不同信号通路促进或抑制器官纤维化。外泌体miRNAs可作为临床诊断器官纤维化及判断其纤维化程度的最新生物指标和纤维化疾病新的治疗靶点。     

外泌体在心血管疾病中的研究进展*

AIM: Exosomes are bi-lipid membrane originated in the cell endocytosis system and secreted into the extracellular matrix. The cells secrete exosomes into extracellular matrix to impact target cells with the significant functions of cell-cell information transmission and immunological regulation. Recent studies show that cell-cell communication regulated by exosomes can be found in both physiological and pathological conditions of cardiovascular diseases (CVD). Exosomes derived from many types of cells (such as myocardial cells, endothelial cells and stem cells) play an important regulatory role in the pathogenetic mechanism of CVD. Meanwhile, exosome-based investigations have shown huge potential for the treatment of CVD. This review will focus on the biological characteristics and functions of exosomes in the diagnosis and treatment of CVD.     

外泌体调控树突状细胞免疫功能的研究进展

树突状细胞（DC）是机体内抗原提呈能力最强的一类抗原提呈细胞（APC）,是联系固有免疫和适应性免疫的纽带。外泌体为体内活细胞分泌的双层囊泡小体,携带多种生物活性物质,参与细胞间信息传递和物质交换。内容物含量、大小、细胞来源等特征的不同组合导致了外泌体的高度异质性,因此,外泌体对DC功能调节的方式及机制具有复杂性和不确定性。本文系统回顾近年外泌体参与DC功能调控的研究进展,并对工程化外泌体的开发策略与应用现状进行总结,以期为后续研究和应用提供参考。     

外泌体miRNA在心血管疾病中的研究进展

<正>心血管疾病(cardiovascular diseases,CVD)是全球高发性疾病,其中冠心病(coronary heart disease,CHD)是世界范围内的主要死亡原因,在老年人群中死亡率和发病率不断上升[1],与微小RNA(microRNA,miRNA,miR)的调节密切相关[2]。研究报道,miRNA调节大量信号通路,可通过外泌体(exosome)实现细胞间传递,参与细胞间的信息交流[3],其严格     

间充质干细胞外泌体在眼部疾病中的研究进展

眼部疾病病因复杂且种类多种多样,主要包括眼眶、角膜、虹膜、视神经、视网膜等疾病,如果不及时治疗或处理不当会导致视力模糊,严重的会导致失明.手术和药物治疗存在一定的局限性.近几年,由于间充质干细胞(MSC)具有免疫调节和促进血管生成等特性,在许多眼部疾病的细胞疗法中被广泛探索.随着无细胞疗法的兴起,间充质干细胞外泌体(M...     

外泌体在前列腺癌诊疗中的研究进展

前列腺癌(PCa)是男性常见的恶性肿瘤。外泌体是存在于人体多种体液中的双层膜囊泡,携带核酸、蛋白等物质,介导细胞间通讯。外泌体可以促进前列腺癌的生长,协助免疫逃逸及化学治疗耐药,诱导血管生成、上皮细胞间充质转化(EMT)并为转移前生态位的形成提供条件,进而促进前列腺癌的侵袭和转移。基于肿瘤细胞与正常细胞分泌的外泌体成分不同,外泌体可作为前列腺癌诊断、预测侵袭转移、评估患者预后及药物疗效的生物标志物,并有望作为药物运输载体,在肿瘤的精准治疗中具有广阔的前景。     

外泌体与神经退行性疾病关系的研究进展

外泌体是一种内吞起源的纳米级细胞外囊泡(EV),可以由真核生物在生理和病理条件下分泌,它含有神经退行性疾病(NDs)发病相关的蛋白,有作为生物标志物的潜力,并可穿过血脑屏障,有助于将药物和其他治疗分子输送到大脑治疗NDs。所以,在本文中,我们将对外泌体在不同NDs发病机制中所起的作用,以及将它们作为疾病诊断生物标志物和治疗手段的相关研究进行综述。     

树突状细胞来源的exosomes研究进展

Exosomes是多种活细胞晚期内体分泌的小囊泡体,不同来源的exosolnes其特异性功能与它所含的特异性蛋白质以及它所处的做环境密切相关。树突状细胞来源的exosomes（Dex）富含树突状细胞的MHC—I／II类分子、协同刺激分子等多种生物活性分子,在体内、外实验中显示出与树突状细胞相似的功能．可诱发机体免疫应答或诱导免疫耐受：作为一种新型的非细胞疫苗,exosomes在抗肿瘤免疫治疗以及抑制移柑{免疫排斥和自身免疫性疾病治疗等各方面的应用前景受到极大的关注。     

