ExRNA Pub Date : 2021-01-01 DOI: 10.21037/exrna-22-1

Stefano Comità, C. Penna, P. Pagliaro

引用次数: 0

Extracellular vesicle-mediated transfer of mitochondria between organs 细胞外囊泡介导的器官间线粒体转移

ExRNA Pub Date : 2021-01-01 DOI: 10.21037/exrna-21-30

Alice C Rodrigues

引用次数: 0

MicroRNAs present in neuron-derived extracellular vesicles extracted from the blood of psychiatric patients as potential biomarkers of mood disorders 从精神病患者血液中提取的神经元源性细胞外囊泡中存在的microrna作为情绪障碍的潜在生物标志物

ExRNA Pub Date : 2021-01-01 DOI: 10.21037/exrna-21-22

M. Dziedzicka-Wasylewska, J. Solich, A. Faron-Górecka

{"title":"MicroRNAs present in neuron-derived extracellular vesicles extracted from the blood of psychiatric patients as potential biomarkers of mood disorders","authors":"M. Dziedzicka-Wasylewska, J. Solich, A. Faron-Górecka","doi":"10.21037/exrna-21-22","DOIUrl":"https://doi.org/10.21037/exrna-21-22","url":null,"abstract":"Mood disorders, including major depressive disorder (MDD), are still a considerable burden for modern society. Despite the availability of approx. fifty different drugs, the treatment of MDD is far from ideal, nor is the full understanding of the mechanism of action of antidepressant drugs (ADs) administered repeatedly (which is necessary to achieve clinical efficacy). There have been several hypotheses explaining the etiopathogenesis of depression. Most of these are based on the mechanisms of action of known ADs, the first of which were discovered by serendipity in the 1950s (imipramine and iproniazid). Later, the mechanism of their acute action (e.g. non-selective inhibition of re-uptake of serotonin and noradrenaline, and inhibition of monoamine oxidase, respectively) has been elucidated, and most of the newly synthesized compounds mimic some or all of their features: being either more selective towards one of the biogenic amines, having an affinity towards various neurotransmitter receptors such as N-methyl D-aspartate (NMDA) receptors for glutamate, or being more selective and reversible monoamine oxidase inhibitors (1). Knowing these mechanisms does not help in achieving a satisfactory clinical outcome, in fact, we still do not understand the etiopathology of MDD and other mood disorders. Most of the numerous behavioral, biochemical, and molecular preclinical studies focus on various kinds of stress since it is regarded as the main factor contributing to mood disorders. Stress is defined as a condition that seriously perturbs the psychological and physiological balance of an individual. Traumatic stress, however, does not affect everyone in the same manner—some susceptible individuals (not only humans but also animals) adapt poorly to stressors and express inappropriate responses that can become persistent states of stress themselves. Resilient individuals can perceive adversity and develop adaptive psychological and physiological responses. The underlying mechanisms of these responses are not fully understood, although they are known to depend on a combination of genetic and non-genetic factors that interact in complex ways. Similarly, lack of response to ADs treatment is very often encountered, despite continuous improvements in treatment recommendations and alternatives to convention pharmacotherapy, including psychotherapy and deep brain stimulation as well as augmenting agents (e.g., atypical antipsychotic drugs or lithium). We still do not know what is the mechanism of such diversity of responses, therefore finding biomarkers useful in the identification of patient subpopulations—potential treatment responders vs. nonresponders, not to mention biomarkers useful to distinguish bipolar from MDD patients—is of utmost importance. The idea that circulating microRNAs (miRNAs) might be a good indicator of processes underlying psychiatric illnesses is present in the scientific literature for some time (2). The first miRNA was discovered in 19","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":"47805756","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}

引用次数: 0

NLRP3 inflammasome activation modulates exosomal RNA content and inhibits inflammatory responses in recipient cells NLRP3炎性小体激活调节外泌体RNA含量并抑制受体细胞的炎症反应

ExRNA Pub Date : 2021-01-01 DOI: 10.21037/exrna-21-19

Wojciech Cypryk, S. Matikainen

{"title":"NLRP3 inflammasome activation modulates exosomal RNA content and inhibits inflammatory responses in recipient cells","authors":"Wojciech Cypryk, S. Matikainen","doi":"10.21037/exrna-21-19","DOIUrl":"https://doi.org/10.21037/exrna-21-19","url":null,"abstract":"Extracellular vesicles (EV) are nanometer-sized membranebound entities secreted by cells, mediating important intercellular communication in orchestration of immune responses (1). The roles of macrophage-derived EV have been implicated in inflammatory conditions including cardiovascular diseases, metabolic conditions and microbial infections (2). Inflammation is in part driven by the function of inflammasomes—cytosolic patter recognition receptors of the innate immune system, among them most prominently by NLRP3 inflammasome activated by a wide range of microbial and endogenous ligands (3). Increased secretion of EVs with modified protein and RNA signatures has been recently linked with the function of the inflammasome (4,5). In a recent paper, Budden and colleagues analyze in detail the pattern of EV secretion regulated by inflammasome activity exerted by treatment of LPS-primed THP1 macrophages with nigericin, a welldescribed canonical inflammasome activator (6). First, they fractionated vesicles by differential centrifugation and size exclusion chromatography (SEC) to obtain preparations of large, intermediate and small EV. Secretion of all vesicle types was markedly enhanced upon nigericin treatment. Importantly, the authors clearly demonstrate that the effect is due to canonical NLRP3 inflammasome activity, as inhibition of caspase-1 and gasdermin D leads to significant reduction of EV secretion. Interestingly, this dependence was not observed when NLRP3 inflammasome was activated by MSU crystals. In line with this result, it has been previously shown that MSU-induced cell death is NLRP3 independent indicating a potential existence of another receptor for MSU mediating EV release and cell death (7,8). In conclusion, the results of Budden and co-worker’s suggest that release of EVs in response to inflammasome activation is not a passive, pyroptosis-driven event, but is instead highly regulated. The authors followed their observations with in-depth transcriptomic analysis of the RNA content of the EV secreted during inflammasome activation and found that intermediate (10K) EV differ substantially from small EV in terms of their RNA transcript composition. However, the overall composition of the fractions is similarly modified regardless of type of the inflammasome-activating stimulus. In an attempt to understand the physiological effects of EV in inflammatory process, the inflammasomeinduced EV isolated from THP-1 macrophages were incubated with naive THP-1 macrophages to monitor their inflammatory response by transcriptomics. To exclude a possible autocrine inflammatory effect, the authors used NLRP3 KO cells as recipients. While SEC-derived small EV did not trigger any significant changes in the phenotype of the recipient cells, the 10K intermediate EV turned out to activate the interferon transcriptional program, causing significant upregulation of interferon stimulated genes (ISGs), including Mx2, ISG15 and OAS3. The same effect was observ","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":"44240783","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}

