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Bioengineered miR-328-3p modulates GLUT1-mediated glucose uptake and metabolism to exert synergistic antiproliferative effects with chemotherapeutics

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Acta Pharmaceutica Sinica B 2020年第1期10卷 159-170页

作者： Wanrong yi Mei-Juan Tu zhenzhen Liu Chao Zhang Neelu Batra Ai-Xi Yu Ai-Ming Yu Department of Orthopaedic Trauma and Microsurgery Zhongnan Hospital of Wuhan UniversityWuhan 430072China Department of Biochemistry&Molecular Medicine UC Davis School of MedicineSacramento 95817CAUSA

MicroRNAs(miRNAs or miRs)are small noncoding RNAs derived from genome to control target gene *** we have developed a novel platform permitting high-yield production of bioengineered miRNA agents(BERA).This study is to produce and utilize novel fully-humanized BERA/miR-3’28-3p molecule(hBERA/miR-3’28)to delineate the role of miR-328-3p in controlling nutrient uptake essential for cell *** first demonstrated successful high-level expression of hBERA/miR-328 in bacteria and purification to high degree of homogeneity(>98%).Biologic miR-328-3p prodrug was selectively processed to miR-328-3p to suppress the growth of highly-proliferative human osteosarcoma(OS)*** glucose transporter protein type 1,gene symbol solute carrier family 2 member 1(GUJTHSLC2A1),we identified and verified large neutral amino acid transporter 1,gene symbol solute carrier family 7 member 5(LPAT1/SLC7A5)as a direct target for miR-3’*** reduction of LAT1 protein levels by miR-3’28-3p did not alter homeostasis of amino acids within OS cells,suppression of GLUT1 led to a significantly lower glucose uptake and decline in intracellular levels of glucose and glycolytic metabolite ***,combination treatment with hBERA/miR-3’28 and cisplatin or doxorubicin exerted a strong synergism in the inhibition of OS cell *** findings support the utility of novel bioengineered RNA molecules and establish an important role of miR-328-3p in the control of nutrient transport and homeostasis behind cancer metabolism.

关键词： Bioengineered RNA MiR-328 LAT1 GLUT1 Chemosensitivity Cancer

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Association of a complete breast cancer pathologic response with axillary lymph node metastasis via neoadjuvant chemotherapy:Results from the CSBrS-012 study

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Chinese Medical Journal 2024年第11期137卷 1369-1371页

作者： Le Ma Pin Gao zhenzhen Liu Dechuang Jiao Rui Ling Jingjing Xiao yi Zhao yitong Wang Hongjian Yang Yunjiang Liu Ke Liu Jianguo Zhang Guangyan Li Dahua Mao yinglei Deng Jianjun He Maimaitiaili Amina Zhigang Yu Wang Fei yinhua Liu Peifen Fu Minya Yao Jiandong Wang Li Zhu Hongchuan Jiang Zuowei Zhao Xingsong Tian Zhongwei Cao Xinyu Ma Kejin Wu Shaomei Fu Ailin Song Yanwei Wang Jin Feng Zhimin Fan Department of Breast Surgery General Surgery CenterThe First Hospital of Jilin UniversityChangchunJilin 130021China Department of Breast Disease Henan Breast Cancer CenterAffiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China Department of Thyroid Breast and Vascular SurgeryXijing HospitalFourth Military Medical UniversityXi’anShaanxi 710032China Surgical Oncology Department Shengjing Hospital of China Medical UniversityShenyangLiaoning 110022China Department of Breast Surgery The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310022China Department of Surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebei 052360China Fourth Department of Breast Surgery Jilin Cancer HospitalChangchunJilin 130012China Department of Breast Surgery The Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiang 150086China Department of Breast Surgery Affiliated Wudang Hospital of Guizhou Medical UniversityGuiyangGuizhou 550009China Department of Breast Surgery The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710061China Department of Breast Surgery The Second HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250033China Breast Disease Center Peking University First HospitalBeijing 100034China Department of Breast Surgery The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310003China Department of General Surgery The First Medical CenterChinese PLA General HospitalBeijing 100852China Department of Breast Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Department of Breast Surgery The Second Affiliated Hospital of Dalian Medical UniversityDalianLiaoning 116023China Department of Breast and Thyroid Surgery Shandong Provincial Hospital Affiliated to Shandong UniversityJinan

