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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.

The Aging Process Alters IL-1β and CD63 Levels Differently in Extracellular Vesicles Obtained from the Plasma and Cerebrospinal Fluid.

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The Aging Process Alters IL-1β and CD63 Levels Differently in Extracellular Vesicles Obtained from the Plasma and Cerebrospinal Fluid.

Neuroimmunomodulation. 2018 Jul 18;:1-5

Authors: Gomes de Andrade G, Reck Cechinel L, Bertoldi K, Galvão F, Valdeci Worm P, Rodrigues Siqueira I

Abstract
OBJECTIVE(S): The aim of this study was to investigate exosomal markers and inflammatory cargo of extracellular vesicles (EVs) obtained from cerebrospinal fluid (CSF) and plasma in the aging process. We also studied the inflammatory cargo by quantifying IL-1β levels.
METHODS: Male Wistar rats, aged 3 and 21 months, were used (n = 12 in each group). The CSF and plasma of animals were collected, and isolation of EVs was performed using a commercial kit. Total protein concentration, acetylcholinesterase (AChE) activity, and CD63 and IL-1β levels were evaluated.
RESULTS: AChE activity in EVs increased in both samples, specifically in the circulating EVs and those in the CSF of the older group. An age-related increase was observed in CD63 levels in EVs from the CSF but a decrease was observed in plasma EVs of the older group. Student's t test showed that the young adult rats had significantly higher circulating IL-1β levels in the EVs compared to the aged ones, without any effect on central content.
CONCLUSION: Our data suggest that the normal aging process causes different changes in the profiles of central and circulating EVs. Altered IL-1β levels in circulating EVs can be linked, at least partly, to age-related inflammatory conditions, and a disruption of the CFS exosomes in aged rats, evaluated by CD63 levels, can be related to susceptibility to neurodegenerative disorders.

PMID: 30021215 [PubMed - as supplied by publisher]

ALIX Regulates Tumor-Mediated Immunosuppression by Controlling EGFR Activity and PD-L1 Presentation.

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ALIX Regulates Tumor-Mediated Immunosuppression by Controlling EGFR Activity and PD-L1 Presentation.

Cell Rep. 2018 Jul 17;24(3):630-641

Authors: Monypenny J, Milewicz H, Flores-Borja F, Weitsman G, Cheung A, Chowdhury R, Burgoyne T, Arulappu A, Lawler K, Barber PR, Vicencio JM, Keppler M, Wulaningsih W, Davidson SM, Fraternali F, Woodman N, Turmaine M, Gillett C, Franz D, Quezada SA, Futter CE, Von Kriegsheim A, Kolch W, Vojnovic B, Carlton JG, Ng T

Abstract
The immunosuppressive transmembrane protein PD-L1 was shown to traffic via the multivesicular body (MVB) and to be released on exosomes. A high-content siRNA screen identified the endosomal sorting complexes required for transport (ESCRT)-associated protein ALIX as a regulator of both EGFR activity and PD-L1 surface presentation in basal-like breast cancer (BLBC) cells. ALIX depletion results in prolonged and enhanced stimulation-induced EGFR activity as well as defective PD-L1 trafficking through the MVB, reduced exosomal secretion, and its redistribution to the cell surface. Increased surface PD-L1 expression confers an EGFR-dependent immunosuppressive phenotype on ALIX-depleted cells. An inverse association between ALIX and PD-L1 expression was observed in human breast cancer tissues, while an immunocompetent mouse model of breast cancer revealed that ALIX-deficient tumors are larger and show an increased immunosuppressive environment. Our data suggest that ALIX modulates immunosuppression through regulation of PD-L1 and EGFR and may, therefore, present a diagnostic and therapeutic target for BLBC.

PMID: 30021161 [PubMed - in process]

Antimargination of Microparticles and Platelets in the Vicinity of Branching Vessels.

