The infection in burn wounds covered by biologic dressings leads to wound deepening and chronic wounds. The introduction of silver nanoparticles (AgNPs) into biologic dressings is a beneficial method to prevent wound infection and simultaneously prom
Introduction: The opportunistic pathogen Candida albicans can form biofilms, resulting in drug resistance with great risk to medical treatment. Methodology: We investigated the ability of C. albicans to form biofilms on different materials, as well as the inhibitory and eradicating effects of cordycepin on biofilm. The action mechanism of cordycepin against biofilm was studied by crystal violet staining, XTT [2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction method, phenol-sulfuric acid method, cellular superficial hydrophobicity (CSH) assay, and confocal laser scanning microscope observation. We also evaluated the acute toxicity of cordycepin in vivo. Results: The results showed facile formation of biofilms by C. albicans on polypropylene. The 50% minimum inhibitory concentration (MIC 50 ) of cordycepin was 0.062 mg/mL. A concentration of 0.125 mg/mL significantly decreased biofilm formation, metabolic activity, secretion of extracellular polysaccharides, and relative CSH. Cordycepin could inhibit biofilm formation at low concentration without affecting fungal growth. In addition, cordycepin effectively eradicated 59.14% of mature biofilms of C. albicans at a concentration of 0.5 mg/mL. For acute toxicity, the LD 50 (50% of lethal dose) of cordycepin was determined as higher than 500 mg/kg for mice. Conclusion: The results of this study show that cordycepin significantly inhibited and eradicated biofilms by decreasing metabolic activity, the ratio of living cells, the hydrophobicity, and damaging the extracellular polysaccharides of biofilm. These findings should facilitate more effective application of cordycepin and suggest a new direction for the treatment of fungal infections. Keywords: cordycepin, Candida albicans , biofilm, inhibition, eradication
SHR4640, a highly selective URAT1 inhibitor, was evaluated to investigate its inhibitory effects on CYP2C8 and CYP3A4 in vivo clinical trial. This study assessed the pharmacokinetic (PK) impact of SHR4640 when co-administered with the CYP2C8 probe substrate repaglinide and the CYP3A4 probe substrate midazolam.
Abstract Nowadays, consumers have an increasing demand for health products. In this study, an oral liquid was developed using a compound extract consisting of three herbal extracts ( Dendrobium nobile Lindl. , Lycium barbarum , and Puerariae lobatae Radix) because the compound extract (a combination of all three extracts) was superior to every single extract in promoting the phagocytic capacity of RAW264.7 macrophages and the proliferation ability of GES‐1 cells. In this oral liquid, the dosage of the stabilizer and the sweetener was selected using a stability test and sensory quality evaluation. When 0.30% (m/v) xanthan gum and 0.20% (m/v) mogroside were added, the oral liquid had not only a good stability but also the highest sensory score for overall acceptability. The chemical composition analysis showed that the oral liquid had various functional ingredients including polysaccharides, phenols, alkaloids, and so forth. The immune‐enhancing efficacy of the oral liquid was evaluated in BALB/c mice by measuring the levels of different immune indicators. The results indicated that the oral liquid obviously enhanced nonspecific and specific immunity. A rat model with ethanol‐induced gastric ulcer was used to examine the protective effect of the oral liquid on the gastric mucosa and to explore the related mechanisms. The oral administration of the oral liquid for days significantly prevented the formation of gastric ulcer. This study provided an effective oral liquid that could enhance immunity and protect gastric mucosa.
This study aimed to examine the anti-biofilm activity and mechanism of gallic acid (GA), kaempferol-7-O-glucoside (K7G) and apigenin-7-O-glucoside (A7G) against Staphylococcus aureus and Escherichia coli.The antibacterial activity of the natural compounds was determined by serial dilution method. The inhibitory activity of natural compounds on biofilms was determined by crystal violet staining method. The effects and mechanisms of natural compounds on bacterial biofilms were analyzed by atomic force microscopy.In our study, compared with GA and K7G, A7G was found to exhibit the strongest anti-biofilm and antibacterial activities. The minimum biofilm inhibitory concentration (MBIC) of A7G against S. aureus and E. coli was 0.20 mg/mL and 0.10 mg/mL, respectively. The inhibition rates of 1/2 MIC of A7G on biofilms of S. aureus and E. coli were 88.9%, and 83.2% respectively. Moreover, atomic force microscope (AFM) images showed the three-dimensional biofilm morphology of S. aureus and E. coli, and the results indicated that A7G was highly effective in biofilm inhibition.It was found that the inhibition of A7G on biofilm was achieved through inhibiting on exopolysaccharides (EPS), quorum sensing (QS), and cell surface hydrophobicity (CSH). A7G exerted strong anti-biofilm activities by inhibiting EPS production, QS, and CSH. Hence, A7G, as a natural substance, could be a promising novel antibacterial and anti-biofilm agent for control of biofilm in food industry.
Abstract Sphingolipids (SLs) are vital for cells as forming membrane and transducing signals. The first step for de novo biosynthesis of SLs is catalyzed by the pyridoxal‐5′‐phosphate (PLP)‐dependent enzyme serine palmitoyltransferase (SPT), which has been proven to be a promising drug target for treating various diseases. However, there are few SPT‐specific inhibitors have been identified so far. Myriocin, a natural fungal product, is confirmed as the most potent inhibitor of SPT and has been widely used, but studies of its molecular mechanism are still underway. Besides, there is no intact co‐crystal structure of SPT‐binding myriocin until now. Aiming to uncover the interaction mechanism between SPT‐ and PLP‐binding myriocin at the molecular level, a systematic computational strategy was performed in this present study. Firstly, covalent docking was implemented to preliminarily predict the binding pose SPT/PLP‐myriocin aldimine and its structurally similar intermediate SPT/PLP‐β‐ketoacid aldimine. Secondly, two binding complexes were treated as initial structures to perform molecular dynamics simulations and binding free energy calculations. The calculated docking scores and predicted binding energies were consistent with the reported bioactivities. Finally, the binding mechanism of myriocin binding with SPT was meticulously described, and the key residues making favorable contributions were highlighted. Taken together, the current study could provide some important information and valuable guidance for further rational screening, design, and modification of potent specific SPT inhibitors.
Heart rate variability (HRV) signals are reported to be associated with the personalized drug response in many diseases such as major depressive disorder, epilepsy, chronic pain, hypertension, etc. But the relationships between HRV signals and the personalized drug response in different diseases and patients are complex and remain unclear. With the fast development of modern smart sensor technologies and the popularization of big data paradigm, more and more data on the HRV and drug response will be available, it then provides great opportunities to build models for predicting the association of the HRV with personalized drug response precisely. We here review the present status of the HRV data resources and models for predicting and evaluating of personalized drug responses in different diseases. The future perspectives on the integration of knowledge and personalized data at different levels such as, genomics, physiological signals, etc. for the application of HRV signals to the precision prediction of drug therapy and their response will be provided.
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