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Nano Research 2023年第7期16卷 7347-7354页

作者： Yingqiu Qi Jinxiu Shen Chen Liu Anni Du Mengdie Chen Xiaocao Meng Hui Wang saiyang zhang Lirong zhang Zhongjun Li Yike Li Yale Yue Huan Min Department of Pharmacology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China Henan Institute of Advanced Technology Zhengzhou UniversityZhengzhou 450001China State Key Laboratory of Esophageal Cancer Prevention&Treatment Zhengzhou 450001China College of Chemistry Institute of Green CatalysisZhengzhou UniversityHenan 450001China

Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor *** surgical resection promotes the local angiogenesis at the tumor site,further exacerbating the proliferation and invasion of residual tumor cells,it is urgent to inhibit angiogenesis after ***,a functional peptide-based nanomedicine was obtained from peptide–drug conjugates,which are composed of a hydrophilic targeting motif(vascular endothelial growth factor family and their receptors(VEGFR)targeting peptide for anti-angiogenesis),an ester-linked hydrophobic oridonin(ORI).The nanomedicine exhibits esterase-catalyzed disassembly and drug release,significantly enhanced the anti-tumor efficacy of chemotherapeutics in a postoperative tumor recurrence model through synergistic anti-angiogenic *** study provides an integrated solution for anti-angiogenesisaugmented chemotherapy and demonstrates the encouraging potential for postoperative treatment.

关键词： esophageal squamous cell carcinomas peptide-based nanomedicine anti-angiogenesis oridonin chemotherapy

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黑老虎果实发育及种子油脂积累规律

林业科学 2023年第2期59卷 75-85页

作者：何铁定邵凤侠张赛阳陈娟杨昌宏王森中南林业科技大学“一带一路”热带干旱经济林工程技术研究中心长沙410004 湖南省"一带一路"热带干旱经济林国际联合研究中心长沙410004 国家林业和草原局经济林育种与栽培重点实验室长沙410004 中国林业科学研究院亚热带林业实验中心分宜336600 通道黑老虎中药材专业合作社怀化418500

【目的】研究黑老虎果实发育及种子油脂积累规律,可为其果实发育期的栽培管理和种子油脂的开发利用提供理论基础。【方法】观测黑老虎果实发育的8个不同时期果实和种子表型、横纵径、形状指数;并利用索氏抽提法、激光共聚焦显微镜观察... 详细信息

【目的】研究黑老虎果实发育及种子油脂积累规律,可为其果实发育期的栽培管理和种子油脂的开发利用提供理论基础。【方法】观测黑老虎果实发育的8个不同时期果实和种子表型、横纵径、形状指数;并利用索氏抽提法、激光共聚焦显微镜观察法和气相色谱法,观测种子含油量、油体形状和分布、脂肪酸组分。【结果】黑老虎果实发育期为110天左右,发育期分为青果期(14~56 DAF)、转色期(56~84 DAF)、红果期(84~112 DAF)3个阶段(DAF:花后天数)。果实和种子的横纵径、质量生长曲线均呈单“S”型变化规律,符合Logistic回归模型,决定系数高达0.967 2~0.998 6。14~98 DAF为果实生长期,横纵径和质量快速增加,成熟时果实横径为115.99 mm、纵径为105.65 mm、单果质量为526.08 g;14~84 DAF为种子生长期,成熟时黑老虎种子横径为12.38 mm、纵径为14.26 mm、种子百粒质量为47.85 g。种子油脂积累规律呈“慢—快—慢”变化,青果期积累缓慢、转色期快速积累、红果期积累减缓,油脂积累方程为y=56.261 2·(1+e^(6.582 1-0.102t))^(-1)。黑老虎种子油体呈圆球形,随着种子发育逐渐体积变大、数量增多逐渐充满整个细胞。油脂积累过程中共检出16种脂肪酸,以棕榈酸、硬脂酸、油酸、亚油酸和亚麻酸为主,其中亚油酸含量最高。成熟的黑老虎种子含油量高达55.51 g·(100g)^(-1),不饱和脂肪酸占比77.10%,亚油酸相对含量为66.88%,属于优质的植物油脂。【结论】黑老虎果实发育规律、种子油脂积累规律均符合Logistic回归模型,Logistic方程能反映果实发育和油脂积累情况,对果实生产具有重要的指导意义。黑老虎种子含油量高、油体形状规则、油脂品质好,其作为植物食用油具有巨大的潜力和开发价值。

关键词：黑老虎果实发育油脂积累油体脂肪酸组成

Synthesis and Bioactivity of Natural Occurring Petasin-Like Derivatives as Antitumor Agents

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Open Journal of Medicinal Chemistry 2015年第2期5卷 23-31页

