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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

Gp78 regulates PMP22 and causes ER stress and autophagy in EV71-VP1-overexpressing mouse Schwann cells

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BIOCELL 2024年第4期48卷 653-664页

作者： danping ZHU GUANGMING liu KUAN FENG SUYUN LI DANDAN HU SIDA YANG PEIQING LI Pediatric Emergency Department Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouChina Department of Child Health Care Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouChina Pediatric Neurology Department Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouChina

Background:During Enterovirus type 71(EV71)infection,the structural viral protein 1(VP1)activates endoplasmic reticulum(ER)stress associated with peripheral myelin protein 22(PMP22)accumulation and induces autophagy.However,the speciﬁc mechanism behind this process remains elusive.Methods:In this research,we used the VP1-overexpressing mouse Schwann cells(SCs)models co-transfected with a PMP22 silencing or Autocrine motility factor receptor(AMFR/gp78)overexpressing vector to explore the regulation of gp78 on PMP22 and its relationship with autophagy and apoptosis.Results:The activity of gp78 could be inﬂuenced by EV71-VP1,leading to a decrease in the ubiquitination and degradation of PMP22,resulting in PMP22 accumulation in ER.In VP1-overexpressing mouse SCs,all three ER stress sensors,including pancreatic endoplasmic reticulum kinase(PERK),activating transcription factor 6(ATF6)and inositol-requiring enzyme 1(IRE1)and the related downstream signals(C/EBP-homologous protein(CHOP)and Caspase 12)were activated,as well as the ER-resident chaperone Glucose-regulated protein 78(GRP78).In addition,VP1 upregulated the autophagy marker Microtubule-associated protein 1 light chain 3 beta(LC3B),while PMP22 silencing or gp78 overexpression reversed the phenomenon.Meanwhile,PMP22 silencing or gp78 overexpression increased proliferation of EV71-VP1-transfected mouse SCs.Conclusion:Gp78 could regulate PMP22 accumulation through ubiquitination degradation and cause ER stress and autophagy in EV71-VP1-overexpressing mouse SCs.Therefore,the gp78/PMP22/ER stress axis might emerge as a promising therapeutic target for myelin and neuronal damage induced by EV71 infection.

关键词： Enterovirus type 71 AMFR/gp78 PMP22 Autophagy Schwann cells

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

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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

Cost-effectiveness evaluation of rapid initiation of antiretroviral therapy based on decision-tree Markov model

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Chinese Medical Journal 2023年第8期136卷 986-988页

作者： Yuan Guan Qi Tang Han Zhu danping liu Tangkai Qi Renfang Zhang Jun Chen Li liu Yinzhong Shen Hongzhou Lu School of Public Health Fudan UniversityShanghai 200032China Shenzhen Key Laboratory of Pathogen and Immunity National Clinical Research Center for Infectious DiseaseShenzhen Third People’s HospitalShenzhenGuangdong 518100China Department of Infection and Immunity Shanghai Public Health Clinical CenterFudan UniversityShanghai 201508China Songjiang District Center for Disease Control and Prevention Shanghai 201620China

To the Editor:Human immunodeficiency virus(HIV)type 1 infection remains a serious and intractable public health problem worldwide.In 2020,there were 37.7 million surviving individuals with HIV infection worldwide and 680,000 HIV-related deaths reported by the Joint United Nations Programme on HIV/acquired immune deficiency syndrome(AIDS)(UNAIDS).

关键词： infection immunodeficiency therapy

GSK3 regulates VRN1 to control flowering time in wheat

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Journal of Integrative Plant Biology 2023年第7期65卷 1605-1608页

作者： Guoqing Cui danping Li Lichao Zhang Chuan Xia Xiuying Kong Xu liu State Key Laboratory of Crop Gene Resources and Breeding Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China

The precise control of flowering time is important for the regional adaptability and productivity of many crops.Various categories of genes related to flowering have been isolated and characterized functionally in wheat(Triticum aestivum) in response to vernalization to adjust flowering initiation. Before vernalization, the inhibitory histone modification H3K27me3 is enriched in the promoter and the first intron of the vernalization gene VRN1.

