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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.

Thyroid-Stimulating Hormone-Stimulated Human Adipocytes Express Thymic Stromal Lymphopoietin.

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Thyroid-Stimulating Hormone-Stimulated Human Adipocytes Express Thymic Stromal Lymphopoietin.

Horm Metab Res. 2018 Feb 19;:

Authors: Ma L, Gagnon A, Landry A, Le T, Xiao F, Sun C, Lochnan HA, Burger D, Sorisky A

Abstract
When recombinant human (rh) thyroid-stimulating hormone (TSH) is administered to thyroid cancer survivors, an acute extra-thyroidal effect raises pro-inflammatory cytokines and activates platelets. Thymic stromal lymphopoietin (TSLP) is a cytokine recently implicated in platelet activation. Our aim was to measure platelet microparticle levels after rhTSH stimulation in vivo, and to investigate TSLP expression in TSH-stimulated human adipocytes in culture. Blood samples for total and platelet microparticle analysis were obtained from thyroid cancer survivors before (day 1) and after rhTSH administration (day 5). Adipocytes, differentiated from stromal preadipocytes isolated from adipose tissue from surgical patients, were stimulated with TSH. TSLP mRNA expression, protein expression, and protein release into the adipocyte medium were measured. The level of platelet microparticles in thyroid cancer patients rose 5-fold after rhTSH stimulation. TSH upregulated TSLP mRNA expression in adipocytes in culture through a pathway that was inhibited by 66% by H89, a protein kinase A inhibitor. TSLP protein expression rose in response to TSH, and TSH-stimulated TSLP release into the medium was completely blocked by dexamethasone. In conclusion, TSLP is a novel TSH-responsive adipokine. Future studies will be needed to address the potential role of adipocyte-derived TSLP and whether it is linked to TSH-dependent platelet activation.

PMID: 29458221 [PubMed - as supplied by publisher]

Long non-coding RNAs within the tumour microenvironment and their role in tumour-stroma cross-talk.

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Long non-coding RNAs within the tumour microenvironment and their role in tumour-stroma cross-talk.

Cancer Lett. 2018 Feb 16;:

Authors: Del Vecchio F, Lee GH, Hawezi J, Bhome R, Pugh S, Sayan E, Thomas G, Packham G, Primrose J, Pichler M, Mirnezami A, Calin G, Bullock M

Abstract
Long non-coding RNAs (lncRNAs) are a diverse class of RNA transcripts which have limited protein coding potential. They perform a variety of cellular functions in health, but have also been implicated during malignant transformation. A further theme in recent years is the critical role of the tumour microenvironment and the dynamic interactions between cancer and stromal cells in promoting invasion and disease progression. Whereas the contribution of deregulated lncRNAs within cancer cells has received considerable attention, their significance within the tumour microenvironment is less well understood. The tumour microenvironment consists of cancer-associated stromal cells and structural extracellular components which interact with one another and with the transformed epithelium via complex extracellular signalling pathways. LncRNAs are directly and indirectly involved in tumour/stroma cross-talk and help stimulate a permissive tumour microenvironment which is more conducive for invasive tumour growth. Furthermore, lncRNAs play key roles in determining the phenotype of cancer associated stromal cells and contribute to angiogenesis and immune evasion pathways, extracellular-matrix (ECM) turnover and the response to hypoxic stress. Here we explore the multifaceted roles of lncRNAs within the tumour microenvironment and their putative pathophysiological effects.

PMID: 29458141 [PubMed - as supplied by publisher]

Reversible Surface Engineering via Nitrone-Mediated Radical Coupling.

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Reversible Surface Engineering via Nitrone-Mediated Radical Coupling.

Langmuir. 2018 Feb 19;:

Authors: Laun J, Marchal W, Trouillet V, Welle A, Hardy AT, Van Bael MK, Barner-Kowollik C, Junkers T

