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Platelet Proteomics

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https://www.readbyqxmd.com/read/29449599/red-blood-cells-are-dynamic-reservoirs-of-cytokines
#1
Elisabeth Karsten, Edmond Breen, Benjamin R Herbert
Red blood cells (RBCs) have been shown to affect immune function and can induce inflammatory responses after transfusion. The transfusion of washed RBCs can significantly reduce adverse effects, however, the soluble factors that may mediate these effects have not been identified. Previous studies have identified, but not quantified, a small number of chemokines associated with RBCs. We isolated RBCs from healthy volunteers and quantified of a panel of 48 cytokines, chemokines, and growth factors in the lysate, cytosol, and conditioned media of these cells using Luminex ® technology...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29432918/exploration-of-the-platelet-proteome-in-patients-with-early-stage-cancer
#2
Siamack Sabrkhany, Marijke J E Kuijpers, Jaco C Knol, Steven W M Olde Damink, Anne-Marie C Dingemans, Henk M Verheul, Sander R Piersma, Thang V Pham, Arjan W Griffioen, Mirjam G A Oude Egbrink, Connie R Jimenez
Platelets play an important role in tumor growth and, at the same time, platelet characteristics are affected by cancer presence. Therefore, we investigated whether the platelet proteome harbors differentially expressed proteins associated with early-stage cancer. For this proof-of-concept study, patients with early-stage lung (n = 8) or head of pancreas cancer (n = 4) were included, as were healthy sex- and age-matched controls for both subgroups. Blood samples were collected from controls and from patients before surgery...
February 9, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29427073/dissecting-the-biochemical-architecture-and-morphological-release-pathways-of-the-human-platelet-extracellular-vesiculome
#3
Silvia H De Paoli, Tseday Z Tegegn, Oumsalama K Elhelu, Michael B Strader, Mehulkumar Patel, Lukas L Diduch, Ivan D Tarandovskiy, Yong Wu, Jiwen Zheng, Mikhail V Ovanesov, Abdu Alayash, Jan Simak
Platelet extracellular vesicles (PEVs) have emerged as potential mediators in intercellular communication. PEVs exhibit several activities with pathophysiological importance and may serve as diagnostic biomarkers. Here, imaging and analytical techniques were employed to unveil morphological pathways of the release, structure, composition, and surface properties of PEVs derived from human platelets (PLTs) activated with the thrombin receptor activating peptide (TRAP). Based on extensive electron microscopy analysis, we propose four morphological pathways for PEVs release from TRAP-activated PLTs: (1) plasma membrane budding, (2) extrusion of multivesicular α-granules and cytoplasmic vacuoles, (3) plasma membrane blistering and (4) "pearling" of PLT pseudopodia...
February 9, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29421274/autonomous-role-of-wiskott-aldrich-syndrome-platelet-deficiency-in-inducing-autoimmunity-and-inflammation
#4
Lucia Sereni, Maria Carmina Castiello, Francesco Marangoni, Achille Anselmo, Dario di Silvestre, Sara Motta, Elena Draghici, Stefano Mantero, Adrian J Thrasher, Silvia Giliani, Alessandro Aiuti, Pierluigi Mauri, Luigi D Notarangelo, Marita Bosticardo, Anna Villa
BACKGROUND: Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency characterized by eczema, infections and susceptibility to develop autoimmunity and malignancies. Thrombocytopenia is a constant finding, but its pathogenesis remains elusive. OBJECTIVE: To dissect the basis of WAS platelet (PLT) defect we used a novel conditional mouse model (CoWas) lacking WASp only in the megakaryocytic lineage in presence of a normal immunological environment and in parallel we analysed samples obtained from WAS patients...
