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UM15 reinforces a lymphocyte-mimicking nanotrap for precise HIV-1 inhibition

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Nano Research 2023年第7期16卷 9906-9920页

作者： Jinbang Zhang Zhengyang Li Jiaxin Li Hui Li Junwei Che Te Zhao Pengfei Zou Jingwan Han Yang Yang Meiyan Yang Yuli Wang Wei Gong Haihua Xiao Zhiping Li Lin Li chunsheng gao State key Laboratory of Toxicology and Medical Countermeasure Beijing Institute of Pharmacology and ToxicologyBeijing 100039China Pharmaceutical College Henan UniversityKaifeng 475001China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China School of Public Health and Health Management Gannan Medical UniversityGanzhou 341000China Institute of Chemistry Chinese Academy of SciencesBeijing 100190China

Even the potential of T cell-mimicking nanotrap for long term viral control due to its overcoming of human immunodeficiency virus(HIV)genetic diversity and viral resistance,the robust HIV inhibition was not expected because these nanotraps displayed no obvious advantages compared with the infinite host cells.Herein,a glycoprotein 120(gp120)-targeting polypeptide UM15 reinforced lymphocyte-mimicking nanotrap was constructed,and its improved HIV-1 inhibiting efficacy was validated.According to the results,the constructed nanotraps exhibited evident escaping ability from uptake of the mononuclear phagocyte system and highly improved binding ability with gp120 proteins.The constructed nanotraps neutralized all tested HIV-1 pseudo typed viruses with IC80 of 21.0μg/mL,and inhibited both X4-tropic and R5-tropic HIV-1 with IC80 of 34.4 and 20.6μg/mL,respectively.Approximately 40%of gp120 was observed to be shed from pseudo virus,and above 40%bystander T cells were prevented from gp120-induced death by the constructed nanotraps.The safety of the constructed nanotraps was confirmed both in vitro and in mice.Therefore,the constructed nanotraps could specifically neutralize free HIV-1,selectively bind with gp120 expressing HIV-1 infected cells,cause gp120 shedding,inhibit gp120-induced bystander T cell killing on the premise of safety,and were considered as promising therapeutic agents for precise inhibition of HIV.

关键词： nanotrap lymphocyte membrane UM15 human immunodeficiency virus-1(HIV-1) glycoprotein 120(gp120)

Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer's disease mice

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Bioactive Materials 2021年第2期6卷 529-542页

作者： Yang Han Chunhong gao Hao Wang Jiejie Sun Meng Liang Ye Feng Qianqian Liu Shiyao Fu Lin Cui chunsheng gao Yi Li Yang Yang Baoshan Sun School of Traditional Chinese Medicine Shenyang Pharmaceutical UniversityShenyang110016PR China State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing100850PR China School of Functional Food and Wine Shenyang Pharmaceutical UniversityShenyang10016PR China Instituto National de Investigação Agrária e Veterinária I.P.Pólo Dois PortosQuinta da AlmoinhaDois Portos2565-191Portugal

Neuronal mitochondrial dysfunction caused by excessive reactive oxygen species(ROS)is an early event of sporadic Alzheimer's disease(AD),and considered to be a key pathologic factor in the progression of AD.The targeted delivery of the antioxidants to mitochondria of injured neurons in brain is a promising therapeutic strategy for AD.A safe and effective drug delivery system(DDS)which is able to cross the blood-brain barrier(BBB)and target neuronal mitochondria is necessary.Recently,bioactive materials-based DDS has been widely investigated for the treatment of AD.Herein,we developed macrophage(MA)membrane-coated solid lipid nanoparticles(SLNs)by attaching rabies virus glycoprotein(RVG29)and triphenylphosphine cation(TPP)molecules to the surface of MA membrane(RVG/TPP-MASLNs)for functional antioxidant delivery to neuronal mitochondria.According to the results,MA membranes camouflaged the SLNs from being eliminated by RESrich organs by inheriting the immunological characteristics of macrophages.The unique properties of the DDS after decoration with RVG29 on the surface was demonstrated by the ability to cross the BBB and the selective targeting to neurons.After entering the neurons in CNS,TPP further lead the DDS to mitochondria driven by electric charge.The Genistein(GS)-encapsulated DDS(RVG/TPP-MASLNs-GS)exhibited the most favorable effects on reliveing AD symptoms in vitro and in vivo by the synergies gained from the combination of MA membranes,RVG29 and TPP.These results demonstrated a promising therapeutic candidate for delaying the progression of AD via neuronal mitochondria-targeted delivery by the designed biomimetic nanosystems.