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Antimargination of Microparticles and Platelets in the Vicinity of Branching Vessels.

Biophys J. 2018 Jul 17;115(2):411-425

Authors: Bächer C, Kihm A, Schrack L, Kaestner L, Laschke MW, Wagner C, Gekle S

Abstract
We investigate the margination of microparticles/platelets in blood flow through complex geometries typical for in vivo vessel networks: a vessel confluence and a bifurcation. Using three-dimensional lattice Boltzmann simulations, we confirm that behind the confluence of two vessels, a cell-free layer devoid of red blood cells develops in the channel center. Despite its small size of roughly 1 μm, this central cell-free layer persists for up to 100 μm after the confluence. Most importantly, we show from simulations that this layer also contains a significant amount of microparticles/platelets and validate this result by in vivo microscopy in mouse venules. At bifurcations, however, a similar effect does not appear, and margination is largely unaffected by the geometry. This antimargination toward the vessel center after a confluence may explain earlier in vivo observations, which found that platelet concentrations near the vessel wall are seen to be much higher on the arteriolar side (containing bifurcations) than on the venular side (containing confluences) of the vascular system.

PMID: 30021115 [PubMed - in process]

Tough Reversible Adhesion Properties of a Dry Self-cleaning Biomimetic Surface.

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Tough Reversible Adhesion Properties of a Dry Self-cleaning Biomimetic Surface.

ACS Appl Mater Interfaces. 2018 Jul 18;:

Authors: Li M, Xu Q, Wu X, Li W, Lan W, Heng L, Street J, Xia Z

Abstract
Geckos have one of the world's most efficient reversible adhesion systems. Even walking in dusty conditions, geckos can dislodge up to 80% of contaminants and recover their adhesion capability after walking as few as 4 steps. Thus far, artificial dry self-cleaning materials inspired by the gecko's hierarchical fibrillar structure have been only able to remove 55% of collected large particle contaminants with 30 steps. Challenges including low mechanical strength, low stiffness, and short fatigue time keep these materials from being used in practical applications. This study involves the novel fabrication of dry self-cleaning surfaces with a high mechanical performance and an outstanding dry self-cleaning property. Imposing a load-drag-pull process similar to a gecko's foot adhesion process, our biomimetic surfaces could dislodge up to 59% of microparticles (~8 μm) with as few as 5 steps. Furthermore, the surface had an excellent screening ability at low temperatures regardless of the surface roughness similarity. The surfaces were also proven to be scratch-resistant. The biomimetic surfaces exhibit the enhanced dry self-cleaning and mechanical properties, and could be promising in the applications such as reusable adhesives, biochips, aerospace satellite waste collection, and screening equipment.

PMID: 30020766 [PubMed - as supplied by publisher]

Sensitive detection of exosomal proteins via a compact surface plasmon resonance biosensor for cancer diagnosis.

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Sensitive detection of exosomal proteins via a compact surface plasmon resonance biosensor for cancer diagnosis.

ACS Sens. 2018 Jul 18;:

Authors: Liu C, Zeng X, An Z, Yang Y, Eisenbaum M, Gu X, Jornet JM, Dy GK, Reid M, Gan Q, Wu Y

