Assay variables and early clinical evaluation of low-angle light scattering for platelet function analysis.

Introduction: The recently developed platelet aggregation technique based on low-angle light scattering (LaSca) in diluted platelet-rich plasma (PRP) requires only a small sample volume and provides information about platelet aggregation and shape change. This study aimed to investigate the influence of preanalytical and analytical variables and to validate the method in a real-life pediatric hematology hospital setting.

Methods: Platelet aggregation was induced by ADP in diluted PRP in the presence of 2 mM calcium at 23 °C.

Cisplatin Resistance and Metabolism: Simplification of Complexity.

Cisplatin is one of the most well-known anti-cancer drugs and has demonstrated efficacy against numerous tumor types for many decades. However, a key challenge with cisplatin, as with any chemotherapeutic agent, is the development of resistance with a resultant loss of efficacy. This resistance is often associated with metabolic alterations that allow insensitive cells to divide and survive under treatment.

Chloride Gradient Is Involved in Ammonium Influx in Human Erythrocytes.

The ammonia/ammonium (NH/NH, AM) concentration in human erythrocytes (RBCs) is significantly higher than in plasma. Two main possible mechanisms for AM transport, including simple and facilitated diffusion, are described; however, the driving force for AM transport is not yet fully characterized. Since the erythroid ammonium channel RhAG forms a structural unit with anion exchanger 1 (eAE1) within the ankyrin core complex, we hypothesized the involvement of eAE1 in AM transport.

Dissecting thrombus-directed chemotaxis and random movement in neutrophil near-thrombus motion in flow chambers.

Background: Thromboinflammation is caused by mutual activation of platelets and neutrophils. The site of thromboinflammation is determined by chemoattracting agents release by endothelium, immune cells, and platelets. Impaired neutrophil chemotaxis contributes to the pathogenesis of Shwachman-Diamond syndrome (SDS).

Binding of coagulation factor IXa to procoagulant platelets revisited: Low affinity and interactions with other factors.

Binding of activated factor IX (fIXa) to the phosphatidylserine-expressing procoagulant platelets is a critical step in blood coagulation, which is necessary for the membrane-dependent intrinsic tenase complex assembly and factor X activation. However, the nature and parameters of the fIXa binding sites on the procoagulant platelet surface remain unclear. We used flow cytometry to elucidate the quantitative details of the fluorescently labeled fIXa binding to gel-filtered activated platelets.

Redox regulation of platelet function and thrombosis.

Platelets are well-known players in several cardiovascular diseases such as atherosclerosis and venous thrombosis. There is increasing evidence demonstrating that reactive oxygen species (ROS) are generated within activated platelets. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a major source of ROS generation in platelets.

Kinetics and regulation of coagulation factor X activation by intrinsic tenase on phospholipid membranes.

Background: Factor X activation by the phospholipid-bound intrinsic tenase complex is a critical membrane-dependent reaction of blood coagulation. Its regulation mechanisms are unclear, and a number of questions regarding diffusional limitation, pathways of assembly and substrate delivery remain open.

Methods: We develop and analyze here a detailed mechanism-driven computer model of intrinsic tenase on phospholipid surfaces.

Chemical Adjustment of Fibrinolysis.

Fibrinolysis is the process of the fibrin-platelet clot dissolution initiated after bleeding has been stopped. It is regulated by a cascade of proteolytic enzymes with plasmin at its core. In pathological cases, the balance of normal clot formation and dissolution is replaced by a too rapid lysis, leading to bleeding, or an insufficient one, leading to an increased thrombotic risk.

Force balance ratio is a robust predictor of arterial thrombus stability.

Thrombus formation on a damaged vessel wall can lead to the formation of a stable occlusive/subocclusive clot or unstable embolizing thrombus. Both outcomes can cause significant health damage. The mechanisms that regulate maximum thrombus size, its stability, and embolization in both micro- and macrocirculation are poorly understood.

The Ways of the Virus: Interactions of Platelets and Red Blood Cells with SARS-CoV-2, and Their Potential Pathophysiological Significance in COVID-19.

