重学科上风ai 巨乳,通过多学科交叉和先进技艺哄骗,加强自主翻新和基础接洽,提升药理学科的笼统竞争力和影响力,同期,加强新药创制过甚哄骗接洽,加速科技效劳的调动与产业化发展。当今,药理学科已酿成5个褂讪的可执续发展的接洽标的:
1.神经精神性疾病药物药理。以神经精神疾病的发病机制与新药研发为主要接洽标的,围绕阿尔茨海默病、帕金森病、抑郁症及脑卒中等神经精神类疾病,开展发病机制的基础接洽与药物研发的翻新接洽,寻求防治神经精神类疾病的分子靶标并提供相应的诊治战略及候选新药。(1)以多种有用模子和多靶点筛选抗老年性死板药物及脑卒中药物。宣武病院李林讲授团队转让企业4 项效劳、新药2个,社会经济效益大。参乌胶囊含6味中药的复方新药,主治阿尔茨海默病(AD)和轻度分解休止(MCI)。获2项中国发明专利授权。完成了诊治轻中度AD和渐忘型MCI病东说念主的II期和III期临床西宾,阐明有用安全。2017年11月向国度药监局肯求坐褥上市注册,正在审评中。二苯乙烯苷(TSG,泰想胶囊)是从补肾中药何首乌中索要的有用部位新药,主治AD。或者作用在AD复杂发病机制的多靶点,尤其是具有神经保护和神经养分/再生作用。获中国发明专利授权2项。已完成诊治轻中度AD病东说念主的II期临床西宾,阐明有用安全。2019年参加III期临床西宾。(2)基于转基因动物和原代细胞,开展帕金森病的发病机制及药物防治作用接洽。(3)抑郁症发病机制与药物扰乱诊治接洽,寻找与抑郁症发生和诊治高度关系的信号转导通路的新靶点分子,开辟抗抑郁新药。(4)一些紧迫或特殊疾病如老年死板、抑郁症、帕金森病等动物、与细胞模子也曾成立,在新药筛选与评价中发扬着不成替代的作用。有讲授4东说念主,副讲授3东说念主,讲师/助研2东说念主。承担国度级课题11项,省部级课题10项,校局级课题17项,总经费2291万元。发表SCI论文29篇,国度发明授权专利7项,国度科技跨越奖二等奖1项,中国病院协会病院科技翻新奖三等奖1项。主编副主编专著3本,培养博士后3名,培养博士4名和硕士11名。
2.心脑血管疾病药物药理。(1)影响钙信号转导机制过甚关系钙拮抗剂的研发。(2)中药过甚有用成份对心脑血管系统的多靶点作用。有讲授/接洽员2东说念主,副讲授3东说念主,中级3东说念主。承担国度级课题6项,省部级课题5项,总经费436万元,发表SCI论文17篇,国度发明授权专利2项,其中一项成功转让企业。主编参编课本5本。培养博士4名,硕士10名。
3.抗肿瘤药物药理与靶向药物洽商。将肿瘤基础接洽与药物发现精好意思集结,并明慧于发现肿瘤的新机制、通过卵白之间的互作分析,笃定新靶点,再与药死亡学学科集结,进行靶向药物洽商,为抗肿瘤新药发现提供接洽平台。(1)结肠癌发病与新靶点发现,逆转肿瘤耐药性药物洽商;(2)肝癌发病机制与新靶点发现,靶向抗肝癌药物洽商;(3)肿瘤微环境与消化说念肿瘤出动和耐药机制接洽。(4)抗肿瘤药物药理学评价及胶质瘤新靶点的发现。讲授1东说念主,副讲授2东说念主,技艺员1东说念主。近5年来,也曾承担国度当然基金和要紧接洽接洽课题10余项,省部级课题5项,北京市属高校高水平教师戎行竖立复古接洽后生拔尖东说念主才栽植接洽花式等。当今在研课题6项,总经费达到1033万元,发表SCI论文26篇。培养博士5名、硕士4名。当今在读博士生4名,硕士接洽生8名。在毕业接洽生中,取得校级优博称呼1位。
4. 基于低氧与组学的分子代谢。(1)生物活性物资或手性分子的代谢、转运与药物能源学。(2)针对代谢酶和转运体为靶点的药效、代谢与药物互相作用。(3)低氧合适的分子代谢机制与关系药物靶点。(4)纳米碳点的制备表征及体内历程。现存讲授1东说念主,副高职称3东说念主,中级1东说念主。主执完成国度和省部级千般课题20余项。在低氧分子代谢、创生手性药物与中药活性要素的代谢转运、药动学接洽方面有显赫效劳。发表学术论文160余篇,其中海外SCI论文50余篇。获国度发明专利授权7项。获北京市及中华医学科技奖等省部院级奖项6项。研制开辟上市抗菌消炎新兽药“消炎醌”、抗血孢子虫药“焦虫净”和强力复合碘消毒剂。主编副主编出书专著(译著)课本10余部。培养博士后2名、博/硕士接洽生40多名。