Abstract
Efficient and simple polymer conjugation reactions are critical for introducing functionalities on surfaces. For polymer surface grafting, post polymerization modifications are often required, which can impose a significant synthetic hurdle. Here, we report two strategies that allow for reversible surface engineering via nitrone-mediated radical coupling (NMRC). Macroradicals stemming from activation of polymers generated by copper-mediated radical polymerization are grafted via radical trapping with a surface-immobilized nitrone or a solution-borne nitrone. Since the product of an NMRC coupling features an alkoxyamine linker, the grafting reactions can be reversed or chain insertions be performed via nitroxide mediated polymerization (NMP). Poly(n-butyl acrylate) (Mn=1570 g·mol-1, Ɖ = 1.12) with bromine terminus was reversibly grafted to planar silicon substrates or silica nanoparticles as successfully evidenced via X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry, and grazing angle attenuated total reflection Fourier-transform infrared spectroscopy (GAATR-FTIR). NMP chain insertions of styrene is evidenced via GAATR-FTIR. On silica nanoparticles, a NMRC grafting density of close to 0.21 chains per nm² was determined by dynamic light scattering and thermogravimetric analysis. Concomitantly, a simple way to decorate particles with nitroxide radicals with precise control over the radical concentration is introduced. Silica microparticles and zinc oxide, barium titanate, and silicon nanoparticles were successfully functionalized.

PMID: 29457981 [PubMed - as supplied by publisher]

Structural Variability of DNA-containing Mg-pyrophosphate microparticles: Optimized Conditions to Produce Particles with Desired Size and Morphology.

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Structural Variability of DNA-containing Mg-pyrophosphate microparticles: Optimized Conditions to Produce Particles with Desired Size and Morphology.

J Biomol Struct Dyn. 2018 Feb 19;:1-28

Authors: Danilevich VN, Mulyukin AL, Machulin AV, Sorokin VV, Kozlov SA

Abstract
Our previous studies demonstrated the formation of structurally diverse DNA-containing microparticles (DNA MPs) in PCR with Mg-pyrophosphate (MgPPi) as the structure-forming component. These DNA MPs were referred to major structural types: microdisks (2D MPs) with nanometer thickness and 3D MPs with sophisticated morphology and constructed from intersecting disks and their segments. Little is known about factors that influence both the morphology and size of DNA MPs, and the present study was aimed at fulfilling this gap. We showed that the addition of Mn2+ cations to PCR mixtures caused the profound changes in MPs morphology, depending on DNA polymerase used (KlenTaq or Taq). Asymmetric PCR with 20-fold decrease in the concentration of one of two primers facilitated the predominant formation of microdisks with unusual structure. The addition of 1 mM Na-pyrophosphate to PCR mixtures with synthesized DNA and subsequent thermal cycling (10-15 cycles) were optimal to produce microdisks or nanometer 3D particles. Using electron microscopy, we studied also the structure of inorganic micro- and nanoparticles from MgPPi, formed during multiple heating and cooling cycles of a mixture of Mg2+ and Na-pyrophosphate in various regimes. Also we found the conditions to yield planar (Mg·Mn)PPi nanocrystals (diameter ~100 nm and thickness ~10 nm) which efficiently adsorbed exogenous DNA. These inorganic nanoparticles are promising for DNA delivery in transfection studies. Mechanisms to be involved in structural modifications of MPs and perspectives of their practical application are discussed.

PMID: 29457757 [PubMed - as supplied by publisher]

Janus-Faced Myeloid-Derived Suppressor Cell Exosomes for the Good and the Bad in Cancer and Autoimmune Disease.

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Janus-Faced Myeloid-Derived Suppressor Cell Exosomes for the Good and the Bad in Cancer and Autoimmune Disease.

Front Immunol. 2018;9:137

Authors: Zöller M

Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells originally described to hamper immune responses in chronic infections. Meanwhile, they are known to be a major obstacle in cancer immunotherapy. On the other hand, MDSC can interfere with allogeneic transplant rejection and may dampen autoreactive T cell activity. Whether MDSC-Exosomes (Exo) can cope with the dangerous and potentially therapeutic activities of MDSC is not yet fully explored. After introducing MDSC and Exo, it will be discussed, whether a blockade of MDSC-Exo could foster the efficacy of immunotherapy in cancer and mitigate tumor progression supporting activities of MDSC. It also will be outlined, whether application of native or tailored MDSC-Exo might prohibit autoimmune disease progression. These considerations are based on the steadily increasing knowledge on Exo composition, their capacity to distribute throughout the organism combined with selectivity of targeting, and the ease to tailor Exo and includes open questions that answers will facilitate optimizing protocols for a MDSC-Exo blockade in cancer as well as for strengthening their therapeutic efficacy in autoimmune disease.

