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https://www.readbyqxmd.com/read/28432223/fli1-level-during-megakaryopoiesis-affects-thrombopoiesis-and-platelet-biology
#1
Karen K Vo, Danuta J Jarocha, Randolph B Lyde, Vincent Hayes, Christopher S Thom, Spencer K Sullivan, Deborah L French, Mortimer Poncz
Friend Leukemia Virus Integration 1 (FLI1), a critical transcription factor (TF) during megakaryocyte differentiation, is amongst genes hemizygously deleted in Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau syndrome (PTSx). Recently, heterozygote human FLI1 mutations have been ascribed to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand these clinical disorders, beginning with iPSCs generated from a PTSx patient and iPSCs from a control line with a targeted heterozygous FLI1 knockout (FLI1(+/-))...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28431006/regulation-of-oxidized-platelet-lipidome-implications-for-coronary-artery-disease
#2
Madhumita Chatterjee, Dominik Rath, Jörg Schlotterbeck, Johannes Rheinlaender, Britta Walker-Allgaier, Nada Alnaggar, Monika Zdanyte, Iris Müller, Oliver Borst, Tobias Geisler, Tilman E Schäffer, Michael Lämmerhofer, Meinrad Gawaz
Aims: Hyperlipidaemia enhances susceptibility to thrombosis, while platelet oxidixed LDL (oxLDL) binding in acute coronary syndrome (ACS) correlates with activation status. This study explores the platelet lipidome in symptomatic coronary artery disease (CAD) patients and the functional consequences of the chemokine CXCL12 and its receptors CXCR-4/-7 on lipid uptake in platelets. Methods and results: Platelet-oxLDL detected by flow cytometry was enhanced (P = 0...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28427942/inhibitory-effects-of-ethyl-pyruvate-on-platelet-aggregation-and-phosphatidylserine-exposure
#3
Wenjin Li, Xinyu Yang, Minyuan Peng, Can Li, Guangfu Mu, Fangping Chen
Ethyl pyruvate (EP) is a stable lipophilic pyruvate derivative. Studies demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti-coagulant effects. Inflammation and coagulation are closely interacted with platelet activation. However, it is unclear whether EP has anti-platelet effects. Therefore, we investigated the anti-platelet effect of EP in this study in vitro. We found that EP inhibited agonists induced platelets aggregation, ATP release and adhesion to collagen. Flow cytometric analysis revealed that EP inhibited agonist induced platelets PAC-1 binding, as well as P-selectin and CD40L expression...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28424777/influence-of-cellular-composition-and-exogenous-activation-on-growth-factor-and-cytokine-concentrations-in-canine-platelet-rich-plasmas
#4
Samuel P Franklin, Kate E Birdwhistell, Alena Strelchik, Bridget C Garner, Benjamin M Brainard
OBJECTIVE: The purposes of this study were to (1) evaluate correlations among platelet, leukocyte, growth factor, and cytokine concentrations in canine platelet-rich plasmas (PRPs) produced from five different canine PRP-concentrating systems and (2) compare the effects of different activation protocols on platelet activation and growth factor release from one of these PRPs. METHODS: PRP was made using blood from 15 dogs and each of 5 different PRP systems in a cross-over design...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28421990/elevated-levels-of-soluble-cd40-ligand-are-associated-with-antiphospholipid-antibodies-in-patients-with-systemic-lupus-erythematosus
#5
Ki-Jo Kim, In-Woon Baek, Chong-Hyeon Yoon, Wan-Uk Kim, Chul-Soo Cho
OBJECTIVES: The CD40L/CD40 pathway is involved in the pathophysiology of atherothrombotic disease, and elevated levels of soluble CD40L (sCD40L) were reported in SLE patients. However, the clinical implication of sCD40L in SLE remains elusive. METHODS: We measured levels of plasma sCD40L in 241 SLE patients and 37 healthy controls and investigated its association with clinical manifestation and laboratory parameters. RESULTS: Levels of plasma sCD40L in SLE patients were significantly elevated compared with healthy controls (p=0...
