ExRNA最新文献

{"title":"Extracellular vesicles as carriers of viruses.","authors":"Zach Troyer, John C Tilton","doi":"10.21037/exrna-21-24","DOIUrl":"https://doi.org/10.21037/exrna-21-24","url":null,"abstract":"An inescapable conclusion of the past decade of research into extracellular vesicles (EVs) during viral infection is the growing recognition that there is not a categorical division between EVs and enveloped viruses, but rather an extensive and intricate overlap leading to the production of a heterogenous mix of submicron particles. Like EVs, enveloped viruses are small, lipid bilayer-enclosed particles and numerous recent reports have demonstrated significant similarity in physical and biochemical composition between EVs and viral particles (1–3). EVs and many viruses use the same cellular machinery to exit the cell and both are capable of transferring proteins and nucleic acids to target cells, which can have functional downstream effects. Furthermore, in addition to these similarities in size, composition, and biogenesis, there is a growing body of evidence that EVs play a major role during the course of viral infections. EVs released from virally-infected cells carry viral components to nearby uninfected cells, sensitizing them for viral spread (4,5). Alternatively, EVs can be released carrying antiviral proteins allowing nearby cells to prepare their defenses for a potential viral encounter (6,7). In “A New Infectious Unit: Extracellular Vesicles Carrying Virus Populations”, Kerviel et al. review a recently recognized phenomenon in which EVs facilitate the spread of viruses by encapsulating multiple virions or naked infectious viral genomes (8), expanding our understanding of the complex overlap between viruses and EVs that plays out at the nanoscale stage. In “vesicle-mediated en bloc viral transmission”, EVs containing non-enveloped viruses, enveloped viruses, or even naked viral genomes are the main carrier of infection and viral transmission rather than individual “free” viral particles. En bloc transmission has been observed in a wide array of viral families, including polioviruses, enteroviruses, Coxsackieviruses, hepatitis A (HAV) and C viruses (HCV), rotaviruses, and polyomaviruses,","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0c/8f/nihms-1758989.PMC9286029.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10472954","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":"Differential impact of inflammasome-induced extracellular vesicles on immune cells: key control by the functional state of the recipient cell","authors":"C. Verderio, Marta Lombardi, F. Di Virgilio","doi":"10.21037/exrna-21-17","DOIUrl":"https://doi.org/10.21037/exrna-21-17","url":null,"abstract":"Inflammasomes are cytoplasmic multiprotein complexes that survey the cytosol of immune cells for pathogen contamination or cellular perturbation by sensing stimuli that activate an inflammatory response and integrating their downstream signaling (1). They act as innate immune sensors and, in response to pathogens/cell damage, trigger pyroptosis, a lytic form of programmed cell death. The term “inflammasome” has been originally coined by Martinon et al. in 2002 who reported the assembly of cytosolic complexes which lead to proteolytic activation of caspases and inflammation (2). Inflammasomes consist of a sensor protein (NLRC4, NLRP or AIM2 protein), an inflammatory caspase, and in some cases an adaptor protein, such as ASC (the adaptor molecule apoptosis-associated speck-like protein containing a CARD). Inflammasomes are activated by a multiplicity of pathogen-derived or endogenous factors, often in an inflammasome-specific fashion (e.g., NLRP1 or NLRC4 activation by anthrax lethal toxin or bacterial flagellin, respectively). The inflammasome subtype most frequently involved in inflammation is NLRP3, typically activated by agents that form plasma membrane pores (e.g., nigericin or extracellular ATP) and thus cause a large intracellular K efflux. Once assembled and activated, the NLRP3 inflammasome triggers pro-caspase-1 cleavage, which generates the enzymatically active caspase-1 that in turn drives the enzymatic activation of the pro-inflammatory cytokines IL-1β and IL-18, as well as of gasdermins, a family of pore-forming effector proteins (Figure 1). Gasdermins have a homologous N-terminal gasdermin domain, which upon proteolytic removal of the inhibitory C-terminal domain forms a pore in the plasma membrane that causes membrane