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Extracellular vesicles

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https://www.readbyqxmd.com/read/29334397/recombinant-phosphatidylserine-binding-nanobodies-for-targeting-of-extracellular-vesicles-to-tumor-cells-a-plug-and-play-approach
#1
Sander A A Kooijmans, Jerney J J M Gitz-Francois, Raymond M Schiffelers, Pieter Vader
Extracellular vesicles (EVs) are increasingly being recognized as candidate drug delivery systems due to their ability to functionally transfer biological cargo between cells. However, manipulation of targeting properties of EVs through engineering of the producer cells can be challenging and time-consuming. As a novel approach to confer tumor targeting properties to isolated EVs, we generated recombinant fusion proteins of nanobodies against the epidermal growth factor receptor (EGFR) fused to phosphatidylserine (PS)-binding domains of lactadherin (C1C2)...
January 15, 2018: Nanoscale
https://www.readbyqxmd.com/read/29334272/extracellular-vesicle-mimetic-nanovesicles-transport-lncrna-h19-as-competing-endogenous-rna-for-the-treatment-of-diabetic-wounds
#2
Shi-Cong Tao, Bi-Yu Rui, Qi-Yang Wang, Ding Zhou, Yang Zhang, Shang-Chun Guo
Diabetic wounds, one of the most enervating complications of diabetes mellitus, affect millions of people worldwide annually. Vascular insufficiency, caused by hyperglycemia, is one of the primary causes and categories of diabetic impaired wound healing. Recently, long noncoding RNA (LncRNA)-H19, which is significantly decreased in diabetes and may be crucial in triggering angiogenesis, has attracted increasing interest. The possible relationship between the decrease of LncRNA-H19 and the impairment of angiogenesis in diabetes could involve impairment of the insulin-phosphatidylinositol 3-kinase (PI3K)-Akt pathway via the interdiction of LncRNA-H19...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29334253/circular-rna-expression-in-extracellular-vesicles-isolated-from-serum-of-patients-with-endometrial-cancer
#3
Hanzi Xu, Zhen Gong, Yang Shen, Yichen Fang, Shanliang Zhong
AIM: We aimed to explore the roles of circular RNAs (circRNAs) in extracellular vesicles (EVs) isolated from serum of patients with endometrial cancer. MATERIALS & METHODS: EVs were isolated from serum samples of three patients with stage III adenocarcinoma aged 50-60 years and three matched healthy controls. RNA was extracted from the EVs and analyzed using RNA-seq technique. RESULTS: We got 209 upregulated circRNAs and 66 downregulated circRNAs...
January 15, 2018: Epigenomics
https://www.readbyqxmd.com/read/29331845/effect-of-levetiracetam-on-extracellular-amino-acid-levels-in-the-dorsal-hippocampus-of-rats-with-temporal-lobe-epilepsy
#4
Pichardo Macías Luz Adriana, Ramírez Mendiola Blanca Alcira, Contreras García Itzel Jatziri, Zamudio Hernández Sergio Roberto, Chávez Pacheco Juan Luis, Sánchez Huerta Karla Berenice, Mendoza Torreblanca Julieta Griselda
Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action that is not completely understood. However, its activity profile may involve effects on excitatory and/or inhibitory neurotransmission since the primary target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all types of synaptic vesicles. Therefore, the objective of the present study was to explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic mini-pumps) on neurotransmitter release and its probable selective effect on extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp), glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo microdialysis under basal and high-K+ conditions) in the dorsal hippocampus (DH), a region that undergoes major synaptic changes during epilepsy...
January 5, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29331674/hiv-activates-the-tyrosine-kinase-hck-to-secrete-adam-protease-containing-extracellular-vesicles
#5
J-H Lee, C Ostalecki, Z Zhao, T Kesti, H Bruns, B Simon, T Harrer, K Saksela, A S Baur
No abstract text is available yet for this article.
