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Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

Engineering 2024年第5期36卷 178-192页

作者： Ruogu Qi Shanshan Wang Jiayi Yu tianming lu Zhiqiang Bi Weibo Liu Yuanyuan Guo Yong Bian Jianliang Shen Xuesong Zhang Wenhao Hu School of Medicine Nanjing University of Chinese MedicineNanjing 210023China Laboratory Animal Center Nanjing University of Chinese MedicineNanjing 210023China Key Laboratory of Carcinogenesis and Translational Research Ministry of Education/BeijingDepartment of Radiation OncologyBeijing Cancer HospitalBeijing 100142China Department of Orthopedics The Fourth Medical CenterThe Chinese People’s Liberation Army General HospitalBeijing 100853China State Key Laboratory of Ophthalmology Optometry and Vision ScienceSchool of Biomedical EngineeringWenzhou Medical UniversityWenzhou 325027China

Multiple myeloma(MM)is the second most prevalent hematological *** MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic *** study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@*** results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in ***,this material demonstrated a capability for drug release triggered by low pH ***,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM ***,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic ***,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

关键词： Multiple myeloma Bortezomib Drug delivery Dual targeting Controlled release

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Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome

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Journal of Pharmaceutical Analysis 2024年第1期14卷 152-155页

作者： Shuyu Zheng Yanlin Xin Jiamin Lin Zejuan Xie Keyu Cheng Shanshan Wang Wenli lu Hao Yang tianming lu Jun Li Ruogu Qi Yuanyuan Guo Department of Biochemistry and Molecular Biology School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing210023China Department of Neurosurgery The Second Affiliated HospitalZhejiang UniversityHangzhou310009China

The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget *** a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(***)and is used as an expectorant for pulmonary disease in Asia[2].

关键词： NSCLC eIF4E treatment

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Sequential dual-locking strategy using photoactivated Pt(Ⅳ)-based metallo-nano prodrug for enhanced chemotherapy and photodynamic efficacy by triggering ferroptosis and macrophage polarization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3251-3265页

作者： Jun Li Qiang Zhang Hao Yang Wenli lu Yulong Fu Yingcai Xiong Xuan Wang tianming lu Yanlin Xin Zejuan Xie Weichao Chen Guoqiang Wang Yuanyuan Guo Ruogu Qi School of Medicine Nanjing University of Chinese MedicineNanjing 210023China Key Laboratory of Mesoscopic Chemistry of Ministry of Education Institute of Theoretical and Computational ChemistrySchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China Laboratory for Manufacturing Low Carbon and Functionalized Textiles College of Textiles&ClothingQingdao UniversityQingdao 266071China

Selective activation of Pt(Ⅳ)prodrugs within tumors has emerged as a promising strategy in tumor *** progress has been made with photo-and ultrasound-activated Pt(Ⅳ)prodrugs,concerns remain over the non-specific activation of photosensitizers(PS)and the potential for phototoxicity and chemical *** this study,a sequential dual-locked Pt(Ⅳ)nano-prodrug that can be activated by both the acidic tumor microenvironment and light was *** Pt(Ⅳ)prodrug was prepared by conjugating PS-locked Pt(Ⅳ)to a polymeric core,which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano *** acidic tumor microenvironment conditions,the metallo-nano prodrug undergoes dissociation of iron,triggering a reduction process in oxaliplatin under light irradiation,resulting in the activation of both chemotherapy and photodynamic therapy(PDT).Additionally,the prodrug could induce metallo-triggered ferroptosis and polarization of tumorassociated macrophages(TAM),thereby enhancing tumor *** dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs,making it a promising new direction in cancer treatment.

关键词： Dual-locking Pt(Ⅳ)reduction Chemotherapy Photodynamic therapy Ferroptosis Macrophage polarization Medicinal inorganic chemistry Metals in medicine

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Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

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Journal of Pharmaceutical Analysis 2023年第8期13卷 908-925页

作者： Qiuyan Guo Jiangpeng Wu Qixin Wang Yuwen Huang Lin Chen Jie Gong Maobo Du Guangqing Cheng tianming lu Minghong Zhao Yuan Zhao Chong Qiu Fei Xia Junzhe Zhang Jiayun Chen Feng Qiu Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China School of Chinese Materia Medica and State Key Laboratory of Component-Based Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin301617China Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China College of Food Science and Engineering Institute of OceanBohai UniversityJinzhouLiaoning121013China State Key Laboratory of Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine ShenzhenGuangdong518033China

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii *** been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune ***,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing *** present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)*** TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total *** the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate *** analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling ***,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

关键词： Tripterygium glycosides tablet Acute liver injury scRNA-seq

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Bailing capsule(百令胶囊)alleviates autoimmune thyroiditis via regulating peroxisome proliferator-activated receptor signaling pathway:a multi-omics analysis

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Journal of Traditional Chinese Medicine 2024年第6期44卷 1217-1226页

