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Nanocarriers for siRNA delivery to overcome cancer multidrug resistance

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chinese Science bulletin 2013年第33期58卷 4021-4030页

作者： MENG QingShuo YIN Qi li yaping Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of Sciences

Multidrug resistance(MDR)is an extremely complexed phenomenon in tumor chemotherapy and is one of the major obstacles for successful *** of RNA interference(RNAi)offers a new strategy with great potential to reverse *** genes,which contribute to the emerging of MDR,can be silenced by ***,many natural barriers have to be overcome for efficient and safe delivery of *** recent years,the various kinds of nanocarriers,such as liposomes,cationic polymers,and inorganic materials,have been developed to deliver siRNA and show good results in reversing *** review mainly summarizes the barriers in siRNA delivery and recent progress in designing nanotechnology-based siRNA delivery systems to overcome tumor MDR.

关键词： siRNA 纳米载体递送耐药性癌症阳离子聚合物多药耐药 RNAi

ETCM v2.0:An update with comprehensive resource and rich annotations for traditional chinese medicine

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药学学报:英文版 2023年第6期13卷 2559-2571页

作者： Yanqiong Zhang Xin li yulong Shi Tong Chen Zhijian Xu Ping Wang Meng yu Wenjia Chen Bing li Zhiwei Jing Hong Jiang Lu Fu Wenjing gao Yanhua Jiang Xia Du Zipeng Gong Weiliang Zhu Hongjun Yang Haiyu Xu institute of chinese materia medica China Academy of Chinese Medical SciencesBeijing 100700China State Key Laboratory of Drug Research Drug Discovery and Design CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China National Resource Center for chinese materia medica Chinese Academy of Chinese Medical SciencesBeijing 100700China institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing 100700China Shaanxi academy of Traditional chinese Medicine Xi'an 710003China State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Provincial Key Laboratory of PharmaceuticsGuizhou Medical UniversityGuiyang 550004China china academy of chinese medical sciences Beijing 100700China

Existing traditional chinese medicine(TCM)-related databases are still insufficient in data standardization,integrity and precision,and need to be updated ***,an Encyclopedia of Traditional chinese Medicine version 2.0(ETCM v2.0,http://***/ETCM2/front/#/)was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient chinese medical books,9872 chinese patent drugs,2079 chinese medicinal materials and 38,298 *** facilitate the mechanistic research and new drug discovery,we improved the target identification method based on a two-dimensional ligand similarity search module,which provides the confirmed and/or potential targets of each ingredient,as well as their binding ***,five TCM formulas/chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0,which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy,to summarize the rules of prescription use,and to find alternative drugs for endangered chinese medicinal ***,ETCM v2.0 provides an enhanced Java Script-based network visualization tool for creating,modifying and exploring multi-scale biological *** v2.0 may be a major data warehouse for the quality marker identification of TCMs,the TCM-derived drug discovery and repurposing,and the pharmacological mechanism investigation of TCMs against various human diseases.

关键词： Traditional chinese medicine Database Target identification Network visualization New drug research and development Molecular mechanism Quality marker Drug repurposing

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膜荚黄芪苷元的结构

化学学报 1983年第12期41卷 1137-1145页

作者：曹正中俞家华甘立宪周维善南京药物研究所中国科学院上海有机化学研究所

从膜荚黄芪的根中分得膜荚黄芪皂苷甲,皂苷乙和皂苷丙.膜荚黄芪皂苷甲是主要成分.药理试验有降压和抗炎作用、皂苷甲经Smith氧化降解得到膜荚黄芪苷元1.用IR,1HNMR,13C NMR,MS和化学降解证明其结构为1.根据镧系位移试剂的1H NMR,1的C20... 详细信息

从膜荚黄芪的根中分得膜荚黄芪皂苷甲,皂苷乙和皂苷丙.膜荚黄芪皂苷甲是主要成分.药理试验有降压和抗炎作用、皂苷甲经Smith氧化降解得到膜荚黄芪苷元1.用IR,1HNMR,13C NMR,MS和化学降解证明其结构为1.根据镧系位移试剂的1H NMR,1的C20和C24的构型分别确定为S和R.