January 4, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29331148/isolation-of-anti-extra-cellular-vesicle-single-domain-antibodies-by-direct-panning-on-vesicle-enriched-fractions
#6
Milica Popovic, Elisa Mazzega, Barbara Toffoletto, Ario de Marco
BACKGROUND: The thorough understanding of the physiological and pathological processes mediated by extracellular vesicles (EVs) is challenged by purification methods which are cumbersome, not reproducible, or insufficient to yield homogeneous material. Chromatography based on both ion-exchange and immune-capture can represent an effective method to improve EV purification and successive analysis. METHODS: Cell culture supernatant was used as a model sample for assessing the capacity of anion-exchange chromatography to separate distinct EV fractions and to isolate nanobodies by direct panning on whole EVs to recover binders specific for the native conformation of EV-surface epitopes and suitable to develop EV immune-capture reagents...
January 13, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29330365/engineered-nanointerfaces-for-microfluidic-isolation-and-molecular-profiling-of-tumor-specific-extracellular-vesicles
#7
Eduardo Reátegui, Kristan E van der Vos, Charles P Lai, Mahnaz Zeinali, Nadia A Atai, Berent Aldikacti, Frederick P Floyd, Aimal H Khankhel, Vishal Thapar, Fred H Hochberg, Lecia V Sequist, Brian V Nahed, Bob S Carter, Mehmet Toner, Leonora Balaj, David T Ting, Xandra O Breakefield, Shannon L Stott
Extracellular vesicles (EVs) carry RNA, DNA, proteins, and lipids. Specifically, tumor-derived EVs have the potential to be utilized as disease-specific biomarkers. However, a lack of methods to isolate tumor-specific EVs has limited their use in clinical settings. Here we report a sensitive analytical microfluidic platform (EVHB-Chip) that enables tumor-specific EV-RNA isolation within 3 h. Using the EVHB-Chip, we achieve 94% tumor-EV specificity, a limit of detection of 100 EVs per μL, and a 10-fold increase in tumor RNA enrichment in comparison to other methods...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29328916/the-neuronal-gene-arc-encodes-a-repurposed-retrotransposon-gag-protein-that-mediates-intercellular-rna-transfer
#8
Elissa D Pastuzyn, Cameron E Day, Rachel B Kearns, Madeleine Kyrke-Smith, Andrew V Taibi, John McCormick, Nathan Yoder, David M Belnap, Simon Erlendsson, Dustin R Morado, John A G Briggs, Cédric Feschotte, Jason D Shepherd
The neuronal gene Arc is essential for long-lasting information storage in the mammalian brain, mediates various forms of synaptic plasticity, and has been implicated in neurodevelopmental disorders. However, little is known about Arc's molecular function and evolutionary origins. Here, we show that Arc self-assembles into virus-like capsids that encapsulate RNA. Endogenous Arc protein is released from neurons in extracellular vesicles that mediate the transfer of Arc mRNA into new target cells, where it can undergo activity-dependent translation...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328915/retrovirus-like-gag-protein-arc1-binds-rna-and-traffics-across-synaptic-boutons
#9
James Ashley, Benjamin Cordy, Diandra Lucia, Lee G Fradkin, Vivian Budnik, Travis Thomson
Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. Here, we report that the Drosophila Arc1 protein forms capsid-like structures that bind darc1 mRNA in neurons and is loaded into extracellular vesicles that are transferred from motorneurons to muscles...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29328396/placenta%C3%A2-associated-serum-exosomal-mir%C3%A2-155-derived-from-patients-with-preeclampsia-inhibits-enos-expression-in-human-umbilical-vein-endothelial-cells
#10
Li Shen, Yujing Li, Ruotian Li, Zhenyu Diao, Muyi Yany, Mengfei Wu, Haixiang Sun, Guijun Yan, Yali Hu
Preeclampsia (PE) is considered to be initiated by abnormal placentation in early pregnancy and results in systemic endothelial cell dysfunction in the second or third trimester. MicroRNAs (miRs) expressed in the human placenta can be secreted into maternal circulation via exosomes, which are secreted extracellular vesicles that serve important roles in intercellular communication. The present study hypothesized that upregulation of placenta‑associated serum exosomal miR‑155 from patients with PE may suppress endothelial nitric oxide synthase (eNOS) expression in endothelial cells...
