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Search terms: exosomes OR "extracellular vesicles" OR microvesicles OR microparticles. Direct link to the PubMed search here.

Association of platelet-derived microvesicles and their phenotypes with carotid atherosclerosis and recurrent vascular events in patients after ischemic stroke.

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Association of platelet-derived microvesicles and their phenotypes with carotid atherosclerosis and recurrent vascular events in patients after ischemic stroke.

Thromb Res. 2019 Feb 02;176:18-26

Authors: Rosińska J, Ambrosius W, Maciejewska J, Narożny R, Kozubski W, Łukasik M

Abstract
INTRODUCTION: Platelet-derived microvesicles (pMVs) exhibit procoagulant and proinflammatory properties and play a role in the development and progression of atherosclerosis. The study examined the association between the total number of pMVs and their phenotypes with carotid atherosclerosis and recurrent vascular events (VEs) in patients in the convalescent phase of ischemic stroke (IS).
MATERIALS AND METHODS: The study group consisted of 72 patients with IS secondary to large artery atherosclerosis (LAA) (n = 40) and small arteries occlusion (SAO) (n = 32) and 69 matched cardiovascular disease risk-factor (RF) controls. Total pMV number, defined as CD61+ microvesicles (MVs), and their phenotypes, defined as the surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers, were characterized and quantified using flow cytometry. The mean common carotid intima-media thickness (CCA mean IMT), maximal common carotid IMT (CCA max IMT) and maximal bifurcation IMT (BIF max IMT) were measured bilaterally using B-mode, color Doppler ultrasonography. All study subjects were observed for one-year to establish the occurrence of VEs.
RESULTS: No differences in pMV parameters between LAA and SAO stroke subjects and between stroke subgroups and controls were found. Stroke patients with carotid atherosclerosis exhibited higher concentration of CD62P+/CD61+ and PAC-1+/CD61+ MVs compared to patients without the atherosclerosis. Positive associations between total number of pMVs, AnV+ MVs and AnV+/CD61+ MVs and atherosclerotic thickening of carotid intima-media in stroke patients were found. Elevated concentration of AnV+/CD61+, PAC-1+/CD61+, CD61P+/CD61+ and CD31+/CD61+ MVs, were revealed in stroke patients who suffered from recurrent VE in one-year follow-up period. Negative correlation of pMVs and CD62P+/CD61+ MVs concentration as well as percentage of total CD61+ in AnV+ population of MVs and time elapsed from IS in convalescent stroke subjects was revealed.
CONCLUSION: Our results confirm positive correlations between total pMV number, the number of PAC-1+/CD61+ and CD62+/CD61+ MVs and carotid atherosclerosis in stroke subjects. Some pMV parameters may exhibit a predictive value for the next VE in groups with a history of stroke. pMVs and some of their phenotypes decline over time elapsed from stroke in convalescent stroke subjects.

PMID: 30763823 [PubMed - as supplied by publisher]

Endothelial Cell-Derived Extracellular Vesicles Mitigate Radiation- Induced Hematopoietic Injury.

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Endothelial Cell-Derived Extracellular Vesicles Mitigate Radiation- Induced Hematopoietic Injury.

Int J Radiat Oncol Biol Phys. 2019 Feb 11;:

Authors: Piryani SO, Jiao Y, Kam AYF, Liu Y, Vo-Dinh T, Chen BJ, Chao NJ, Doan PL

