Role Of Extracellular Vesicles Research Articles

Bone Marrow Stromal Cell Mediated Drug Resistance in AML Cells: Role of Extracellular Vesicles and AKT Signaling

Accumulating evidence suggests that bone marrow stromal micro-environment act as sanctuary site for acute myeloid leukemia (AML) cells and affords protection from conventional chemotherapy agents. Recently, there has been considerable interest in extracellular vesicles (EVs) and their role in intercellular communication. We had previously reported that there is significant stromal cell mediated drug resistance in acute promyelocytic leukemia (APL) which was predominantly driven by up-regulation of the NF-kB pathway in the malignant cells (Ganesan S et al, Leukemia 2016). Though there are reports of similar stromal cell mediated protection against chemotherapy in non-M3 AML cells, there is limited data on the role EVs play, if any, in inducing such chemotherapy resistance. We undertook a preliminary study to evaluate the role of EVs in inducing resistance to chemotherapeutic agents in AML.We demonstrated that direct stromal co-culture experiments with AML cell lines as well as primary AML cells showed a significant stromal mediated protective effect against both cytosine arabinoside (AraC) and daunorubicin (DNR) [U937: AraC p < 0.01, DNR p < 0.001 (n=5); primary AML cells: AraC p < 0.01, DNR p < 0.001 (n=26)]. Gene expression profiling (GEP) analysis of AML cell line U937 co-cultured with HS-5 revealed a significant enrichment of genes involved in PI3K-AKT signaling pathway (p < 0.0001) followed by NF-kB pathway genes. It has been previously reported that on direct co-culture with stromal cells there is activation of the PI3K-AKT pathway in AML cells leading to drug resistance (Tabe Y et al. Cancer Res 2007). It is also well recognized that PI3K-AKT pathway can drive NF-kB signaling, which is consistent with our earlier reported observation in APL. We hypothesize that this effect of PI3K-AKT activation could be mediated by EVs without direct malignant and stromal cell interaction as well. Towards this, we isolated stromal EVs as previously described (Suzanne M et al, Blood 2016). The size and concentration of EVs was characterized by NanoSight and flow cytometry (data not shown).We demonstrated an activation of PI3K-AKT signaling by showing phosphorylation of AKT (P-AKTser473) in U937 cells when treated with stromal EVs (figure 1A). We further demonstrated that stromal EVs were able to mediate a protective effect against AraC and DNR similar to that seen on direct co-culture with HS-5 cells [AraC p < 0.01, DNR p < 0.01 (n=3)]. This was further confirmed by looking at the pathway genes using Q-PCR, where an increased expression of PI3K-AKT signaling was observed in AML cells upon treatment with stromal EVs. The activation PI3K signaling was also confirmed by showing down regulation of PTEN [p < 0.01 (n=5)] which is a negative regulator of PI3K-AKT signaling. Further, to demonstrate the role of stromal EVs induced PI3K-AKT signaling in drug resistance, we treated the leukemic cells with a small molecule inhibitor of PI3 kinase (LY294002-10uM) along with AraC and DNR in the presence of stromal EVs. We noted that inhibiting PI3K-AKT signaling along with AraC or DNR was able to overcome the resistance mediated by stromal EVs (figure 1B). The mechanism of inducing apoptosis by LY294002 along with DNR or AraC (in the presence of stroma or stromal EVs) probably involves a TP53 dependent apoptosis pathway as evidenced through upregulation of TP53 and its target apoptotic genes such as BAD, CASP9 and PUMA (AraC- figure 1C, DNR - data not shown).Our study thus illustrates the complexity of cellular crosstalk between leukemic cells and its microenvironment in inducing drug resistance. This resistance can be mediated by non-contact setting via stromal EVs through up regulation of PI3K-AKT signaling in myeloid leukemic cells. Our data highlights the need for additional studies that are required to explore and characterize in detail the cargo of these EVs and the mechanisms by which they mediate drug resistance. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The role of extracellular vesicles in regulating local and systemic inflammation in cardiovascular disease

