4. 科研工作
近年来的研究方向：
1) 创新药物基础和临床研究：课题组近年来开展化学1.1类抗肿瘤新药的临床试验研究，新型抗自身免疫性疾病药物羧胺三唑的临床前研究，以及羧胺三唑临床新用途的研究。
2) 炎-癌转化机制：课题组近年来对炎症与肿瘤的关联，炎-癌转化的机理以及羧胺三唑在“炎-癌”链中的作用开展研究。
课题组承担的科研项目：
叶菜英：科技部新药创制科技重大专项：抗肿瘤、糖尿病、神经退行性疾病新药临床前药效学评价技术平台的建立；科技部新药创制科技重大专项：新药临床前研究新型抗自身免疫疾病药物羧胺三唑的临床前研究；科技部新药创制科技重大专项：以离子通道为靶标的重大新药创制--新药CAI的临床前研究；张德昌、叶菜英，国际科技合作重点项目：单抗与新型抗癌药合用的高效低毒抗癌疗法及其机理研究 。张德昌：国家自然科学基金项目：兼具抗炎抗肿瘤作用的药物及炎-癌转化机理研究 。郭磊：国家自然基金青年基金：环核苷酸/PDEs与SIRT1蛋白在慢性气道炎症反应中的相互调节及羧胺三唑的抗炎机制研究；所长基金：减轻神经元炎性损害对肌萎缩性脊髓侧索硬化症的防治意义及Translational Research of CAI Therapy against Cancer Cachexia项目。朱蕾：国家自然基金青年基金：炎症体介导实验性关节炎滑膜细胞活化的病理机制及羧胺三唑的治疗作用；所长基金：炎症体对佐剂性关节炎滑膜细胞活化的调控及羧胺三唑的作用。鞠瑞：国家自然基金青年基金：羧胺三唑联合糖酵解抑制剂对肿瘤相关巨噬细胞中炎性细胞因子表达的作用及其机制研究；国家自然基金：羧胺三唑抑制肿瘤细胞线粒体氧化磷酸化的作用机理及基于此作用的药效优化研究。
5. 近5年代表性论文
1) Carboxyamidotriazole synergizes with sorafenib to combat non-small cell lung cancer through inhibition of NANOG and aggravation of apoptosis. J Pharmacol Exp Ther. 2017, 362(2):219-229.
2) Carboxyamidotriazole alleviates muscle atrophy in tumor-bearing mice by inhibiting NF-κB and activating SIRT1. Naunyn Schmiedebergs Arch Pharmacol. Naunyn Schmiedebergs Arch Pharmacol. 2017, 390(4):423-433.
3) Therapeutic efficacy of carboxyamidotriazole on 2,4,6-trinitrobenzene sulfonic acid-induced colitis model is associated with the inhibition of NLRP3 inflammasome and NF-κB activation. Int Immunopharmacol. 2017;45:16-25.
4) Carboxyamidotriazole inhibits oxidative phosphorylation in cancer cells and exerts synergistic anti-cancer effect with glycolysis inhibition. Cancer Lett. 2016, 370(2): 232-241.
5) Activation of NALP1 inflammasomes in rats with adjuvant arthritis; a novel therapeutic target of carboxyamidotriazole in a model of rheumatoid arthritis. Br J Pharmacol. 2015, 172(13): 3446-3459.
6) Carboxyamidotriazole: a novel inhibitor of both cAMP-phosphodiesterases and cGMP-phosphodiesterases. Eur J Pharmacol. 2015, 746:14-21.
7) Carboxyamidotriazole ameliorates experimental colitis by inhibition of cytokine production, nuclear factor-κB activation, and colonic fibrosis. J Pharmacol Exp Ther. 2012, 342(2):356-365.
8) Inhibition of pro-inflammatory cytokines in tumour associated macrophages is a potential anti-cancer mechanism of carboxyamidotriazole, Eur J Cancer, 2012, 48(7): 1085-1095
9) Anti-inflammatory and analgesic potency of carboxyamidotriazole, a tumorostatic agent, J Pharmacol Exp Ther, 2008, 325(1): 10-16.