关键词： aestivum precise flowering

中医教材在变应性鼻炎中医诊疗指南制定中的证据价值探讨

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中医杂志 2024年第4期65卷 368-375页

作者：刘翠芳卫东锋杨伟谢飞彪郑丹平向兴华刘孟宇中国中医科学院中医临床基础医学研究所北京市100700 湖南科技大学数学与计算科学学院中国中医科学院中医药信息研究所

目的以变应性鼻炎为例,探讨中医类教材相关诊疗方案作为中医诊疗指南中证据应用的可行性与合理性。方法检索1949年10月至2022年12月出版的教材,检索截至2022年12月发表的变应性鼻炎中医诊疗指南,提取教材中变应性鼻炎相关章节诊疗内容,... 详细信息

目的以变应性鼻炎为例,探讨中医类教材相关诊疗方案作为中医诊疗指南中证据应用的可行性与合理性。方法检索1949年10月至2022年12月出版的教材,检索截至2022年12月发表的变应性鼻炎中医诊疗指南,提取教材中变应性鼻炎相关章节诊疗内容,比较分析不同时期的教材之间、现行不同版本教材之间、现行教材与指南之间的异同点。结果共纳入1975年至2021年中医耳鼻喉科的国家规划教材12本及变应性鼻炎中医诊疗指南4份。不同时期教材显示了诊疗方案的演变过程,从2003年出版的教材开始增加了肺经伏热证,并丰富了涂鼻法、滴鼻法等特色疗法,以及预防调摄、预后转归的内容,主要证型为肺气虚寒证、脾气虚弱证、肾阳不足证及肺经伏热证,常见推荐方剂分别为温肺止流丹、玉屏风散合苍耳子散,补中益气汤、参苓白术散,肾气丸或真武汤,辛夷清肺饮。现行不同版本教材之间比较显示其证型一致,方药略有差异。现行不同版本教材与指南的比较显示,教材推荐方剂增加了苍耳子散、小青龙汤、真武汤等,丰富了特色疗法如吹鼻、嗅法、塞鼻、洗鼻等,并增加了用药加减、预防调摄、预后转归等信息,可为指南补充相应证据。结论教材可以作为中医诊疗指南制定证据的有力补充,但仍需进一步研究教材证据的质量评价体系,以提高其应用于指南证据的可信度。

关键词：变应性鼻炎中医诊疗指南教材证据

SERPINB7对乳腺癌细胞增殖、凋亡、迁移和侵袭的影响

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江苏医药 2024年第1期50卷 10-15,F0003页

作者：刘志伟崔丹萍蒋婷婷浙江临海浙江省台州医院药剂科 317000 浙江临海浙江省台州医院老年医学科 317000 浙江临海浙江省台州医院审计部 317000

目的探讨丝氨酸蛋白酶抑制剂B7(SERPINB7)对乳腺癌细胞增殖、凋亡、迁移和侵袭的作用及其可能机制。方法将人乳腺癌细胞系MCF-7分为sh-SERPINB7组、空白对照组(BC组)和阴性对照组(NC组);其中,sh-SERPINB7组和NC组分别转染SERPINB7 RN... 详细信息

