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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 Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer.

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The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer.

Cell Rep. 2018 Apr 24;23(4):1178-1191

Authors: Shelton PM, Duran A, Nakanishi Y, Reina-Campos M, Kasashima H, Llado V, Ma L, Campos A, García-Olmo D, García-Arranz M, García-Olmo DC, Olmedillas-López S, Caceres JF, Diaz-Meco MT, Moscat J

Abstract
Most colorectal cancer (CRC)-related deaths are due to liver metastases. PKCζ is a tumor suppressor in CRC with reduced expression in metastasis. Given the importance of microRNAs (miRNAs) in regulating cellular plasticity, we performed an unbiased screening and identified the miR-200 family as the most relevant miRNAs downregulated by PKCζ deficiency. The regulation of the intracellular levels of miR-200 by PKCζ is post-transcriptional and involves their secretion in extracellular vesicles. Here, we identified ADAR2 as a direct substrate of PKCζ in CRC cells. Phosphorylation of ADAR2 regulates its editing activity, which is required to maintain miR-200 steady-state levels, suggesting that the PKCζ/ADAR2 axis regulates miR-200 secretion through RNA editing. Loss of this axis results in epithelial-to-mesenchymal transition (EMT) and increased liver metastases, which can be inhibited in vivo by blocking miR-200 release. Therefore, the PKCζ/ADAR2 axis is a critical regulator of CRC metastases through modulation of miR-200 levels.

PMID: 29694894 [PubMed - in process]

The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection.

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The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection.

Cell Rep. 2018 Apr 24;23(4):1085-1098

Authors: Alhallaf R, Agha Z, Miller CM, Robertson AAB, Sotillo J, Croese J, Cooper MA, Masters SL, Kupz A, Smith NC, Loukas A, Giacomin PR

Abstract
Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1β. However, the roles for inflammasomes during parasitic helminth infections remain unclear. We demonstrate that mice and humans infected with gastrointestinal nematodes display increased IL-18 secretion, which in Trichuris-infected or worm antigen-treated mice and in macrophages co-cultured with Trichuris antigens or exosome-like vesicles was dependent on the NLRP3 inflammasome. NLRP3-deficient mice displayed reduced pro-inflammatory type 1 cytokine responses and augmented protective type 2 immunity, which was reversed by IL-18 administration. NLRP3-dependent suppression of immunity partially required CD4+ cells but was apparent even in Rag1-/- mice that lack adaptive immune cells, suggesting that NLRP3 influences both innate and adaptive immunity. These data highlight a role for NLRP3 in limiting protective immunity to helminths, suggesting that targeting the NLRP3 inflammasome may be an approach for limiting the disease burden associated with helminth infections.

PMID: 29694887 [PubMed - in process]

Telocytes in skeletal, cardiac and smooth muscle interstitium: morphological and functional aspects.

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Telocytes in skeletal, cardiac and smooth muscle interstitium: morphological and functional aspects.

Histol Histopathol. 2018 Apr 25;:11994

Authors: Marini M, Rosa I, Ibba-Manneschi L, Manetti M

Abstract
Telocytes (TCs) represent a new distinct type of cells found in the stromal compartment of many organs, including the skeletal, cardiac and smooth muscles. TCs are morphologically defined as interstitial cells with a small cellular body from which arise very long (up to hundreds of micrometers) and thin moniliform processes (named telopodes) featuring the alternation of slender segments (called podomers) and small dilated portions (called podoms) accommodating some organelles. Although these stromal cells are mainly characterized by their ultrastructural traits, in the last few years TCs have been increasingly studied for their immunophenotypes, microRNA profiles, and gene expression and proteomic signatures. By their long-distance spreading telopodes, TCs build a three-dimensional network throughout the whole stromal space and communicate with each other and neighboring cells through homocellular and heterocellular junctions, respectively. Moreover, increasing evidence suggests that TCs may exert paracrine functions being able to transfer genetic information and signaling molecules to other cells via the release of different types of extracellular vesicles. A close relationship between TCs and stem/progenitor cell niches has also been described in several organs. However, the specific functions of TCs located in the muscle interstitium remain to be unraveled. Here, we review the morphological and possible functional aspects of TCs in skeletal, cardiac and smooth muscle tissues. The potential involvement of TCs in muscle tissue pathological changes and future possibilities for targeting TCs as a novel promising therapeutic strategy to foster muscle tissue regeneration and repair are also discussed.