Abstract
Exosomes are small extracellular vesicles released by cells for cell-cell communication. They play important roles in cancer development, metastasis and drug resistance. Exosomal proteins have been demonstrated by many studies as promising biomarkers for cancer screening, diagnosis and monitoring. Among many detection techniques, surface plasmon resonance (SPR) is a highly sensitive, label-free and real-time optical detection method. Commercial prism-based wavelength/angular-modulated SPR sensors afford high sensitivity and resolution, but their large footprint and high cost limit their adaptability for clinical settings. Recently a nanoplasmonic exosome (nPLEX) assay was developed to detect exosomal proteins for ovarian cancer diagnosis. However, comparing with conventional SPR biosensors, the broad applications of nanoplasmonic biosensors are limited by the difficult and expensive fabrication of nanostructures. We have developed an intensity-modulated, compact SPR biosensor (25 cm × 10 cm × 25 cm) which uses conventional SPR sensing mechanism and does not require nanostructure fabrication. Calibration from glycerol showed that the compact SPR biosensor offered sensitivity of 9.258×103%/RIU and resolution of 8.311×10-6 RIU. We have demonstrated the feasibility of the compact SPR biosensor in lung cancer diagnosis using exosomal epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) as biomarkers. It detected higher level of exosomal EGFR from A549 nonsmall cell lung cancer (NSCLC) cells than BEAS-2B normal cells. With human serum samples, the compact SPR biosensor detected similar levels of exosomal EGFR in NSCLC patients and normal controls, and higher expression of exosomal PD-L1 in NSCLC patients than normal controls. The compact SPR biosensor showed higher detection sensitivity than ELISA and similar sensing accuracy as ELISA. It is a simple and user-friendly sensing platform, which may serve as an in vitro diagnostic test for cancer.

PMID: 30019892 [PubMed - as supplied by publisher]

Worm expulsion of Gymnophalloides seoi from C57BL/6 mice: role of metacercarial exosomes in upregulating TLR2 and MUC2 expression in intestinal tissues.

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Worm expulsion of Gymnophalloides seoi from C57BL/6 mice: role of metacercarial exosomes in upregulating TLR2 and MUC2 expression in intestinal tissues.

Parasitol Res. 2018 Jul 17;:

Authors: Song H, Jung BK, Cho J, Chai JY

Abstract
Gymnophalloides seoi worms were rapidly expelled from C57BL/6 mice within days 3-6 post-infection probably due to operation of mucosal innate immunity. To understand better the mucosal immunity related to worm expulsion from the host, we isolated exosomes of G. seoi metacercariae and investigated their role in induction of mRNA and protein expression of several Toll-like receptors and mucin-related factors in vitro. G. seoi-secreted exosomes were collected using differential ultracentrifugation, and cellular internalization of the exosomes into HT-29 intestinal epithelial cells was visualized by confocal microscopy. The expression of TLR2 and MUC2 in HT-29 cells was up-regulated in stimulation with the exosomes. We suggest that G. seoi-secreted exosomes offer a new point of view in the mechanism of worm expulsion from the host through enhancement of TLR2 and MUC2 expression.

PMID: 30019213 [PubMed - as supplied by publisher]

Extracellular Vesicles: A Novel Target for Exercise-Mediated Reductions in Type 2 Diabetes and Cardiovascular Disease Risk.

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Extracellular Vesicles: A Novel Target for Exercise-Mediated Reductions in Type 2 Diabetes and Cardiovascular Disease Risk.

J Diabetes Res. 2018;2018:7807245

Authors: Eichner NZM, Erdbrügger U, Malin SK

Abstract
Regular exercise is important for reducing type 2 diabetes (T2D) and/or cardiovascular disease (CVD) risk. However, only about 40-50% of this CVD risk reduction is accounted for by adiposity, hyperglycemia, hypertension, and dyslipidemia. Herein, we present the novel hypothesis that extracellular vesicles (EVs) are candidate biomarkers that may relate to impaired endothelial function and insulin resistance independent of obesity risk factors. EVs are small membrane-bound particles that are generated by cells following stimulation, stress, or activation. They carry markers of their parent cell and are thought to be potent bioactivators and communicators. We discuss the underlying physiology of specific cell type EVs, as well as examine how acute and chronic exercise interventions impact EV count and phenotype. We also propose that current gaps in the field are in part related to use of different detection techniques and the lack of standardized measurements of EV affecting the pre- and postanalytical phase. Ultimately, improving the understanding of how EVs impact cardiometabolic health and their function will lead to improved approaches for enhancing diagnostic options as well as designing exercise interventions that treat and/or prevent T2D and CVD.

