Utility of the Specialized Pro-Resolving Mediators as Diagnostic and Prognostic Biomarkers in Disease.

A precision medicine approach is widely acknowledged to yield more effective therapeutic strategies in the treatment of patients with chronic inflammatory conditions than the prescriptive paradigm currently utilized in the management and treatment of these patients. This is because such an approach will take into consideration relevant factors including the likelihood that a patient will respond to given therapeutics based on their disease phenotype. Unfortunately, the application of this precision medicine paradigm in the daily treatment of patients has been greatly hampered by the lack of robust biomarkers, in particular biomarkers for determining early treatment responsiveness.

Disrupted Resolution Mechanisms Favor Altered Phagocyte Responses in COVID-19.

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Platelets orchestrate the resolution of pulmonary inflammation in mice by T reg cell repositioning and macrophage education.

Beyond hemostasis, platelets actively participate in immune cell recruitment and host defense, yet their potential in the resolution of inflammatory processes remains unknown. Here, we demonstrate that platelets are recruited into the lung together with neutrophils during the onset of inflammation and alongside regulatory T (T reg) cells during the resolution phase. This partnering dichotomy is regulated by differential adhesion molecule expression during resolution.

Biosynthetic metabolomes of cysteinyl-containing immunoresolvents.

Resolution of inflammation is an active process regulated by specialized proresolving mediators where we identified 3 new pathways producing allylic epoxide-derived mediators that stimulate regeneration [, peptido-conjugates in tissue regeneration (CTRs)]. Here, using self-limited peritonitis in mice, we identified endogenous maresin (MaR) CTR (MCTR), protectin (PD) CTR (PCTR), and resolvin CTR in infectious peritoneal exudates and distal spleens, as well as investigated enzymes involved in their biosynthesis. PCTRs were identified to be temporally regulated in peritoneal exudates and spleens.

Resolvin D4 attenuates the severity of pathological thrombosis in mice.

Deep vein thrombosis (DVT) is a common cardiovascular disease with a major effect on quality of life, and safe and effective therapeutic measures to efficiently reduce existent thrombus burden are scarce. Using a comprehensive targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics approach, we established temporal clusters of endogenously biosynthesized specialized proresolving mediators (SPMs) and proinflammatory and prothrombotic lipid mediators during DVT progression in mice. Administration of resolvin D4 (RvD4), an SPM that was enriched at the natural onset of thrombus resolution, significantly reduced thrombus burden, with significantly less neutrophil infiltration and more proresolving monocytes in the thrombus, as well as an increased number of cells in an early apoptosis state.

Cutting Edge: Human Vagus Produces Specialized Proresolving Mediators of Inflammation with Electrical Stimulation Reducing Proinflammatory Eicosanoids.

Inflammatory resolution is a process that, when uncontrolled, impacts many organs and diseases. As an active, self-limited inflammatory process, resolution involves biosynthesis of specialized proresolving mediators (SPM) (e.g.