Abstract
PURPOSE: Extracellular vesicles (EVs) are shed vesicles that bear a combination of nucleic acids and proteins. EVs are becoming recognized as a mode of cell-to-cell communication. Since hematopoietic stem cells (HSCs) reside in proximity to endothelial cells (ECs), we investigated whether EC-derived EVs could regulate HSC regeneration following ionizing radiation.
METHODS AND MATERIALS: We generated EVs derived from primary murine marrow ECs. We sought to determine the response of irradiated hematopoietic stem and progenitor cells to syngeneic or allogeneic EVs in culture assays. Starting 24 hours following either sub-lethal or lethal irradiation, mice were treated with EVs or saline or cultured, primary marrow endothelial cells to determine the hematopoietic response in vivo.
RESULTS: We demonstrate that EVs bear nuclear material and express EC-specific markers. Treatment with EVs promoted cell expansion and increased colony forming units compared to irradiated, hematopoietic cell cultures treated with cytokines alone. Following total body irradiation, EV- treated mice displayed preserved marrow cellularity, marrow vessel integrity, and prolonged overall survival compared to controls treated with saline. Treatment of irradiated HSPCs with EVs from different genetic strains showed similar results to treatment of HSPCs from syngeneic EVs. Mechanistically, treatment of irradiated HSPCs with EVs resulted in decreased levels of annexin V+ apoptotic cell death, which is mediated in part by tissue inhibitor of metalloproteinase-1.
CONCLUSIONS: Our findings show that syngeneic or allogeneic EVs could be cell-derived therapy to deliver physiologic doses of nucleic acids and growth factors to hematopoietic cells in order to accelerate hematopoietic regeneration.

PMID: 30763662 [PubMed - as supplied by publisher]

Correlative light and electron microscopy is a powerful tool to study interactions of extracellular vesicles with recipient cells.

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Correlative light and electron microscopy is a powerful tool to study interactions of extracellular vesicles with recipient cells.

Exp Cell Res. 2019 Feb 11;:

Authors: Arasu UT, Härkönen K, Koistinen A, Rilla K

Abstract
Extracellular vesicles (EVs) and their interactions with recipient cells constitute a rapidly growing research area. However, due to the limitations in current methodologies, the mechanisms of these interactions are still unclear. Microscopic studies of EVs are challenging, because their typical diameter is near the resolution limit of light microscopy, and electron microscopy has restricted possibilities for protein labelling. The objective of this study was to combine these two techniques to demonstrate in detail the interactions of EVs by recipient cells. Hyaluronan synthase 3 (HAS3) is an integral transmembrane protein that is enriched in EVs. In this work, GFP-HAS3 was utilized to study the interactions of EVs with the recipient cells. Surprisingly, confocal analysis correlation with scanning electron microscopy (SEM) revealed that most of the EVs were indeed lying on the recipient cell's plasma membrane, while the level of EV-derived intracellular signal was low. Immunoelectron microscopy supported this finding. Furthermore, hyaluronan oligosaccharides decreased the numbers of bound EVs, suggesting that CD44 participates in the regulation of their binding. This study indicates that correlative light and electron microscopy is a reliable method to analyze EV interactions with recipient cells. Detailed 3D confocal imaging of EV carrying a GFP-label on their plasma membrane combined with high-resolution electron microscopy provides significantly more information than either of the techniques alone. In the future studies it is crucial to utilize these techniques and their combinations to solve in detail the ambiguous fate of EV in target cells. Furthermore, live cell imaging at high resolution will be required to obtain definite answers on the detailed mechanisms of binding, fusion and endocytosis of EVs.

PMID: 30763584 [PubMed - as supplied by publisher]

Analysis of Pseudomonas aeruginosa biofilm membrane vesicles supports multiple mechanisms of biogenesis.

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Analysis of Pseudomonas aeruginosa biofilm membrane vesicles supports multiple mechanisms of biogenesis.