5.代谢疾病药理。(1)代谢性病发生发展中的关节信号分子及代谢物汇聚接洽;(2)代谢性疾病模子及紧迫技艺的开辟、哄骗;(3)陌生遗传性代谢病的基因诊治接洽。有讲授1东说念主,承担国度级课题1项,省部级课题1项。栽植博士生2名、硕士生2名。
近五年承担的省部级以上科研花式
1 国度当然科学基金花式:偏向型配体S1P-FBAL激活G卵白偶联受体S1PR2上调二氢嘧啶脱氢酶(DPD)导致结直肠癌5-FU耐药性机制接洽,时候:2022年1月-2025年12月。
2 国度当然基金面上花式: 基于PPARγ调控汇聚接洽白花蛇舌草-半枝莲药对重塑肿瘤微环境抗炎性肠癌的作用及机制,时候:2022年1月-2025年12月。
3 国度当然科学基金面上花式:星形胶质细胞E3泛素联贯酶c-Cbl对帕金森病中神经炎症的调度及机制接洽,时候:2022年1月-2025年12月。
4 国度当然科学基金花式:舛错联贯卵白43磷酸化改变导致舛错通说念休止性心律失常的机制,时候:2022年1月-2025年12月。
5 科技部国度重心研发接洽花式:中药配伍诊治膀胱过度行径症的药学、药理机制及安全性评价接洽。时候:2021年8月-2023年7月。
6 国度当然科学基金面上花式:基于多组学和酵母低氧模子的神经酰胺关节代谢路线、调控汇聚及抗低氧作用真是证,时候:2021年1月-2024年12月。
7 国度当然科学基金花式:CXCR7偏向信号转导通过上调外泌体miRNAs促进结直肠癌肺出动前微环境重塑的分子机制及药物新靶标接洽,时候:2021年1月-2024年12月。
8 国度当然科学基金花式:磷酸胆碱磷酸酶-1负调控棕色脂肪激活与能量代谢的作用及机理接洽,时候:2021年1月-2023年12月。
9 国度当然科学基金花式:敲低胰岛素样滋长因子1受体(IGF-1R)激活RNA病毒感受器RIG-I和MDA-5机制接洽及药理学效应,时候:2020年1月-2023年12月。
10 国度当然科学基金花式:腹黑疾病舛错联贯卵白43重构机制过甚潜在靶点的接洽,时候:2020年1月-2023年12月。
11 国度当然科学基金花式:CXCR7/CXCR4异二聚体(CXCR4/CXCR7heterodimer)通过信号转导偏移促进组卵白去甲基化:结直肠癌发病新机制接洽及防治战略探索,时候:2019年1月-2022年12月。
12 国度当然科学基金花式,新式抗抑郁剂JZ-1201通过5-HT1A受体调度GABA/Glu系统均衡的作用机制接洽,时候:2019年1月-2022年12月。
13 国度当然基金面上花式:白花蛇舌草-半枝莲药对通过有氧糖酵解路线协同抗肿瘤的机理接洽,时候:2018年1月-2021年12月。
14 国度当然科学基金面上花式:基于组学和斑马鱼模子的缺氧关节代谢路线、调控网路及关系活性物资的分析表征和确证,时候:2018年1月-2021年12月。
15 国度当然科学基金面上花式:缺氧造反缺氧中药红景天活性要素代谢、转运与药代能源学及作用的影响过甚分子机制,时候:2016年1月-2019年12月。
16 国度当然科学基金后生花式:MUC1介导的半枝莲总黄酮配伍5-氟尿嘧啶协同抗胰腺癌作用机制接洽,时候:2011年1月-2016年12月。
17 北京市教委专项重心花式:CaM/CaMKII在糖尿病血管内皮损害和LMWF 防治血管归并症中的作用机制接洽,时候:2017年1月-2019年12月。
18 北京市当然基金面上花式:白花蛇舌草半枝莲药对黄酮类有用部位协同抗肿瘤的机制接洽,时候:2017.01-2019.12。
19 北京市当然科学基金面上花式:泛素联贯酶c-Cbl对小胶质细胞炎症反馈的调控过甚与帕金森病的关系性接洽, 时候:2021.01-2023.12。
授权专利
1 国度发明专利:一种诊治消化说念癌症的药物组合物2021年3月,授权号:ZL201911341629.1
近五年发表的代表性接洽论文ai 巨乳
(一)神经退行性疾病药物的新靶点与新药开辟
1 Gao Nana,Zheng Wei,Jie Xiong,Xiaorong Li,Jin Zengliang.GW117 :a novel serotonin (5-HT2C) receptor antagonist and melatonin (MT1/MT2) receptor agonist with potential antidepressant-like activity in rodents,CNS Neuroscience & Therapeutics,2021;27:702–713;
