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Fine-tuning the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies via branched aliphatic functionalization

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Nano Research 2024年第4期17卷 2908-2918页

作者： Guanting Li Fengli Xia Hongying Xiao Shunzhe Zheng Shuwen Fu Han Qiao Qianhui Jin Xuanbo Zhang Dun Zhou Chutong Tian Jin Sun Zhonggui He Bingjun Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Emergency Department The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery ***,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous *** rational design of camptothecins-based prodrug nanoassemblies remains a ***,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug ***,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical *** length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and ***,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and *** findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based nanomedicines.

关键词： prodrug nanoassembly self-assembly antitumor efficacy tolerance 7-ethyl-10-hydroxycamptothecin(SN_(3)8)

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The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1400-1411页

作者： Shuo Wang Tian Liu Yuetong Huang Chaoying Du Danping Wang Xiyan Wang Qingzhi Lv Zhonggui He Yinglei Zhai Bingjun Sun Jin Sun Wuya college of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Medical Devices Shenyang Pharmaceutical UniversityShenyang 110016China School of pharmacy Binzhou Medical UniversityBinzhou 256600China

The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly *** the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug *** study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’*** extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative *** use of C_(20) can balance efficacy and *** results provide a great reference for the rational design of prodrug nanoassemblies.

关键词： Prodrugs Nanoassemblies Self-assembly Branched-chain fatty alcohols Disulfide bond Docetaxel Efficacy Safety

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Comparative study of the effects of Tartary buckwheat seed and sprout consumption on the physiological indices and gut microbiota of C57BL/6J mice

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Food Science and Human Wellness 2024年第2期13卷 791-800页

作者： Guohui Nan Haixia Zhao Qiong Wu Lisong Liu Zichao Guan Chenglei Li Huala Wu Dabing Xiang Qi Wu college of Life Science Sichuan Agricultural UniversityYa'an 625014China Faculty of Quality Management and Inspection&Quarantine Yibin UniversityYibin 644000China college of pharmacy and Biological Engineering Chengdu UniversityChengdu 610106China

Tartary buckwheat(Fagopyrum tataricum)is a well-known pseudocereal for its health and economic ***,abundant antinutritional factors(ANFs)reduces its health *** reported,germination can improve the nutritional profile of *** this study,we systematically evaluate the safety of Tartary buckwheat seeds(TB)and Tartary buckwheat sprouts(TBS)used as high active *** evaluating nutrition levels,bioactive compounds and ANFs in TBS during germinating,5^(th)-day TBS were selected as the raw material.C57BL/6J mice were gavaged daily with distilled water,TB,or TBS for 6 *** physiological indices related to ANFs were *** showed that the TB intake tends to generate negative effects on the gut microbiota,and ***,upon TB intake,the Fe^(3+)content in serum,trypsin activity in pancreas and jejunum decreased,while the cytokine,IgE,and histamine levels in serum,water content in faeces,cytokine levels in liver and jejunum ***,TBS did not induce any obvious negative effects on the above relevant indices and showed better lipid-lowering ***,TBS are safer and more effective as a raw material to produce the functional food for long-term consumption with the intention of preventing and treating hyperlipidaemia.

关键词： Tartary buckwheat Tartary buckwheat sprouts Antinutritional factors Gut microbiota Health effect

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Selective dissolution for stabilizing solid electrolyte interphase

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Chinese Chemical Letters 2024年第5期35卷 1-2页

作者： Kezhen Qi Shu-yuan Liu Ruchun Li college of pharmacy Dali UniversityDali 671000China Faculty of Chemistry and Chemical Engineering Yunnan Normal UniversityKunming 650500China

With pursuing high energy density batteries,traditional graphite anode could be unable to meet current needs[1-4].The high-capacity anodes have attracted increasing attention,such as lithium anodes and alloy-type anodes[5-8].Silicon anode,as a high-capacity alloy-type anode(3579 mAh/g),has attracted great attention[9].However,due to its unique electrochemical mechanism,significant changes in volume and morphology during charge/discharge process could lead to the decrease in cycling stability[9,10].Therefore,it is still challenging for silicon anode in tackling volume expansion and unstable interfaces.