PMID: 30018986 [PubMed - in process]

Future Perspectives on the Role of Stem Cells and Extracellular Vesicles in Vascular Tissue Regeneration.

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Future Perspectives on the Role of Stem Cells and Extracellular Vesicles in Vascular Tissue Regeneration.

Front Cardiovasc Med. 2018;5:86

Authors: Cunnane EM, Weinbaum JS, O'Brien FJ, Vorp DA

Abstract
Vascular tissue engineering is an area of regenerative medicine that attempts to create functional replacement tissue for defective segments of the vascular network. One approach to vascular tissue engineering utilizes seeding of biodegradable tubular scaffolds with stem (and/or progenitor) cells wherein the seeded cells initiate scaffold remodeling and prevent thrombosis through paracrine signaling to endogenous cells. Stem cells have received an abundance of attention in recent literature regarding the mechanism of their paracrine therapeutic effect. However, very little of this mechanistic research has been performed under the aegis of vascular tissue engineering. Therefore, the scope of this review includes the current state of TEVGs generated using the incorporation of stem cells in biodegradable scaffolds and potential cell-free directions for TEVGs based on stem cell secreted products. The current generation of stem cell-seeded vascular scaffolds are based on the premise that cells should be obtained from an autologous source. However, the reduced regenerative capacity of stem cells from certain patient groups limits the therapeutic potential of an autologous approach. This limitation prompts the need to investigate allogeneic stem cells or stem cell secreted products as therapeutic bases for TEVGs. The role of stem cell derived products, particularly extracellular vesicles (EVs), in vascular tissue engineering is exciting due to their potential use as a cell-free therapeutic base. EVs offer many benefits as a therapeutic base for functionalizing vascular scaffolds such as cell specific targeting, physiological delivery of cargo to target cells, reduced immunogenicity, and stability under physiological conditions. However, a number of points must be addressed prior to the effective translation of TEVG technologies that incorporate stem cell derived EVs such as standardizing stem cell culture conditions, EV isolation, scaffold functionalization with EVs, and establishing the therapeutic benefit of this combination treatment.

PMID: 30018970 [PubMed]

Exosome-related lncRNAs as predictors of HCC patient survival: a prognostic model.

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Exosome-related lncRNAs as predictors of HCC patient survival: a prognostic model.

Am J Transl Res. 2018;10(6):1648-1662

Authors: Hou Y, Yu Z, Tam NL, Huang S, Sun C, Wang R, Zhang X, Wang Z, Ma Y, He X, Wu L

Abstract
OBJECTIVES: Accumulating evidence suggests that long non-coding RNA (lncRNA) may affect hepatocellular carcinoma (HCC) progression. However, the mechanism remains unclear. Previous studies have shown that exosomes may promote tumor progression by transporting proteins. Our study aimed to determine the prognostic value of lncRNAs in HCC and the underlying mechanism.
METHODS: A dataset comprising a HCC cohort of 364 patients from The Cancer Genome Atlas (TCGA) was analyzed to identify lncRNAs with prognostic value. Co-expression and competing endogenous RNA (ceRNA) networks were constructed to investigate the mechanism of exosome-related lncRNAs. To confirm the bioinformatics analysis results, 95 pairs of clinical samples were evaluated by digoxigenin-labeled chromogenic in situ hybridization (CISH).
RESULTS: Five lncRNAs (CTD-2116N20.1, AC012074.2, RP11-538D16.2, LINC00501 and RP11-136I14.5) with significant differences were identified (P<0.001). A prognostic nomogram was constructed with a C-index of 0.701. The co-expression and ceRNA networks showed possible mechanisms for CTD-2116N20.1 and RP11-538D16.2. The CISH results confirmed that CTD-2116N20.1 and RP11-538D16.2 were correlated with a poor prognosis for HCC patients.
CONCLUSION: Our findings provide an independent and effective prognostic model to predict the survival rate of HCC patients. RP11-538D16.2 and CTD-2116N20.1 are highlighted as important exosome-related lncRNAs.

