Exosome-cargoed microRNAs: Potential therapeutic molecules for diabetic wound healing

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Exosomes: Emerging implementation of nanotechnology for detecting and managing novel corona virus- SARS-CoV-2

The spread of SARS-CoV-2 as an emerging novel coronavirus disease (COVID-19) had progressed as a worldwide pandemic since the end of 2019. COVID-19 affects firstly lungs tissues which are known for their very slow regeneration. Afterwards, enormous cytokine stimulation occurs in the infected cells immediately after a lung infection which necessitates good management to save patients. Exosomes are extracellular vesicles of nanometric size released by reticulocytes on maturation and are known to m...     

Exosomes are an effective vaccine against congenital toxoplasmosis in mice

Toxoplasmosis is a serious disease in humans and may cause abortion or congenital infection if a woman is exposed to the disease for the first time during pregnancy. Infection before pregnancy normally results in immunity protecting the foetus, suggesting that it may be possible to block vertical transmission of the parasite by appropriate vaccination before pregnancy. We found that the vaccination of CBA/J mice, before pregnancy, with exosomes secreted by SRDCs pulsed in vitro with Toxoplasma gondii-derived antigens (TAg) induced a protective response in the pups. Indeed, vaccination resulted in the presence of significantly fewer cysts in pup brains. This protection was associated with strong humoral responses in the serum in vivo. We also observed cellular responses in vivo, with cell proliferation associated with the production of cytokines by the splenocytes. Thus, exosomes are nucleic acid-free vesicles able to induce immune responses correlated with protection against T. gondii infection in a congenital model. They are therefore a potentially useful tool for vaccination against infectious disease.     

The predictive value of plasma exosomal lncRNAs/mRNAs in NSCLC patients receiving immunotherapy

PurposeThere is an urgent need to explore the use of plasma-derived exosomal long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) as potential biomarkers to select the most suitable patient population to receive immunotherapy for advanced NSCLC with no actionable molecular markers.Patients and methodsIn the present study, 7 patients with advanced NSCLC who received nivolumab were enrolled for molecular studies. Plasma-derived exosomal lncRNAs/mRNAs expression profiles differed between patients exhibiting differential immunotherapy efficacy.ResultsIn the non-responders, 299 differentially expressed exosomal mRNAs and 154 lncRNAs were significantly upregulated. In GEPIA2, 10 mRNAs were upregulated in the NSCLC patients compared to that of the normal population. The up-regulation of CCNB1 related to the cis-regulation of lnc-CENPH-1 and lnc-CENPH-2. KPNA2, MRPL3, NET1 and CCNB1 were trans-regulated by lnc-ZFP3-3. In addition, IL6R exhibited a trend of increased expression in the non-responders at baseline, and this expression was further downregulated after treatment in responders. The association between CCNB1 with lnc-CENPH-1 and lnc-CENPH-2, as well as the lnc-ZFP3-3-TAF1 pair, may represent potential biomarkers of poor immunotherapy efficacy. Patients may obtain increased effector T cell function when IL6R is suppressed by immunotherapy.ConclusionsOur study suggests that plasma-derived exosomal lncRNA and mRNA expression profiles differ between responders and non-responders to nivolumab immunotherapy. Lnc-ZFP3-3-TAF1-CCNB1 pair and IL6R might be key factors predicting efficiency of immunotherapy. Large scale clinical studies seem warranted to further validate the potential of plasma-derived exosomal lncRNAs and mRNAs as a biomarker to aid the selection of NSCLC patients for nivolumab immunotherapy.     

Altered level of plasma exosomes in patients with Gaucher disease

Mutations in the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), the lysosomal storage disorder (LSD), and are the most common genetic risk factor of Parkinson's disease (PD). Lysosome functionality plays a critical role for secretion of extracellular vesicles (EVs) and their content. Here we compared EVs from the blood plasma of 8 GD patients and 8 controls in terms of amounts, size distribution, and composition of their protein cargo. EVs were isolated via sequential centrifugation and characterized by сryo-electron microscopy (cryo-EM), nanoparticle tracking analysis (NTA), and dynamic light scattering (DLS). The presence of exosomal markers HSP70 and tetrasponins were analyzed by Western blot and flow cytometry. Protein profiling was performed by mass-spectrometry (shotgun analysis).Here, for the first time we reported an increased size and altered morphology in exosomes derived from blood plasma of GD patients. An increased size of plasma exosomes from GD patients compared to controls was demonstrated by cryo-EM and DLS (р<0.0001, p < 0.001, respectively) and confirmed by mode size detected by NTA (p < 0.02). Cryo-EM demonstrated an increased number of double and multilayer vesicles in plasma EVs from GD patients. We found that the EVs were enriched with the surface exosomal markers (CD9, СD63, CD81) and an exosome-associated protein HSP70 in case of the patients with the disease. Proteomic profiling of exosomal proteins did not reveal any proteins associated with PD pathogenesis. Thus, we showed that lysosomal dysfunction in GD patients lead to a striking alteration of plasma exosomes in size and morphology.     

间充质干细胞来源的外泌体在子痫前期中的实验研究进展

子痫前期是妊娠期常见并发症,严重威胁母婴健康,目前临床上尚无有效治疗方法。间充质干细胞来源的外泌体（mesenchymal stem cell-derived exosomes,MSC-exos）是纳米级别微粒子,携带有蛋白质、脂质和核酸等生物活性物质,是细胞间通讯的媒介。MSC-exos可参与免疫调节、促进细胞增殖与...     

外泌体源性miRNA在子痫前期发病机制中的研究进展

子痫前期作为一种妊娠期特有的高血压综合征,严重威胁母婴安全,但目前尚无准确的生物标志物作为诊断依据且其病因和发病机制尚未完全阐明。外泌体是广泛存在于体液中的细胞外囊泡,携带多种蛋白质、脂质和核酸等生物活性分子,具有多种生物学功能,其所携带的miRNA具有特异性、多元性、抗降解、能被稳定检出的特点。研究发现子痫前期患者胎盘组织分泌的外泌体中有多种差异表达的miRNA,表明其可能参与了子痫前期的发生发展,可能作为子痫前期预测的潜在靶点。本文对外泌体源性miRNA的结构、功能及其与子痫前期发病机制的研究进展进行综述,旨在为子痫前期早期预测及诊治提供新思路。     

外泌体在骨代谢中的作用

外泌体是多种细胞在生理或病理状态下主动分泌到细胞外的纳米级囊泡,富含蛋白质、核酸、脂质等生物活性物质,参与细胞间信息交流与传递.目前已有研究表明,外泌体能通过信号蛋白、miRNAs等调控成骨细胞、破骨细胞及骨髓间充质干细胞的增殖、分化,介导骨生成和骨吸收过程,在多种骨代谢疾病的发生、发展中起重要作用.     

外排体与缺血性卒中

外排体是由多种类型细胞分泌的直径约40~100 nm的膜性小囊泡.外排体携带有脂质、蛋白质、mRNA、微小RNA等,在细胞通讯中扮演着重要角色.文章对外排体的来源、一般特性、生物学功能以及在缺血性卒中病理生理学和神经功能恢复中的可能作用和机制进行了综述.