To the Editor:In the last decade,neoadjuvant chemotherapy(NAC)has become a well-accepted treatment option for breast cancer,although few detailed description of NAC in China has yet been reported.[1]A previous study found that among patients with clinically node-negative(cN0)breast cancer,97.7%(432/442)with breast pathologic complete response(bpCR)had ypN0(absence of metastases in the axillary lymph nodes);and 71.6%(882/1232)without bpCR achieved ypN0(P<0.001).As for human epidermal growth factor receptor 2(HER2)positive or triple-negative breast cancer(TNBC)that achieved bpCR.

关键词： breast pathologic chemotherapy

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Real-time evolution of up-conversion nanocrystals from tailored metastable intermediates

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Nano Research 2023年第1期16卷 1552-1557页

作者： Peng Zhang Xue Yu Ping Xia zhenzhen Cui Jianhong yi Caiju Li Peng Song Feng Zhao Ting Wang Jianbei Qiu Xuhui Xu Faculty of Materials Science and Engineering Key Laboratory of Advanced Materials of Yunnan ProvinceKunming University of Science and TechnologyKunming 650093China Yunnan AFPN Technology Company Limited Kunming 650093China School of Mechanical Engineering Institute for Advanced StudyInstitute for Advanced Materials Deformation and Damage from Multi-ScaleChengdu UniversityChengdu 610106China College of Materials and Chemistry&Chemical Engineering Chengdu University of TechnologyChengdu 610059China

In-situ observation of the growth and decomposition processes is significantly important for guiding the fabrication of upconversion nanocrystals(UCNCs)with high ***,the high crystallization energy and rapid nucleation rate of the corresponding crystals make real-time observation still a huge ***,the in-situ nucleation-growth-degradation processes of the UCNCs are investigated by employing tailored metastable intermediates,which possess a slowing-down nucleation rate under electron beam *** non-classical nucleation processes of the UCNCs,containing the coalescence of clusters and the subsequent crystallization,are ***,the Ostwald ripening and oriented attachment processes,which determine the particle size and morphology,are unambiguously ***,the degrading process of the UCNCs is observed to be triggered by surface *** work provides an insight into the real-time evolution dynamics of the UCNCs,which further sheds light on the fabrication of nano-sized up-conversion phosphors.

关键词： up-conversion nanocrystals metastable intermediates real-time evolution in-situ transmission electron microscopy(TEM)

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基于Simulation X的多轴转向系统功能安全仿真分析

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山东科学 2024年第3期37卷 85-92页

作者：陈志韬周怡刘相新白锦洋刘洋王真真北京航天发射技术研究所北京100076 中信科智联科技(北京)有限公司北京100089

基于ISO 26262《道路车辆功能安全》的标准要求,对特种车的多轴电液转向系统进行分析,以提高系统的安全性和可靠性。运用Simulation X软件建立详细的多轴特种车仿真模型,通过模拟故障模式注入进行仿真试验。对仿真结果和数据进行分析,... 详细信息

基于ISO 26262《道路车辆功能安全》的标准要求,对特种车的多轴电液转向系统进行分析,以提高系统的安全性和可靠性。运用Simulation X软件建立详细的多轴特种车仿真模型,通过模拟故障模式注入进行仿真试验。对仿真结果和数据进行分析,评估得到故障的严重性、暴露度和可控性,从而确定相应的汽车安全完整性等级。基于故障注入仿真的汽车功能安全分析方法,在系统早期设计阶段可以作为评估架构安全性的重要手段。

关键词：多轴车电液转向系统 Simulation X 故障注入仿真汽车安全完整性等级

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Effect of transcutaneous electrical nerve stimulation at acupoints on patients with type 2 diabetes mellitus:a randomized controlled trial

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Journal of Traditional Chinese Medicine 2015年第2期35卷 134-140页

作者： Wu Zhiyuan Yang Ming Jia Jie Wu yi Huang Tiansheng Li Mingfen He Zhijie Guo zhenzhen Leung Mason Chin Pang Department of Rehabilitation Huashan Hospital Affiliated to Fudan University Department of Gastroenterology Shanghai Jiading Traditional Chinese Medicine Hospital Department of Rehabilitation Sciences The Hong Kong Polytechnic University