PMID: 30018707 [PubMed]

Therapeutic Prospects of Extracellular Vesicles in Cancer Treatment.

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Therapeutic Prospects of Extracellular Vesicles in Cancer Treatment.

Front Immunol. 2018;9:1534

Authors: Chulpanova DS, Kitaeva KV, James V, Rizvanov AA, Solovyeva VV

Abstract
Extracellular vesicles (EVs) are released by all cells within the tumor microenvironment, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune system cells. The EVs carry the cargo of parental cells formed of proteins and nucleic acids, which can convey cell-to-cell communication influencing the maintenance and spread of the malignant neoplasm, for example, promoting angiogenesis, tumor cell invasion, and immune escape. However, EVs can also suppress tumor progression, either by the direct influence of the protein and nucleic acid cargo of the EVs or via antigen presentation to immune cells as tumor-derived EVs carry on their surface some of the same antigens as the donor cells. Moreover, dendritic cell-derived EVs carry major histocompatibility complex class I and class II/peptide complexes and are able to prime other immune system cell types and activate an antitumor immune response. Given the relative longevity of vesicles within the circulation and their ability to cross blood-brain barriers, modification of these unique organelles offers the potential to create new biological-tools for cancer therapy. This review examines how modification of the EV cargo has the potential to target specific tumor mechanisms responsible for tumor formation and progression to develop new therapeutic strategies and to increase the efficacy of antitumor therapies.

PMID: 30018618 [PubMed]

Exosome-associated Shiga toxin 2 is released from cells and causes severe toxicity in mice.

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Exosome-associated Shiga toxin 2 is released from cells and causes severe toxicity in mice.

Sci Rep. 2018 Jul 17;8(1):10776

Authors: Watanabe-Takahashi M, Yamasaki S, Murata M, Kano F, Motoyama J, Yamate J, Omi J, Sato W, Ukai H, Shimasaki K, Ikegawa M, Tamura-Nakano M, Yanoshita R, Nishino Y, Miyazawa A, Natori Y, Toyama-Sorimachi N, Nishikawa K

Abstract
Shiga toxin (Stx), a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), is classified into two subgroups, Stx1 and Stx2. Clinical data clearly indicate that Stx2 is associated with more severe toxicity than Stx1, but the molecular mechanism underlying this difference is not fully understood. Here, we found that after being incorporated into target cells, Stx2, can be transported by recycling endosomes, as well as via the regular retrograde transport pathway. However, transport via recycling endosome did not occur with Stx1. We also found that Stx2 is actively released from cells in a receptor-recognizing B-subunit dependent manner. Part of the released Stx2 is associated with microvesicles, including exosome markers (referred to as exo-Stx2), whose origin is in the multivesicular bodies that formed from late/recycling endosomes. Finally, intravenous administration of exo-Stx2 to mice causes more lethality and tissue damage, especially severe renal dysfunction and tubular epithelial cell damage, compared to a free form of Stx2. Thus, the formation of exo-Stx2 might contribute to the severity of Stx2 in vivo, suggesting new therapeutic strategies against EHEC infections.

PMID: 30018364 [PubMed - in process]

Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome.

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Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome.

