Meta-Analysis of the Efficacy and Safety of Finerenone in Diabetic Kidney Disease.

BACKGROUND: The phase III clinical trial of the nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94-8862) has been completed, aiming to investigate renal and cardiovascular outcomes in type 2 diabetes (T2D) with chronic kidney disease (CKD). However, the efficacy and safety of finerenone in renal function remain controversial. The purpose of this study was to explore the efficacy and safety of finerenone in treating the patients with diabetic kidney disease (DKD). METHODS: Databases of PubMed, Cochrane Library, Embase, and Web of Science were searched for randomized controlled trials (RCTs) on patients with DKD receiving finerenone treatment from inception to September 2021. Data including patient characteristics and interested outcomes were extracted, and the dichotomous data and continuous variables were evaluated using risk ratio (RR) with 95% confidence intervals (CIs) and mean differences (MD) with 95% CIs, respectively. RESULTS: A total of 4 RCTs involving 13,945 patients were included in this meta-analysis. Analysis results demonstrated that patients receiving finerenone showed a significant decrease in changing urinary albumin-to-creatinine ratio (UACR) from baseline (MD: -0.30; 95% CI [-0.33, -0.27], p = 0.46, I2 = 0%) (p < 0.05). The number of patients with ≥40% reduction in estimated glomerular filtration rate (eGFR) from baseline in the finerenone group was significantly smaller than that in the placebo group (RR: 0.85; 95% CI [0.78, 0.93], p = 0.60, I2 = 0%) (p < 0.05). No difference was found in adverse events between the finerenone and placebo groups (RR: 1.00; 95% CI [0.98, 1.01], p = 0.94, I2 = 0%) (p = 0.65). The incidence of hyperkalemia was higher in the finerenone group than that in the placebo group (RR: 2.03; 95% CI [1.83, 2.26], p = 0.95, I2 = 0%) (p < 0.05). CONCLUSION: Finerenone contributes to the reduction of UACR and can ameliorate the deterioration of renal function in patients with T2D and CKD. The higher risk of hyperkalemia was found in the finerenone group compared with placebo; however, there was no difference in the risk of overall adverse events.

Effects of Ag/ZnO nanocomposite at sub-minimum inhibitory concentrations on virulence factors of Streptococcus mutans.

OBJECTIVE: Streptococcus mutans (S. mutans), the main pathogen of dental caries, could be well killed by Ag/ZnO nanocomposite. However, effects on virulence factors remain to be elucidated. This study investigated effects of Ag/ZnO at sub-minimum inhibitory concentrations (sub-MICs) on virulence factors of S. mutans and related genes expressions. DESIGN: Effects of Ag/ZnO on the growth of S. mutans was investigated by growth curves and MTT staining method. The influence of Ag/ZnO at sub-MICs on biofilm formation was measured by the crystal violet staining method and observed by a scanning electron microscopy. Adherence, cell-surface hydrophobicity, acidogenicity and extracellular polysaccharides (EPS) of S. mutans after treatment by Ag/ZnO at sub-MICs were also investigated. Virulence factors related genes expressions after treated by Ag/ZnO at 1/2 MIC was conducted by the quantitative real-time PCR (qRT-PCR) method. RESULTS: Sub-MICs of Ag/ZnO exhibited a dose-dependent inhibition on the virulence factors of S. mutans. Specially, Ag/ZnO at 1/2 MIC decreased 69.00 % biofilm formation, 31.78 % sucrose-independent and 48.08 % sucrose-dependent adherence, 69.44 % cell-surface hydrophobicity and 72.45 % water-soluble and 90.60 % water-insoluble EPS. Furthermore, the expression of virulence factors related genes was significantly suppressed by Ag/ZnO at 1/2 MIC. CONCLUSIONS: Ag/ZnO at sub-MICs inhibited multiple virulence factors of S. mutans through downregulating the related genes. Ag/ZnO nanocomposite could be used for prevention of dental caries at low dosage.

Rapid Antibiofilm Effect of Ag/ZnO Nanocomposites Assisted by Dental LED Curing Light against Facultative Anaerobic Oral Pathogen Streptococcus mutans.

The integration of nanomaterials with clinical therapeutic instruments is a promising approach to improve the effects of nanomaterials. We reported an efficient synergistic antibacterial strategy formed through the combination of Ag/ZnO nanocomposites with a light-emitting diode (LED) curing light, which is a commonly used small instrument in dental clinics. The as-designed integration depicted a significantly enhanced bactericidal effect on facultative anaerobic oral pathogen Streptococcus mutans (S. mutans) both in planktonic and biofilm phases over a very short irradiation time (≤5 min). Further study showed that the combination of LED and Ag/ZnO nanocomposites induced more ·OH and ·O2- generation, which is responsible for the enhanced antibacterial activity. Moreover, this combination could destroy S. mutans biofilm by killing the bacteria embedded within biofilm, inhibiting exopolysaccharide production and down-regulating the biofilm-related gene expression. Therefore, it is proposed that this combination could be applied in dental clinics to realize dental caries prevention and dental restoration simultaneously.

Antibacterial activity and mechanism of Ag/ZnO nanocomposite against anaerobic oral pathogen Streptococcus mutans.

Dental caries is a widespread disease mainly caused by the anaerobic oral pathogen Streptococcus mutans (S. mutans). Ag/ZnO nanocomposite is an efficient antibacterial agent because of its high antibacterial activity and low cytotoxicity. In this study, rod-like Ag/ZnO nanocomposite was synthesized through a deposition-precipitation method and characterized by X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The activity of Ag/ZnO nanocomposite against S. mutans was evaluated by determining the minimal inhibitory concentration, minimum bactericidal concentration and growth inhibition curve. The results showed that Ag/ZnO nanocomposite displayed higher activity against S. mutans compared with pure ZnO nanorods. Moreover, the antibacterial mechanism was investigated by determining the bacterial membrane potential, release of K+, intracellular reactive oxygen generation and lipid peroxidation. Disruption of membrane function and oxidation of biomacromolecules played important role in the antibacterial action of Ag/ZnO nanocomposite. This work proposes a potentially effective dental antibacterial agent against the dental caries-causing S. mutans.