PMID: 29456536 [PubMed]

Exosomes Serve as Nanoparticles to Deliver Anti-miR-214 to Reverse Chemoresistance to Cisplatin in Gastric Cancer.

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Exosomes Serve as Nanoparticles to Deliver Anti-miR-214 to Reverse Chemoresistance to Cisplatin in Gastric Cancer.

Mol Ther. 2018 Jan 08;:

Authors: Wang X, Zhang H, Bai M, Ning T, Ge S, Deng T, Liu R, Zhang L, Ying G, Ba Y

Abstract
Chemoresistance is one of the causes of adverse effects in gastric cancer, including a poor response to cisplatin (DDP). Exosomes loaded with microRNA (miRNA), mRNA, and other non-coding RNAs could regulate drug resistance. Exo-anti-214 was extracted and verified. A Cell Counting Kit-8 (CCK-8) cell viability assay, flow cytometry, and transwell and immunofluorescence assays were performed to determine whether exo-anti-214 could sensitize cells to DDP in vitro. A combination of intravenously injected exo-anti-214 and intraperitoneal DDP was utilized in vivo. Additionally, potential targets of miR-214 were screened by mass spectrometry (MS) and confirmed via western blotting (WB). The levels of miR-214 in the human immortalized gastric epithelial cell line ges-1 and the human gastric adenocarcinoma cell lines SGC7901 and SGC7901/DDP gradually increased. Exo-anti-214 could fuse with cells and regulate potential targets, reducing cell viability, suppressing migration, and promoting apoptosis in vitro. Caudally injected exo-anti-214 was applied to reverse chemoresistance and repress tumor growth in vivo due to the downregulation of miR-214 and overexpression of possible target proteins in tumors. Exo-anti-214 could reverse the resistance to DDP in gastric cancer, which might serve as a potential alternative for the treatment of cisplatin-refractory gastric cancer in the future.

PMID: 29456019 [PubMed - as supplied by publisher]

Design and biological response of doxycycline loaded chitosan microparticles for periodontal disease treatment.

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Design and biological response of doxycycline loaded chitosan microparticles for periodontal disease treatment.

Carbohydr Polym. 2018 Apr 15;186:260-272

Authors: Gjoseva S, Geskovski N, Sazdovska SD, Popeski-Dimovski R, Petruševski G, Mladenovska K, Goracinova K

Abstract
The aim of this study was to develop chitosan (CS) microparticulated mucoadhesive drug delivery system (DDS) with improved therapeutic performance and biological responce. Ionotropic gelation/spray drying process was used for preparation of doxycycline hyclate (DOXY) loaded low and medium molecular weight (LMw and MMw) CS/sodium tripolyphosphate microparticles (CS/TPP MPs), further coated with ethyl cellulose (EC) using coacervation/solvent displacement technique. The relevant physico-chemical and biopharmaceutical properties were optimized using experimental design approach. Both coated and uncoated CS/TPP MPs showed high mucoadhesive potential and did not affect the viability of the tested epithelial cell line. The MPs induced slow and gradual apoptotic response in murine macrophage cell line RAW 264.7 and the observed effect depended upon formulation type and MP concentration. Biological effect of the CS-based MPs observed in our experiments point to synergism of the biological response of the carrier with the anti-inflammatory effect of DOXY.

PMID: 29455987 [PubMed - in process]

Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling.

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Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling.

Mol Cancer. 2018 Feb 19;17(1):35

Authors: Hsu MC, Hung WC

Abstract
Originally identified as a metabolic enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP in the glycolytic pathway, pyruvate kinase M2-type (PKM2) has been shown to exhibit novel biological activities in the nucleus and outside the cells. Although cell-based studies reveal new non-canonical functions of PKM2 in gene transcription, epigenetic modulation and cell cycle progression, the importance of these non-canonical functions in PKM2-mediated tumorigenesis is still under debate because studies in genetically modified mice do not consistently echo the findings observed in cultured cancer cells. In addition to regulation of gene expression, the existence of PKM2 in exosomes opens a new venue to study the potential role of this glycolytic enzyme in cell-cell communication and extracellular signal initiation. In this review, we briefly summarize current understanding of PKM2 in metabolic switch and gene regulation. We will then emphasize recent progress of PKM2 in extracellular signaling and tumor microenvironment reprogramming. Finally, the discrepancy of some PKM2's functions in vitro and in vivo, and the application of PKM2 in cancer detection and treatment will be discussed.

