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Comparative analysis of diverse toxins from a new pharmaceutical centipede,Scolopendra mojiangica

Zoological Research 2020年第2期41卷 138-147页

作者： Zi-Chao Liu Jin-Yang Liang Xin-Qiang Lan Tao Li Jia-Rui Zhang Fang Zhao Geng Li Pei-Yi Chen Yun Zhang Wen-Hui Lee Feng Zhao key laboratory of Ethnic Medical Resources Research and Southeast Asian International Cooperation of Yunnan Universities Department of Biology and ChemistryPuer UniversityPuerYunnan 665000China key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Engineering Research Center for Exploitation and Utilization of Leech Resources in Universities of Yunnan Province School of Agronomy and Life SciencesKunming UniversityKunmingYunnan 650214China key laboratory of active molecules and drug development Puer UniversityPuerYunnan 665000China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China Institute of Comparative Study of Traditional Materia Medica Institute of Integrative Medicine of Fudan UniversityShanghai 200032China Nanshan College Guangzhou Medical UniversityGuangzhouGuangdong 511436China

As the oldest venomous animals,centipedes use their venom as a weapon to attack prey and for *** venom,which contains many bioactive and pharmacologically active compounds,has been used for centuries in Chinese medicine,as shown by ancient *** on comparative analysis,we revealed the diversity of and differences in centipede toxin-like molecules between Scolopendra mojiangica,a substitute pharmaceutical material used in China,and *** *** than 6000 peptides isolated from the venom were identified by electrospray ionization-tandem mass spectrometry(ESI-MS/MS)and inferred from the *** a result,in the proteome of ***,246 unique proteins were identified:one in five were toxin-like proteins or putative toxins with unknown function,accounting for a lower percentage of total proteins than that in *** mining identified approximately 10 times more toxin-like proteins,which can characterize the precursor structures of mature toxinlike ***,the constitution and quantity of the toxin transcripts in these two centipedes were *** toxicity assays,the crude venom showed strong insecticidal and hemolytic *** findings highlight the extensive diversity of toxin-like proteins in *** and provide a new foundation for the medical-pharmaceutical use of centipede toxin-like proteins.

关键词： Centipede Toxins Pharmaceutical use Proteotranscriptomic analysis

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Deciphering the high-carbonization-temperature triggered enzymatic activity of wool-derived N,S-co-doped carbon nanosheets

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Chinese Chemical Letters 2024年第3期35卷 182-188页

作者： Jiachen Zhao Deshuai Yu Jianmin Chen Shihao Lin Yonghua Tang Chaoyu Fan Dongfang Zhou Youhui Lin Department of Physics Research Institute for Biomimetics and Soft MatterFujian Provincial Key Laboratory for Soft Functional Materials ResearchXiamen UniversityXiamen 361005China School of Pharmacy and Medical Technology Putian UniversityPutian 351100China key laboratory of Mental Health of the Ministry of Education NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China key laboratory of Pharmaceutical Analysis and laboratory Medicine(Putian University) Fujian Province UniversityPutian 351100China

It is well-established that high carbonization temperature will trigger the enzyme-like activity of carbon-based ***,the catalytic mechanism is still ambiguous,which hinders the further rational design of nanomaterials as enzyme ***,N,S-rich carbonized wool nanosheets(CWs)were synthesized at different pyrolysis *** expected,only CWs treated with high-temperature possess intrinsic oxidase-and peroxidase-like ***,density functional theory(DFT)calculations demonstrate that graphitic nitrogen and the co-existence of nitrogen and sulfur in the carbon matrix serve as the active sites for the enzyme-like *** importantly,combining theoretical calculations and experimental observations,the high-temperature triggered catalytic mechanism can be ascribed to the fact that an appropriate high-temperature maximizes the graphitization degree to a certain extent,at which most of the catalytic active sites are well retained rather than ***,coupling with excellent photothermal conversion efficiency and catalytic performance,CWs can be applied to photothermal-catalytic cancer therapy under near-infrared region(NIR)light *** believe this work will contribute to understanding the catalytic mechanism of carbon-based nanozymes and promote the development of new biomedical and pharmaceutical applications.

