检索结果-南通市图书馆

Neural Regeneration Research 2024年第2期19卷 416-424页

作者： Guixiang Wang Wenjia Wang Ye Zhang Xiaoying Gou Qingqing Zhang Yanmiao Huang Kuo Zhang Haotian Zhang Jingyu Yang Yuting Li Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyangLiaoning ProvinceChina Department of Pharmacology Shenyang Pharmaceutical UniversityShenyangLiaoning ProvinceChina

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

关键词： adolescence adulthood ethanol dentate gyrus EZH2 in vivo tracing lineage progression mTOR neural stem cell newborn dendritic spine newborn neurons

The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies

在线全文

学校读者我要写书评

暂无评论

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

β-Carboline alkaloids from the roots of Peganum harmala L.

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Natural Medicines 2024年第2期22卷 171-177页

作者： LI Shengge ZHANG Qin WANG Yuetong LIN Bin LI Dahong HUA Huiming HU Xu Henan Key Laboratory of Zhang Zhongjing Formulate and Herbs for Immunoregulation Zhang Zhongjing Traditional School of Chinese MedicineNanyang Institute of TechnologyNanyang 473004China Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala L.Among these compounds,1 and 2 were characterized as rareβ-carboline-quinazoline dimers exhibiting axial chirality.Compound 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring,and compound 4 was a novel annomontineβ-carboline.The structures of these compounds were elucidated by spectroscopic data and quantum mechanical calculations.The biosynthetic pathways of 1−3 were proposed.Additionally,the cytotoxicity of some isolates against four cancer cell lines(HL-60,A549,MDA-MB-231,and DU145)was evaluated.Notably,compound 4 exhibited significant cytotoxicity against HL-60,A549,and DU145 cells with IC_(50) values of 12.39,12.80,and 30.65μmol·L^(−1),respectively.Furthermore,compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC_(50) value of 17.32μmol·L^(−1).

关键词： β-Carboline alkaloids Peganum harmala Structure elucidation Cytotoxic activity

Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Asian Journal of pharmaceutical Sciences 2024年第2期19卷 170-187页

作者： Bao Li Haoran Niu Xiaoyun Zhao Xiaoyu Huang Yu Ding Ke Dang Tianzhi Yang Yongfeng Chen Jizhuang Ma Xiaohong Liu Keda Zhang Huichao Xie Pingtian Ding School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics shenyang pharmaceutical university shenyang 110016 China Department of Basic pharmaceutical Sciences School of Pharmacy Husson university Bangor ME 04401USA College of Pharmacy Shenzhen Technology UniversityShenzhen 518118China

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

关键词： Anti-angiogenesis Tumor apoptosis Nanoparticles VEGF siRNA Hypoxia inducible factor(HIF)-1 protein Phenethyl isothi ocyanate(PEITC)

Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Asian Journal of pharmaceutical Sciences 2024年第2期19卷 153-169页

作者： Cong Li Lihong Wang Kexin Zhang Zeyu Wang Zhihang Li Zehao Li Lijiang Chen School of pharmaceutical Science Liaoning UniversityShenyang 110036China

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

关键词： Postoperative tumor treatment Immunotherapy Scaffold-based cancer vaccine Inflammatory neutrophils Sialic acid-modied liposome

Fine-tuning the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies via branched aliphatic functionalization

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Nano Research 2024年第4期17卷 2908-2918页

作者： Guanting Li Fengli Xia Hongying Xiao Shunzhe Zheng Shuwen Fu Han Qiao Qianhui Jin Xuanbo Zhang Dun Zhou Chutong Tian Jin Sun Zhonggui He Bingjun Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Emergency Department The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery systems.However,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous injection.The rational design of camptothecins-based prodrug nanoassemblies remains a challenge.Herein,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies.Correspondingly,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical nanoparticles.The length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and pharmacokinetics.Overall,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and tolerance.The findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based nanomedicines.

关键词： prodrug nanoassembly self-assembly antitumor efficacy tolerance 7-ethyl-10-hydroxycamptothecin(SN_(3)8)

Long-term efficacy and safety of Huangqi(Radix Astragali Mongolici)-based Traditional Chinese Medicine in diabetic peripheral neuropathy:a Meta-analysis of randomized controlled trials

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Traditional Chinese Medicine 2024年第2期44卷 229-242页

作者： PING Jing HAO Hongzheng WU Zhenqi ZOU Meijuan LI Zuojing CHENG Gang School of Life Sciences and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110000China Department of Endocrinology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110000China Department of Research Administration Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110000China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110000China