关键词： Macrophage-membrane coating Biomimetic nanosystems Neuronal mitochondria targeting Blood-brain barrier Alzheimer's disease Genistein

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基于临床定位构建中药疗效评价体系的思考

中华中医药杂志 2024年第2期39卷 626-630页

作者：雷翔商洪才高春升崔天红程金莲北京岐黄科技有限公司北京100055 北京中医药大学中医内科学教育部重点实验室北京100700 首都医科大学附属北京中医医院北京100010

中医药的临床疗效是其存在和发展的根本,如何评价中医药临床疗效是业界研究的热点和难点,虽业内对现有的中医药疗效评价体系多有诟病,但又迟迟难以形成新的评价体系。文章根据以患者为中心,以临床价值为导向研发中药的理念,提出基于临... 详细信息

中医药的临床疗效是其存在和发展的根本,如何评价中医药临床疗效是业界研究的热点和难点,虽业内对现有的中医药疗效评价体系多有诟病,但又迟迟难以形成新的评价体系。文章根据以患者为中心,以临床价值为导向研发中药的理念,提出基于临床定位构建中药疗效评价体系和标准的思路,并对中药临床疗效评价标准制定过程中行业学会、监管部门和生产企业共同参与的重要性进行论述,旨在促进中药疗效评价体系的发展。

关键词：中医药临床定位疗效评价临床研究评价体系

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Carrier-free highly drug-loaded biomimetic nanosuspensions encapsulated by cancer cell membrane based on homology and active targeting for the treatment of glioma

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Bioactive Materials 2021年第12期6卷 4402-4414页

作者： Yueyue Fan Yuexin Cui Wenyan Hao Mengyu Chen Qianqian Liu Yuli Wang Meiyan Yang Zhiping Li Wei Gong Shiyong Song Yang Yang chunsheng gao College of Pharmacy Henan UniversityKaifeng475000PR China State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing100850PR China

Nanosuspensions,as a new drug delivery system for insoluble drugs,are only composed of a drug and a small amount of stabilizer,which is dispersed in an aqueous solution with high drug-loading,small particle size,high dispersion,and large specific surface area.It can significantly improve the dissolution,bioavailability,and efficacy of insoluble drugs.In this study,paclitaxel nanosuspensions((PTX)NS)were prepared by an ultrasonic precipitation method,with the characteristics of simple preparation and easy repetition.With the help of a homologous targeting mechanism,a kind of glioma C6 cancer cell membrane(CCM)-coated(PTX)NS was developed and modified with DWSW peptide to obtain DWSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting.The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier(BBB)and selectively target tumor tissues.Cell uptake experiments and in vivo imaging confirmed that the uptake of DWSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased.Cytotoxicity test and in vivo anti-glioma studies showed that DWSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice.Finally,the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape.This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.

关键词： Nanosuspensions Cancer cell membrane Biomimetic drug-delivery systems Gliomas Blood-brain barrier Paclitaxel

Cell relay-delivery improves targeting and therapeutic efficacy in tumors

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Bioactive Materials 2021年第6期6卷 1528-1540页

作者： Ye Feng Qianqian Liu Yi Li Yang Han Meng Liang Hao Wang Qing Yao Yuli Wang Meiyan Yang Zhiping Li Wei Gong Yang Yang chunsheng gao State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing100850PR China Hubei University of Science and Technology Xianning437100PR China School of Traditional Chinese Medicine Shenyang Pharmaceutical UniversityShenyang110016PR China