关键词： Carbon-based nanozyme Catalytic mechanism Density functional theory High-temperature carbonization

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The role of Smad signaling in vascular and hematopoietic development revealed by studies using genetic mouse models

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Science China(Life Sciences) 2010年第4期53卷 485-489页

作者： LAN Yu & YANG Xiao State key laboratory of Proteomics, Genetic laboratory of development and Diseases, Institute of Biotechnology, Beijing 100071, China 1. State key laboratory of Proteomics Genetic Laboratory of Development and Diseases Institute of Biotechnology Beijing 100071 China

Smads are intracellular mediators of transforming growth factor β (TGF-β) superfamily signaling. In this review, we focus on the genetic mouse models for Smad pathways, which have provided functional evidence regarding the complex circuitry in angiogenesis and hematopoiesis during development. In the early stages of vascular development, TGF-β signaling is a contri buting factor in angiogenesis and vascular maturation. Whereas in the later embryogenesis, selected molecules of Smad pathways, such as TGF-β type II receptor (TbRII), ALK5, and Smad5, seem to be dispensable for vessel morphogenesis and integrity. TGF-β signaling is not required in the induction of hematopoietic precursors from mesoderm, but inhibits the subsequent expansion of committed hematopoietic precursors. By contrast, bone morphogenetic protein 4 (BMP4) has long been acknowledged pivotal in mesoderm induction and hematopoietic commitment during development. However, recent genetic evidence shows the BMP4-ALK3 axis is not crucial for the formation of hematopoietic cells from FLK1+ mesoderm. Because of the highly redundant mechanisms within the Smad pathways, the precise role of the Smad signaling involved in vascular and hematopoietic development remains nebulous. The generation of novel cell lineage restricted Cre transgenes would shed new light on the future relevant investigations.

关键词： Smad transforming growth factor β (TGF-β) bone morphogenetic protein (BMP) angiogenesis hematopoiesis knockout development

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Altered integrity of hepatocyte tight junctions in rats with triptolide-induced cholestasis

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Chinese Journal of Natural Medicines 2021年第3期19卷 188-194页

作者： HUANG Shan LIU Li MEI Hui-Fang ZHANG Qian-Wen ZHANG Xi XU Xiao-Ting WANG Xin-Zhi HUANG Xin WANG Tao JIANG Zhen-Zhou ZHANG Lu-Yong SUN Li-Xin Jiangsu key laboratory of drug Screening China Pharmaceutical UniversityNanjing 210009China Center for drug Research and development Guangdong Pharmaceutical UniversityGuangzhou 510006China Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical UniversityNanjing 210009China Changde Vocational Technology College Changde 415000China

Triptolide(TP),an active component of Tripterygium wilfordii Hook.f.(TWHF),has been widely used for centuries as a traditional Chinese ***,the clinical application of TP has been restricted due to multitarget toxicity,such as *** this study,28 days of oral TP administration(100,200,or 400μg·kg^(-1)·d^(-1))induced the occurrence of cholestasis in female Wistar rats,as evidenced by increased serum levels ofγ-glutamyl transpeptidase(γ-GGT),alkaline phosphatase(ALP)and hepatic total bile acids(TBAs).In addition,the heptocyte polarity associated with the strcture of tight junctions(TJs)was disrupted in both rats and sandwich-cultured primary *** revealed decreased expression of the TJ-associated proteins occludin,claudin^(-1),and zonula occludens protein(ZO^(-1)),and downregulated m RNA levels of these TJs was also detected by real-time *** immunofluorescence analysis showed abnormal subcellular localization of occludin,claudin^(-1) and ZO^(-1),which was also confirmed by transmission electron ***,the concentration of FITC-dextran,a marker of paracellular penetration,was found to increase rapidly in bile increased rapidly(within 6 minutes)after treatment with TP,which indicated the functional impairment of *** together,these results suggest that the administration of TP for 28 consecutive days to rats could induce cholestatic injury in the liver,and the increased paracellular permeability might play an important role in these pathological changes.

