Megakaryocyte- and erythroblast-specific cell-free DNA patterns in plasma and platelets reflect thrombopoiesis and erythropoiesis levels.

Circulating cell-free DNA (cfDNA) fragments are a biological analyte with extensive utility in diagnostic medicine. Understanding the source of cfDNA and mechanisms of release is crucial for designing and interpreting cfDNA-based liquid biopsy assays. Using cell type-specific methylation markers as well as genome-wide methylation analysis, we determine that megakaryocytes, the precursors of anuclear platelets, are major contributors to cfDNA (~26%), while erythroblasts contribute 1-4% of cfDNA in healthy individuals.

Integrin αβ-Targeted Self-Assembled Nanocarriers for Tumor Bioimaging.

Recent developments in near-infrared (NIR) dyes and imaging modalities enable tumor fluorescent images in preclinical and clinical settings. However, NIR dyes have several drawbacks, and therefore, there is an unmet diagnostic need for NIR dye encapsulation in appropriate pharmaceutical nanocarriers with targeting abilities for the purpose of achieving effective diagnosis and image-guided surgeries. Because integrin receptors are established diagnostic targets, the cyclic Arg-Gly-Asp (RGD) peptides, recognizing the αβ integrin, have been extensively investigated for radiology and bioimaging of tumors.

Bleeding Risk Assessment and the Role of Primary Hemostasis Screening in Patients Undergoing Kidney Biopsy.

Background: Risk factors for bleeding complications after percutaneous kidney biopsy (PKB) and the role of primary hemostasis screening are not well established.

Objectives: To determine the role of primary hemostasis screening and complication outcomes among individuals who underwent PKB.

Methods: We reviewed data of 456 patients who underwent PKB from 2010 to 2016 in a large university hospital.

Assessment of procoagulant potential in patients with reactive thrombocytosis and its association with platelet count.

Objective: We aimed to determine hemostatic changes and characterize the procoagulant potential among patients with reactive thrombocytosis (RT).

Methods: Sixty patients with RT (median platelet count 718 × 10 /L) and 20 healthy persons were tested for complete blood count, C-reactive protein, von Willebrand factor (VWF), factor VIII and fibrinogen, and thrombin generation. Platelet studies, including light transmission aggregometry and Cone and Plate(let) Analyzer, were also conducted.

Cisplatin-conjugated gold nanoparticles as a theranostic agent for head and neck cancer.

Background: The purpose of this study was to develop a nanoplatform, which simultaneously acts as radiosensitizer, drug carrier, and tumor imaging agent for head and neck cancer.

Methods: We synthesized 20 nm gold nanoparticles, coated with glucose and cisplatin (CG-GNPs). Their penetration into tumor cells and their cellular toxicity were evaluated in vitro.

A Multifunctional Biocompatible Drug Candidate is Highly Effective in Delaying Pathological Signs of Alzheimer's Disease in 5XFAD Mice.

Background: Metal-ion-chelation was suggested to prevent zinc and copper ions-induced amyloid-β (Aβ) aggregation and oxidative stress, both implicated in the pathophysiology of Alzheimer's disease (AD). In a quest for biocompatible metal-ion chelators potentially useful for AD therapy, we previously tested a series of nucleoside 5'-phosphorothioate derivatives as agents for decomposition of Cu(I)/Cu(II)/Zn(II)-Aβ-aggregates, and as inhibitors of OH radicals formation in Cu(I) or Fe(II) /H2O2 solution. Specifically, in our recent study we have identified 2-SMe-ADP(α-S), designated as SAS, as a most promising neuroprotectant.

The macromolecular architecture of platelet-derived microparticles.

Platelets are essential for hemostasis and wound healing. They are involved in fundamental processes of vascular biology such as angiogenesis, tissue regeneration, and tumor metastasis. Upon activation, platelets shed small plasma membrane vesicles termed platelet-derived microparticles (PMPs).

Platelets and their microparticles as key players in pathophysiological responses.

Platelets are known to play a central role in primary hemostasis as well as in the pathophysiology of thrombotic disorders. However, in addition to hemostasis, platelets are involved in a variety of pathophysiological responses including immune responses, inflammation, angiogenesis, tissue regeneration, and cancer metastasis. Recent studies revealed a significant role for platelet-derived microparticles (PMP), in these responses.

Differential impact of selective serotonin reuptake inhibitors on platelet response to clopidogrel: a randomized, double-blind, crossover trial.

Study Objective: To assess the effect of two selective serotonin reuptake inhibitors (SSRIs), fluvoxamine and citalopram, that markedly differ in their level of cytochrome P450 (CYP) 2C19 inhibition, on the laboratory response to clopidogrel, a prodrug requiring metabolism by the CYP system, and especially CYP2C19, to produce its active form.

Design: Randomized, double-blind, crossover trial.

Setting: Clinical research unit of an academic medical center.

A mouse model to study thrombotic complications of thalassemia.

Patients with β-thalassemia major and mainly intermedia have an increased risk for developing venous and arterial thrombosis which may be related to circulating pathological red blood cells (RBC) and continuous platelet activation. In the present study we used a modified thalassemic mice model in conjunction with a "real-time" carotid thrombus formation procedure to investigate thrombotic complications of thalassemia. Heterozygous Th3/+ mice, which lack one copy of their β-major and β-minor globin genes, exhibit anomalies in RBC size and shape, chronic anemia and splenomegaly which recapitulate the phenotype of human β-thalassemia intermedia.

Vipegitide: a folded peptidomimetic partial antagonist of α2β1 integrin with antiplatelet aggregation activity.

