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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 modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies.This 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’sensitivity.The extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C_(20) can balance efficacy and safety.These 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

Metallothionein Genes in the Nematode Caenorhabditis elegans and Metal Inducibility in Mammalian Culture Cells

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Biomedical and Environmental Sciences 1994年第3期7卷 222-231页

作者： FUMIHIKO KUGAWA HIROKO YAMAMOTO SHIGEHIRO OSADA MASATADA AOKI MASAYOSHI IMAGAWA AND TSUTOMU NISHIHARA (college of pharmacy, Nihon University, 7-7-1 Narashino-dai, Funabashi,Chiba 274 and Faculty of Pharmaceutical Sciences, Osaka University,1-6 Yama college of pharmacy Nihon University Chiba Japan.

Genomic DNAs of metallothionein Ⅰ and Ⅱ in Caenorhabditis elegans (CeMT-Ⅰand CeMT-Ⅱ) were isolated by YAC library/polytene filter hybridization followed by subcloning of corresponding cosmid clones. Both genes are mapped at chromosome V. Although the similarities of 5'-flanking regions and coding regions have shown only 55-58%, the introns are split at the same position in both genes, indicating that these two genes are originally from the same gene. While several metal responsive elements are conserved among eukaryotes, only one metal responsive element was found in the promoter region in CeMT-Ⅱ and not in CeMT-Ⅰ. Indced, neither of 5'-flanking regions of CeMT-Ⅰ nor CeMT-Ⅱ connected to chloramphenicol acetyltransferase reporter gene is responsive to heavy metals in mammalian culture cells by transient transfection analysis. These results would suggest that the metal regulatory factors in C.elegans might be different from those conserved in invertebrates and vertebrates, although the MTs in C elegans revealed the similarities to mammalian MTs in several points

关键词： MT gene Metallothionein Genes in the Nematode Caenorhabditis elegans and Metal Inducibility in Mammalian Culture Cells

Multi-stimuli-responsive aggregation-induced emission copper iodide cluster

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Science China Chemistry 2024年第4期67卷 1193-1197页

作者： Bo Li Yuan-Yuan Liu Peng Luo Ye-Ru Liu Ying-Jun Chen Kai Li Shuang-Quan Zang college of Chemistry and pharmacy Engineering Nanyang Normal UniversityNanyang 473061China Green Catalysis Center and college of Chemistry Zhengzhou UniversityZhengzhou 450001China

Stimuli-responsive luminescent materials have attracted significant attention in the development of smart photoactive materials for both fundamental research and technological applications.In this work,a new copper iodide cluster(1)with aggregationinduced emission(AIE)characteristic,was obtained combining Cu_(4)I_(4) core with rhodamine B derivative ligand.1 has reversible and distinct multi-stimuli-responsive luminescence for external temperature,volatile organic compound,and mechanical force.Significantly,1 exhibited unusual large blue shift(84 nm)after being ground,which originated from the change of intermolecular interactions.Moreover,1 exhibits high oxygen quenching efficiency for 82.2% at 1 bar.Mechanistic studies showed that the multi-stimuli-responsive luminescence properties of 1 can be attributed to the regulation of cluster-centered luminescence process,metal-to-ligand charge transfer process,halide-to-metal charge transfer luminescence process and aggregationinduced barrier to oxygen process.This work not only reports an AIE copper iodide cluster,but also provides a new strategy to develop multi-stimuli-responsive luminescence materials.

关键词： copper iodide cluster aggregation-induced emission multi-stimuli-response

Effect of heparin on apoptosis in human nasopharyngeal carcinoma CNE2 cells

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Cell Research 2001年第4期11卷 311-315页

作者： LI HONG LIANG , KAI HE YE , HAI WEI ZHANG , YING RU LUO , XIAN DA REN, AI HUA XIONG, RUI SITU Department of Pharmacology ,pharmacy college, Department of Pathology Medical college, Jinan University, Guangzhou 510632, China Department of Pharmacology Pharmacy College Jinan University Guangzhou China Department of Pathology Medical college Jinan University Guangzhou China