January 8, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29327816/brain-cortex-microglia-derived-exosomes-novel-nanoparticles-for-glioma-therapy
#11
Adriana-Natalia Murgoci, Dasa Cizkova, Petra Majerova, Eva Petrovova, Lubomir Medvecky, Isabelle Fournier, Michel Salzet
The function and integrity of nervous system require interactive exchanges among neurons and glial cells. Exosomes and other extracellular vesicles (EVs) are emerging as a key mediator of intercellular communication, capable to transfer nucleic acids, proteins and lipids, influencing numerous functional and pathological aspects of both donor and recipient cells. The immune response mediated by microglia derived exosomes are most prominently involved in the spread of neuroinflammation, neurodegenerative disorders and brain cancer...
January 12, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/29325643/the-secret-life-of-exosomes-what-bees-can-teach-us-about-next-generation-therapeutics
#12
REVIEW
Eduardo Marbán
Mechanistic exploration has pinpointed nanosized extracellular vesicles, known as exosomes, as key mediators of the benefits of cell therapy. Exosomes appear to recapitulate the benefits of cells and more. As durable azoic entities, exosomes have numerous practical and conceptual advantages over cells. Will cells end up just being used to manufacture exosomes, or will they find lasting value as primary therapeutic agents? Here, a venerable natural process-the generation of honey-serves as an instructive parable...
January 16, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29323722/exosomal-mirnas-as-novel-cancer-biomarkers-challenges-and-opportunities
#13
Mahsa Salehi, Mohammadreza Sharifi
A biomarker with high specificity and sensitivity, is a basic requirement for non-invasive cancer diagnosis. Exosomes are a type of lipid bilayer extracellular vesicles (EVs), containing different components, including proteins, lipids, DNA, messenger RNA (mRNA) and non-coding RNAs. Increasing evidence indicates that nucleic acids are protected by exosome lipid membrane. These vesicles are almost released from all cell types, into biological fluids. In cancer, the expression of microRNAs (miRNAs), located in the tumor cell-derived exosomes, is deregulated and it could be led to metastasis and therapy resistance...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29323709/osteosarcoma-derived-extracellular-vesicles-induce-a-tumour-like-phenotype-in-normal-recipient-cells
#14
Enrica Urciuoli, Ezio Giorda, Marco Scarsella, Stefania Petrini, Barbara Peruzzi
Osteosarcoma is the most common primary bone cancer and the most frequent cause of bone cancer-related deaths in children and adolescents. Osteosarcoma cells are able to establish a crosstalk with resident bone cells leading to the formation of a deleterious vicious cycle. We hypothesized that osteosarcoma cells can release, in the bone microenvironment, transforming Extracellular Vesicles (EVs) involved in regulating bone cell proliferation and differentiation, thereby promoting tumour growth. We assessed EV production by three osteosarcoma cell lines with increasing aggressiveness in order to investigate their roles in the communication between osteosarcoma cells and normal recipient cells...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29323194/human-mesenchymal-stromal-cell-derived-extracellular-vesicles-modify-microglial-response-and-improve-clinical-outcomes-in-experimental-spinal-cord-injury
#15
Katherine A Ruppert, Tin T Nguyen, Karthik S Prabhakara, Naama E Toledano Furman, Amit K Srivastava, Matthew T Harting, Charles S Cox, Scott D Olson
No current clinical intervention can alter the course of acute spinal cord injury (SCI), or appreciably improve neurological outcome. Mesenchymal stromal cells (MSCs) have been shown to modulate the injury sequelae of SCI largely via paracrine effects, although the mechanisms remain incompletely understood. One potential modality is through secretion of extracellular vesicles (EVs). In this study, we investigate whether systemic administration of EVs isolated from human MSCs (MSCEv) has the potential to be efficacious as an alternative to cell-based therapy for SCI...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320704/extracellular-vesicles-provide-a-means-for-tissue-crosstalk-during-exercise
#16
Martin Whitham, Benjamin L Parker, Martin Friedrichsen, Janne R Hingst, Marit Hjorth, William E Hughes, Casey L Egan, Lena Cron, Kevin I Watt, Rhiannon P Kuchel, Navind Jayasooriah, Emma Estevez, Tim Petzold, Catherine M Suter, Paul Gregorevic, Bente Kiens, Erik A Richter, David E James, Jørgen F P Wojtaszewski, Mark A Febbraio
Exercise stimulates the release of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognizing that many circulating proteins are packaged in extracellular vesicles (EVs), we employed quantitative proteomic techniques to characterize the exercise-induced secretion of EV-contained proteins. Following a 1-hr bout of cycling exercise in healthy humans, we observed an increase in the circulation of over 300 proteins, with a notable enrichment of several classes of proteins that compose exosomes and small vesicles...
