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An O-acetylated glucomannan from Bletilla striata: Structural characterization and ADP-dependent platelet-activating hemostatic activity.

Previous work demonstrated that crude Bletilla striata polysaccharides exhibited hemostatic effects against gastric bleeding through the activation of ADP pathway, whereas their key homogeneous active constituent remains structurally undefined. Herein, bioactivity-guided fractionation afforded a novel homogeneous polysaccharide BSP-60 (6271 Da), identified as the core hemostatic component. Differing markedly from all reported B. striata polysaccharide, BSP-60 consists of glucose (Glcp) and mannose (Manp) at a molar ratio of 1:1.88, featuring a linear unbranched chain of regularly alternating →

Mice with reduced protease-activated receptor 4 reactivity show decreased venous thrombosis and platelet procoagulant activity.

BACKGROUND: Hypercoagulation and thrombin generation are major risk factors for venous thrombosis. Sustained thrombin signaling through protease-activated receptor (PAR) 4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single nucleotide polymorphism in PAR4 (rs2227376) changes proline to leucine extracellular loop 3, which decreases PAR4 reactivity and is associated with a lower risk for venous thromboembolism (VTE) in a genome wide association studies meta-analysis. OBJECTIVES: The goal of this study was to determine the mechanism for the ass…

Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex.

The infrequent occurrence of septic shock in patients with inherited deficiencies of the terminal complement components experiencing meningococcal disease led us to suspect that the terminal complement complex is involved in vascular leakage. To this end, the permeabilizing effect of the cytolytically inactive soluble terminal complement complex (SC5b-9) was tested in a Transwell system measuring the amount of fluorescein-labeled BSA (FITC-BSA) leaked through a monolayer of endothelial cells. The complex caused increased permeability to FITC-BSA after 15 min as opposed to the prompt response t

Alloantibody IgG subclasses have differential activity in clearing transfused platelets in mice.

Platelet transfusion is a necessary life-sustaining therapy for extreme thrombocytopenia from multiple etiologies. However, refractoriness develops in some patients such that transfused platelets are rapidly cleared and refractory patients are at risk for catastrophic hemorrhage. One cause of refractoriness is humoral immunization to major histocompatibility complex I (MHC-I) alloantigens. However, ∼50% of patients with alloantibodies to MHC-I do not become refractory. The factors that determine whether an alloimmunized patient is refractory remain undefined. Both mice and humans encode 4 dist

Upregulation of coagulation pathway and enhanced platelet activity in hypoxia-exposed rat blood.

To investigate the effects of chronic hypoxia on platelet characteristics and overall coagulation function, and to elucidate the mechanisms underlying high-altitude-induced blood system disorders. Rats were exposed to chronic hypoxic conditions. Platelet counts were measured using routine blood analysis. Plasma levels of platelet activation markers (P-selectin and sCD40L) were quantified by ELISA. A label-free quantitative proteomic approach was employed to identify alterations in the platelet coagulation cascade proteome, with key findings validated by western blotting. Coagulation function w…

Коэффициент активации талонов при множественном склерозе: от периферической воспаления до центральной нейродегенерации.

Множественный склероз (MS) представляет собой хроническое воспалительное и нейродегенеративное заболевание, при котором периферическая иммунная активация, дисфункция мозгового барьера (BBB) и повреждение центральной нервной системы (CNS) тесно взаимосвязаны. Фактор активации талонов (PAF) является мощным посредником, занимающимся воспалением фосфолипида, активацией тромбоцитов, окислительным стрессом и нейронным сигналом. Повышение уровней PAF в плазме и цереброспиновой жидкости (CSF) пациентов с MS свидетельствует о их вовлеченности как в периферийные, так и в центральные процессы заболеваний

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease in which peripheral immune activation, blood-brain barrier (BBB) dysfunction, and central nervous system (CNS) injury are closely interconnected. Platelet-activating factor (PAF) is a potent phospholipid mediator involved in inflammation, platelet activation, oxidative stress, an…

Mitogen-activated protein kinase 1 regulates platelet function and thrombus formation.

BACKGROUND: Mitogen-activated protein kinase (MAPK)1 or ERK2 is a Ser/Thr kinase, and its inhibition by pharmacologic inhibitors attenuated platelet function. However, conflicting results for different inhibitors were obtained due to off-target effects. Moreover, whether MAPK1 affects platelet function is unknown. OBJECTIVES: This study intended to evaluate the role of MAPK1 in platelet activity and thrombus formation. METHODS: Megakaryocyte/platelet-specific MAPK1 knockout mice were generated and used to assess platelet aggregation, activation, procoagulant activity, spreading and clot retr

Clinical Values of Serum Platelet-Activating Factor in Hypertensive Disorders Complicating Pregnancy.

INTRODUCTION: Serum platelet-activating factor (PAF) was proven to be associated with gestational hypertension. However, the predictive value of serum PAF at early pregnancy for the occurrence and outcomes of hypertensive disorders complicating pregnancy (HDCP) remained unclear. METHODS: The demographic and clinical characteristics of patients were compared among the different subgroups. The serum PAF level was determined using an enzyme-linked immunosorbent assay. The predictive value of serum PAF for the occurrence and outcomes of HDCP was evaluated using receiver operating characteristic c

PTH-driven modulation of platelet activity via the NOX2 pathway in postsurgical hypoparathyroidism.