Sci Rep. 2018 Jul 17;8(1):10813

Authors: Sork H, Corso G, Krjutskov K, Johansson HJ, Nordin JZ, Wiklander OPB, Lee YXF, Westholm JO, Lehtiö J, Wood MJA, Mäger I, El Andaloussi S

Abstract
Extracellular vesicles (EVs) mediate cell-to-cell communication by delivering or displaying macromolecules to their recipient cells. While certain broad-spectrum EV effects reflect their protein cargo composition, others have been attributed to individual EV-loaded molecules such as specific miRNAs. In this work, we have investigated the contents of vesicular cargo using small RNA sequencing of cells and EVs from HEK293T, RD4, C2C12, Neuro2a and C17.2. The majority of RNA content in EVs (49-96%) corresponded to rRNA-, coding- and tRNA fragments, corroborating with our proteomic analysis of HEK293T and C2C12 EVs which showed an enrichment of ribosome and translation-related proteins. On the other hand, the overall proportion of vesicular small RNA was relatively low and variable (2-39%) and mostly comprised of miRNAs and sequences mapping to piRNA loci. Importantly, this is one of the few studies, which systematically links vesicular RNA and protein cargo of vesicles. Our data is particularly useful for future work in unravelling the biological mechanisms underlying vesicular RNA and protein sorting and serves as an important guide in developing EVs as carriers for RNA therapeutics.

PMID: 30018314 [PubMed - in process]

VAMP-associated protein-A and oxysterol-binding protein-related protein 3 promote the entry of late endosomes into the nucleoplasmic reticulum.

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VAMP-associated protein-A and oxysterol-binding protein-related protein 3 promote the entry of late endosomes into the nucleoplasmic reticulum.

J Biol Chem. 2018 07 17;:

Authors: Santos F, Rappa G, Karbanova J, Kurth T, Corbeil D, Lorico A

Abstract
The endocytic pathway plays an instrumental role in recycling internalized molecules back to the plasma membrane or to direct them to lysosomes for degradation. We recently reported a new role of endosomes - the delivery of components from extracellular vesicles (EVs) to the nucleoplasm of recipient cells. Using indirect immunofluorescence, fluorescence resonance energy transfer, immunoisolation techniques, and RNA interference, we report here a tripartite protein complex (referred to as the VOR complex) that is essential for the nuclear transfer of EV-derived components by orchestrating the specific localization of late endosomes into nucleoplasmic reticulum. We found that the VOR complex contains the endoplasmic reticulum-localized vesicle-associated membrane protein (VAMP)-associated protein A (VAP-A), the cytoplasmic oxysterol-binding protein-related protein 3 (ORP3), and late endosome-associated small GTPase Rab7. The silencing of VAP-A or ORP3 abrogated the association of Rab7-positive late endosomes with nuclear envelope invaginations, and, hence, the transport of endocytosed EV-derived components to the nucleoplasm of recipient cells. We conclude that the VOR complex can be targeted to inhibit EV-mediated intercellular communication, which can have therapeutic potential for managing cancer in which the release of EVs is dysregulated.

PMID: 30018135 [PubMed - as supplied by publisher]

Mechanisms by which dendritic cells present tumor microparticle antigens to CD8+ T cells.

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Mechanisms by which dendritic cells present tumor microparticle antigens to CD8+ T cells.

Cancer Immunol Res. 2018 Jul 17;:

Authors: Ma J, Wei K, Zhang H, Tang K, Li F, Zhang T, Liu J, Xu P, Yu Y, Sun W, Zhu L, Chen J, Zhou L, Liang X, Lv J, Fiskesund R, Liu Y, Huang B

Abstract
Tumor cell-derived microparticles (T-MPs) contain tumor antigen profiles as well as innate signals, endowing them with vaccine potential; however, the precise mechanism by which DCs present T-MP antigens to T cells remains unclear. Here, we show that T-MPs activate a lysosomal pathway that is required for DCs presenting tumor antigens of T-MPs. DCs endocytose T-MPs to lysosomes, where T-MPs increase lysosomal pH from 5.0 to a peak of 8.5 via NOX2-catalyzed reactive oxygen species (ROS) production. This increased pH, coupled with T-MP-driven lysosomal centripetal migration, promotes the formation of MHC class I-tumor antigen peptide complexes. Concurrently, endocytosis of T-MPs results in the upregulation of CD80 and CD86. T-MP-increased ROS activate lysosomal Ca2+ channel Mcoln2, leading to Ca2+ release. Released Ca2+ activates transcription factor EB (TFEB), a lysosomal master regulator that directly binds to CD80 and CD86 promoters, promoting gene expression. These findings elucidate a pathway through which DCs efficiently present tumor antigen from T-MPs to CD8+ T cells, potentiating T-MPs as a novel tumor cell-free vaccine with clinical applications.