permeabilization, cell swelling and pyroptosis (3). Appropriate inflammasome activation is vital for the immune cells to cope with pathogens or tissue damage, but aberrant inflammasome activation is associated to uncontrolled tissue responses and various inflammatory diseases. Some inflammasome sensors, such as NLRP3, have been identified as drivers of chronic inflammatory pathologies. In particular, gain-of-function mutations in NLRP3 inflammasomes cause cryopyrin-associated periodic syndromes (CAPS) that are characterized by chronic systemic inflammation. Extracellular NLRP3 inflammasome oligomeric particles have been previously identified in the supernatant of activated macrophages and in the blood of CAPS patients (4). It has long been known that one of the functional consequence of inflammasome activation is the release of extracellular vesicles (EVs) from immune cells (5-8). EVs are heterogeneous membrane structures released by all cell types, which contain and transfer cellular components from a donor to a recipient cell and act as potent mediators of cell-to-cell communication. Immune cells-derived EVs, i.e., released by monocytes, microglia, dendritic cells and macrophages, were originally reported to serve as","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42247393","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":"Extracellular microRNAs in follicular fluids: implication for reproductive diseases","authors":"Zihui Wang, Yanchufei Zhang, A. Yang, Yuxuan Ren, Qipeng Zhang, Peng Wang","doi":"10.21037/exrna-20-3","DOIUrl":"https://doi.org/10.21037/exrna-20-3","url":null,"abstract":"MicroRNAs (miRNAs), a class of small non-coding RNAs, are important regulators on a post-transcriptional level. As a classical non-coding RNA, miRNAs are expressed in various tissue and are involved in many biological processes. More recently, increasing evidence has confirmed the existence of the secreted miRNAs in follicular fluid, which shed a light on the local intercellular communication. Interestingly, the miRNA profile of follicular fluids is different temporally, suggesting that miRNA secretion is finely controlled during times of development and aging. The secretion of miRNAs by somatic cells in the ovary follicle is an important resource of follicular fluid miRNAs. Comparing the miRNAs profile between follicular fluid and plasma could reveal critical miRNAs that come from circulation. The physiological functions of miRNAs in follicular fluid are believed to be a versatile message carrier for cell communications, however, due to the lack of cell-type-specific labeling methods, the route of information transmission remains elusive. It is well known that miRNA expression changes in different disease state, so it might be suitable as a biomarker. Further investigating the regulatory mechanisms mediated by these secreted miRNAs can help to understand the molecular mechanisms of oocyte maturation, early embryo development, and implantation. Therefore, this review summarizes the functions of extracellular follicular fluid miRNAs, and discusses recent progress on the potential of secreted miRNA as a biomarker in reproductive diseases.","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68332160","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":"Functional prediction of human erythrocytic miR-451a on Plasmodium falciparum 3D7 transcriptome—an in-silico study","authors":"Urja Joshi, Maulik Patel, H. Pandya, L. George, H. Highland","doi":"10.21037/exrna-21-5","DOIUrl":"https://doi.org/10.21037/exrna-21-5","url":null,"abstract":"Department of Zoology, Biomedical Technology and Human Genetics, School of Sciences, Gujarat University, Ahmedabad, India; Department of Botany, Bioinformatics and CCIM, School of Sciences, Gujarat University, Ahmedabad, India; Department of Biochemistry, School of Sciences, Gujarat University, Ahmedabad, India Contributions: (I) Conception and design: LB George; (II) Administrative support: H Pandya; (III) Provision of study materials or patients: M Patel; (IV) Collection and assembly of data: U Joshi; (V) Data analysis and interpretation: H Highland; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Urja Joshi. Department of Zoology, Biomedical Technology and Human Genetics, Department of Biochemistry, School of Sciences, Gujarat University, Ahmedabad 380009, India. Email: urjajoshi@gujaratuniversity.ac.in.","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49300129","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":"Extracellular