关键词： electrolyte cycling unstable

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Balancing efficacy and safety of doxorubicin-loaded albumin nanoparticles utilizing pH-sensitive doxorubicin-fatty acid prodrugs

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Nano Research 2024年第7期17卷 5491-5500页

作者： Yuanhao Yu Shiyi Zuo Jiaxuan Song Lingxiao Li Tian Liu Jiayu Guo Yaqiao Li Danping Wang Qi Lu Helin Wang Dun Zhou Zhonggui He Xiaohong Liu Bingjun Sun Jin Sun School of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Wuya college of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of pharmacy The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China

albumin nanoparticles(ANPs)offer unique advantages for antitumor drug delivery system,including non-immunogenicity and inherent tumor-targeting *** present,only a few products,such as ABRAXANE®and FYARRO™,have been approved for clinical *** poor affinity of doxorubicin(DOX)for albumin,coupled with its numerous severe adverse reactions,poses challenges in the fabrication of desirable albumin nanoparticles loaded with *** this study,we developed prodrugs by conjugating fatty acids of varying lengths with *** aim was to investigate the balance between efficacy and safety through the selection of appropriate *** synthesized five pH-sensitive doxorubicin-fatty acid *** to free DOX,all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 ***,DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor ***,the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids,impacting their in vivo pharmacokinetics,antitumor effectiveness and tumor *** research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs,and it builds a good platform for creating ANPs which prioritize high drug loading,high efficiency,and minimal side effects.

关键词： fatty acid prodrug albumin doxorubicin pH-sensitive bond nanomedicines

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Antioxidant peptides from Lateolabrax japonicus to protect against oxidative stress injury in Drosophila melanogaster via biochemical and gut microbiota interaction assays

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Food Science and Human Wellness 2024年

作者： Chen Li Lichan Li Jing Cheng Xu Chen Mohamed A.Farag Xixi Cai Shaoyun Wang college of Chemical Engineering college of Biological Science and Engineering Fuzhou University Pharmacognosy Department Faculty of pharmacy Cairo University

Identification of natural substances with antioxidant properties is ongoing research for addressing issues related to oxidative stress especially attributed to environmental effects. Our previous study demonstrated that Lateolabrax japonicus peptides （LPH）， rich in Glu， Gly， and hydrophobic amino acids， exhibited remarkable antioxidant activity in vitro， with though its action mechanism yet to be revealed. Therefore， to assess the in vivo antioxidative properties of LPH， we employed H2O2to generate oxidative stress in Drosophila melanogaster model. Results indicated that LPH significantly prolonged the lifespan of Drosophila subjected to oxidative stress mostly mediated via LPH's enhancement of the antioxidant defense system and intestinal functions. Antioxidant effects were manifested by a decrease in malondialdehyde （MDA） levels， elevated superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） activities， decreased levels of reactive oxygen species （ROS） in intestinal epithelial cells， and the preservation of intestinal length. LPH effectively controlled the excessive proliferation and differentiation of oxidative stress-induced Drosophila intestinal stem cells. At the gene level， LPH upregulated the expression of antioxidant-related Nrf2 genes while concurrently downregulated mTOR expression level. Furthermore， high-throughput 16S rDNA sequencing revealed that the addition of LPH significantly influenced the diversity and abundance of the intestinal microbiota in H2O2-induced Drosophila. These findings provide a deeper understanding of the antioxidative mechanism of LPH， suggesting its potential applications in food industry and to be assessed using other in vivo oxidative stress models.

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Plant based metabolomics:a future prospective and versatile tool for metabolite databases of Curcuma longa

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未来食品学报(英文) 2024年第1期4卷 37-47页

作者： Shuvendhu Gupta Amrat Pal Singh Gurpreet Singh Xianting Ding alok Sharma Department of Pharmacognosy ISF College of PharmacyMoga 142001India Department of Pharmaceutical Chemistry ISF College of PharmacyMoga 142001India School of Biomedical Engineering Med-X Research InstituteShanghai Jiao Tong UniversityShanghai 200030China

