Diclofenac potassium (DCF-K) is a widely used nonsteroidal anti-inflammatory drug with enhanced therapeutic effects mediated by its bioactive metabolites, particularly 4′-hydroxydiclofenac (4′-OH-DCF) and 5-hydroxydiclofenac (5-OH-DCF). However, the accurate detection of DCF-K and its metabolites in complex biological matrices remains challenging due to trace concentrations and matrix interference. To address this challenge, a chitosan-bentonite molecularly imprinted polymer (CB-MIP) was developed using a dual-role strategy, where chitosan-bentonite (CB) serves as both substrate and functional monomer, combined with a hierarchical functional monomer system (acrylamide as an auxiliary monomer) to enhance binding affinity and selectivity for the specific capture of DCF-K and its metabolites. Comprehensive characterization confirmed the successful synthesis of CB-MIP, revealing improved stability, hydrophilicity, and a mesoporous structure. CB-MIP exhibited good adsorption capacity for DCF-K (17.2× higher than CB), with Langmuir isotherm and pseudo-second-order kinetics indicating monolayer chemisorption. Selectivity studies demonstrated good recognition capability for DCF-K, achieving a selectivity factor up to 77.3 against structural analogs and co-administered drugs. Furthermore, cluster analysis revealed the CB-MIP sensitivity to DCF-K concentration variations as low as 0.3 μg·mL −1 in complex matrices. Mechanistic studies identified electrostatic and hydrogen bonding interactions as the primary binding forces, validated by electrostatic potential simulations, hydrogen-bond modeling, and spectroscopic analyses. Practical application in mouse plasma and liver samples confirmed efficient enrichment and detection of DCF-K and metabolites (4′-OH-DCF, 5-OH-DCF, diclofenac acyl glucuronide) using CB-MIP coupled with HPLC/UPLC-MS/MS, achieving high sensitivity (limit of detection: 0.231 μg·mL −1 in liver) and reproducibility (relative standard deviation: 1.22 %–5.81 %). This work establishes CB-MIP as a robust pretreatment material for targeted drug/metabolite analysis in complex biological systems.
Lan Sugui,Li Zhirong,Su Aiqiu,Peng Yanhong,Liao Yanke,Liu Xuemei,Tan Qiang
The purpose of this study was focused on the mechanisms of the cross-resistance to tetracycline (TET), piperacillin Sodium (PIP), and gentamicin (GEN) in Staphylococcus aureus (SA) mediated by Rhizoma Coptidis extracts (RCE). The selected strains were exposed continuously to RCE at the sublethal concentrations for 12 days, respectively. The susceptibility change of the drug-exposed strains was determined by analysis of the minimum inhibitory concentration. The 16S rDNA sequencing method was used to identify the RCE-exposed strain. Then the expression of resistant genes in the selected isolates was analyzed by transcriptome sequencing. The results indicated that RCE could trigger the preferential cross-resistance to TET, PIP, and GEN in SA. The correlative resistant genes to the three kinds of antibiotics were upregulated in the RCE-exposed strain, and the mRNA levels of the resistant genes determined by RT-qPCR were consistent with those from the transcriptome analysis. It was suggested from these results that the antibacterial Traditional Chinese Medicines might be a significant factor of causing the bacterial antibiotic-resistance.
Jie Jing,Chunlan Zeng,Long Tian,Jiaqi Han,Longming Chen,Taoran Wang,Zhao Meng,Qingbin Meng
The overuse and misuse of antibiotics resulted in the emergence of multidrug-resistant bacteria. As a promising solution, antimicrobial peptides have attracted much attention. In this research, a series of peptides derived from MP9 through the substitution of tryptophan for alanine and the rearrangement of amino acid residues were designed and synthesized. MP9–10 displayed the highest anti-multidrug-resistant bacterial activity and the lowest cytotoxicity as well as hemolysis among all the derivates. Membrane disruption was the main mechanism for MP9–10 to kill bacteria. The in vivo results on mice also demonstrated that MP9–10 had the capacity to treat infections caused by Staphylococcus aureus bacteria. In summary, MP9–10 is a promising candidate for the treatment of multidrug-resistant bacterial infections.
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