PLoS One. 2019;14(2):e0212275

Authors: Cooke AC, Nello AV, Ernst RK, Schertzer JW

Abstract
Outer Membrane Vesicles (OMVs) are ubiquitous in bacterial environments and enable interactions within and between species. OMVs are observed in lab-grown and environmental biofilms, but our understanding of their function comes primarily from planktonic studies. Planktonic OMVs assist in toxin delivery, cell-cell communication, horizontal gene transfer, small RNA trafficking, and immune system evasion. Previous studies reported differences in size and proteomic cargo between planktonic and agar plate biofilm OMVs, suggesting possible differences in function between OMV types. In Pseudomonas aeruginosa interstitial biofilms, extracellular vesicles were reported to arise through cell lysis, in contrast to planktonic OMV biogenesis that involves the Pseudomonas Quinolone Signal (PQS) without appreciable autolysis. Differences in biogenesis mechanism could provide a rationale for observed differences in OMV characteristics between systems. Using nanoparticle tracking, we found that P. aeruginosa PAO1 planktonic and biofilm OMVs had similar characteristics. However, P. aeruginosa PA14 OMVs were smaller, with planktonic OMVs also being smaller than their biofilm counterparts. Large differences in Staphylococcus killing ability were measured between OMVs from different strains, and a smaller within-strain difference was recorded between PA14 planktonic and biofilm OMVs. Across all conditions, the predatory ability of OMVs negatively correlated with their size. To address biogenesis mechanism, we analyzed vesicles from wild type and pqsA mutant biofilms. This showed that PQS is required for physiological-scale production of biofilm OMVs, and time-course analysis confirmed that PQS production precedes OMV production as it does in planktonic cultures. However, a small sub-population of vesicles was detected in pqsA mutant biofilms whose size distribution more resembled sonicated cell debris than wild type OMVs. These results support the idea that, while a small and unique population of vesicles in P. aeruginosa biofilms may result from cell lysis, the PQS-induced mechanism is required to generate the majority of OMVs produced by wild type communities.

PMID: 30763382 [PubMed - in process]

Differential miRNA Loading Underpins Dual Harmful and Protective Roles for Extracellular Vesicles in Atherogenesis.

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Differential miRNA Loading Underpins Dual Harmful and Protective Roles for Extracellular Vesicles in Atherogenesis.

Circ Res. 2019 Feb 15;124(4):467-469

Authors: Blaser MC, Aikawa E

PMID: 30763209 [PubMed - in process]

Microparticle-induced vascular injury in mice following decompression is inhibited by hyperbaric oxygen: Effects on microparticles and interleukin-1β.

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Microparticle-induced vascular injury in mice following decompression is inhibited by hyperbaric oxygen: Effects on microparticles and interleukin-1β.

J Appl Physiol (1985). 2019 Feb 14;:

Authors: Thom SR, Bhopale VM, Yang M

Abstract
Hyperbaric oxygen (HBO2) became a mainstay for treating decompression sickness (DCS) because bubbles are associated with the disorder. Inflammatory processes including production of circulating microparticles (MPs) have now been shown to occur with DCS, leading to questions regarding pathophysiology and the role for HBO2. We investigated effects of HBO2 on mice exposed to 790 kPa air pressure for 2 hours, which triggers elevations of MPs ladened with interleukin (IL)-1β that cause diffuse vascular injuries. Exposure to 283 kPa O2 (HBO2) inhibited MPs elevations at 2 hours post-decompression by 50% when applied either prophylactically or as treatment after decompression; and MPs number remained suppressed for 13 hours in the prophylactic group. Particle content of IL-1β at 2 hours post-decompression was 139.3 + 16.2 (mean + SE, n=11, p<0.05) pg/million MPs, versus 8.2 + 1.0 (n=15) in control mice; whereas it was 31.5 + 6.1 (n=6, not significant vs control [NS]) in mice exposed to HBO2 prophylactically, and 16.6 + 6.3 (n=7, NS) when HBO2 was administered post-decompression. IL-1β content in MPs was similar in HBO2-exposed mice at 13 hours post decompression. HBO2 also inhibited decompression-associated neutrophil activation and diffuse vascular leak. Immunoprecipitation studies demonstrated that HBO2 inhibits high pressure-mediated neutrophil NLRP3 inflammasome oligomerization. Further, MPs isolated from decompressed mice cause vascular injuries when injected into naïve mice, but if decompressed mice were exposed to HBO2 before MPs harvest, vascular injuries are inhibited. We conclude that HBO2 impedes high pressure/decompression- mediated inflammatory events by inhibiting inflammasome formation and IL-1β production.

PMID: 30763157 [PubMed - as supplied by publisher]

Size-dependent sub-proteome analysis of urinary exosomes.

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Size-dependent sub-proteome analysis of urinary exosomes.

