Unresolved inflammation is associated with several widely occurring diseases such as arthritis, periodontal diseases, cancer, and atherosclerosis. Endogenous mechanisms that curtail excessive inflammation and prompt its timely resolution are of considerable interest. In recent years, previously unrecognized chemical mediators derived from polyunsaturated fatty acids were identified that control the acute inflammatory response by activating local resolution programs. Among these are the so-called specialized pro-resolving lipid mediators (SPMs) that include lipoxins (LX), resolvins (Rv), protectins (PD), and maresins (MaR), because they are enzymatically biosynthesized during resolution of self-limited inflammation. They each possess distinct chemical structures and regulate cellular pathways by their ability to activate pro-resolving G-protein coupled receptors (GPCRs) in a stereospecific manner. For instance, RvD1 controls several miRNAs of interest in self-limited acute inflammation that counter-regulate the mediators and proteins that are involved in inflammation. Here, we overview some of the biosynthesis and mechanisms of SPM actions with focus on the recently reported miR involved in their pro-resolving responses that underscore their beneficial actions in the regulation of acute inflammation and its timely resolution. The elucidation of these mechanisms operating in vivo to keep acute inflammation within physiologic boundaries as well as stimulate resolution have opened resolution pharmacology and many new opportunities to target inflammation-related human pathologies via activating resolution mechanisms.
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http://dx.doi.org/10.3389/fimmu.2012.00298 | DOI Listing |
Menopause
January 2025
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Objective: Although dysregulated inflammation has been postulated as a biological mechanism associated with post-acute sequelae of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection (PASC) and shown to be a correlate and an outcome of PASC, it is unclear whether inflammatory markers can prospectively predict PASC risk. We examined the association of leukocyte count and high-sensitivity C-reactive protein (hsCRP) concentrations, measured ~25 years prior to the coronavirus disease 2019 (COVID-19) pandemic, with PASC, PASC severity, and PASC-associated cognitive outcomes at follow-up among postmenopausal women.
Methods: Using biomarker data from blood specimens collected during pre-pandemic enrollment (1993-1998) and data on 1,237 Women's Health Initiative participants who completed a COVID-19 survey between June 2021 and February 2022, we constructed multivariable regression models that controlled for pertinent characteristics.
Pediatr Nephrol
January 2025
Department of Pediatrics, University of California San Diego, 3020 Children's Way MC 5137, San Diego, CA, 92123, USA.
Background: Inadequate treatment of acute rejection (AR) in pediatric kidney transplant recipients (KTR) can contribute to early allograft failure. Serum creatinine is an insensitive marker of allograft function, especially in the pediatric population, and may not detect ongoing rejection after treatment. We evaluated the utility of follow-up biopsies to detect persistent inflammation and future episodes of rejection.
View Article and Find Full Text PDFJ Intensive Med
January 2025
Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China.
Background: Receptor-interacting protein kinase 1 (RIPK1), a serine/threonine protein kinase, is mainly activated by pro-inflammatory cytokines and pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its activation could result in apoptosis, necroptosis, or inflammation. This study was conducted to evaluate the safety and efficacy of a potent and selective inhibitor of RIPK1, SIR1-365, in hospitalized patients with severe coronavirus disease 2019 (COVID-19).
Methods: This multicenter, randomized, double-blind, phase 1b study screened patients from December 18, 2020 until November 27, 2021.
Eur Clin Respir J
January 2025
Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Brisbane, Queensland, Australia.
Therapeutic drug monitoring (TDM) of elexacaftor/tezacaftor/ivacaftor (ETI) remains challenging due to a lack of clarity around the parameters that govern ETI plasma concentrations, whilst the use of concomitant CYP3A inducers rifabutin and rifampicin is not recommended. We present the complexities of TDM for ETI performed in a person with cystic fibrosis and refractory pulmonary disease. Utilising National Association of Testing Authorities (NATA) accredited assays and target considerations published by the Therapeutic Goods Administration (TGA), Australia, ETI plasma concentration variability was monitored over the course of an acute admission with added complexity from an antibiotic regimen including rifabutin, a moderate cytochrome P450 3A (CYP3A) inducer, and clofazimine, a mild CYP3A inhibitor.
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