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The Preparation of Cationic Folic Acid and Its Application in drug Delivery System

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Chinese Journal of Polymer Science 2014年第12期32卷 1714-1723页

作者： Yang Hu Lu Gan Qian-xuan Li Hong Tao 叶霖 Ai-ying Zhang Zeng-guo Feng School of Materials Science and Engineering Beijing Institute of Technology Information Center China Food and Drug Administration Graduate School of Frontier Science University of Tokyo

The cationic folic acid（CFA） was prepared by introducing triethylenetetramine into folic acid with EDCI/NHS and characterized by IR, NMR and mass spectra. It was found that approximately one of two carboxyls in the folic acid molecule was substituted to form CFA. The conversion of γ-carboxyl is found to be 59% higher than 30% of γ-carboxyl. The CFA and doxorubicin hydrochloride can be loaded on the ionic shell of PTX-encapsulated micelle to form CFA loaded binary drug carrier via static interaction in aqueous solutions. The successful loading was demonstrated by zeta potential measurement and the drug load amount（DLA） of CFA was measured by HPLC. In vitro cytotoxicity results revealed the CFA drug carrier showed higher cytotoxicity to cancer cell MDA-MB-321 than the binary drug carrier without CFA and the positive control, while it showed lower cytotoxicity to normal cell HUVEC than the positive control, and similar cytotoxicity with the binary drug carrier without CFA. These results as well as confocal laser scanning microscopy observation indicate the synthesized CFA drug carrier possesses active tumor-targeting property.

关键词： Folic acid Cationize Tumor-targeting drug carrier Cytotoxicity.

Synthesis and cytotoxic activities of E-resveratrol derivatives

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Chinese Journal of Natural Medicines 2015年第5期13卷 375-382页

作者： HONG Ting JIANG Wei DONG Huai-Ming QIU Sheng-Xiang LU Yu Sino-German Joint Research institute of Nanchang University Jiangxi Provincial institute for food and drug Control Jiangxi Provincial Engineering Research Center for Drug and Medical Device Quality Chinese Academy of Sciences South China Botanical Garden

The present study was designed to synthesize derivatives of E-resveratrol and evaluate their cytotoxic activity in *** functional groups were conjugated with the phenolic hydroxyl group of E-resveratrol,and the double bond of E-resveratrol was *** in vitro cytotoxicity of the synthetic derivatives was evaluated against three tumor cell lines(A549,LAC,and He La) using the MTT ***-six E-resveratrol derivatives were synthesized and their structures were confirmed by 1H NMR,MS,IR,and elemental *** 1-6,12,15-21,and 23-26 were reported for the first *** them,Compounds 1,2,4,5,and 9-11,showed significant cytotoxicity against tumor cells;especially,Compound 1 showed an IC50 value of 4.38 μmol·L-1 in the A549 cells which was 15-fold more active than E-resveratrol;Compound 9 showed an IC50 value of 1.41 μmol·L-1 in the He La cell line which was 90-fold more active than E-resveratrol,and close to *** structure–activity relationships were also *** 1,2 and 9-11 may serve as potential lead compounds for the discovery of new anticancer drugs.

关键词： E-resveratrol derivatives Synthesis Cytotoxic activity Structure–activity relationships

Anomaly Detection Based on Multi-Detector Fusion Used in Turbine

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Journal of Harbin institute of Technology(New Series) 2013年第1期20卷 113-117页

作者： Hui-Xin He Ning Li Geng-Feng Zheng Xu-Zhou Lin Da-Ren Yu School of Astronautics Harbin Institute of Technology National institutes for food and drug Control Fujian Special Equipment Ispection and Research institute

In order to improve the gas turbine engine health monitoring capability, using multiple detector fusion method in the monitoring system of gas turbine data monitor. Multi detector frame fusion includes point bias anomaly detector, contextual bias anomaly detector and collective bias anomaly detector, common to analyze the new arrival data, and the possible abnormal state to vote and weighted statistics as a result output. The experimental results show the method can effectively detect the mutation phenomenon, relatively slow changes and abnormal behavior discordant to the conditions. The framework applied to the gas turbine engine can effectively enhance the health diagnosis ability, will be highly applied for real industry.