In order to study the mechanism of the effect of heparin on apoptosis in carcinoma cells, the nasopha- ryngeal carcinoma cell line CNE2 was used to identify the effect of heparin on apoptosis associated with the expression of c-myc,bax, bcl-2 proteins by use of Hoechst 33258 staining, terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL), agarose gel electrophoresis, and flow cytometry, as well as Western blot analysis. The results showed that heparin induced apoptosis of cNE2 cens including the morphologic changes such as reduction in the volume, and the nuclear chromatin condensation, as well as the 'ladder pattern' revealed by agarose gel electrophoresis of DNA in a concentration-dependent manner. The number of TUNEL-positive cells was dramatically increased to 33.6+1.2% from 2.8+0.3% by treat- ment with heparin in different concentrations (10~40 kU/L). The apoptotic index was increased to 32.5% from 3.5% by detecting SubG1 peaks on flow cytometry. Western blot analysis showed that levels of bcl-2, bax and c-myc were significantly overexpressed by treatment with the increase of heparin concentrations. These results suggest that heparin induces apoptosis of CNE2 cells, which may be regulated by differential expression of apoptosis-related genes.

关键词： Heparin agarose gel electrophoresis flow cytometry apoptosis protein kinase C(PKC)

Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana Sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao Department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India Department of Pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia Department of Pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

Morroniside protects cultured human umbilical vein endothelial cells from damage by high ambient glucose

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Acta Pharmacologica Sinica 2004年第4期25卷 14-17页

作者： Hui-qin XU2, Hai-ping HAO2, Xu ZHANG3,Yang PAN2 2college of pharmacy 3BasicMedicine college, Nanjing Universityof Traditional ChineseMedicine, Nanjing 210029, China college of pharmacy Nanjing University of Traditional Chinese Medicine Nanjing 210029 Basic Medicine college Nanjing University of Traditional Chinese Medicine Nanjing 210029

AIM: To determine whether morroniside, a compound in Cornus officinalis Sieb et Zucc can prevent cultured human umbilical vein endothelial cells (HUVEC) from damage by high ambient glucose. METHODS: HUVEC was incubated in glucose, 5 or 30 mmol/L, either alone or in the presence of morroniside (final concentration 100, 10, and 1 μmol/L, respectively) for 48 h. The proliferation of HUVEC was quantified by MTT method; its cycle was analyzed by flow cytometry; morphological change was observed with fluorescence microscopy. RESULTS: Survival of HUVEC cultured in high ambient glucose was significantly decreased when compared to that in normal concentration of glucose (P<0.01). High ambient glucose also lowered the rate of cells entering into S-phase, along with severe morphological damage. With the intervention of morroniside (final concentration 100 and 10 μmol/L), the cell survival was significantly recovered (P<0.01, P<0.05, respectively), accompanied with increased S-phase rate and less extent of morphological damage. CONCLUSION: Morroniside protected HUVEC against high ambi- ent glucose induced injury, which suggested that morroniside could exert a beneficial effect on preventing diabetic angiopathies.

关键词： morroniside umbilical veins endothelial cells diabetic angiopathies

Inhalable iron redox cycling powered nanoreactor for amplified ferroptosis-apoptosis synergetic therapy of lung cancer

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Nano Research 2024年第6期17卷 5435-5451页

作者： Linjing Wu Wenhao Wang Mengqin Guo Fangqin Fu Wenhua Wang Tszching Sung Meihong Zhang Ziqiao Zhong Chuanbin Wu Xin Pan Zhengwei Huang college of pharmacy Jinan UniversityGuangzhou 511436China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China