2 Nana Gao,Murezati Tiliwaerde,Wei Zheng,Jie Xiong,Xiao-rong Li,Zengliang Jin.Neuropharmacological and antidepressant-like effects of ZY-1408: A novel serotonin/norepinephrine reuptake inhibitor and serotonin receptor 2C antagonist.Neuropharmacology. 2021 Jan;182:108376.
3 Fuyao Xiao, Xiaojie Zhang, Pinfei Ni , Haibo Yu, Qiming Gao, Mengyao Li, Peiyun Huo, Ziwei Wei, Sihan Wang, Yi Zhang, Rui Zhao, Aixue Li, Zhirui Li, Yuejia Li, Haixiao Cheng, Libo Du, Suping Ren, Qun Yu, Yang Liu, Yuming Zhao Voltage-dependent potassium channel Kv4.2 alleviates the ischemic stroke impairments through activating neurogenesis. Neurochemistry International 150 (2021) 105155.
4 Xiaojie Zhang,Qiming Gao,Qianfen Zhuang, Lu Zhang, Sihan Wang, Libo Du, Wenxi Yuan, Caifang Wang, Qiu Tian, Hua Yu, Yuming Zhao and Yang Liu. A dual-functional nanovehicle with fluorescent tracking and its targeted killing effects on hepatocellular carcinoma cells. RSC advances 2021,11,10986-10995.
5 Yan Gao, Juntong Li, Jianping Li, shifeng chu, Zhao Zhang, Li Zhang, Yali Li, Jiaqing Yan, Lin Li, Naihong Chen, Lan Zhang. Tetrahydroxy stilbene glycoside alleviated inflammatory damage by mitophagy via AMPK related PINK1/Parkin signaling pathway. Biochemical Pharmacology, 2020, 177:113997.
6 Fan Z, Pan Y, Zhang Z, Yang H, Yu S, Zheng Y, Ma J, Wang X. Systemic activation of NLRP3 inflammasome and plasma alpha-synuclein levels are correlated with motor severity and progression in Parkinson's disease. J Neuroinflammation, 2020, 17(1):11.
7 Yue Li, Yuming Zhao, Chong Gao, Meiling Wu, Kwok-Fai So, Yao Tong, Jiangang Shen. Caveolin-1 Derived from Brain Microvascular Endothelial Cells Inhibits Neuronal Differentiation of Neural Stem/Progenitor Cells In Vivo and In Vitro. Neuroscience 448 (2020) 172–190.
