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https://www.readbyqxmd.com/read/28742189/novel-endogenous-negative-modulators-of-platelet-function-as-potential-anti-thrombotic-targets
#1
Y-J Li, H-X Zhu, D Zhang, H-C Li, P Ma, L-Y Huang
Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, granule release and finally thrombus formation...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28741407/pericytes-secrete-pro-regenerative-molecules-in-response-to-platelet-derived-growth-factor-bb
#2
Abderahim Gaceb, Ilknur Özen, Thomas Padel, Marco Barbariga, Gesine Paul
Brain pericytes not only maintain the anatomical, biochemical and immune blood-brain barrier, but display features of mesenchymal stem cells (MSCs) in vitro. MSCs have pro-regenerative properties attributed to their secretome. However, whether also brain pericytes possess such pro-regenerative capacities is largely unknown. Here we characterize the secretome and microvesicle (MV) release of human brain pericytes mediated by platelet-derived growth factor-BB (PDGF-BB)/PDGF receptor beta (PDGFRβ) signalling...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28740549/targeted-delivery-to-tumor-associated-pericytes-via-an-affibody-with-high-affinity-for-pdgfr%C3%AE-enhances-the-in-vivo-antitumor-effects-of-human-trail
#3
Ze Tao, Hao Yang, Qiuxiao Shi, Qing Fan, Lin Wan, Xiaofeng Lu
Human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) has exhibited superior in vitro cytotoxicity in a variety of tumor cells. However, hTRAIL showed a disappointing anticancer effect in clinical trials, although hTRAIL-based regimens were well tolerated. One important reason might be that hTRAIL was largely trapped by its decoy receptors, which are ubiquitously expressed on normal cells. Tumor-targeted delivery might improve the tumor uptake and thus enhance the antitumor effect of hTRAIL...
2017: Theranostics
https://www.readbyqxmd.com/read/28739590/mast-cells-granular-contents-are-crucial-for-deep-vein-thrombosis-in-mice
#4
Tatyana Ponomaryov, Holly Payne, Larissa Fabritz, Denisa D Wagner, Alexander Brill
Rationale: Deep vein thrombosis (DVT) and its complication pulmonary embolism have high morbidity reducing quality of life and leading to death. Cellular mechanisms of DVT initiation remain poorly understood. Objective: We sought to determine the role of mast cells (MCs) in DVT initiation and validate MCs as a potential target for DVT prevention. Methods and Results: In a mouse model, DVT was induced by partial ligation (stenosis) of the inferior vena cava (IVC). We demonstrated that two strains of mice deficient for MCs were completely protected from DVT...
July 24, 2017: Circulation Research
https://www.readbyqxmd.com/read/28738291/inflammation-responsive-self-regulated-drug-release-from-ultrathin-hydrogel-coating
#5
Min He, Qian Wang, Zhenqiang Shi, Yi Xie, Weifeng Zhao, Changsheng Zhao
Heterotopic ossification(HO) is a potential severe complication after many biomaterial implanting surgeries, and the inflammation environment caused by the implanting-associated infections is considered as the main nosogenesis. Herein, an inflammation-responsive drug release system was designed by chemically conjugating indometacin (via ester group) onto hydrogel coating to realize local self-regulated drug release to prevent HO. In our strategy, poly(3-mercaptopropyl)trimethoxysilane-co-acrylic acrylate and polyvinyl alcohol (providing anchoring sites for drug molecules) were firstly synthesized and functionalized with ene-groups, then a hydrogel layer was formed and covalently attached onto thiol-modified substrate via thiol-ene click chemistry, followed by grafting indometacin...
July 18, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28738008/randomized-placebo-controlled-study-of-the-effects-of-yunnan-baiyao-on-hemostasis-in-horses
#6
SallyAnne L Ness, Amelia H Frye, Thomas J Divers, Mark Rishniw, Hollis N Erb, Marjory B Brooks
OBJECTIVE To determine effects of oral administration of Yunnan Baiyao on platelet activation, coagulation, and fibrinolysis in healthy horses. ANIMALS 12 healthy adult horses. PROCEDURES In a randomized blinded crossover study that included a 4-week washout period between treatments, horses were orally administered a paste containing Yunnan Baiyao (15 mg/kg) or placebo at 12-hour intervals for 3 days. Blood samples were collected before start of treatment (time 0) and at 24 and 72 hours for a CBC, measurement of fibrinogen concentration, coagulation screening tests, and a panel of assays to assess platelet activation (including ADP- and collagen-induced aggregation and closure times, flow-cytometric variables of platelet-leukocyte aggregates, platelet membrane P-selectin and phosphatidylserine expression, and microparticle release), von Willebrand factor (vWF) concentration, and cofactor activity...
