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

No Postage Required: Extracellular Vesicles Deliver the Message.

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No Postage Required: Extracellular Vesicles Deliver the Message.

Am J Physiol Cell Physiol. 2019 Apr 17;:

Authors: Isenberg JS, Adams JC

PMID: 30995107 [PubMed - as supplied by publisher]

Mapping aldehydic load in vivo by positron emission tomography with [18F]NA3BF3.

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Mapping aldehydic load in vivo by positron emission tomography with [18F]NA3BF3.

Chem Commun (Camb). 2019 Apr 17;:

Authors: Kirby A, Suchý M, Brouwer A, Shuhendler A

Abstract
A new radiotracer, [18F]NA3BF3, capable of rapid, stable, and catalyst-free complexation of aldehydes in vivo is reported. [18F]NA3BF3 was shown to bind aldehydes in live subjects using locally administered aldehyde-presenting microparticles, and was then applied to mapping aldehydic load in a mouse model of sepsis. [18F]NA3BF3 may enable the direct investigation of the chemical biology of aldehydes in living subjects, and may open avenues for the adoption of endogenous aldehydic load as an imaging biomarker of inflammatory pathology.

PMID: 30994648 [PubMed - as supplied by publisher]

Controlled Release of Therapeutic Agents with NIR Laser for Synergistic Photo-Chemotherapy towards Cervical Cancer.

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Controlled Release of Therapeutic Agents with NIR Laser for Synergistic Photo-Chemotherapy towards Cervical Cancer.

Anal Chem. 2019 Apr 17;:

Authors: Zhu L, Wang C, Pang DW, Zhang ZL

Abstract
Different kinds of artificial drug delivery systems (DDS) have been widely exploited and utilized towards effective tumor therapy. Establishing a biocompatible DDS with a flexible release of the therapeutic agents has been one of the challenges and impetus to the development of tumor diagnosis and therapy fields. Herein, the chemotherapeutic agents doxorubicin hydrochloride (DOX) and photosensitizer indocyanine green (ICG) were simultaneously packaged into the cavity of Microvesicles (MVs) through electroporation technique. With the aid of MVs based DDS, the packaged therapeutic agents could be effectively delivered into the target tumor cells. The ambient temperature sharply increased owe to the controllable external NIR laser irradiation, which induced the crack of MVs based DDS, directly accompanied with the dynamic and controllable release of DOX and ICG. Almost all the tumor cells could be killed by the synergistic effect of the released DOX and ICG. This research successfully established a smart DDS with NIR laser inducing controllable release of therapeutic agents for effectively synergistic photo-chemotherapy towards cervical cancer.

PMID: 30994332 [PubMed - as supplied by publisher]

Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma.

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Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma.

Angiogenesis. 2019 Apr 15;:

Authors: Wu XG, Zhou CF, Zhang YM, Yan RM, Wei WF, Chen XJ, Yi HY, Liang LJ, Fan LS, Liang L, Wu S, Wang W

Abstract
AIMS: Recently, cancer-derived exosomes were shown to have pro-metastasis function in cancer, but the mechanism remains unclear. Angiogenesis is essential for tumor progression and is a great promising therapeutic target for advanced cervical cancer. Here, we investigated the role of cervical cancer cell-secreted exosomal miR-221-3p in tumor angiogenesis.
METHODS AND RESULTS: miR-221-3p was found to be closely correlated with microvascular density in cervical squamous cell carcinoma (CSCC) by evaluating the microvascular density with immunohistochemistry and miR-221-3p expression with in situ hybridization in clinical specimens. Using the groups of CSCC cell lines (SiHa and C33A) with miR-221-3p overexpression and silencing, the CSCC exosomes were characterized by electron microscopy, western blotting, and fluorescence microscopy. The enrichment of miR-221-3p in CSCC exosomes and its transfer into human umbilical vein endothelial cells (HUVECs) were confirmed by qRT-PCR. CSCC exosomal miR-221-3p promoted angiogenesis in vitro in Matrigel tube formation assay, spheroid sprouting assay, migration assay, and wound healing assay. Then, exosome intratumoral injection indicated that CSCC exosomal miR-221-3p promoted tumor growth in vivo. Thrombospondin-2 (THBS2) was bioinformatically predicted to be a direct target of miR-221-3p, and this was verified by using the in vitro and in vivo experiments described above. Additionally, overexpression of THBS2 in HUVECs rescued the angiogenic function of miR-221-3p.
CONCLUSIONS: Our results suggest that CSCC exosomes transport miR-221-3p from cancer cells to vessel endothelial cells and promote angiogenesis by downregulating THBS2. Therefore, CSCC-derived exosomal miR-221-3p could be a possible novel diagnostic biomarker and therapeutic target for CSCC progression.