关键词： fusion industry data anomaly detection

Critical role of bioinformatics in translating huge amounts of next-generation sequencing data into personalized medicine

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Science China(Life Sciences) 2013年第2期56卷 110-118页

作者： HONG HuiXiao ZHANG WenQian SHEN Jie SU ZhenQiang NING BaiTang HAN Tao PERKINS Roger SHI LeMing TONG WeiDa Division of Bioinformatics and Biostatistics National Center for Toxicological ResearchUS Food and Drug Administration Beijing Genomic institute Beishan Industrial Zone Division of Systems Biology National Center for Toxicological ResearchUS Food and Drug Administration

Realizing personalized medicine requires integrating diverse data types with *** most vital data are genomic information for individuals that are from advanced next-generation sequencing(NGS) technologies at *** technologies continue to advance in terms of both decreasing cost and sequencing speed with concomitant increase in the amount and complexity of the *** prodigious data together with the requisite computational pipelines for data analysis and interpretation are stressors to IT infrastructure and the scientists conducting the work *** is increasingly becoming the rate-limiting step with numerous challenges to be overcome for translating NGS data for personalized *** review some key bioinformatics tasks,issues,and challenges in contexts of IT requirements,data quality,analysis tools and pipelines,and validation of biomarkers.

关键词： personalized medicine next-generation sequencing bioinformatics short reads alignment assemble data analysis

Common endocrine system adverse events associated with immune checkpoint inhibitors

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Cancer Pathogenesis and Therapy 2024年第3期2卷 164-172页

作者： Ying Li Junfeng Zhao Yue Wang Yali Xu Ruyue Li Ying Zhao Xue Dong Xiujing Yao Yintao Li Department of Medical Oncology Shandong Cancer Hospital and InstituteShandong First Medical UniversityShandong Academy of Medical SciencesJinanShandong 250000China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical UniversityShandong Academy of Medical SciencesJinanShandong 250000China National institutes for food and drug Control Beijing 102629China Department of Pathology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250000China Department of Medical Oncology Shandong Cancer Hospital and InstituteAffiliated Hospital of Weifang Medical UniversitySchool of Clinical MedicineWeifang Medical UniversityWeifangShandong 261000China

Immune checkpoint inhibitors(ICIs),a novel anti-tumor therapeutic modality,are monoclonal antibodies targeting certain immune checkpoints(ICs)that reactivate T cells to achieve anti-tumor immunity by targeting,binding,and blocking *** inhibitory antibodies against the ICs cytotoxic T-lymphocyte antigen and programmed death receptor-1 have demonstrated efficacy and durable anti-tumor activity in patients with *** may prevent autoimmune ***,ICIs may disrupt ICs properties and trigger autoimmune-related adverse reactions involving various organ systems including the cardiovascular,pulmonary,gastrointestinal,renal,musculoskeletal,dermal,and endocrine *** 10%of patients with damage to target organs such as the thyroid,pituitary,pancreas,and adrenal glands develop endocrine system immune-related adverse events(irAEs)such as thyroid dysfunction,pituitary gland inflammation,diabetes mellitus,and primary adrenal ***,the symptoms of immunotherapy-associated endocrine system irAEs may be nonspecific and similar to those of other treatment-related adverse reactions,and failure to recognize them early may lead to *** detection and treatment of immunotherapy-associated endocrine irAEs is essential to improve the efficacy of immunotherapy,prognosis,and the quality of life of *** study aimed to review the mechanisms by which ICIs cause endocrine irAEs providing guidance for the development of appropriate management ***,we discuss(1)the biological mechanisms of ICs in tumorigenesis and progression,focusing on cytotoxic T-lymphocyte antigen and programmed cell death-1/programmed cell death-ligand 1;and(2)the epidemiology,clinical symptoms,diagnosis,and treatment of four immunotherapy-related endocrine complications.

关键词： Immune checkpoint inhibitors Immune checkpoints Cytotoxic T-lymphocyte antigen 4 Programmed cell death-1 Programmed cell death-ligand 1 Endocrine autoimmune-related adverse reactions

Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern

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Journal of Molecular Cell Biology 2024年第3期16卷 9-23页

作者： Ilaria Frasson Linda Diamante Manuela Zangrossi Elena Carbognin Anna Dalla Pietà Alessandro Penna Antonio Rosato Ranieri Verin Filippo Torrigiani Cristiano Salata Marìa Paula Dizanzo Lorenzo Vaccaro Davide Cacchiarelli Sara N.Richter Marco Montagner Graziano Martello Department of Molecular Medicine University of PaduaPadua 35121Italy Department of Biology Armenise/Harvard Pluripotent Stem Cell Biology LaboratoryUniversity of PaduaPadua 35131Italy Department of Surgery Oncology and GastroenterologyUniversity of PaduaPadua 35128Italy Veneto institute of Oncology IOV-IRCCS Padua 35128Italy Department of Comparative Biomedicine and food Science University of PaduaPadua 35020Italy Telethon institute of Genetics and Medicine(TIGEM) Armenise/Harvard Laboratory of Integrative GenomicsPozzuoli 80078Italy Department of Translational Medicine University of Naples Federico IINaples 80138Italy School for Advanced Studies Genomics and Experimental Medicine ProgramUniversity of Naples Federico IINaples 80138Italy Microbiology and Virology Unit Padua University HospitalPadua 35128Italy

