冠状动脉粥样硬化性心脏病患者心外膜脂肪组织的生物信息学研究

背景 心血管疾病（CVD）是常见病和多发病,患病率和死亡率呈快速上升趋势。动脉粥样硬化（AS是缺血性CVD的病理基础,研究表明心外膜脂肪组织（EAT）通过分泌外泌体（EXO）和生物活性物质促进AS进展,但其作用机制仍需进一步研究。目的 通过生物信息学方法挖掘冠状动脉粥样硬化性心脏病（CAD）患者EAT中的关键基因,探讨免疫细胞浸润情况,联合CAD患者EXO间差异表达基因（DEGs）推测EAT来源EXO间DEGs并进行验证,从细胞及分子水平上探讨EAT在CAD疾病过程中的作用机制。方法 从基因表达综合数据库（GEO）中下载关于EAT的数据集GSE64554、GSE120774,根据临床信息将EAT的测序数据分为CAD组和健康对照组,使用R语言及相关软件包进行生物信息学分析。首先使用R语言筛选CAD组与健康对照组EAT间DEGs,并进行GO富集分析和KEGG通路富集分析,构建蛋白质-蛋白质相互作用（PPI）网络,评估所选基因的生物学功能及可能参与其调控的转录因子。构建GSE64554数据集中EAT的加权基因共表达网络（WGCNA）,获取同CAD表型相关的基因模块,将所获EAT间DEGs与模...     

肥大细胞源性外来体参与构建针刺穴位效应启动小网络的探讨

外来体是由细胞分泌的囊泡小体,是囊泡运输的常见形式,参与细胞间信息交流。国内外现有研究和本课题组前期工作表明,针刺效应的产生与穴位局部神经、肥大细胞及相关信号分子等因素相关。外来体参与神经细胞信息传递、肥大细胞功能活动、信号分子释放等生理功能。基于外来体与神经、肥大细胞、信号分子的密切关系,我们认为针刺引起穴位局部肥大细胞释放的外来体是针刺穴位初始效应的关键因素之一,在神经-肥大细胞-信号分子的网络联系中具有信使作用。     

以树突细胞为基础的抗乙型肝炎病毒免疫治疗现状与展望

DC是强大的APC,制备HBV抗原特异性DC疫苗,诱生抗原特异性CTL,可以有效控制HBV感染;DC还可分泌Exosome,后者作为新型非细胞结构性疫苗,有望成为抗HBV免疫治疗的生力军。     

外泌体miRNA在口腔疾病中的研究进展

外泌体是活细胞分泌至细胞外基质的纳米级囊泡,在细胞之间的物质交换和信号转导方面发挥重要作用,能将其携带的脂质、蛋白质、核酸传递至受体细胞,调节受体细胞的生理、病理过程。微小RNA(microRNA、miRNA)作为外泌体中重要的"货物"被转运至受体细胞,调控受体细胞信号通路,从而对疾病的进展起着调节的作用。近年来,外泌体miRNA在牙周疾病、黏膜相关疾病、口腔癌等疾病中的研究日益增多。本文就外泌体miRNA在口腔疾病中的调控机制进行综述,并讨论外泌体miRNA作为生物标志物在口腔疾病诊断中的潜在前景。     

Exosome在细菌和病毒感染中的作用研究

【摘要】外泌题（Exosome）作为生物活性载体,最早被认为仅仅负责细胞垃圾清运工作;然而近年来大量关于exosome与人类免疫缺陷病毒、乙型肝炎病毒、结核分枝杆菌以及其他病原体的研究成果,揭示了exosome功能的复杂性和多样性,如转运和传送各种调节因子、病原体核酸和蛋白质以及宿主细胞的miRNA和细胞因子至未感染细胞,以调节机体的免疫应答。Exosome既可以激活免疫促进炎症反应,也可以抑制免疫反应助力病毒的扩散。本文对exosome在细菌性和病毒性感染中扮演的角色及相关机制作一综述。     

Membrane transporters in salivary exosomes and microvesicles as biomarkers of systemic or oral disease

Backgroundsaliva is useful to assess health or disease states. Recently, proteomic technologies have allowed rapid progress in saliva analysis.Highlight(1) saliva contains three main types of extracellular vesicles; (2) the vesicles are exosomes, microvesicles, and apoptotic bodies; (3) proteome is analyzed in saliva, salivary exosomes, and salivary microvesicles; (4) membrane transporters are in saliva, and salivary exosomes and/or microvesicles; (5) biomarker discovery in exosomes and microvesicles of saliva is progressing.Conclusionmembrane transporters such as aquaporin, ion channels, carriers in saliva, and salivary exosomes or microvesicles, might be valuable biomarkers of systemic or oral health.     