PMID: 30993566 [PubMed - as supplied by publisher]

Exosome mediated differentiation of megakaryocytes: a study on TLR mediated effects.

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Exosome mediated differentiation of megakaryocytes: a study on TLR mediated effects.

J Thromb Thrombolysis. 2019 Apr 16;:

Authors: Kovuru N, Raghuwanshi S, Gutti RK

Abstract
Megakaryocytes are large polyploid bone marrow cells whose function is to produce circulatory platelets. Megakaryocytes are also known to release extracellular vesicles (EVs) of varying sizes. Toll like receptors (TLRs), present on the sentinel cells are essential components of the innate immune response, these receptors are also expressed by platelets and megakaryocytes. Our data provide the evidence that TLR-2 induced MKEVs are able to recapitulate TLR-2 signalling in megakaryocytic cell line (Dami cells) and that likely induces megakaryocytic maturation by increasing the production of cytokines involved in MK maturation. TLR-2 induced MKEVs may be involved in replenishment of the immune effector platelets in circulation and its progenitor megakaryocyte in bone marrow for the physiological need of the platelets by inducing the maturation of megakaryocyte.

PMID: 30993517 [PubMed - as supplied by publisher]

Saturated fatty acid stimulates production of extracellular vesicles by renal tubular epithelial cells.

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Saturated fatty acid stimulates production of extracellular vesicles by renal tubular epithelial cells.

Mol Cell Biochem. 2019 Apr 16;:

Authors: Cobbs A, Chen X, Zhang Y, George J, Huang MB, Bond V, Thompson W, Zhao X

Abstract
Lipotoxicity, an accumulation of intracellular lipid metabolites, has been proposed as an important pathogenic mechanism contributing to kidney dysfunction in the context of metabolic disease. Palmitic acid, a predominant lipid derivative, can cause lipoapoptosis and the release of inflammatory extracellular vesicles (EVs) in hepatocytes, but the effect of lipids on EV production in chronic kidney disease remains vaguely explored. This study was aimed to investigate whether palmitic acid would stimulate EV release from renal proximal tubular epithelial cells. Human and rat proximal tubular epithelial cells, HK-2 and NRK-52E, were incubated with 1% bovine serum albumin (BSA), BSA-conjugated palmitic acid (PA), and BSA-conjugated oleic acid (OA) for 24-48 h. The EVs released into conditioned media were isolated by ultracentrifugation and quantified by nanoparticle-tracking analysis (NTA). According to NTA, the size distribution of EVs was 30-150 nm with similar mode sizes in all experimental groups. Moreover, BSA-induced EV release was significantly enhanced in the presence of PA, whereas EV release was not altered by the addition of OA. In NRK-52E cells, PA-enhanced EV release was associated with an induction of cell apoptosis reflected by an increase in cleaved caspase-3 protein by Western blot and Annexin V positive cells analyzed by flow cytometry. Additionally, confocal microscopy confirmed the uptake of lipid-induced EVs by recipient renal proximal tubular cells. Collectively, our results indicate that PA stimulates EV release from cultured proximal tubular epithelial cells. Thus, extended characterization of lipid-induced EVs may constitute new signaling paradigms contributing to chronic kidney disease pathology.