Extracellular vesicles are heterogeneous structures surrounded by cell membranes and carry complex contents including nucleotides, proteins, and lipids. These proteins include cytokines and chemokines that are important for exaggerating local and systemic inflammation in disease. Extracellular vesicles are mainly categorized as exosomes and micro-vesicles, which are directly shed from the endosomal system or originated from the cell membrane, respectively. By transporting several bioactive molecules to recipient cells and tissues, extracellular vesicles have favorable, neutral, or detrimental impacts on their targets, such as switching cell phenotype, modulating gene expression, and controlling biological pathways such as inflammatory cell recruitment, activation of myeloid cells and cell proliferation. Extracellular vesicles mediate these functions via both autocrine and paracrine signaling. In the cardiovascular system, extracellular vesicles can be secreted by multiple cell types like cardiomyocytes, smooth muscle cells, macrophages, monocytes, fibroblasts, and endothelial cells, and affect functions of cells or tissues in distant organs. These effects involve maintaining homeostasis, regulating inflammation, and triggering pathological process in cardiovascular disease. In this review, we mainly focus on the role of micro-vesicles and exosomes, two important subtypes of extracellular vesicles, in local and systemic inflammation in cardiovascular diseases such as myocardial infarction, atherosclerosis and heart failure. We summarize recent findings and knowledge on the effect of extracellular vesicles in controlling both humoral and cellular immunity, and the therapeutic approaches to harness this knowledge to control exacerbated inflammation in cardiovascular diseases.

The Role of Extracellular Vesicles in Disease Progression and Detection of Hepatocellular Carcinoma.

Simple SummaryExtracellular vesicles (EVs) are particles naturally released from cells and mediate intercellular communication. Recently, emerging studies have shown that EVs play a crucial role in regulating progression of hepatocellular carcinoma (HCC), which is one of the leading causes of cancer-related death worldwide. With the advances of technologies in isolating EVs from patients’ blood, EVs are regarded as promising biomarkers for detecting HCC at an earlier stage. This review provides an overview of the current EVs isolation methods, the biological roles of EVs in mediating disease progression, and the feasibility of EVs’ use for detection of HCC. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and one of the leading causes of cancer-related death worldwide. Despite the improvements in surveillance and treatment, the prognosis of HCC remains poor. Extracellular vesicles (EVs) are a heterogeneous group of phospholipid bilayer-enclosed particles circulating in the bloodstream and mediating intercellular communication. Emerging studies have shown that EVs play a crucial role in regulating the proliferation, immune escape, and metastasis of HCC. In addition, because EVs are present in the circulation at relatively early stages of disease, they are getting attention as an attractive biomarker for HCC detection. Over the past decade, dedicated efforts have been made to isolate EVs more efficiently and make them useful tools in different clinical settings. In this review article, we provide an overview of the EVs isolation methods and highlight the role of EVs as mediators in the pathogenesis and progression of HCC. Lastly, we summarize the potential applications of EVs in early-stage HCC detection.

Role of Extracellular Vesicles in Placental Inflammation and Local Immune Balance.

Background Pregnancy maintenance depends on the formation of normal placentas accompanied by trophoblast invasion and vascular remodeling. Various types of cells, such as trophoblasts, endothelial cells, immune cells, mesenchymal stem cells (MSCs), and adipocytes, mediate cell-to-cell interactions through soluble factors to maintain normal placental development. Extracellular vesicles (EVs) are diverse nanosized to microsized membrane-bound particles released from various cells. EVs contain tens to thousands of different RNA, proteins, small molecules, DNA fragments, and bioactive lipids. EV-derived microRNAs (miRNAs) and proteins regulate inflammation and trophoblast invasion in the placental microenvironment. Maternal-fetal communication through EV can regulate the key signaling pathways involved in pregnancy maintenance, from implantation to immune regulation. Therefore, EVs and the encapsulating factors play important roles in pregnancy, some of which might be potential biomarkers. Conclusion In this review, we have summarized published studies about the EVs in the placentation and pregnancy-related diseases. By summarizing the role of EVs and their delivering active molecules in pregnancy-related diseases, it provides novel insight into the diagnosis and treatment of diseases.