RNA in Alzheimer’s disease","authors":"D. Hicks","doi":"10.21037/EXRNA-21-2","DOIUrl":"https://doi.org/10.21037/EXRNA-21-2","url":null,"abstract":"Extracellular vesicles (EVs) are released from all cells and represent a heterogeneous mixture of species, differing in size, function, cargo and cellular origin. EVs contain a diverse cargo, including a multitude of, predominantly non-coding, RNA species (exRNA). Alterations in exRNA have been associated with various diseases, including Alzheimer’s disease (AD). AD is a progressive neurodegenerative disease of unknown aetiology which is often associated with diagnosis in the later stages of disease and poor therapeutic options. Given the huge number of people affected by AD, both directly and indirectly, the disease has a significant social and economic burden. Thus, there is a critical need for novel mechanistic and therapeutic avenues of discovery. Hence exRNA “fingerprints” may assist with earlier, more reliable diagnoses and greater insight into disease mechanisms. However, given the large variation in study populations (stage of AD, genetic background) and analysis methods (e.g., biofluids, RNA extraction protocols), there is limited concordance in the published literature. Most studies focus on miRNA alterations, and several independent studies have reported downregulation of miR-125b, miR-29b, miR-342, miR-107, miR-142 and miR-15b in plasma/serum/blood and also miR-29c, miR-127 and miR-139 in CSF. Going forward, as exRNA consortia are assembled, protocols are standardised and novel technologies are leveraged, this field holds great promise","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44969864","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":"A matter of fat: protecting the injured heart","authors":"Daniel Paget, Naveed Akbar","doi":"10.21037/exrna-21-28","DOIUrl":"https://doi.org/10.21037/exrna-21-28","url":null,"abstract":"","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49609707","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":"Packaged or unpackaged: appearance and transport of extracellular noncoding RNAs in the plant apoplast","authors":"Sabrine Nasfi, K. Kogel","doi":"10.21037/exrna-22-11","DOIUrl":"https://doi.org/10.21037/exrna-22-11","url":null,"abstract":"","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44979967","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":"‘Treasure’ in garbage bags: extracellular vesicles based biomarker for neurological diseases","authors":"Ashish Kumar, G. Deep","doi":"10.21037/exrna-21-25","DOIUrl":"https://doi.org/10.21037/exrna-21-25","url":null,"abstract":"Extracellular vesicles (EVs) are microto nano-sized membrane-bound vesicles that are secreted by all cell types except viruses as part of their normal physiological function to maintain cellular homeostasis. Initially, EVs were considered as ‘garbage bags’ that cells utilize to throw their metabolic waste out. However, these vesicles were later recognized to play a crucial role in intercellular communication by transferring various biomolecules (loaded as cargos) such as proteins, nucleic acids (mostly non-coding RNAs), lipids and metabolites. Majorly EVs are divided into three subclasses: apoptotic bodies, microvesicles (MVs), and exosomes. Apoptotic bodies are released from the cells undergoing programmed cell death and range from ~50 to 5 μm in size (1,2). MVs are ~100 to ≥1,000 nm in size and arise by outward budding of the plasma membrane (3). Exosomes are derived from the endosomal system and released to the extracellular environment as ~30–150 nm size vesicles. EVs isolated from in vivo system cannot be distinguished if they are generated from the endosomal pathway or released from the outward budding of the plasma membrane. Also, due to their overlapping size and lack of specific biomarkers, it is difficult to discriminate these vesicles and, therefore, collectively referred as EVs. In the last decade, small EVs (sEVs), mainly enriched in exosomes, have garnered much attention for their role as biomarkers for several diseases, including cancer (4,5), cardiovascular disease (6,7), diabetes, and obesity (8,9), inflammation (10) and psychiatric disorders (11,12). The possible isolation of sEVs from almost every biological fluid and the recent methodological advancement to isolate cell type-specific sEVs pose them as an attractive target for the development of non/less invasive