The role of exosomes in metastasis and progression of melanoma

The mechanisms of melanoma metastasis have been the subject of extensive research for decades. Improved diagnostic and therapeutic strategies are of increasing importance for the treatment of melanoma due to its high burden of mortality in the advanced stages of the disease. Intercellular communication is a critical event for the progression of cancer. Collective evidence suggests that exosomes, small extracellular membrane vesicles released by the cells, are important facilitators of intercellular communication between the cells and the surrounding environment. Although the emerging field of exosomes is rapidly gaining traction in the scientific community, there is limited knowledge regarding the role of exosomes in melanoma. This review discusses the multifaceted role of melanoma-derived exosomes in promoting the process of metastasis by modulating the invasive and angiogenic capacity of malignant cells. The future implications of exosome research and the therapeutic potential of exosomes are also discussed.     

外泌体在血液肿瘤微环境中的作用及其诊治意义

外泌体是细胞外囊泡的一类主要成分，是正常生理情况下组织细胞间信号传递的重要介质；在多种血液肿瘤研究中发现外泌体是骨髓微环境各成分间相互作用的关键载体，由于其广泛存在并含有特定的核酸、蛋白等分子，外泌体被作为潜在的生物标志物和治疗靶点/载体，在血液肿瘤诊治中的重要性近年正逐步受到关注。     

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...     

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。     

内皮祖细胞来源外泌体在体外循环致脑损伤中作用研究

目的 探讨内皮祖细胞来源的外泌体在体外循环引起的脑损伤中的作用机制.方法 选取雄性SD大鼠45只,随机分为假手术组、体外循环组与外泌体处理组,每组15只.假手术组大鼠采用气管插管机械通气,仅在右股动脉、右颈内静脉穿刺置管;体外循环组建立无血预充非停跳体外循环术后认知功能障碍模型;外泌体处理组大鼠动物模型同体外循环组,待生命体征稳定后给予无菌状态下尾静脉注射200μl外泌体悬浮液.采用Garcia神经功能评价标准评估大鼠神经功能状况;采用TUNEL染色法检测神经细胞的凋亡;采用酶联免疫吸附法检测白细胞介素(IL)-1β、IL-6、IL-10、肿瘤坏死因子α(TNF-α)、血清酸性钙结合蛋白(S-100β)、神经元特异性烯醇化酶(NSE)水平;免疫蛋白印迹法检测B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、天冬氨酸特异性半胱氨酸蛋白酶-3(Caspase-3)表达水平;流式细胞术检测辅助性T细胞17(Th17)、调节性T细胞(Treg)百分比含量.结果 与假手术组比较,体外循环组、外泌体处理组各个时间点大鼠的Gar-cia神经功能评分均明显升高,脑细胞凋亡明显,差异均有统计学意义(P<0.05).与体外循环组比较,外泌体处理组各个时间点大鼠的Garcia神经功能评分明显降低,凋亡阳性细胞明显减少,差异均有统计学意义(P<0.05).体外循环组、外泌体处理组中IL-1β、TNF-α、IL-6、S-100β及NSE水平均明显高于假手术组,IL-10水平明显低于假手术组,差异均有统计学意义(P<0.05).外泌体处理组IL-1β、TNF-α、IL-6、S-100β及NSE水平均明显低于体外循环组,IL-10水平明显高于体外循环组,差异均有统计学意义(P<0.05).与假手术比较,体外循环组、外泌体处理组Bcl-2表达水平降低,Bax、Caspase-3表达水平升高,差异均有统计学意义(P<0.05).与体外循环组比较,外泌体处理组Bcl-2表达水平升高,Bax、Caspase-3表达水平降低,差异均有统计学意义(P<0.05).与假手术组比较,体外循环组、外泌体处理组中CD4+IL-17+T细胞百分比明显升高,CD4+FOXP3+T细胞百分比明显降低,差异均有统计学意义(P<0.05).与体外循环组比较,外泌体处理组CD4+IL-17+T细胞百分比明显降低,CD4+FOXP3+T细胞百分比明显升高,差异均有统计学意义(P<0.05).结论 内皮祖细胞来源的外泌体能通过调节Th17/Treg细胞的动态平衡,改善体外循环后脑损伤,其机制与抑制IL-1β、IL-6、TNF-α等炎症因子的分泌和Caspase-3/Bax/Bcl-2信号通路的活化有关.     

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.