10) 羧胺三唑对RBL-2H3细胞活化脱颗粒的影响. 基础医学与临床，2017, 37 (4): 479-483.
11) 羧胺三唑联合地塞米松有效缓解小鼠过敏性气道炎症. 中国医药生物技术，2017, 12 (3) : 242-247.
12) 羧胺三唑与SAHA联合用药抑制Lewis肺癌细胞的体内外研究，癌症进展, 2016, 14（4）：324 ~ 331.
13) 羧胺三唑对大鼠佐剂性关节炎的治疗作用，中国医学科学院学报，2016, 38（1）：17 ~ 22.
14) 羧胺三唑抑制肺癌Lewis细胞生长的机制及抑瘤作用优化探索，中华临床医师杂志(电子版)，2015，9（10）：1879 ~ 1882
15) 利用四唑盐染料WST反映巨噬细胞受脂多糖刺激活化后的氧化应激和代谢变化，中国医药生物技术，2015，10（3）： 242 ~ 247.
16) 羧胺三唑通过肿瘤相关巨噬细胞间接抑制肿瘤细胞的迁移，中华临床医师杂志(电子版)，2014，8（6）：1080 ~ 1085.
17) 羧胺三唑对肺腺癌细胞自噬的影响，中华临床医师杂志(电子版)，2013，7（11）：4883 ~ 4888.
18) 羧胺三唑对TNF-α诱导的佐剂性关节炎大鼠成纤维样滑膜细胞中细胞因子分泌和NF-κB活化的影响，中华临床医师杂志(电子版)，2013，7（11）：4849 ~ 4853.
19) 羧胺三唑对TNF-α诱导的成纤维样滑膜细胞增殖及MMP-1、MMP-3表达的影响，中华临床医师杂志(电子版)，2013，7（10）：4354 ~ 4357.
20) 羧胺三唑对脂多糖诱导的RAW264.7细胞分泌炎症因子的影响，中华临床医师杂志(电子版)，2013，7（9）：3888 ~ 3891.
21) 羧胺三唑联合小剂量地塞米松抗肿瘤作用研究，中华临床医师杂志(电子版)，2013，7（7）：2949 ~ 2953.
22) 羧胺三唑对角叉菜胶诱导急性炎症的抗炎作用，中国临床药理学与治疗学，2013，18（06）：601 ~ 606.
23) 羧胺三唑在BV2细胞模型中的抗炎作用，基础医学与临床，2011，31（6）：621 ~ 624.
24) 羧胺三唑与小剂量地塞米松合用对A549 肺癌移植瘤生长抑制作用的研究，中国医药生物技术，2011，6（2）：101 ~ 105.
5. 近5年代表性论文
1) Mingyang Wang, Lu Feng, Ji Zheng, Junya Liu, Shujie Fan, Jun Zhao, Nan Yang, Yanyong Liu*, Zhanjun Yang*, Caiying Ye*, Pingping Zuo. Improvement of mitochondrial function mediated the neuroprotective effect of 5-(4-hydroxy-3-dimethoxybenzylidene)-2-thioxo-4-thiazolidinone in rats with cerebral ischemia reperfusion injuries. Oncotarget 2017; 8(37): 61193-61202.
2) Mingyang Wang#, Yi Zhang#, Lu Feng,Ji Zheng, Shujie Fan, Junya Liu, Nan Yang*, Yanyong Liu*, Pingping Zuo. Compound porcine cerebroside and ganglioside injection attenuates cerebral ischemia–reperfusion injury in rats by targeting multiple cellular processes. Neuropsychiatric Disease and Treatment 2017; 13: 927-935.
3) Wei Huang#, Xia Yuan, Ting Sun, Shujie Fan, Jun Wang, Quan Zhou, Wei Guo, Fuxiang Ran, Zemei Ge, Huayu Yang, Runtao Li*, Jingrong Cui*. Proteasome inhibitor YSY01A abrogates constitutive STAT3 signaling via down-regulation of Gp130 and JAK2 in human A549 lung cancer cells. Frontiers in Pharmacology 2017; 8: 476.