Anal Bioanal Chem. 2019 Feb 14;:

Authors: Guan S, Yu H, Yan G, Gao M, Sun W, Zhang X

Abstract
Exosomes are cell-derived functional microparticles which exist in most body fluids. They carry abundant signaling molecules to transfer information between cells and microenvironment. Research on exosomes' heterogeneity and constitute variations has been a heated topic in recent years. In this work, size-dependent sub-proteome analysis of urinary exosomes was investigated by size exclusion chromatography (SEC) firstly. The particle size of urinary exosomes is distributed in four main ranges naturally. We found out that these fractions contained sub-proteomes with great difference in constitution. In each fraction, 206, 134, 157, and 276 unique proteins were identified by LC-MS/MS. Differential expression of exosomal markers such as TSG101, CD9, CD63, and caveolin-1 was observed in these fractions by western blots. Biological function annotation indicated that the proteins identified in each fraction were involved in different molecular and cellular processes. It is proven that SEC can serve as an efficient analytical tool for exosomes isolation and fractionation. This work provides a new strategy to classify exosomes into sub-populations for comprehensive study of heterogeneous functionalities. Graphical abstract ᅟ.

PMID: 30762101 [PubMed - as supplied by publisher]

Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders.

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Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders.

Nano Lett. 2019 Feb 14;:

Authors: Perets N, Betzer O, Shapira R, Brenstein S, Angel A, Sadan T, Ashery U, Popovtzer R, Offen D

Abstract
Exosomes, nano-vesicles that are secreted by different cell types, enable intercellular communication at local or distant sites. Though they have been found to cross the blood brain barrier, their migration and homing abilities within the brain remain unstudied. We have recently developed a method for longitudinal and quantitative in vivo neuroimaging of exosomes, based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with gold nanoparticles as labeling agents. Here, we used this technique to track the migration and homing patterns of intranasally administrated exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) in different brain pathologies, including stroke, autism, Parkinson's disease and Alzheimer's disease. We found that MSC-exo specifically targeted and accumulated in pathologically-relevant murine models brains regions up to 96 hrs post administration, while in healthy controls they showed a diffuse migration pattern and clearance by 24 hrs. The neuro-inflammatory signal in pathological brains was highly correlated with MSC-exo accumulation, suggesting that the homing mechanism is inflammatory-driven. In addition, MSC-exo were selectively uptaken by neuronal cells, but not glial cells, in the pathological regions. Taken together, these findings can significantly promote the application of exosomes for therapy and targeted drug delivery in various brain pathologies.

PMID: 30761901 [PubMed - as supplied by publisher]

Clinical applications of microenvironment-controlled immunosuppressive properties of mesenchymal stem cells-derived exosomes: a review.

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Clinical applications of microenvironment-controlled immunosuppressive properties of mesenchymal stem cells-derived exosomes: a review.

J Biol Regul Homeost Agents. 2018 Jul-Aug;32(4 Suppl. 1):15-20

Authors: 4° JOINT MEETING OF PATHOLOGY AND LABORATORY MEDICINE SIPMET–SIPMEL - SECOND JOINT MEETING IN COLLABORATION WITH ASIP–AMP–UEMS–WASPALM - 4° SIPMEL NATIONAL CONGRESS - 34° SIPMET NATIONAL CONGRESS - 4° CONGRESS OF PATHOLOGY AND LABORATORY MEDICINE, Domenis R, Cifù A, Fabris M, Curcio F

PMID: 30761862 [PubMed - in process]

[Diagnostic and prognostic significance of urinary microvesicles].

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[Diagnostic and prognostic significance of urinary microvesicles].

Urologiia. 2018 Oct;(4):170-171

Authors: Baksheeva EG, Tsybikov NN

Abstract
In recent years, researchers have become increasingly interested in urinary microvesicles. They contain disease-specific biomarkers and can be used for predicting and diagnosing various diseases of the urinary system without resorting to invasive procedures. This review presents data on domestic and international research investigating the importance and potential application of urinary microvesicles for the diagnosis and prediction of diseases of the urinary system.

PMID: 30761809 [PubMed - in process]

Mesenchymal Stem Cell Therapy for Osteoarthritis: The Critical Role of the Cell Secretome.

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Mesenchymal Stem Cell Therapy for Osteoarthritis: The Critical Role of the Cell Secretome.