OBJECTIVE:To assess the long-term effectiveness of Huangqi(Radix Astragali Mongolici,HQ)-based Traditional Chinese Medicine(TCM)in the treatment of diabetic peripheral neuropathy(DPN).METHODS:Nine databases were searched to retrieve available randomized controlled trials that compared HQbased TCM and Western Medicines in the treatment of DPN.The methodological quality of the included studies was assessed using the Cochrane bias risk tool,and RevMan 5.4 was used for data analysis.The effect estimates of interest were risk ratio(RR),mean difference(MD)or standardized mean difference(SMD)with 95%confidence interval(CI).RESULTS:The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM[RR=1.30,95%CI(1.21,1.40),P<0.00001]or HQ-based TCM combined with Western Medicines[RR=1.25,95%CI(1.19,1.31),P<0.00001]exhibited higher total efficacy rates than individuals who received Western Medicine alone.The results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores[MD=-1.50,95%CI(-1.83,-1.17),P<0.00001],and reduced serum interleukin 6[SMD=-0.57,95%CI(-0.87,-0.27),P=0.0002]and tumor necrosis factors-αlevels[SMD=-0.60,95%CI(-0.95,-0.25),P=0.0009].In addition,both HQ-based TCM and HQbased TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine alone.In terms of blood lipids,oxidative stress and adverse drug reactions,there were no significant differences between the HQ-based TCM groups and the Western Medicine control group.CONCLUSION:The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN,although further well-designed RCTs are required to validate these findings.

关键词： Huangqi(Radix Astragali Mongolici) medicine Chinese traditional diabetic peripheral neuropathy Meta-analysis

A review of structural modification and biological activities of oleanolic acid

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Natural Medicines 2024年第1期22卷 15-30页

作者： YANG Huali DENG Minghui JIA Hongwei ZHANG Kaicheng LIU Yang CHENG Maosheng XIAO Wei State Key Laboratory of New-tech for Chinese Medicine pharmaceutical Process Jiangsu Kanion Pharmaceutical Co.Ltd.Lianyungang 222001China Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of Education School of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityShenyang 110016China

Oleanolic acid(OA),a pentacyclic triterpenoid,exhibits a broad spectrum of biological activities,including antitumor,antiviral,antibacterial,anti-inflammatory,hepatoprotective,hypoglycemic,and hypolipidemic effects.Since its initial isolation and identification,numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives.Despite this,there has been a dearth of comprehensive reviews in the past two decades,leading to challenges in subsequent research on OA.Based on the main biological activities of OA,this paper comprehensively summarized the modification strategies and structureactivity relationships(SARs)of OA and its derivatives to provide valuable reference for future investigations into OA.

关键词： Oleanolic acid Derivatives Pentacyclic triterpenoid Structural modification Biological activities

Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury

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2期35卷 323-328页

作者： Qiu Wang Qikun Jiang Dan Li Zimeng Yang Lin Gao Fan Liu Chang Li Yao Feng Zhonggui He Cong Luo Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Kangya of Ningxia pharmaceutical Co.Ltd. Yinchuan 750000China

Small interfering RNA(siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory diseases.Nevertheless,the effective delivery of siRNA to desired destination still remains challenging due to poor stability,high molecular weight and negative charge.Currently,ionizable lipid nanoparticle(LNP)has been extensively used as vector for effective delivery of siRNA.Herein,we report a mannose-modified LNP(M-MC_(3) LNP@TNFα)loading tumor necrosis factorα(TNFα)siRNA for targeting liver macrophages,achieving effectively inhibit acute liver injury.The M-MC_(3) LNP@TNFαnot only increases the internalization of LNP by macrophages,but also enhances the gene silencing efficiency of TNFαin vitro.Additionally,the M-MC_(3) LNP@TNFαexhibits higher accumulation in liver of healthy mice than that of MC_(3) LNP@TNFα(un-modified LNP)owing to the targeting effect of mannose.As expected,the M-MC_(3) LNP@TNFαsignificantly suppresses the expression of TNFαand ameliorates liver damage in acute liver injury model.Such a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.

关键词： Lipid nanoparticle Targeting siRNA delivery Acute liver injury Gene silencing Tumor necrosis factorα

Balancing efficacy and safety of doxorubicin-loaded albumin nanoparticles utilizing pH-sensitive doxorubicin-fatty acid prodrugs

在线全文

学校读者我要写书评

暂无评论

Nano Research 2024年第6期17卷 5491-5500页

作者： Yuanhao Yu Shiyi Zuo Jiaxuan Song Lingxiao Li Tian Liu Jiayu Guo Yaqiao Li Danping Wang Qi Lu Helin Wang Dun Zhou Zhonggui He Xiaohong Liu Bingjun Sun Jin Sun School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacy The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China

Albumin nanoparticles(ANPs)offer unique advantages for antitumor drug delivery system,including non-immunogenicity and inherent tumor-targeting capacity.At present,only a few products,such as ABRAXANE®and FYARRO™,have been approved for clinical applications.The poor affinity of doxorubicin(DOX)for albumin,coupled with its numerous severe adverse reactions,poses challenges in the fabrication of desirable albumin nanoparticles loaded with DOX.In this study,we developed prodrugs by conjugating fatty acids of varying lengths with DOX.Our aim was to investigate the balance between efficacy and safety through the selection of appropriate modules.We synthesized five pH-sensitive doxorubicin-fatty acid prodrugs.Compared to free DOX,all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 nm.Additionally,DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor cells.Significantly,the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids,impacting their in vivo pharmacokinetics,antitumor effectiveness and tumor accumulation.This research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs,and it builds a good platform for creating ANPs which prioritize high drug loading,high efficiency,and minimal side effects.

关键词： fatty acid prodrug albumin doxorubicin pH-sensitive bond nanomedicines