8 Lin Li, Lan Zhang, Cui-cui Yang. Multi-target strategy and experimental studies of traditional Chinese medicine for Alzheimer’s disease therapy. Current Topics in Medicinal Chemistry, 2016, 16(5):537-548.
9 Zhao YM, Liu DM, Li J, Zhang XJ, Wang XL. L-NBP, a multiple growth factor activator, attenuates ischemic neuronal impairments possibly through promoting neuritogenesis. Neurochemistry International 124 (2019) 94–105.
10 Xiaomin Yin, Chen Chen , Ting Xu , Lin Li, Lan Zhang. Tetrahydroxystilbene glucoside modulates amyloid precursor protein processing via activation of AKT-GSK3β pathway in cells and in APP/PS1 transgenic mice. Biochemical and Biophysical Research Communications, 2018, 495:672-678.
11 Ru-yi Zhang, Lan Zhang, Li Zhang, Yu-lan Wang, Lin Li. Anti-amyloidgenic and neurotrophic effects of tetrahydroxystilbeneglucoside on a chronic mitochondrial dysfunction rat model induced by sodium azide. Journal of Natural Medicines, 2018, 72:596-606.
12 Fan Z, Liang Z, Yang H, Pan Y, Zheng Y, Wang X. Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia. J Neuroinflammation, 2017, 14(1):256.
13 Jinzhou Tian, Jing Shi, Tao Li, Lin Li, Zhiliang Wang, Xiaobin Li, Zu Lv, Qingshan Zheng, Mingqing Wei, Yongyan Wang. Efficacy and safety of an herbal therapy in patients with amnestic mild cognitive impairment: a 24-week randomized phase III trial. Evidence-Based Complementary and Alternative Medicine, 2017, DOI: 10.1155/2017/4251747.
(二)心脑血管疾病药物药理
1 Sun Z ,Wang L,Han L,Wang Y,Zhou Y,Li Q ,Wu Y, Shaletanati T,Hou Y,Wu L, LiuR,FuZ,YouH,LiB,ZhengY,Luo D. Functional Calsequestrin-1 Is Expressed in the Heart and Its Deficiency Is Causally Related to Malignant Hyperthermia-Like Arrhythmia.Circulation2021, Sep;144(10):788-804.
2 Fu Z, Wu L, Xue J, Zhang L, Li C, You H, Luo D. Connexin43 hyper-phosphorylation at serine 282 triggers cardiomyocyte apoptosis through mitochondrial apoptotic pathway. Acta Pharmacologica Sinica 2021, 0:1–9; https://doi.org/10.1038/s41401-021-00824-z.
3 Yingxu Li , Bing Li , Xuechun Wang, Yan Meng, Lu Bai, Yuanyuan Zheng. Safe and efficient magnetic resonance imaging of acute myocardial infarction with gadolinium-doped carbon dots. Nanomedicine (Lond).2020;15:2385-2398.
4 Yang Y,Yan X, XueJ,Zheng Y,Chen M, SunZ,Liu T,Wang C,You H,Luo D. Connexin43 dephosphorylation at serine 282 is associated with connexin43-mediated cardiomyocyte apoptosis. Cell Death and Differ. 2019, 26(7):1332-1345.
5 Sun Z,Yang Y, WuL,Shaletanati T,You H,Zheng Y,Luo D. Connexin 43-serine 282 modulates serine 279 phosphorylation in cardiomyocytes. Biochem Biophys Res Commun2019, 513(3):567-572.
6 Xue J,Yan X, YangY,Chen M,Wu L,Gou Z,Sun Z,Shaletanati T,Zheng Y,Luo D.Connexin 43 dephosphorylation contributes to arrhythmias and cardiomyocyte apoptosis in ischemia/reperfusion hearts. Basic Res Cardiol2019, 114(5):40.
