Freeze-dried plasma: Hemostasis and biophysical analyses for damage control resuscitation.

Background: Effective hemorrhage protocols prioritize immediate hemostatic resuscitation to manage hemorrhagic shock. Prehospital resuscitation using blood products, such as whole blood or alternatively dried plasma in its absence, has the potential to improve outcomes in hemorrhagic shock patients. However, integrating blood products into prehospital care poses substantial logistical challenges due to issues with storage, transport, and administration in field environments.

Small molecules targeting GRP78 mitigate anti-GRP78 autoantibody-mediated tissue factor procoagulant activity in cultured endothelial cells.

Background: The 78-kDa glucose-regulated protein (GRP78) expressed on the cell surface (csGRP78) has been reported to regulate tissue factor (TF) procoagulant activity (PCA) in lesion-resident endothelial cells (ECs), which is further enhanced by circulating anti-GRP78 autoantibodies that bind to the Leu-Leu epitope in GRP78.

Objectives: Determine the effects of the engagement of the anti-GRP78 autoantibody to csGRP78 on ECs and the underlying mechanisms that impact TF PCA.

Methods: Immunofluorescent staining was used to determine the presence of csGRP78 in tumor necrosis factor α-treated ECs.

Ligand-dependent interactions between SR-B1 and S1PR1 in macrophages and atherosclerotic plaques.

HDLs carry sphingosine-1-phosphate (S1P) and stimulate signaling pathways in different cells including macrophages and endothelial cells, involved in atherosclerotic plaque development. HDL signaling via S1P relies on the HDL receptor scavenger receptor class B, type I (SR-B1) and the sphingosine-1-phosphate receptor 1 (S1PR1), which interact when both are heterologously overexpressed in the HEK293 cell line. In this study, we set out to test if SR-B1 and S1PR1 interacted in primary murine macrophages in culture and atherosclerotic plaques.

Bystander activated CD8 T cells mediate neuropathology during viral infection via antigen-independent cytotoxicity.

Although many viral infections are linked to the development of neurological disorders, the mechanism governing virus-induced neuropathology remains poorly understood, particularly when the virus is not directly neuropathic. Using a mouse model of Zika virus (ZIKV) infection, we found that the severity of neurological disease did not correlate with brain ZIKV titers, but rather with infiltration of bystander activated NKG2DCD8 T cells. Antibody depletion of CD8 or blockade of NKG2D prevented ZIKV-associated paralysis, suggesting that CD8 T cells induce neurological disease independent of TCR signaling.

PAR4 Inhibition Reduces Coronary Artery Atherosclerosis and Myocardial Fibrosis in SR-B1/LDLR Double Knockout Mice.

Background: SR-B1 (scavenger receptor class B type 1)/LDLR (low-density lipoprotein receptor) double knockout mice fed a high-fat, high-cholesterol diet containing cholate exhibit coronary artery disease characterized by occlusive coronary artery atherosclerosis, platelet accumulation in coronary arteries, and myocardial fibrosis. Platelets are involved in atherosclerosis development, and PAR (protease-activated receptor) 4 has a prominent role in platelet function in mice. However, the role of PAR4 on coronary artery disease in mice has not been tested.