The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma.

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

Role of extracellular vesicles in liver diseases and their therapeutic potential.

More than eight hundred million people worldwide have chronic liver disease, with two million deaths per year. Recurring liver injury results in fibrogenesis, progressing towards cirrhosis, for which there doesn't exists any cure except liver transplantation. Better understanding of the mechanisms leading to cirrhosis and its complications is needed to develop effective therapies. Extracellular vesicles (EVs) are released by cells and are important for cell-to-cell communication. EVs have been reported to be involved in homeostasis maintenance, as well as in liver diseases. In this review, we present current knowledge on the role of EVs in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, alcohol-associated liver disease, chronic viral hepatitis, primary liver cancers, acute liver injury and liver regeneration. Moreover, therapeutic strategies involving EVs as targets or as tools to treat liver diseases are summarized.

Extracellular Vesicles and Pancreatic Cancer: Insights on the Roles of miRNA, lncRNA, and Protein Cargos in Cancer Progression.

Pancreatic cancer (PC) is among the most devastating digestive tract cancers worldwide. This cancer is characterized by poor diagnostic detection, lack of therapy, and difficulty in predicting tumorigenesis progression. Although mutations of key oncogenes and oncosuppressor involved in tumor growth and in immunosurveillance escape are known, the underlying mechanisms that orchestrate PC initiation and progression are poorly understood or still under debate. In recent years, the attention of many researchers has been concentrated on the role of extracellular vesicles and of a particular subset of extracellular vesicles, known as exosomes. Literature data report that these nanovesicles are able to deliver their cargos to recipient cells playing key roles in the pathogenesis and progression of many pancreatic precancerous conditions. In this review, we have summarized and discussed principal cargos of extracellular vesicles characterized in PC, such as miRNAs, lncRNAs, and several proteins, to offer a systematic overview of their function in PC progression. The study of extracellular vesicles is allowing to understand that investigation of their secretion and analysis of their content might represent a new and potential diagnostic and prognostic tools for PC.

An Overview of Chemical and Biological Materials lead to Damage and Repair of Heart Tissue.

Cardiovascular diseases (CVDs) are major causes of mortality in developing countries. One of the challenges during CVDs studies is the creation of a damaged model of the heart. Many injured models of cardiac diseases are created by using chemical and biological materials. Many approaches were applied to simulate heart injury for investigating CVDs. In previous years, animal models could be used as a useful pattern in many investigations about the pathogenesis of the heart. Nowadays it has been proven that there are many differences between human and animal models in terms of responses or reactions to treatments. For such reasons, researchers prefer to use cellular models alongside the animal models for studying heart diseases. In this review, we collected information about some chemical and biological materials used to create damaged-heart models both in vitro and in vivo. After explaining the materials that induce cardiac damage, we explicate some methods for repairing the damage of heart. Finally, the role of extracellular vesicles as an important biological candidate for repairing heart damage is briefly discussed. This mini-review tried to explain some methods which can induce cardiac damage and repair of heart cells by use chemical and biological materials. We considered that various molecular pathways play a role in restoration and that most of these pathways are connected in a complex network and, to this end, different chemicals and drugs have been studied to date. Nonetheless, more studies are needed to ensure the performance and safety of the drugs and chemicals produced.

Evaluating the role of extracellular vesicles as a biomarker under transmission electron microscope in prostate cancer and benign prostate hyperplasia patients.

