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Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.
Bioconjug Chem
January 2025
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-5127, United States.
Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119.
View Article and Find Full Text PDFProtection of β2GPI-Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation.
Blood
January 2025
Cleveland Clinic, Cleveland, Ohio, United States.
Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI in coagulation in vivo is not understood. To address this issue, we developed β2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the development of thrombosis in wild-type (WT) and Apoh-/- mice using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and activation of platelets from WT and Apoh-/- mice in the absence and presence of β2GPI.
View Article and Find Full Text PDFCarbonate fluorapatite coatings on phillipsite represent a significant sink of phosphorus in abyssal plains of the western Pacific Ocean.
Proc Natl Acad Sci U S A
February 2025
Department of Earth System Sciences, Center for Earth System Research and Sustainability, University of Hamburg, Hamburg 20146, Germany.
As an essential micronutrient, phosphorus plays a key role in oceanic biogeochemistry, with its cycling intimately connected to the global carbon cycle and climate change. Authigenic carbonate fluorapatite (CFA) has been suggested to represent a significant phosphorus sink in the deep ocean, but its formation mechanisms in oceanic low-productivity settings remain poorly constrained. Applying X-ray absorption near edge structure, transmission electron microscopy, and laser ablation inductively coupled plasma mass spectrometer analyses, we report a unique mineral assemblage where CFA crystals coat phillipsite in abyssal sediments of the East Mariana Basin and the Philippine Sea.
View Article and Find Full Text PDFDaytime DNase-I Administration Protects Mice From Ischemic Stroke Without Inducing Bleeding or tPA-Induced Hemorrhagic Transformation, Even With Aspirin Pretreatment.
Stroke
February 2025
Neurovascular Research Unit, Pharmacology Department, Complutense Medical School, Instituto Investigación Hospital 12 Octubre, Madrid, Spain (G.D., B.D., A.M., J.M.P., I.L.).
Background: Acute ischemic stroke treatment typically involves tissue-type plasminogen activator (tPA) or tenecteplase, but about 50% of patients do not achieve successful reperfusion. The causes of tPA resistance, influenced by thrombus composition and timing, are not fully clear. Neutrophil extracellular traps (NETs), associated with poor outcomes and reperfusion resistance, contribute to thrombosis.
View Article and Find Full Text PDFMultimodal assessment predicts cognitive impairment after aneurysmal subarachnoid hemorrhage: a prospective cohort study.
Int J Surg
January 2025
Department of neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Background: Risk factors and mechanisms of cognitive impairment (CI) after aneurysmal subarachnoid hemorrhage (aSAH) are unclear. This study used a neuropsychological battery, MRI, ERP and CSF and plasma biomarkers to predict long-term cognitive impairment after aSAH.
Materials And Methods: 214 patients hospitalized with aSAH (n = 125) or unruptured intracranial aneurysms (UIA) (n = 89) were included in this prospective cohort study.
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