作者： Xiaolong Shi saiyang zhang Jianghao Wang Tingyu Li Junju Liu Yi Hou Lei Liu Dongjun Fu Haiwei Xu Hongmin Hongmin Yanbing zhang School of Pharmaceutical Science Zhengzhou University Zhengzhou China Collaborative Innovation Center of New Drug Research and Safety Evaluation Henan Province Zhengzhou China

Petasin is a potential antitumor against human neuroblastoma cell SK-N-SH by inhibiting the ERK1/2 phosphorylation. In view of its great activity and new antiproliferative mechanisms, a series of petasin derivatives were designed and synthesized, which showed great antiproliferative activity. Among them compounds 1h and 1f were more effective against SK-N-SH cells than petasin with the IC50 values of 0.87 and 2.63 μM, respectively.

关键词： Petasin SK-N-SH Mechanism Derivative Antiproliferative Activity

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杂交石竹授粉受精及其胚胎发育过程的观察

西北植物学报 2016年第10期36卷 1984-1989页

作者：张赛阳栗燕郝鹏博杨秋生河南农业大学林学院郑州450002

以‘杂交石竹’为试验材料,利用荧光显微镜观察其授粉后花粉萌发、花粉管生长情况,采用石蜡切片法对其受精及胚胎发育过程进行观察研究。结果表明：（1）授粉后1h母本柱头上少量花粉开始萌发;授粉后4h大量花粉萌发,花粉管生长至柱头中... 详细信息

以‘杂交石竹’为试验材料,利用荧光显微镜观察其授粉后花粉萌发、花粉管生长情况,采用石蜡切片法对其受精及胚胎发育过程进行观察研究。结果表明：（1）授粉后1h母本柱头上少量花粉开始萌发;授粉后4h大量花粉萌发,花粉管生长至柱头中部有胼胝质出现;授粉后6h花粉管生长至子房组织并有少量与胚珠结合;授粉后15h柱头中出现大量胼胝质,花粉管与胚珠结合数增多;授粉后24h胚珠周围出现多条花粉管,其中1条花粉管进入胚珠,部分进入胚囊的花粉管卷曲盘绕生长并产生胼胝质;精细胞与极核的融合主要发生在授粉后17-48h,与卵细胞融合主要于授粉后1-3d。（2）杂交石竹胚发育经过原胚、球形胚、棒状形胚、心形胚、鱼雷形胚和子叶形胚阶段。（3）杂交障碍表现为：只有游离的胚乳核而无胚发育的胚囊、合子未分裂、两极核未融合、球形胚败育。研究表明,杂交石竹存在受精前和受精后障碍,这是导致其结实率低的主要原因。

关键词：杂交石竹花粉萌发花粉管生长受精胚胎发育

新型喹啉-吲哚衍生物的设计、合成及抗肿瘤活性研究

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有机化学 2021年第9期41卷 3617-3624页

作者：王胜辉关永风刘秀娟原信颖蔚广曦李银茹张雁冰宋健李雯张赛扬郑州大学基础医学院郑州450001 郑州大学化工学院郑州450001 郑州大学药学院郑州450001

作为开发新型有效抗癌药物的进一步工作,采用分子杂交策略和路易斯酸催化偶联反应设计合成了一系列新型喹啉-吲哚类化合物.使用噻唑蓝(MTT)法评估了所合成的化合物对人胃癌细胞(MGC-803)、人食管癌细胞(Kyse450)和人结肠癌细胞(HCT-116... 详细信息

作为开发新型有效抗癌药物的进一步工作,采用分子杂交策略和路易斯酸催化偶联反应设计合成了一系列新型喹啉-吲哚类化合物.使用噻唑蓝(MTT)法评估了所合成的化合物对人胃癌细胞(MGC-803)、人食管癌细胞(Kyse450)和人结肠癌细胞(HCT-116)的体外抑制活性.其中,2-氯-4-(5-甲氧基-1H-吲哚-3-基)喹啉(9b)展示较好的体外抗肿瘤活性,对MGC-803、Kyse450和HCT-116三种人源癌细胞IC50值分别为0.58,0.60和0.68µmol·L^(-1),优于阳性对照药5-氟尿嘧啶(5-Fu)对这三种肿瘤细胞的抑制活性.进一步机制研究表明,化合物9b能够剂量依赖地抑制人胃癌细胞MGC-803和HGC-27的增殖和克隆形成.化合物9b能够诱导人胃癌细胞MGC-803和HGC-27内源性凋亡和下调相关凋亡蛋白的表达,并使细胞周期阻滞在G2/M期.以上结果表明,化合物9b可以作为先导化合物,用于进一步研究开发新型高效抗肿瘤药物.