PMID: 30018046 [PubMed - as supplied by publisher]

Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis.

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Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis.

Mol Ther. 2018 Jul 05;:

Authors: Casella G, Colombo F, Finardi A, Descamps H, Ill-Raga G, Spinelli A, Podini P, Bastoni M, Martino G, Muzio L, Furlan R

Abstract
Extracellular vesicles (EVs) play a major role in cell-to-cell communication in physiological and pathological conditions, and their manipulation may represent a promising therapeutic strategy. Microglia, the parenchymal mononuclear phagocytes of the brain, modulate neighboring cells also through the release of EVs. The production of custom EVs filled with desired molecules, possibly targeted to make their uptake cell specific, and their administration in biological fluids may represent a valid approach for drug delivery. We engineered a murine microglia cell line, BV-2, to release EVs overexpressing the endogenous "eat me" signal Lactadherin (Mfg-e8) on the surface to target phagocytes and containing the anti-inflammatory cytokine IL-4. A single injection of 107 IL-4+Mfg-e8+ EVs into the cisterna magna modulated established neuroinflammation and significantly reduced clinical signs in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Injected IL-4+Mfg-e8+ EVs target mainly phagocytes (i.e., macrophages and microglia) surrounding liquoral spaces, and their cargo promote the upregulation of anti-inflammatory markers chitinase 3-like 3 (ym1) and arginase-1 (arg1), significantly reducing tissue damage. Engineered EVs may represent a biological drug delivery tool able to deliver multiple functional molecules simultaneously to treat neuroinflammatory diseases.

PMID: 30017878 [PubMed - as supplied by publisher]

Pressure-driven spontaneous ion concentration polarization using an ion-selective membrane.

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Pressure-driven spontaneous ion concentration polarization using an ion-selective membrane.

Anal Biochem. 2018 Jul 12;:

Authors: Lee SJ, Lee J, Kim K

Abstract
In this study, the spontaneous ion concentration polarization phenomenon induced by pressure via a cation-selective membrane was theoretically and experimentally investigated. Unlike conventional electrokinetic ion concentration polarization, which uses electric current as a driving flux of cations through the membrane, advection caused by pressure is used as a transmembrane driving flux of cations to spontaneously and stably generate an ion depletion zone in the present ion concentration polarization. The ion depletion zone produced in a simple experimental setup was used to filter electrolyte and preconcentrate ions and microparticles. Different from the general assumption of the negligible thickness of the electric double layer in microchannels, the low concentration in the ion depletion zone considerably increased the length of the electric double layer. This enhanced the formation of the ion depletion zone. The results of the present study can improve the understanding on ion transport in the ion concentration polarization system and can be utilized to develop a portable water desalination device for rural/remote areas and for preconcentrating biomolecules.

PMID: 30017636 [PubMed - as supplied by publisher]

Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transition.

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Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transition.

Biochem Biophys Res Commun. 2018 Jul 12;:

Authors: Fujiwara T, Eguchi T, Sogawa C, Ono K, Murakami J, Ibaragi S, Asaumi JI, Okamoto K, Calderwood SK, Kozaki KI

Abstract
Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.

PMID: 30017201 [PubMed - as supplied by publisher]

Distinct non-invasive evaluation values of tumor-derived cell-free microRNAs, circulating microvesicles and exosomal microRNAs after renal carcinoma cryoablation.

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Distinct non-invasive evaluation values of tumor-derived cell-free microRNAs, circulating microvesicles and exosomal microRNAs after renal carcinoma cryoablation.