OBJECTIVE:To examine whether transcutaneous electric nerve stimulation at acupoints(Acu-TENS)improved the biochemical and physical indices of patients with type 2 diabetes mellitus(T2DM).METHODS:Ninety subjects with T2DM were divided randomly into a control group(n = 30),aerobic exercise group(n- 30),or Acu-TENS group(n = 30).In addition to conventional diabetes drug treatment,patients in the Acu-TENS group received acupoint stimulation,the aerobic exercise group engaged in walking exercises,and the control group was given sham electrical *** groups were treated for 30 min for each session and five times a week for 2 *** indices of glycosylated hemoglobin,2 h postprandial glucose,fasting serum insulin,triglyceride,total cholesterol,and body mass index were assessed at pre-treatment,post-treatment,and follow-up,which was 2 months after ***:The indices of the control group were not changed(P > 0.05) at the three time *** the pre-treatment measurement,there were significant differences(P > 0.05) in indices among the three *** post-treatment,each index of the two groups was lower than that of the control group(P < 0.05),and improved in comparison with the pre-treatment measurement(P < 0.05).In follow-up,each index of the aerobic exercise group and Acu-TENS group increased,but was still decreased compared with the pre-treatment value(P < 0.05),excluding body mass ***:Acu-TENS could improve the state of patients with T2 DM and be used as a therapy in clinical application.

关键词： Diabetes mellitus type 2 Transcutaneous electric nerve stimulation Acupuncture points Exercise

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miR-660-3p靶向NFAM1对RSV诱导支气管上皮细胞凋亡及炎症因子分泌的影响

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山东医药 2024年第13期64卷 30-35页

作者：童珍珍高雅丽许娟娟黄方许诣陈霞上海市嘉定区安亭医院呼吸内科上海201805 华中科技大学同济医学院附属协和医院呼吸内科湖北文理学院附属医院襄阳市中心医院儿科

目的探讨微小RNA-660-3p(miR-660-3p)靶向具有ITAM基序1的NFAT活化蛋白(NFAM1)对呼吸道合胞病毒(RSV)诱导支气管上皮细胞凋亡和炎症因子分泌的影响。方法体外传代培养人支气管上皮细胞16HBE。取对数生长期16HBE细胞,随机分为对照组、RS... 详细信息

目的探讨微小RNA-660-3p(miR-660-3p)靶向具有ITAM基序1的NFAT活化蛋白(NFAM1)对呼吸道合胞病毒(RSV)诱导支气管上皮细胞凋亡和炎症因子分泌的影响。方法体外传代培养人支气管上皮细胞16HBE。取对数生长期16HBE细胞,随机分为对照组、RSV组、miR-660-3p+RSV组、miR-NC+RSV组、pcDNA-NC+RSV组、pcDNA-NFAM1+RSV组、miR-660-3p+pcDNA-NC+RSV组、miR-660-3p+pcDNA-NFAM1+RSV组,miR-NC+RSV组转染NC mimics,miR-660-3p+RSV组转染miR-660-3p mimics,pcDNA-NFAM1+RSV组转染pcDNA-NFAM1,pcDNA-NC+RSV组转染pcDNA-NC,miR-660-3p+pcDNA-NC+RSV组共转染pcDNA-NC和miR-660-3p mimics,miR-660-3p+pcDNA-NFAM1+RSV组共转染pcDNA-NFAM1和miR-660-3p mimics,对照组和RSV组不予转染;除对照组外,其余各组均予RSV感染,MOI设定为0.0001。收集各组细胞,采用RT-qPCR法检测miR-660-3p、NFAM1 mRNA表达,采用流式细胞术检测细胞凋亡率,采用Western blotting法检测Cleaved-Caspase-3、NFAM1蛋白表达;收集各组培养上清液,采用ELISA法检测TNF-α、IL-6、IL-1β。通过starBase数据库预测NFAM1与miR-660-3p的靶向结合位点,并采用双荧光素酶报告基因实验验证miR-660-3p与NFAM1的靶向调控关系。结果与对照组比较,RSV组miR-660-3p表达降低,NFAM1 mRNA与蛋白及Cleaved-Caspase-3蛋白表达升高,细胞凋亡率及培养上清液TNF-α、IL-6、IL-1β水平升高(P均0.05)。与miR-660-3p+pcDNA-NC+RSV组比较,miR-660-3p+pcDNA-NFAM1+RSV组Cleaved-Caspase-3蛋白表达以及细胞凋亡率和培养上清液TNF-α、IL-6、IL-1β水平升高(P均<0.05)。结论miR-660-3p可通过靶向负调控NFAM1抑制RSV诱导支气管上皮细胞凋亡及炎症因子分泌。