Linear peptides containing the sequence WKTSRTSHY were used as lead compounds to synthesize a novel peptidomimetic antagonist of α2β1 integrin, with platelet aggregation-inhibiting activity, named Vipegitide. Vipegitide is a 13-amino acid, folded peptidomimetic molecule, containing two α-aminoisobutyric acid residues at positions 6 and 8 and not stable in human serum. Substitution of glycine and tryptophan residues at positions 1 and 2, respectively, with a unit of two polyethylene glycol (PEG) molecules yielded peptidomimetic Vipegitide-PEG2, stable in human serum for over 3 hours.

Platelet lysates stimulate angiogenesis, neurogenesis and neuroprotection after stroke.

Platelets contain chemo-attractants and mitogens that have a major role in tissue repair. Therefore we hypothesised that tissue regeneration secondary to activation of endogenous neural stem cells (eNSC) can be enhanced by delivering platelets to the ischaemic brain. To examine these potential therapeutic effects we injected platelet-poor plasma (PPP), fibroblast growth factor (FGF2) and platelet lysate (PLT) to the lateral ventricles after permanent middle cerebral artery occlusion (PMCAO) in rats.

The oxidant-scavenging abilities in the oral cavity may be regulated by a collaboration among antioxidants in saliva, microorganisms, blood cells and polyphenols: a chemiluminescence-based study.

Saliva has become a central research issue in oral physiology and pathology. Over the evolution, the oral cavity has evolved the antioxidants uric acid, ascorbate reduced glutathione, plasma-derived albumin and antioxidants polyphenols from nutrients that are delivered to the oral cavity. However, blood cells extravasated from injured capillaries in gingival pathologies, or following tooth brushing and use of tooth picks, may attenuate the toxic activities of H2O2 generated by oral streptococci and by oxidants generated by activated phagocytes.

Identification of α2β1 integrin inhibitor VP-i with anti-platelet properties in the venom of Vipera palaestinae.

Integrins are receptors of the extracellular matrix (ECM), playing a vital role in pathophysiological processes. They bind to ECM ligands like collagens and can mediate wound healing as well as tumor metastasis and thrombosis, thus being a part of cell adhesion and migration as well as platelet aggregation. For this reason, identifying α2β1 integrin-specific antagonists can assist in the development of drugs to treat tumor progression, angiogenesis, and cardiovascular diseases.

The role of platelets and their microparticles in rehabilitation of ischemic brain tissue.

Stroke is a leading cause of mortality and chronic disability. Therapies aimed at reducing stroke related morbidity are currently limited. Therefore it is very important to develop effective treatments that will maximize rehabilitation after stroke.

Involvement of platelet derived microparticles in tumor metastasis and tissue regeneration.

Platelets play a major role in hemostasis, but are also involved in vascular biology processes such as angiogenesis and tumor metastasis. Activated platelets release many proteins favoring wound healing and promoting angiogenesis. Microparticles (MP) are small plasma membrane vesicles shed from cells upon their activation or apoptosis.

Identification of a promising drug candidate for the treatment of type 2 diabetes based on a P2Y(1) receptor agonist.

The activation by extracellular nucleotides of pancreatic P2Y receptors, particularly, the P2Y(1)R subtype, increases insulin secretion. Therefore, we developed analogues of the P2Y(1)R receptor agonist 2-MeS-ADP, as potential antidiabetic drugs. Analogue 3A was found to be a potent P2Y(1)R agonist (EC(50) = 0.

Platelet microparticles induce angiogenesis and neurogenesis after cerebral ischemia.

Activated platelets shed microparticles, which contain a variety of growth factors central to angiogenesis and neurogenesis. The aim of this study was to explore whether platelet derived microparticles (PMP) can boost endogenous neural stem cells dependent repair mechanisms following stroke in a rat model. To examine the effects of PMP therapy in-vivo, we delivered PMP or vehicle via a biodegradable polymer to the brain surface after permanent middle cerebral artery occlusion (PMCAO) in rats.

Comparative analysis of platelet-derived microparticles reveals differences in their amount and proteome depending on the platelet stimulus.

Platelet-derived microparticles (PMP) are elevated in a number of disorders (e.g. cardiovascular disease and cancer).

Platelet microparticles promote neural stem cell proliferation, survival and differentiation.

Platelet microparticles (PMP) are small subcellular fragments, shed upon platelet activation. PMP host a variety of cytokines and growth factor that were previously shown to affect angiogenesis and postischemic tissue regeneration. This study attempted to explore the effect of PMP on neural stem cell (NSC) proliferation, survival and differentiation.

Underdiagnosed menorrhagia in adolescents is associated with underdiagnosed anemia.

Objective: To test the hypothesis that adolescent girls with menorrhagia rarely seek medical attention.

Study Design: A total of 705 adolescent girls attended a lecture on menorrhagia, completed an initial anonymous questionnaire, and were asked to participate in a more comprehensive study comprising a detailed bleeding questionnaire, a pictorial blood loss assessment chart, and blood tests.

Results: A total of 105 adolescents (15%) reported they had heavy periods on the initial questionnaire.

Development, cell differentiation, angiogenesis--microparticles and their roles in angiogenesis.

Cells of various types release small membrane vesicles called microparticles (MP) on their activation, as well as during the process of apoptosis. The properties and roles of MP generated in different contexts are diverse and are determined by their parent cell and the pathway of their generation, which affects their content. MP are involved in multiple cellular functions, including immunomodulation, inflammation, coagulation, and intercellular communication.

Frontiers in platelet inhibition.

Anti-platelet drugs play a key role in cardiovascular medicine since the introduction of aspirin as an anti-thrombotic agent some 50 years ago. After many years of a "monopoly" of aspirin, ADP receptor P2Y12 inhibitors were introduced with a significant improvement in clinical outcome. Nowadays dual anti-platelet therapy is the common practice for both acute events and secondary prevention in selected groups of patients.