PMID: 29455645 [PubMed - in process]

Role of Exosomes Derived from miR-133b Modified MSCs in an Experimental Rat Model of Intracerebral Hemorrhage.

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Role of Exosomes Derived from miR-133b Modified MSCs in an Experimental Rat Model of Intracerebral Hemorrhage.

J Mol Neurosci. 2018 Feb 17;:

Authors: Shen H, Yao X, Li H, Li X, Zhang T, Sun Q, Ji C, Chen G

Abstract
Intracerebral hemorrhage (ICH) has poor outcomes due to high mortality and morbidity, but until now, the effective treatments remain limited. MicroRNAs (miRNAs) are vital regulators of gene expression and demonstrated to be linked to the pathogenesis of various central nervous system (CNS) diseases. Exosomes are considered as cell-to-cell communication vectors and secreted largely by mesenchymal stromal cells (MSCs). The present study investigated the role of miR-133b delivered by exosomes secreted from MSCs to brain tissues in rats after ICH. An autologous arterial blood ICH model in adult male Sprague-Dawley (SD) rats was used in this study. At 72 h after transfection with miR-133b mimics in MSCs, miR-133b-modified MSC-derived exosomes were collected from medium of MSCs and then injected to rats via tail vein. The levels of miR-133b in secreted exosomes and brain tissues of rats in various groups and the levels of RhoA, phosphorylations of extracellular signal regulating kinase (ERK1/2), and cAMP response element-binding protein (CREB) were detected by real-time PCR and western blot analysis, respectively. The effects of miR-133b on neuronal apoptosis and degeneration were respectively evaluated by TUNEL and fluoro-jade B staining. The miR-133b levels were reduced in brain tissues of rats at 24 h and peaked at 72 h after ICH. At 24 h after miR-133b-modified exosome administration, the level of miR-133b was significantly increased, while the apoptotic and neurodegenerative neurons were obviously reduced in brain tissues after ICH. The results of western blot analysis showed that miR-133b modified exosomes treatment remarkably suppressed RhoA expression and activated ERK1/2/CREB in brain tissues after ICH. Collectively, our investigation suggested that exosomes derived from miR-133b modified MSCs exhibited neuroprotective role for anti-apoptotic effect of miR-133b mediating RhoA and ERK1/2/CREB in rats after ICH.

PMID: 29455449 [PubMed - as supplied by publisher]

Optical Fiber Tips for Biological Applications: from Light Confinement, Biosensing to Bioparticles Manipulation.

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Optical Fiber Tips for Biological Applications: from Light Confinement, Biosensing to Bioparticles Manipulation.

Biochim Biophys Acta. 2018 Feb 15;:

Authors: Paiva JS, Jorge PAS, Rosa CC, Cunha JPS

Abstract
BACKGROUND: The tip of an optical fiber has been considered an attractive platform in Biology. The simple cleaved end of an optical fiber can be machined, patterned and/or functionalized, acquiring unique properties enabling the exploitation of novel optical phenomena. Prompted by the constant need to measure and manipulate nanoparticles, the invention of the Scanning Near-Field Optical Microscopy (SNOM) triggered the optimization and development of novel fiber tip microfabrication methods. In fact, the fiber tip was soon considered a key element in SNOM by confining light to sufficiently small extensions, challenging the diffraction limit. As result and in consequence of the newly proposed "Lab On Tip" concept, several geometries of fiber tips were applied in three main fields: imaging (in Microscopy/Spectroscopy), biosensors and micromanipulation (Optical Fiber Tweezers, OFTs). These are able to exert forces on microparticles, trap and manipulate them for relevant applications, as biomolecules mechanical study or protein aggregates unfolding.
SCOPE OF REVIEW: This review presents an overview of the main achievements, most impactful studies and limitations of fiber tip-based configurations within the above three fields, along the past 10 years.
MAJOR CONCLUSIONS: OFTs could be in future a valuable tool for studying several cellular phenomena such as neurodegeneration caused by abnormal protein fibrils or manipulating organelles within cells. This could contribute to understand the mechanisms of some diseases or biophenomena, as the axonal growth in neurons.
GENERAL SIGNIFICANCE: To the best of our knowledge, no other review article has so far provided such a broad view. Despite of the limitations, fiber tips have key roles in Biology/Medicine.

PMID: 29454758 [PubMed - as supplied by publisher]

 

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