Extracellular vesicles and circulating nucleic acids最新文献

{"title":"HIV-1 Tat induced microglial EVs leads to neuronal synaptodendritic injury: microglia-neuron cross-talk in NeuroHIV.","authors":"Muthukumar Kannan, Seema Singh, Divya T Chemparathy, Abiola A Oladapo, Dinesh Y Gawande, Shashank M Dravid, Shilpa Buch, Susmita Sil","doi":"10.20517/evcna.2022.14","DOIUrl":"10.20517/evcna.2022.14","url":null,"abstract":"<p><strong>Aim: </strong>Activation of microglial NLRP3 inflammasome is an essential contributor to neuroinflammation underlying HIV-associated neurological disorders (HAND). Under pathological conditions, microglia-derived-EVs (MDEVs) can affect neuronal functions by delivering neurotoxic mediators to recipient cells. However, the role of microglial NLRP3 in mediating neuronal synaptodendritic injury has remained unexplored to date. In the present study, we sought to assess the regulatory role of HIV-1 Tat induced microglial NLRP3 in neuronal synaptodendritic injury. We hypothesized that HIV-1 Tat mediated microglia EVs carrying significant levels of NLRP3 contribute to the synaptodendritic injury, thereby affecting the maturation of neurons.</p><p><strong>Methods: </strong>To understand the cross-talk between microglia and neuron, we isolated EVs from BV2 and human primary microglia (HPM) cells with or without NLRP3 depletion using siNLRP3 RNA. EVs were isolated by differential centrifugation, characterized by ZetaView nanoparticle tracking analysis, electron microscopy, and western blot analysis for exosome markers. Purified EVs were exposed to primary rat neurons isolated from E18 rats. Along with green fluorescent protein (GFP) plasmid transfection, immunocytochemistry was performed to visualize neuronal synaptodendritic injury. Western blotting was employed to measure siRNA transfection efficiency and the extent of neuronal synaptodegeneration. Images were captured in confocal microscopy, and subsequently, Sholl analysis was performed for analyzing dendritic spines using neuronal reconstruction software Neurolucida 360. Electrophysiology was performed on hippocampal neurons for functional assessment.</p><p><strong>Results: </strong>Our findings demonstrated that HIV-1 Tat induced expression of microglial NLRP3 and IL1β, and further that these were packaged in microglial exosomes (MDEV) and were also taken up by the neurons. Exposure of rat primary neurons to microglial Tat-MDEVs resulted in downregulation of synaptic proteins- PSD95, synaptophysin, excitatory vGLUT1, as well as upregulation of inhibitory proteins- Gephyrin, GAD65, thereby implicating impaired neuronal transmissibility. Our findings also showed that Tat-MDEVs not only caused loss of dendritic spines but also affected numbers of spine sub-types- mushroom and stubby. Synaptodendritic injury further affected functional impairment as evidenced by the decrease in miniature excitatory postsynaptic currents (mEPSCs). To assess the regulatory role of NLRP3 in this process, neurons were also exposed to Tat-MDEVs from NLRP3 silenced microglia. Tat-MDEVs from NLRP3 silenced microglia exerted a protective role on neuronal synaptic proteins, spine density as well as mEPSCs.</p><p><strong>Conclusion: </strong>In summary, our study underscores the role of microglial NLRP3 as an important contributor to Tat-MDEV mediated synaptodendritic injury. While the role of NLRP3 in inflammation is we","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10796546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations before the application of 5-hydroxymethylation levels of long non-coding RNAs for non-invasive cancer diagnosis.","authors":"Zhou Zhang,&nbsp;Chang Zeng,&nbsp;Wei Zhang","doi":"10.20517/evcna.2021.22","DOIUrl":"https://doi.org/10.20517/evcna.2021.22","url":null,"abstract":"<p><p>Previous studies have suggested that aberrant 5-hydroxymethylcytosines (5hmC) modifications are related to cancer pathobiology. Genome-wide profiling 5hmC in circulating cell-free DNA (cfDNA) using the highly sensitive chemical labeling-based 5hmC-Seal technique has been demonstrated to have the potential to be a robust epigenomic tool for cancer biomarker discovery. Prior studies have mostly focused on cfDNA-derived 5hmC-Seal data summarized in well-annotated genic features (e.g., gene bodies) or unbiased bins. Zhou et al. recently proposed long non-coding RNAs (lncRNAs) as an alternative molecular target for biomarker discovery using publicly available 5hmC-Seal data. Considering its potential clinical impact, we would like to comment on Zhou <i>et al</i>. and advocate more serious consideration of critical issues such as the availability of clinical information and technical variables, especially when performing secondary analysis using publicly available data, with the aim of improving data transparency and translatability.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797161/pdf/nihms-1771817.