April 18, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28413027/matrix-metalloproteinases-and-platelet-function
#6
Paolo Gresele, Emanuela Falcinelli, Manuela Sebastiano, Stefania Momi
Platelets contain and release several matrix metalloproteinases (MMPs) and their tissue inhibitors of matrix metalloproteinases (TIMPs), including MMP-1, -2, -3, -9, and -14 and TIMP-1, -2, and -4. Although devoid of a nucleus, platelets also synthesize TIMP-2 upon activation. Platelet-released MMPs/TIMPs, as well as MMPs generated by other cells within the cardiovascular system, modulate platelet function in health and disease. In particular, a normal hemostatic platelet response to vessel wall injury may be transformed into pathologic thrombus formation by the release from platelets and/or by the local generation of some MMPs...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28412904/the-role-of-exosomes-and-exosome-derived-micrornas-in-atherosclerosis
#7
Xinjie Lu
BACKGROUND: Atherosclerosis is the leading cause of death and morbidity throughout industrialized nations, accounting for one-fifth of all deaths globally. Exosomes are bi-lipid membranous vesicles containing protein, lipid and nucleic acid contents that are released from cells via the endolysosomal pathway. Exosomes are derived from several cells including macrophages, dendritic cells, platelets as well as human serum. METHODS: In this review, an overview of recent advances and the evidence for the role exosomes and exosome-derived microRNAs (miRNAs) in atherosclerosis are provided...
April 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28412719/combined-measurement-of-factor-xiii-and-d-dimer-is-helpful-for-differential-diagnosis-in-patients-with-suspected-pulmonary-embolism
#8
Ning Tang, Ziyong Sun, Dengju Li, Jun Yang, Shiyu Yin, Qing Guan
BACKGROUND: D-dimer has been used to rule out pulmonary embolism (PE). Based on previous reports of decreased concentrations of coagulation factor XIII (FXIII) in venous thromboembolism, and no change in FXIII concentration in patients with acute cardiovascular disease, we evaluated the benefit of simultaneously measuring D-dimer and FXIII concentrations for diagnosing PE. METHODS: In this prospective single-center study, we enrolled 209 patients initially suspected of having PE, and measured their D-dimer and FXIII concentrations...
April 17, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28412372/flavonoids-and-platelet-aggregation-a-brief-review
#9
REVIEW
Caterina Faggio, Antoni Sureda, Silvia Morabito, Ana Sanches Silva, Andrei Mocan, Seyed Fazel Nabavi, Seyed Mohammad Nabavi
Platelets are small anucleated fragments derived from a megakaryocyte precursor. Platelets play a key role in many physiological functions especially in hemostasis and wound healing processes in order to maintain the integrity of the circulatory system. In addition, activated platelets release cytokines and chemokines which modulate the immune response and, in some cases of hyperactivation, they could be associated to the pathogenesis of inflammatory diseases. Flavonoids are polyphenolic compounds ubiquosly found in plants known to be potent antioxidants with positive effects against diverse diseases such as cancer, neurodegenerative or cardiovascular disease...
April 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28411253/a-new-path-to-platelet-production-through-matrix-sensing
#10
Vittorio Abbonante, Christian Andrea Di Buduo, Cristian Gruppi, Carmelo De Maria, Elise Spedden, Aurora De Acutis, Cristian Staii, Mario Raspanti, Giovanni Vozzi, David Kaplan, Francesco Moccia, Katya Ravid, Alessandra Balduini
Megakaryocytes in the bone marrow are immersed in a network of extracellular matrix (ECM) components that regulate platelet release into the circulation. Combining biological and bioengineering approaches, we found that the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechano-sensitive ion channel, is induced upon megakaryocyte adhesion on softer matrices. This response promoted platelet production by triggering a cascade of events that lead to calcium influx, β1 integrin activation and internalization, and Akt phosphorylation, responses not found on stiffer matrices...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28409633/tunable-nitric-oxide-release-from-s-nitroso-n-acetylpenicillamine-via-catalytic-copper-nanoparticles-for-biomedical-applications
#11
Jitendra Pant, Marcus James Goudie, Sean P Hopkins, Elizabeth J Brisbois, Hitesh Handa
The quest for novel therapies to prevent bacterial infections and blood clots (thrombosis) is of utmost importance in biomedical research due to exponential growth in cases of thrombosis, blood infections, and the emergence of multi-drug resistant strains of bacteria. Endogenous nitric oxide (NO) is a cellular signaling molecule that plays a pivotal role in host immunity against pathogens, prevention of clotting, and regulation of systemic blood pressure among several biological functions. The physiological effect of NO is dose dependent, that necessitates the need of tunable release kinetics which is the objective of this study...