目的探讨丝氨酸蛋白酶抑制剂B7(SERPINB7)对乳腺癌细胞增殖、凋亡、迁移和侵袭的作用及其可能机制。方法将人乳腺癌细胞系MCF-7分为sh-SERPINB7组、空白对照组(BC组)和阴性对照组(NC组);其中,sh-SERPINB7组和NC组分别转染SERPINB7 RNA干扰慢病毒和阴性对照慢病毒。采用qRT-PCR法检测SERPINB7 mRNA表达,CCK-8法、流式细胞术、细胞划痕实验和Transwell实验分别检测细胞增殖、凋亡、迁移和侵袭,Western blot法检测SERPINB7、Bax、Bcl-2、Snail、Slug、转化生长因子β(TGF-β)、Smad3和磷酸化Smad3(p-Smad3)的蛋白表达。结果 MCF-7细胞中SERPINB7蛋白表达高于人正常乳腺上皮细胞系MCF-10A(P<0.05)。与BC组和NC组相比,sh-SERPINB7组MCF-7细胞中SERPINB7 mRNA表达以及Bcl-2、Snail、Slug、TGF-β、p-Smad3蛋白表达降低,细胞凋亡率升高,细胞划痕愈合率和侵袭细胞数减少,Bax蛋白表达增加(P<0.05)。结论 SERPINB7高表达于乳腺癌细胞,敲低SERPINB7可能通过抑制TGF-β/Smad3信号通路抑制乳腺癌细胞的迁移、侵袭,并促进其凋亡。

关键词：乳腺癌丝氨酸蛋白酶抑制剂B7 细胞迁移细胞侵袭

Denoising enabled channel estimation for underwater acoustic communications:A sparsity-aware model-driven learning approach

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Intelligent and Converged Networks 2023年第1期4卷 1-14页

作者： Sicong liu Younan Mou Xianyao Wang danping Su Ling Cheng School of Informatics Xiamen UniversityXiamen 361005China National Mobile Communications Research Laboratory Southeast UniversityNanjing 210096China the Information Engineering University of the WitwatersrandJohannesburg 2050South Africa

It has always been difficult to achieve accurate information of the channel for underwater acoustic communications because of the severe underwater propagation conditions,including frequency-selective property,high relative mobility,long propagation latency,and intensive ambient noise,etc.To this end,a deep unfolding neural network based approach is proposed,in which multiple layers of the network mimic the iterations of the classical iterative sparse approximation algorithm to extract the inherent sparse features of the channel by exploiting deep learning,and a scheme based on the Sparsity-Aware DNN(SA-DNN)for UAC estimation is proposed to improve the estimation accuracy.Moreover,we propose a Denoising Sparsity-Aware DNN(DeSA-DNN)based enhanced method that integrates a denoising CNN module in the sparsity-aware deep network,so that the degradation brought by intensive ambient noise could be eliminated and the estimation accuracy can be further improved.Simulation results demonstrate that the performance of the proposed schemes is superior to the state-of-the-art compressed sensing based and iterative sparse recovery schems in the aspects of channel recovery precision,pilot overhead,and robustness,particularly under unideal circumstances of intensive ambient noise or inadequate measurement pilots.

关键词： Orthogonal Frequency Division Multiplexing(OFDM) Underwater Acoustic Communications(UAC) sparse recovery deep learning sparse learning denoising approximate message passing

玉米-杂粕型饲粮中添加复合纤维素酶对蛋鸡生产性能、肝脏糖代谢、内源消化酶活性和肠道中葡萄糖转运载体基因表达的影响

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动物营养学报 2024年第2期36卷 935-945页

作者：常丹萍刘观忠杨博文赵国先张东远冯志华李茜张海华王珏河北农业大学动物科技学院保定071000 中科康源(唐山)生物技术有限公司迁安064400 河北省畜牧兽医研究所保定071000 河北科技师范学院秦皇岛066000

本试验旨在研究玉米-杂粕型饲粮中添加不同水平的复合纤维素酶对蛋鸡生产性能、蛋品质、肝脏中糖代谢相关酶活性、内源消化酶活性以及肠道中葡萄糖转运载体基因表达的影响,并筛选出复合纤维素酶的适宜添加量。选取288只健康状况良好的5... 详细信息

