Targeting CARD9 with Small-Molecule Therapeutics Inhibits Innate Immune Signaling and Inflammatory Response to Pneumocystis carinii beta-Glucans
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Authors: Kottom, Theodore J.; Carmona, Eva M.; Limper, Andrew H.
Abstract
Pneumocystis jirovecii, the opportunistic fungus that causes Pneumocystis pneumonia (PCP) in humans, is a significant contributor to morbidity and mortality in immunocompromised patients. Given the profound deleterious inflammatory effects of the major beta-glucan cell wall carbohydrate constituents of Pneumocystis through Dectin-1 engagement and downstream caspase recruitment domain-containing protein 9 (CARD9) immune activation, we sought to determine whether the pharmacodynamic activity of the known CARD9 inhibitor BRD5529 might have a therapeutic effect on macrophage innate immune signaling and subsequent downstream anti-inflammatory activity. The small-molecule inhibitor BRD5529 was able to significantly reduce both phospho-p38 and phospho-pERK1 signaling and tumor necrosis factor alpha (TNF-alpha) release during stimulation of macrophages with Pneumocystis cell wall beta-glucans.
Local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing in periodontitis: Randomized, placebo-controlled, double-blind split-mouth clinical trial
CLINICAL ORAL INVESTIGATIONS
Authors: Perez-Pacheco, Cindy Grace; Fernandes, Natalie Ap Rodrigues; Primo, Fernando Lucas; Tedesco, Antonio Claudio; Bellile, Emily; Retamal-Valdes, Belen; Feres, Magda; Guimaraes-Stabili, Morgana Rodrigues; Rossa Jr, Carlos
Abstract
Objective Assess a single local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing (SRP) in nonsurgical periodontal treatment (NPT). Materials and methods Twenty healthy subjects with periodontitis received SRP+PLGA/PLA nanoparticles loaded with 50 mu g of curcumin (N-Curc) or SRP+empty nanoparticles. Probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP) were monitored at baseline, 30, 90, and 180 days. IL-1 alpha, IL-6, TNF alpha, and IL-10 in the gingival crevicular fluid (GCF) were assessed by ELISA, and counts of 40 bacterial species were determined by DNA hybridization at baseline, 3, 7, and 15 days post-therapy. Results PPD, CAL, and BOP were similarly and significantly improved in both experimental groups. There was no difference in GCF cytokine levels between experimental groups, although IL-6 was decreased at 3 days only in the N-Curc group. NPT reduced counts of red complex bacterial species in both groups. Veillonella Parvula counts increased significantly only in N-Curc group at 7 days, whereas Aggregatibacter actinomycetemcomitans counts increased significantly only in the control group from day 3 to day 15. Conclusion We conclude that a single local administration of nanoencapsulated curcumin in periodontally diseased sites had no additive benefits to NPT.