April 14, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28408920/endoscopic-assisted-linea-alba-reconstruction-new-technique-for-treatment-of-symptomatic-umbilical-trocar-and-or-epigastric-hernias-with-concomitant-rectus-abdominis-diastasis
#12
Ferdinand Köckerling, Marinos Damianos Botsinis, Christine Rohde, Wolfgang Reinpold, Christine Schug-Pass
BACKGROUND: Patients with symptomatic umbilical, trocar, and/or epigastric hernias and concomitant rectus abdominis diastasis represent a growing clinical problem. The optimal management of this complex hernia situation is the subject of debate in the literature. This paper reports the early results of an innovative surgical technique aimed at managing this hernia situation. METHODS: Endoscopic-assisted linea alba reconstruction (ELAR) with mesh augmentation is a surgical technique long known in the literature for its good outcome for incisional hernia repair (myofascial release, overlapping herniorrhaphy, Gibson's operation, shoelace repair, anterior rectus sheath repair, dynamic patch plasty) via a small access route...
2017: European Surgery: ACA: Acta Chirurgica Austriaca
https://www.readbyqxmd.com/read/28408624/activated-protein-c-inhibits-neutrophil-extracellular-trap-formation-in-vitro-and-activation-in-vivo
#13
Laura D Healy, Cristina Puy, José A Fernández, Annachiara Mitrugno, Ravi S Keshari, Nyiawung A Taku, Tiffany T Chu, Xiao Xu, András Gruber, Florea Lupu, John H Griffin, Owen J T McCarty
Activated protein C (APC) is a multi-functional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms...
April 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28404690/pharmacologic-characterization-of-valbenazine-nbi-98854-and-its-metabolites
#14
Dimitri E Grigoriadis, Evan Smith, Sam R J Hoare, Ajay Madan, Haig Bozigian
The vesicular monoamine transporter 2 (VMAT2) is an integral presynaptic protein that regulates the packaging and subsequent release of dopamine and other monoamines from neuronal vesicles into the synapse. Valbenazine (NBI-98854), a novel compound that selectively inhibits VMAT2, is being developed for the treatment of tardive dyskinesia. Valbenazine is converted to two significant circulating metabolites in vivo, namely, (+)-α-dihydrotetrabenazine (R,R,R-DHTBZ) and a mono-oxy metabolite, NBI-136110. Radioligand binding studies were conducted to assess and compare valbenazine, tetrabenazine and their respective metabolites in their abilities to selectively and potently inhibit [(3)H]-DHTBZ binding to VMAT2 in rat striatal, rat forebrain, and human platelet homogenates...
April 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28404545/doxepin-inhibits-gpvi-dependent-platelet-ca-2-signaling-and-collagen-dependent-thrombus-formation
#15
Sascha Geue, Britta Walker-Allgaier, Daniela Eißler, Roland Tegtmeyer, Malte Schaub, Florian Lang, Meinrad Gawaz, Oliver Borst, Patrick Münzer
Platelet adhesion, activation and aggregation are essential for primary haemostasis, but are also critically involved in the development of acute arterial thrombotic occlusion. Stimulation of the collagen receptor glyocoprotein VI (GPVI) leads to PLCγ-dependent IP3 production with subsequent platelet activation, due to increased intracellular calcium concentration ([Ca(2+)]i). Although it has been described that tricyclic antidepressants potentially impair platelet activation, nothing is hitherto known about potential effects of the tricyclic antidepressant doxepin on platelet Ca(2+) signaling and thrombus formation...