4) Dongmei Li#, Ji Zheng#, Mingyang Wang, Lu Feng, Yanyong Liu*, Nan Yang*, Pingping Zuo. Wuling powder prevents the depression-like behavior in learned helplessness mice model through improving the TSPO mediated-mitophagy. Journal of Ethnopharmacology 2016; 186: 181-188.
5) Dongmei Li, Ji Zheng, Mingyang Wang, Lu Feng, Yanyong Liu*, Nan Yang*, Pingping Zuo. Changes of TSPO-mediated mitophagy signaling pathway in learned helplessness mice. Psychiatry Research. 2016; 245: 141-147.
6) Yao Jiang#, Nan Yang#, Huifeng Zhang, Bo Sun, Chunying Hou, Chao Ji, Ji Zheng, Yanyong Liu*, Pingping Zuo*. Enhanced in vivo Antitumor Efficacy of Dual-functional Peptide-modified Docetaxel Nanoparticles through Tumor Targeting and Hsp90 Inhibition. Journal of Controlled Release 2016; 221: 26-36.
7) Chunying Hou, Bo Sun, Yao Jiang, Ji Zheng, Nan Yang, Chao Ji, Zhen Liang, Jiaojiao Shi, Rui Zhang, Yanyong Liu*, Caiying Ye*, Pingping Zuo*. MicroRNA-31 inhibits lung adenocarcinoma stem-like cells via down-regulation of MET-PI3K-Akt signaling pathway. Anti-Cancer Agents in Medicinal Chemistry 2016; 16: 501-518.
8) Nan Yang#, Zhili Ren#, Ji Zheng#, Lu Feng, Dongmei Li, Kai Gao, Lianfeng Zhang, Yanyong Liu*, Pingping Zuo. 5-(4-hydroxy-3-dimethoxybenzylidene)-rhodanine (RD-1)-improved mitochondrial function prevents anxiety- and depressive-like states induced by chronic corticosterone injections in mice. Neuropharmacology 2016; 105: 587-593.
9) Wei Huang#, Quan Zhou#, Xia Yuan, Zemei Ge, Fuxiang Ran, Huayu Yang, Guangliang Qiang, Runtao Li*, Jingrong Cui*. Proteasome inhibitor YSY01A enhances cisplatin cytotoxicity in cisplatin-resistant human ovarian cancer cells. Journal of Cancer 2016, 7(9): 1133-1141.
10) Wei Huang#, Zizheng Dong, Yifan Chen, Fang Wang, Chao Wang, Hui Peng, Yantao He, Giao Hangoc, Karen Pollok, George Sandusky, Xinyuan Fu, Hal Broxmeyer, Zhongyin Zhang, Jingyuan Liu*, Jianting Zhang*. Small-molecule inhibitors targeting the DNA-binding domain of STAT3 suppress tumor growth, metastasis and STAT3 target gene expression in vivo. Oncogene 2016; 35(6): 802-811.
11) Hailin Long#, Zhongbin Cheng, Wei Huang, Qi Wu, Xiaodan Li, Jingrong Cui, Peter Proksch, Wenhan Lin*. Diasteltoxins A-C, Asteltoxin-Based Dimers from a Mutant of the Sponge-Associated Emericella variecolor Fungus. Organic Letters 2016; 18(18): 4678-4681.
12) Guangliang Qiang#, Wei Huang, Chaoyang Liang, Rui Xu, Jue Yan, Yanyan Xu, Ye Wang, Jiping Da, Bin Shi, Yongqing Guo, Deruo Liu*. Association between histopathological subtype, 18F-fluorodeoxyglucose uptake and epidermal growth factor receptor mutations in lung adenocarcinoma. Oncology Letters 2016, 11: 1769-1777.