Fenton reaction centered ferroptosis-apoptosis synergetic therapy has emerged as a promising tumor elimination strategy.However,the low intracellular Fenton level and accumulation of therapeutics at the lesion site greatly limit the efficacy of ferroptosis therapy.To overcome these two bottlenecks,an inhalable metal polyphenol network(MPN)-hybrid liposome,encoded as LDG,was proposed for enhancing the intracellular Fenton reaction level by co-delivering the ferroptosis inducer dihydroartemisinin(DHA)and the ferrous ion(Fe2+)donor MPN.The synthesized LDG had excellent nebulization performance which significantly improved the accumulation in the lungs,about 8.2 times of intravenous injection.In terms of anticancer mechanisms,MPN raised the intracellular level of Fe2+by constructing iron cycling in the weakly acidic environment of tumors.Triggered by Fe2+,DHA with peroxide-bridge structure underwent a high level of Fenton-like reaction,promoted the production of intracellular reactive oxygen species(ROS)and induced strong ferroptosis while cooperating with apoptosis.LDG exhibited extraordinary antitumor ability in an orthotopic lung tumor model,whose tumor inhibition efficiency was 1.53(P=0.0014)and 1.32(P=0.0183)times of the LG group(liposomes coated with gallic acid(GA)-Fe MPN)and LD group(liposomes loaded with DHA),respectively,showing the strongest anticancer effect.In conclusion,the constructed MPN-hybrid liposomes could be a potent custom nanoplatform for pulmonary delivery and underscored the great potential of ferroptosis-apoptosis synergetic therapy.

关键词： lung cancer pulmonary delivery ferroptosis metallic polyphenol network

Clinical characteristics of delayed generalized erythema associated with cytarabine

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Chronic Diseases and Translational Medicine 2024年第1期10卷 78-80页

作者： He Jiang Jun Lu Mei Wang college of pharmacy Anhui University of Chinese MedicineHefeiAnhuiChina Department of pharmacy Children's Hospital of Soochow UniversitySuzhouJiangsuChina

To the Editor,Cytarabine is one of the most used drugs for the treatment of hematological malignancies such as leukemia and non-Hodgkin's lymphoma.In cells,cytarabine is activated into ara-CTP,which can replace deoxycytidine triphosphate(dCTP)and become incorporated into the DNA of proliferating cells.Thus,it can block DNA synthesis,resulting in proliferation arrest and cell death.

关键词： death drugs Clinical

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

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Animal Models and Experimental Medicine 2024年第3期7卷 259-274页

作者： Huirong Xu Meiyue Dong Ruikun Du Chengcheng Zhang Zinuo Chen Guangyu Tian Qinghua Cui Kejian Li college of Traditional Chinese Medicine Shandong University of Traditional Chinese MedicineJinanChina Innovative Institute of Chinese Medicine and pharmacy Shandong University of Traditional Chinese MedicineJinanChina Qingdao Academy of Chinese Medical Sciences Shandong University of Traditional Chinese MedicineQingdaoChina college of pharmacy Shandong University of Traditional Chinese MedicineJinanChina

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

关键词： network pharmacology pharmacodynamical material basis serum pharmacochemistry viral pneumonia YangshenDingzhi granules

Development of lithium-free P2-type high-sodium content cathode materials with enhanced cycle and air stability for sodium-ion batteries

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Rare Metals 2024年第1期43卷 113-123页

作者： Jin-Lv Tian Lin-Rong Wu Hai-Jun Zhao Shou-Dong Xu Liang Chen Ding Zhang Xiao-Chuan Duan college of Chemical Engineering and Technology Taiyuan University of TechnologyTaiyuan 030024China college of Chemistry Taiyuan University of TechnologyTaiyuan 030024China School of Chemical Engineering and pharmacy Wuhan Institute of TechnologyWuhan 430205China

The effect of partial substitution of Mg for Ni on a high-sodium and lithium-free layered P2-type Na_(45/54)Mg_(6)/_(54)Ni_(12/54)Mn_(34/54)O_(2) cathode with high initial Coulombic efficiency and excellent cyclic stability has been investigated in this study.Based on the crystal structural analysis,the Mg doping can retain the P2 structure up to 4.3 V,thus restraining the detrimental phase transformation of P2-02during the Na-ion intercalation/deintercalation process.Therefore,the obtained Mg-doped P2-type cathode exhibits a reversible specific capacity of 109 mAh·g^(-1) at 0.1C between 2.0 and 4.3 V and a retention rate of 81.5% after 200cycles at 1C.In addition,the full cell consisting of Mg-doped P2-type cathode and hard carbon anode shows a capacity retention rate of 85.6% after 100 cycles.This study provides new insight into the development of durable cathode materials for sodium-ion batteries.

关键词： Sodium-ion batteries Cathode material High sodium content Air stability