To our knowledge, EVs (extracellular vesicles) are heterogenous encapsulated nanoparticles generated by the biological cells. EVs can be found in blood, urine and tissue of origin. They contain DNAs, RNAs, proteins specific to the cell of origin. It has been found that in PCa, increase in number of EVs can modulate phenotype and function of the recipient cells. This prospective randomized double-blind pilot study was conducted in the SMS Medical College, Jaipur in collaboration with All India Institute of Medical Sciences, New Delhi. For morphometric analysis, the number of extracellular vesicles per micrograph were counted under transmission electron microscope. Out of 16 patients taken in our study, six were in group 1 (BPH group) and 10 were in group 2 (PCa group). The mean number of EVs was significantly higher in the cells of group 2 in comparison to the group 1. Among the PCa patients, mean number of EVs were 25, 30, 35, 43, 46 for the Gleason score 6, 7, 8, 9, 10 respectively. In our study the mean number of EVs in the newly diagnosed PCa group was less as compared to the CSPC and CRPC group. EVs are membrane bound particles shed regularly from the cells in the extracellular milieu under normal physiological and pathological conditions. In our study the number of EVs were more in the PCa cells in comparison with the BPH cells and among the PCa cells they bear a positive correlation with the Gleason score, thus EVs have the potential to become a biomarker.

The Role of Extracellular Vesicles in the Development of a Cancer Stem Cell Microenvironment Niche and Potential Therapeutic Targets: A Systematic Review.

Simple SummaryCancer stem cells (CSCs) are cancer cells that possess traits usually attributed to stem cells. An increase in CSCs can lead to more rapid cancer progression, treatment resistance and the increased likelihood of recurrence. To promote CSC survival and associated cancer progression, cancer cells enter into reciprocal crosstalk with the surrounding tissue environment, as well as with distant metastatic sites. This mechanism of communication relies, in part, on secreted factors, of which extracellular vesicles (EVs) are thought to have a critical role. This systematic review evaluates the current knowledge of cancer communication via EVs to alter the microenvironment to increase the survival and maintenance of CSCs. A total of 16 studies spanning the EV content, pathway alterations and CSC-targeting treatments provide new insights into how EVs mediate CSC traits and identify the gaps in our understanding of how modulation of the microenvironment plays a key role.Cancer stem cells (CSCs) have increasingly been shown to be a crucial element of heterogenous tumors. Although a relatively small component of the population, they increase the resistance to treatment and the likelihood of recurrence. In recent years, it has been shown, across multiple cancer types (e.g., colorectal, breast and prostate), that reciprocal communication between cancer and the microenvironment exists, which is, in part, facilitated by extracellular vesicles (EVs). However, the mechanisms of this method of communication and its influence on CSC populations is less well-understood. Therefore, the aim of this systematic review is to determine the evidence that supports the role of EVs in the manipulation of the tumor microenvironment to promote the survival of CSCs. Embase and PubMed were used to identify all studies on the topic, which were screened using PRISMA guidelines, resulting in the inclusion of 16 studies. These 16 studies reported on the EV content, pathways altered by EVs and therapeutic targeting of CSC through EV-mediated changes to the microenvironment. In conclusion, these studies demonstrated the role of EV-facilitated communication in maintaining CSCs via manipulation of the tumor microenvironment, demonstrating the potential of creating therapeutics to target CSCs. However, further works are needed to fully understand the targetable mechanisms upon which future therapeutics can be based.