Front Bioeng Biotechnol. 2019;7:9

Authors: Mancuso P, Raman S, Glynn A, Barry F, Murphy JM

Abstract
Osteoarthritis (OA) is an inflammatory condition still lacking effective treatments. Mesenchymal stem/stromal cells (MSCs) have been successfully employed in pre-clinical models aiming to resurface the degenerated cartilage. In early-phase clinical trials, intra-articular (IA) administration of MSCs leads to pain reduction and cartilage protection or healing. However, the consistent lack of engraftment indicates that the observed effect is delivered through a "hit-and-run" mechanism, by a temporal release of paracrine molecules. MSCs express a variety of chemokines and cytokines that aid in repair of degraded tissue, restoration of normal tissue metabolism and, most importantly, counteracting inflammation. Secretion of therapeutic factors is increased upon licensing by inflammatory signals or apoptosis, induced by the host immune system. Trophic effectors are released as soluble molecules or carried by extracellular vesicles (ECVs). This review provides an overview of the functions and mechanisms of MSC-secreted molecules found to be upregulated in models of OA, whether using in vitro or in vivo models.

PMID: 30761298 [PubMed]

Cytokine Targeting by miRNAs in Autoimmune Diseases.

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Cytokine Targeting by miRNAs in Autoimmune Diseases.

Front Immunol. 2019;10:15

Authors: Salvi V, Gianello V, Tiberio L, Sozzani S, Bosisio D

Abstract
Persistent and excessive cytokine production is a hallmark of autoimmune diseases and may play a role in disease pathogenesis and amplification. Therefore, cytokine neutralization is a useful therapeutic strategy to treat immune-mediated conditions. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in diverse biological processes. Altered miRNA levels are observed in most autoimmune diseases and are recognized to influence autoimmunity through different mechanisms. Here, we review the impact of altered miRNA levels on the expression of cytokines that play a relevant pathogenic role in autoimmunity, namely primary pro-inflammatory cytokines, the IL-17/IL-23 axis, type I interferons and IL-10. Regulation can be either "direct" on the target cytokine, or "indirect," meaning that one given miRNA post-transcriptionally regulates the expression of a protein that in turn influences the level of the cytokine. In addition, miRNAs associated with extracellular vesicles can regulate cytokine production in neighboring cells, either post-transcriptionally or via the stimulation of innate immune RNA-sensors, such as Toll-like receptors. Because of their tremendous potential as physiological and pathological regulators, miRNAs are in the limelight as promising future biopharmaceuticals. Thus, these studies may lead in the near future to the design and testing of therapeutic miRNAs as next generation drugs to target pathogenic cytokines in autoimmunity.

PMID: 30761124 [PubMed - in process]

Regulation of myelination by exosome associated retinoic acid release from NG2-positive cells.

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Regulation of myelination by exosome associated retinoic acid release from NG2-positive cells.

J Neurosci. 2019 Feb 13;:

Authors: Goncalves MB, Wu Y, Clarke E, Grist J, Hobbs C, Trigo D, Jack J, Corcoran JPT

Abstract
In the central nervous system, oligodendrocytes are responsible for myelin formation and maintenance. Following spinal cord injury, oligodendrocyte loss and an inhibitory milieu compromise remyelination and recovery. Here we explored the role of retinoic acid receptor (RAR) β signalling in remyelination. Using a male Sprague-Dawley rat model of PNS-CNS injury, we show that oral treatment with an RARβ agonist induces neuronal expression of the proteoglycan decorin and promotes myelination and differentiation of oligodendrocyte precursor cells (NG2+cells) in a decorin mediated neuron-glia crosstalk. Decorin promoted the activation of RARα in NG2+cells, by increasing the availability of the endogenous ligand retinoic acid (RA). NG2+cells synthesise RA which is released in association with exosomes. We found that decorin prevents this secretion through regulation of the EGFR-calcium pathway. Using functional and pharmacological studies we further show that RARα signalling is both required and sufficient for oligodendrocyte differentiation. These findings illustrate that RARβ and RARα are important regulators of oligodendrocyte differentiation, providing new targets for myelination.SIGNIFICANCE STATEMENTThis study identifies novel therapeutic targets for remyelination after PNS-CNS injury. Pharmacological and knock down experiments show that the retinoic acid (RA) signalling promotes differentiation of oligodendrocyte precursor cells (OPCs) and remyelination in a cross-talk between neuronal Retinoic acid receptor (RAR)β and RARα in NG2+cells. We show that stimulation of RARα is required for the differentiation of OPCs and we describe for the first time how oral treatment with a RARβ agonist leads to the endogenous synthesis of RA through retinaldehyde dehydrogenase 2 (Raldh2) in NG2 cells and controls exosome-associated-RA intracellular levels through a decorin-Ca2+ pathway. Although RARβ has been implicated in distinct aspects of CNS regeneration, this study identifies a novel function for both RARβ and RARα in remyelination.

