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Aug 23, 2016

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EV literature (RSS feed from PubMed)

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

VESICLES BEARING GIFTS: THE FUNCTIONAL IMPORTANCE OF MICRO-RNA TRANSFER IN EXTRACELLULAR VESICLES IN CHRONIC KIDNEY DISEASE.

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VESICLES BEARING GIFTS: THE FUNCTIONAL IMPORTANCE OF MICRO-RNA TRANSFER IN EXTRACELLULAR VESICLES IN CHRONIC KIDNEY DISEASE.

Am J Physiol Renal Physiol. 2018 Aug 15;:

Authors: Abbasian N, Herbert K, Pawluczyk I, Burton J, Bevington A

Abstract
Extracellular vesicles (EVs), including microparticles (MPs) and exosomes (EXOs), are derived from a wide range of mammalian cells including blood platelets, endothelial cells, and kidney cells and can be detected in body fluids including blood and urine. While EVs are well established as diagnostic markers under pathophysiological and stress conditions, there is also mounting evidence of their functional significance as vehicles for communication between cells mediated by the presence of nucleic acids, especially microRNAs (miRs), encapsulated in the EVs. miRs regulate gene expression, are transported both in MPs and EXOs, and exert profound effects in the kidney. Here we review current understanding of the links between EVs and miRs, discuss the importance of miRs in kidney disease, and shed light on the role of EVs in transferring miRs through the circulation between the renal, vascular and inflammatory cell populations that are functionally important in patients with CKD.

PMID: 30110570 [PubMed - as supplied by publisher]

Extracellular vesicles from human liver stem cells inhibit tumor angiogenesis.

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Extracellular vesicles from human liver stem cells inhibit tumor angiogenesis.

Int J Cancer. 2018 Aug 15;:

Authors: Lopatina T, Grange C, Fonsato V, Tapparo M, Brossa A, Fallo S, Pitino A, Herrera-Sanchez MB, Kholia S, Camussi G, Bussolati B

Abstract
Human liver stem-like cells (HLSC) and derived extracellular vesicles (EVs) were previously shown to exhibit anti-tumor activity. In the present study, we investigated whether HLSC-derived EVs (HLSC-EVs) were able to inhibit tumor angiogenesis in vitro and in vivo, in comparison with EVs derived from mesenchymal stem cells (MSC-EVs). The results obtained indicated that HLSC-EVs, but not MSC-EVs, inhibited the angiogenic properties of tumor-derived endothelial cells (TEC) both in vitro and in vivo in a model of subcutaneous implantation in Matrigel. Treatment of TEC with HLSC-EVs led to the down-regulation of pro-angiogenic genes. Since HLSC-EVs carry a specific set of microRNAs (miRNAs) that could target these genes, we investigated their potential role by transfecting TEC with HLSC-EV specific miRNAs. We observed that four miRNAs, namely miR-15a, miR-181b, miR-320c, and miR-874, significantly inhibited the angiogenic properties of TEC in vitro, and decreased the expression of some predicted target genes (ITGB3, FGF1, EPHB4, and PLAU). In parallel, TEC treated with HLSC-EVs significantly enhanced expression of miR-15a, miR-181b, miR-320c, and miR-874 associated with the down-regulation of FGF1 and PLAU. In summary, HLSC-EVs possess an anti-tumorigenic effect, based on their ability to inhibit tumor angiogenesis. This article is protected by copyright. All rights reserved.

PMID: 30110127 [PubMed - as supplied by publisher]

Nanoscale Functionalized Particles with Rotation-Controlled Capture in Shear Flow.

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Nanoscale Functionalized Particles with Rotation-Controlled Capture in Shear Flow.

ACS Appl Mater Interfaces. 2018 Aug 15;:

Authors: Shave MK, Kalasin S, Ying E, Santore MM

Abstract
Important processes in nature and technology involve the adhesive capture of flowing particles or cells on the walls of a conduit. This paper introduces engineered spherical microparticles whose capture rates are limited by their near surface motions in flow. Specifically, these microparticles are sparsely functionalized with nanoscopic regions ("patches") of adhesive functionality, without which they would be nonadhesive. Not only is particle capture on the wall of a shear-chamber limited by surface chemistry as opposed to transport, but also the capture rates depend specifically on particle rotations that result from the vorticity of the shear flow field. These particle rotations continually expose new particle surface to the opposing chamber wall, sampling the particle surface for an adhesive region and controlling the capture rate. Control studies with the same patchy functionality on the chamber wall rather than the particles reveal a related signature of particle capture but substantially faster (still surface limited) particle capture rates. Thus, when the same functionality is placed on the wall rather than the particles, the capture is faster because it depends on the particle translation past a functionalized wall rather than on the particle rotations. The dependence of particle capture on functionalization of the particles versus the wall is consistent with the faster near-wall particle translation in shearing flow compared with the velocity of the rotating particle surface near the wall. These findings, in addition to providing a new class of nanoscopically patchy engineered particles, provide insight into the capture and detection of cells presenting sparse distinguishing surface features and the design of delivery packages for highly targeted pharmaceutical delivery.