OBJECTIVE: Postsurgical chronic hypoparathyroidism (HypoPT) has been linked to an increased cardiovascular risk, but the underlying pathophysiological mechanisms remain incompletely understood. Emerging evidence suggests a potential direct role of parathyroid hormone (PTH) in modulating platelet function and oxidative stress, both contributors to atherothrombosis. Our study aimed to investigate the impact of PTH on platelet function and activation, with a particular focus on NOX2-mediated platelet activation in patients with HypoPT. METHODS: We conducted a cross-sectional study involving 24 p…

Flow cytometry for comprehensive assessment of platelet functional activity in response to ADP stimulation.

OBJECTIVES: Flow cytometry with adenosine diphosphate (ADP) allows to characterize molecular changes of platelet function caused by this physiologically important activation, but the methodology has not been thoroughly investigated, standardized and characterized yet. We analyzed the influence of several major variables and chose optimal conditions for platelet function assessment. METHODS: For activation, 2.5 μM CaCl2 , 5 μM ADP and antibodies were added to diluted blood and incubated for 15 min. We analyzed kinetics of antibody binding and effects of their addition sequence, agonist concent

Tramadol regulates the activation of human platelets via Rac but not Rho/Rho-kinase.

Tramadol is a useful analgesic which acts as a serotonin and noradrenaline reuptake inhibitor in addition to μ-opioid receptor agonist. Cytoplasmic serotonin modulates the small GTPase activity through serotonylation, which is closely related to the human platelet activation. We recently reported that the combination of subthreshold collagen and CXCL12 synergistically activates human platelets. We herein investigated the effect and the mechanism of tramadol on the synergistic effect. Tramadol attenuated the synergistically stimulated platelet aggregation (300 μM of tramadol, 64.3% decrease, p<…

Glucose-decorated engineering platelets for active and precise tumor-targeted drug delivery.

Precise targeted delivery of therapeutic agents is crucial for tumor therapy. As an emerging fashion, cell-based delivery provides better biocompatibility and lower immunogenicity and enables a more precise accumulation of drugs in tumor cells. In this study, a novel engineering platelet was constructed through cell membrane fusion with a synthesized glycolipid molecule, DSPE-PEG-Glucose (DPG). The obtained glucose-decorated platelets (DPG-PLs) maintained their resting state with structural and functional integrities, while they would be activated and triggered to release their payloads once t

Phenotypic Characterization of Acoustically Enriched Extracellular Vesicles from Pathogen-Activated Platelets.

Extracellular vesicles (EVs) are derived from the membrane of platelets and released into the circulation upon activation or injury. Analogous to the parent cell, platelet-derived EVs play an important role in hemostasis and immune responses by transfer of bioactive cargo from the parent cells. Platelet activation and release of EVs increase in several pathological inflammatory diseases, such as sepsis. We have previously reported that the M1 protein released from the bacterial pathogen Streptococcus pyogenes directly mediates platelet activation. In this study, EVs were isolated from these pa…

N-Stearoylethanolamine Inhibits Integrin-Mediated Activation, Aggregation, and Adhesion of Human Platelets.

N-stearoylethanolamine (NSE), a lipid mediator that belongs to the N-acylethanolamine (NAE) family, has anti-inflammatory, antioxidant, and … rinogen to GPIIb/IIIa on activated platelets. These effects could be explained by the inhibition of platelet activation mediated by integrin receptors: the GPIb-IX-V complex for ristocetin-induced activation and GPIIb/IIIa when epinephrine and low doses of ADP were applied. The anti-platelet effect of NSE complements its anti-inflammatory effect and allows us to prio …

Platelet-Activating Biominerals Enhanced Injectable Hydrogels With Superior Bioactivity for Bone Regeneration.

Refractory bone fracture, which is difficult to be treated, is a common clinical disease. Taking inspiration from the natural process of bone regeneration, we provide a biomimetic strategy to develop a new injectable biomaterial for repairing bone defects, which is mainly composed of platelets, fibrins, and biominerals. Biomineral nanoparticles (EACPNs) with an amorphous phase are prepared by an enzyme-catalyzed route and display a platelet-activating property. The composite hydrogel (EPH) of EACPNs, fibrins, and platelets is injectable, and has similar chemical properties to natural materials

Fibrin and Platelet-Rich Composition in Retrieved Thrombi Hallmarks Stroke With Active Cancer.

BACKGROUND AND PURPOSE: We aim to investigate whether histopathologic examination of thrombi retrieved from acute ischemic stroke patients undergoing endovascular treatment could distinguish cancer-related stroke from other etiologies. METHODS: Thrombi from patients undergoing endovascular treatment were analyzed. The etiology of stroke was divided into cardioembolism, large artery atherosclerosis, and active cancer groups. All selected thrombi were subjected to hematoxylin and eosin staining. The percentages of fibrin/platelets, red blood cells, and white blood cells within a thrombus were q

Platelet activating factor receptor acts to limit colitis-induced liver inflammation.

Liver inflammation is a common extraintestinal manifestation in inflammatory bowel disease (IBD), yet, the mechanisms driving gut-liver axis inflammation remain poorly understood. IBD leads to a breakdown in the integrity of the intestinal barrier causing an increase in portal and systemic gut-derived antigens, which challenge the liver. Here, we examined the role of platelet activating factor receptor (PAFR) in colitis-associated liver damage using dextran sulfate sodium (DSS) and anti-CD40-induced colitis models. Both DSS and anti-CD40 models exhibited liver inflammation associated with coli