PMID: 30993495 [PubMed - as supplied by publisher]

Exosome-Like Vesicles as New Mediators and Therapeutic Targets for Treating Insulin Resistance and β-Cell Mass Failure in Type 2 Diabetes Mellitus.

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Exosome-Like Vesicles as New Mediators and Therapeutic Targets for Treating Insulin Resistance and β-Cell Mass Failure in Type 2 Diabetes Mellitus.

J Diabetes Res. 2019;2019:3256060

Authors: Ge Q, Xie XX, Xiao X, Li X

Abstract
Exosome-like vesicles (ELVs), the smallest class of extracellular vesicles released from cells, function in cellular crosstalk and therefore profoundly affect physiologic responses and pathologic progression. A growing body of evidence supports a novel role for ELVs as important mediators and therapeutic targets due to their effects on regulation of both insulin signaling and β-cell mass. Pathologic conditions associated with type 2 diabetes (such as high blood glucose, inflammation, hypoxia, and fatty acids) can alter the quantity and components of ELVs secreted from the pancreas or peripheral insulin-targeting tissues. These released ELVs can either enter the blood circulation or be taken up by neighboring cells or macrophages, which can lead to insulin resistance or β-cell apoptosis. This review focuses on the roles of ELVs in insulin resistance and β-cell failure and also highlights the potential use of ELVs and exosome-based delivery systems in therapeutic interventions aimed at treating type 2 diabetes mellitus as well as the challenges associated with exosome-targeting therapeutics.

PMID: 30993115 [PubMed - in process]

Sirt6-induced autophagy restricted TREM-1-mediated pyroptosis in ox-LDL-treated endothelial cells: relevance to prognostication of patients with acute myocardial infarction.

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Sirt6-induced autophagy restricted TREM-1-mediated pyroptosis in ox-LDL-treated endothelial cells: relevance to prognostication of patients with acute myocardial infarction.

Cell Death Discov. 2019;5:88

Authors: Zi Y, Yi-An Y, Bing J, Yan L, Jing T, Chun-Yu G, Fan P, Hao L, Jia-Ni T, Han-Jin H, Fei C, Xue-Bo L

Abstract
Inflammation mediated by myeloid cells trigger receptors 1 (TREM-1) is important for atherosclerosis development, while sirtuin 6 (Sirt6) levels decrease in atheroscleoritc plaque. Here we demonstrate that oxidatively modified low density lipoprotein (ox-LDL)-treated endothelial cells (ECs) exhibited increased TREM-1-mediated pyroptosis and decreased Sirt6-induced autophagy. We show that high sTREM-1 and low sSirt6 levels were independent predictors of boosted endothelial microparticles (EMPs) on admission, and were associated with increased risk for all-cause mortality and major adverse cardiovascular events (MACE) at median 24 months (interquartile range, 18-26) follow-up in acute myocardial infarction (AMI) patients. Additionally, blockage of Sirt6-induced autophagy led to augmented TREM-1-mediated pyroptosis, whereas Sirt6 overexpression attenuated ECs inflammation and pyroptosis following ox-LDL treatment. Our findings indicate that TREM-1 and in a reversed trend Sirt6 appeared to be markers of endothelial inflammation with potential for use in risk stratification.

PMID: 30993014 [PubMed]

Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm.

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Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm.

Biomark Res. 2019;7:8

Authors: Yin K, Wang S, Zhao RC

Abstract
Mesenchymal stem/stromal cells (MSCs) have been demonstrated to hold great potential for the treatment of several diseases. Their therapeutic effects are largely mediated by paracrine factors including exosomes, which are nanometer-sized membrane-bound vesicles with functions as mediators of cell-cell communication. MSC-derived exosomes contain cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. Increasing evidence suggests that MSC-derived exosomes might represent a novel cell-free therapy with compelling advantages over parent MSCs such as no risk of tumor formation and lower immunogenicity. This paper reviews the characteristics of MSC exosomes and their fate after in vivo administration, and highlights the therapeutic potential of MSC-derived exosomes in liver, kidney, cardiovascular and neurological disease. Particularly, we summarize the recent clinical trials performed to evaluate the safety and efficacy of MSC exosomes. Overall, this paper provides a general overview of MSC-exosomes as a new cell-free therapeutic paradigm.