亚甲蓝治疗缺血性脑卒中的研究进展

脑卒中作为全球高致死、高致残的疾病,一直被广泛研究。亚甲蓝作为一种被美国食品药品管理局（FDA）批准用于治疗高铁血红蛋白血症和氰化物中毒的药物已有一百二十余年,而在近期研究中发现其具有神经保护作用,并在缺血性脑卒中的动物模型中展现出良好的保护作用。我们就近年来亚甲蓝治疗缺血性脑卒中的研究进行简要综述。     

IL-18基因修饰对肺癌细胞来源exosome诱导杀伤肿瘤细胞作用的影响

目的: 研究细胞介素18( IL-18 )基因修饰对肺癌细胞来源exosome诱导杀伤肿瘤细胞作用的影响,以探讨高效exosome疫苗的制备。方法: 提取 IL-18 基因修饰的NCI-H460细胞(IL-18/H460)、pcDNA3.1⁺载体修饰细胞(DNA3.1/H460)及未修饰NCI-H460细胞(NCI-H460)上清液的exosome,透射电镜下观察exosome形态;用Western blotting方法检测exosome中热休克蛋白70(HSP70)、人白细胞抗原(HLA)及IL-18的表达;用exosome直接刺激活化T细胞,用乳酸脱氢酶(LDH)法测定T细胞对NCI-H460细胞的杀伤作用;用exosome冲击树突状细胞(DCs),然后活化T细胞,测定对NCI-H460细胞的杀伤作用,计算杀伤率。结果: 透射电镜下观察exosome具有典型的形态;3组exosome中均有HSP70及HLA蛋白表达,IL-18/H460组有IL-18蛋白表达。效靶比25∶ 1、10∶ 1、5∶ 1时exosome直接提高活化T细胞的杀伤率,IL-18/H460组为(38.45±5.42)%、(25.17±3.94)%和(11.75±3.22)%,exosome冲击DCs活化T细胞的杀伤率,IL-18/H460组为(89.05±4.06)%、(64.97±6.02)%和(40.16±4.98)%,均高于其余2组。Exosome冲击DCs活化T细胞的杀伤作用强于exosome直接刺激活化的T细胞。结论: IL-18 基因修饰能增强NCI-H460细胞来源exosome诱导的杀伤肿瘤细胞作用。     

The role of iron neurotoxicity in ischemic stroke

Stroke is the second leading cause of death worldwide, and its incidence is expected to rise with the projected increase in the number of aging population. Disturbances of brain iron homeostasis have been linked to acute neuronal injury following cerebral ischemia. Free iron catalyzes the conversion of superoxide and hydrogen peroxide into hydroxyl radicals, which promote oxidative stress leading to subsequent cell death/apoptosis. In recent years, considerable evidence has emerged regarding the role of iron neurotoxicity following experimental cerebral ischemia. Few clinical studies have also attempted to investigate the role of iron in stroke patients. The present review will examine the currently available evidence for iron-mediated neurotoxicity and the potential mechanisms underlying deregulation of iron homeostasis in the brain following cerebral ischemia. Understanding the changes in brain iron metabolism and its relationship to neuronal injury in ischemic stroke could provide new therapeutic targets to improve the outcome of stroke patients.     

细胞分泌的囊状小体exosomes的研究进展

有多种细胞都能分泌一种被称为exosomes的小囊泡，这些囊泡由细胞内的内吞小体出泡产生，它包裹着特殊的蛋白质，在信息传递中起着很重要的作用。特别是在免疫系统中，exosomes能够将外来抗原传递给T细胞，并且在免疫调节中发挥作用。exosomes作为一种免疫治疗的新手段，可以应用在肿瘤治疗和免疫耐受等方面。     

凋亡细胞与外染色体的免疫调节作用

树突状细胞（DC）是专职的抗原递呈细胞（APC）,它能够引起同种异体移植物排斥的抗供者T细胞反应。利用供者来源的凋亡细胞或外染色体在原位将供者同种异体抗原递呈给受者的静止DC来诱导耐受,凋亡细胞和外染色体的免疫调节作用为诱导移植耐受提供了一条新的途径。     

Role of dyslipidemia in ischemic stroke patients treated in the telestroke network