作者： WANG Qixin XU Liting WU Jiangpeng HE Xueling TANG Huan CHENG Guangqing lu tianming DAI Chuanhao GUO Qiuyan WANG Jigang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China School of Chinese Materia Medica and State Key Laboratory of Component-based Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin 301617China

OBJECTIVE: To investigate the efficacy and potential mechanism of Bailing capsule( 百令胶囊, BL) antiautoimmune thyroiditis(AIT). METHODS: Based on the AIT rat model, the effect of BL in alleviating AIT was evaluated by detecting serum thyroid index free triiodothyronine(FT3), free thyroxine(FT4), thyroid-stimulating hormone(TSH), thyroglobulin antibody(TGAb), thyroid peroxidase antibody(TPOAb), and inflammatory factors Interferon-gamma(IFN-γ), Interleukin-4,-10, and-12(IL-4, IL-10, and IL-12) as well as thyroid tissue Hematoxylin-eosin(HE) staining and ultrastructure observation. The mechanism of BL was explored by combining transcriptome and proteome analysis, and further verified by Western blot(WB). RESULTS: BL effectively reduced serum FT3, FT4, TGAb, and TPOAb levels in AIT rats, restored TSH balance, inhibited the release of pro-inflammatory cytokines IFN-γ and IL-12, promoted the production of anti-inflammatory cytokines IL-4 and IL-10, and significantly reduced IFN-γ/IL-4 and IL-12/IL-10, improved thyroid follicular structure, and protected thyroid tissue from injury. Kyoto Encyclopedia of Genes and Genomes and protein interaction network analysis showed that BL affected the expression of fatty acidbinding protein 4, acyl-Co A synthetase long-chain family member 1, and acyl-Co A dehydrogenase long chain to regulate the peroxisome proliferator-activated receptor signaling pathway, thereby inhibiting the fatty acid metabolism and the inflammatory state of AIT ***: BL could effectively reduce thyroid inflammation in AIT model rats. The possible BL mechanism was to regulate the peroxisome proliferatoractivated receptor signaling pathway and inhibit fatty acid metabolism. This study suggested that BL has the potential to be used in clinical treatment of AIT.

关键词： thyroiditis autoimmune cordyceps fatty acid peroxisome proliferator-activated receptors Bailing capsule

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网络化作战体系中目标重要度评估方法

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陆军工程大学学报 2023年第4期2卷 78-84页

作者：鲁磊卢厚清卢天鸣张挺陆军工程大学野战工程学院江苏南京210007 中国电子科技集团第二十八研究所江苏南京210007 61175部队江苏南京210049

针对网络化作战体系中目标重要度评估问题,结合层次分析和复杂网络方法,从目标节点特征、网络指标积极效应、网络指标消极效应3个方面提出新的评估方法。从能力视角描述目标自身特征;基于复杂网络理论,从积极效应层面描述目标的资源关... 详细信息

针对网络化作战体系中目标重要度评估问题,结合层次分析和复杂网络方法,从目标节点特征、网络指标积极效应、网络指标消极效应3个方面提出新的评估方法。从能力视角描述目标自身特征;基于复杂网络理论,从积极效应层面描述目标的资源关联性、流转时效性、协同性和连通关键性,从消极效应层面描述目标的离散度;构建效能函数计算目标的网络关键度;根据目标自身特征和网络关键度给出目标的评估分。该方法综合考虑了目标自身特征以及目标在作战体系中的地位和作用,实验表明评估结果准确、可靠。

关键词：战场目标目标重要度复杂网络积极效应消极效应

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实践性研究的工程思维方法

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实验室研究与探索 2018年第4期37卷 254-257页

作者：周光发卢天鸣江苏警官学院基础部南京210031 南京理工大学机械工程学院南京210007

工程思维是一种筹划型思维。工程思维适应了实践性问题所具有的不确定性、集成性、艺术性等特点,是实践性研究的一种重要方法。实践性研究的工程思维方法,要求研究者重视对特定约束和资源条件的分析,综合运用多种不同的工具,给出解决所... 详细信息

工程思维是一种筹划型思维。工程思维适应了实践性问题所具有的不确定性、集成性、艺术性等特点,是实践性研究的一种重要方法。实践性研究的工程思维方法,要求研究者重视对特定约束和资源条件的分析,综合运用多种不同的工具,给出解决所研究问题的严格、科学、规范的操作程序。采用系统分析的方法对实践性研究进行系统的总体设计,采用工作分解结构、网络计划等图表方法对研究过程进行周密的计划安排,采用软件能力成熟度模型等标准化方法对研究活动进行实时动态管控,使用定性与定量相综合的方法对研究成果的价值进行系统评价。实践性研究人员要正确认识理性与非理性、共性与个性、继承与创新的关系,通过工程思维提高研究成果的实用化水平。

关键词：工程思维思维方式实践性研究研究方法

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