Ginsenoside Rg1 ameliorates blood–brain barrier disruption and traumatic brain injury via attenuating macrophages derived exosomes miR-21 release

During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood–brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1β-induced macrophages (IIM)-Exos-miR-21 can activate NF-κB signaling pathway and induce the expressions of MMP-1, -3 and -9 and downregulate the levels of tight junction proteins (TJPs) deteriorating the BBB. Rg1 reduced miR-21-5p content in IIM-Exos (RIIM-Exos). The interaction of NMIIA–HSP90 controlled the release of Exos-miR-21, this interaction was restricted by Rg1. Rg1 could inhibit the Exos-miR-21 release in peripheral blood flow to brain, enhancing TIMP3 protein expression, MMPs proteolysis, and restricting TJPs degradation thus protected the BBB integrity. Conclusively, Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease.     

Lipotoxic hepatocyte-derived exosomal miR-1297 promotes hepatic stellate cell activation through the PTEN signaling pathway in metabolic-associated fatty liver disease

BACKGROUNDExosomes play an important role in metabolic-associated fatty liver disease (MAFLD), but the mechanism by which exosomes participate in MAFLD still remain unclear.AIMTo figure out the function of lipotoxic exosomal miR-1297 in MAFLD.METHODSMicroRNA sequencing was used to detect differentially expressed miRNAs (DE-miR) in lipotoxic exosomes derived from primary hepatocytes. Bioinformatic tools were applied to analyze the target genes and pathways regulated by the DE-miRs. Quantitative real-time PCR (qPCR) was conducted for the verification of DE-miRs. qPCR, western blot, immunofluorescence staining and ethynyl-20-deoxyuridine assay were used to evaluate the function of lipotoxic exosomal miR-1297 on hepatic stellate cells (LX2 cells). A luciferase reporter experiment was performed to confirm the relationship of miR-1297 and its target gene PTEN. RESULTSMicroRNA sequencing revealed that there were 61 exosomal DE-miRs (P < 0.05) with a fold-change > 2 from palmitic acid treated primary hepatocytes compared with the vehicle control group. miR-1297 was the most highly upregulated according to the microRNA sequencing. Bioinformatic tools showed a variety of target genes and pathways regulated by these DE-miRs were related to liver fibrosis. miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes by qPCR. Fibrosis promoting genes (α-SMA, PCNA) were altered in LX2 cells after miR-1297 overexpression or miR-1297-rich lipotoxic exosome incubation via qPCR and western blot analysis. Immunofluorescence staining and ethynyl-20-deoxyuridine staining demonstrated that the activation and proliferation of LX2 cells were also promoted after the above treatment. PTEN was found to be the target gene of miR-1297 and knocking down PTEN contributed to the activation and proliferation of LX2 cells via modulating the PI3K/AKT signaling pathway.CONCLUSIONmiR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes. The lipotoxic hepatocyte-derived exosomal miR-1297 could promote the activation and proliferation of hepatic stellate cells through the PTEN/PI3K/AKT signaling pathway, accelerating the progression of MAFLD.     

miRNAs介导辐射旁效应研究进展

辐射旁效应是指受辐射的细胞产生信号,并诱导未受辐照的细胞产生反应,即受辐射和未受辐射细胞之间的通讯以及这两种细胞内的信号转导效应。辐射对肿瘤细胞造成杀伤作用的同时,也会产生辐射旁效应给邻近的正常组织带来潜在危险。研究发现,电离辐射可直接改变miRNAs表达,并影响未受辐射的邻近组织中基因的表达,因此,miRNAs可能是受辐射细胞和未受辐射细胞之间信号通路调节的重要物质。本文就miRNAs在辐射旁效应中的作用进行综述。     

Exosomal vaccines containing the S protein of the SARS coronavirus induce high levels of neutralizing antibodies

Infection with the SARS-associated coronavirus (SARS-CoV) induces an atypical pulmonary disease with a high lethality rate. Although the initial SARS epidemic was contained, sporadic outbreaks of the disease still occur, suggesting a continuous need for a vaccine against this virus. We therefore explored exosome-based vaccines containing the spike S proteins of SARS-CoV. S-containing exosomes were obtained by replacing the transmembrane and cytoplasmic domains of the S protein by those of VSV-G. The immunogenicity and efficacy of the S-containing exosomes were tested in mice and compared to an adenoviral vector vaccine expressing the S protein. Both, S-containing exosomes and the adenoviral vector vaccine induced neutralizing antibody titers. After priming with the SARS-S exosomal vaccine and boosting with the adenoviral vector the neutralizing antibody titers exceeded those observed in the convalescent serum of a SARS patient. Both approaches were effective in a SARS-S-expressing tumor challenge model and thus warrant further investigation.