PMID: 30760627 [PubMed - as supplied by publisher]

Brain insulin resistance and altered brain glucose are related to memory impairments in schizophrenia.

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Brain insulin resistance and altered brain glucose are related to memory impairments in schizophrenia.

Schizophr Res. 2019 Feb 11;:

Authors: Wijtenburg SA, Kapogiannis D, Korenic SA, Mullins RJ, Tran J, Gaston FE, Chen S, Mustapic M, Hong LE, Rowland LM

Abstract
Memory is robustly impaired in schizophrenia (SZ) and related to functional outcome. Memory dysfunction has been shown to be related to altered brain glucose metabolism and brain insulin resistance in animal models and human studies of Alzheimer's disease. In this study, differences in brain glucose using magnetic resonance spectroscopy (MRS) and blood Extracellular Vesicle (EV) biomarkers of neuronal insulin resistance (i.e. Akt and signaling effectors) between SZ and controls were investigated, as well as whether these measures were related to memory impairments. Neuronal insulin resistance biomarkers showed a trend for being lower in SZ compared to controls, and memory measures were lower in SZ compared to controls. Occipital cortex glucose was higher in SZ compared to controls indicating lower brain glucose utilization. Linear regression analyses revealed significant relationships between neuronal insulin resistance biomarkers, memory measures, and brain glucose. More specifically, p70S6K, an insulin signaling effector, was related to verbal learning and brain MRS glucose in the SZ group. For the first time, we show that memory impairments in SZ may be related to brain glucose and brain insulin resistance. These data suggest that brain insulin resistance may play a role in the pathophysiology of learning and memory dysfunction in SZ.

PMID: 30760413 [PubMed - as supplied by publisher]

Follicular fluid exosomes act on the bovine oocyte to improve oocyte competence to support development and survival to heat shock.

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Follicular fluid exosomes act on the bovine oocyte to improve oocyte competence to support development and survival to heat shock.

Reprod Fertil Dev. 2019 Feb 14;:

Authors: Rodrigues TA, Tuna KM, Alli AA, Tribulo P, Hansen PJ, Koh J, Paula-Lopes FF

Abstract
Addition of follicular fluid to oocyte maturation medium can affect cumulus cell function, increase competence of the oocytes to be fertilised and develop to the blastocyst stage and protect the oocyte from heat shock. Here, it was tested whether exosomes in follicular fluid are responsible for the effects of follicular fluid on the function of the cumulus-oocyte complex (COC). This was accomplished by culturing COCs during oocyte maturation at 38.5°C (body temperature of the cow) or 41°C (heat shock) with follicular fluid or exosomes derived from follicular fluid and evaluating various aspects of function of the oocyte and the embryo derived from it. Negative effects of heat shock on cleavage and blastocyst development, but not cumulus expansion, were reduced by follicular fluid and exosomes. The results support the idea that exosomes in follicular fluid play important roles during oocyte maturation to enhance oocyte function and protect it from stress.

PMID: 30760387 [PubMed - as supplied by publisher]

Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury.

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Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury.