关键词：支气管哮喘微小RNA-660-3p 具有ITAM基序1的NFAT活化蛋白细胞凋亡炎症因子

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基于网络药理学及分子对接方法探究舒胸方治疗冠心病的机制研究

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广东化工 2024年第2期51卷 133-137页

作者：杨策冉珍珍龙冰冰易东阳朱小龙陈芸彤庞毅王文祥重庆三峡医药高等专科学校药学院重庆404120 三峡库区道地药材开发利用重庆市重点实验室重庆404120 重庆文理学院重庆402160

目的:研究舒胸方治疗冠心病(CHD)的分子机制。方法:应用TCMSP获取舒胸方中红花、川芎、三七的化学成分,GeneCards和OMIM数据库预测舒胸方活性成分和冠心病靶点;用STRING数据库绘制成分-靶点PPI网络图;以Cytoscape软件绘制“成分-靶点-... 详细信息

目的:研究舒胸方治疗冠心病(CHD)的分子机制。方法:应用TCMSP获取舒胸方中红花、川芎、三七的化学成分,GeneCards和OMIM数据库预测舒胸方活性成分和冠心病靶点;用STRING数据库绘制成分-靶点PPI网络图;以Cytoscape软件绘制“成分-靶点-疾病”网络图,对于所获得的靶点和化合物分子信息应用微生信平台分别再进行GO和KEGG富集分析;使用PDB、Pubchem数据库和AutoDockTools软件对舒胸方核心化合物和CHD核心靶点进行分子对接。结果:筛得舒胸方中497个化学成分及8408个CHD的相关靶点;PPI网络分析获取353个交集靶点后,根据Degree值得到30个核心靶点,其主要核心靶点包括SRC、STAT3、PIK3R1等。GO功能富集分析得到112条与生物过程相关条目、102条与分子功能相关条目、63条与细胞组分相关条目(P<0.05),KEGG通路富集分析得到P13K-Akt、MAPK等164条通路(P<0.05)分子对接结果显示木脂素与SRC,6-羟基黄酮与STAT3,杨酶酮与PIK3R1具有较高的对接活性。结论:舒胸方的多种活性成分,如木脂素,6-羟基黄酮,杨酶酮可能通过抑制SRC,STAT3、PIK3R1的基因表达进而调控PI3K-AKT、MAPK等信号通路来治疗CHD。

关键词：舒胸方网络药理学冠心病分子对接作用机制

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Longitudinal survey and interdisciplinary research on healthy aging

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China Population and Development Studies 2020年第3期3卷 293-296页

作者： yi Zeng zhenzhen Zheng Center for Healthy Aging and Development Studies National School of DevelopmentPeking UniversityBeijingChina Center for Study of Aging and Human Development Duke UniversityDurhamUSA Institute of Population and Labor Economics Chinese Academy of Social SciencesBeijingChina

The collection of papers in this special issue of China Population and Develop-ment Studies includes a review on Chinese Longitudinal Healthy Longevity Survey(CLHLS)and four reports on preliminary findings from the 8th wave of CLHLS conducted in *** of China,which is the largest developing country with 1.4 billion peo-ple in total in 2019,is aging rapidly due to rapid declines in both fertility and mor-tality.