biomarkers for complicated diseases like psychiatric disorders. Analyzing the cargos of neuron-derived EVs (NDEVs) have been shown to predict the development of Alzheimer’s disease (AD) up to 10 years before the clinical onset (13). Ledreux et al. reported that the NDEVs isolated from the individuals with Down syndrome and AD are loaded with p-Tau and have the tau seeding capacity to spread tau pathology in the mouse brain (14). Recently, our group also reported the utility of NDEVs and other brain cell-derived EVs in identifying the neurodegenerative and pro-inflammatory effects of oxycodone self-administration in cynomolgus monkeys (15).","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48048006","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":"Targeting EGFR-steered cancer via erasing a circular RNA","authors":"Alice Rodriguez-Fuguet, Wen-Cai Zhang","doi":"10.21037/exrna-22-9","DOIUrl":"https://doi.org/10.21037/exrna-22-9","url":null,"abstract":"","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44254962","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":"Extracellular Vesicle associated circRNAs for the diagnosis and prognosis of prostate cancer—a commentary","authors":"E. Martens-Uzunova","doi":"10.21037/exrna-21-20","DOIUrl":"https://doi.org/10.21037/exrna-21-20","url":null,"abstract":"With more than 1.4 million cases in 2020 worldwide, prostate cancer (PCa) is the second most common cancer in men and the fourth most common cancer overall (1). Despite relatively low mortality rates and favorable overall survival, the high incidence of PCa accounts for a significant number of deaths each year. A main risk factor in PCa is increased age. This poses a major health concern due to the increasing proportion of elderly man in the general population and the increased risk of over-treatment following the early diagnosis of large proportion of indolent tumors (2,3). PCa is usually suspected based on digital rectal examination (DRE) and/or elevated blood levels of Prostate Specific Antigen (PSA, kallikrein-related peptidase 3, KLK). Definitive diagnose is made based on histopathological verification on prostate tissue, obtained by (repeated) transperineal or transrectal biopsies and in some cases during transurethral rejection of the prostate (TURP) to relieve symptoms from benign prostate hyperplasia (BPH), a common pathology in older men (2,3). Subsequent patient stratification into low, intermediate, or high risk cancer is done based on the combination of parameters including PSA levels, and histopathological tumor grade and stage. Unfortunately, PSA has low specificity as a diagnostic biomarker, while transperineal or transrectal biopsy is highly invasive and associated with risk of complications. Furthermore, these procedures do not always give a definitive diagnosis for a considerable proportion of the patients, which undergo subsequent cycles of repetitive biopsies and postponed treatment. On the other hand, many patients that carry indolent low-grade prostate tumors, receive the diagnose cancer, which is often associated with high psychological health burden for them and their families. The successful development of a non-invasive biomarker test that spares invasive biopsy procedures and can detect PCa in body fluids like blood or urine is a currently unmet clinical need. Ideally, such “liquid biopsy” biomarker will detect significant, life-threatening PCa with high specificity and sensitivity, adding value to existing risk calculators in the prevention of overdiagnosis and overtreatment. In the July issue of Molecular Cancer, He and colleagues (4) address this outstanding challenge by targeting patients at intermediate or high risk of biochemical recurrence of localized or locally-advanced PCa. This patient group is characterized with relatively low PSA levels (2–10 ng/mL) but biopsy results indicate aggressive tumors with high tumor grade (ISUP prognostic grade group 2 or greater, ≥ GG2) (5). He et al. investigate whether a noninvasive liquid biopsy of urine samples could detect high grade PCa before traditional tissue biopsy is taken. The authors take an innovative approach looking to identify prognostic circular RNAs (circRNAs) in the cargo of membrane bound vesicles released in urine from cells of the kidneys, bladder and pro","PeriodicalId":33060,"journal":{"name":"ExRNA","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47493064","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}