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https://www.readbyqxmd.com/read/28719859/-curcumin-loaded-poly-d-l-lactide-co-glycolide-nanovesicles-induce-antinociceptive-effects-and-reduce-pronociceptive-cytokine-and-bdnf-release-in-spinal-cord-after-acute-administration-in-mice
#1
Stefano Pieretti, Amalendu P Ranjan, Amalia Di Giannuario, Anindita Mukerjee, Francesca Marzoli, Rita Di Giovannandrea, Jamboor K Vishwanatha
Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia...
July 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28719210/thermally-regulated-reversible-formation-of-vesicle-like-assemblies-by-hexaproline-amphiphiles
#2
Carles Felip-León, Francisco Galindo, Juan F Miravet, Valeria Castelletto, Ian W Hamley
Peptides composed of hexaproline and glutamic acid (P6E) or lysine (P6K) as C-terminal units show thermally promoted aggregation, affording vesicle-like assemblies upon heating to 80 ºC. The aggregation is analyzed by dynamic light scattering (DLS), with number averaged diameters of ca. 600 and 300 nm respectively for P6E and P6K. NMR studies reveal that upon heating the amount of NMR-visible species is reduced to ca. 50% and that an important conformational change is experienced by the molecules in solution...
July 18, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28719054/evolutionary-cell-biology-of-proteins-from-protists-to-humans-and-plants
#3
REVIEW
Helmut Plattner
During evolution, the cell as a fine-tuned machine had to undergo permanent adjustments to match changes in its environment, while "closed for repair work" was not possible. Evolution from protists (protozoa and unicellular algae) to multicellular organisms may have occurred in basically two lineages, Unikonta and Bikonta, culminating in mammals and angiosperms (flowering plants), respectively. Unicellular models for unikont evolution are myxamoebae (Dictyostelium) and increasingly also choanoflagellates, whereas, for bikonts, ciliates are preferred models...
July 18, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28718905/a-novel-cell-cell-communication-mechanism-in-the-nervous-system-exosomes
#4
REVIEW
Guan Zhang, Ping Yang
Exosomes are small extracellular membrane-based vesicles with a variety of cargoes that are involved in numerous physiological and pathological processes in the nervous system. Accumulating evidence has implicated that exosomes are emerging as a novel form of intercellular communication within the nervous system. In this review, we first illustrate exosome metabolism including its formation, secretion, transport, and uptake. Second, we compare exosomes to synaptic vesicles in terms of intercellular messengers and communicators...
July 18, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28718768/selective-and-regulated-trapping-of-nicotinic-receptor-weak-base-ligands-and-relevance-to-smoking-cessation
#5
Anitha P Govind, Yolanda F Vallejo, Jacob R Stolz, Jing-Zhi Yan, Geoffrey T Swanson, William N Green
To better understand smoking cessation, we examined the actions of varenicline (Chantix) during long-term nicotine exposure. Varenicline reduced nicotine upregulation of α4β2-type nicotinic receptors (α4β2Rs) in live cells and neurons, but not for membrane preparations. Effects on upregulation depended on intracellular pH homeostasis and were not observed if acidic pH in intracellular compartments was neutralized. Varenicline was trapped as a weak base in acidic compartments and slowly released, blocking (125)I-epibatidine binding and desensitizing α4β2Rs...
July 18, 2017: ELife
https://www.readbyqxmd.com/read/28717925/complex-biomembrane-mimetics-on-the-sub-nanometer-scale
#6
REVIEW
Frederick A Heberle, Georg Pabst
Biomimetic lipid vesicles are indispensable tools for gaining insight into the biophysics of cell physiology on the molecular level. The level of complexity of these model systems has steadily increased, and now spans from domain-forming lipid mixtures to asymmetric lipid bilayers. Here, we review recent progress in the development and application of elastic neutron and X-ray scattering techniques for studying these systems in situ and under physiologically relevant conditions on the nanometer to sub-nanometer length scales...
