J. Sanz-Ros, C. Mas-Bargues, Nekane Romero-García, Javier Huete-Acevedo, M. Dromant, C. Borrás
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.
{"title":"MicroRNA biogenesis pathway alterations in aging","authors":"J. Sanz-Ros, C. Mas-Bargues, Nekane Romero-García, Javier Huete-Acevedo, M. Dromant, C. Borrás","doi":"10.20517/evcna.2023.29","DOIUrl":"https://doi.org/10.20517/evcna.2023.29","url":null,"abstract":"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.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80773281","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}
Qi Chen, Jie Chen, Yi-Ning Liu, Su-Hua Qi, Lin-Yan Huang
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 in vivo. 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.
{"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":"https://doi.org/10.20517/evcna.2023.32","url":null,"abstract":"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 in vivo. 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.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76107997","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}
Dhanu Gupta, O. Wiklander, Matthew J. A. Wood, S. El-Andaloussi
The field of extracellular vesicles (EVs) has seen a tremendous paradigm shift in the past two decades, from being regarded as cellular waste bags to being considered essential mediators in intercellular communication. Their unique ability to transfer macromolecules across cells and biological barriers has made them a rising star in drug delivery. Mounting evidence suggests that EVs can be explored as efficient drug delivery vehicles for a range of therapeutic macromolecules. In contrast to many synthetic delivery systems, these vesicles appear exceptionally well tolerated in vivo. This tremendous development in the therapeutic application of EVs has been made through technological advancement in labelling and understanding the in vivo biodistribution of EVs. Here in this review, we have summarised the recent findings in EV in vivo pharmacokinetics and discussed various biological barriers that need to be surpassed to achieve tissue-specific delivery.
{"title":"Biodistribution of therapeutic extracellular vesicles","authors":"Dhanu Gupta, O. Wiklander, Matthew J. A. Wood, S. El-Andaloussi","doi":"10.20517/evcna.2023.12","DOIUrl":"https://doi.org/10.20517/evcna.2023.12","url":null,"abstract":"The field of extracellular vesicles (EVs) has seen a tremendous paradigm shift in the past two decades, from being regarded as cellular waste bags to being considered essential mediators in intercellular communication. Their unique ability to transfer macromolecules across cells and biological barriers has made them a rising star in drug delivery. Mounting evidence suggests that EVs can be explored as efficient drug delivery vehicles for a range of therapeutic macromolecules. In contrast to many synthetic delivery systems, these vesicles appear exceptionally well tolerated in vivo. This tremendous development in the therapeutic application of EVs has been made through technological advancement in labelling and understanding the in vivo biodistribution of EVs. Here in this review, we have summarised the recent findings in EV in vivo pharmacokinetics and discussed various biological barriers that need to be surpassed to achieve tissue-specific delivery.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91285401","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}
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.