February 5, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29405767/assessment-of-oxidative-stress-of-platelets-among-chronic-heroin-and-hashish-addicts
#5
M A Bani-Ahmad, A G Mustafa, Aab Ahmad, Ama Rahim
INTRODUCTION: Illicit drugs abuse is associated with several clinical life-threatening consequences that are primarily mediated by oxidative damage to multiple cellular components with a subsequent cellular dysfunction and death. Primarily, this study aimed to investigate oxidative stress to protein and lipid components of circulatory platelets among chronic heroin and hashish addicts. METHODS: Platelet lysates were prepared from 20 chronic intravenously administrated heroin addicts and 20 chronic smoked hashish addicts...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29389080/identification-of-host-response-in-cerebral-malaria-patients-using-quantitative-proteomic-analysis
#6
Manish Kumar, Chakrakodi N Varun, Gourav Dey, Raju Ravikumar, Anita Mahadevan, Susarla Krishna Shankar, T S Keshava Prasad
PURPOSE: The objective of this study was to study the altered proteome in the frontal lobe of patients with CM. Unbiased analysis of differentially abundant proteins could lead to identification of host responses against P. falciparum infection, which will aid in better understanding of the molecular mechanism of pathophysiology in CM. EXPERIMENTAL DESIGN: We employed TMT-based quantitative proteomic analysis using high-resolution mass spectrometry. In brief, proteins were isolated from frontal lobe samples, which were collected at autopsy from three cases of CM and three control subjects...
February 1, 2018: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29385765/pharmacogenomic-impact-of-cyp2c19-variation-on-clopidogrel-therapy-in-precision-cardiovascular-medicine
#7
REVIEW
Sherry-Ann Brown, Naveen Pereira
Variability in response to antiplatelet therapy can be explained in part by pharmacogenomics, particularly of the CYP450 enzyme encoded by CYP2C19. Loss-of-function and gain-of-function variants help explain these interindividual differences. Individuals may carry multiple variants, with linkage disequilibrium noted among some alleles. In the current pharmacogenomics era, genomic variation in CYP2C19 has led to the definition of pharmacokinetic phenotypes for response to antiplatelet therapy, in particular, clopidogrel...
January 30, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29378352/atherothrombosis-and-thromboembolism-position-paper-from-the-second-maastricht-consensus-conference-on-thrombosis
#8
H M H Spronk, T Padro, J E Siland, J H Prochaska, J Winters, A C van der Wal, J J Posthuma, G Lowe, E d'Alessandro, P Wenzel, D M Coenen, P H Reitsma, W Ruf, R H van Gorp, R R Koenen, T Vajen, N A Alshaikh, A S Wolberg, F L Macrae, N Asquith, J Heemskerk, A Heinzmann, M Moorlag, N Mackman, P van der Meijden, J C M Meijers, M Heestermans, T Renné, S Dólleman, W Chayouâ, R A S Ariëns, C C Baaten, M Nagy, A Kuliopulos, J J Posma, P Harrison, M J Vries, H J G M Crijns, E A M P Dudink, H R Buller, Y M C Henskens, A Själander, S Zwaveling, O Erküner, J W Eikelboom, A Gulpen, F E C M Peeters, J Douxfils, R H Olie, T Baglin, A Leader, U Schotten, B Scaf, H M M van Beusekom, L O Mosnier, L van der Vorm, P Declerck, M Visser, D W J Dippel, V J Strijbis, K Pertiwi, A J Ten Cate-Hoek, H Ten Cate
Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1...
February 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29369476/platelets-contribute-to-the-initiation-of-colitis-associated-cancer-by-promoting-immunosuppression
#9
L Servais, O Wéra, J Dibato Epoh, C Delierneux, N Bouznad, S Rahmouni, G Mazzucchelli, D Baiwir, P Delvenne, P Lancellotti, C Oury
BACKGROUND: Clinical and experimental evidence support a role for inflammation in the development of colorectal cancer, though the mechanisms are not fully understood. Beyond thrombosis and hemostasis, platelets are key actors of inflammation; they also have been involved in cancer. However, whether platelets participate in the link between inflammation and cancer is unknown. OBJECTIVE: To investigate the contribution of platelets and platelet-derived proteins to inflammation-elicited colorectal tumor development...
January 25, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29360642/tie2-protects-the-vasculature-against-thrombus-formation-in-systemic-inflammation
#10
Sarah J Higgins, Karen De Ceunynck, John Kellum, Xiuying Chen, Xuesong Gu, Sharjeel A Chaudhry, Sol Schulman, Towia A Libermann, Shulin Lu, Nathan I Shapiro, David C Christiani, Robert Flaumenhaft, Samir M Parikh
Disordered coagulation contributes to death in sepsis and lacks effective treatments. Existing markers of disseminated intravascular coagulation (DIC) reflect its sequelae rather than its causes, delaying diagnosis and treatment. Here we show that disruption of the endothelial Tie2 axis is a sentinel event in septic DIC. Proteomics in septic DIC patients revealed a network involving inflammation and coagulation with the Tie2 antagonist, Angiopoietin-2 (Angpt-2), occupying a central node. Angpt-2 was strongly associated with traditional DIC markers including platelet counts, yet more accurately predicted mortality in two large independent cohorts (combined N = 1077)...