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39873577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Summary of Prof. Yin’s CSEMV-EVCNA award lecture 2021","authors":"Ying Zhang, Hang Yin","doi":"10.20517/evcna.2022.16","DOIUrl":"https://doi.org/10.20517/evcna.2022.16","url":null,"abstract":"Extracellular vesicles (EVs) have been regarded as influential intracellular delivering parcels that possess tremendous potential because of their strict and complex secretion regulation processes. However, traditional detection methods cannot monitor the secretion of EVs due to their small particle diameters. Inspired by their peculiar diverse appearances and lipid membranes ingredients, we developed an innovative strategy to detect EVs in any kind of fluids by using rationally designed peptide probes that particularly recognize the highly curved surface of EVs. These peptide probes also serve as novel tools to selectively target cancerous cells with specific lipid compositions and distributions. With this strategy, we discovered a series of EV-secreting regulation mechanisms and identified their roles within physiological processes. Recently, we found that the transportation of oligodeoxynucleotides and cell division control protein 42 homolog from TLR9-activated macrophages to naïve cells via EVs exerts synergetic effects in the propagation of the intracellular immune response, which suggests a general mechanism for EV-mediated uptake of pathogen-associated molecular patterns.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84490349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights of engineering plant exosome-like nanovesicles as a nanoplatform for therapeutics and drug delivery","authors":"S. A. U. Shinge, Yin Xiao, Jiang Xia, Yujie Liang, Lijuan Duan","doi":"10.20517/evcna.2021.25","DOIUrl":"https://doi.org/10.20517/evcna.2021.25","url":null,"abstract":"Plant exosome-like nanovesicles (PELNVs) are membrane-encapsulated nanostructures released from cells into their surroundings. PELNVs have an important role in intercellular and interspecies communication in all three domains of life. They act as protective compartments for the long-distance transit of signal molecules like proteins, nucleic acids, lipids, and other metabolites. A range of plants and vegetables can emit PELNVs. The importance of PELNVs in interspecies communication stems from their concentration in biomolecules (lipids, proteins, and miRNAs), lack of toxicity, ease of internalization by cells, and anti-inflammatory, immune-modulatory, and regenerative characteristics. PELNVs derived from numerous fruits and vegetables are biocompatible, biodegradable, and abundant in various plant species. Moreover, their convincing physicochemical characteristics underpin their modulative role in physiological and pathological processes, all of which have fueled speculation that these nanovesicles could be particularly adept at developing future-generation bio-therapeutic platforms. The goal of this review was not only to present an overview of the identified roles of PELNVs in physiology and pathology, but also to provide new insight toward their engineering for effective therapeutics and drug delivery nanoplatforms, a clue for future direction to the ongoing research gaps.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83405570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered mammalian and bacterial extracellular vesicles as promising nanocarriers for targeted therapy","authors":"Han Liu, Zhen Geng, Jiacan Su","doi":"10.20517/evcna.2022.04","DOIUrl":"https://doi.org/10.20517/evcna.2022.04","url":null,"abstract":"Extracellular vesicles (EVs), which are nanocarriers with phospholipid bilayer structures released by most cells, play a key role in regulating physiological and pathological processes. EVs have been investigated due to their loading capacity, low toxicity, immunogenicity, and biofunctions. Although EVs have shown good potential as therapeutic vehicles, natural EVs have a poor targeting ability, which substantially reduces the therapeutic effect. Through the addition of a targeting unit into the membrane surface of EVs or inside EVs by engineering technology, the therapeutic agent can accumulate in specific cells and tissues. Here, we focus on mammalian EVs (MEVs) and bacterial EVs (BEVs), which are the two most common types of EVs in the biomedical field. In this review, we describe engineered MEVs and BEVs as promising nanocarriers for targeted therapy and summarize the biogenesis, isolation, and characterization of MEVs and BEVs. We then describe engineering techniques for enhancement of the targeting ability of EVs. Moreover, we focus on the applications of engineered MEVs and BEVs in targeted therapy, including the treatment of cancer and brain and bone disease. We believe that this review will help improve the understanding of engineered MEVs and BEVs, thereby promoting their application and clinical translation.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88062365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obituary for Prof. Dr. Johng Sik Rhim","authors":"","doi":"10.20517/evcna.2022.15","DOIUrl":"https://doi.org/10.20517/evcna.2022.15","url":null,"abstract":"","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88910623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rigor and reproducibility: status and challenges for single vesicle analysis.","authors":"John P Nolan, Daniel T Chiu, Joshua A Welsh","doi":"10.20517/evcna.2022.28","DOIUrl":"10.20517/evcna.2022.28","url":null,"abstract":"<p><p>This report summarises the presentations and activities of the SELECTBIO Workshop on Rigor and Reproducibility in EV Research and Single EV Analysis held in San Diego, USA, in December 2021. The motivation for the session was the recognition that progress in the extracellular vesicle (EV) field is limited by the availability of rigorous and reproducible EV measurement tools. These tools are absolutely required for EVs to evolve from a research lab curiosity to something that will improve our ability to understand, diagnose, treat, and prevent disease. The program focused on guidelines for EV measurement and characterization as laid out in the recent MISEV2018 and MIFlowCyt-EV publications, their implementation in routine practice, and their continued evolution as new EV measurement technologies are introduced. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9672547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered induced-pluripotent stem cell derived monocyte extracellular vesicles alter inflammation in HIV humanized mice.","authors":"Bing Sun,&nbsp;Scott Kitchen,&nbsp;Norina Tang,&nbsp;Andreas Garza,&nbsp;Sheela Jacob,&nbsp;Lynn Pulliam","doi":"10.20517/evcna.2022.11","DOIUrl":"https://doi.org/10.20517/evcna.2022.11","url":null,"abstract":"<p><strong>Aim: </strong>A peripheral inflammatory response can drive neuroinflammation in a number of infections including human immunodeficiency virus (HIV). Monocyte/macrophage (M/Mφ) activation is a hallmark of acute HIV infection and a source of chronic inflammation in a subset of HIV-infected individuals. We sought to decrease peripheral inflammation and M/Mφ transmigration after HIV infection by engineering extracellular vesicles (EV) to antagonize a microRNA (miR) associated with inflammation. We hypothesized that induced pluripotent stem cell (iPSC)-derived monocyte EVs (mEVs), engineered to contain an antagomir to miR-155 (αmiR mEV) would target monocyte inflammation and influence neuroinflammation in an HIV-infected humanized mice.</p><p><strong>Methods: </strong>mEVs were characterized by tetraspanins, nanoparticle tracking analysis, electron microscopy, and their preferential entry into circulating monocytes as well as testing for endogenous selected miRNAs. HIV-infected humanized mice were treated with control or antagomir155 mEVs. Plasma viral load was measured plus activation markers on lymphocytes and monocytes and the number of macrophages in the brain was quantified.</p><p><strong>Results: </strong>mEVs preferentially entered peripheral monocytes. HIV infection increased C-C chemokine receptor type 5 (CCR5) and major histocompatibility complex, class II, DR (HLA-DR) expression on T cells and monocytes. Treatments with mEVs did not decrease plasma HIV viral load; however, mEVs alone resulted in a decrease in %CCR5+ and %HLA-DR+ on T cells and an increase in %CCR5+ monocytes. αmiR mEVs decreased %CCR5 on M/Mφ. The mEV-treated HIV-infected mice did not show an increase in macrophage transmigration to the brain.</p><p><strong>Conclusion: </strong>mEVs alone caused an unexpected decrease in lymphocyte activation and increase in monocyte %CCR5; however, this did not translate to an increase in macrophage transmigration to the brain.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9324444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleic acid functionalized extracellular vesicles as promising therapeutic systems for nanomedicine","authors":"Chunping Liu, Dongyue He, Huan Cen, Huiqi Chen, Longmei Li, G. Nie, Zixue Zhong, Qingfeng He, Xiaofei Yang, Sien Guo, Lei Wang, Zhijin Fan","doi":"10.20517/evcna.2021.21","DOIUrl":"https://doi.org/10.20517/evcna.2021.21","url":null,"abstract":"Extracellular vesicles (EVs), as natural carriers, are regarded as a new star in nanomedicine due to their excellent biocompatibility, fascinating physicochemical properties, and unique biological regulatory functions. However, there are still some challenges to using natural EVs, including poor targeting ability and the clearance from circulation, which may limit their further development and clinical use. Nucleic acid has the functions of programmability, targeting, gene therapy, and immune regulation. Owing to the engineering design and modification by integrating functional nucleic acid, EVs offer excellent performances as a therapeutic system in vivo. This review briefly introduces the function and mechanism of nucleic acid in the diagnosis and treatment of diseases. Then, the strategies of nucleic acid-functionalized EVs are summarized and the latest progress of nucleic acid-functionalized EVs in nanomedicine is highlighted. Finally, the challenges and prospects of nucleic acid-functionalized EVs as a promising diagnostic system are proposed.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78397901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meeting report of the 2nd Lugano ExoDay: extracellular vesicles as next-generation clinical biomarkers and therapeutic agents","authors":"C. Balbi, M. Cretich, L. Barile","doi":"10.20517/evcna.2022.17","DOIUrl":"https://doi.org/10.20517/evcna.2022.17","url":null,"abstract":"an excellent and well-presented overview of the complexity of extracellular vesicles. the second lecture. The speaker addressed basic questions regarding the role of tumor-released EVs in mediating the pro-metastatic effects of chemotherapy. He showed advanced and elegant research in his laboratory, providing evidence that two classes of cytotoxic drugs are broadly employed in preoperative (neoadjuvant) breast cancer therapy, elicit tumor-derived EVs with enhanced pro-metastatic capacity. Mechanistically he showed that chemotherapy-elicited EVs are enriched in annexin A6 (ANXA6), a Ca 2+ -dependent protein that promotes NF- κ B-dependent endothelial cell activation, Ccl2 induction, and Ly6C+CCR2+ monocyte expansion in the pulmonary pre-metastatic niche to facilitate the establishment of lung metastasis [3] . Genetic inactivation of Anxa6 in cancer cells or Ccr2 in host cells blunts the pro-metastatic effects of chemotherapy-elicited EVs. ANXA6 is detected and potentially enriched, in the circulating EVs of breast cancer patients undergoing neoadjuvant chemotherapy. the application of of the","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75023253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}