Role of Extracellular Vesicles in human uveitis

Abstract Non-infectious uveitis (NIU) is a significant cause of blindness. It is an immune mediated disease however the exact pathogenesis remains elusive. Considerable evidence exists on the immunomodulatory effects of Extracellular Vesicles (EVs) in various diseases; but little is known on the role of EVs in uveitis patients. We have previously shown that cytokine stimulated ARPE19 cells, release EVs; these EVs are capable of inhibiting T cell proliferation, inducing proinflammatory cytokine production from monocytes and monocyte cell death, in PBMCs from uveitis patients. The purpose of this study was to isolate EVs from uveitis patients and to determine their immune-modulatory potential in-vitro. EVs were isolated from the serum of NIU patients using Size Exclusion Chromatography (SEC) and set up in culture with PBMCs or ARPE19 cells; after stimulation cells were stained to determine activation and cytokine production. A higher number of EVs were isolated from patients, as compared to healthy controls; but EVs from both, were of the appropriate size, had a low protein content and were positive for the exosome associated markers CD9, CD63 and CD81. EVs from patients expressed increased levels of CD8, CD29, CD44, and HLA-DR/DP/DQ, indicating their potential to activate cells in-vivo as compared to controls. An upregulation of CD69 and CD25 on T cells and increased IFNg production was observed when the cells were cultured with EVs from patients. Incubating ARPE19 cells with the EVs from patients, increased the expression of MCP1 and IL8 in the cells. Preliminary data indicates that EVs isolated from uveitis patients can induce a robust activation of cells in-vitro. Current experiments are underway to further substantiate these results.

A modified clot-based assay to measure negatively charged procoagulant phospholipids

Growing evidence supports a role for extracellular vesicles (EVs) in haemostasis and thrombosis due to exposure of negatively charged procoagulant phospholipids (PPL). Current commercial PPL-dependent clotting assays use chemically phospholipid depleted plasma to measure PPL activity. The purpose of our study was to modify the PPL assay by substituting the chemically phospholipid depleted plasma with PPL depleted plasma obtained by ultracentrifugation This in order to get readily access to a sensitive and reliable assay to measure PPL activity in human plasma and cell supernatants. The performance of the assay was tested, including the influence of individual coagulation factors and postprandial lipoproteins and compared to a commercial PPL assay (STA-Procoag-PPL). The two PPL assays displayed similar sensitivity to exogenously added standardized phospholipids. The PPL activity measured by the modified assay strongly correlates with the results from the commercial assay. The intraday- and between-days coefficients of variation ranged from 2–4% depending on the PPL activity in the sample. The modified PPL assay was insensitive to postprandial lipoprotein levels in plasma, as well as to tissue factor (TF) positive EVs from stimulated whole blood. Our findings showed that the modified assay performed equal to the comparator, and was insensitive to postprandial lipoproteins and TF+ EVs.

The Role of Extracellular Vesicles in Mediating Resistance to Anticancer Therapies.

Although advances in targeted therapies have driven great progress in cancer treatment and outcomes, drug resistance remains a major obstacle to improving patient survival. Several mechanisms are involved in developing resistance to both conventional chemotherapy and molecularly targeted therapies, including drug efflux, secondary mutations, compensatory genetic alterations occurring upstream or downstream of a drug target, oncogenic bypass, drug activation and inactivation, and DNA damage repair. Extracellular vesicles (EVs) are membrane-bound lipid bilayer vesicles that are involved in cell–cell communication and regulating biological processes. EVs derived from cancer cells play critical roles in tumor progression, metastasis, and drug resistance by delivering protein and genetic material to cells of the tumor microenvironment. Understanding the biochemical and genetic mechanisms underlying drug resistance will aid in the development of new therapeutic strategies. Herein, we review the role of EVs as mediators of drug resistance in the context of cancer.

The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma.

The long-underestimated role of extracellular vesicles in cancer is now reconsidered worldwide by basic and clinical scientists, who recently highlighted novel and crucial activities of these moieties. Extracellular vesicles are now considered as king transporters of specific cargoes, including molecular components of parent cells, thus mediating a wide variety of cellular activities both in normal and neoplastic tissues. Here, we discuss the multifunctional activities and underlying mechanisms of extracellular vesicles in neuroblastoma, the most frequent common extra-cranial tumor in childhood. The ability of extracellular vesicles to cross-talk with different cells in the tumor microenvironment and to modulate an anti-tumor immune response, tumorigenesis, tumor growth, metastasis and drug resistance will be pinpointed in detail. The results obtained on the role of extracellular vesicles may represent a panel of suggestions potentially useful in practice, due to their involvement in the response to chemotherapy, and, moreover, their ability to predict resistance to standard therapies—all issues of clinical relevance.

