The differential formation and composition of leukocyte-platelet aggregates induced by various cellular stimulants.

Background: Leukocyte-platelet aggregates comprise a pathogenic link between hemostasis and immunity, but the prerequisites and mechanisms of their formation remain not understood.

Aims: To quantify the formation, composition, and morphology of leukocyte-platelet aggregates in vitro under the influence of various cellular activators.

Methods: Phorbol-12-myristate-13-acetate (PMA), lipopolysaccharide (LPS), thrombin receptor-activating peptide (TRAP-6), and adenosine diphosphate (ADP) were used as cellular activators.

Protease activated receptor-4: ready to be part of the antithrombosis spectrum.

Purpose Of Review: Cardiovascular disease is a major cause of death worldwide. Platelets play a key role in this pathological process. The serine protease thrombin is a critical regulator of platelet reactivity through protease activated receptors-1 (PAR1) and PAR4.

Activation of Piezo1 channels in compressed red blood cells augments platelet-driven contraction of blood clots.

Background: Piezo1 is a mechanosensitive cationic channel that boosts intracellular [Ca]. Compression of red blood cells (RBCs) during platelet-driven contraction of blood clots may cause the activation of Piezo1.

Objectives: To establish relationships between Piezo1 activity and blood clot contraction.

A familial case of MYH9 gene mutation associated with multiple functional and structural platelet abnormalities.

Mutations in the MYH9 gene result in macrothrombocytopenia often associated with hemorrhages. Here, we studied the function and structure of platelets in three family members with a heterozygous mutation R1933X in the MYH9 gene, characteristic of closely related disorders known as the May-Hegglin anomaly and Sebastian syndrome. The examination included complete blood count, blood smear microscopy, platelet flow cytometry (expression of P-selectin and active integrin αIIbβ3 before and after activation), the kinetics of platelet-driven contraction (retraction) of blood clots, as well as scanning/transmission electron microscopy of platelets.

[Activity of ankylosing spondylitis in women within one year after childbirth].

Aim: To assess the dynamics of activity of ankylosing spondylitis (AS) during the year after childbirth, to identify predictors of high activity.

Materials And Methods: 75 pregnant with confirmed AS (modified New York criteria, 1984) were included for prospective observation. Of these, 44 women were followed up for 1 year after delivery.

[Peculiarities of blood coagulation disorders in patients with COVID-19].

Aim: To study the relationship of hemostatic disorders with inflammation and estimate their role in the course and outcomes of COVID-19.

Materials And Methods: We examined 215 consecutive patients with moderate and severe forms of acute COVID-19. The patients were on anticoagulants and immunosuppressive drugs.

Chronic Immune Platelet Activation Is Followed by Platelet Refractoriness and Impaired Contractility.

Autoimmune diseases, including systemic lupus erythematosus (SLE), have a high risk of thrombotic and hemorrhagic complications associated with altered platelet functionality. We studied platelets from the blood of SLE patients and their reactivity. The surface expression of phosphatidylserine, P-selectin, and active integrin αIIbβ3 were measured using flow cytometry before and after platelet stimulation.

Osteogenic Commitment of MSC Is Enhanced after Interaction with Umbilical Cord Blood Mononuclear Cells In Vitro.

The effectiveness of stroma-dependent expansion of hematopoietic cells ex vivo may depend on the level of commitment of multipotent mesenchymal stromal cells (MSC). Markers of MSC osteodifferentiation and the level of soluble hematopoiesis regulators were determined during their interaction with umbilical cord blood mononuclears. After 72-h co-culturing, an increase in the expression of ALPL and alkaline phosphatase activity was revealed.

Altered platelet and coagulation function in moderate-to-severe COVID-19.

To reveal if coagulopathies relate to the course of COVID-19, we examined 255 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about ¼ of cases were associated with high levels of C-reactive protein and antiphospholipid antibodies, which impeded coagulation in vitro.

Сord blood hematopoietic stem cells ex vivo enhance the bipotential commitment of adipose mesenchymal stromal progenitors.

Aims: Stroma-dependent ex vivo expansion of hematopoietic stem progenitor cells (HSPCs) is a valid approach for cell therapy needs. Our goal was to verify whether HSPCs can affect stromal cells to optimize their functions during ex vivo expansion.

Main Methods: HSPCs from cord blood (cb) were cocultured with growth-arrested adipose mesenchymal stromal cells (MSCs).

Behavioral Responses and Immune and Cytogenetic Parameters of Food-Restricted Mice.

The experiments on mice showed that subchronic food restriction to 40 and 8% of unrestricted ration is a strong stressor inducing devastation of lymphoid organs, primarily the thymus and spleen. The mice in the group with severe food restriction (8% of normal ration) demonstrated increased front paw grip force. We also observed an increase in spontaneous motor activity in these animals correlated with food restriction.

Differential Expression of Bipotent Commitment-Related Genes in Multipotent Mesenchymal Stromal Cells at Different O Levels.

The transcriptomic profile associated with osteo- and adipogenic differentiation in growth-arrested multipotent mesenchymal stromal cells (MSCs) from human adipose tissue was analyzed in vitro at 20% (standard laboratory) and 5% (tissue-related) O levels. Compared with day 7, at 5% O on day 14 spontaneous upregulation of osteo- (RUNX2, SP7, BGLAP, and SPP1) and adipogenic differentiation (CEBPA, PPARG, and ADIPOQ) genes in MSCs was observed (p < 0.05).