July 17, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28717426/extracellular-vesicles-released-following-heat-stress-induce-bystander-effect-in-unstressed-populations
#7
Findlay Bewicke-Copley, Laura Ann Mulcahy, Laura Ann Jacobs, Priya Samuel, Naveed Akbar, Ryan Charles Pink, David Raul Francisco Carter
Cells naïve to stress can display the effects of stress, such as DNA damage and apoptosis, when they are exposed to signals from stressed cells; this phenomenon is known as the bystander effect. We previously showed that bystander effect induced by ionising radiation are mediated by extracellular vesicles (EVs). Bystander effect can also be induced by other types of stress, including heat shock, but it is unclear whether EVs are involved. Here we show that EVs released from heat shocked cells are also able to induce bystander damage in unstressed populations...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717425/high-throughput-nanoparticle-tracking-analysis-for-monitoring-outer-membrane-vesicle-production
#8
Matthias J H Gerritzen, Dirk E Martens, René H Wijffels, Michiel Stork
Outer membrane vesicles (OMVs) are spherical membrane nanoparticles released by Gram-negative bacteria. OMVs can be quantified in complex matrices by nanoparticle tracking analysis (NTA). NTA can be performed in static mode or with continuous sample flow that results in analysis of more particles in a smaller time-frame. Flow measurements must be performed manually despite the availability of a sample changer on the NanoSight system. Here we present a method for automated measurements in flow mode. OMV quantification in flow mode results in lower variance in particle quantification (coefficient of variation (CV) of 6%, CV static measurements of 14%)...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717424/low-active-loading-of-cargo-into-engineered-extracellular-vesicles-results-in-inefficient-mirna-mimic-delivery
#9
Dhruvitkumar S Sutaria, Jinmai Jiang, Ola A Elgamal, Steven M Pomeroy, Mohamed Badawi, Xiaohua Zhu, Ryan Pavlovicz, Ana Clara P Azevedo-Pouly, Jeffrey Chalmers, Chenglong Li, Mitch A Phelps, Thomas D Schmittgen
Extracellular vesicles (EVs) hold great potential as novel systems for nucleic acid delivery due to their natural composition. Our goal was to load EVs with microRNA that are synthesized by the cells that produce the EVs. HEK293T cells were engineered to produce EVs expressing a lysosomal associated membrane, Lamp2a fusion protein. The gene encoding pre-miR-199a was inserted into an artificial intron of the Lamp2a fusion protein. The TAT peptide/HIV-1 transactivation response (TAR) RNA interacting peptide was exploited to enhance the EV loading of the pre-miR-199a containing a modified TAR RNA loop...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717423/contribution-of-neuroblastoma-derived-exosomes-to-the-production-of-pro-tumorigenic-signals-by-bone-marrow-mesenchymal-stromal-cells
#10
Rie Nakata, Hiroyuki Shimada, G Esteban Fernandez, Rob Fanter, Muller Fabbri, Jemily Malvar, Pascale Zimmermann, Yves A DeClerck
The bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines. Using three different purification methods, we then demonstrate that NB-derived exosomes were captured by MSCs and induced the production of pro-tumorigenic cytokines and chemokines, including interleukin-6 (IL-6), IL-8/CXCL8, vascular endothelial cell growth factor and monocyte-chemotactic protein-1, with exosomes prepared by size exclusion chromatography having the highest activity...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717422/exosomes-purified-from-a-single-cell-type-have-diverse-morphology
#11
Davide Zabeo, Aleksander Cvjetkovic, Cecilia Lässer, Martin Schorb, Jan Lötvall, Johanna L Höög
Extracellular vesicles (EVs) are produced by all known organisms and are important for cell communication and physiology. Great morphological diversity has been described regarding EVs found in body fluids such as blood plasma, breast milk, and ejaculate. However, a detailed morphological analysis has never been performed on exosomes when purified from a single cell type. In this study we analysed and quantified, via multiple electron microscopy techniques, the morphology of exosomes purified from the human mast cell line HMC-1...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717421/isolation-of-membrane-vesicles-from-prokaryotes-a-technical-and-biological-comparison-reveals-heterogeneity
#12
Priscila Dauros Singorenko, Vanessa Chang, Alana Whitcombe, Denis Simonov, Jiwon Hong, Anthony Phillips, Simon Swift, Cherie Blenkiron
Prokaryotes release membrane vesicles (MVs) with direct roles in disease pathogenesis. MVs are heterogeneous when isolated from bacterial cultures so Density Gradient Centrifugation (DGC) is valuable for separation of MV subgroups from contaminating material. Here we report the technical variability and natural biological heterogeneity seen between DGC preparations of MVs for Mycobacterium smegmatis and Escherichia coli and compare these DGC data with size exclusion chromatography (SEC) columns. Crude preparations of MVs, isolated from cultures by ultrafiltration and ultracentrifugation were separated by DGC with fractions manually collected as guided by visible bands...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717420/comprehensive-toxicity-and-immunogenicity-studies-reveal-minimal-effects-in-mice-following-sustained-dosing-of-extracellular-vesicles-derived-from-hek293t-cells
#13
Xiaohua Zhu, Mohamed Badawi, Steven Pomeroy, Dhruvitkumar S Sutaria, Zhiliang Xie, Alice Baek, Jinmai Jiang, Ola A Elgamal, Xiaokui Mo, Krista La Perle, Jeffrey Chalmers, Thomas D Schmittgen, Mitch A Phelps
Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune responses which may contribute to toxicities or enhanced EV clearance. Furthermore, EVs from different cell sources or EVs comprising various cargo may differ with respect to immunogenicity or toxicity. To assess EV-induced immune response and toxicity, we dosed C57BL/6 mice with EVs intravenously and intraperitoneally for 3 weeks...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717419/platelet-extracellular-vesicles-induce-a-pro-inflammatory-smooth-muscle-cell-phenotype
#14
Tanja Vajen, Birke J Benedikter, Alexandra C A Heinzmann, Elena M Vasina, Yvonne Henskens, Martin Parsons, Patricia B Maguire, Frank R Stassen, Johan W M Heemskerk, Leon J Schurgers, Rory R Koenen
Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin αIIbβ3, while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717418/a-novel-community-driven-software-for-functional-enrichment-analysis-of-extracellular-vesicles-data
#15
Mohashin Pathan, Shivakumar Keerthikumar, David Chisanga, Riccardo Alessandro, Ching-Seng Ang, Philip Askenase, Arsen O Batagov, Alberto Benito-Martin, Giovanni Camussi, Aled Clayton, Federica Collino, Dolores Di Vizio, Juan Manuel Falcon-Perez, Pedro Fonseca, Pamali Fonseka, Simona Fontana, Yong Song Gho, An Hendrix, Esther Nolte-'t Hoen, Nunzio Iraci, Kenneth Kastaniegaard, Thomas Kislinger, Joanna Kowal, Igor V Kurochkin, Tommaso Leonardi, Yaxuan Liang, Alicia Llorente, Taral R Lunavat, Sayantan Maji, Francesca Monteleone, Anders Øverbye, Theocharis Panaretakis, Tushar Patel, Héctor Peinado, Stefano Pluchino, Simona Principe, Goran Ronquist, Felix Royo, Susmita Sahoo, Cristiana Spinelli, Allan Stensballe, Clotilde Théry, Martijn J C van Herwijnen, Marca Wauben, Joanne L Welton, Kening Zhao, Suresh Mathivanan
Bioinformatics tools are imperative for the in depth analysis of heterogeneous high-throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture "what the community needs in a tool". Here, we describe a novel community-driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717417/analysis-of-extracellular-rna-in-cerebrospinal-fluid
#16
Julie A Saugstad, Theresa A Lusardi, Kendall R Van Keuren-Jensen, Jay I Phillips, Babett Lind, Christina A Harrington, Trevor J McFarland, Amanda L Courtright, Rebecca A Reiman, Ashish S Yeri, M Yashar S Kalani, P David Adelson, Jorge Arango, John P Nolan, Erika Duggan, Karen Messer, Johnny C Akers, Douglas R Galasko, Joseph F Quinn, Bob S Carter, Fred H Hochberg
We examined the extracellular vesicle (EV) and RNA composition of pooled normal cerebrospinal fluid (CSF) samples and CSF from five major neurological disorders: Alzheimer's disease (AD), Parkinson's disease (PD), low-grade glioma (LGG), glioblastoma multiforme (GBM), and subarachnoid haemorrhage (SAH), representing neurodegenerative disease, cancer, and severe acute brain injury. We evaluated: (I) size and quantity of EVs by nanoparticle tracking analysis (NTA) and vesicle flow cytometry (VFC), (II) RNA yield and purity using four RNA isolation kits, (III) replication of RNA yields within and between laboratories, and (IV) composition of total and EV RNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing (RNASeq)...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717416/feasibility-of-urinary-extracellular-vesicle-proteome-profiling-using-a-robust-and-simple-clinically-applicable-isolation-method
#17
Irene V Bijnsdorp, Olga Maxouri, Aarzo Kardar, Tim Schelfhorst, Sander R Piersma, Thang V Pham, Andre Vis, R Jeroen van Moorselaar, Connie R Jimenez
Extracellular vesicles (EVs) secreted by prostate cancer (PCa) cells contain specific biomarkers and can be isolated from urine. Collection of urine is not invasive, and therefore urinary EVs represent a liquid biopsy for diagnostic and prognostic testing for PCa. In this study, we optimised urinary EV isolation using a method based on heat shock proteins and compared it to gold-standard ultracentrifugation. The urinary EV isolation protocol using the Vn96-peptide is easier, time convenient (≈1.5 h) and no special equipment is needed, in contrast to ultracentrifugation protocol (>3...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717032/th17-mediated-cross-protection-against-pneumococcal-carriage-by-vaccination-with-a-variable-antigen
#18
Kirsten Kuipers, Wouter S P Jong, Christa E van der Gaast-de Jongh, Diane Houben, Fred van Opzeeland, Elles Simonetti, Saskia van Selm, Ronald de Groot, Marije I Koenders, Taj Azarian, Elder Pupo, Peter van der Ley, Jeroen D Langereis, Aldert Zomer, Joen Luirink, Marien I de Jonge
Serotype-specific protection against a Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission and limit emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of LPS-detoxified outer membrane vesicles (OMVs) from Salmonella Typhimurium displaying the variable N-terminus of PspA (α1α2) for intranasal vaccination, which induced strong Th17 immunity associated with substantial reduction of pneumococcal colonization...
July 17, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28717005/lipid-oxidation-inactivates-the-anticoagulant-function-of-protein-z-dependent-protease-inhibitor-zpi
#19
Xin Huang, Baoxin Liu, Yidong Wei, Ryan Beyea, Han Yan, Steven T Olson
Lipid oxidation due to oxidative stress plays an important role in the pathogenesis of inflammatory and thrombotic cardiovascular diseases. Several findings suggest that lipid peroxidation can alter the function of coagulation proteins and contribute to a hypercoagulable state, but the molecular mechanisms are unclear. Here, we report that oxidized phospholipids suppress the anticoagulant function of the serpin, protein Z-dependent protease inhibitor (ZPI), a specific inhibitor of membrane-associated factor Xa (FXa) that requires protein Z (PZ), phospholipid and calcium as cofactors...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#20
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
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