Biochem Biophys Res Commun. 2018 Jul 11;:

Authors: Zhang J, Wang W, Chen S, Wang Y, Xia S

Abstract
The detection of peripheral circulating tumor-derived components, such as cell-free microRNAs, circulating microvesicles, and exosomal microRNAs, has been shown as a promising noninvasive strategy. However, the different roles of these components in tumor therapy evaluations have remained largely undefined. In this paper, we employed an in vivo model of the human clear cell renal cell carcinoma line Caki-1-bearing mice to evaluate the therapeutic effects of cryoablation, which is a new minimally invasive treatment for renal cell carcinoma. At different times after cryoablation, we found that the levels of the cell-free microRNAs miR-122, miR-155 and miR-210 were first increased and then decreased. Additionally, the number of large-sized microvesicles was increased after cryoablation, but the number of small-sized circulating microvesicles did not change. Furthermore, the exosomal microRNAs miR-126-3p, miR-17-5p, and miR-21-3p rapidly decreased one day after cryoablation, an effect that was well correlated with the treatment degree. Therefore, we suggest that these circulating components may have different levels of importance in the evaluation of the efficacy of renal cell cryoablation, furthermore, exosomal microRNAs may be more suitable for the early postoperative judgment of tumor elimination effects, which are worth further exploration in clinical practice.

PMID: 30017193 [PubMed - as supplied by publisher]

Chitosan/alginate microparticles for the oral delivery of fowl typhoid vaccine: Innate and acquired immunity.

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Chitosan/alginate microparticles for the oral delivery of fowl typhoid vaccine: Innate and acquired immunity.

Vaccine. 2018 Jul 12;:

Authors: Onuigbo E, Iseghohimhen J, Chah K, Gyang M, Attama A

Abstract
Oral fowl typhoid (FT) vaccine is necessary for improved flock vaccinations and economic growth. This study was undertaken to evaluate the immune responses of birds given oral fowl typhoid vaccine coated with chitosan/alginate microparticles and comparing it with the conventional subcutaneous route of administration. Preliminary studies were done to evaluate the particle size, encapsulation efficiency and agglutination. Sixty day-old chicks were divided into three groups of twenty birds each. This comprised a negative control group NEG 451 (non-vaccinated and non-challenged used as control for cytokine quantification), SC 634 (live 9R vaccine by the injection route) and OCV 567 (live 9R vaccine coated with chitosan/alginate microparticles). Vaccination was done at 10 weeks and 14 weeks of age followed by challenge at 16 weeks of age. IgG was measured using ELISA. mRNA fold expression of IFN-γ in spleen was calculated using qRT-PCR. Particle sizes ranged between 0.55 µm and 10 µm. Encapsulation efficiency was above 60%. ELISA showed E-values of 0.10 ± 0.14, 0.07 ± 0.01 and 0.02 ± 0.01 for OCV 567, SC 634 and NEG 451 respectively after primary vaccination. Also E-values were 0.25 ± 0.16, 0.19 ± 0.04 and 0.0008 ± 0.005 for SC 634, OCV 567 and NEG451 respectively after boost vaccination. The expression of IFN-γin spleen using 2-ΔΔ CT calculation was upregulated with values of 1.97 and 0.75 for OCV 567 and SC 634 respectively. After challenge with the 85-kb virulence plasmid SG9, there was 100% protection of the birds in both OCV 567 and SC 634 groups with no mortality. In conclusion, there was no significant difference at p < 0.05 of the means ± SD in immune responses between the oral fowl typhoid vaccine coated with chitosan/alginate microparticles and the subcutaneous route of administration. However, it is noteworthy to mention that the protective efficacy of the oral route is due to the chitosan/alginate biopolymers which coated the vaccine preventing destruction in the gastrointestinal tract.

PMID: 30017142 [PubMed - as supplied by publisher]

 

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