The hematological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important in COVID-19 pathophysiology. However, the interactions of SARS-CoV-2 with platelets and red blood cells are still poorly understood. There are conflicting data regarding the mechanisms and significance of these interactions.

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.

HO-Responsive Polymeric Micelles of Biodegradable Aliphatic Poly(carbonate)s as Promising Therapeutic Agents for Inflammatory Diseases.

Excessive amounts of reactive oxygen species (ROS) cause various biological damages and are involved in many diseases, such as cancer, inflammatory and thrombotic complications, and neurodegenerative diseases. Thus, ROS-responsive polymers with inherent ROS scavenging activity and biodegradability are extremely needed for the efficient treatment of ROS-related diseases. Here, this work fabricates the amphiphilic diblock copolymer PEG-b-PBC via ring-opening polymerization (ROP) of phenylboronic acid ester conjugated cyclic carbonate monomer.

Perfluorocarbon Nanoparticles Incorporating Ginkgolide B: Artificial O Carriers with Antioxidant Activity and Antithrombotic Effect.

Ischemic stroke primarily leads to insufficient oxygen delivery in ischemic area. Prompt reperfusion treatment for restoration of oxygen is clinically suggested but mediates more surging reactive oxygen species (ROS) generation and oxidative damage, known as ischemia-reperfusion injury (IRI). Therefore, the regulation of oxygen content is a critical point to prevent cerebral ischemia induced pathological responses and simultaneously alleviate IRI triggered by the sudden oxygen restoration.

Novel hemizygous variant leads to combined immunodeficiency with defective platelet calcium signaling and cell mobility.

Background: To date, fewer than 20 patients have been identified as having germline biallelic mutations in the coronin-1A gene () and its protein with clinical features of combined immunodeficiency characterized by T-cell lymphopenia ranging from the severe phenotype to the mild phenotype, recurrent infections, and lymphoproliferative disorders. However, the effects of CORO1A protein disruption on actin-dependent functions in primary cells have not been fully delineated.

Objective: We sought to characterize the underlying defects of actin-dependent cellular functions in a female patient with combined immunodeficiency caused by a novel missense variant in the gene in combination with a heterozygous microdeletion of chromosome 16p11.

Comparison of platelet proteomic profiles between children and adults reveals origins of functional differences.

Background: Platelets are blood cells responsible for the prevention of blood loss upon vessel wall disruption. It has been demonstrated that platelet functioning differs significantly between adult and pediatric donors. This study aimed to identify potential differences between the protein composition of platelets of pediatric, adolescent, and adult donors.

Platelets provide robustness of spatial blood coagulation to the variation of initial conditions.

Activated platelets provide phospholipid surface and secrete coagulation factors, enhancing blood clotting. We investigated the role of platelets in the regulation of blood coagulation spatial dynamics. We activated blood clotting with tissue factor-bearing (TF) surface in platelet-rich plasma (PRP) or platelet-free plasma (PFP).

Phenylboronic Ester-Bridged Chitosan/Myricetin Nanomicelle for Penetrating the Endothelial Barrier and Regulating Macrophage Polarization and Inflammation against Ischemic Diseases.

The brain and liver are more susceptible to ischemia and reperfusion (IR) injury (IRI), which triggers the reactive oxygen species (ROS) burst and inflammatory cascade and results in severe neuronal damage or hepatic injury. Moreover, the damaged endothelial barrier contributes to proinflammatory activity and limits the delivery of therapeutic agents such as some macromolecules and nanomedicine despite the integrity being disrupted after IRI. Herein, we constructed a phenylboronic-decorated chitosan-based nanoplatform to deliver myricetin, a multifunctional polyphenol molecule for the treatment of cerebral and hepatic ischemia.

Platelet functional abnormalities in pediatric patients with kaposiform hemangioendothelioma/Kasabach-Merritt phenomenon.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy that is commonly associated with a life-threatening thrombocytopenic condition, Kasabach-Merritt phenomenon (KMP). Platelet CLEC-2, tumor podoplanin interaction is considered the key mechanism of platelet clearance in these patients. Here, we aimed to assess platelet functionality in such patients.