{"title":"Breaking free: endocytosis and endosomal escape of extracellular vesicles","authors":"L. Ribovski, B. Joshi, J. Gao, I. Zuhorn","doi":"10.20517/evcna.2023.26","DOIUrl":"https://doi.org/10.20517/evcna.2023.26","url":null,"abstract":"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.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88111033","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}
Kexin Jiao, Chun Liu, Saraswat Basu, N. Raveendran, T. Nakano, S. Ivanovski, Pingping Han
Regenerative medicine involves the restoration of tissue or organ function via the regeneration of these structures. As promising regenerative medicine approaches, either extracellular vesicles (EVs) or bioprinting are emerging stars to regenerate various tissues and organs (i.e., bone and cardiac tissues). Emerging as highly attractive cell-free, off-the-shelf nanotherapeutic agents for tissue regeneration, EVs are bilayered lipid membrane particles that are secreted by all living cells and play a critical role as cell-to-cell communicators through an exchange of EV cargos of protein, genetic materials, and other biological components. 3D bioprinting, combining 3D printing and biology, is a state-of-the-art additive manufacturing technology that uses computer-aided processes to enable simultaneous patterning of 3D cells and tissue constructs in bioinks. Although developing an effective system for targeted EVs delivery remains challenging, 3D bioprinting may offer a promising means to improve EVs delivery efficiency with controlled loading and release. The potential application of 3D bioprinted EVs to regenerate tissues has attracted attention over the past few years. As such, it is timely to explore the potential and associated challenges of utilizing 3D bioprinted EVs as a novel ‘cell-free’ alternative regenerative medicine approach. In this review, we describe the biogenesis and composition of EVs, and the challenge of isolating and characterizing small EVs - sEVs (< 200 nm). Common 3D bioprinting techniques are outlined and the issue of bioink printability is explored. After applying the following search strategy in PubMed: ‘bioprinted exosomes’ or ‘3D bioprinted extracellular vesicles’, eight studies utilizing bioprinted EVs were found that have been included in this scoping review. Current studies utilizing bioprinted sEVs for various in vitro and in vivo tissue regeneration applications, including angiogenesis, osteogenesis, immunomodulation, chondrogenesis and myogenesis, are discussed. Finally, we explore the current challenges and provide an outlook on possible refinements for bioprinted sEVs applications.
再生医学涉及通过这些结构的再生来恢复组织或器官的功能。作为有前途的再生医学方法，细胞外囊泡(EVs)或生物打印是再生各种组织和器官(即骨骼和心脏组织)的新兴明星。作为一种极具吸引力的无细胞、现成的用于组织再生的纳米治疗剂，EV是由所有活细胞分泌的双层脂质膜颗粒，通过交换EV货物的蛋白质、遗传物质和其他生物成分，作为细胞间的通讯媒介发挥着关键作用。3D生物打印结合了3D打印和生物学，是一种最先进的增材制造技术，它使用计算机辅助过程在生物墨水中实现3D细胞和组织结构的同时图案化。尽管开发一种有效的靶向电动汽车递送系统仍然具有挑战性，但3D生物打印可能提供一种有前途的方法，可以通过控制装载和释放来提高电动汽车的递送效率。在过去的几年里，生物3D打印电动汽车在组织再生方面的潜在应用引起了人们的关注。因此，现在是时候探索利用3D生物打印电动汽车作为一种新的“无细胞”替代再生医学方法的潜力和相关挑战。本文综述了电动汽车的生物起源和组成，以及小型电动汽车- sev (< 200 nm)的分离和表征所面临的挑战。概述了常见的3D生物打印技术，并探讨了生物墨水可打印性的问题。在PubMed中应用以下搜索策略:“生物打印外泌体”或“3D生物打印细胞外囊泡”后，发现有8项利用生物打印ev的研究已被纳入本范围综述。本文讨论了目前利用生物打印的sev进行各种体外和体内组织再生应用的研究，包括血管生成、成骨、免疫调节、软骨形成和肌肉生成。最后，我们探讨了当前面临的挑战，并对生物打印sev应用的可能改进进行了展望。
{"title":"Bioprinting extracellular vesicles as a ‘cell-free' regenerative medicine approach","authors":"Kexin Jiao, Chun Liu, Saraswat Basu, N. Raveendran, T. Nakano, S. Ivanovski, Pingping Han","doi":"10.20517/evcna.2023.19","DOIUrl":"https://doi.org/10.20517/evcna.2023.19","url":null,"abstract":"Regenerative medicine involves the restoration of tissue or organ function via the regeneration of these structures. As promising regenerative medicine approaches, either extracellular vesicles (EVs) or bioprinting are emerging stars to regenerate various tissues and organs (i.e., bone and cardiac tissues). Emerging as highly attractive cell-free, off-the-shelf nanotherapeutic agents for tissue regeneration, EVs are bilayered lipid membrane particles that are secreted by all living cells and play a critical role as cell-to-cell communicators through an exchange of EV cargos of protein, genetic materials, and other biological components. 3D bioprinting, combining 3D printing and biology, is a state-of-the-art additive manufacturing technology that uses computer-aided processes to enable simultaneous patterning of 3D cells and tissue constructs in bioinks. Although developing an effective system for targeted EVs delivery remains challenging, 3D bioprinting may offer a promising means to improve EVs delivery efficiency with controlled loading and release. The potential application of 3D bioprinted EVs to regenerate tissues has attracted attention over the past few years. As such, it is timely to explore the potential and associated challenges of utilizing 3D bioprinted EVs as a novel ‘cell-free’ alternative regenerative medicine approach. In this review, we describe the biogenesis and composition of EVs, and the challenge of isolating and characterizing small EVs - sEVs (< 200 nm). Common 3D bioprinting techniques are outlined and the issue of bioink printability is explored. After applying the following search strategy in PubMed: ‘bioprinted exosomes’ or ‘3D bioprinted extracellular vesicles’, eight studies utilizing bioprinted EVs were found that have been included in this scoping review. Current studies utilizing bioprinted sEVs for various in vitro and in vivo tissue regeneration applications, including angiogenesis, osteogenesis, immunomodulation, chondrogenesis and myogenesis, are discussed. Finally, we explore the current challenges and provide an outlook on possible refinements for bioprinted sEVs applications.