7 Liu T, Wang Z, Chen X, You H, Xue J, Cai D, Zheng Y, Xu Y, Luo D. Low molecular-weight fucoidan protects against hindlimb ischemic injury in type 2 diabetic micethrough enhancing endothelial nitric oxide synthase phosphorylation. J Diabetes 2018, 10(11):820-834.
8 Wang Z,Liu T,Chen X,You H,Zhang Q,Xue J,Zheng Y,Luo D. Lowmolecularweightfucoidanameliorateshindlimbischemicinjuryintype2diabeticrats. J Ethnopharmacol2018, 210:434-442.
9 Wang H,Wang C,Wang L,Liu T,Wang Z,You H,Zheng Y,Luo D. Orai1downregulationimpairslymphocytefunctionintype2diabetesmellitus. Biochem Biophys Res Commun2018, 500(2):384-390.
10 Li S,Xue J,Sun Z,Liu T,Zhang L,Wang L,You H,Fan Z,Zheng Y,Luo D. CaMKIIPotentiatesStore-OperatedCa2+EntryThroughEnhancingSTIM1AggregationandInteractionwithOrai1. Cell Physiol Biochem2018, 46(3):1042-1054.
11 Zheng Y, Liu T, Wang Z, Xu Y, Zhang Q, Luo D. Low molecular weight fucoidan attenuates liver injury via SIRT1/AMPK/PGC1α axis in db/db mice. Int J Biol Macromolecules 2018, 112:929-936.
12 Wang Z, Liu T, Chen X, You H, Zhang Q, Xue J, Zheny Y, Luo D. Low molecular weight fucoidan ameliorates hindlimb ischemic injury in type 2 diabetic rats. J Ethnopharmacol 2017, 210:434-442.
(三)抗肿瘤接洽
1 Lu L, Zhan S, Liu X, Zhao X,Lin X,Xu H. Antitumor Effects and the Compatibility Mechanisms of Herb PairScleromitrion diffusum(Willd.) R. J. Wang-Sculellaria barbataD. Don.Front Pharmacol. 2020;11:292. doi: 10.3389/fphar.2020.00292. eCollection 2020.
2 Zhang YH, Luo DD, Wan SB, Qu XJ.S1PR2 inhibitors potently reverse 5-FU resistance by downregulating DPD expression in colorectal cancer. Pharmacol Res. 2020 May;155:104717.
3 Zhang YH, Shi WN, Wu SH, Miao RR, Sun SY, Luo DD, Wan SB, Guo ZK, Wang WY, Yu XF, Cui SX, Qu XJ. SphK2 confers 5-fluorouracil resistance to colorectal cancer via upregulating H3K56ac-mediated DPD expression. Oncogene. 2020 Jul;39(29):5214-5227.
4 Xu H, Yuan R, Liu X, Li X, Qiao G, Li C, Gedanken A,Lin X. Zn-doped CuO nanocomposites inhibit tumor growth by NF-κB pathway cross-linked autophagy and apoptosis.Nanomedicine (Lond). 2019;14(2):131-149.
5 Su S, Xu H, Chen X, Qiao G, Farooqi AA, Tian Y, Yuan R, Liu X, Li C, Li X, Wu N,Lin X. CS5931, A Novel Marine Polypeptide, Inhibits Migration and Invasion of Cancer Cells Via Interacting with Enolase 1. Recent Pat Anticancer Drug Discov. 2018;13(3):360-367.
6 Xu H, Chen Q, Wang H, Xu P, Yuan R, Li X, Bai L, Xue M*. Inhibitory effects of lapachol on rat C6 glioma in vitro and in vivo by targeting DNA topoisomerase I and topoisomerase II. Journal of Experimental & Clinical Cancer Research. 2016; 35:178-187.
7 Yuan R, Xu H, Liu X, Tian Y, Li C, Chen X, Su S, Perelshtein I, Gedanken A, Lin X. Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Human Cancer Cells through Reactive Oxygen Species-Mediated NF-κB Activations. ACS Appl. Mater. Interfaces 2016, 8, 31806−31812.
