ABSTRACT
INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA)-caused infections greatly threaten public health. The discovery of natural-product-based anti-MRSA agents for treating infectious diseases has become one of the current research focuses. OBJECTIVES: This study aims to identify promising anti-MRSA agents with a clear mechanism based on natural norharmane modified by quaternization or dimerization. METHODS: A total of 32 norharmane analogues were prepared and characterized. Their antibacterial activities and resistance development propensity were tested by the broth double-dilution method. Cell counting kit-8 and hemolysis experiments were used to assess their biosafety. The plasma stability, bactericidal mode, and biofilm disruption effects were examined by colony counting and crystal violet staining assays. Fluorescence microscopy, metabolomic analysis, docking simulation and spectra titration revealed its anti-MRSA mechanisms. The mouse skin infection model was used to investigate the in vivo efficacy. RESULTS: Compound 5a was selected as a potential anti-MRSA agent, which exhibited potent anti-MRSA activity in vitro and in vivo, low cytotoxicity and hemolysis under an effective dose. Moreover, compound 5a showed good stability in 50% plasma, a low tendency of resistance development and capabilities to disrupt bacterial biofilms. The mechanism studies revealed that compound 5a could inhibit the biosynthesis of bacteria cell walls, damage the membrane, disturb energy metabolism and amino acid metabolism pathways, and interfere with protein synthesis and nucleic acid function. CONCLUSIONS: These results suggested that compound 5a is a promising candidate for combating MRSA infections, providing valuable information for further exploiting a new generation of therapeutic antibiotics.
ABSTRACT
Purpose: The number of families who lost their only child was over one million in 2012 in China, and it is growing rapidly every year. Without their only child, they will inevitably worry about their health and life for their later years. It is important to explore the quality of life and influencing factors of the parents. Methods: The cluster sampling method was adopted to select the participants in Wuhu city, Anhui province, central China. The generalized linear regression models were performed to analyze factors influencing EQ-VAS scores. Results: The parents with different monthly income (P = 0.001) and self-rated health status (P < 0.001) had different EQ-VAS scores. Educational level, self-rated health status, number of chronic diseases, depression and having grandchildren were significantly associated with their EQ-VAS score. Conclusion: The government should encourage public medical institutions to provide convenient health management and medical services to this vulnerable group. Priority treatment should be given to the parents who already have multiple diseases. The parents who were depressed should be given timely intervention. The government should give more financial subsidies to the parents who need to raise their grandchildren.