PMID: 30109808 [PubMed - as supplied by publisher]

Highly efficient antibody purification with controlled orientation of protein A on magnetic nanoparticles.

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Highly efficient antibody purification with controlled orientation of protein A on magnetic nanoparticles.

Medchemcomm. 2018 Jan 01;9(1):108-112

Authors: Kim S, Sung D, Chang JH

Abstract
In this study, we prepared protein A grafted magnetic nanoparticles for the industrial large-scale purification of antibodies with enhancement of binding capacity and immobilization by controlled orientation with chlorophenylsilane (CPTMS) on the surface. For site-specific immobilization of protein A, genetically modified protein A with a cysteine residue was expressed in E. coli and purified by affinity chromatography. To improve the surface area to volume ratio and increase the immobilization amount of protein A, chlorophenylsilane functionalized magnetic nanoparticles (CPTMS@MNPs) were prepared, which are smaller nanoparticles with an average diameter of 20 nm compared to commercial magnetic microparticles (Dynabeads) with an average size of 2.8 μm. The CPTMS@MNPs showed the enhancement of protein A immobilization and binding capacity to antibodies, being 11.5-fold and 7-fold higher than those of commercial Dynabeads, respectively. In addition, the CPTMS@MNPs retained about 80% of the initial protein binding capacity until the third stage of recycling. Therefore, protein A grafted CPTMS@MNPs may be useful for the industrial large-scale purification of antibodies.

PMID: 30108904 [PubMed]

Encapsulation of nor-β-lapachone into poly(d,l)-lactide-co-glycolide (PLGA) microcapsules: full characterization, computational details and cytotoxic activity against human cancer cell lines.

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Encapsulation of nor-β-lapachone into poly(d,l)-lactide-co-glycolide (PLGA) microcapsules: full characterization, computational details and cytotoxic activity against human cancer cell lines.

Medchemcomm. 2017 Oct 01;8(10):1993-2002

Authors: Costa MP, Feitosa ACS, Oliveira FCE, Cavalcanti BC, Dias GG, Caetano EWS, Sales FAM, Freire VN, Di Fiore S, Fischer R, Ladeira LO, da Silva Júnior EN, Pessoa C

Abstract
In this work, we characterize nor-β-lapachone-loaded (NβL-loaded) microcapsules prepared using an emulsification/solvent extraction technique. Features such as surface morphology, particle size distribution, zeta potential, optical absorption, Raman and Fourier transform infrared spectra, thermal analysis data, drug encapsulation efficiency, drug release kinetics and in vitro cytotoxicity were studied. Spherical microcapsules with a size of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Quantum DFT calculations were also performed to estimate typical interaction energies between a single nor-β-lapachone molecule and the surface of the microparticles. The NβL-loaded PLGA microcapsules exhibited a pronounced initial burst release. After the in vitro treatment with NβL-loaded microcapsules, a clear phagocytosis of the spheres was observed in a few minutes. The cytotoxic activity against a set of cancer cell lines was investigated.

PMID: 30108718 [PubMed]

Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma.

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Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma.

J Extracell Vesicles. 2018;7(1):1505403

Authors: Vagner T, Spinelli C, Minciacchi VR, Balaj L, Zandian M, Conley A, Zijlstra A, Freeman MR, Demichelis F, De S, Posadas EM, Tanaka H, Di Vizio D

Abstract
Cancer-derived extracellular vesicles (EVs) are membrane-enclosed structures of highly variable size. EVs contain a myriad of substances (proteins, lipid, RNA, DNA) that provide a reservoir of circulating molecules, thus offering a good source of biomarkers. We demonstrate here that large EVs (L-EV) (large oncosomes) isolated from prostate cancer (PCa) cells and patient plasma are an EV population that is enriched in chromosomal DNA, including large fragments up to 2 million base pair long. While L-EVs and small EVs (S-EV) (exosomes) isolated from the same cells contained similar amounts of protein, the DNA was more abundant in L-EV, despite S-EVs being more numerous. Consistent with in vitro observations, the abundance of DNA in L-EV obtained from PCa patient plasma was variable but frequently high. Conversely, negligible amounts of DNA were present in the S-EVs from the same patients. Controlled experimental conditions, with spike-ins of L-EVs and S-EVs from cancer cells in human plasma from healthy subjects, showed that circulating DNA is almost exclusively enclosed in L-EVs. Whole genome sequencing revealed that the DNA in L-EVs reflects genetic aberrations of the cell of origin, including copy number variations of genes frequently altered in metastatic PCa (i.e. MYC, AKT1, PTK2, KLF10 and PTEN). These results demonstrate that L-EV-derived DNA reflects the genomic make-up of the tumour of origin. They also support the conclusion that L-EVs are the fraction of plasma EVs with DNA content that should be interrogated for tumour-derived genomic alterations.

