The proteome of human salivary fluid has the potential to open new doors for disease biomarker discovery. A recent study to comprehensively identify and catalog the human ductal salivary proteome led to the compilation of 1166 proteins. The protein complexity of both saliva and plasma is large, suggesting that a comparison of these two proteomes will provide valuable insight into their physiological significance and an understanding of the unique and overlapping disease diagnostic potential that each fluid provides. To create a more comprehensive catalog of human salivary proteins, we have first compiled an extensive list of proteins from whole saliva (WS) identified through MS experiments. The WS list is thereafter combined with the proteins identified from the ductal parotid, and submandibular and sublingual (parotid/SMSL) salivas. In parallel, a core dataset of the human plasma proteome with 3020 protein identifications was recently released. A total of 1939 nonredundant salivary proteins were compiled from a total of 19 474 unique peptide sequences identified from whole and ductal salivas; 740 out of the total 1939 salivary proteins were identified in both whole and ductal saliva. A total of 597 of the salivary proteins have been observed in plasma. Gene ontology (GO) analysis showed similarities in the distributions of the saliva and plasma proteomes with regard to cellular localization, biological processes, and molecular function, but revealed differences which may be related to the different physiological functions of saliva and plasma. The comprehensive catalog of the salivary proteome and its comparison to the plasma proteome provides insights useful for future study, such as exploration of potential biomarkers for disease diagnostics.

Objectives: This study retrospectively compares the effectiveness of methylprednisolone to dexamethasone in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) requiring intensive care. Design: This is an institutional review board approved cohort study in patients with COVID-19 requiring intensive care unit (ICU) admission. Patients admitted and requiring oxygen supplementation were treated with no steroids, methylprednisolone, or dexamethasone. Setting: This study takes place in the ICU’s at a large, tertiary, public teaching hospital serving a primarily low-income community in urban Los Angeles. Patients: All eligible patients admitted to the ICU for COVID-19 respiratory failure from March 1 to July 31, 2020 were included in this study. Interventions: A total of 262 patients were grouped as receiving usual care (n = 75), methylprednisolone dosed at least at 1mg/kg/day for ≥ 3 days (n = 104), or dexamethasone dosed at least at 6 mg for ≥7 days (n = 83). Measurements and Main Results: All-cause mortality within 50 days of initial corticosteroid treatment as compared to usual care was calculated. The mortality effect was then stratified based on levels of respiratory support received by the patient. In this cohort of 262 patients with severe COVID-19, all-cause mortalities in the usual care, methylprednisolone, and dexamethasone groups were 41.3%, 16.4% and 26.5% at 50 days ( P < 0.01) respectively. In patients requiring mechanical ventilation, mortality was 42% lower in the methylprednisolone group than in the dexamethasone group (hazard ratio 0.48, 95% CI: 0.235-0.956, P = 0.0385). Conclusions: In COVID-19 patients requiring mechanical ventilation, sufficiently dosed methylprednisolone can lead to a further decreased mortality as compared to dexamethasone.

The contribution of integrin receptors to the regulation of endothelial permeability was studied using cultured bovine pulmonary microvascular endothelial cell (BPMVEC) monolayers by the measurement of hydraulic conductivity (Lp). Treatment of monolayers with a peptide containing the sequence Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) (0.85 mM) to compete for the RGD sequence of extracellular matrix (ECM) proteins increased endothelial Lp threefold, whereas the control peptide Gly-Arg-Gly-Glu-Ser-Pro had no effect on Lp. This action of GRGDSP on Lp was not significantly altered by dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP; 0.5 mM). Endothelial Lp increased twofold when the monolayers were challenged with alpha-thrombin (5 x 10(-8) M for 10 min), and this response was completely reversed by DBcAMP. The strength of adhesion of endothelial cells was estimated by evaluating the ability of endothelial cells to remain attached to ECM after treating the monolayers with 0.05% trypsin plus 0.5 mM EDTA. Exposure of the monolayers to either GRGDSP or alpha-thrombin significantly reduced the strength of adhesion to the ECM. DBcAMP prevented the antiadhesive effect of alpha-thrombin but not that of GRGDSP. Treatment of the monolayers with either alpha-thrombin or GRGDSP caused formation of intercellular gaps, but only the thrombin-induced intercellular gaps were accompanied by reorganization of actin filaments. These results indicate that integrin binding to ECM proteins regulates an important determinant of endothelial permeability and that alpha-thrombin and GRGDSP increase endothelial cell monolayer permeability by different mechanisms.