Extracellular vesicles and circulating nucleic acids最新文献

{"title":"Does the interplay between human endogenous retrovirus K and extracellular vesicles contribute to aging?","authors":"Catherine DeMarino, Avindra Nath, Zhengping Zhuang, Tara T. Doucet-O’Hare","doi":"10.20517/evcna.2023.45","DOIUrl":"https://doi.org/10.20517/evcna.2023.45","url":null,"abstract":"The role of extracellular vesicles (EVs), including retroviral-like particles (RVLPs), in pathogenic processes is currently a subject of active investigation. Several studies have identified mechanistic links between the increased presence of EVs and the process of senescence. A recent study reveals that the reverse transcribed complementary DNA (cDNA) of a human endogenous retroviral sequence can activate the innate immune system and result in tissue damage and/or the spread of cellular senescence to distant tissues. Several studies have linked EVs to age-related diseases, such as Alzheimer’s disease and Parkinson’s disease, and have included isolation of EVs from individuals with these diseases. Loss of epigenetic regulation, immune activation, and environmental stimuli can all lead to the expression of endogenous retroviruses and the incorporation of their proteins and transcripts into EVs. In addition, EVs disseminating these endogenous retroviral components have now been shown to act in a paracrine manner in multiple human diseases. Further investigation of the connection between EVs containing endogenous retroviral protein products or nucleotides should be pursued in models of age-related diseases.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"17 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136159434","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":"Hepatocellular carcinoma cell-derived small extracellular vesicle-associated CD147 serves as a diagnostic marker and promotes endothelial cell angiogenesis via the PI3K/Akt pathway","authors":"De-Fa Huang, Wen-Juan Zhang, Jie Chen, Zhi-Gang Jiao, Xiao-Ling Wang, Ding-Yu Rao, Wei-Song Li, Die Hu, Fang-Fang Xie, Xiao-Xing Wang, Zheng-Zhe Li, Xiao-Mei Yi, Ji-Yang Wu, Yu Jiang, Qi Wang, Tian-Yu Zhong","doi":"10.20517/evcna.2023.30","DOIUrl":"https://doi.org/10.20517/evcna.2023.30","url":null,"abstract":"Aim: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The process of HCC development is closely related to angiogenesis. Plasma exosomes have diagnostic value in many diseases and have become a current research hotspot. We aimed to identify a key molecule in small extracellular vesicles (sEVs) involved in angiogenesis as a diagnostic marker for HCC and uncover the mechanism underlying its regulation in the angiogenesis process. Methods: Nano‐flow cytometer (nFCM) was used to detect CD147 expression in plasma-derived sEVs in 155 HCC patients, 59 liver cirrhosis (LC), and 82 healthy donors (HD). The mechanism of hepatocellular carcinoma cell-derived sEVs CD147 promoting angiogenesis was elucidated by cell proliferation assay, scratch wound healing assay, transwell assay, tube formation assay, and in vivo Matrigel plug angiogenesis assay. Results: We found that CD147 expression was significantly higher in HCC tissue samples than in normal tissues. We also found a significantly larger number of CD147-positive small extracellular vesicles (CD147+ sEVs) in the plasma of HCC patients than LC patients and HD. Furthermore, we showed that hepatocellular carcinoma cell (HepG2)-derived CD147+ sEVs promoted cell proliferation, migration, invasion, and angiogenesis in human umbilical vein endothelial cells. The CD147+ sEVs upregulated vascular endothelial growth factor A (VEGFA) by activating the PI3K/Akt pathway, thereby promoting angiogenesis. Conclusion: HCC-derived sEVs-associated CD147 serves as a diagnostic marker and promotes endothelial cell angiogenesis via the PI3K/Akt pathway.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"61 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135923776","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":"Exosome-based drug delivery systems for the treatment of diabetes and its complications: current opinion.","authors":"Qi Chen, Jie Chen, Yi-Ning Liu, Su-Hua Qi, Lin-Yan Huang","doi":"10.20517/evcna.2023.32","DOIUrl":"10.20517/evcna.2023.32","url":null,"abstract":"<p><p>Diabetes medication is based on controlling blood glucose and delaying the onset of related complications and is not a complete cure for diabetes. Conventional drug therapy fails to stop progressive islet β cell failure in diabetic patients. Recent studies have shown that \"exosome-based therapy\" holds great promise in treating diabetes and its complications. Exosomes are small vesicles that are stable in the bloodstream and can