本试验旨在研究玉米-杂粕型饲粮中添加不同水平的复合纤维素酶对蛋鸡生产性能、蛋品质、肝脏中糖代谢相关酶活性、内源消化酶活性以及肠道中葡萄糖转运载体基因表达的影响,并筛选出复合纤维素酶的适宜添加量。选取288只健康状况良好的53周龄海兰褐蛋鸡,随机分为4组,每组6个重复,每个重复12只鸡。对照组饲喂玉米-杂粕(豆粕-棉籽粕-菜籽粕)型饲粮,3个试验组在玉米-杂粕型饲粮中分别添加200、400、600 mg/kg复合纤维素酶(主要成分为纤维素酶、木聚糖酶、淀粉酶和蛋白酶)。预试期7 d,正试期84 d。结果显示:1)与对照组相比,400 mg/kg组产蛋率显著提高(P0.05)。3)与对照组相比,玉米-杂粕型饲粮中添加400或600 mg/kg复合纤维素酶可以显著提高蛋鸡肝脏中丙酮酸激酶活性(P<0.05)。4)与对照组相比,400 mg/kg组蛋鸡空肠中淀粉酶与胰蛋白酶活性显著提高(P<0.05)。5)与对照组相比,玉米-杂粕型饲粮中添加400或600 mg/kg复合纤维素酶均可以显著提高蛋鸡空肠中钠-葡萄糖协同转运蛋白-1(SGLT-1)mRNA相对表达量(P<0.05)。综上可知,在玉米-杂粕型饲粮中添加复合纤维素酶可以通过提高饲粮中营养物质的释放量而增强蛋鸡小肠消化酶活性及肝脏中糖代谢相关酶活性,还能提高空肠中SGLT-1 mRNA相对表达量,进而改善生产性能。在本试验条件下,蛋鸡玉米-杂粕型饲粮中复合纤维素酶的最适添加量为400 mg/kg。

关键词：蛋鸡复合纤维素酶玉米-杂粕型饲粮生产性能肝脏糖代谢葡萄糖转运载体

当归补血汤与阿托伐他汀通过活化IGF1/IGF1R通路降低动脉粥样硬化斑块易损性

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南开大学学报（自然科学版） 2024年第2期57卷 39-45页

作者：陶宛璐刘金兰王丹萍黄稳莹王景颖周怡君吴文桐崔璨单鸣刘金鑫山东第二医科大学附属医院老年医学科山东潍坊261031 山东第二医科大学附属医院临床研究中心山东潍坊261041 山东第二医科大学附属医院全科医学科山东潍坊261031 山东第二医科大学附属医院肾内科山东潍坊261031 山东第二医科大学临床医学院山东潍坊261053 哈尔滨医科大学附属第二医院内分泌与代谢科黑龙江哈尔滨150086 青岛大学附属医院临床研究中心山东青岛266000

为了探索当归补血汤(DBT)的抗动脉粥样硬化作用机制并比较其与阿托伐他汀抗动脉硬化作用的异同,利用高脂高胆固醇饮食饲喂ApoE-/-雄鼠(16周)模仿动脉粥样硬化易损斑块模型,分别给与DBT和立普妥干预8周,检测动脉粥样硬化进展相关指标.结... 详细信息

为了探索当归补血汤(DBT)的抗动脉粥样硬化作用机制并比较其与阿托伐他汀抗动脉硬化作用的异同,利用高脂高胆固醇饮食饲喂ApoE-/-雄鼠(16周)模仿动脉粥样硬化易损斑块模型,分别给与DBT和立普妥干预8周,检测动脉粥样硬化进展相关指标.结果表明,DBT与立普妥均能降低血脂,减少巨噬细胞表型,抑制炎症因子和MMPs表达并促进细胞增殖,从而逆转动脉粥样硬化进展,减轻斑块负荷、降低斑块易损性,两给药组组间比较无统计学差异.结论是DBT有不弱于他汀类药物的抗动脉粥样硬化作用,可能的机制是通过上调IGF1表达并活化IGF1/IGF1R通路实现.

关键词：动脉粥样硬化斑块易损性当归补血汤阿托伐他汀胰岛素样生长因子1