13) Nan Yang#, Yao Jiang#, Huifeng Zhang#, Bo Sun, Chunying Hou, Ji Zheng, Yanyong Liu*, Pingping Zuo*. Active targeting docetaxel-PLA nanoparticles eradicate the circulating lung cancer stem like cells and inhibit the liver metastasis. Molecular Pharmaceutics 2015; 12: 232-239.
14) Bo Sun, Nan Yang, Yao Jiang, Huifeng Zhang, Chunying Hou, Chao Ji, Yanyong Liu*, Pingping Zuo*. Antagomir-1290 suppresses CD133+ cells in non-small cell lung cancer by targeting fyn-related Src family tyrosine kinase. Tumor Biology 2015; 36: 6223-6230.
15) Zhen Liang#, Nan Yang#, Yao Jiang, Chunying Hou, Ji Zheng, Jiaojiao Shi, Rui Zhang, Dongmei Li, Yanyong Liu*, Pingping Zuo*. Targeting Docetaxel-PLA nanoparticles simultaneously inhibit tumor growth and liver metastases of small cell lung cancer. International Journal of Pharmaceutics 2015; 494 (1): 337-345.
16) Zhili Ren#, Nan Yang#, Chao Ji, Ji Zheng, Tao Wang, Yanyong Liu*, Pingping Zuo*. Neuroprotective effects of 5-(4-hydroxy-3-dimethoxybenzylidene)-thiazolidinone in MPTP induced Parkinsonism model in mice. Neuropharmacology 2015; 93:209-218.
17) Rui Zhang, Nan Yang, Chao Ji, Ji Zheng, Zhen Liang, Chun-Ying Hou, Yan-Yong Liu*, Ping-Ping Zuo*. Aceglutamide attenuated motor dysfunctions induced by cerebral ischemia injury through suppressing TRAF1-mediated apoptosis signaling pathway. Restorative Neurology and Neuroscience 2015; 33:741–759.
18) Nan Yang, He Liu, Yao Jiang, Ji Zheng, Dong-mei Li, Chao Ji, Yan-yong Liu*, Pingping Zuo. Improved cognitive function in minimal hepatic encephalopathy rat model: neuroplasticity enhancement. Neural Regeneration Research 2015; 10(9): 1457-1462.
19) Ting Sun#, Xia Yuan, Wei Huang, Wei Guo, Zemei Ge, Runtao Li*, Jingrong Cui*. Effects and mechanism of proteasome inhibitor YSY01A alone or in combination with cisplatin against A549 cells in vitro. Journal of Chinese Pharmaceutical Science 2015; 24(9): 607-616.
20) Bingjie Xue#, Wei Huang, Xia Yuan, Bo Xu, Yaxin Lou, Quan Zhou, Fuxiang Ran, Zemei Ge, Runtao Li*, Jingrong Cui*. YSY01A, a novel proteasome inhibitor, induces cell cycle arrest on G2 phase in MCF-7 cells via ERα and PI3K/Akt pathways. Journal of Cancer 2015; 6(4): 319-326.
21) Nan Yang#, Yan-yong Liu#, Yinglu Ji, Zhili Ren, Jie Meng, Chao Ji, Jian Liu, Ji Zheng, Xiaochun Wu*, Pingping Zuo*, Haiyan Xu*. Motor coordination dysfunction induced by gold nanorods core/silver shell nanostructures in mice: disruption in mitochondrial transport and neurotransmitter release involved. RSC Advances 2014; 4: 59472- 59480.
22) Zhang H, N Yang, B. Sun, Y. Jiang, C. Hou, C. Ji, Y. Zhang, Yanyong Liu*, Pingping Zuo*. CD133 positive cells isolated from A549 cell line exhibited high liver metastatic potential. Neoplasma 2014; 61: 153-160.
23) Wei Huang#, Zizheng Dong#, Fang Wang#, Hui Peng, Jingyuan Liu, Jianting Zhang*. A small molecule compound targeting STAT3 DNA-binding domain inhibits cancer cell proliferation, migration, and invasion. ACS Chemical Biology, 2014, 9(5): 1188-1196.
