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Patterns of trauma-induced coagulopathy in injured children: A principal component analysis investigating endothelial, coagulation, and platelet biomarkers.
J Trauma Acute Care Surg
January 2025
From the Department of Surgery (K.M.M.), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Department of Surgery (E.V.F.), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Surgery and Critical Care Medicine (P.C.S., C.M.L.), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and Department of Surgery (B.A.G.), University of Texas Southwestern, Dallas, Texas.
Background: Trauma-induced coagulopathy is common and associated with poor outcomes in injured children. Our aim was to identify patterns of coagulopathy after injury using endothelial, platelet, and coagulation biomarkers, and associate these phenotypes with relevant patient factors and clinical outcomes in a pediatric trauma cohort.
Methods: Principal component (PC) analysis was performed on data from injured children between 2018 and 2022.
Intravital Imaging of Disease Mechanisms in a Mouse Model of CCM Skin Lesions-Brief Report.
Arterioscler Thromb Vasc Biol
January 2025
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Sweden (M.M.O., A.N., M.D., H.S., T.M., K.G.).
Background: Cerebral cavernous malformation (CCM) is a disease characterized by vascular malformations that primarily develop in the brain. These malformations are prone to leak, and their rupture or thrombotic closure can cause life-threatening hemorrhages and strokes. Mouse models have been instrumental to study the disease, but most cause premature lethality, precluding the investigation of disease mechanisms through intravital microscopy.
View Article and Find Full Text PDFThrombomodulin Improves Cognitive Deficits in Heat-Stressed Mice.
Int J Neuropsychopharmacol
July 2024
Department of Medical Research.
Background: Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed (HS) mice.
View Article and Find Full Text PDFTFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia.
Nat Commun
May 2024
Department of Physiology and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages.
View Article and Find Full Text PDFThrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.
Cell Death Discov
April 2024
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway.
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