检索结果-南通市图书馆

Chinese Journal of Natural Medicines 2024年第1期22卷 75-88页

作者： SONG Jiangzhou ZOU Guiqing ZHAO Zhou ZHU Ya XUE Jiayu AO Lanjia SUN Huiyong HAO Haiping ZHANG Bo XU Xiaowei State Key laboratory of Natural Medicines Key Lab of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China State Key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

NAD(P)H:quinone oxidoreductase 1(NQO1)is a flavin protease highly expressed in various cancer ***1 catalyzes a futile redox cycle in substrates,leading to substantial reactive oxygen species(ROS)*** ROS generation results in extensive DNA damage and elevated poly(ADP-ribose)polymerase 1(PARP1)-mediated consumption of nicotinamide adenine dinucleotide(NAD^(+)),ultimately causing cell *** phosphoribosyltransferase(NAMPT),the rate-limiting enzyme in the NAD^(+)salvage synthesis pathway,emerges as a critical target in cancer *** concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+*** this study,we designed,synthesized,and assessed a novel series of proqodine A derivatives targeting both NQO1 and *** these,compound T8 demonstrated potent antitumor ***,T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and *** discovery offers a promising new molecular entity for advancing anticancer research.

关键词： NQO1 ROS NAMPT NAD^(+) T8

Emerging mechanisms of non-alcoholic steatohepatitis and novel drug therapies

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of Natural Medicines 2024年第8期22卷 724-745页

作者： CHEN Hao ZHOU Yang HAO Haiping XIONG Jing Department of Pharmacology School of PharmacyChina Pharmaceutical UniversityNanjing 210009China Jiangsu Provincial Key laboratory of Drug Metabolism and pharmacokinetics State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China

Non-alcoholic fatty liver disease(NAFLD)has become a leading cause of chronic liver disease *** initiates with simple steatosis(NAFL)and can progress to the more severe condition of non-alcoholic steatohepatitis(NASH).NASH often advances to end-stage liver diseases such as liver fibrosis,cirrhosis,and hepatocellular carcinoma(HCC).Notably,the transition from NASH to end-stage liver diseases is irreversible,and the precise mechanisms driving this progression are not yet fully ***,there is a critical need for the development of effective therapies to arrest or reverse this *** review provides a comprehensive overview of the pathogenesis of NASH,examines the current therapeutic targets and pharmacological treatments,and offers insights for future drug discovery and development strategies for NASH therapy.

关键词： Metabolic dysfunction Drug development Bile acids Liver-gut axis Inflammation Fibrosis

Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2024年第7期35卷 377-382页

作者： Mengjuan Sun Muye Zhou Yifang Xiao Hailei Tang Jinhua Chen Ruitao Zhang Chunjiayu Li Qi Ya Qian Chen Jiasheng Tu Qiyue Wang Chunmeng Sun NMPA Key laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients China Pharmaceutical UniversityNanjing 210009China State Key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 211198China Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Jiangsu Provincial Key laboratory of Drug Metabolism and pharmacokinetics China Pharmaceutical UniversityNanjing 210009China School of Pharmaceutical Science Nanjing Tech UniversityNanjing 211816China

Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral *** with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid *** address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this *** micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),*** net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of ***-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral *** indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse ***,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.

关键词： Polyion complex micelle Size-switchable Revisable size-change pH response Antiangiogenic cancer

Di-PEGylated insulin:A long-acting insulin conjugate with superior safety in reducing hypoglycemic events

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第6期14卷 2761-2772页

作者： Zhipeng Zeng Runcheng Tan Shi Chen Haolin Chen Zhijia Liu Lixin Liu Mingqiang Li Yongming Chen laboratory of Biomaterials and Translational Medicine Center for NanomedicineThe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China School of Materials Science and Engineering Center of Functional BiomaterialsKey Laboratory of Polymeric Composite Materials and Functional Materials of Ministry of EducationSun Yat-sen UniversityGuangzhou 510275China

Although the discovery of insulin 100 years ago revolutionized the treatment of diabetes,its therapeutic potential is compromised by its short half-life and narrow therapeutic *** long-acting insulin analogs,such as insulin-polymer conjugates,are mainly used to improve pharmacokinetics by reducing renal ***,these conjugates are synthesized without sacrificing the bioactivity of insulin,thus retaining the narrow therapeutic index of native insulin,and exceeding the efficacious dose still leads to ***,we report a kind of di-PEGylated insulin that can simultaneously reduce renal clearance and receptor-mediated *** impairing the binding affinity to the receptor and the activation of the receptor,di-PEGylated insulin not only further prolongs the half-life of insulin compared to classical mono-PEGylated insulin but most importantly,increases its maximum tolerated dose *** target of long-term glycemic management in vivo has been achieved through improved pharmacokinetics and a high *** work represents an essential step towards long-acting insulin medication with superior safety in reducing hypoglycemic events.

