Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration.

Pathologies such as malaria, hemorrhagic stroke, sickle cell disease, and thalassemia are characterized by the release of hemoglobin degradation products from damaged RBCs. Hematin (liganded with OH) and hemin (liganded with Cl)-are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe. In the present study, using the original LaSca-TM laser particle analyzer, flow cytometry, and confocal microscopy, we showed that both hematin and hemin induce dose-dependent RBC spherization and hemolysis with ghost formation.

Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation.

WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities.

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.

Hysteroscopic injections of autologous endometrial cells and platelet-rich plasma in patients with thin endometrium: a pilot randomized study.

The aim of this study was to evaluate the efficacy of hysteroscopically controlled injections of autologous platelet-rich plasma (PRP) and autologous endometrial cells as a treatment for infertile women with thin endometrium. The study enrolled 115 patients with thin endometrium (< 7 mm at implantation window) and infertility, who were divided into groups: Group 1 (the control) underwent conservative therapy; Group 2 received intraendometrial PRP injections instead of the conservative therapy; Group 3 received identical injections after conservative therapy; Group 4 received injections of the autologous endometrial cells suspended in PRP. A single injection dose of PRP contained 0.

Procoagulant Activity in Amniotic Fluid Is Associated with Fetal-Derived Extracellular Vesicles.

Procoagulant activity in amniotic fluid (AF) is positively correlated with phosphatidylserine (PS) and tissue factor (TF)-expressing(+) extracellular vesicles (EVs). However, it is unknown if pathological fetal conditions may affect the composition, phenotype, and procoagulant potency of EVs in AF. We sought to evaluate EV-dependent procoagulant activity in AF from pregnant people with fetuses with or without diagnosed chromosomal mutations.

Traumatic vessel injuries initiating hemostasis generate high shear conditions.

Blood flow is a major regulator of hemostasis and arterial thrombosis. The current view is that low and intermediate flows occur in intact healthy vessels, whereas high shear levels (>2000 s-1) are reached in stenosed arteries, notably during thrombosis. To date, the shear rates occurring at the edge of a lesion in an otherwise healthy vessel are nevertheless unknown.

Acylated 1-1,2,4-Triazol-5-amines Targeting Human Coagulation Factor XIIa and Thrombin: Conventional and Microscale Synthesis, Anticoagulant Properties, and Mechanism of Action.

We herein report the conventional and microscale parallel synthesis of selective inhibitors of human blood coagulation factor XIIa and thrombin exhibiting a 1,2,4-triazol-5-amine scaffold. Structural variations of this scaffold allowed identifying derivative , a potent 29 nM inhibitor of FXIIa, with improved selectivity over other tested serine proteases and also finding compound with 27 nM inhibitory activity toward thrombin. For the first time, acylated 1,2,4-triazol-5-amines were proved to have anticoagulant properties and the ability to affect thrombin- and cancer-cell-induced platelet aggregation.

In vitro megakaryocyte culture from human bone marrow aspirates as a research and diagnostic tool.

Megakaryocytes (MKs) are relatively rare in bone marrow, comprising <0.05% of the nucleated cells, which makes direct isolation from human bone marrow impractical. As such, in vitro expansion of primary MKs from patient samples offers exciting fundamental and clinical opportunities.

Platelet-derived extracellular vesicles infiltrate and modify the bone marrow during inflammation.

During inflammation, steady-state hematopoiesis switches to emergency hematopoiesis to repopulate myeloid cells, with a bias toward the megakaryocytic lineage. Soluble inflammatory cues are thought to be largely responsible for these alterations. However, how these plasma factors rapidly alter the bone marrow (BM) is not understood.

Molecular mechanisms of splenectomy-induced hepatocyte proliferation.

Functional and anatomical connection between the liver and the spleen is most clearly manifested in various pathological conditions of the liver (cirrhosis, hepatitis). The mechanisms of the interaction between the two organs are still poorly understood, as there have been practically no studies on the influence exerted by the spleen on the normal liver. Mature male Sprague-Dawley rats of 250-260 g body weight, 3 months old, were splenectomized.