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Platelet activating factor

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https://www.readbyqxmd.com/read/28528433/hydrolysis-of-phosphatidylcholine-isoprostanes-ptdcho-ip-by-peripheral-human-group-iia-v-and-x-secretory-phospholipases-a2-spla2
#1
Arnis Kuksis, Waldemar Pruzanski
Biologically active F- and E/D-type-prostane ring isomers (F2-IP and E2/D2-IP, respectively) are produced in situ by non-enzymatic peroxidation of arachidonic acid esterified to GroPCho (PtdCho-IP) and are universally distributed in tissue lipoproteins and cell membranes. Previous work has shown that platelet-activating factor acetylhydrolases (PAF-AH) are the main endogenous PLA2 involved in degradation of PtdCho-IP. The present study shows that the PtdCho-IP are also subject to hydrolysis by group IIA, V and X secretory PLA2, which also have a wide peripheral tissue distribution...
May 20, 2017: Lipids
https://www.readbyqxmd.com/read/28527913/von-willebrand-factor-deficiency-reduces-liver-fibrosis-in-mice
#2
Nikita Joshi, Anna K Kopec, Jessica L Ray, Holly Cline-Fedewa, Dafna J Groeneveld, Ton Lisman, James P Luyendyk
Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet-adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general population, the role of VWF in acute and chronic liver injury has not been examined in depth in experimental settings. We tested the hypothesis that VWF deficiency inhibits experimental liver injury and fibrosis. Wild-type (WT) and VWF-deficient mice were challenged with carbon tetrachloride (CCl4) and the impact of VWF deficiency on acute liver injury and chronic liver fibrosis was determined...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28527393/a-combination-of-platelet-features-allows-detection-of-early-stage-cancer
#3
Siamack Sabrkhany, Marijke J E Kuijpers, Sander M J van Kuijk, Linda Sanders, Sharo Pineda, Steven W M Olde Damink, Anne-Marie C Dingemans, Arjan W Griffioen, Mirjam G A Oude Egbrink
BACKGROUND: Detection of early-stage cancer significantly improves patient survival. As platelets play an important role in cancer progression, we aimed to investigate whether platelets can be used for the discovery of early-stage cancer. METHODS: Patients with lung (n = 86) or head of pancreas (n = 42) cancer were included, as were healthy sex- and age-matched controls (n = 92). Blood was collected before initiation of treatment. Platelet count, volume and activation status were quantified in whole blood...
May 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28526707/s-nitrosylation-of-vasp-at-cysteine-64-mediates-inflammation-stimulated-increase-in-microvascular-permeability
#4
Patricia Zamorano, Natalie Marin, Francisco Córdova, Alejandra Aguilar, Cynthia J Meininger, Mauricio P Boric, Nikola Golenhofen, Jorge Contreras, José Sarmiento, Walter N Duran, Fabiola A Sánchez
We tested the hypothesis that platelet-activating factor (PAF) induces S-nitrosylation of vasodilator-stimulated phosphoprotein (VASP) as a mechanism to reduce microvascular endothelial barrier integrity and stimulate hyperpermeability. PAF elevated S-nitrosylation of VASP above baseline levels in different endothelial cells and caused hyperpermeability. To ascertain the importance of eNOS subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX)...
May 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28526409/expression-and-purification-of-functional-pdgf-receptor-beta
#5
Qingbin Shang, Liang Zhao, Xiaojing Wang, Meimei Wang, Sen-Fang Sui, Li-Zhi Mi
Platelet Derived Growth Factor receptors (PDGFRs), members of receptor tyrosine kinase superfamily, play essential roles in early hematopoiesis, angiogenesis and organ development. Dysregulation of PDGF receptor signaling under pathological conditions associates with cancers, vascular diseases, and fibrotic diseases. Therefore, they are attractive targets in drug development. Like any other membrane proteins with a single-pass transmembrane domain, the high-resolution structural information of the full-length PDGF receptors is still not resolved...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526067/the-chimeric-monoclonal-antibody-mhcsz-123-against-human-von-willebrand-factor-a3-domain-inhibits-high-shear-arterial-thrombosis-in-a-rhesus-monkey-model
#6
Shundong Ji, Miao Jiang, Bin Yan, Fei Shen, Yang He, Aini Wan, Lijun Xia, Changgeng Ruan, Yiming Zhao
BACKGROUND: SZ-123, a murine monoclonal antibody that targets the human von Willebrand factor (VWF) A3 domain and blocks the binding of collagen, is a powerful antithrombotic. In a Rhesus monkey model of thrombosis, SZ-123 had no side effects, such as bleeding or thrombocytopenia. METHODS: The mouse/human chimeric version of SZ-123, MHCSZ-123, was developed and maintained inhibitory capacities in vitro and ex vivo after injection into monkeys. CHO-S cells were selected for stable expression of MHCSZ-123...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28523822/development-of-a-novel-flow-cytometric-immunobead-array-to-quantify-vwf-ag-and-vwf-gpibr-and-its-application-in-acute-myocardial-infarction
#7
Bin Yan, Mengqiao Xu, Yunxiao Zhao, Haijun Guo, Lijun Xia, Changgeng Ruan, Yiming Zhao
OBJECTIVES: Both von Willebrand disease (VWD) and acute myocardial infarction (AMI) involve quantitative and qualitative changes in von Willebrand factor (VWF). Our objective was to develop a rapid and precise flow cytometric immunobead array (FCIA) to quantify VWF antigen (VWF:Ag) and ristocetin-triggered platelet glycoprotein Ib binding (VWF:GPIbR), and apply it in a clinical setting. METHODS: Microbeads, coated with monoclonal antibodies for SZ29 or SZ151 IgG, were incubated with diluted plasma...
