The isolation and identification of antitumor-active phthalides targeting nuclear receptor TR3 from Angelica sinensis

近年来，分子靶向药物已成为抗癌新药研究的新趋势，而核受体作为作用靶点之一尤其备受关注。TR3/Bcl-2细胞凋亡途径是一条孤儿核受体TR3参与，独特有效的癌细胞凋亡调控通路。本研究对传统中药材当归进行针对性的组分分离，诣在筛选出具有靶向核受体TR3发挥抗癌作用潜力的化合物。 本研究借助多种色谱学分离手段，对当归的化学成分进行了细致分离，并通过理化性质和现代的波普解析手段分别鉴定了其化学结构，最终得到28个化合物。包括简单苯酞类化合物10个：Z-蒿本内酯（1）、E-蒿本内酯（2）、丁基苯酞（3）、洋川芎内酯G（8）、Z-8-羟基正丁烯苯酞（15）、Z-6，7-epoxyligustilide（...Recent years, molecular targeted drugs have become a new trend of research and development of new anti-cancer drugs. As one of the targets, nuclear receptors are especially closely watched. TR3/Bcl-2 apoptosis pathway is an unique and effective regulation pathways of cancer cells apoptosis with the orphan nuclear receptor TR3 participation. The aim of our study was to isolate the compounds target...学位：医学硕士院系专业：药学院_药物化学学号：3232014115340

Identification of Polygonatum from Wuyishan and Its Surrounding Areas by ISSR Molecular Markers and Their HPLC Fingerprints

采用ISSR分子标记鉴定方法及HPLC色谱方法对武夷山及周边地区5份黄精植物样本进行DNA分子标记鉴定及指纹图谱分析,并通过聚类分析软件分别探讨其遗传相关聚类图谱。ISSR分子标记法能较好地对5份黄精植物样本进行区分,HPLC指纹图谱分析同样表明5份黄精样本化学成分存在一定的差别。DNA分子标记及HPLC指纹图谱分析的遗传相关聚类分析结果相似,表明武夷山及周边地区的野生黄精种质资源存在明显的差别。The purpose of this project was to identify and analyze the genetic relationships of 5 kinds of Polygonatum in Wuyishan and its surrounding areas. Using ISSR marker and HPLC molecular identification method for chromatographic methods analysis of DNA markers for identification and fingerprinting of 5 Polygonatum samples, the genetic correlation map of Polygonatum was studied by cluster analysis software. ISSR molecular marker method could be used to distinguish Polygonatum of Wuyishan and its surrounding areas. HPLC fingerprint analysis also showed that there were some differences in the composition of Wuyishan and its surrounding distribution. The results of genetic correlation cluster analysis were similar by ISSR and HPLC. There were obvious differences in the germplasm resources of Wuyishan and its surrounding areas from the DNA molecular markers and HPLC fingerprinting analysis results.福建省科技厅自然科学基金重点项目（2013Y0018）;福建省科技厅自然科学基金青年项目（2015J01065

大型原油蒸馏过程能量全局优化控制策略

本文研究了大型原油蒸馏过程能量全局优化控制问题。通过对原油蒸馏装置备用能环节能量传递关系的分析，将全装置能量系统分解为四个能量子系统。在对常压塔、减压塔、换热网络和加热炉等四个能量子系统优化控制问题求解的基础上，运用大系统理论分解协调的原理，求解了原油蒸馏过程的能量全局优化控制问题。对某炼厂大型原油蒸馏装置现场操作数据优化计算结果表明，本文提出的能量全局优化控制策略将使装置的总能耗降低8.46％

原油蒸馏过程换热网络——加热炉联合系统的最优操作

〕本文研究了原油蒸馏过程换热网络一加热炉联合系统的最优控制问题。首先分别讨论换热网络和 加热炉的最优操作间题, 在此基础上, 考虑到这两个系统之间存在的关联, 提出了换热网络一加热炉联合系 统的最优操作问题。在应用大系统分解协调理论求解该问题时, 针对系统之间的特殊性, 提出了一种新的协 调算法—预估平衡协调法。由某炼油厂大型原油蒸馏过程换热网络一加热炉联合系统的仿真结果表明, 本文 提出的最优操作方法将带来显著的节能效果

原油蒸馏过程换热网络的最优操作

本文研究了原油蒸馏过程换热网络的最优操作。针对上海高桥石化公司炼油厂号 原油蒸馏装置换热硫程的特点, 通过建立加热炉冷进料段的热平衡模型, 提出了考虑加 热炉冷进料影响的整个换热过程最优操作问题。这是一个具有个优化变量的非线性规 划间题。操作优化间题的求解是在对换热过程进行综合模拟的基础上进行的。对现场操 作数据的优化计算结果表明, 换热网络的终温可以提高3℃左右

