Trauma-targeted delivery of tranexamic acid improves hemostasis and survival in rat liver hemorrhage model.

Background: Trauma-associated hemorrhage and coagulopathy remain leading causes of mortality. Such coagulopathy often leads to a hyperfibrinolytic phenotype where hemostatic clots become unstable because of upregulated tissue plasminogen activator (tPA) activity. Tranexamic acid (TXA), a synthetic inhibitor of tPA, has emerged as a promising drug to mitigate fibrinolysis.

Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and improve 'golden hour' survival in a porcine model of traumatic arterial hemorrhage.

Traumatic non-compressible hemorrhage is a leading cause of civilian and military mortality and its treatment requires massive transfusion of blood components, especially platelets. However, in austere civilian and battlefield locations, access to platelets is highly challenging due to limited supply and portability, high risk of bacterial contamination and short shelf-life. To resolve this, we have developed an I.

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding.

Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders.

MCP-1 downregulates MMP-9 export via vesicular redistribution to lysosomes in rat portal fibroblasts.

Portal fibroblasts (PF) are one of the two primary cell types contributing to the myofibroblast population of the liver and are thus essential to the pathogenesis of liver fibrosis. Monocyte chemoattractant protein-1 (MCP-1) is a known profibrogenic chemokine that may be of particular importance in biliary fibrosis. We examined the effect of MCP-1 on release of matrix metalloproteinase-9 (MMP-9) by rat PF.

Posttranslational regulation of tissue inhibitor of metalloproteinase-1 by calcium-dependent vesicular exocytosis.

Liver myofibroblasts derived from hepatic stellate cells (HSC) are critical mediators of liver fibrosis. Release of tissue inhibitor of metalloproteinase-1 (TIMP-1) advances liver fibrosis by blocking fibrinolysis. The mechanisms responsible for the posttranslational regulation of TIMP-1 by myofibroblastic HSC are unknown.

CXCL12 induces hepatic stellate cell contraction through a calcium-independent pathway.

Liver fibrosis, with subsequent development of cirrhosis and ultimately portal hypertension, results in the death of patients with end-stage liver disease if liver transplantation is not performed. Hepatic stellate cells (HSCs), central mediators of liver fibrosis, resemble tissue pericytes and regulate intrahepatic blood flow by modulating pericapillary resistance. Therefore, HSCs can contribute to portal hypertension in patients with chronic liver disease (CLD).