This study highlights the P2RX7 gene as a possible factor of susceptibility to EARR. A more extensive genetic profile may improve this model.

Antimicrobial peptides (AMPs) are a promising solution to face the antibiotic-resistant problem because they display little or no resistance effects. Dimeric analogues of select AMPs have shown pharmacotechnical advantages, making these molecules promising candidates for the development of novel antibiotic agents. Here, we evaluate the effects of dimerization on the structure and biological activity of the AMP aurein 1.2 (AU). AU and the C- and N-terminal dimers, (AU)2K and E(AU)2, respectively, were synthesized by solid-phase peptide synthesis. Circular dichroism spectra indicated that E(AU)2 has a "coiled coil" structure in water while (AU)2K has an α-helix structure. In contrast, AU displayed typical spectra for disordered structures. In LPC micelles, all peptides acquired a high amount of α-helix structure. Hemolytic and vesicle permeabilization assays showed that AU has a concentration dependence activity, while this effect was less pronounced for dimeric versions, suggesting that dimerization may change the mechanism of action of AU. Notably, the antimicrobial activity against bacteria and yeast decreased with dimerization. However, dimeric peptides promoted the aggregation of C. albicans. The ability to aggregate yeast cells makes dimeric versions of AU attractive candidates to inhibit the adhesion of C. albicans to biological targets and medical devices, preventing disease caused by this fungus.

It is well known that cationic antimicrobial peptides (cAMPs) are potential microbicidal agents for the increasing problem of antimicrobial resistance. However, the physicochemical properties of each peptide need to be optimized for clinical use. To evaluate the effects of dimerization on the structure and biological activity of the antimicrobial peptide Ctx-Ha, we have synthesized the monomeric and three dimeric (Lys-branched) forms of the Ctx-Ha peptide by solid-phase peptide synthesis using a combination of 9-fluorenylmethyloxycarbonyl (Fmoc) and t-butoxycarbonyl (Boc) chemical approaches. The antimicrobial activity assay showed that dimerization decreases the ability of the peptide to inhibit growth of bacteria or fungi; however, the dimeric analogs displayed a higher level of bactericidal activity. In addition, a dramatic increase (50 times) in hemolytic activity was achieved with these analogs. Permeabilization studies showed that the rate of carboxyfluorescein release was higher for the dimeric peptides than for the monomeric peptide, especially in vesicles that contained sphingomyelin. Despite different biological activities, the secondary structure and pore diameter were not significantly altered by dimerization. In contrast to the case for other dimeric cAMPs, we have shown that dimerization selectively decreases the antimicrobial activity of this peptide and increases the hemolytic activity. The results also show that the interaction between dimeric peptides and the cell wall could be responsible for the decrease of the antimicrobial activity of these peptides.

IRAK1 polymorphism is proposed as a protective variant for EARR.

Aim: This study assessed the effect of fatigue load cycling on human premolars restored with MOD restorations (direct and indirect approaches) on cuspal deflection, compared to intact teeth (unprepared) and unrestored teeth with an inlay preparation. Materials and methods:MOD inlay preparations were performed on sixty premolars with their roots embedded in acrylic resin. These teeth were divided into six groups (n = 10): (1) intact teeth; (2) unrestored and prepared teeth; (3) teeth restored with direct composite resin; (4) teeth restored with an indirect composite resin; (5) teeth restored with injected ceramic inlays (IPS Empress 2 (Ivoclar); (6) teeth restored with CAD/CAM inlays made of feldspathic ceramic (Vita Mark II). All of the indirect restorations were adhesively cemented. Strain-gauges were bonded to the buccal and lingual surfaces of the specimens. Compressive axial loading of 100N was applied on the occlusal face of the specimens to measure the cuspal deflection (microstrain) under compressive loading. These measurements were obtained before and after mechanical cycling (1 Hz, 37°C, 100,000x). Results:Comparing the results obtained before and after fatiguing, the cuspal deflection increased only in the CAD/CAM approach. The prepared tooth group had the highest cuspal deflection, before and after mechanical cycling. Conclusion:The evaluated restoring approaches decrease the cuspal deflection, consequently appear to improve the cuspal reinforcement.

Chemical fractionation of the methanolic extract of leaves of Leiothrix spiralis Ruhland afforded the flavonoids luteolin-6-C-β-D-glucopyranoside (1), 7-methoxyluteolin-6-C-β-D-glucopyranoside (2), 7-methoxyluteolin-8-C-β-D-glucopyranoside (3), 4′-methoxyluteolin-6-C-β-D-glucopyranoside (4), and 6-hydroxy-7-methoxyluteolin (5), and the xanthones 8-carboxymethyl-1,5,6-trihydroxy-3-methoxyxanthone (6), 8-carboxy-methyl-1,3,5,6-tetrahydroxyxanthone (7). Methanolic extract, fractions, and isolated compounds of the leaves of L. spiralis were assayed against Gram-positive (Staphylococcus aureus, Bacillus subtilis and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella setubal and Helicobacter pylori) and fungi (the yeasts Candida albicans, C. tropicalis, C. krusei and C. parapsilosis). We observed the best minimum inhibitory concentration values for the methanolic extract against Candida parapsilosis, for the fraction 5 + 6 against Gram-negative bacteria E. coli and P. aeruginosa, and compound 7 against all tested Candida strains. The methanolic extract contents suggest that this species may be a promising source of compounds to produce natural phytomedicines.

Increasingly more young patients have been submitted to reconstruction of the Temporomandibular Joint (TMJ), so, the prostheses must to present more functional longevity. Objective: To evaluate the effect of diamond-like carbon film (DLC) over titanium alloy (Ti6Al4V) and polyethylene (UHWPE) samples, their mechanical and chemical properties and cellular cytotoxicity. Methods: Titanium and UHWPE specimens, with 2.5 cm in diameter and 2 mm thickness were coated through plasma enhanced chemical vapor deposition (PECVD) with DLC or DLC doped with silver (DLC-Ag). Scanning electron microscopy (SEM) morphological analysis, Energy-dispersive spectroscopy (EDS) chemical analysis, scratching test, mechanical fatigue test, surface roughness analysis, and cellular cytotoxicity were performed. Data were statistically analyzed using one-way ANOVA (p < 0.05) or two-way ANOVA and multiple comparison Tukey test. Results: In the SEM analysis, morphological differences were observed on substrates after DLC deposition. The film chemically modified the substrate surfaces, according to the EDS analysis. The initial critical load failure occurred at 6.1 N for DLC and 9.7 N for the DLC-Ag film. The DLC film deposition over the polyethylene promoted a decrease in the polymer's damaged area after mechanical fatigue cycling. The cytotoxicity analysis demonstrated less biocompatibility in experimental groups, when compared to control, however, increased biocompatibility was observed, at 10 days, in all groups. Conclusion: The diamond-like carbon coating enhanced the chemical and mechanical properties from substrates, however modified biological interaction course of the titanium alloy (Ti6Al4V) and polyethylene (UHWPE) samples. Parameters for film deposition remain to be improved in order to obtain best biocompatibility.

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