Cell-mediated drug delivery system(CDDS)has shown great potential for cancer therapy.However,a single cell-mediated drug delivery mechanism has not generally been successful,particularly for systemic administration.To augment the antitumor therapy efficacy,herein,we propose a strategy of cell relay-delivery for the use of artificially damaging/aging erythrocytes to hitchhike on circulating monocytes/macrophages for intratumoral accumulation of anticancer drugs.This biomimetic relay-delivery strategy was derived from the manner in which circulating monocytes/macrophages in body specifically engulf damaged/senescent erythrocytes and actively transmigrate into the tumor bulk.The strategy elegantly combines the natural functions of both cells,which therefore provides a new perspective to challenge current obstacles in drug delivery.According to the strategy,we developed biotinylated erythrocyte-poly(lactic-co-glycolic acid)(PLGA)nanoparticle hybrid DDSs(bE-NPs)using avidin-biotin coupling.In such a system,biotinylated erythrocytes can mimic the natural property of damaged/senescent erythrocytes,while PLGA NPs are capable of encapsulating anticancer drugs and promoting sustained drug release.Anticancer drugs can effectively target tumor sites by two steps.First,by using biotinylated erythrocytes as the carrier,the drug-loaded PLGA NPs could be specifically phagocytized by monocytes/macrophages.Second,by taking advantage of the tumor-tropic property of monocytes/macrophages,the drug-loaded PLGA NPs could be efficiently transported into the tumor bulk.After encapsulating vincristine(VIN)as the model drug,bE-NPs exhibited the most favorable antitumor effects in vitro and in vivo by the cell relay-delivery effect.These results demonstrate that the cell relay-delivery provides a potential method for improving tumor treatment efficacy.

关键词： Cell relay-delivering Cell-mediated drug delivery Hitchhiking Solid tumor

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光对秋水仙碱稳定性的影响及光稳定剂筛选

军事医学 2024年第5期48卷 376-381页

作者：杨国宝董静龚伟杨美燕高春生王玉丽杨阳军事科学院军事医学研究院

目的提高秋水仙碱（COL）在制剂缓释微丸中的光稳定性。方法对COL光化降解动力学进行研究，了解其降解规律，通过添加光稳定剂屏蔽光线以抑制COL发生光化降解，并考察了光稳定剂种类、颜色、用量、位置对COL缓释微丸光稳定性的影响。... 详细信息

目的提高秋水仙碱（COL）在制剂缓释微丸中的光稳定性。方法对COL光化降解动力学进行研究，了解其降解规律，通过添加光稳定剂屏蔽光线以抑制COL发生光化降解，并考察了光稳定剂种类、颜色、用量、位置对COL缓释微丸光稳定性的影响。结果以中间独立层的方式，用载药微丸重量4%的红氧化铁作为保护层制备的缓释微丸光照10d,COL光化降解产物含量未见增长。结论 COL缓释微丸中使用红氧化铁作为光稳定剂，能够有效避免COL发生光化降解。

关键词：秋水仙碱缓释微丸光化降解光稳定性光稳定剂氧化铁

新型自组装抗菌肽CR-16的性质及抑菌活性研究

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军事医学 2024年第5期48卷 369-375页

作者：崔亚楠邹鹏飞龚伟王玉丽高春生杨阳杨美燕军事科学院军事医学研究院

目的研究新型自组装多肽CR-16的性质及其对于大肠杆菌的抑菌活性，为细菌感染的治疗提供实验依据。方法在抗菌肽BuforinⅡ和LfcinB结构基础上，设计并合成了新型抗菌肽CR-16，采用粒径、电位、透射电镜、X线衍射仪等手段表征该抗菌肽... 详细信息