January 9, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29319803/down-regulation-of-glutamate-release-from-hippocampal-neurons-by-sialidase
#17
Minami Akira, Ami Ishii, Sumika Shimba, Takahiro Kano, Eri Fujioka, Saki Sai, Nagisa Oshio, Sayaka Ishibashi, Tadanobu Takahashi, Yuuki Kurebayashi, Hiroaki Kanazawa, Nobuhiro Yuki, Tadamune Otsubo, Kiyoshi Ikeda, Takashi Suzuki
Sialidase, which removes sialic acid residues in sialylglycoconjugates, is essential for hippocampal memory and synaptic plasticity. Enzyme activity of sialidase is rapidly increased in response to neural excitation. Because sialic acid bound to gangliosides such as the tetra-sialoganglioside GQ1b is crucial for calcium signaling and neurotransmitter release, neural activity-dependent removal of sialic acid may affect hippocampal neurotransmission. In the present study, we found that 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (DANA), a sialidase inhibitor, increased expression of ganglioside GQ1b/GT1a in hippocampal acute slices...
January 8, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/29319164/microvesicles-intercellular-messengers-in-cutaneous-wound-healing
#18
REVIEW
Alexandra Laberge, Syrine Arif, Véronique J Moulin
Longtime considered as inert cellular debris, microvesicles (MVs) have gained tremendous attention in the past decade. MVs are 100-1000 nm vesicles released into the extracellular environment by the outward budding and fission of the plasma membrane. They are now regarded as essential mediators of cell-to-cell interactions in a variety of physiological and pathological processes. In this review, we discuss the increasingly recognized contribution of MVs to the biology of wound healing. We highlight current concepts relating to the biogenesis and mode of action of MVs...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29318971/-phenserine-and-inhibiting-pre-programmed-cell-death-in-pursuit-of-a-novel-intervention-for-alzheimer-s-disease
#19
Robert E Becker, Nigel H Greig, Debomoy K Lahiri, Joseph Bledsoe, Sarah Majercik, Clive Ballard, Dag Aarsland, Lon S Schneiderh, Douglas Flanagan, Ramprakash Govindarajani, Mary Sano, Luigi Ferrucci, Dimitrios Kapogiannisk
BACKGROUND: Concussion (mild) and other moderate traumatic brain injury (TBI) and Alzheimer's disease (AD) share overlapping neuropathologies, including neuronal pre-programmed cell death (PPCD), and clinical impairments and disabilities. Multiple clinical trials targeting mechanisms based on the Amyloid Hypothesis of AD have so far failed, indicating that it is prudent for new drug developments to also pursue mechanisms independent of the Amyloid Hypothesis. To address these issue, we have proposed the use of an animal model of concussion/TBI as a supplement to AD transgenic mice to provide an indication of an AD drug candidate's potential for preventing PPCD and resulting progression towards dementia in AD...
January 10, 2018: Current Alzheimer Research
https://www.readbyqxmd.com/read/29316942/comparison-of-membrane-affinity-based-method-with-size-exclusion-chromatography-for-isolation-of-exosome-like-vesicles-from-human-plasma
#20
Ruzena Stranska, Laurens Gysbrechts, Jens Wouters, Pieter Vermeersch, Katarzyna Bloch, Daan Dierickx, Graciela Andrei, Robert Snoeck
BACKGROUND: Plasma extracellular vesicles (EVs), especially exosome-like vesicles (ELVs), are being increasingly explored as a source of potential noninvasive disease biomarkers. The discovery of blood-based biomarkers associated with ELVs requires methods that isolate high yields of these EVs without significant contamination with highly abundant plasma proteins and lipoproteins. The rising interest in blood-based EV-associated biomarkers has led to the rapid development of novel EV isolation methods...
January 9, 2018: Journal of Translational Medicine
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