Adipose tissue-derived stromal cells retain immunosuppressive and angiogenic activity after coculture with cord blood hematopoietic precursors.

Adipose-tissue derived stromal cells (ASCs) are currently considered as a full value alternative source of bone marrow MSCs for prevention of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation due to their immunosuppressive potential. Besides, ASCs are known to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs). Ex vivo expansion enables to amplify significantly the number of HSPCs of different commitment.

In systemic lupus erythematosus anti-dsDNA antibodies can promote thrombosis through direct platelet activation.

Systemic lupus erythematosus (SLE) is associated with a high risk of venous and arterial thrombosis, not necessarily associated with prothrombotic antiphospholipid antibodies (Abs). Alternatively, thrombosis may be due to an increased titer of anti-dsDNA Abs that presumably promote thrombosis via direct platelet activation. Here, we investigated effects of purified anti-dsDNA Abs from the blood of SLE patients, alone or in a complex with dsDNA, on isolated normal human platelets.

Differential sensitivity of various markers of platelet activation with adenosine diphosphate.

A number of techniques have been available to assess platelet activation, but their relative sensitivity is unknown and their usage is variable and not based on any rational criteria. Here, we compared the ability of several techniques based on morphological and biochemical markers to detect the first signs of ADP-induced platelet activation. Scanning electron microscopy of platelets was performed in parallel with flow cytometry to quantify the surface expression of P-selectin (marked by labeled anti-CD62P antibodies), active αIIbβ3-intergrin (assessed by the binding of labeled fibrinogen) and phosphatidylserine (assessed by the binding of labeled Annexin V).

Lytic Susceptibility, Structure, and Mechanical Properties of Fibrin in Systemic Lupus Erythematosus.

Among complications of systemic lupus erythematosus (SLE), thrombotic events are relatively common and contribute significantly to the morbidity and mortality rates. An increased risk of thrombosis in various diseases has been shown to be associated with the lytic stability and mechanical stiffness of the fibrin clot determined by its structure. Here we studied alterations of the fibrin clot properties in relation to disease severity in SLE patients.

Platelet factor 4-containing immune complexes induce platelet activation followed by calpain-dependent platelet death.

Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy sometimes associated with thrombosis. The hallmark of HIT is antibodies to the heparin/platelet factor 4 (PF4) complex that cause thrombocytopenia and thrombosis through platelet activation. Despite the clinical importance, the molecular mechanisms and late consequences of immune platelet activation are not fully understood.

Fatal dysfunction and disintegration of thrombin-stimulated platelets.

Platelets play a key role in the formation of hemostatic clots and obstructive thrombi as well as in other biological processes. In response to physiological stimulants, including thrombin, platelets change shape, express adhesive molecules, aggregate, and secrete bioactive substances, but their subsequent fate is largely unknown. Here we examined late-stage structural, metabolic, and functional consequences of thrombin-induced platelet activation.

Hematopoiesis-supportive function of growth-arrested human adipose-tissue stromal cells under physiological hypoxia.

Ex vivo expansion of hematopoietic progenitors is considered as an attractive tool to increase the number of stem and progenitor cells (HSPCs) for cell therapy. The efficacy of ex vivo expansion is strongly depends on the feeder cell activity to mimic hematopoietic microenvironment. Here we demonstrated, that combination of mitomycin C-induced growth arrest and tissue-related O (physiological hypoxia) modulated stromal capacity of adipose tissue derived stromal cells (ASCs).

Effect of 30-Day Hindlimb Unloading and Hypergravity on Bone Marrow Stromal Progenitors in C57Bl/6N Mice.

We studied the effect of 30-day hindlimb unloading and subsequent simulated hypergravity on the cellularity and proliferative, clonogenic, and differentiation potential of bone marrow stromal progenitors in mice. Clonogenic and differentiation activity of stromal cells decreased after unloading; proliferative and differentiation activity of bone marrow stromal progenitors increased after hypergravity simulation. Our findings demonstrated negative effect of unloading on functional activity of mouse bone marrow stromal progenitors.

Stromal and Hematopoietic Progenitors from C57/BI/6N Murine Bone Marrow After 30-Day "BION-M1" Spaceflight.

Elucidation of the spaceflight (SF) effects on the adult stem and progenitor cells is an important goal in space biology and medicine. A unique opportunity for this was provided by project "BION-M1". The purpose of this study was to evaluate the effects of 30-day SF on biosatellite, 7-day recovery (SFR), and subsequent ground control (GC) experiment on the mononuclear cells (MNCs) from C57/BI/6N murine tibia bone marrow.

Reduced Contraction of Blood Clots in Venous Thromboembolism Is a Potential Thrombogenic and Embologenic Mechanism.

Contraction (retraction) of the blood clot is a part of the clotting process driven by activated platelets attached to fibrin that can potentially modulate the obstructiveness and integrity of thrombi. The aim of this work was to reveal the pathogenic importance of contraction of clots and thrombi in venous thromboembolism (VTE). We investigated the kinetics of clot contraction in the blood of 55 patients with VTE.

Evaluation of committed and primitive cord blood progenitors after expansion on adipose stromal cells.

Umbilical cord blood mononuclear fraction is a valuable source of hematopoietic stem and progenitor cells (CB HSPCs). The rarity of this population is a serious limitation of its application in cell therapy. Ex vivo expansion enables to significantly amplify the number of hematopoietic precursors of different commitment.