Crit Care. 2019 Feb 13;23(1):44

Authors: Zhou Y, Li P, Goodwin AJ, Cook JA, Halushka PV, Chang E, Zingarelli B, Fan H

Abstract
BACKGROUND: The acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar-capillary barrier resulting in accumulation of proteinaceous edema and increased inflammatory cells in the alveolar space. We previously found that endothelial progenitor cell (EPC) exosomes prevent endothelial dysfunction and lung injury in sepsis in part due to their encapsulation of miRNA-126. However, the effects of EPC exosomes in acute lung injury (ALI) remain unknown.
METHODS: To determine if EPC exosomes would have beneficial effects in ALI, intratracheal administration of lipopolysaccharide (LPS) was used to induce ALI in mice. Lung permeability, inflammation, and the role of miRNA-126 in the alveolar-epithelial barrier function were examined.
RESULTS: The intratracheal administration of EPC exosomes reduced lung injury following LPS-induced ALI at 24 and 48 h. Compared to placebo, intratracheal administration of EPC exosomes significantly reduced the cell number, protein concentration, and cytokines/chemokines in the bronchoalveolar lavage fluid (BALF), indicating a reduction in permeability and inflammation. Further, EPC exosomes reduced myeloperoxidase (MPO) activity, lung injury score, and pulmonary edema, demonstrating protection against lung injury. Murine fibroblast (NIH3T3) exosomes, which do not contain abundant miRNA-126, did not provide these beneficial effects. In human small airway epithelial cells (SAECs), we found that overexpression of miRNA-126-3p can target phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), while overexpression of miRNA-126-5p inhibits the inflammatory alarmin HMGB1 and permeability factor VEGFα. Interestingly, both miR-126-3p and 5p increase the expression of tight junction proteins suggesting a potential mechanism by which miRNA-126 may mitigate LPS-induced lung injury.
CONCLUSIONS: Our data demonstrated that human EPC exosomes are beneficial in LPS-induced ALI mice, in part through the delivery of miRNA-126 into the injured alveolus.

PMID: 30760290 [PubMed - in process]

Exosomes: A Promising Avenue for the Diagnosis of Breast Cancer.

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Exosomes: A Promising Avenue for the Diagnosis of Breast Cancer.

Technol Cancer Res Treat. 2019 Jan 01;18:1533033818821421

Authors: Meng Y, Sun J, Wang X, Hu T, Ma Y, Kong C, Piao H, Yu T, Zhang G

Abstract
Currently, despite the advances in individualized treatment, breast cancer still remains the deadliest form of cancer in women. Diagnostic, prognostic, and therapy-predictive methods are mainly based on the evaluation of tumor tissue samples and are aimed to improve the overall therapeutic level. Therefore, the exploration of a series of circulating biomarkers, which serve as the information source of tumors and could be obtained by peripheral blood samples, represents a high field of interest. Apart from classical biomarkers, exosomes, which are nanovesicles, are emerging as an accessible and efficient source of cell information. The purpose of this review is to summarize the peculiarities of the presently available breast cancer exosomal biomarkers; the review also provides the prediction of a multitude of potential target genes of exosomal microRNAs using 4 databases.

PMID: 30760122 [PubMed - in process]

Circulating Endothelial Cells, Circulating Endothelial Progenitor Cells, and Circulating Microparticles in Type 1 Diabetes Mellitus.

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Circulating Endothelial Cells, Circulating Endothelial Progenitor Cells, and Circulating Microparticles in Type 1 Diabetes Mellitus.

Clin Appl Thromb Hemost. 2019 Jan-Dec;25:1076029618825311

Authors: Zahran AM, Mohamed IL, El Asheer OM, Tamer DM, Abo-ELela MGM, Abdel-Rahim MH, El-Badawy OHB, Elsayh KI

Abstract
BACKGROUND AND AIM:: Hyperglycemia in type 1 diabetes (T1D) is accompanied by endothelial cell dysfunction which is known to contribute to the pathogenesis of cardiovascular disorders. The aim of the current study was to explore the profile of circulating endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), endothelial and platelet derived micropaticles (EMPs, PMPs) and total microparticles (TMPs), in T1D children in relation to each other and to the metabolic disorders accompanying T1D.
PATIENTS AND METHODS:: Thirty T1D patients and 20 age and sex matched healthy volunteers were assessed for HbA1c level and lipid profile. Quantification of CECs, EPCs, TMPs, EMPs and PMPs was done by flow cytometry.
RESULTS:: The mean levels of EMPs, PMPs, TMPs and CECs were significantly higher in diabetic children compared to controls. Meanwhile, the levels of EPCs were significantly lower in diabetic children compared to controls. Both PMPs and CECs showed the highest significant differences between patients and controls and their levels were directly related to HbA1c, total cholesterol, LDL and triglycerides. A moderate correlation was observed between the frequency of PMPs and CECs. EPCs revealed negative correlations with both LDL and triglycerides. TMPs were only related to LDL, while EMPs were only related to HbA1c.
CONCLUSION:: Although there is disturbance in the levels of EMPs, PMPs, TMPs, CECs and EPCs in type 1 diabetic children compared to the controls, only the levels of PMPs and CECs were closely affected by the poor glycemic control and dyslipidemia occurring in T1D; thus may contribute to a higher risk of cardiovascular diseases.