关键词： Diabetes Insulin Therapeutic index Hypoglycemia PEGylation Receptor-mediated clearance Half-life Diabetic nephropathy

The First-in-Human Whole-Body Dynamic pharmacokinetics Study of Aptamer

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Research 2024年第1期2023卷 119-130页

作者： Ding Ding Haitao Zhao Dali Wei Qinglai Yang Cai Yang Ruowen Wang Yumei Chen Lianghua Li Shuxian An Qian Xia Gang Huang Jianjun Liu Zeyu Xiao Weihong Tan Institute of Molecular Medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of Medicineand College of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Nuclear Medicine Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Center for Molecular Imaging Probes Cancer Research InstituteUniversity of South ChinaHengyangHunan 421001China The Key laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Molecular Science and Biomedicine laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangshaHunan 410082China Shanghai Key laboratory of Molecular Imaging Shanghai University of Medicine and Health SciencesShanghai 201318China Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of MedicineShanghai200127China

Serving as targeting ligands,aptamers have shown promise in precision ***,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical *** bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled *** specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in *** preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human *** advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.

关键词： metabolism dosage Whole

Progress in pathogenesis and treatment of type A hepatic encephalopathy in acute liver failure:a comprehensive review

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Pharmacology Discovery 2024年第1期4卷 1-11页

作者： Ye-Xin Xu He Wang Kang-Rui Hu Bo-Yu Shen Lin Xie Guang-Ji Wang Yan Liang Key Lab of Drug Metabolism&pharmacokinetics State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China

Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into ***,hepatic encephalopathy can be divided into three types(A,B,and C)according to the *** A hepatic encephalopathy(AHE)caused by acute liver failure seriously affects the prognosis of patients,ranging from mild neuropsychological changes to coma,brain edema,and even *** far,the research on the pathogenesis of AHE has focused on the toxic effects of ammonia on the central nervous system,metabolic disorders(glutamine and lactate accumulation),neurotransmission alteration,systemic inflammation,especially *** these mechanisms are not independent,but mutually have synergistic *** clinic,treatment of AHE based on only one mechanism is often *** clarify the pathogenesis and the interaction among the mechanisms will be beneficial to the effective treatment of AHE and reduce the *** aim of this review is to provide comprehensive scientific evidence for the clinical treatment of AHE via collecting and analyzing the latest mechanism of AHE,and clarifying the relationship among these mechanisms combing the investigation of the latest research progress of drug treatment of acute liver ***,we find that the pathogenesis of AHE is a complex neurocognitive disorder shaped by interactions among hyperammonemia,inflammation,and changes in neurotransmission,the signaling pathways thereby integrating the inflammatory and neurological inputs to impact pathophysiological or neurobehavioral outcomes.

关键词： type A hepatic encephalopathy ammonia glutamine lactate,inflammation,blood-brain barrier,neurotransmission

SIRT1 activation synergizes with FXR agonism in hepatoprotection via governing nucleocytoplasmic shuttling and degradation of FXR

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2023年第2期13卷 559-576页

作者： Shuang Cui Huijian Hu An Chen Ming Cui Xiaojie Pan Pengfei Zhang Guangji Wang Hong Wang Haiping Hao State Key laboratory of Natural Medicines Key Laboratory of Drug Metabolism&PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China

Farnesoid X receptor(FXR)is widely accepted as a promising target for various liver diseases;however,panels of ligands in drug development show limited clinical benefits,without a clear ***,we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury,which represents the major culprit that limits the clinical benefits of FXR agonists against liver *** inflammatory and apoptotic stimulation,enhanced FXR acetylation at K217,closed to the nuclear location signal,blocks its recognition by importin KPNA3,thereby preventing its nuclear ***,reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1,and thereby facilitating FXR export to the *** governs nucleocytoplasmic shuttling of FXR,resulting in enhanced cytosolic retention of FXR that is amenable to degradation by ***1 activators reduce FXR acetylation and prevent its cytosolic *** importantly,SIRT1 activators synergize with FXR agonists in combating acute and chronic liver *** conclusion,these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.