PMID: 30992990 [PubMed]

circRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/ IGF-1R axis.

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circRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/ IGF-1R axis.

Clin Sci (Lond). 2019 Apr 16;:

Authors: Tian L, Cao J, Jiao H, Zhang J, Ren X, Liu X, Liu M, Sun Y

Abstract
BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with Laryngeal squamous cell carcinoma (LSCC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for LSCC from the aspect of circRNA-miRNA-mRNA interaction.
METHODS: We investigated the expression of circRNAs in 3 paired LSCC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between LSCC tissues and non-cancerous matched tissues, including 527 up-regulated circRNAs 414 down-regulated circRNAs. We focused on hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2.
RESULTS: circRASSF2 was found to be significantly upregulated in LSCC tissues and LSCC cell lines compared with paired adjacent non-tumorous tissues and normal cells. Moreover, knockdown of circRASSF2 significantly inhibited cell proliferation and migration in vitro , which was blocked by miR-302b-3p inhibitor. Bioinformatics analysis predicted that there is a circRASSF2/miR-302b-3p/IGF-1R axis in LSCC progression. Dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-302b-3p, and IGF-1R. Western blot verified that inhibition of circRASSF2 decreased IGF-1R expression. Furthermore, silencing circRASSF2 suppressed LSCC growth in vivo Importantly, we demonstrated that circRASSF2 was upregulated in serum exosomes from LSCC patients. Altogether, silencing circRASSF2 suppresses progression of LSCC by interacting with miR-302b-3p and decreasing inhibiting IGF-1R expression.
CONCLUSION: In conclusion, these data suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via a miR-302b-3p / IGF-1R axis.

PMID: 30992382 [PubMed - as supplied by publisher]

Exosomal transfer of long non-coding RNA SBF2-AS1 enhances chemoresistance to temozolomide in glioblastoma.

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Exosomal transfer of long non-coding RNA SBF2-AS1 enhances chemoresistance to temozolomide in glioblastoma.

J Exp Clin Cancer Res. 2019 Apr 16;38(1):166

Authors: Zhang Z, Yin J, Lu C, Wei Y, Zeng A, You Y

Abstract
BACKGROUND: Acquired drug resistance is a constraining factor in clinical treatment of glioblastoma (GBM). However, the mechanisms of chemoresponsive tumors acquire therapeutic resistance remain poorly understood. Here, we aim to investigate whether temozolomide (TMZ) resistance of chemoresponsive GBM was enhanced by long non-coding RNA SBF2 antisense RNA 1 (lncRNA SBF2-AS1) enriched exosomes.
METHOD: LncSBF2-AS1 level in TMZ-resistance or TMZ-sensitive GBM tissues and cells were analyzed by qRT-PCR and FISH assays. A series of in vitro assay and xenograft tumor models were performed to observe the effect of lncSBF2-AS1 on TMZ-resistance in GBM. CHIP assay were used to investigate the correlation of SBF2-AS1 and transcription factor zinc finger E-box binding homeobox 1 (ZEB1). Dual-luciferase reporter, RNA immunoprecipitation (RIP), immunofluorescence and western blotting were performed to verify the relation between lncSBF2-AS1, miR-151a-3p and XRCC4. Comet assay and immunoblotting were performed to expound the effect of lncSBF2-AS1 on DNA double-stand break (DSB) repair. A series of in vitro assay and intracranial xenografts tumor model were used to determined the function of exosomal lncSBF2-AS1.
RESULT: It was found that SBF2-AS1 was upregulated in TMZ-resistant GBM cells and tissues, and overexpression of SBF2-AS1 led to the promotion of TMZ resistance, whereas its inhibition sensitized resistant GBM cells to TMZ. Transcription factor ZEB1 was found to directly bind to the SBF2-AS1 promoter region to regulate SBF2-AS1 level and affected TMZ resistance in GBM cells. SBF2-AS1 functions as a ceRNA for miR-151a-3p, leading to the disinhibition of its endogenous target, X-ray repair cross complementing 4 (XRCC4), which enhances DSB repair in GBM cells. Exosomes selected from temozolomide-resistant GBM cells had high levels of SBF2-AS1 and spread TMZ resistance to chemoresponsive GBM cells. Clinically, high levels of lncSBF2-AS1 in serum exosomes were associated with poor response to TMZ treatment in GBM patients.
CONCLUSION: We can conclude that GBM cells remodel the tumor microenvironment to promote tumor chemotherapy-resistance by secreting the oncogenic lncSBF2-AS1-enriched exosomes. Thus, exosomal lncSBF2-AS1 in human serum may serve as a possible diagnostic marker for therapy-refractory GBM.