关键词：膜荚黄芪苷元 NMR 基峰相对丰度 MS 偶合常数次甲基针晶

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天目山藜蘆中的植物鹼

化学学报 1956年第4期 299-304页

作者：朱任宏王友海中国科学院药物研究所中国科学院药物研究所上海

從天目山藜廬中分得两种新植物鹼,暂命名为天目藜廬鹼甲和天目藜廬鹼乙。前者实验式为C27H43ON,熔點172—174°,[a]D16=-99.3°,已製成其结晶的盐酸盐等。後者的实验式为C34H51O8N,熔點231°,[a]D13=+24°,亦已製成其结晶的盐酸盐等。... 详细信息

從天目山藜廬中分得两种新植物鹼,暂命名为天目藜廬鹼甲和天目藜廬鹼乙。前者实验式为C27H43ON,熔點172—174°,[a]D16=-99.3°,已製成其结晶的盐酸盐等。後者的实验式为C34H51O8N,熔點231°,[a]D13=+24°,亦已製成其结晶的盐酸盐等。当天目藜廬鹼乙水解後,可得其结晶的胺鹼的盐酸盐,熔點192°。另從上海购买的藜廬中,分得一金黄色针状色素,实验式为C10H8O3,熔點172°,已製成其结晶的乙酸酯和溴化物。

关键词：天目山植物抽提液

Characterization of a small-molecule inhibitor targeting NEMO/IKKβto suppress colorectal cancer growth

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1219-1231页

作者： Zhenlong yu Jian gao Xiaolei Zhang yulin Peng Wenlong Wei Jianrong Xu Zhenwei li Chao Wang Meirong Zhou Xiangge Tian Lei Feng Xiaokui Huo Min liu Mingliang Ye De-an Guo Xiaochi Ma Pharmaceutical Research Center Second Affiliated HospitalDalian Medical UniversityDalian 116000China College of Pharmacy College(Institute)of Integrative MedicineDalian Medical UniversityDalian 116044China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China CAS Key Laboratory of Separation sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China shanghai Research Center for Modernization of Traditional chinese Medicine National Engineering Research Center for TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China academy of Integrative Medicine Shanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai 201203China Neurology Department Dalian University Affiliated Xinhua HospitalDalian 116021China

NEMO/IKKβcomplex is a central regulator of NF-κB signaling pathway,its dissociation has been considered to be an attractive therapeutic ***,using a combined strategy of molecular pharmacological phenotyping,proteomics and bioinformatics analysis,Shikonin(SHK)is identified as a potential inhibitor of the IKKβ/NEMO *** destabilizes IKKβ/NEMO complex with IC_(50) of 174 nM,thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in *** addition,we also elucidated the potential target sites of SHK in the NEMO/IKKβ*** study provides some new insights for the development of potent small-molecule PPI inhibitors.

关键词： IKKβ colorectal cancer

Structural insights into signal transduction of the purinergic receptors P2Y_(1)R and P2Y_(12)R

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Protein & Cell 2023年第5期14卷 382-386页

作者： Beibei li Shuo Han Mu Wang yu yu limin Ma Xiaojing Chu Qiuxiang Tan Qiang Zhao Beili Wu AS Key Laboratory of Receptor Research State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of chinese academy of sciences Beijing 100049China School of life Science and Technology ShanghaiTech UniversityShanghai 201210China Zhongshan institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan 528400China School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China

Dear Editor,The purinergic receptors(P2YRs)are involved in a variety of physiological processes,including proliferation,chemotaxis,cancer metastasis,cardiovascular events,neurodegenerative diseases and aging(Weisman et al.,2012).Thus far,eight human P2YRs have been characterized and are classified into two subfamilies based on their sequence homology and signal transduction mechanisms,including P2Y1 R-like receptors that signal preferentially through Gq/11 proteins and P2Y12R-like receptors that activate Gi/o proteins(Abbracchio et al.,2006).

关键词： P2Y cardiovascular

Single-cell RNA sequencing reveals a hierarchical transcriptional regulatory network of terpenoid biosynthesis in cotton secretory glandular cells

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Molecular Plant 2023年第12期16卷 1990-2003页

作者： Jia-ling lin Longxian Chen Wen-Kai Wu Xiao-Xiang Guo Cheng-Hui yu Min Xu Gui-Bin Nie Jun-ling Dun Yan li Baofu Xu ling-Jian Wang Xiao-Ya Chen Wei gao Jin-Quan Huang State Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyUniversity of CASChinese Academy of SciencesShanghai 200032China School of life Science and Technology ShanghaiTech UniversityShanghai 200031China Chongqing Key Laboratory of Micro-Nano Systems and Intlligent Transduction Collaborative InnovationNational Research Base of Inteligent Manufacturing ServiceChongqing Technology and Business UniversityChongqing 400067China Analytical Applications Center Shimadzu(China)Co.Ltd.Shanghai 200233China Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Insttute for Drug DiscoveryYantai 264117ShandongChina State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China shanghai Key Laboratory of Plant Functional Genomics and Resources Shanghai Chenshan Botanical GardenShanghai 201602China National Key Laboratory of Cotton Bio-breeding and Integrated Utilization(Henan University) Henan 475004China