PMID: 30108686 [PubMed]

Exosomes derived from cancerous and non-cancerous cells regulate the anti-tumor response in the tumor microenvironment.

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Exosomes derived from cancerous and non-cancerous cells regulate the anti-tumor response in the tumor microenvironment.

Genes Cancer. 2018 Mar;9(3-4):87-100

Authors: Bae S, Brumbaugh J, Bonavida B

Abstract
The tumor microenvironment (TME) is a unique platform of cancer biology that considers the local cellular environment in which a tumor exists. Increasing evidence points to the TME as crucial for either promoting immune tumor rejection or protecting the tumor. The TME includes surrounding blood vessels, the extracellular matrix (ECM), a variety of immune and regulatory cells, and signaling factors. Exosomes have emerged to be molecular contributors in cancer biology, and to modulate and affect the constituents of the TME. Exosomes are small (40-150 nm) membrane vesicles that are derived from an endocytic nature and are later excreted by cells. Depending on the cells from which they originate, exosomes can play a role in tumor suppression or tumor progression. Tumor-derived exosomes (TDEs) have their own unique phenotypic functions. Evidence points to TDEs as key players involved in tumor growth, tumorigenesis, angiogenesis, dysregulation of immune cells and immune escape, metastasis, and resistance to therapies, as well as in promoting anti-tumor response. General exosomes, TDEs, and their influence on the TME are an area of promising research that may provide potential biomarkers for therapy, potentiation of anti-tumor response, development of exosome-based vaccines, and exosome-derived nanocarriers for drugs.

PMID: 30108680 [PubMed]

New role of hypoxia in pathophysiology of multiple myeloma through miR-210.

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New role of hypoxia in pathophysiology of multiple myeloma through miR-210.

EXCLI J. 2018;17:647-662

Authors: Saba F, Soleimani M, Abroun S

Abstract
Bone is one of the most common sites of complication in multiple myeloma (MM) progression and bone remodeling gets definitively perturbed during disease progression. Hypoxia and miR-210 play an important role in hematological malignancies. In an attempt to elucidate the specificity of the pathways of hypoxia and miR-210 in suppression of osteoblastic differentiation in MM patients, we examined the effect of miR-210 and hypoxia on expression of important cytokines and genes of myeloma cells. Differentiation of BM-MSCs towards osteoblastic cells in response to microvesicles (MVs) was also investigated. Finally, we proposed a molecular model on how HIF-1α may promote bone lesions in MM patients. To validate the effect of miR-210 and HIF-1α on targeted genes, the shRNA of HIF-1α and off-hsa-miR-210 were transfected into RPMI-8226 cells. BM-MSCs were cultured in osteoblastic inducer and 50 µg/mL of MVs derived from both hypoxic and normoxic myeloma cells. We designed an in vitro study to establish the effects of HIF-1α and miR-210 on the crosstalk between MM and osteoblasts. We here showed that hypoxia-induced miR-210 increased the mRNA expression of VLA-4, CXCR4, IL-6 and TGF-β in myeloma cells. MiR-210 is mandatory for the hypoxia-increased resistance of MM cells to melphalan. Moreover, MVs derived from hypoxic myeloma cells substantially decreased osteoblast differentiation. Considered comprehensively, our findings explain one of the reasons of bone loss that occurs at the sites of MM and a nascent crosstalk model in MM pathogenesis.

PMID: 30108468 [PubMed]

HMGB1+ platelet microparticles damage the endothelium.

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HMGB1+ platelet microparticles damage the endothelium.

Nat Rev Rheumatol. 2018 Aug 14;:

Authors: Bernard NJ

PMID: 30108366 [PubMed - as supplied by publisher]

In vitro performances of novel co-spray-dried azithromycin/rifampicin microparticles for Rhodococcus equi disease treatment.

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In vitro performances of novel co-spray-dried azithromycin/rifampicin microparticles for Rhodococcus equi disease treatment.