PMID: 30992025 [PubMed - in process]

Extracellular Vesicles as Biological Shuttles for Targeted Therapies.

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Extracellular Vesicles as Biological Shuttles for Targeted Therapies.

Int J Mol Sci. 2019 Apr 15;20(8):

Authors: Raimondo S, Giavaresi G, Lorico A, Alessandro R

Abstract
The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)-specialized membrane-bound nanocarriers for intercellular communication-suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.

PMID: 30991632 [PubMed - in process]

Extracellular microvesicle microRNAs as predictive biomarkers for targeted therapy in metastastic cutaneous malignant melanoma.

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Extracellular microvesicle microRNAs as predictive biomarkers for targeted therapy in metastastic cutaneous malignant melanoma.

PLoS One. 2018;13(11):e0206942

Authors: Svedman FC, Lohcharoenkal W, Bottai M, Brage SE, Sonkoly E, Hansson J, Pivarcsi A, Eriksson H

Abstract
BACKGROUND: Mitogen activated-protein kinase pathway inhibitors (MAPKis) improve treatment outcome in patients with disseminated BRAFV600 mutant cutaneous malignant melanoma (CMM) but responses are of limited duration due to emerging resistance. Although extensive research in mechanisms of resistance is being performed, predictive biomarkers for durable responses are still lacking. We used miRNA qPCR to investigate if different levels of extracellular microvesicle microRNA (EV miRNA) in matched plasma samples collected from patients with metastatic IV BRAFV600 mutated CMM before, during and after therapy with MAPKis could serve as predictive biomarkers.
MATERIALS AND METHODS: EV miRNAs were extracted from plasma samples from 28 patients collected before and during therapy, measured by quantitative PCR-array and correlated to therapy outcome.
RESULTS: Increased levels of EV let-7g-5p during treatment compared to before treatment (EV let-7g-5p_delta) were associated with better disease control with MAPKis (odds ratio 8568.4, 95% CI = 4.8-1.5e+07, P = 0.000036). Elevated levels of EV miR-497-5p during therapy were associated with prolonged progression free survival (PFS) (hazard ratio = 0.27, 95% CI = 0.13-0.52, P <0.000061).
CONCLUSIONS: EV miRNAs let-7g-5p and miR-497-5p were identified as putative novel predictive biomarkers of MAPKi treatment benefit in metastatic CMM patients highlighting the potential relevance of assessing EV miRNA during and after treatment to unravel novel mechanisms of resistance.

PMID: 30399176 [PubMed - indexed for MEDLINE]

Cancer cells deliver a suppressive cargo.

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Cancer cells deliver a suppressive cargo.

Nat Immunol. 2018 03;19(3):207-208

Authors: Takaoka A

PMID: 29476187 [PubMed - indexed for MEDLINE]

 

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