1.Study on the pharmacological effects and mechanism of Gegen-Zhimu herb pair in preventing and treating Alzheimer's disease by UHPLC-Q/TOF-MS metabolomics strategy
Liang CHAO ; Hui WANG ; Shuqi SHEN ; Piaoxue YOU ; Kaihong JI ; Zhanying HONG
Journal of Pharmaceutical Practice and Service 2025;43(1):30-40
Objective To evaluate the efficacy of Puerariae lobatae radix (PLR) and Anemarrhenae Rhizoma (AR) in preventing and treating Alzheimer’s disease (AD) and explore its potential mechanism of action by LC-MS serum metabolomics strategy. Methods The AD rat model was established by administering aluminum chloride (AlCl3) and D-galactose (D-gal) for 20 weeks. The traditional Chinese medicine intervention group was given the PLR, AR, and PLR-AR extracts for 8 weeks by gavage. The model effect and efficacy were evaluated by Morris water maze test and biochemical indicators including SOD, NO, and MDA; Metabolomics research based on the UHPLC-Q/TOF-MS method was conducted, and relevant metabolic pathways were analyzed through the MetaboAnalyst online website. Results The learning and memory abilities of AD model rats were significantly decreased compared with the control group, and the levels of oxidative stress and lipid peroxides were significantly increased (P<0.05), while the SOD content was decreased considerably (P<0.01). The learning and memory abilities of AD model rats were improved, oxidative stress and lipid peroxidation levels were reversed, and serum SOD content was increased significantly after the intervention of PLR-AR, with better effects than single drugs. Through metabolomics, 70 differential metabolites were identified between the AD model group and the control group, mainly involving 10 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and unsaturated fatty acid biosynthesis, et.al. The intervention of PLR-AR could adjust 47 metabolites, with 20 metabolites showing significant differences (P<0.05). The significantly adjusted metabolites involve 6 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, et al. Conclusion The combination of PLR and AR could significantly improve the learning and memory abilities of AD rat models. The mechanism may be related to the improvement of oxidative stress and lipid peroxidation levels, the increase of serum SOD content, and the regulation of phenylalanine, tyrosine, and tryptophan biosynthesis pathways.
2.Whole genome analysis of two strains of Acinetobacter baumannii encoding class B and Class D carbapenemases
WANG Xiao ; XU Tongsheng ; YOU Shuqi
China Tropical Medicine 2024;24(11):1390-
Objective To elucidate the molecular characteristics of two Acinetobacter baumannii strains producing NDM-1, OXA-23, and OXA-51 carbapenemases through whole genome sequencing technology, explore the mechanism of drug resistance, evolutionary pathways, and transmission potential, and provide data support for the formulation of clinical infection control strategies. Methods Two strains of Acinetobacter baumannii producing class B and class D carbapenemases, sourced from the ICU environment of two hospitals in Shanghai, were selected as study subjects. Next-generation sequencing technology was used to obtain the whole genome sequences of the strains. The whole genome map of the strains was drawn based on GCskew and Prokka tools on the Proksee website. Drug susceptibility experiments and BacWGSTdb 2.0 online analysis platform were used to screen for drug resistance genes to analyze the drug resistance of strains. Virulence genes, multilocus sequence typing (MLST), capsule serotype, and plasmid migration were evaluated based on the VFDB database, PubMLST database, OriTfinder, Kptive, and other tools, and an evolutionary tree was drawn by Neighbor-Joining method. Results Whole genome data showed that both strains belong to ST164_Pasteur/ST1418_Oxford-KL47/OCL5 type. All of them carry seven resistance genes (blaADC-25, blaCARB-5, blaCARB-16, blaCARB-49, blaNDM-1, blaOXA-23, blaOXA-91) and non-mobile plasmids. They possess 45 virulence genes related to outer membrane proteins and efflux pumps and are closely related to 5 strains from Malaysia and China (Changsha, Nanchang, and Hangzhou). Conclusions For the first time, the coexistence of OXA-23, OXA-51, NDM-1 producing Acinetobacter baumannii has been detected in the ICU environment in Shanghai, potentially posing a serious threat to public health. It is necessary to strengthen the monitoring and research of such strains to develop effective prevention and control strategies.

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