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80484083","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}
Over the years, the influence of secretory mechanisms on intercellular communication has been extensively studied. In the central nervous system (CNS), both trans-synaptic (neurotransmitter-based) and long-distance (extracellular vesicles-based) communications regulate activities and homeostasis. In less than a couple of decades, however, there has been a major paradigm shift in our understanding of intercellular communication. Increasing evidence suggests that besides secretory mechanisms (via extracellular vesicles), several cells are capable of establishing long-distance communication routes referred to as Tunneling Nanotubes (TNTs). TNTs are membranous bridges classically supported by F-Actin filaments, allowing for the exchange of different types of intracellular components between the connected cells, ranging from ions and organelles to pathogens and toxic protein aggregates. The roles of TNTs in pathological spreading of several neurodegenerative conditions such as Prion diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) have been well established. However, the fragile nature of these structures and lack of specific biomarkers raised some skepticism regarding their existence. In this review, we will first place TNTs within the spectrum of intercellular communication mechanisms before discussing their known and hypothesized biological relevance in vitro and in vivo in physiological and neurodegenerative contexts. Finally, we discuss the challenges and promising prospects in the field of TNT studies.
{"title":"Hijacking intercellular trafficking for the spread of protein aggregates in neurodegenerative diseases: a focus on tunneling nanotubes (TNTs)","authors":"Ranabir Chakraborty, Sevan Belian, C. Zurzolo","doi":"10.20517/evcna.2023.05","DOIUrl":"https://doi.org/10.20517/evcna.2023.05","url":null,"abstract":"Over the years, the influence of secretory mechanisms on intercellular communication has been extensively studied. In the central nervous system (CNS), both trans-synaptic (neurotransmitter-based) and long-distance (extracellular vesicles-based) communications regulate activities and homeostasis. In less than a couple of decades, however, there has been a major paradigm shift in our understanding of intercellular communication. Increasing evidence suggests that besides secretory mechanisms (via extracellular vesicles), several cells are capable of establishing long-distance communication routes referred to as Tunneling Nanotubes (TNTs). TNTs are membranous bridges classically supported by F-Actin filaments, allowing for the exchange of different types of intracellular components between the connected cells, ranging from ions and organelles to pathogens and toxic protein aggregates. The roles of TNTs in pathological spreading of several neurodegenerative conditions such as Prion diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) have been well established. However, the fragile nature of these structures and lack of specific biomarkers raised some skepticism regarding their existence. In this review, we will first place TNTs within the spectrum of intercellular communication mechanisms before discussing their known and hypothesized biological relevance in vitro and in vivo in physiological and neurodegenerative contexts. Finally, we discuss the challenges and promising prospects in the field of TNT studies.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88018729","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}
Extracellular vesicles (EVs) are nano-sized, lipid compartments that mediate the intercellular transport of lipids, proteins, nucleic acids and metabolites. During infectious diseases, EVs released by host cells promote immune responses, while those released by pathogens attempt to subvert host immunity. There is a growing body of research investigating the role of fungal EVs in plant pathosystems. It is becoming clear that EVs released by fungal phytopathogens play a role during infection through the transport of protein effectors, toxic metabolites and RNA. Here, we discuss recent findings on EVs in fungal phytopathogens, including the methods employed in their isolation, their characterization, contents and functionality, as well as the key questions remaining to be addressed.