关键词： Triptolide Cholestatic injury Tight junction Sandwich-cultured primary hepatocytes

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Overcoming the cellular barriers and beyond: Recent progress on cell penetrating peptide modified nanomedicine in combating physiological and pathological barriers

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Asian Journal of Pharmaceutical Sciences 2022年第4期17卷 523-543页

作者： Yingke Liu Zhihe Zhao Man Li State key laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China key laboratory of drug-Targeting and drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

The complex physiological and pathological conditions form barriers against efficient drug *** penetrating peptides(CPPs),a class of short peptides which translocate drugs across cell membranes with various mechanisms,provide feasible solutions for efficient delivery of biologically active agents to circumvent biological *** years of development,the function of CPPs is beyond cell *** CPPs with bioactivity or active targeting capacity have been designed and successfully utilized in delivery of various cargoes against tumor,myocardial ischemia,ocular posterior segment disorders,*** this review,we summarize recent progress in CPP-functionalized nano-drug delivery systems to overcome the physiological and pathological barriers for the applications in cardiology,ophtalmology,mucus,neurology and cancer,*** also highlight the prospect of clinical translation of CPP-functionalized drug delivery systems in these areas.

关键词： Cell penetrating peptide Nanomedicine Physiological barriers drug delivery system

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Structural Modification for Antitumor Nitrogenous Steroids

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Chinese Journal of Structural Chemistry 2017年第12期36卷 2007-2019页

作者：谢田鹏杨康张立志陈德胜邹坤黄年玉 Hubei key laboratory of Natural Products Research and development College of Biological and Pharmaceutical Sciences China Three Gorges University

Natural steroids have been showing notable cytotoxic activities, which are quite interesting lead compounds for the development of anticancer drug including estramustine and prednimustine. Considering that these semi-synthetic molecules are nitrogen mustard functionalized steroidal derivatives, the present review is focused on the methodologies of introducing nitrogen atom or nitrogen-containing heterocycles on A^D rings or side chains of steroids, and analysis of the structure-activity relationship（SAR） for these man-made cytotoxic steroids.

关键词： steroids structural modification N-hetercycles antitumor structure-activity relationship

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Research advancement of DNA-based intelligent hydrogels:Manufacture, characteristics, application of disease diagnosis and treatment

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Chinese Chemical Letters 2024年第10期35卷 92-101页

作者： Zhe-Han Yang Jie Yin Lei Xin Yuanfang Li Yijie Huang Ruo Yuan Ying Zhuo Chongqing key laboratory of Catalysis and Functional Organic molecules College of Environment and ResourcesChongqing Technology and Business UniversityChongqing 400067China key laboratory of Luminescence and Real-Time Analytic Chemistry(Southwest University) Ministry of EducationCollege of Chemistry and Chemical EngineeringSouthwest UniversityChongqing 400715China

DNA-based hydrogels are exceptional materials for biological applications because of their numerous advantages such as biodegradability,biocompatibility,hydrophilicity,super absorbency,porosity,and *** these advantages,the ability of DNA-based hydrogels to respond to specific physical and chemical triggers and undergo reversible phase transitions has garnered significant attention in the fields of disease diagnosis(biosensors)and treatment(drug delivery).This article focuses on the recent advancements in the research of DNA-based hydrogels and discusses the different types of these hydrogels,the synthetic methods,their unique properties,and their applications in biosensors and drug *** types of DNA hydrogels are categorized based on their building blocks,and the process of synthesis as well as the unique characteristics of DNA-based hydrogels are ***,DNA-based responsive hydrogels utilized as intelligent materials for the development of biosensors are ***,this article also presents the current status of DNA-based responsive hydrogels in drug delivery for cancer treatment,wound healing,and other therapeutic ***,this paper discusses the current challenges in expanding the practical application of DNA-based hydrogels.

关键词： DNA-based hydrogel Intelligent hydrogel Manufacture Characteristics Diseasediagnosis and treatment

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mRNA cancer vaccines:Advances,trends and challenges

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Acta Pharmaceutica Sinica B 2022年第7期12卷 2969-2989页

作者： Qing He Hua Gao Dejiang Tan Heng Zhang Jun-zhi Wang National Institutes for Food and drug Control State Key Laboratory for Evaluation and Standardization of Innovative Vaccines and Biotechnology ProductsBeijing 102629China

Patients exhibit good tolerance to messenger ribonucleic acid(m RNA)vaccines,and the choice of encoded molecules is flexible and *** vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex(MHC)restriction,are relatively easy to control and can be rapidly mass *** 2021,the *** and drug Administration(FDA)approved the first m RNA-based coronavirus disease 2019(COVID-19)vaccine produced by Pfizer and Bio NTech,which has generated enthusiasm for m RNA vaccine research and *** on the above characteristics and the development of m RNA vaccines,m RNA cancer vaccines have become a research hotspot and have undergone rapid development,especially in the last five *** review analyzes the advances in m RNA cancer vaccines from various perspectives,including the selection and expression of antigens/targets,the application of vectors and adjuvants,different administration routes,and preclinical evaluation,to reflect the trends and challenges associated with these vaccines.