PurposeThe relationship between the telestroke technology and clinical risk factors in a dysplipidemic ischemic stroke population and neurologic outcomes is not fully understood. This issue was investigated in this study.Patients and methodsWe analyzed retrospective data collected from a regional stroke registry to identify demographic and clinical risk factors in patients with improving (NIHSS ​≤ ​7) or worsening (NIHSS ​> ​7) neurologic outcome in dyslipidemic ischemic stroke population. We used logistic multivariate models to identify independent predictors of improving or worsening outcome based on dyslipidemia disease status in ischemic stroke patients.ResultsIn the adjusted analysis for dyslipidemic ischemic stroke population, cholesterol reducer use (odd ratio; [OR] ​= ​0.393, 95% confidence interval [CI], 0.176–0.879, P ​= ​0.023) and direct admission (OR ​= ​0.435, 95% CI, 0.199–0.953, P ​= ​0.037) were more likely to be associated with neurologic improvement and no clinical or demographic factors were associated with poor neurologic outcome in dyslipidemic ischemic stroke patients treated in the telestroke network.For the ischemic stroke population without dyslipidemia, increasing age (OR ​= ​1.070, 95% CI, 1.031–1.109, P ​< ​0.001), coronary artery disease (OR ​= ​3.633, 95% CI, 1.307–10.099, P ​= ​0.013), history of drug or alcohol abuse (OR ​= ​6.548, 95% CI, 1.106–38.777, P ​= ​0.038), and improvement in ambulatory outcome (OR ​= ​2.880, 95% CI, 1.183–7.010, P ​= ​0.020) were associated with worsening neurological functions, while being Caucasian (OR ​= ​0.294, 95% CI, 0.098–0.882, P ​= ​0.029) was associated with improving neurologic functions.ConclusionDemographic and clinical risk factors among the dysplipidemic ischemic stroke population in the telestroke network were not associated with worsening neurologic functions.     

低氧对巨噬细胞外泌体的表达及其对骨肉瘤细胞的化疗抗性影响的体外研究

目的在体外探究低氧对巨噬细胞外泌体分泌的影响及对骨肉瘤细胞顺铂耐药性的改变。方法Transwell侵袭实验检测不同氧浓度(1%O2的低氧与常氧)条件下骨肉瘤细胞MG63对巨噬细胞的趋化能力;在低氧与常氧条件下将MG63与巨噬细胞进行共培养,流式细胞术及RT-PCR检测巨噬细胞的分化;分离纯化来源于不同氧浓度条件下培养的M2型巨噬细胞外泌体,利用透射电镜、纳米粒径、Western blot进行鉴定,双免疫荧光进行示踪MG63对外泌体的摄取;克隆形成实验及流式细胞术检测来源于不同氧浓度下的巨噬细胞外泌体对MG63的增殖、凋亡影响;CCK-8检测来源于不同氧浓度下的巨噬细胞外泌体对MG63顺铂耐药性的影响。结果低氧能够促进骨肉瘤细胞对巨噬细胞的趋化能力,并进一步诱导巨噬细胞向M2型分化;成功分离不同氧浓度下培养的M2巨噬细胞外泌体,且低氧能够显著上调巨噬细胞对外泌体的分泌;低氧能够明显上调巨噬细胞外泌体对骨肉瘤细胞增殖能力的促进作用,抑制骨肉瘤细胞发生凋亡,并上调骨肉细胞对顺铂的耐药性。结论在体外低氧能够促进骨肉瘤细胞对巨噬细胞的趋化能力,并进一步通过诱导巨噬细胞向M2型分化及提高M2型巨噬细胞外泌体的分泌,进而上调骨肉瘤细胞的增殖能力,抑制其凋亡,最终导致骨肉瘤细胞产生顺铂耐药性。     

Score for atrial fibrillation detection in acute stroke and transient ischemic attack patients in a Brazilian population: The acute stroke atrial fibrillation scoring system

OBJECTIVE:

Atrial fibrillation is a common arrhythmia that increases the risk of stroke by four- to five-fold. We aimed to establish a profile of patients with atrial fibrillation from a population of patients admitted with acute ischemic stroke or transient ischemic attack using clinical and echocardiographic findings.

METHODS:

We evaluated patients consecutively admitted to a tertiary hospital with acute ischemic stroke or transient ischemic attack. Subjects were divided into an original set (admissions from May 2009 to October 2010) and a validation set (admissions from November 2010 to April 2013). The study was designed as a cohort, with clinical and echocardiographic findings compared between patients with and without atrial fibrillation. A multivariable model was built, and independent predictive factors were used to produce a predictive grading score for atrial fibrillation (Acute Stroke AF Score-ASAS).

RESULTS:

A total of 257 patients were evaluated from May 2009 to October 2010 and included in the original set. Atrial fibrillation was diagnosed in 17.5% of these patients. Significant predictors of atrial fibrillation in the multivariate analysis included age, National Institutes of Health Stroke Scores, and the presence of left atrial enlargement. These predictors were used in the final logistic model. For this model, the area under the receiver operating characteristic curve was 0.79. The score derived from the logistic regression analysis was The model developed from the original data set was then applied to the validation data set, showing the preserved discriminatory ability of the model (c statistic = 0.76).

CONCLUSIONS:

Our risk score suggests that the individual risk for atrial fibrillation in patients with acute ischemic stroke can be assessed using simple data, including age, National Institutes of Health Stroke Scores at admission, and the presence of left atrial enlargement.