May 18, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28521243/shikonin-alleviates-allergic-airway-remodeling-by-inhibiting-the-erk-nf-%C3%AE%C2%BAb-signaling-pathway
#8
Tian-Yue Wang, Qian-Lan Zhou, Miao Li, Yun-Xiao Shang
Shikonin is a naphthoquinone extracted from the root of Lithospermum erythrorhizon, and has been reported to suppress allergic airway inflammation in mice. However, the underlying mechanisms are unclear and need to be further elucidated. In this study, shikonin (0.5, 2 or 4mg/kg) was given intraperitoneally to ovalbumin (OVA)-challenged BALB/c mice. We found that the pathological airway remodeling of asthmatic mice was alleviated by shikonin, and the infiltrated inflammatory cells and collagen deposition in their lungs were reduced...
May 15, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28516512/defective-%C3%AE-2-antiplasmin-cross-linking-and-thrombus-stability-in-a-case-of-acquired-factor-xiii-deficiency
#9
Joanne L Mitchell, Sonja Wright, Sajida Kazi, Henry G Watson, Nicola J Mutch
Acquired factor XIII (FXIII) deficiency is a rare and life-threatening condition that is often misdiagnosed or missed completely. A 72-year-old woman presented with symptoms of major unprovoked bleeding but routine coagulation screening tests and platelet count were normal. Low activated FXIII (FXIIIa) activity levels and abnormal urea clot stability led to diagnosis of acquired FXIII deficiency. A modified Bethesda inhibitor titre of 1.6 Bethesda units/ml indicated the presence of a FXIII inhibitor. Bleeding responded to a single dose of FXIII concentrate and immunosuppression with prednisolone induced remission...
May 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28515093/circulating-soluble-p-selectin-must-dimerize-to-promote-inflammation-and-coagulation-in-mice
#10
Sumith R Panicker, Padmaja Mehta-D'souza, Nan Zhang, Arkadiusz G Klopocki, Bojing Shao, Rodger P McEver
Leukocyte adhesion to P-selectin on activated platelets and endothelial cells induces shedding of the P-selectin ectodomain into the circulation. Plasma soluble P-selectin (sP-selectin) is elevated 3-4-fold in patients with cardiovascular disease. Circulating sP-selectin is thought to trigger signaling in leukocytes that directly contributes to inflammation and thrombosis. However, sP-selectin likely circulates as a monomer, and in vitro studies suggest that sP-selectin must dimerize to induce signaling in leukocytes...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28514863/surface-dependent-contact-activation-of-factor-xii-and-blood-plasma-coagulation-induced-by-mixed-thiol-surfaces
#11
James W Bauer, Li-Chong Xu, Erwin A Vogler, Christopher A Siedlecki
Studies of the activation of FXII in both platelet poor plasma and in neat buffer solutions were undertaken for a series of mixed thiol self-assembled monolayers spanning a broad range of water wettability. A wide spectrum of carboxyl/methyl-, hydroxyl/methyl-, and amine/methyl-thiol modified surfaces were prepared, characterized, and then utilized as the procoagulant materials in a series of FXII activation studies. X-ray photoelectron spectroscopy was utilized to verify the sample surface's thiol composition and contact angles measured to determine the sample surface's wettability...
May 17, 2017: Biointerphases
https://www.readbyqxmd.com/read/28514643/yorkie-regulates-epidermal-wound-healing-in-drosophila-larvae-independently-of-cell-proliferation-and-apoptosis
#12
Chang-Ru Tsai, Aimee E Anderson, Sirisha Burra, Juyeon Jo, Michael J Galko
Yorkie (Yki), the transcriptional co-activator of the Hippo signaling pathway, has well-characterized roles in balancing apoptosis and cell division during organ growth control. Yki is also required in diverse tissue regenerative contexts. In most cases this requirement reflects its well-characterized roles in balancing apoptosis and cell division. Whether Yki has repair functions outside of the control of cell proliferation, death, and growth is not clear. Here we show that Yki and Scalloped (Sd) are required for epidermal wound closure in the Drosophila larval epidermis...