The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants,some of which are resistant to vaccines and drugs targeting viral *** host dependency factors,*** proteins required for viral replication,would help prevent the development of ***,it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host *** this end,we compared three variants of concern and found that the host transcriptional response was conserved,differing only in kinetics and *** regularly interspaced short palindromic repeats screening identified host genes required for each variant during *** of the genes were shared by multiple *** validated our hits with small molecules and repurposed the US food and drug Administration-approved *** the drugs were highly active against all the tested variants,including new variants that emerged during the study(Delta and Omicron).Mechanistically,we identified reactive oxygen species production as a key step in early viral *** such as N-acetyl cysteine(NAC)were effective against all the variants in both human lung cells and a humanized mouse *** study supports the use of available antioxidant drugs,such as NAC,as a general and effective anti-COVID-19 approach.

关键词： SARS-CoV-2 variants of concern host dependency factors antivirals N-acetyl cysteine

Spectroscopy Investigation on Conformational Transition of Tea Glycoconjugate from Green Tea

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Chinese Journal of Chemistry 2004年第11期22卷 1387-1390页

作者：陈海霞张民谢笔钧 food Science and Technology Department Huazhong Agricultural University Wuhan Hubei 430070 China institute of Marine drug and food Ocean University of China Qingdao Shandong 266003 China

The conformational transition of a new glycoconjugate, tea glycoconjugate (TGC), was investigated by spec-troscopy techniques including circular dichroism (CD) and ultraviolet (UV) spectroscopy. The solution behaviors of TGC in the mediums of different temperature, pH value, and ions were compared. Results showed that the native conformation of TGC was partially ordered. The CD value and UV absorbance of TGC altered with the change of pH value, temperature, the addition of ions, and also accompanied order-disorder transition. Especially the condi-tions with temperature higher than the glass transition temperature (Tg=62 ℃), higher pH value or lower pH value will have the most impact on the conformation of TGC, which will destroy the hydrogen bonds between the TGC molecules. The results indicated that the outside factors play important roles on the stability of the conformation of TGC.

关键词： tea glycoconjugate conformational transition circular dichroism ultraviolet spectroscopy

Elicitation of strong immune responses by a DNA vaccine expressing a secreted form of hepatitis C virus envelope protein E2 in murine and porcine animal models

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World Journal of Gastroenterology 2006年第44期12卷 7126-7135页

作者： Yi-Ping Li Hye Na Kang Lorne A Babiuk Qiang Liu Vaccine and Infectious Disease Organization University of Saskatchewan Saskatoon Saskatchewan Canada Danish institute for food and Veterinary Research Arhus N Denmark Korea food and drug Administration Seoul Republic of Korea

AIM： To characterize the immunogenicity of a hepatitis C virus （HCV） E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models. METHODS： A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without boosting with a recombinant E2 protein vaccine formulated with CpG ODN and 10% Emulsigen. The immunogenicity of HCV E2 vaccines was analyzed by ELISA for antibody responses, MTT assay for lymphocyte proliferation, ELISPOT for the number of interferon-γ secreting cells, and cytotoxic T lymphocyte assays. RESULTS： Intradermal injection of E2 DNA vaccine induced strong Th1-1ike immune responses in mice. In piglets, E2 DNA vaccine elicited moderate and more balanced immune responses. A DNA vaccine prime and protein boost vaccination strategy induced significantly higher E2-specific antibody levels and shifted the immune response towards Th2-1ike ones in piglets. CONCLUSION： A DNA vaccine expressing a secreted form of HCV E2 protein elicited E2-specific immune responses in mice and piglets. Recombinant E2 protein vaccination following DNA immunization significantly increased the antibody response in piglets. These HCV E2 vaccines may represent promising hepatitis C vaccine candidates for further investigations.

关键词： Hepatitis C virus E2, DNA vaccine DNA vaccine prime-protein boost

Synthesis of Obyanamide, a Marine Cytotoxic Cyclic Depsipeptide

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Chinese Chemical Letters 2006年第3期17卷 285-288页

作者： Wei ZHANG Ni SONG Zhong Zhen LI Ying Xia LI Key Laboratory of Marine drugs the Ministry of Education of China Marine Drug and Food Institute Ocean University of China Qingdao 266003

The synthesis of a marine cytotoxic cyclic depsipeptide obyanamide has been accomplished. The key steps include assembling liner pentapeptide via Yamaguchi esterification and HATU-promoted ring closing. The structure of the synthetic sample was identified by ^1H and ^13C NMR, H-H COSY, HMQC, HMBC, and HRESIMS, but appears to be different from that of the marine natural product.

关键词： Obyanamide synthesis cyclic depsipeptide natural product.