Objective: To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives (methyl, ethyl, propyl, and butyl) against resistance mechanisms in Staphylococcus aureus strains. Methods: Ferulic acid derivatives were obtained by esterification with methanol, ethanol, propanol, and butanol, and then characterized by hydrogen and carbon-13 nuclear magnetic resonance analysis. The minimum inhibitory concentrations (MIC) of ferulic acid and its esterified derivatives, ethidium bromide, and norfloxacin were obtained using the microdilution test, while the efflux pump inhibition test was conducted by examining reduction in the MICs of norfloxacin and ethidium bromide. Molecular docking was also carried out using the Schrodinger Suite 2015 molecular modeling software. A three-dimensional model of NorA efflux pump was generated using I-TASSER. The best scoring model was used as a receptor for ligand-receptor docking. Results: The methyl and butyl ester derivatives did not demonstrate significant antimicrobial activity. However, a significant synergic effect was evidenced when norfloxacin was combined with the ethyl and propyl esterified derivatives. The docking study demonstrated favorable energy of interaction between ferulate derivatives and NorA, and amino acid residues TYR57, TYR58, and LEU255 were present commonly in stabilizing all complexes. The PCA analysis corroborated the docking hypothesis that the lipophilic character and hydrogen bond interactions were the most relevant characteristics involved with NorA inhibitors. The pharmacokinetic parameters of ferulic acid derivatives showed good ADMET properties, demonstrating that they can be easily absorbed and have no effect or inhibit the cytochrome P450 enzyme complex, revealing their potential as drug candidates. Conclusions: This study provides strong evidence that the molecular basis for this activity is potentially due to the NorA efflux pump.

Objective To evaluate gene polymorphisms and their association with susceptibility to dengue. Methods A retrospective case-control study was performed with 262 subjects, comprising 78 dengue fever (DF) patients, 49 dengue hemorrhagic fever (DHF) patients and 135 healthy controls. Genotypic and allelic profiles were identified using polymerase chain reaction based in real time and amplification-refractory mutation system. Results We observed a protective association of IL-10 (−819 C/T) C allele (P = 0.028, OR = 0.56, CI = 0.34–0.91) against DHF, while the C/T (P = 0.047, OR = 2.10, CI = 1.01–4.38) and T/T (P = 0.008, OR = 3.82, CI = 1.38–10.59) genotypes were associated with DHF and DF, respectively. The dominant model TNFA −308 GA + AA (P = 0.043, OR = 0.45, CI = 0.20–1.00) genotypes were found to have protective effect against dengue infection. A protective association among the IFNG (+874 A/T) A/T genotype against DF (P = 0.02, OR = 0.46, CI = 0.24–0.89) and DHF (P = 0.034, OR = 0.43, CI = 0.19–0.95) was observed. When the studied single-nucleotide polymorphism was analyzed in combination, the combination GTA (P = 0.022, OR = 2.95, CI = 1.18–7.41) was statistically significantly associated with susceptibility to DF and the combination GCT (P = 0.035, OR = 0.28, CI = 0.08–0.90) with protection against the development of DHF. Conclusions This research identifies the association of the IFNG (+874 A/T), TNFA (−308G/A), IL-10 (−819 C/T) genotypes as a factor for protection, susceptibility and severity to dengue.

OBJECTIVE: To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast β-glucans, minerals and silymarin (Silybum marianum), on lipid and glycidic metabolism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice. METHODS: After an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice. RESULTS: After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-α, AMP-activated protein kinase-1α, peroxisome proliferator-activated receptor γ co-activator-1α, and mitochondrial transcription factor A expression levels were augmented; however, levels of inhibitor of nuclear factor-κB kinase subunit α and p65 nuclear factor-κB expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic-pituitary-adrenal axis immune interface status, was found to be modulated by the supplement. CONCLUSION We discovered that the novel supplement was able to modify different antioxidant, metabolic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.
Animals ; Antioxidants ; Dietary Supplements ; Glucans ; Hypothalamo-Hypophyseal System ; Liver ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Milk Thistle ; Minerals ; Pituitary-Adrenal System ; Prebiotics ; Saccharomyces cerevisiae