May 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28513821/platelets-in-sepsis-are-there-any-new-aspects
#13
Małgorzata Lipinska-Gediga
Platelets display a number of properties besides the crucial function of repairing a damaged vascular endothelium and stopping bleeding. Platelets constitutively express molecules that are classically acknowledged to function in primary haemostasis. Platelets specialize in pro-inflammatory activities, and can secrete a large number of molecules, many of which display biological response modifier functions. Recently, platelets expressing receptors for infectious and possibly non-infectious danger signals were shown to be involved in pathophysiological reactions including an immune-inflammatory response...
May 17, 2017: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/28511645/therapeutic-potential-of-tas-115-via-c-met-and-pdgfr%C3%AE-signal-inhibition-for-synovial-sarcoma
#14
Shutaro Yamada, Yoshinori Imura, Takaaki Nakai, Sho Nakai, Naohiro Yasuda, Keiko Kaneko, Hidetatsu Outani, Satoshi Takenaka, Kenichiro Hamada, Akira Myoui, Nobuhito Araki, Takafumi Ueda, Kazuyuki Itoh, Hideki Yoshikawa, Norifumi Naka
BACKGROUND: The prognosis of synovial sarcoma (SS), an aggressive soft tissue sarcoma, remains poor. We previously reported that c-MET or platelet-derived growth factor receptor α (PDGFRα) signalling pathway is related to SS progression based upon the findings of phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs. Here we aimed to investigate the therapeutic potential of TAS-115 against SS...
May 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28509340/prf-based-matrices-to-improve-angiogenesis-in-an-in-vitro-co-culture-model-for-bone-tissue-engineering
#15
Eva Dohle, Karima El Bagdadi, Robert Sader, Joseph Choukroun, C James Kirkpatrick, Shahram Ghanaati
In the context of prevascularization strategies for tissue engineering purposes, co-culture systems consisting of outgrowth endothelial cells (OECs) and primary osteoblasts (pOBs) have been established as a promising in vitro tool to study regeneration mechanisms and to identify factors that might positively influence repair processes like wound healing or angiogenesis. The development of autologous injectable platelet rich fibrin (PRF), which can be generated from peripheral blood in a minimal invasive procedure, fulfils several requirements for clinically applicable cell-based tissue engineering strategies...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28508859/plastic-roles-of-pericytes-in-the-blood-retinal-barrier
#16
Do Young Park, Junyeop Lee, Jaeryung Kim, Kangsan Kim, Seonpyo Hong, Sangyeul Han, Yoshiaki Kubota, Hellmut G Augustin, Lei Ding, Jin Woo Kim, Hail Kim, Yulong He, Ralf H Adams, Gou Young Koh
The blood-retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507166/matrix-stiffness-regulates-migration-of-human-lung-fibroblasts
#17
Shuichi Asano, Satoru Ito, Kota Takahashi, Kishio Furuya, Masashi Kondo, Masahiro Sokabe, Yoshinori Hasegawa
In patients with pulmonary diseases such as idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome, progressive pulmonary fibrosis is caused by dysregulated wound healing via activation of fibroblasts after lung inflammation or severe damage. Migration of fibroblasts toward the fibrotic lesions plays an important role in pulmonary fibrosis. Fibrotic tissue in the lung is much stiffer than normal lung tissue. Emerging evidence supports the hypothesis that the stiffness of the matrix is not only a consequence of fibrosis, but also can induce fibroblast activation...
May 2017: Physiological Reports
https://www.readbyqxmd.com/read/28506734/mtor-vegf-pdgfr-and-c-kit-signaling-pathway-activation-in-kaposi-sarcoma
#18
Darcy A Kerr, Satya Vara Prasad Busarla, Devon C Gimbel, Aliyah R Sohani, Rosalynn M Nazarian
Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (n=274), most (90%) associated with human immunodeficiency virus (HIV)...
May 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28504693/cyclin-dependent-kinase-7-is-a-therapeutic-target-in-high-grade-glioma
#19
S A Greenall, Y C Lim, C B Mitchell, K S Ensbey, B W Stringer, A L Wilding, G M O'Neill, K L McDonald, D J Gough, B W Day, T G Johns
High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the tumors unresponsive or able to adapt to therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient-derived primary HGG cell lines and ex vivo HGG patient tissue slices, using proliferation assays, microarray analysis, high-resolution respirometry, cell cycle analysis and in vivo tumor orthografts...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28503993/dual-inhibition-of-pi3k-and-mtor-by-vs-5584-suppresses-thrombus-formation
#20
Thomas Später, Isabelle Müller, Hermann Eichler, Michael D Menger, Matthias W Laschke, Emmanuel Ampofo
VS-5584 is a highly selective dual kinase inhibitor which suppresses phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) activity. Because these kinases are crucially involved in primary hemostasis, we herein investigated the effect of this compound on thrombus formation in vitro and in vivo. Pretreatment of washed platelets (WP) or platelet-rich plasma (PRP) with VS-5584 inhibited the agonist-induced activation of surface glycoprotein complex (GP)IIb/IIIa and the upregulation of P-selectin...
May 15, 2017: Platelets
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