August 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28733990/dimethyl-fumarate-modulates-neutrophil-extracellular-trap-formation-in-a-glutathione-and-superoxide-dependent-manner
#7
J H O Hoffmann, K Schaekel, D Hartl, A H Enk, E N Hadaschik
BACKGROUND: Neutrophil (polymorphonuclear) granulocytes (PMN) were shown to contribute to the pathogenesis of psoriasis by releasing IL-17 and LL-37/ DNA complexes via neutrophil extracellular traps (NET), webs of chromatin strands decorated with antimicrobial peptides, in psoriatic skin. Fumaderm(®) , a fumaric acid ester (FAE) formulation consisting of different FAE salts has been successfully used to treat psoriasis for decades. Most recently, FAE treatment was reported to inhibit NET formation in murine epidermolysis bullosa acquisita...
July 22, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28728412/role-of-interfaces-in-the-elasticity-and-failure-of-clay-organic-nanocomposites-toughening-upon-interface-weakening
#8
Gyorgy Hantal, Laurent Brochard, Roland J-M Pellenq, Franz-Josef Ulm, Benoit Coasne
Synthetic organic-inorganic composites constitute a new class of engineering materials finding applications in an increasing range of fields. The interface between the constituting phases plays a pivotal role in the enhancement of mechanical properties. In exfoliated clay-organic nanocomposites, individual, high aspect ratio clay sheets are dispersed in the organic matrix providing large interfaces and hence efficient stress transfer. In this study, we aim at elucidating molecular-scale reinforcing mechanisms in a series of model clay-organic composite systems by means of reactive molecular simulations...
July 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28727490/comparison-of-the-release-of-micrornas-and-extracellular-vesicles-from-platelets-in-response-to-different-agonists
#9
Ashley R Ambrose, Mohammed A Alsahli, Sameer A Kurmani, Alison H Goodall
On activation platelets release microRNAs and extracellular vesicles (EV) into circulation. The release of EV from platelets has been shown to be dependent on the agonist; in this study, we investigated whether the microRNA profile or EV released from platelets was also agonist specific. Washed platelets from healthy subjects were maximally stimulated with agonists specific for the receptors for collagen (Glycoprotein VI (GPVI)), thrombin (PAR1/PAR4), or ADP (P2Y1/P2Y12) with/without inhibiting secondary mediators, using aspirin to block cyclooxygenase-1 and apyrase to remove ADP...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28727479/extracellular-chloride-is-required-for-efficient-platelet-aggregation
#10
Kirk A Taylor, Darren G S Wilson, Matthew T Harper, Nicholas Pugh
Anion channels perform a diverse range of functions and have been implicated in ATP release, volume regulation, and phosphatidylserine exposure. Platelets have been shown to express several anion channels but their function is incompletely understood. Due to a paucity of specific pharmacological blockers, we investigated the effect of extracellular chloride substitution on platelet activation using aggregometry and flow cytometry. In the absence of extracellular chloride, we observed a modest reduction of the maximum aggregation response to thrombin or collagen-related peptide...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28726976/absence-of-transforming-growth-factor-beta-1-in-murine-platelets-reduces-neointima-formation-without-affecting-arterial-thrombosis
#11
Katrin Schaefer, Eva Schütz, Magdalena L Bochenek, Dennis R Riehl, Markus Bosmann, Thomas Münzel, Stavros Konstantinides, Katrin Schäfer
Platelet degranulation at the site of vascular injury prevents bleeding and may affect the chronic vascular wound healing response. Transforming Growth Factor (TGF)-β1 is a major component of platelet α-granules known to accumulating in thrombi. It was our aim to determine the role of TGFβ1 released from activated platelets for neointima formation following arterial injury and thrombosis. Mice with platelet-specific deletion of TGFβ1 (Plt.TGFβ-KO) underwent carotid artery injury. Immunoassays confirmed the absence of active TGFβ1 in platelet releasates and plasma of Plt...
July 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28726538/marked-bleeding-diathesis-in-patients-with-platelet-dysfunction-due-to-a-novel-mutation-in-rasgrp2-encoding-caldag-gefi-p-gly305asp
#12
Emilse Bermejo, Maria F Alberto, David S Paul, Aaron A Cook, Paquita Nurden, Analia Sanchez Luceros, Alan T Nurden, Wolfgang Bergmeier
Congenital platelet function disorders are often the result of defects in critical signal transduction pathways required for platelet adhesion and clot formation. Mutations affecting RASGRP2, the gene encoding the Rap GTPase activator, CalDAG-GEFI, give rise to a novel, and rare, group of platelet signal transduction abnormalities. We here report platelet function studies for two brothers (P1 and P2) expressing a novel variant of RASGRP2, CalDAG-GEFI(p.Gly305Asp). P1 and P2 have a lifelong history of bleeding with severe epistaxis successfully treated with platelet transfusions or rFVIIa...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28725970/ion-release-in-ceramic-bearings-for-total-hip-replacement-results-from-an-in-vitro-and-an-in-vivo-study
#13
Jan Philippe Kretzer, Ulrike Mueller, Marcus R Streit, Hartmuth Kiefer, Robert Sonntag, Robert M Streicher, Joern Reinders
INTRODUCTION: Literature on the potential release of trace elements following implantation of Zirconia-platelet toughened alumina (ZPTA) ceramic components is scant. The present study therefore analysed the in vitro and in vivo potential release of ions from ZPTA bearings. MATERIAL AND METHODS: An in vitro and in vivo study was conducted. The in vitro study compared leaching in bovine serum from two groups: ZPTA ceramic heads and Co-28Cr-6Mo alloy heads, both 28-mm diameter...