Integral assays of hemostasis in hospitalized patients with COVID-19 on admission and during heparin thromboprophylaxis.

Background: Blood coagulation abnormalities play a major role in COVID-19 pathophysiology. However, the specific details of hypercoagulation and anticoagulation treatment require investigation. The aim of this study was to investigate the status of the coagulation system by means of integral and local clotting assays in COVID-19 patients on admission to the hospital and in hospitalized COVID-19 patients receiving heparin thromboprophylaxis.

Bioinspired Platelet-Anchored Electrospun Meshes for Tight Inflammation Manipulation and Chronic Diabetic Wound Healing.

Tight manipulation of the initial leukocytes infiltration and macrophages plasticity toward the M2 phenotype remain a challenge for diabetic wound healing. Inspired by the platelet function and platelet-macrophage interaction, a platelet-anchored polylactic acid-b-polyethylene glycol-b-polylactic acid (PLA-PEG-PLA) electrospun dressing is developed for inflammatory modulation and diabetic wounds healing acceleration. PLA-PEG-PLA electrospun meshes encapsulated with thymosin β4 (Tβ4) and CaCl is fabricated with electrospinning, followed by immersion of electrospun mesh in platelet-rich plasma to firmly anchor the platelets.

Accelerated death of megakaryocytes from Wiskott-Aldrich syndrome patients.

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder caused by WAS gene mutations resulting in haematopoietic/immune cell defects. Recent studies report accelerated death of WAS platelets and lymphocytes. Data on megakaryocyte (MK) maturation, viability and their possible role in thrombocytopenia development in WAS are limited.

New Hybrid Tetrahydropyrrolo[3,2,1-]quinolin-1-ylidene-2-thioxothiazolidin-4-ones as New Inhibitors of Factor Xa and Factor XIa: Design, Synthesis, and In Silico and Experimental Evaluation.

Despite extensive research in the field of thrombotic diseases, the prevention of blood clots remains an important area of study. Therefore, the development of new anticoagulant drugs with better therapeutic profiles and fewer side effects to combat thrombus formation is still needed. Herein, we report the synthesis and evaluation of novel pyrroloquinolinedione-based rhodanine derivatives, which were chosen from 24 developed derivatives by docking as potential molecules to inhibit the clotting factors Xa and XIa.

Novel SLFN14 mutation associated with macrothrombocytopenia in a patient with severe haemorrhagic syndrome.

Background: Platelet-type bleeding disorder 20 (BDPLT20), as known as SLFN14-related thrombocytopenia, is a rare inherited thrombocytopenia (IT). Previously, only 5 heterozygous missense mutations in the SLFN14 gene have been reported.

Methods: A comprehensive clinical and laboratory examination of a 17-year-old female patient with macrothrombocytopenia and severe mucocutaneous bleeding was performed.

Bioactive fibrous scaffolds with programmable release of polypeptides regulate inflammation and extracellular matrix remodeling.

Inflammation manipulation and extracellular matrix (ECM) remodeling for healthy tissue regeneration are critical requirements for tissue engineering scaffolds. To this end, the bioactive polycaprolactone (PCL)-based scaffolds are fabricated to release aprotinin and thymosin β4 (Tβ4) in a programmable manner. The core part of the fiber is composed of hyaluronic acid and Tβ4, and the shell is PCL, which is further coated with heparin/gelatin/aprotinin to enhance biocompatibility.

Bioactive engineered scaffolds based on PCL-PEG-PCL and tumor cell-derived exosomes to minimize the foreign body reaction.

Long-term presence of M1 macrophages causes serious foreign body reaction (FBR), which is the main reason for the failure of biological scaffold integration. Inducing M2 polarization of macrophages near scaffolds to reduce foreign body response has been widely researched. In this work, inspired by the special capability of tumor exosomes in macrophages M2 polarization, we integrate tumor-derived exosomes into biological scaffolds to minimize the FBR.