April 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28403020/understanding-the-impact-of-preservation-methods-on-the-integrity-and-functionality-of-placental-allografts
#16
Amy Johnson, Alexandra Gyurdieva, Sandeep Dhall, Alla Danilkovitch, Yi Duan-Arnold
INTRODUCTION: Human placental membranes (hPMs) have a long history in treating burns and wounds. The composition of hPMs includes structural matrix, growth factors, and neonatal cells, all of which contribute to their regenerative potential. However, most hPM products are devitalized after dehydration and irradiation. We compared the functionality of single-layer viable cryopreserved human amniotic membrane (vCHAM) with multilayer devitalized dehydrated human amnion/chorion membrane (dHACM) in wound-relevant models to determine the effect of different processing methods on hPMs...
April 12, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28400314/peg-pe-clay-composite-carriers-for-doxorubicin-effect-of-composite-structure-on-release-cell-interaction-and-cytotoxicity
#17
Hagay Kohay, Can Sarisozen, Rupa Sawant, Aditi Jhaveri, Vladimir P Torchilin, Yael G Mishael
A novel drug delivery system for doxorubicin (DOX), based on organic-inorganic composites was developed. DOX was incorporated in micelles (M-DOX) of polyethylene glycol-phosphatidylethanolamine (PEG-PE) which in turn were adsorbed by the clay, montmorillonite (MMT). The nano-structures of the PEG-PE/MMT composites of LOW and HIGH polymer loadings were characterized by XRD, TGA, FTIR, size (DLS) and zeta measurements. These measurements suggest that for the LOW composite a single layer of polymer intercalates in the clay platelets and the polymer only partially covers the external surface, while for the HIGH composite two layers of polymer intercalate and a bilayer may form on the external surface...
April 8, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28400236/synthesis-antiplatelet-and-antithrombotic-activities-of-resveratrol-derivatives-with-no-donor-properties
#18
Luiz Antonio Dutra, Jéssica Frade O Guanaes, Nadine Johmann, Maria Elisa Lopes Pires, Chung Man Chin, Sisi Marcondes, Jean Leandro Dos Santos
Resveratrol (RVT) is a stilbene with a protective effect on the cardiovascular system; however, drawbacks including low bioavailability and fast metabolism limit its efficacy. In this work we described new resveratrol derivatives with nitric oxide (NO) release properties, ability to inhibit platelet aggregation and in vivo antithrombotic effect. Compounds (4a-f) were able to release NO in vitro, at levels ranging from 24.1% to 27.4%. All compounds (2a-f and 4a-f) have exhibited platelet aggregation inhibition using as agonists ADP, collagen and arachidonic acid...
April 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28396539/transcriptome-analysis-of-human-reninomas-as-an-approach-to-understanding-juxtaglomerular-cell-biology
#19
Alexandre G Martini, Lucie K Xa, Marie-Josée Lacombe, Alexis Blanchet-Cohen, Chantal Mercure, Benjamin Haibe-Kains, Edith C H Friesema, Anton H van den Meiracker, Kenneth W Gross, Michel Azizi, Pierre Corvol, Geneviève Nguyen, Timothy L Reudelhuber, A H Jan Danser
Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular cells of the kidney. Chronic stimulation of renin release results in a recruitment of new juxtaglomerular cells by the apparent conversion of adjacent smooth muscle cells along the afferent arterioles. Because juxtaglomerular cells rapidly dedifferentiate when removed from the kidney, their developmental origin and the mechanism that explains their phenotypic plasticity remain unclear...
April 10, 2017: Hypertension
https://www.readbyqxmd.com/read/28393518/enhancing-vascularization-through-the-controlled-release-of-platelet-derived-growth-factor-bb
#20
Silvia Minardi, Laura Pandolfi, Francesca Taraballi, Xin Wang, Enrica De Rosa, Zachary D Mills, Xuewu Liu, Mauro Ferrari, Ennio Tasciotti
Using delivery systems to control the in vivo release of growth factors (GFs) for tissue engineering applications is extremely desirable as the clinical use of GFs is limited by their fast in vivo turnover. Hence, the development of effective platforms that are able to finely control the release of GFs in vivo remains a challenge. Herein, we investigated the ability of multiscale microspheres, composed by a nanostructured silicon multistage vector (MSV) core and a poly(dl-lactide-co-glycolide) acid (PLGA) forming outer shell (PLGA-MSV), to release functional platelet-derived growth factor-BB (PDGF-BB) to induce in vivo localized neovascularization...
April 18, 2017: ACS Applied Materials & Interfaces
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