引用次数: 0

Why should the molecular characterization of inflammasome-induced exosomal cargo be done? 为什么要对炎症小体诱导的外泌体货物进行分子表征？

ExRNA Pub Date : 2021-01-01 DOI: 10.21037/exrna-21-16

A. Engin, A. Engin

{"title":"Why should the molecular characterization of inflammasome-induced exosomal cargo be done?","authors":"A. Engin, A. Engin","doi":"10.21037/exrna-21-16","DOIUrl":"https://doi.org/10.21037/exrna-21-16","url":null,"abstract":"Exosomes (EXSs) are nano-sized and circulat ing membrane-bound extracellular vesicles (EVs) which protect the stability of their cargo, including messenger ribonucleic acid (mRNA), microRNA (miRNA) and other proteins from degradation. Upon taken up by recipient cells, they deliver their cargo molecules to the target cells. When inflammatory stimuli activate innate immune signaling receptors, cargo molecules modify the molecules of recipient cell. Because molecules carried with EXS-cargo are thought to be biomarkers, the role of EXSs is emerging as an important new area of biomedical research. In addition to inflammatory mediators, EXSs, which are secreted by macrophages play pivotal roles in intercellular communications and multi biological functions (1). The immune response-related proteins and signaling pathways are specifically enriched in inflammasome-derived EXSs. This type of EXSs directly activates nuclear factor kappa B (NF-κB) signaling pathway and expresses pro-interleukin 1-beta (pro-IL-1β) and pro-IL-18 via its transcriptional upregulation (2). EXSs as potential carriers for targeted gene, are thought to promote inflammation via releasing of inflammasome components during the inflammatory response. Of note, there is a need for further studies to elucidate the role of EXSs by using improved detection and characterization methods (3). Indeed, inflammasomes are critical for both local and systemic inflammation. Canonical type NODlike receptor protein 3 (NLRP3) inflammasome is known to sense multiple microbial and endogenous danger signals, and its activation results in caspase-1, IL-1β and IL-18, dependent processes. However, non-canonical, caspase4/5-dependent inflammasomes bind to intracellular lipopolysaccharides (LPS), and directly regulate pyroptosis (4,5). Contrarily, Budden et al. have proposed that the pathways eliciting caspase 1-driven cell death strongly induce EXS release, whereas stimuli, which do not induce pyroptosis are weaker stimuli for EXS release (6). In this context two noteworthy results are emerged in this study. EXSs released from inflammasome-activated macrophages have a specific RNA signature and contain interferonbeta (IFN-β). IFN-β is responsible for the induction of IFN-stimulated genes (ISGs) in EXS recipient cells, independently of NLRP3 expression. Thereby, this cargo induces an IFN signature in bystander cells and leads to silencing of NLRP3 inflammasome response (6). In this situation, IFN-β inhibits NLRP3 inflammasomes in a signal transducer and activator of transcription 1 (STAT1)dependent manner, while decreases the amounts of pro-IL1β in a STAT3-dependent manner (7). In case of toll-like receptor (TLR) activation, Toll/IL-1 receptor homology (TIR)-domain-containing adaptor protein-inducing IFN-β (TRIF) interacts with receptor-interacting protein 1 (RIP1), which is responsible for the activation of NFκB. Thus, stimulation with TLR ligands induces type I IFN production in addition to proinflammatory si","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":"47042479","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}

引用次数: 0

Persistence of fibrogenic process in direct-acting antiviral (DAA) treated patients? 直接作用抗病毒药物(DAA)治疗患者的纤维化过程是否持续?

ExRNA Pub Date : 2021-01-01 DOI: 10.21037/exrna-22-13

Cecilia Battistelli, M. Tripodi

引用次数: 0

The extracellular miRNA fingerprint of kidney disease: a narrative review 肾脏疾病的细胞外miRNA指纹图谱:一个叙述性的回顾

ExRNA Pub Date : 2021-01-01 DOI: 10.21037/exrna-22-2

V. Miguel

引用次数: 2

The abundance of a transfer RNA-derived RNA fragment small RNA subpopulation is enriched in cauda spermatozoa 尾精子中富含转移RNA衍生的RNA片段小RNA亚群

ExRNA Pub Date : 2020-11-01 DOI: 10.1186/s41544-020-00058-x

Simone J. Stanger, I. Bernstein, A. Anderson, Kate Hutcheon, Matthew D. Dun, A. Eamens, B. Nixon