effectively deliver therapeutic drugs to specific tissues or organs through intercellular communication. Using exosomes as carriers for drug delivery offers several advantages. This review summarizes the benefits of exosomal drug delivery systems, drug loading methods, and their applications in treating diabetes and its complications. However, there are still challenges to overcome in using exosomal drug delivery systems, such as large-scale production, assessing the contents of exosomes, and monitoring the safety and effectiveness of the treatment <i>in vivo</i>. In conclusion, this review proposes the therapeutical potential of exosomes as drug carriers for developing novel drugs to provide new strategies for treating diabetes and its complications.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"26 1","pages":"502-517"},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76107997","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":"Conference report for the 2nd annual American Society for Intercellular Communication (ASIC) meeting, 2022.","authors":"Ashley E Russell,&nbsp;Michael W Graner,&nbsp;Shilpa Buch","doi":"10.20517/evcna.2022.43","DOIUrl":"10.20517/evcna.2022.43","url":null,"abstract":"on the role of EVs in inflammation and cardiovascular disease (CVD) during HIV infection. Rates of CVD in people living with HIV (PLWH) tend to be higher than in the uninfected population","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"4 3","pages":"323-337"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222066","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":"Milk-borne small extracellular vesicles: kinetics and mechanisms of transport, distribution, and elimination.","authors":"Alice Ngu, Javaria Munir, Janos Zempleni","doi":"10.20517/evcna.2023.25","DOIUrl":"10.20517/evcna.2023.25","url":null,"abstract":"<p><p>Small extracellular vesicles (sEVs) in milk have the qualities desired for delivering therapeutics to diseased tissues. The production of bovine milk sEVs is scalable (10²¹ annually per cow), and they resist degradation in the gastrointestinal tract. Most cells studied to date internalize milk sEVs by a saturable process that follows Michaelis-Menten kinetics. The bioavailability of oral milk sEVs is approximately 50%. In addition to crossing the intestinal mucosa, milk sEVs also cross barriers such as the placenta and blood-brain barrier, thereby enabling the delivery of therapeutics to hard-to-reach tissues. In time course studies, levels of milk sEVs peaked in the intestinal mucosa, plasma, and urine approximately 6 h and returned to baseline 24 h after oral gavage in mice. In tissues, milk sEV levels peaked 12 h after gavage. Milk sEVs appear to be biologically safe. No cytokine storm was observed when milk sEVs were added to cultures of human peripheral blood mononuclear cells or administered orally to rats. Liver and kidney function and erythropoiesis were not impaired when milk sEVs were administered to rats by oral gavage for up to 15 days. Protocols for loading milk sEVs with therapeutic cargo are available. Currently, the use of milk sEVs (and other nanoparticles) in the delivery of therapeutics is limited by their rapid elimination through internalization by macrophages and lysosomal degradation in target cells. This mini review discusses the current knowledge base of sEV tissue distribution, excretion in feces and urine, internalization by macrophages, and degradation in lysosomes.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"4 3","pages":"339-346"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222067","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":"MicroRNA biogenesis pathway alterations in aging.","authors":"Jorge Sanz-Ros, Cristina Mas-Bargues, Nekane Romero-García, Javier Huete-Acevedo, Mar Dromant, Consuelo Borrás","doi":"10.20517/evcna.2023.29","DOIUrl":"10.20517/evcna.2023.29","url":null,"abstract":"<p><p>Aging is characterized by genomic instability and dysregulation of gene expression. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in post-transcriptional gene regulation. This work explores the impact of dysregulated miRNA biogenesis on the aging process. During aging, alterations in the transcription of primary miRNAs (pri-miRNAs) occur due to genomic changes, DNA damage, and epigenetic modifications. The microprocessor complex, comprising DGCR8 and Drosha proteins, is vital for pri-miRNA processing. Age-related changes in this complex affect miRNA biogenesis and miRNA expression profiles, linking these alterations with age-related conditions. Conversely, interventions like caloric restriction and mTOR inhibition enhance microprocessor activity, suggesting a connection between microprocessor