PMID: 29693711 [PubMed - as supplied by publisher]

An Examination of Critical Parameters in Hybridization-Based Epigenotyping using Magnetic Microparticles.

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An Examination of Critical Parameters in Hybridization-Based Epigenotyping using Magnetic Microparticles.

Biotechnol Prog. 2018 Apr 25;:

Authors: Tam BE, Hao Y, Sikes HD

Abstract
Gene-specific promoter methylation is involved in gene silencing and is an important cancer biomarker. Cancer-specific methylation patterns have been observed and clinically validated for numerous gene promoters, but the knowledge gleaned from this large body of work is currently under-utilized in the clinic. Methylation-specific PCR is currently the gold standard method for clinical methylation assessment, but several research groups have proposed hybridization-based techniques which could be simpler to implement and provide more accurate results. However, the sensitivity of this easier alternative must be improved dramatically in order to compete with methylation-specific PCR. Efficient sample capture is a key step in maximizing sensitivity, so here we investigate the key parameters involved in i.) maximizing the capture of gene-specific target DNA molecules at the surfaces of functionalized, magnetic microparticles and ii.) recognizing DNA methylation using an engineered methyl-CpG-binding domain (MBD) protein. The magnetic bead density, the probe concentration, and the MBD concentration were very important for maximizing detection, and other variables such as the hybridization time also impacted the target capture efficiency but had a smaller effect on the overall methylation assay. The effect of genomic DNA on the capture of the target sequence was also investigated, and model methylated versus unmethylated target sequences could be distinguished in the presence of 1 ng/μL genomic DNA. The findings we report related to the underlying binding events involved in hybridization-based epigenotyping can be leveraged in combination with the many signal amplification and detection approaches that are currently being developed. This article is protected by copyright. All rights reserved.

PMID: 29693329 [PubMed - as supplied by publisher]

Microvesicles shed from bortezomib-treated or lenalidomide-treated human myeloma cells inhibit angiogenesis in vitro.

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Microvesicles shed from bortezomib-treated or lenalidomide-treated human myeloma cells inhibit angiogenesis in vitro.

Oncol Rep. 2018 Apr 23;:

Authors: Guo HM, Sun L, Yang L, Liu XJ, Nie ZY, Luo JM

Abstract
Angiogenesis plays a significant role in the pathogenesis of multiple myeloma (MM). Microvesicles (MVs), a type of extracellular vesicles, are known as important players in cell-to-cell communication. MM-derived MVs have exhibited the activity of promoting angiogenesis. Bortezomib and lenalidomide are important drugs for treating myeloma. Therefore, the aim of the present study was to investigate whether and how MVs secreted from human myeloma cells exposed to bortezomib and lenalidomide affect angiogenesis. RPMI-8226 human myeloma cells and human umbilical vein endothelial cells (HUVECs) were used. MVs were isolated from the drug-treated RPMI-8226 cells. The number of the MVs were analyzed with flow cytometry. The expression of pro-angiogenic factors was analyzed with PCR and ELISA. The angiogenic potential of HUVECs was examined. NF-κB activation was analyzed using PCR, immunofluorescent staining and western blotting assays. We showed that bortezomib treatment induced an increase in the number of MVs shed from myeloma cells, but the number of MVs was not significantly altered by lenalidomide. The expression levels of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) were reduced in the MVs from the RPMI-8226 cells exposed to bortezomib and lenalidomide. Consequently, these MVs exhibited reduced angiogenic potential, as evaluated by wound healing tests, Boyden chamber assays and tube formation assays. Co-culturing HUVECs with drug-treated MVs inhibited NF-κB activation in the HUVECs and reduced the secretion of pro-angiogenic factors. In conclusion, bortezomib and lenalidomide treatment of cultured myeloma cells can block MV-induced angiogenesis and hence provides another mechanism for anti-angiogenic therapy.

PMID: 29693175 [PubMed - as supplied by publisher]

Chronic obstructive pulmonary disease: MicroRNAs and exosomes as new diagnostic and therapeutic biomarkers.

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Chronic obstructive pulmonary disease: MicroRNAs and exosomes as new diagnostic and therapeutic biomarkers.