关键词： mRNA Cancer vaccine Tumor-associated antigens Neoantigens mRNA delivery vectors Adjuvants Administration routes

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Advances in intelligent mass spectrometry data processing technology for in vivo analysis of natural medicines

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Chinese Journal of Natural Medicines 2024年第10期22卷 900-913页

作者： CHEN Simian DAI Binxin ZHANG Dandan YANG Yuexin ZHANG Hairong ZHANG Junyu LU Di WU Caisheng Fujian Provincial key laboratory of Innovative drug Target Research and State key laboratory of Cellular Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiamen 361102China Xiamen key laboratory for Clinical Efficacy and Evidence-Based Research of Traditional Chinese Medicine Xiamen UniversityXiamen 361102China

Natural medicines(NMs)are crucial for treating human *** characterizing their bioactive components in vivo has been a key focus and challenge in NM ***-performance liquid chromatography-high-resolution mass spectrometry(HPLC-HRMS)systems offer high sensitivity,resolution,and precision for conducting in vivo analysis of ***,due to the complexity of NMs,conventional data acquisition,mining,and processing techniques often fail to meet the practical needs of in vivo NM *** the past two decades,intelligent spectral data-processing techniques based on various principles and algorithms have been developed and applied for in vivo NM ***,improvements have been achieved in the overall analytical performance by relying on these techniques without the need to change the instrument *** improvements include enhanced instrument analysis sensitivity,expanded compound analysis coverage,intelligent identification,and characterization of nontargeted in vivo compounds,providing powerful technical means for studying the in vivo metabolism of NMs and screening for pharmacologically active *** review summarizes the research progress on in vivo analysis strategies for NMs using intelligent MS data processing techniques reported over the past two *** discusses differences in compound structures,variations among biological samples,and the application of artificial intelligence(AI)neural network ***,the review offers insights into the potential of in vivo tracking of NMs,including the screening of bioactive components and the identification of pharmacokinetic *** aim is to provide a reference for the integration and development of new technologies and strategies for future in vivo analysis of NMs.

关键词： High-performance liquid chromatography–High-resolution mass spectrometry Data-acquisition Data-processing Artificial Intelligence Metabolomics

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Overcoming Mycobacterium tuberculosis through small molecule inhibitors to break down cell wall synthesis

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3201-3214页

作者： Wenbin Kuang Haolin Zhang Xiao Wang Peng Yang State key laboratory of Natural Medicines and Jiang Su key laboratory of drug Design and Optimization China Pharmaceutical UniversityNanjing 210009China Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical UniversityNanjing 210009China

Mycobacterium tuberculosis(MTB) utilizes multiple mechanisms to obtain antibiotic resistance during the treatment of infections. In addition, the biofilms, secreted by MTB, can further protect the latter from the contact with drug molecules and immune cells. These self-defending mechanisms lay a formidable challenge to develop effective therapeutic agents against chronic and recurring antibiotictolerant MTB infections. Although several inexpensive and effective drugs(isoniazid, rifampicin, pyrazinamide and ethambutol) have been discovered for the treatment regimen, MTB continues to cause considerable morbidity and mortality worldwide. Antibiotic resistance and tolerance remain major global issues, and innovative therapeutic strategies are urgently needed to address the challenges associated with pathogenic bacteria. Gratifyingly, the cell wall synthesis of tubercle bacilli requires the participation of many enzymes which exclusively exist in prokaryotic organisms. These enzymes, absent in human hepatocytes, are recognized as promising targets to develop anti-tuberculosis drug. In this paper, we discussed the critical roles of potential drug targets in regulating cell wall synthesis of MTB. And also, we systematically reviewed the advanced development of novel bioactive compounds or drug leads for inhibition of cell wall synthesis, including their discovery, chemical modification, in vitro and in vivo evaluation.

关键词： Mycobacterium tuberculosis Small molecule inhibitor Cell wall synthesis Antibiotic resistance

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