目的研究新型自组装多肽CR-16的性质及其对于大肠杆菌的抑菌活性，为细菌感染的治疗提供实验依据。方法在抗菌肽BuforinⅡ和LfcinB结构基础上，设计并合成了新型抗菌肽CR-16，采用粒径、电位、透射电镜、X线衍射仪等手段表征该抗菌肽的性质。在测定临界胶束浓度的基础上，采用原子力显微镜、圆二色谱法等对分子的自组装性能进行考察。采用二倍稀释法测定该肽的最小抑菌浓度，并运用透射电子显微镜分析其对细菌外膜的影响。结果抗菌肽CR-16能够成功自组装，自组装体呈现规则圆球状，性质稳定。抑菌实验表明，CR-16对3种大肠杆菌的生长均有抑制作用。值得重视的是，CR-16对产新德里金属-β-内酰胺酶1(NDM-1)的耐碳青霉烯类大肠杆菌生长有明显抑制作用，显示了其在抗细菌感染及抗耐药菌感染中的良好前景。结论 CR-16抗菌肽可以实现自组装，并且对大肠杆菌具有抑菌活性。

关键词：抗菌肽自组装抗生素耐药大肠杆菌抑菌活性

Corrigendum to“Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer’s disease mice”[Bioactive materials 6(2021)529-542]

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Bioactive Materials 2022年第1期7卷 73-73页

作者： Yang Han Chunhong gao Hao Wang Jiejie Sun Meng Liang Ye Feng Qianqian Liu Shiyao Fu Lin Cui chunsheng gao Yi Li Yang Yang Baoshan Sun Shenyang Pharmaceutical University Shenyang110016PR China State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing100850PR China Instituto National de Investigacao Agraria e Veterinaria I.P.Polo Dois PortosQuinta da AlmoinhaDois Portos2565-191Portugal

The authors regret publishing the incorrect address and affiliation.They have been now revised as follows:1.The Addresses are updated from.“a School of Traditional Chinese Medicine,Shenyang Pharmaceutical University,Shenyang,110016,PR China b State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Institute of Pharmacology and Toxicology,Beijing,100850,PR China c School of Functional Food and Wine,Shenyang Pharmaceutical University,Shenyang,10016,PR China.

关键词： Alzheimer Cor Modified

A Chromosome-Level Genome Assembly of Garlic (Allium sativum) Provides Insights into Genome Evolution and Allicin Biosynthesis

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Molecular Plant 2020年第9期13卷 1328-1339页

作者： Xiudong Sun Siyuan Zhu Ningyang Li Yi Cheng Jing Zhao Xuguang Qiao Li Lu Shiqi Liu Yanzhou Wang Chan Liu Benping Li Wu Guo Shuang gao Zemao Yang Fu Li Zheng Zeng Qing Tang Yupeng Pan Mengjiao Guan Jian Zhao Xiaomi ng Lu Huanwe n Meng Zhenlin Han Chun she ng gao Wenkai Jiang Xing Zhao Shilin Tian Jianguang Su Zhihui Cheng Touming Liu Shandong Agricultural University Tai'an 271018China Institute of Bast Fiber Crops Chinese Academy of Agricultural SciencesChangsha 410205China Northwest A&F University Yangling 712100China Novogene Bioinformatics Institute Beijing 100083China School of Pharmaceutical Sciences Wuhan UniversityWuhan 430071China

Garlic,an economically important vegetable,spice,and medicinal crop,produces highly enlarged bulbs and unique organosulfur compounds.Here,we report a chromosome-level genome assembly for garlic,with a total size of approximately 16.24 Gb,as well as the annotation of 57561 predicted protein-coding genes,making garlic the first Allium species with a sequenced genome.Analysis of this garlic genome assembly reveals a recent burst of transposable elements,explaining the substantial expansion of the garlic genome.We examined the evolution of certain genes associated with the biosynthesis of allicin and inulin neoseries-type fructans,and provided new insights into the biosynthesis of these two compounds.Furthermore,a large-scale transcriptome was produced to characterize the expression patterns of garlic genes in different tissues and at various growth stages of enlarged bulbs.The reference genome and large-scale transcriptome data generated in this study provide valuable new resources for research on garlic biology and breeding.

关键词： garlic genome genome evolution allicin inulin neoseries-type fructans expression profiling