Plants can synthesize a wide range of terpenoids in response to various environmental ***,the specific regulatory mechanisms governing terpenoid biosynthesis at the cellular level remain largely *** this study,we employed single-cell RNA sequencing to comprehensively characterize the transcriptome profile of cotton leaves and established a hierarchical transcriptional network regulating cellspecific terpenoid *** observed substantial expression levels of genes associated with the biosynthesis of both volatile terpenes(such asβ-caryophyllene andβ-myrcene)and non-volatile gossypol-type terpenoids in secretory glandular ***,two novel transcription factors,namely GoHSFA4a and GoNAC42,are identified to function downstream of the Gossypium PIGMENT GLAND FORMATION *** transcription factors could directly regulate the expression of terpenoid biosynthetic genes in secretory glandular cells in response to developmental and environmental *** convenient retrieval of the single-cell RNA sequencing data generated in this study,we developed a user-friendly web *** findings not only offer valuable insights into the precise regulation of terpenoid biosynthesis genes in cotton leaves but also provide potential targets for cotton breeding endeavors.

关键词： hierarchical network cotton

Ocellatuspyrones A‒G,new antibacterial polypropionates from the chinese mollusk Placobranchus ocellatus

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Marine life Science & Technology 2023年第3期5卷 373-386页

作者： Song-Wei li Dan-Dan yu Ming-Zhi Su li-Gong Yao Hong Wang Xueting liu yue-Wei Guo Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals College of Pharmaceutical ScienceZhejiang University of TechnologyHangzhou 310014China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug DiscoveryYantai 264117China

Marine invertebrates serve as rich sources of secondary metabolites with intriguing chemical diversities and a wide spectrum of biological ***,marine shell-less sacoglossan mollusks have attracted much attentions due to the fact that mollusks apply complex metabolites as chemical defense agents against to their *** the purpose of discovering bioactive secondary metabolites to develop marine-derived medicines from the South china Sea,we have conducted a chemical study on the photosynthetic mollusk Placobranchus *** a result,seven newγ-pyrone polypropionates,namely(±)-ocellatuspyrone A(1),(±)-ocellatuspyrone B(2),and ocellatuspyrones C−G(5,9−12),along with fve known polypropionates,have been isolated and characterized from the South china Sea photosynthetic mollusk Placobranchus *** spectroscopic analysis,single crystal X-ray difraction analysis,modifed Mosher’s method,ECD comparison,CD exciton chirality method,TDDFT-ECD calculation,and chemical conversion were used to determine the structures and absolute confgurations of the new compounds and the stereochemistry of undefned known compounds 4,6 and *** these isolated polypropionates were evaluated in bioassays for their biological activities,including antibacterial,neuroprotective efect,anti-infammatory,PTP1B inhibitory,and antiviral *** 7,8 and 11 were found for the frst time to show antibacterial activity against fsh pathogenic bacteria Streptococcus parauberis(the main pathogen causing fsh streptococcal infections and acute death)with MIC values of 35.8,34.2,and 37.4μg/mL,respectively,which might be potential novel antibacterial agents for the treatment of fsh infectious diseases.

关键词： Placobranchus ocellatus γ-pyrone polypropionate Photosynthetic mollusk Antibacterial activity

Functional Metabolomics Reveals that Astragalus Polysaccharides Improve lipids Metabolism through Microbial Metabolite 2-Hydroxybutyric Acid in Obese Mice

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Engineering 2022年第2期8卷 111-122页

作者： Bingbing li Ying Hong yu Gu Shengjie Ye Kaili Hu Jian Yao Kan Ding Aihua Zhao Wei Jia Houkai li institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai 201203China shanghai institute of materia medica Chinese Academy of SciencesShanghai 201203China shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China University of Hawaii Cancer Center HonoluluHI 96813USA

Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic ***,the underlying mechanisms are not well *** metabolomics is increasingly used to investigate systemic effects on the host by iden-tifying metabolites with particular *** study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides(APS)by adopting a functional metabolomics *** effects of APS were determined in eight-week high-fat diet(HFD)-fed obese ***,gas chromatography–time-of-flight mass spectrometry(GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues,and liquid chromatography–tandem mass spectrom-etry(LC–MS/MS)-based targeted metabolomics was *** potential functions of the metabo-lites were tested with in vitro and in vivo models of metabolic *** results first confirmed the metabolic benefits of APS in obese ***,metabolomics analysis revealed that APS supplemen-tation reversed the HFD-induced metabolic changes,and identified 2-hydroxybutyric acid(2-HB)as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by *** study indicated that 2-HB inhibited oleic acid(OA)-induced triglyceride(TG)*** was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 ***,it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose(HFHS)-fed *** conclusion,our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation,which modulated lipid metabolism both in vitro and in *** results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.

关键词： Astragalus polysaccharides(APS) Functional metabolomics 2-Hydroxybutyric acid Obesity