8 Xu H, Yang T, Liu X, Tian Y, Chen X, Yuan R, Su S, Lin X, Du G*. Luteolin synergizes the antitumor effects of 5-fluorouracil against human hepatocellular carcinoma cells through apoptosis induction and metabolism. Life Sci. 2016; 144:138-147.
9 Wang D, Wang X, Si M, Yang J, Sun S, Wu H, Cui S, Qu X, Yu X. Exosome-encapsulated miRNAs contribute to CXCL12/CXCR4-induced liver metastasis of colorectal cancer by enhancing M2 polarization of macrophages. Cancer Lett. 2020 Apr 1;474:36-52.
性感美女(四)基于低氧与组学的分子代谢
1 Yi Ma, Yi Wu, Zhengchao Xia, Jingyi Li, Xiaorong Li, Pingxiang Xu, Xuelin Zhou and Ming Xue. Anti-Hypoxic Molecular Mechanisms of Rhodiola crenulata Extractin Zebrafish as Revealed by Metabonomics. Frontiers in Pharmacology.2019. 10:1356.
2 Wu Yi,Ma Yi,Li Jing,Zhou Xuelin, Li Lei,Xu PingXiang, Li Xiaorong, Xue Ming. The bioinformatics and metabolomics research on anti-hypoxic molecular mechanisms of Salidroside via regulating the PTEN mediated PI3K/Akt/NF-κB signaling pathway. Chinese Journal of Natural Medicines, 2021.19(6) 442-453.
3 Qunying Chen, Lu Bai, Xuelin Zhou, Pingxiang Xu, Xiaorong Li, Huanli Xu, Yuanyuan Zheng, Yuming Zhao, Shousi Lu, and Ming Xue. Development of long-circulating lapachol nanoparticles: formation, characterization, pharmacokinetics, distribution and cytotoxicity. RSC Advances, 2020, 10: 30025.
4 Yi Ma, Yi Wu, Zhengchao Xia, Jingyi Li, Xiaorong Li, Pingxiang Xu, Xuelin Zhouand Ming Xue.Anti-Hypoxic Molecular Mechanisms of Rhodiola crenulata Extract in Zebrafish as Revealed by Metabonomics. Frontiers in pharmacology, 2019, 12: 01356.
5 Zhengchao Xia, Xuelin Zhou, Jingyi Li, Lei Li, Yi Ma, Yi Wu, Zhong Huang, Xiaorong Li, Pingxiang Xu, Ming Xue. Multiple-omics techniques reveal the role of glycerophospholipid metabolic pathway in the response of Saccharomyces cerevisiae against hypoxic stress. Frontiers in Microbiology, 2019, 10:1398.
6 Pingxiang Xu, Ying Liu, Liyun Wang, Yi Wu, Xuelin Zhou, Junhai Xiao, Jianquan Zheng, Ming Xue. Phencynonate S-isomer as a eutomer is a novel central anticholinergic drug for anti-motion sickness. Scientific Reports, 2019, 9:2000.
7 Wenwen Gong, Pingxiang Xu, Shanshan Guo, Xiaorong Li, Zengliang Jin, Yuming Zhao, Ming Fan and Ming Xue. Effect of hypoxia on the pharmacokinetics and metabolism of zaleplon as a probe of CYP3A1/2 activity. RSC Advances, 2017, 7, 25414-21.
8 Shousi Lu, Shanshan Guo, Pingxiang Xu, Xiaorong, Li, Yuming Zhao, Wei Gu, Ming Xue. hydrothermal synthesis of nitrogen-doped carbon dots with real-time live-cell imaging and blood–brain barrier penetration capabilities. International Journal of Nanomedicine, 2016, 11, 6325–6335.
9 Huanli Xu, Qunying Chen, Hong Wang, Pingxiang Xu, Ru Yuan, Xiaorong Li, Lu Bai, Ming Xue. Inhibitory effects of lapachol on rat C6 glioma in vitro and in vivo by targeting DNA topoisomerase I and topoisomerase II. Journal of Experimental & Clinical Cancer Research, 2016, 35, 178-187.
(五)代谢疾病药理
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