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Oridonin restores hepatic lipid homeostasis in an LXRa-ATGL/EPT1 axis-dependent manner

Journal of Pharmaceutical Analysis 2023年第11期13卷 1281-1295页

作者： Yulian Chen Huanguo Jiang Zhikun Zhan Jindi Lu tanwei gu Ping Yu Weimin Liang Xi Zhang Shilong Zhong Lan Tang NMPA Key Laboratory for Research and Evaluation of Drug Metabolism Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou510515China Department of Pharmacy Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou510515China

Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory *** date,there is still a lack of effective and economical therapies for ***(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia *** this paper,we showed that ORI exerted significant protective effects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRa *** is reported that LXRa regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanolamine(PE)by promoting ATGL and EPT1 ***,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRadependent manner,and the results showed the TG reduction and PE *** detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATGL and EPT1 genes,*** together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRa-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.

关键词： Oridonin Lipid homeostasis TG reduction PE elevation LXRa-ATGL/EPT1 axis

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A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3232-3250页

作者： Ping Yu tanwei gu Yueyang Rao Weimin Liang Xi Zhang Huanguo Jiang Jindi Lu Jianglian She Jianmin guo Wei Yang Yonghong Liu Yingfeng Tu Lan Tang Xuefeng Zhou guangdong Provincial Key Laboratory of New Drug Screening Guangdong-Hong Kong-Macao Joint Laboratory for New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China NMPA Key Laboratory for Research and Evaluation of Drug Metabolism School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China guangdong Lewwin Pharmaceutical Research Institute Co. Ltd.Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and ResearchGuangdong Engineering Research Center for Innovative Drug Evaluation and ResearchGuangzhou 510990China

Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its *** study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)***,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS *** to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed *** developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 *** encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,*** main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated *** summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.

关键词： Acute kidney injury Piericidin glycoside Peroxiredoxin 1 Nanodrug Kim-1 targeted ADME Marine drug Druggability

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深层水平位移光纤传感监测技术浅析

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煤炭科技 2018年第3期39卷 34-37页

作者：王波张承飞顾德志刘锋南京维景数据工程有限公司江苏南京210000 贵州省地质矿产勘查开发局一〇六地质大队贵州贵阳563000 南京探维工程技术有限公司江苏南京210000

通过对深层水平位移传统监测方法与分布式光纤传感监测方法、原理及优缺点分析,并将两种方法应用于某基坑监测项目,通过两者在实际应用中的监测结果对比分析,认为基于分布式光纤的测斜监测系统可以很好地应用到实际工程当中,并能够弥补... 详细信息

通过对深层水平位移传统监测方法与分布式光纤传感监测方法、原理及优缺点分析,并将两种方法应用于某基坑监测项目,通过两者在实际应用中的监测结果对比分析,认为基于分布式光纤的测斜监测系统可以很好地应用到实际工程当中,并能够弥补传统水平位移监测方法的不足,同时,运用多种解调技术进行联合监测,能够实现监测效果的最优化。说明分布式光纤传感监测技术广阔应用前景。

关键词：深层水平位移传感监测分布式光纤钢绞线光缆

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