PMID: 30760002 [PubMed - in process]

Role of Exosomes in the Regulation of T-cell Mediated Immune Responses and in Autoimmune Disease.

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Role of Exosomes in the Regulation of T-cell Mediated Immune Responses and in Autoimmune Disease.

Cells. 2019 Feb 12;8(2):

Authors: Anel A, Gallego-Lleyda A, de Miguel D, Naval J, Martínez-Lostao L

Abstract
: T-cell mediated immune responses should be regulated to avoid the development of autoimmune or chronic inflammatory diseases. Several mechanisms have been described to regulate this process, namely death of overactivated T cells by cytokine deprivation, suppression by T regulatory cells (Treg), induction of expression of immune checkpoint molecules such as CTLA-4 and PD-1, or activation-induced cell death (AICD). In addition, activated T cells release membrane microvesicles called exosomes during these regulatory processes. In this review, we revise the role of exosome secretion in the different pathways of immune regulation described to date and its importance in the prevention or development of autoimmune disease. The expression of membrane-bound death ligands on the surface of exosomes during AICD or the more recently described transfer of miRNA or even DNA inside T-cell exosomes is a molecular mechanism that will be analyzed.

PMID: 30759880 [PubMed]

Functionalized Porous Silica-Based Nano/Micro Particles for Environmental Remediation of Hazard Ions.

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Functionalized Porous Silica-Based Nano/Micro Particles for Environmental Remediation of Hazard Ions.

Nanomaterials (Basel). 2019 Feb 12;9(2):

Authors: Li CM, Wang XP, Jiao ZH, Zhang YS, Yin XB, Cui XM, Wei YZ

Abstract
The adsorption and separation of hazard metal ions, radioactive nuclides, or minor actinides from wastewater and high-level radioactive waste liquids using functional silica-based nano/micro-particles modified with various inorganic materials or organic groups, has attracted significant attention since the discovery of ordered mesoporous silica-based substrates. Focusing on inorganic and organic modified materials, the synthesis methods and sorption performances for specific ions in aqueous solutions are summarized in this review. Three modification methods for silica-based particles, the direct synthesis method, wetness impregnation method, and layer-by-layer (LBL) deposition, are usually adopted to load inorganic material onto silica-based particles, while the wetness impregnation method is currently used for the preparation of functional silica-based particles modified with organic groups. Generally, the specific synthesis method is employed based on the properties of the loading materials and the silicon-based substrate. Adsorption of specific toxic ions onto modified silica-based particles depends on the properties of the loaded material. The silicon matrix only changes the thermodynamic and mechanical properties of the material, such as the abrasive resistance, dispersibility, and radiation resistance. In this paper, inorganic loads, such as metal phosphates, molybdophosphate, titanate-based materials, and hydrotalcite, in addition to organic loads, such as 1,3-[(2,4-diethylheptylethoxy)oxy]-2,4-crown-6-Calix{4}arene (Calix {4}) arene-R14 and functional 2,6-bis-(5,6-dialkyl-1,2,4-triazin-3-yl)-pyridines(BTP) are reviewed. More specifically, we emphasize on the synthesis methods of such materials, their structures in relation to their capacities, their selectivities for trapping specific ions from either single or multi-component aqueous solutions, and the possible retention mechanisms. Potential candidates for remediation uses are selected based on their sorption capacities and distribution coefficients for target cations and the pH window for an optimum cation capture.

PMID: 30759816 [PubMed]

 

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