{"title":"Extracellular Vesicles in Phytopathogenic Fungi","authors":"Brian D. Rutter, R. Innes","doi":"10.20517/evcna.2023.04","DOIUrl":"https://doi.org/10.20517/evcna.2023.04","url":null,"abstract":"Extracellular vesicles (EVs) are nano-sized, lipid compartments that mediate the intercellular transport of lipids, proteins, nucleic acids and metabolites. During infectious diseases, EVs released by host cells promote immune responses, while those released by pathogens attempt to subvert host immunity. There is a growing body of research investigating the role of fungal EVs in plant pathosystems. It is becoming clear that EVs released by fungal phytopathogens play a role during infection through the transport of protein effectors, toxic metabolites and RNA. Here, we discuss recent findings on EVs in fungal phytopathogens, including the methods employed in their isolation, their characterization, contents and functionality, as well as the key questions remaining to be addressed.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90394854","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}
W. Xie, C. Delebinski, D. Gürgen, Maik Schröder, G. Seifert, M. Melzig
Aim: 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. Viscum album 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. Methods: The anti-cancer effects of miRNAs from V. album 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 in vivo. Results: Among these abundant miRNAs in V. album 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 in vivo. Conclusion: This study demonstrated the significant potential of val-miR218 regarding proliferation inhibition in various tumor cell lines in vitro and for osteosarcoma in vivo. 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.
目的:近年来，人们对植物源性mirna的治疗潜力越来越感兴趣，它们被认为是药用植物中的新型生物活性成分。Viscum album L.是中欧地区常用的辅助癌症治疗药物，含有大量与癌症、心血管疾病、神经系统疾病等人类疾病相关的mirna。本研究旨在探讨槲寄生mirna，特别是val-miR218是否对骨肉瘤具有抗癌活性。方法:对紫花苜蓿microrna的抗癌作用进行评价。通过RNA-seq鉴定了val-miR218的靶点。RT-qPCR和western blot分析证实了靶点mRNA和蛋白的表达。通过双荧光素酶实验验证了val-miR218与miRNA识别元件(MREs)之间的相互作用。在体内研究了val-miR218对骨肉瘤的抑制作用。结果:在V. album L.丰富的microrna中，val-miR218对骨肉瘤具有较高的潜在抗癌作用。为了阐明其作用的分子机制，我们对value - mir218相关rna及其下调rna进行了测序。因此，有61个基因被认为是val-miR218的直接靶点。有趣的是，这些靶点与细胞周期、DNA复制和细胞形态等基本细胞功能相关，这表明val-miR218通过影响基本细胞活性显著抑制细胞生长，并在G0/G1期阻滞骨肉瘤细胞。槲寄生细胞外囊泡为val-miR218提供了充分的保护，并促进了人类细胞对val-miR281的摄取。此外，val-miR218在体内表现出明显的抗肿瘤作用。结论:本研究证明了val-miR218在体外对多种肿瘤细胞系和体内骨肉瘤的增殖抑制方面具有显著的潜力。由于化疗过程中出现的问题越来越多，新的治疗方法变得越来越重要。药用植物来源的mirna具有显著的抗癌作用，为治疗癌症提供了一种有前景的治疗策略。
{"title":"Inhibition of osteosarcoma by European Mistletoe derived val-miR218","authors":"W. Xie, C. Delebinski, D. Gürgen, Maik Schröder, G. Seifert, M. Melzig","doi":"10.20517/evcna.2023.15","DOIUrl":"https://doi.org/10.20517/evcna.2023.15","url":null,"abstract":"Aim: 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. Viscum album 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. Methods: The anti-cancer effects of miRNAs from V. album 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 in vivo. Results: Among these abundant miRNAs in V. album 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 in vivo. Conclusion: This study demonstrated the significant potential of val-miR218 regarding proliferation inhibition in various tumor cell lines in vitro and for osteosarcoma in vivo. 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.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83278313","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}
Adnan Shami-Shah, Benjamin G Travis, David R. Walt
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.
