The chronic infections related to biofilm and intracellular bacteria are always hard to be cured because of their inherent resistance to both antimicrobial agents and host defenses. Herein we develop a facile approach to overcome the above conundrum through phosphatidylcholine-decorated Au nanoparticles loaded with gentamicin (GPA NPs). The nanoparticles were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS) and ultraviolet−visible (UV−vis) absorption spectra which demonstrated that GPA NPs with a diameter of approximately 180 nm were uniform. The loading manner and release behaviors were also investigated. The generated GPA NPs maintained their antibiotic activities against planktonic bacteria, but more effective to damage established biofilms and inhibited biofilm formation of pathogens including Gram-positive and Gram-negative bacteria. In addition, GPA NPs were observed to be nontoxic to RAW 264.7 cells and readily engulfed by the macrophages, which facilitated the killing of intracellular bacteria in infected macrophages. These results suggested GPA NPs might be a promising antibacterial agent for effective treatment of chronic infections due to microbial biofilm and intracellular bacteria.
Microbial biofilms, prevalent in nature and inherently resistant to both antimicrobial agents and host defenses, can cause serious problems in the chemical, medical and pharmaceutical industries. Herein we demonstrated that conjugation of an aminoglycoside antibiotic (streptomycin) to chitosan could efficiently damage established biofilms and inhibit biofilm formation. This method was suitable to eradiate biofilms formed by Gram-positive organisms, and it appeared that antibiotic contents, molecular size and positive charges of the conjugate were the key to retain this anti-biofilm activity. Mechanistic insight demonstrated chitosan conjugation rendered streptomycin more accessible into biofilms, thereby available to interact with biofilm bacteria. Thus, this work represent an innovative strategy that antibiotic covalently linked to carbohydrate carriers can overcome antibiotic resistance of microbial biofilms, and might provide a comprehensive solution to combat biofilms in industrial and medical settings.
miRNAs are expressed in many mammalian cells, acting specific roles in regulating gene expression or mediating special mRNAs cleavage by targeting their 3'-untranslated region (3'UTR). Some miRNAs are essential and important for animal development. However, it is still unclear what the relationship is between miR-34c and mammalian spermatogonial stem cells (SSCs). We found that a conserved microRNA-34c through its target-Nanos2, regulating SSCs' differentiation in mouse. Immunohistochemistry analysis of Nanos2 and miR-34c FISH results revealed the opposite expression trends between them. Seven bioinformatics websites and programs predicted that miR-34c has interaction sites in Nanos2's 3'UTR. Dual-luciferase reporter vector and mutated dual-luciferase reporter vector analysis validated that they are interacted. After transfection miR-34c mimics into mouse SSCs, or miR-34c lentiviral vector in vitro co-cultivation with seminiferous tubules, and Western blot analysis demonstrated that miR-34c over-expression could suppress Nanos2 expression in post-transcription level. Our experiments identified that miR-34c may promote meiosis process by interacting with Nanos2 leading up-regulation of Stra8 in mouse spermatogonial stem cells.
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