关键词：喹啉吲哚抗肿瘤活性增值凋亡细胞周期阻滞

Erosion Mechanism of Al_(2)O_(3)-SiC Castables for Lining Maintenance in Blast Furnace Hearths

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China's Refractories 2022年第2期31卷 17-23页

作者： SUN saiyang MA Xiaoqing WANG Xingwei ZHAO Yong zhang Ronghui FEI Weibao Beijing Allied Rongda Engineering Material Co. Ltd.Beijing 101400China Nanjing Allied Rongda Engineering Material Co. Ltd.Nanjing 210036China Dalian Special Steel Co. Ltd.Dalian 116105China

Al_(2)O_(3)-SiC castables,for the relining of BF hearths in mid-campaign repair,were sampled and investigated after two years’*** chemical and mineralogical characteristics of the residual castables were analyzed by X-ray diffraction,scanning electron microscopy,and energy dispersive X-ray spectrometry to study the erosion *** results show that as gaseous K diffuses in the castables,leucite(KAlSi_(2)O_(8))and multiple cracks are *** iron and slag penetrate through the cracks to form anorthite([Ca,Na][Al,Si]_(4)O_(8))and iron,which will not form an embrittlement layer similar to carbon *** entire repair of the hearth with Al_(2)O_(3)-SiC castables combined with the design of thin-wall lining hearth eliminates“elephant foot shaped”erosion,greatly prolonging the service life of the hearth lining.

关键词： alumina-silicon carbide castables blast furnace hearth repair erosion mechanism thin-wall lining

Cardiac fibroblast heat shock protein 47 aggravates cardiac fibrosis post myocardial ischemia-reperfusion injury by encouraging ubiquitin specific peptidase 10 dependent Smad4 deubiquitination

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4138-4153页

作者： saiyang Xie Yun Xing Wenke Shi Min zhang Mengya Chen Wenxi Fang Shiqiang Liu Tong zhang Xiaofeng Zeng Si Chen Shasha Wang Wei Deng Qizhu Tang Department of Cardiology Renmin Hospital of Wuhan UniversityWuhan 430060China Hubei Key Laboratory of Metabolic and Chronic Diseases Wuhan 430060China Cardiovascular Research Institute of Wuhan University Wthan 430060China

Despite complications were significantly reduced due to the popularity of percutaneous coronary intervention(PCI) in clinical trials, reperfusion injury and chronic cardiac remodeling significantly contribute to poor prognosis and rehabilitation in AMI patients. We revealed the effects of HSP47 on myocardial ischemia-reperfusion injury(IRI) and shed light on the underlying molecular *** generated adult mice with lentivirus-mediated or miRNA(mi1/133TS)-aided cardiac fibroblastselective HSP47 overexpression. Myocardial IRI was induced by 45-min occlusion of the left anterior descending(LAD) artery followed by 24 h reperfusion in mice, while ischemia-mediated cardiac remodeling was induced by four weeks of reperfusion. Also, the role of HSP47 in fibrogenesis was evaluated in cardiac fibroblasts following hypoxia-reoxygenation(HR). Extensive HSP47 was observed in murine infarcted hearts, human ischemic hearts, and cardiac fibroblasts and accelerated oxidative stress and apoptosis after myocardial IRI. Cardiac fibroblast-selective HSP47 overexpression exacerbated cardiac dysfunction caused by chronic myocardial IRI and presented deteriorative fibrosis and cell ***47 upregulation in cardiac fibroblasts promoted TGFβ1-Smad4 pathway activation and Smad4 deubiquitination by recruiting ubiquitin-specific peptidase 10(USP10) in fibroblasts. However, cardiac fibroblast specific USP10 deficiency abolished HSP47-mediated fibrogenesis in hearts. Moreover, blockage of HSP47 with Col003 disturbed fibrogenesis in fibroblasts following HR. Altogether, cardiac fibroblast HSP47 aggravates fibrosis post-myocardial IRI by enhancing USP10-dependent Smad4 deubiquitination,which provided a potential strategy for myocardial IRI and cardiac remodeling.