Sophisticated analytical instruments are used for quality evaluation and scientific validation to compliance the Sophisticated analytical instruments are used for quality evaluation and scientific validation to compliance the market ***,increase in demand of Curcuma longa has led to a high swing in small and medium food *** present review is devoted to an in-depth information on metabolite database of *** from different analytical techniques such as high-performance thin-layer chromatography(HPTLC),liquid chromatography-mass spectrometry,gas chromatography-mass spectrometry and nuclear magnetic *** work highlights different extraction methods,phytochemistry along with structure activity relationship,nutritional profiling,market viability and pharmacology of *** bioactives of *** depends on various factors such as plants growth,temperature,humidity,soil type,collection,drying and extraction *** factors can contribute in quality evaluation of the food supplements if need to be *** introduction of omics approaches can helpful to explore the quality and identification of potential lead of *** results could play an essential role in the area of food-phyto based ***,metabolomics techniques may provide a analytical platfom by combination of different"omics"data souces for future esearch to food sand herbal based products.

关键词： Curcuma longa Omics approaches Multidisciplinary method Quality control Metabolomics

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Natural products from untapped sources as a potent reserve against antimicrobial resistance crisis

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Chinese Journal of Natural Medicines 2024年第7期22卷 577-579页

作者： GU Xiaoxia SUN Weiguang HU Zhengxi Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of PharmacyTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Since the discovery of penicillin in 1928,antibiotics have revolutionized modern medicine by effectively treating infectious diseases and saving countless ***,the widespread development of antimicrobial resistance(AMR)now threatens the efficacy and longevity of these critical drugs.A study published in The Lancet reported that bacterial AMR contributed to approximately 4.95 million deaths globally in 2019,with 1.27 million directly attributable to AMR(Fig.1)[1].Natural products(NPs)continue to play a crucial role in discovering new antibiotics.

关键词： Natural products Untapped sources Antimicrobial resistance

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Beyond 1,4-addition of in-situ generated(aza-)quinone methides and indole imine methides

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Chinese Chemical Letters 2024年第7期35卷 35-53页

作者： Yan-Li Li Zhi-Ming Li Kai-Kai Wang Xiao-Long He Medical college Xinxiang UniversityXinxiang 453000China School of pharmacy Xinxiang UniversityXinxiang 453000China School of Food and Bioengineering Xihua UniversityChengdu 610039China

The conjugate addition of in-situ generated(aza-)quinone methides(QMs)and indole imine methides(IIMs)emerged as a powerful protocol to access densely functionalized benzenes and *** alcohols,aminobenzhydryl alcohols,and varied indolylmethanols served as most effective precursors for the in-situ generation of such reactive species under acid *** relevant propargylic alcohol has proven to be an elegant precursor to generate the propargylic-QMs and-IIMs via the acid promoted dehydration process,thus enabling diverse challenging remote activation to proceed conjugate1,6-and 1,***,the heteroarene has proven to be workable to transfer the LUMO of the p-QMs and 2-IIMs,thus inducing the remote nucleophilic dearomative *** conjugate additions of(aza-)p-QMs and varied IIMs has made significant contribution in the field of remote activation chemistry in past *** review summarizes the latest advances of the remote conjugate additions of the in-situ generated QMs and IIMs.

关键词： Conjugate addition QMs IIMs LUMO Remote activation Dearomative addition

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One-step pore diffusion mechanism of Li+ in solid electrolyte interphase for fast-charging lithium-ion battery

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Rare Metals 2024年第7期43卷 3438-3440页

作者： Shan Wang Shu-Yuan Liu alireza Khataee Ke-Zhen Qi college of pharmacy Dali University Research Laboratory of Advanced Water and Wastewater Treatment Processes Department of Applied ChemistryFaculty of ChemistryUniversity of Tabriz Peoples' Friendship University of Russia (RUDN University)

Li+transport in solid electrolyte interphase is recognized as important factor,which has become a research ***,an one-step pore diffusion mechanism for Li+transport through solid electrolyte interphase was proposed,which was different from previous two-step *** one-step pore diffusion process could effectively eliminate the dynamic limitations of Li+transport in solid electrolyte interphase （SEI） for rapid charging *** work will contribute to the development of rapid charging lithium-ion batteries.

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