关键词： aging Population survey

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Resveratrol compares with melatonin in improving in vitro porcine oocyte maturation under heat stress

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Journal of Animal Science and Biotechnology 2017年第1期8卷 89-98页

作者： Yu Li Jing Wang zhenzhen Zhang Jinyun yi Changjiu He Feng Wang Xiuzhi Tian Minghui Yang Yukun Song Pingli He Guoshi Liu National Engineering Laboratory for Animal Breeding Key Laboratory of Animal Genetics and Breeding of the Ministry of AgricultureBeijing Key Laboratory for Animal Genetic ImprovementCollege of Animal Science and TechnologyChina Agricultural University College of Animal Science and Technology Jilin Agricultural University

Background： Resveratrol, an important phyto-antioxidant commonly found in grapes, mulberry, and other plants,has a variety of functions including anti-aging, anti-cancer and anti-inflammatory activities. In the current study, we investigated the beneficial effects of resveratrol on in vitro porcine oocyte maturation under heat stress（HS）. The effect of resveratrol, melatonin and their combination on alleviating HS was compared according to the maturation rate of oocytes and the development competence of embryos after parthenogenetic activation（PA）.Results： Supplementation with resveratrol（2.0 μmol/L） not only improved the nuclear maturation but also raised the blastocyst rate of porcine embryos＇ PA from oocytes that underwent HS by increasing their glutathione（GSH）level, reducing reactive oxygen species（ROS） and up-regulating the expression of Sirtuin 1（SIRT1）. It was also found that melatonin（10^-7mol/L） and the combination of resveratrol（2.0 μmol/L） plus melatonin（10^-7mol/L） exhibited more potent effects than resveratrol alone regarding their protective activities on oocyte maturation under ***： This study compared the efficiencies of resveratrol, melatonin and their combination for protecting porcine oocytes from heat stress. The mechanisms are attributed to the fact that each treatment may have different ability to regulate the synthesis of steroid hormones and the expression of mature related genes.

关键词： Combination Maturation Melatonin Oocyte Porcine Resveratrol

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基于网络药理学、分子对接和实验验证探究清金益气颗粒抗疲劳作用机制

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药物评价研究 2024年第9期47卷 1960-1970页

作者：张雨航温涛杨志华潘桂赟宋志会郭泽慧孟琪峰李真真吕清波王怡天津中医药大学天津301617

目的探究清金益气颗粒抗疲劳的作用及潜在作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、高通量中药实验和参考指南数据库(HERB)、PubChem、Swiss Target Prediction等数据库获取药物活性成分和作用靶点;通过GeneCards、O... 详细信息

目的探究清金益气颗粒抗疲劳的作用及潜在作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、高通量中药实验和参考指南数据库(HERB)、PubChem、Swiss Target Prediction等数据库获取药物活性成分和作用靶点;通过GeneCards、OMIM数据库收集疲劳的作用靶点;利用VENNY 2.1获取药物与疾病交集靶点,再联合Cytoscape 3.9.1软件构建药物-活性成分-疲劳交集靶点相互关系网络;将交集靶点导入STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络并利用DAVID数据库对交集靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,预测清金益气颗粒抗疲劳的作用机制;选取关键活性成分和核心靶点进行分子对接。通过负重力竭游泳实验观察小鼠负重力竭游泳时间;非负重游泳实验测定小鼠血清乳酸(BLA)、尿素氮(BUN)、乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、肝糖原(LG)、肌糖原(MG)、葡萄糖(GLU)等指标评价清金益气颗粒抗疲劳药效。结果网络药理学和分子对接结果显示清金益气颗粒抗疲劳的210个潜在作用靶点主要富集在磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-AKT)、丝裂原活化蛋白激酶(MAPK)、缺氧诱导因子1(HIF-1)、叉头框蛋白O(FoxO)等信号通路上,其主要活性成分和关键靶点蛋白结合能力较好。动物实验结果表明,清金益气颗粒可通过延长小鼠负重5%力竭游泳时间,降低非负重游泳小鼠血清中BLA、BUN、MDA水平,增加机体LG、MG、GLU水平储存和LDH、SOD、GSH-Px活性发挥抗疲劳作用。结论清金益气颗粒可能通过调节PI3K-AKT、MAPK、HIF-1、FoxO等信号通路影响机体能量代谢和氧化应激发挥抗疲劳的作用。

关键词：清金益气颗粒抗疲劳网络药理学分子对接能量代谢氧化应激

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