Inhibitory effect of anti-human NRP-1 monoclonal antibody on hepatocellular carcinoma cell line HepG2 and its mechanism in vitro

目的研究抗人神经纤毛蛋白-1(Neuropilin1,NRP-1)单克隆抗体对肝癌Hep G2细胞的生长抑制作用及其机制。方法小鼠腹水法制备抗NRP-1单克隆抗体(NRP-1 m Ab)并用r Protein A亲和柱纯化抗体,间接ELISA检测抗体的滴度水平。Western blot检测NRP-1 m Ab对Hep G2细胞的特异性,细胞免疫荧光和流式细胞术检测NRP-1蛋白在肝癌细胞株Hep G2上的表达,MTT法检测NRP-1 m Ab对Hep G2的生长抑制作用,Western blot检测ERK1/2、P-ERK1/2、Akt、P-Akt蛋白的表达水平。结果 SDS-PAGE和间接ELISA检测纯化的NRP-1 m Ab纯度为95%以上,效价为1×10~(-6);Western blot检测结果显示NRP-1 m Ab可与Hep G2细胞膜上的NRP-1蛋白特异性结合。细胞免疫荧光染色结果显示NRP-1定位于Hep G2细胞膜,流式细胞术结果显示NRP-1蛋白在Hep G2细胞上表达水平较高;MTT法检测结果显示NRP-1 m Ab对Hep G2细胞有生长抑制作用。Western blot检测到在不同浓度NRP-1 m Ab作用下,Hep G2细胞裂解液P-ERK1/2、P-Akt蛋白的条带信号逐渐减弱。结论纯化的NRP-1m Ab能抑制Hep G2细胞的生长,其抑制作用是通过EGF和HGF信号通路实现的。The aim of the experimental is to investigate the inhibitory effect of anti-human nerve cilia protein1(Neuropilin-1,NRP-1) monoclonal antibody(NRP-1 mAb) on hepatocellular carcinoma cell line HepG2 and its mechanism in vitro.Anti-human NRP-1 monoclonal antibody(NRP-1 mAb) was prepared from mouse ascites and purified by rProteinA affinity column assay.The titer of antibody was determined using indirect ELISA assay;the characteristic of NRP-1 mAb binding to NRP-1 was determined using Western blotting;the expression of NRP-1protein in hepatocellular carcinoma cell line HepG2 was determined using immunofluorescence assay and flow cytometry assay.Growth inhibition of HepG2 cells treated with different concentrations of NRP-1 mAb was determined using MTT assay,while Western blotting was used to detect the expression levels of ERK1/2,P-ERK1/2,Akt and P-Akt proteins.The results of SDS-PAGE and indirect ELISA showed that the purity of purified NRP-1mAb was more than 95%and the titer was 1×10~(-6).Western blotting analysis suggested that NRP-1 mAb could bind specifically to NRP-1 on HepG2 cell;immunofluorescence staining showed that NRP-1 was located in the membrane of HepG2 cells.Flow cytometry analysis showed that the expression level of NRP-1 on HepG2 cell was relatively high.Western blotting analysis suggested that P-ERK1/2 and P-Akt expression levels were down-regulated after having incubated HepG2 cells with different concentrations of NRP-1 mAb.In conclusion,NRP-1 mAb could inhibit the growth of HepG2 cells(P<0.05),and its inhibitory effect is achieved by reducing the P-ERK1/2 and P-Akt expression.南京军区医学科技创新项目(12MA061,15MS104

Effects of the Xitongxiao prescription on apoptosis and proliferation of chondrocytes in knee