J Res Med Sci. 2018;23:27

Authors: Salimian J, Mirzaei H, Moridikia A, Harchegani AB, Sahebkar A, Salehi H

Abstract
Chronic obstructive pulmonary disease (COPD) is known as a progressive lung disease and the fourth leading cause of death worldwide. Despite valuable efforts, there is still no accurate diagnostic and prognostic tool for COPD. Hence, it seems that finding new biomarkers could contribute to provide better therapeutic platforms for COPD patients. Among various biomarkers, microRNAs (miRNAs) have emerged as new biomarkers for the prognosis and diagnosis of patients with COPD. It has been shown that deregulation of miRNAs targeting a variety of cellular and molecular pathways such as Notch, Wnt, hypoxia-inducible factor-1α, transforming growth factor, Kras, and Smad could be involved in COPD pathogenesis. Multiple lines of evidence have indicated that extracellular vesicles such as exosomes could carry a variety of cargos (i.e., mRNAs, miRNAs, and proteins) which transfer various cellular and molecular signals to recipient cells. Here, we summarized various miRNAs which could be applied as diagnostic and prognostic biomarkers in the treatment of patients with COPD. Moreover, we highlighted the role of extracellular vesicles containing miRNAs as diagnostic and prognostic biomarkers in COPD patients.

PMID: 29692824 [PubMed]

Exosomes and Stem Cells in Degenerative Disease Diagnosis and Therapy.

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Exosomes and Stem Cells in Degenerative Disease Diagnosis and Therapy.

Cell Transplant. 2018 Jan 01;:963689717723636

Authors: Chang YH, Wu KC, Harn HJ, Lin SZ, Ding DC

Abstract
Stroke can cause death and disability, resulting in a huge burden on society. Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by motor dysfunction. Osteoarthritis (OA) is a progressive degenerative joint disease characterized by cartilage destruction and osteophyte formation in the joints. Stem cell therapy may provide a biological treatment alternative to traditional pharmacological therapy. Mesenchymal stem cells (MSCs) are preferred because of their differentiation ability and possible derivation from many adult tissues. In addition, the paracrine effects of MSCs play crucial anti-inflammatory and immunosuppressive roles in immune cells. Extracellular vesicles (EVs) are vital mediators of cell-to-cell communication. Exosomes contain various molecules such as microRNA (miRNA), which mediates biological functions through gene regulation. Therefore, exosomes carrying miRNA or other molecules can enhance the therapeutic effects of MSC transplantation. MSC-derived exosomes have been investigated in various animal models representing stroke, PD, and OA. Exosomes are a subtype of EVs. This review article focuses on the mechanism and therapeutic potential of MSC-derived exosomes in stroke, PD, and OA in basic and clinical aspects.

PMID: 29692195 [PubMed - as supplied by publisher]

Glycocalyx shedding is markedly increased during the acute phase of Takotsubo cardiomyopathy.

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Glycocalyx shedding is markedly increased during the acute phase of Takotsubo cardiomyopathy.

Int J Cardiol. 2017 Sep 15;243:296-299

Authors: Nguyen TH, Liu S, Ong GJ, Stafford I, Frenneaux MP, Horowitz JD

Abstract
BACKGROUND: Acute myocardial infarction (AMI) and other forms of myocardial acute oxidative stress are associated with variable "shedding" of the endothelial glycocalyx (GCS) which can be quantitated ex vivo by release into plasma of glycocalyx components such as Syndecan-1 (SD-1). Previous studies have implicated release of both catecholamines and BNP as potential accentuating factors in GCS: since these are prominent aspects of the pathogenesis of Takotsubo cardiomyopathy (TTC), we hypothesised that TTC is associated with increased GCS and the extent of GCS is predictable on the basis of NT-proBNP and catecholamine releases.
METHODS: SD-1 concentrations were measured in 48 TTC patients acutely and after 3months, and compared with those in 12 healthy controls, and 17 patients with AMI. Correlations were sought between SD-1 levels markers of severity of TTC episodes in individual patients.
RESULTS: Acute SD-1 concentrations in TTC patients were elevated significantly (p<0.0001, 1-way ANOVA) compared to control values. There were no significant correlations between SD-1 concentrations and any markers of severity of acute TTC episodes, such as NT-proBNP or catecholamine release. Over 3months, SD-1 concentrations fell significantly (p=0.0002) to approximately the same values as in control subjects.
CONCLUSIONS: TTC is associated acutely with a marked increase in GCS. Potentially, GCS might contribute to increased coronary vascular permeability in TTC, thus dissociating development of myocardial oedema from severity of associated inflammation. Prevention of GCS represents a potential therapeutic option in TTC.

PMID: 28528983 [PubMed - indexed for MEDLINE]

 

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