Research progress on the role of extracellular vesicles in the diagnosis and treatment of chronic periodontitis

Chronic periodontitis is a disease of periodontal supporting tissue infection caused by various causes. It was believed that the oral bacteria were the initiator of chronic periodontitis, and the host immune factors would affect the developing process and outcome of periodontitis, although the specific regulatory mechanism was not completely clear. Extracellular vesicles, subcellular components produced by cell paracrine, may carry a variety of genetic information to mediate intercellular communication. Extracellular vesicles have been found to be closely related to tumors and cardiovascular, cerebrovascular, neurological and immune system diseases and provide a research pathway for the early diagnosis, etiological therapy and vaccine design. Various extracellular vesicles are released from periodontal ligament stem cells, gingival mesenchymal stem cells, bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, immune cells and periodontal pathogenic bacteria. These extracellular vesicles release for mutual communication and regulation, and further affect the pathogenesis of chronic periodontitis. In the present article, the characteristics of extracellular vesicles from periodontal tissues and periodontal pathogenic bacteria were introduced, the research progress of extracellular vesicles involved in the regulation of chronic periodontitis was reviewed and the potential value of extracellular vesicles in the diagnosis and treatment of chronic periodontitis was prospected.

Professional killers: The role of extracellular vesicles in the reciprocal interactions between natural killer, CD8+ cytotoxic T-cells and tumour cells.

Extracellular vesicles (EVs) mediate the cross‐talk between cancer cells and the cells of the surrounding Tumour Microenvironment (TME). Professional killer cells include Natural Killer (NK) cells and CD8+ Cytotoxic T‐lymphocytes (CTLs), which represent some of the most effective immune defense mechanisms against cancer cells. Recent evidence supports the role of EVs released by NK cells and CTLs in killing cancer cells, paving the road to a possible therapeutic role for such EVs. This review article provides the state‐of‐the‐art knowledge on the role of NK‐ and CTL‐derived EVs as anticancer agents, focusing on the different functions of different sub‐types of EVs. We also reviewed the current knowledge on the effects of cancer‐derived EVs on NK cells and CTLs, identifying areas for future investigation in the emerging new field of EV‐mediated immunotherapy of cancer.

Overcoming Chemoresistance via Extracellular Vesicle Inhibition.

With the ever-growing number of cancer deaths worldwide, researchers have been working hard to identify the key reasons behind the failure of cancer therapies so the efficacy of those therapies may be improved. Based on extensive research activities and observations done by researchers, chemoresistance has been identified as a major contributor to the drastic number of deaths among cancer patients. Several factors have been linked to formation of chemoresistance, such as chemotherapy drug efflux, immunosuppression, and epithelial-mesenchymal transition (EMT). Lately, increasing evidence has shed light on the role of extracellular vesicles (EVs) in the regulation of chemoresistance. However, there is limited research into the possibility that inhibiting EV release or uptake in cancer cells may curb chemoresistance, allowing chemotherapy drugs to target cancer cells without restriction. Prominent inhibitors of EV uptake and release in cancer cells have been compiled and contrasted in this review. This is in the hope of sparking greater interest in the field of EV-mediated chemoresistance, as well as to provide an overview of the field for fundamental and clinical research communities, particularly in the field of cancer resistance research. In-depth studies of EV-mediated chemoresistance and EV inhibitors in cancer cells would spur significant improvement in cancer treatments which are currently available.