目的：探讨膝痛消方对促进软骨细胞增殖和抑制IL-1β诱导的软骨细胞凋亡的作用。方法：体外培养膝关节软骨细胞，用阿利新蓝染色方法检测软骨细胞蛋白多糖，用Ⅱ型胶原免疫荧光染色检测软骨细胞Ⅱ型胶原的表达，以鉴定软骨细胞；用MTS检测软骨细胞的增殖；用IL-1β诱导软骨细胞凋亡，AnnexinV/PI双染检测细胞凋亡。结果：膝关节剥离得到的细胞形态为多角形或梭形，阿利新蓝与Ⅱ型胶原免疫荧光染色均呈阳性，证明分离培养的细胞为软骨细胞。MTS实验结果发现膝痛消方提取物处理软骨细胞后检测到的OD值随浓度增加而增加且显著高于对照组。此外，IL-1β处理诱导软骨细胞凋亡，而膝痛消方提取物能够有效地抑制IL-1β引起的细胞凋亡。结论：膝痛消方能促进软骨细胞的增殖，抑制IL-1β诱导的软骨细胞的凋亡。以上发现为膝痛消方临床上治疗膝关节骨性关节炎提供药理作用依据。Objective:To investigate the effects of the Xitongxiao prescription on the cell proliferation and the inhibition of IL-1β-induced apoptosis of chondrocytes.Methods:To identify chondrocytes,the articular chondrocytes were cultured in vitro;staining with alcian blue was used to detect the protein polysaccharide,and staining with collagen immunofluorescence was used to examine the expression of type II collagen in chondrocytes.The proliferation of chondrocytes was determined by MTS.Apoptosis of chondrocytes was induced by IL-1β,and the effect of apoptosis was tested by Annexin V/PI double staining.Results:The morphology of the cells obtained from the knee joint was polygonal or fusiform.The tested results of Alcian blue and collagen immunofluorescence staining were positive.These together certified that the isolated cells were knee chondrocytes.MTS assay results showed that the detected OD values were dosedependently increased and they were significantly higher than those of the control group.In addition,the apoptosis of chondrocytes was induced by IL-1βtreatment.While the extract of the Xitongxiao prescription could effectively inhibit the IL-1β-induced apoptosis of chondrocytes.Conclusion:The Xitongxiao prescription could promote the proliferation of chondrocytes and inhibit the apoptosis of chondrocytes induced by IL-1β.The above findings may provide one of pharmacological mechanisms of the Xitongxiao for clinical treatment of knee osteoarthritis.厦门市科技计划项目(3502z20144031);福建省自然科学基金计划资助项目(2015J01065)

Research of pharmacological effect basis of usual clinical medications with camellia oil

目的探讨茶油多种临床用药可能的药理药效基础。方法将油茶籽经两次95%的乙醇回流提取后浓缩至不含乙醇和水的提取物,取其中的茶油部分作为试验药物;用肿瘤坏死因子-α(Tnf-α)处理人乳腺癌细胞系(MCf-7)细胞建立细胞炎症模型,进一步用蛋白质印迹技术观察药物处理对细胞炎症因子Iκb-α表达的影响进而评价茶油是否具有抗炎活性。结果从油茶籽提取得到的茶油显著地抑制细胞中Tnf-α诱导的Iκb-α的降解从而抑制炎症发生。结论茶油对细胞显示良好的抗炎作用,这种特性可能是其临床应用于治疗皮肤过敏、暗疮、疥癣、小儿红屁股、以及皮肤烧烫伤等多种与炎症相关疾病的药理基础之一。Objective To explore the possible pharmacological effect basis of usual clinical medications with camellia oil.Methods After twice 95% ethanol reflux extraction of camellia seed, the solution was concentrated to the extractive without ethanol and water.Camellia oil in the extractive was taken as study drug.Human breast adenocarcinoma cell line(MCF-7) cell was managed by tumor necrosis factor(TNF)-α to build a cell inflammation model.Influence of drug treatment on cell inflammatory cytokines IκB-α was observed by Western blot, in order to make evaluation on whether camellia oil possesses anti-inflammatory activity.ResultsCamellia oil extracted from camellia seed had significantly inhibiting effect on degradation of IκB-α induced by TNF-α, so as to suppress occurrence of inflammation.Conclusion Camellia oil has precise anti-inflammation effect on cells, and this effect may be one of its pharmacological basis for treating inflammation related diseases as skin allergy, pimples, scabies, pediatric bunda vermelha, skin burn and scald.厦门市科技计划项目(项目编号:3502Z20123015); 国家自然科学基金(项目编号:81102332

厦门饮用水有机污染物危害的研究

厦门饮用水有机污染物危害的研究厦门市卫生防疫站高振华，梁荣春国家海洋局第三研究所郑金树厦门大学抗癌研究中心于侣仙，廖绵初许多研究表明，城市饮用水中存在着致突变的有机物，它们来源于水源水的污染、饮水氯化消毒的副产物三卤甲烷（THM3）等。因此，近年来饮..

蚕豆根尖微核技术在饮用水致突变性研究中的应用

采用蚕豆根尖微核（Mn）监测技术，对饮用水有机污染物的诱变性进行了研究。结果表明：饮用水诱变性强度，枯水期＞平水期＞丰水期。采用混凝沉淀工艺，出厂水Mn比进厂水降低40.6%。用气浮法制水工艺的出厂水Mn在正常范围内