Sci Rep. 2018 Aug 14;8(1):12149

Authors: Rampacci E, Marenzoni ML, Chiaradia E, Passamonti F, Ricci M, Pepe M, Coletti M, Giovagnoli S

Abstract
This work was aimed at providing clues on the in vitro performances of novel azithromycin/rifampicin combinations, in the form of co-spray-dried microparticles (AZM/RIF MP), against Rhodococcus equi, an animal and emerging human pathogen found responsible for worrying zoonosis. Various AZM/RIF combinations were spray-dried and characterized for their morphology and size. Susceptibility studies included determination of MIC, MBC, Fractional Inhibitory/Bactericidal Concentration Indexes and intracellular activity in R. equi-infected THP-1 cells. Cytotoxicity was tested on BEAS-2B cells through MTT assay and combination index assessment for drug interaction. Spray-dried MP were collapsed and 3-10 times smaller than commercial powders. Drug combinations showed an enhancement of in vitro antibacterial activity with a remarkable synergistic bactericidal effect. Azithromycin MP and AZM/RIF MP 2:1 led to a CFU reduction of >90% up to 4 days after treatment at all tested concentrations (p = 0.001) but AZM/RIF MP 2:1 were at least four-fold more potent than AZM MP alone. IC50 values of >100 mg/L supported low cytotoxicity of drug combinations and the combination index suggested an antagonistic toxic effect. Co-spray-drying enhanced powder dispersibility and solubility, which may improve bioavailability as well as provide administration alternatives. The novel AZM/RIF MP combinations could result a valid platform to develop new treatment strategies against R. equi infections in animals and humans.

PMID: 30108265 [PubMed - in process]

Urinary exosome miR-146a is a potential marker of albuminuria in essential hypertension.

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Urinary exosome miR-146a is a potential marker of albuminuria in essential hypertension.

J Transl Med. 2018 Aug 14;16(1):228

Authors: Perez-Hernandez J, Olivares D, Forner MJ, Ortega A, Solaz E, Martinez F, Chaves FJ, Redon J, Cortes R

Abstract
BACKGROUND: There is increasing interest in using extracellular vesicle-derived microRNAs (miRNAs) as biomarkers in renal dysfunction and injury. Preliminary evidence indicates that miRNAs regulate the progression of glomerular disease. Indeed, exosomes from the renal system have provided novel evidence in the clinical setting of albuminuria. Thus, the aim of this study was to quantify the urinary miRNAs present in exosome and microvesicles (MVs), and to assess their association with the presence of increased urinary albumin excretion in essential hypertension.
METHODS: Exosomes were collected from urine specimens from a cohort of hypertensive patients with (n = 24) or without albuminuria (n = 28), and from 20 healthy volunteers as a control group. Urinary exosomes were phenotyped by Western blot, tunable resistive pulse sensing, and electronic microscopy. Expression of miR-146a and miR-335* was analysed by qRT-PCR and any associations between albuminuria and exosomal miRNAs were analysed.
RESULTS: Urinary miRNAs are highly enriched in exosome subpopulations compared to MVs, both in patients with or without increased albuminuria (p < 0.001), but not in the control group. High albuminuria was associated with 2.5-fold less miR-146a in exosomes (p = 0.017), whereas miR-146a levels in MV did not change. In addition, exosome miR-146a levels were inversely associated with albuminuria (r = 0.65, p < 0.0001), and discriminated the presence of urinary albumin excretion presence [area under the curve = 0.80, 95% confidence interval: 0.66-0.95; p = 0.0013].
CONCLUSIONS: Our results indicate that miRNAs were enriched in the urinary exosome subpopulation in hypertensive patients and that low miR-146a expression in exosomes was associated with the presence of albuminuria. Thus, urinary exosome miR-146a may be a potentially useful tool for studying early renal injury in hypertension.

PMID: 30107841 [PubMed - in process]

Development of a Sampling Collection Device with Diagnostic Procedures.

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Development of a Sampling Collection Device with Diagnostic Procedures.

Anal Chem. 2016 08 02;88(15):7591-6

Authors: Cheng JY, Feng MJ, Wu CC, Wang J, Chang TC, Cheng CM

Abstract
Cervicovaginal fluid plays an important role in the detection of many female genital diseases, but the lack of suitable collection devices in the market severely challenges test success rate. Appropriate clinical sampling devices for cervicovaginal fluid collection would help physicians detect diseases and disease states more rapidly, efficiently, and accurately. The objective of this study was to develop a readily usable sampling collection device that would eliminate macromolecular interference and accurately provide specimens for further studies. This study was designed to develop an effective device to collect cervicovaginal fluid from women with symptoms of endometrial lesions, women appearing in the clinic for a routine Papanicolaou smear, and/or women seeking a routine gynecologic checkup. Paper-based assay, ELISA, and qNano were used to provide accurate diagnoses. A total of 103 patients successfully used the developed device to collect cervicovaginal fluid. Some of the collected specimens were used to detect glycogen, lactate, and pH for determining pathogen infection. Other specimen samples were tested for the presence of female genital cancer by comparing interleukin 6 concentration and microvesicle concentration. We proposed a noninvasive screening test for the diagnosis of female genital diseases using a dual-material collection device. The outer, nonwoven fabric portion of this device was designed to filter macromolecules, and the inner cotton portion was designed to absorb cervicovaginal fluid.

PMID: 27338148 [PubMed - indexed for MEDLINE]

 

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