function, aging-related pathways, and lifespan extension. Exportin-5 mediates the transport of pre-miRNAs from the nucleus to the cytoplasm. Although the role of miRNA export in aging is not well understood, accelerated export of pre-miRNAs is observed in response to DNA damage, and nucleocytoplasmic transport has been linked to cellular senescence. Dicer is responsible for processing pre-miRNAs into mature miRNAs. Reduced Dicer expression during aging is reported in various organisms and tissues and is associated with premature aging phenotypes. Conversely, the upregulation of Dicer improves stress resistance and metabolic adaptations induced by caloric restriction and exercise training. Understanding the role of miRNA biogenesis disruption in aging provides insights into the molecular mechanisms of aging and age-related diseases. Targeting this pathway may hold promise for therapeutic strategies and contribute to healthy aging.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"101 1","pages":"486-501"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80773281","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":"Advances in extracellular vesicle isolation methods: a path towards cell-type specific EV isolation.","authors":"Adnan Shami-Shah, Benjamin G Travis, David R Walt","doi":"10.20517/evcna.2023.14","DOIUrl":"10.20517/evcna.2023.14","url":null,"abstract":"<p><p>Extracellular vesicles are small, heterogenous, phospholipid-rich vesicles that are secreted by all cells into the extracellular space. They play a key role in intercellular communication because they can transport a variety of biomolecules such as proteins, lipids, and nucleic acids between cells. As categorized by the International Society of Extracellular Vesicles (ISEV), the term EV encompasses different sub-types, including exosomes, microvesicles, and apoptotic bodies, which differ in their size, origin, and cargo. EVs can be isolated from biological fluids such as blood, urine, and cerebrospinal fluid, and their biomolecular content can be analyzed to monitor the progression of certain diseases. Therefore, EVs can be used as a new source of liquid biomarkers for advancing novel diagnostic and therapeutic tools. Isolating and analyzing EVs can be challenging due to their nanoscopic size and low abundance. Several techniques have been developed for the isolation and characterization of EVs, including ultracentrifugation, density gradient separation, size-exclusion chromatography, microfluidics, and magnetic bead-based/affinity methods. This review highlights advances in EV isolation techniques in the last decade and provides a perspective on their advantages, limitations, and potential application to cell-type specific EV isolation in the future.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"1 1","pages":"447-460"},"PeriodicalIF":0.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83806732","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":"Inhibition of osteosarcoma by European Mistletoe derived val-miR218.","authors":"Wenyan Xie, Catharina Delebinski, Dennis Gürgen, Maik Schröder, Georg Seifert, Matthias F Melzig","doi":"10.20517/evcna.2023.15","DOIUrl":"10.20517/evcna.2023.15","url":null,"abstract":"<p><strong>Aim: </strong>In recent years, there has been a growing interest in the therapeutic potential of plant-derived miRNAs, which have been considered new bioactive ingredients in medicinal plants. <i>Viscum album</i> L., commonly used as an adjuvant cancer therapy in central Europe, contains a large number of miRNAs associated with human diseases such as cancer, cardiovascular diseases, and neurological disorders. This study aimed to investigate whether mistletoe miRNAs, specifically val-miR218, exert anti-cancer activity against osteosarcoma.</p><p><strong>Methods: </strong>The anti-cancer effects of miRNAs from <i>V. album</i> L. were evaluated. The targets of val-miR218 were identified by RNA-seq. The mRNA and protein expression of the targets was confirmed by RT-qPCR and western blot analyses. The interaction between the val-miR218 and miRNA recognition elements (MREs) was validated by the dual-luciferase assay. The inhibitory effect of val-miR218 against osteosarcoma was investigated <i>in vivo</i>.</p><p><strong>Results: </strong>Among these abundant miRNAs in <i>V. album</i> L., val-miR218 showed high potential anti-cancer effects against osteosarcoma. To clarify its molecular mechanism of action, we sequenced val-miR218 associated RNAs and their down-regulated RNAs. As a result, 61 genes were considered the direct targets of val-miR218. Interestingly, these targets were related to essential cellular functions such as cell cycle, DNA replication, and cell morphology, suggesting that val-miR218 significantly inhibited cell growth and arrested osteosarcoma cells in G0/G1 phase by influencing basic cell activities. Mistletoe extracellular vesicles offered val-miR218 adequate protection and facilitated the uptake of val-miR281 by human cells. Moreover, val-miR218 showed significant anti-tumor effects <i>in vivo</i>.