Терапевтические мишени при коагулопатии COVID-19

В обзоре представлены сведения о некоторых биохимических и клеточных механизмах патогенеза потенциально смертельного вирусного заболевания, получившего название COVID-19, провоцируемого вирусами из семейства коронавирусов SARS-CoV-2. Наибольшую опасность для жизни и здоровья пациентов представляет коагулопатия, обусловленная ответной реакцией на инфекцию — чрезмерной генерацией клетками пациента внеклеточных мембранных нановезикул (ВМН), которые могут спровоцировать активизацию гемостаза, приводящую к разрушительной полиорганной недостаточности. Вирусы также способны генерировать внеклеточные везикулы, называемые виросомами. Встраивая вирусные компоненты в свои виросомы, вирусы повышают персистентность за счет маскировки своих геномов, умножая вирусную инфекцию. В статье охарактеризованы свойства нейтрофильных гранулоцитов, активирующихся при инфицировании, и представлены сведения о молекулярных механизмах действия их компонентов при попадании во внеклеточное пространство. ВМН уже имеют практическое применение в качестве вакцинных носителей для иммунизации человека и животных против многих инфекционных заболеваний. В настоящее время актуальнейшей темой, обуславливающей большой практический интерес, стала роль ВМН в индуцировании иммунитета против коронавирусной инфекции. Охарактеризованы другие возможные терапевтические мишени. Virus-induced coagulopathy is a typical example of the tight connection between inflammation and thrombosis. These two reactions are linked by pro-inflammatory agents, generated by activated neutrophils and their neutrophil extracellular traps (NETs). Extracellular membrane nanobubbles (EMNs), formed by a wide variety of cell types, have recently been identified as new entrants that play a key role in coagulopathy. EMNs directly and indirectly activate coagulation systems that lead to the further upregulation of inflammation and life-threatening organ dysfunction and thrombosis. EMNs are known to be responsible for the secretion, exchange, and transmission of important active biomolecules in COVID-19. Indeed, EMNs represent an essential mechanism in intercellular communication, and the roles of EMNs in infection and thrombosis have been increasingly recognized. The extracellular microvesicles of viruses, virosomes, represent a new type of infectious agents, which determines new therapeutic goals in solving the problems of controlling viral infections. Understanding the biological nature of all these microvesicles when studying them in vivo is of paramount importance for the development of diagnostic and therapeutic methods.

Radioiodine labeling and in vivo trafficking of extracellular vesicles

Biodistribution and role of extracellular vesicles (EVs) are still largely unknown. Reliable tracking methods for EVs are needed. In this study, nuclear imaging using radioiodine were developed and applied for tracking EVs derived from cell lines. EVs were obtained from supernatant of thyroid cancer cell (Cal62) and natural killer cells (NK92-MI) using sequential ultracentrifuges. Sulfosuccinimidyl-3-(4-hydroxypheynyl) propionate were labeled to membrane of Cal62 and NK92-MI cell derived EVs, then the EVs were labeled with radioiodine (I-131 and I-125) using pre-coated iodination tubes (RI-EVs). In vivo gamma camera images were obtained after intravenous injection of the RI-EVs, and ex vivo biodistribution study was also performed. EVs were labeled with radioiodine and radiochemical purity of the RI-EV was more than 98%. Results of nanoparticle tracking analysis and electron microscopy showed that there was no significant difference in EVs before and after the radioiodine labeling. After intravenous injection of RI-EVs to mice, gamma camera imaging well visualized the real-time biodistribution of the RI-EVs. RI-EVs were mainly visualized at liver, spleen, and lung. Nuclear imaging system of EVs derived from thyroid cancer and NK cells using radioiodine labeling of the EVs was established. Thus, this system might be helpful for in vivo tracking of EVs.

The role of extracellular vesicles in the regulation of redox homeostasis during exercise: a focus on Nrf2 and antioxidant enzymes

The role of extracellular vesicles in the regulation of redox homeostasis during exercise: a focus on Nrf2 and antioxidant enzymes