January 23, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29340032/c3g-promotes-a-selective-release-of-angiogenic-factors-from-activated-mouse-platelets-to-regulate-angiogenesis-and-tumor-metastasis
#11
Víctor Martín-Granado, Sara Ortiz-Rivero, Rita Carmona, Sara Gutiérrez-Herrero, Mario Barrera, Laura San-Segundo, Celia Sequera, Pedro Perdiguero, Francisco Lozano, Francisco Martín-Herrero, José Ramón González-Porras, Ramón Muñoz-Chápuli, Almudena Porras, Carmen Guerrero
Previous observations indicated that C3G (RAPGEF1) promotes α-granule release, evidenced by the increase in P-selectin exposure on the platelet surface following its activation. The goal of the present study is to further characterize the potential function of C3G as a modulator of the platelet releasate and its implication in the regulation of angiogenesis. Proteomic analysis revealed a decreased secretion of anti-angiogenic factors from activated transgenic C3G and C3G∆Cat platelets. Accordingly, the secretome from both transgenic platelets had an overall pro-angiogenic effect as evidenced by an in vitro capillary-tube formation assay with HUVECs (human umbilical vein endothelial cells) and by two in vivo models of heterotopic tumor growth...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29323256/splicing-of-platelet-resident-pre-mrnas-upon-activation-by-physiological-stimuli-results-in-functionally-relevant-proteome-modifications
#12
Giovanni Nassa, Giorgio Giurato, Giovanni Cimmino, Francesca Rizzo, Maria Ravo, Annamaria Salvati, Tuula A Nyman, Yafeng Zhu, Mattias Vesterlund, Janne Lehtiö, Paolo Golino, Alessandro Weisz, Roberta Tarallo
Platelet activation triggers thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. Current therapies still fail to prevent thrombotic events in numerous patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how megakaryocyte-derived mRNAs are regulated in these anucleate cell fragments. Proteogenomics was applied here to investigate this phenomeon in platelets activated in vitro with Collagen or Thrombin Receptor Activating Peptide...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317355/identification-of-candidate-serum-biomarkers-of-childhood-onset-growth-hormone-deficiency-using-swath-ms-and-feature-selection
#13
Ignacio Ortea, Isabel Ruiz-Sánchez, Ramón Cañete, Javier Caballero-Villarraso, María Dolores Cañete
A typical clinical manifestation of growth hormone deficiency (GHD) is a short stature resulting from delayed growth, but GHD affects bone health, cardiovascular function and metabolic profile and therefore quality of life. Although early GH treatment during childhood has been shown to improve outcomes, no single biochemical parameter is currently available for the accurate diagnosis of GHD in children. There is hence a need for non-invasive biomarkers. In this study, the relative abundance of serum proteins from GHD children and healthy controls was measured by next-generation proteomics SWATH-MS technology...
January 6, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29304526/thromboelastometry-and-platelet-function-during-acclimatization-to-high-altitude
#14
Alistair S Rocke, Gordon G Paterson, Matthew T Barber, Alexander I R Jackson, Shona Main, Calum Stannett, Martin F Schnopp, J Kenneth Baillie, Elizabeth H Horne, Carl Moores, Paul Harrison, Alastair F Nimmo, A A Roger Thompson
Interaction between hypoxia and coagulation is important given the increased risk of thrombotic diseases in chronically hypoxic patients who reside at sea level and in residents at high altitude. Hypoxia alters the proteome of platelets favouring a prothrombotic phenotype, but studies of activation and consumption of specific coagulation factors in hypoxic humans have yielded conflicting results. We tested blood from 63 healthy lowland volunteers acclimatizing to high altitude (5,200 m) using thromboelastometry and assays of platelet function to examine the effects of hypoxia on haemostasis...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29278785/gender-related-increase-of-tropomyosin-1-abundance-in-platelets-of-alzheimer-s-disease-and-mild-cognitive-impairment-patients
#15
Christina Maria Reumiller, Georg Johannes Schmidt, Ina Dhrami, Ellen Umlauf, Eduard Rappold, Maria Zellner
The incidence of Alzheimer's disease (AD) is higher in elderly women than in men. The molecular background for this gender-related risk, however, is largely unknown. In a previous proteomics study we identified significantly elevated levels of monoamine oxidase-B and tropomyosin-1 in AD patients together with significant changes of the genetic AD risk factors apolipoprotein E4 (APOE4) and glutathione S-transferase omega 1 (GSTO1) in platelets - a promising source for AD blood biomarkers. The present study aimed to investigate the gender-specificity as well as disease-stage dependency of these biomarkers in AD patients and those with mild cognitive impairment (MCI)...