关键词： Heat shock protein 47 Myocardial ischemia-reperfusion injury Ubiquitin-specific protease 10 Cardiac fibrosis s Smad4 Fibroblast Cell proliferation Cardiae dysfunction

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新型香豆素类衍生物的合成及抗肿瘤活性研究

有机化学 2020年第6期40卷 1598-1607页

作者：时蕾李子秋崔鑫鑫朱挺庞晓静李龙辉罗德福刘方芳赵冰玉龙跃张赛扬郑州大学化学学院郑州450001 郑州大学药学院郑州450001 郑州大学基础医学院郑州450001

为了寻找结构新颖、活性较好的抗肿瘤化合物,设计合成了19个未见文献报道的3,4,5-三甲氧基苯基香豆素类化合物,并用核磁共振(NMR)和高分辨质谱(HRMS)等方法对化合物结构进行表征.用四甲基偶氮唑盐(MTT)法评价了该类化合物对人前列腺癌细... 详细信息

为了寻找结构新颖、活性较好的抗肿瘤化合物,设计合成了19个未见文献报道的3,4,5-三甲氧基苯基香豆素类化合物,并用核磁共振(NMR)和高分辨质谱(HRMS)等方法对化合物结构进行表征.用四甲基偶氮唑盐(MTT)法评价了该类化合物对人前列腺癌细胞(PC-3)、人食管癌细胞(EC-109)和人胃癌细胞(MGC-803)三种肿瘤细胞的抑制活性.结果显示,N-苄基-2-((4-甲基-2H-色烯-2-酮-7-基)氧基)-N-(3,4,5-三甲氧基苯基)乙酰胺(4a)和N-((5-氯苯并[b]噻吩-3-基)甲基)-2-((4-甲基-2H-色烯-2-酮-7-基)氧基)-N-(3,4,5-三甲氧基苯基)乙酰胺(4n)对三种肿瘤细胞的抑制活性优于阳性对照药5-氟尿嘧啶,其中化合物4n对人前列腺癌细胞(PC-3)的抑制活性最好,其IC(50)为4.18μmol/L.

关键词：香豆素抗肿瘤合成

新型三甲氧基苯基喹啉衍生物的设计、合成及抗肿瘤活性研究

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有机化学 2020年第4期40卷 978-987页

作者：吴博文崔鑫鑫朱挺王胜辉陆超凡王金杰党贺祥张赛扬丁丽娜金成允新药创制与药物安全性评价河南省协同创新中心郑州450001 郑州大学基础医学院郑州450001 教育部药物制备关键技术重点实验室郑州450001 郑州大学河南省先进技术研究院郑州450001

为了寻找新型高效抗肿瘤候选药物,设计并合成了一系列新型三甲氧基苯基-喹啉杂合体,并评估了目标化合物对三种不同肿瘤细胞EC-109(人食管癌细胞),PC-3(人前列腺癌细胞)和MGC-803(人胃癌细胞)的抗增殖活性.结果表明N-(3-(氯甲基)苄基)-3,... 详细信息

为了寻找新型高效抗肿瘤候选药物,设计并合成了一系列新型三甲氧基苯基-喹啉杂合体,并评估了目标化合物对三种不同肿瘤细胞EC-109(人食管癌细胞),PC-3(人前列腺癌细胞)和MGC-803(人胃癌细胞)的抗增殖活性.结果表明N-(3-(氯甲基)苄基)-3,4,5-三甲氧基-N-(喹啉-8-基)苯甲酰胺(12j)对PC-3细胞具有良好的抗增殖活性,IC50值为9.23μmol/L.同时,化合物12j抑制PC-3细胞增殖和克隆形成.进一步机制研究表明,化合物12j可以将PC-3细胞阻滞在G2/M期,并通过激活内源性和外源性凋亡途径诱导细胞凋亡.

关键词：喹啉三甲氧基苯基抗肿瘤活性细胞周期阻滞凋亡

In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1662-1670页

作者： Zhong Li Jimin Xu Yuekun Lang Xiangmeng Wu saiyang Hu Subodh Kumar Samrat Anil M.Tharappel Lili Kuo David Butler Yongcheng Song Qing-Yu zhang Jia Zhou Hongmin Li Department of Pharmacology and Toxicology College of PharmacyTucsonAZ 85721-0207USA Wadsworth Center New York State Department of HealthAlbanyNY 12208USA Chemical Biology Program Department of Pharmacology and ToxicologyUniversity of Texas Medical BranchGalvestonTX 77555USA The Neural Stem Cell Institute RensselaerNY 12144USA Department of Pharmacology and Chemical Biology Baylor College of MedicineHoustonTX 77030USA

Zika virus(ZIKV)causes significant human diseases without specific *** we found erythrosin B,an FDA-approved food additive,inhibited viral NS2B−NS3 interactions,leading to inhibition of ZIKV infection in cell *** this study,we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse *** results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid *** pharmacokinetics studies indicated that erythrosin B had a low absorption profile,mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B,compared to vehicle *** structure−activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B−NS3 interactions,protease activity and antiviral *** contrast,introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities,suggesting that the isobenzofuran ring is well tolerated for *** studies indicated that all derivatives are nontoxic to human ***,our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.

关键词： Flavivirus Zika virus Dengue virus Antiviral Protease inhibitor Erythrosin B