July 20, 2017: International Orthopaedics
https://www.readbyqxmd.com/read/28725494/apixaban-for-treatment-of-confirmed-heparin-induced-thrombocytopenia-a-case-report-and-review-of-literature
#14
Daniel E Ezekwudo, Rebecca Chacko, Bolanle Gbadamosi, Syeda Batool, Sussana Gaikazian, Theodore E Warkentin, Jo-Ann I Sheppard, Ishmael Jaiyesimi
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening condition caused by the binding of platelet-activating antibodies (IgG) to multimolecular platelet factor 4 (PF4)/heparin complexes because of heparin exposure. The by-product of this interaction is thrombin formation which substantially increases the risk of venous and/or arterial thromboembolism. Currently, only one anticoagulant, argatroban, is United States Food and Drug Administration-approved for management of HIT; however, this agent is expensive and can only be given by intravenous infusion...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28723729/wnt-signaling-in-cardiovascular-disease-opportunities-and-challenges
#15
Austin Gay, Dwight A Towler
PURPOSE OF REVIEW: Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members - the plasma membrane receptors for the cadre of Wnt polypeptide morphogens - contribute to the control of cardiovascular homeostasis. RECENT FINDINGS: Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease...
July 18, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28719356/co-incubation-of-pmn-and-caco-2-cells-modulates-inflammatory-potential
#16
M B Schaefer, C A Schaefer, M Hecker, R E Morty, M Witzenrath, W Seeger, K Mayer
Polymorphonuclear granulocytes (PMN) are activated in inflammatory reactions. Intestinal epithelial cells are relevant for maintaining the intestinal barrier. We examined interactions of PMN and intestinal epithelial cell-like CaCo-2 cells to elucidate their regulation of inflammatory signalling and the impact of cyclooxygenase (COX), nitric oxide (NO) and platelet-activating factor (PAF). Human PMN and CaCo-2 cells, separately and in co-incubation, were stimulated with the calcium ionophore A23187 or with N-Formyl-methionyl-leucyl-phenylalanin (fMLP) that activates PMN only...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28718457/towards-production-of-novel-catalyst-powders-from-supported-size-selected-clusters-by-multilayer-deposition-and-dicing
#17
Nan Jian, Karl Bauer, Richard E Palmer
A multilayer deposition method has been developed with the potential to capture and process atomic clusters generated by a high flux cluster beam source. In this deposition mode a series of sandwich structures each consisting of three layers-a carbon support layer, cluster layer and polymer release layer-is sequentially deposited to form a stack of isolated cluster layers, as confirmed by through-focal aberration-corrected HAADF STEM analysis. The stack can then be diced into small pieces by a mechanical saw...
August 11, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28717419/platelet-extracellular-vesicles-induce-a-pro-inflammatory-smooth-muscle-cell-phenotype
#18
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/28717145/acetylsalicylic-acid-differentially-limits-the-activation-and-expression-of-cell-death-markers-in-human-platelets-exposed-to-staphylococcus-aureus-strains
#19
Adrien Chabert, Pauline Damien, Paul O Verhoeven, Florence Grattard, Philippe Berthelot, Fabrice Zeni, Laurence Panicot-Dubois, Stéphane Robert, Françoise Dignat-George, Marie-Ange Eyraud, Bruno Pozzetto, Bernard Payrastre, Fabrice Cognasse, Olivier Garraud, Hind Hamzeh-Cognasse
Beyond their hemostatic functions, platelets alter their inflammatory response according to the bacterial stimulus. Staphylococcus aureus is associated with exacerbated inflammation and thrombocytopenia, which is associated with poor prognosis during sepsis. Acetylsalicylic acid and statins prevent platelet aggregation and decrease the mortality rate during sepsis. Therefore, we assessed whether these two molecules could reduce in vitro platelet activation and the inflammatory response to S. aureus. Platelets were exposed to clinical strains of S...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714241/cytokine-profiles-in-tibetan-macaques-following-%C3%AE-1-3-galactosyltransferase-knockout-pig-liver-xenotransplantation
#20
Zhuochao Zhang, Xiao Li, Hong Zhang, Xuan Zhang, Hui Chen, Dengke Pan, Hongchen Ji, Liang Zhou, Juan Ling, Jingshi Zhou, Shuqiang Yue, Desheng Wang, Zhaoxu Yang, Kaishan Tao, Kefeng Dou
BACKGROUND: Pig-to-nonhuman primate orthotopic liver xenotransplantation is often accompanied by thrombocytopenia and coagulation disorders. Furthermore, the release of cytokines can trigger cascade reactions of coagulation and immune attacks within transplant recipients. To better elucidate the process of inflammation in liver xenograft recipients, we utilized a modified heterotopic auxiliary liver xenotransplantation model for xeno-immunological research. We studied the cytokine profiles and the relationship between cytokine levels and xenograft function after liver xenotransplantation...
July 17, 2017: Xenotransplantation
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