</p><p><strong>Conclusion: </strong>This study demonstrated the significant potential of val-miR218 regarding proliferation inhibition in various tumor cell lines <i>in vitro</i> and for osteosarcoma <i>in vivo</i>. Due to the increasing problems during chemotherapy, new therapeutic approaches are becoming more critical. The significant anti-cancer effects of medicinal plants derived miRNAs indicate a promising therapeutic strategy for treating cancer.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"60 1","pages":"306-322"},"PeriodicalIF":0.0,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83278313","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":"Breaking free: endocytosis and endosomal escape of extracellular vesicles.","authors":"Laís Ribovski, Bhagyashree Joshi, Jie Gao, Inge Zuhorn","doi":"10.20517/evcna.2023.26","DOIUrl":"10.20517/evcna.2023.26","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are natural micro-/nanoparticles that play an important role in intercellular communication. They are secreted by producer/donor cells and subsequent uptake by recipient/acceptor cells may result in phenotypic changes in these cells due to the delivery of cargo molecules, including lipids, RNA, and proteins. The process of endocytosis is widely described as the main mechanism responsible for cellular uptake of EVs, with endosomal escape of cargo molecules being a necessity for the functional delivery of EV cargo. Equivalent to synthetic micro-/nanoparticles, the properties of EVs, such as size and composition, together with environmental factors such as temperature, pH, and extracellular fluid composition, codetermine the interactions of EVs with cells, from binding to uptake, intracellular trafficking, and cargo release. Innovative assays for detection and quantification of the different steps in the EV formation and EV-mediated cargo delivery process have provided valuable insight into the biogenesis and cellular processing of EVs and their cargo, revealing the occurrence of EV recycling and degradation, next to functional cargo delivery, with the back fusion of the EV with the endosomal membrane standing out as a common cargo release pathway. In view of the significant potential for developing EVs as drug delivery systems, this review discusses the interaction of EVs with biological membranes en route to cargo delivery, highlighting the reported techniques for studying EV internalization and intracellular trafficking, EV-membrane fusion, endosomal permeabilization, and cargo delivery, including functional delivery of RNA cargo.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"11 1","pages":"283-305"},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88111033","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":"Opportunities for engineering outer membrane vesicles using synthetic biology approaches.","authors":"Richard J R Kelwick, Alexander J Webb, Paul S Freemont","doi":"10.20517/evcna.2023.21","DOIUrl":"10.20517/evcna.2023.21","url":null,"abstract":"<p><p>Gram-negative bacteria naturally shed lipid vesicles, which contain complex molecular cargoes, from their outer membrane. These outer membrane vesicles (OMVs) have important biological functions relating to microbial stress responses, microbiome regulation, and host-pathogen interactions. OMVs are also attractive vehicles for delivering drugs, vaccines, and other therapeutic agents because of their ability to interact with host cells and their natural immunogenic properties. OMVs are also set to have a positive impact on other biotechnological and medical applications including diagnostics, bioremediation, and metabolic engineering. We envision that the field of synthetic biology offers a compelling opportunity to further expand and accelerate the foundational research and downstream applications of OMVs in a range of applications including the provision of OMV-based healthcare technologies. In our opinion, we discuss how current and potential future synergies between OMV research and synthetic biology approaches might help to further accelerate OMV research and real-world applications for the benefit of animal and human health.</p>","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"35 8 1","pages":"255-261"},"PeriodicalIF":0.0,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82802165","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}