关键词： FXR Nuclear receptor Acetylation Phosphorylation Nucleocytoplasmic shuttling Degradation Nonalcoholic steatohepatitis Combinatorial drugs

Formulation,characterization and in vivo and in vitro evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement

在线全文

学校读者我要写书评

暂无评论

Journal of Traditional Chinese Medicine 2024年第1期44卷 54-62页

作者： LI Xiuyan LUO Yuting WANG Jinhui DU Zhimin Key laboratory of Basic and Application Research of Beiyao Heilongjiang University of Chinese MedicineMinistry of EducationHarbin 150040China College of Pharmacy Harbin Medical UniversityHarbin 150081China Institute of Clinical Pharmacology the Second Affliated Hospital of Harbin Medical University(University Key aboratory of Drug ResearchHeilongjiang Province)Harbin 150086China Department of Clinical Pharmacology College of Pharmacy Harbin Medical UniversityHarbin 150081China State Key laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacao 999078China

OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in ***:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as *** analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of *** prescriptions were screened via the dissolution degree determination *** Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid *** toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for ***:AE-SD showed that AE existed in the carrier in an amorphous *** with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug ***,it was more suitable as a carrier material for *** addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of *** dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also *** on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than *** results showed that the drug metabolism in AE-SD was better,and the residence time was *** toxicology study showed that both AE and AE-SD had no ***:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,

关键词： aloe-emodin solid dispersion solvent evaporation drug liberation pharmacokinetics

TCP-1,a novel peptide to diagnose early colon cancer

在线全文

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2024年第3期35卷 226-233页

作者： Hang Yu Baoying Wen Min Huang Ru Feng Libin Pan Manyi Xu Hao Lin Lin Cong Sen Zhang Yan Li Chi-Hin Cho Chongjing Zhang Xiaoguang Chen Yan Wang State Key laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesBeijing 100050China School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong KongChina

A nine cyclic peptide(TCP-1)showed excellent specificity for colon ***-1 binds with human tumor tissues at early stages and mice tumor with diameters of 1-4 mm,suggesting that TCP-1 may be used for early diagnosis of colon *** mechanism of the targeted binding of TCP-1 to colon cancer was also studied using immunoprecipitation,LC-MS and *** screening and identifying of the possible binding target proteins of TCP-1,keratin,typeⅡcytoskeletal 5 was speculated to be the specific binding target protein of TCP-1 in human tumor *** studies were conducted to investigate the target-mediated drug disposition of the new tumor-specific peptide by LC-MS/*** tissue distribution study showed that TCP-1 was found only in colon tumors(the target site)in tumor mice did not bind to any other *** TCP-1 to tumor markedly increased its removal rate from blood circulation but mildly extended its staying time in *** tumor mice,a lower AUC of TCP-1(reduced by almost 35%)and 2-fold higher clearance were found compared to that of normal *** proposed metabolic pathway of TCP-1 in the kidney was also determined using LC-MS^(n)-*** high specificity and low toxicity of the peptide may be caused by its extremely tight binding to the *** applications for future clinical use,including MRI and PET/CT were also explored,and this research may promote the development of colon cancer diagnostic technology research and provide new ideas and technical routes for tumor diagnostic technology.

关键词： Colon cancer TCP-1 Peptide Cytokeratin 5 pharmacokinetics/pharmacodynamics(PK/PD)

Evaluation of the metabolism of PEP06,an endostatin-RGDRGD 30-amino-acid polypeptide and a promising novel drug for targeting tumor cells

在线全文

学校读者我要写书评

暂无评论

Journal of Pharmaceutical Analysis 2022年第5期12卷 766-773页

作者： Liyun Niu Huiyu Zhou Yueru Lian Ya Gao Yulu Liu Ruolan Gu Zhuona Wu Xiaoxia Zhu Hui Gan Zhiyun Meng Guifang Dou State Key laboratory of Drug Metabolism and pharmacokinetics Department of Pharmaceutical SciencesBeijing Institute of Radiation MedicineBeijing100850China Henan University KaifengHenan475004China

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N *** active endostatin fragment of PEP06 directly targets tumor cells and exerts an antitumoral ***,little is known about the kinetics and degradation products of PEP06 in vitro or in *** this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage ***06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of *** identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino *** metabolites were C and N terminal truncated products of *** structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized *** have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.

关键词： PEP06 HRMS Metabolic stability Metabolites identification