{"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":"https://doi.org/10.20517/evcna.2023.14","url":null,"abstract":"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.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83806732","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}
B. Hanson, B. Paternoster, Nikita Povarnitsyn, E. Scotchman, L. Chitty, N. Chandler
Prenatal testing is important for the early detection and diagnosis of rare genetic conditions with life-changing implications for the patient and their family. Gaining access to the fetal genotype can be achieved using gold-standard invasive sampling methods, such as amniocentesis and chorionic villus sampling, but these carry a small risk of miscarriage. Non-invasive prenatal diagnosis (NIPD) for select rare monogenic conditions has been in clinical service in England since 2012 and has revolutionised the field of prenatal diagnostics by reducing the number of women undergoing invasive sampling procedures. Fetal-derived genomic material is present in a highly fragmented form amongst the maternal cell-free DNA (cfDNA) in circulation, with sequence coverage across the entire fetal genome. Cell-free fetal DNA (cffDNA) is the foundation for NIPD, and several technologies have been clinically implemented for the detection of paternally inherited and de novo pathogenic variants. Conversely, a low abundance of cffDNA within a high background of maternal cfDNA makes assigning maternally inherited variants to the fetal fraction a significantly more challenging task. Research is ongoing to expand available tests for maternal inheritance to include a broader range of monogenic conditions, as well as to uncover novel diagnostic avenues. This review covers the scope of technologies currently clinically available for NIPD of monogenic conditions and those still in the research pipeline towards implementation in the future.
{"title":"Non-invasive prenatal diagnosis (NIPD): current and emerging technologies","authors":"B. Hanson, B. Paternoster, Nikita Povarnitsyn, E. Scotchman, L. Chitty, N. Chandler","doi":"10.20517/evcna.2022.44","DOIUrl":"https://doi.org/10.20517/evcna.2022.44","url":null,"abstract":"Prenatal testing is important for the early detection and diagnosis of rare genetic conditions with life-changing implications for the patient and their family. Gaining access to the fetal genotype can be achieved using gold-standard invasive sampling methods, such as amniocentesis and chorionic villus sampling, but these carry a small risk of miscarriage. Non-invasive prenatal diagnosis (NIPD) for select rare monogenic conditions has been in clinical service in England since 2012 and has revolutionised the field of prenatal diagnostics by reducing the number of women undergoing invasive sampling procedures. Fetal-derived genomic material is present in a highly fragmented form amongst the maternal cell-free DNA (cfDNA) in circulation, with sequence coverage across the entire fetal genome. Cell-free fetal DNA (cffDNA) is the foundation for NIPD, and several technologies have been clinically implemented for the detection of paternally inherited and de novo pathogenic variants. Conversely, a low abundance of cffDNA within a high background of maternal cfDNA makes assigning maternally inherited variants to the fetal fraction a significantly more challenging task. Research is ongoing to expand available tests for maternal inheritance to include a broader range of monogenic conditions, as well as to uncover novel diagnostic avenues. This review covers the scope of technologies currently clinically available for NIPD of monogenic conditions and those still in the research pipeline towards implementation in the future.","PeriodicalId":73008,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87386427","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}
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