December 23, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29274201/itraq-based-proteomic-analysis-reveals-protein-profile-in-plasma-from-children-with-autism
#16
Liming Shen, Kaoyuan Zhang, Chengyun Feng, Youjiao Chen, Shuiming Li, Javed Iqbal, Liping Liao, Yuxi Zhao, Jian Zhai
PURPOSE: Autism is a childhood neurological disorder with poorly understood etiology and pathology. This study is designed to identify differentially expressed proteins which might serve as potential biomarkers for autism. EXPERIMENTAL DESIGN: We performed iTRAQ (isobaric tags for relative and absolute quantitation) analysis for normal and autistic children's plasma of the same age group. RESULTS: The results showed that 24 differentially expressed proteins were identified between autistic subjects and controls...
December 23, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29242851/in-depth-ptdins-3-4-5-p3-signalosome-analysis-identifies-dapp1-as-a-negative-regulator-of-gpvi-driven-platelet-function
#17
Tom N Durrant, James L Hutchinson, Kate J Heesom, Karen E Anderson, Len R Stephens, Phillip T Hawkins, Aaron J Marshall, Samantha F Moore, Ingeborg Hers
The class I phosphoinositide 3-kinase (PI3K) isoforms play important roles in platelet priming, activation, and stable thrombus formation. Class I PI3Ks predominantly regulate cell function through their catalytic product, the signaling phospholipid phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3], which coordinates the localization and/or activity of a diverse range of binding proteins. Notably, the complete repertoire of these class I PI3K effectors in platelets remains unknown, limiting mechanistic understanding of class I PI3K-mediated control of platelet function...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29211968/men-and-women-differ-in-the-biochemical-composition-of-platelet-rich-plasma
#18
Grace Xiong, Nithya Lingampalli, Jayme C B Koltsov, Lawrence L Leung, Nidhi Bhutani, William H Robinson, Constance R Chu
BACKGROUND: Autologous platelet-rich plasma (PRP) is widely used for a variety of clinical applications. However, clinical outcome studies have not consistently shown positive effects. The composition of PRP differs based on many factors. An improved understanding of factors influencing the composition of PRP is important for the optimization of PRP use. HYPOTHESIS: Age and sex influence the PRP composition in healthy patients. STUDY DESIGN: Controlled laboratory study...
February 2018: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/29182335/the-proteomic-landscape-of-patient-derived-cd4-t-cells-in-recent-onset-type-1-diabetes
#19
Marlen F Lepper, Uli Ohmayer, Christine von Toerne, Nicole Maison, Anette-Gabriele Ziegler, Stefanie M Hauck
The pathophysiology underlying the autoimmune disease type 1 diabetes (T1D) is poorly understood. Obtaining an accurate proteomic profile of the T helper cell population is essential for understanding the pathogenesis of T1D. Here, we performed in-depth proteomic profiling of peripheral CD4+ T cells in a pediatric cohort in order to identify cellular signatures associated with the onset of T1D. Using only 250,000 CD4+ T cells per patient, isolated from biobanked PBMC samples, we identified nearly 6,000 proteins using deep-proteome profiling with LC-MS/MS data-independent acquisition...
November 28, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29167233/granzyme-a-in-human-platelets-regulates-the-synthesis-of-proinflammatory-cytokines-by-monocytes-in-aging
#20
Robert A Campbell, Zechariah Franks, Anish Bhatnagar, Jesse W Rowley, Bhanu K Manne, Mark A Supiano, Hansjorg Schwertz, Andrew S Weyrich, Matthew T Rondina
Dysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream cytokine synthesis in aging remains poorly understood. Platelets and monocytes were isolated from healthy younger (age <45, n = 37) and older (age ≥65, n = 30) adults and incubated together under autologous and nonautologous conditions. Synthesis of inflammatory cytokines by monocytes, alone or in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging...
November 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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