羟基喜树碱联合丝裂霉素诱导人白血病K562细胞凋亡

观察羟基喜树碱与丝裂霉索联合应用对人白血病细胞K562的作用效果,并探讨其机制。不同浓度羟基喜树碱与丝裂霉素单独及联合作用于人白血病细胞K562后,应用台盼蓝拒染法检测细胞生长抑制率,计算合用指数（CI）,流式细胞仪（FCM）检测K562细胞凋亡率,吖啶橙（AO）荧光染色和透射电镜观察凋亡形态学变化。结果表明：单独应用时羟基喜树碱和丝裂霉素的IC50分别是8μ/mL和12．5μg/mL,联合应用时IC50下降为4μg/mL（HCPT）和3．6μg/mL（MMC）,CI=0．78,为协同效应。羟基喜树碱与丝裂霉素单独及联合应用均可诱导K562细胞凋亡。2种药物联合应用时的凋亡率高于各自单独用药。羟基喜树碱与丝裂霉素联合应用可以通过共同诱导细胞凋亡。协同抑制人白血病细胞生长。     

Processing of nanolitre liquid plugs for microfluidic cell-based assays

Plugs, i.e. droplets formed in a microchannel, may revolutionize microfluidic cell-based assays. This study describes a microdevice that handles nanolitre-scale liquid plugs for the preparation of various culture setups and subsequent cellular assays. An important feature of this mode of liquid operation is that the recirculation flow generated inside the plug promotes the rapid mixing of different solutions after plugs are merged, and it keeps cell suspensions homogeneous. Thus, serial dilutions of reagents and cell suspensions with different cell densities and cell types were rapidly performed using nanolitres of solution. Cells seeded through the plug processing grew well in the microdevice, and subsequent plug processing was used to detect the glucose consumption of cells and cellular responses to anticancer agents. The plug-based microdevice may provide a useful platform for cell-based assay systems in various fields, including fundamental cell biology and drug screening applications.     

藻胆蛋白在大肠杆菌中的重组表达及其光谱学性质与抗氧化活性研究

研究发现从红藻坛紫菜中提取的多糖具有优异的抗氧化活性。本文研究了坛紫菜多糖及其硫酸衍生物对两种突变剂环磷酰胺和丝裂霉素C诱导的大蒜根尖细胞微核率、有丝分裂指数和染色体畸变率的影响作用,以及抗脂质过氧化作用。结果表明,两种多糖均表现出明显地抑制微核和染色体畸变作用,明显地提高有丝分裂指数。其影响作用具有明显的剂量依赖性。当多糖浓度为100 mg/L时,多糖表现出最大抑制效应或增强效应。同时,硫酸化衍生物表现出比原料多糖更优异的抗细胞内脂质过氧化作用。分析表明坛紫菜多糖表现出的抗突变作用与抗脂质过氧化作用具有一定关系。同时也表明硫酸基对于抗突变作用的间接影响。结果显示坛紫菜多糖具有成为抗突变活性物质的潜力。     

Modulating the burst drug release effect of waterborne polyurethane matrix by modifying with polymethylmethacrylate

To reduce cost and increase environmental friendliness, waterborne polyurethane (WPU) is a tempting choice in the field of green chemistry. Biodegradable WPU was synthesized using lysine as an internal emulsifier. WPU was further modified using methylate methacrylate (MMA) as an acrylic monomer. Unsaturated pre-PU was synthesized by using unsaturated end-capping agent 2-hydroxyethyl methacrylate and further extended by MMA to form acrylate modified WPU. A permanent covalent linkage was established between WPU and PMMA as confirmed by FTIR spectroscopy. The focus of this research work was to study the dependence of drug delivery, mechanical, thermal, surface, and structural properties of WPU, on the MMA repeating unit content (10%–40%). For drug release studies mitomycin c was taken as a model anticancer drug. Furthermore, these materials were subjected to in vitro and in vivo cytotoxicity evaluation, which shows that synthesized acrylate modified WPU are biocompatible. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47253.     

白蛋白纳米球药物载体的制备及表征

以超声乳化-化学交联方法制备了粒径为60~100 nm的负载丝裂霉素的白蛋白纳米球. 含有丝裂霉素和白蛋白的水相经超声乳化,在油相中形成纳米乳滴,然后加入戊二醛,使纳米乳滴发生交联形成纳米球. 通过比较形成乳液的稳定性选择了最适的乳化剂,系统考察了交联剂戊二醛的用量对所制纳米球性质的影响. 结果表明,戊二醛用量增加,则纳米球产率、载药量和药物包封率均增加,而粒径和溶胀度下降,体外释药速度亦下降. 戊二醛用量使醛基与白蛋白氨基摩尔比为16:1时最佳. 纳米球的体外释药为双相释药,两个释药相均符合Higuchi方程.     

Synergistic Effect of Combinatorial Treatment with Curcumin and Mitomycin C on the Induction of Apoptosis of Breast Cancer Cells: A cDNA Microarray Analysis

In order to explore the synergistic mechanisms of combinatorial treatment using curcumin and mitomycin C (MMC) for breast cancer, MCF-7 breast cancer xenografts were conducted to observe the synergistic effect of combinatorial treatment using curcumin and MMC at various dosages. The synergistic mechanisms of combinatorial treatment using curcumin and MMC on the inhibition of tumor growth were explored by differential gene expression profile, gene ontology (GO), ingenuity pathway analysis (IPA) and Signal–Net network analysis. The expression levels of selected genes identified by cDNA microarray expression profiling were validated by quantitative RT-PCR (qRT-PCR) and Western blot analysis. Effect of combinatorial treatment on the inhibition of cell growth was observed by MTT assay. Apoptosis was detected by flow cytometric analysis and Hoechst 33258 staining. The combinatorial treatment of 100 mg/kg curcumin and 1.5 mg/kg MMC revealed synergistic inhibition on tumor growth. Among 1501 differentially expressed genes, the expression of 25 genes exhibited an obvious change and a significant difference in 27 signal pathways was observed (p < 0.05). In addition, Mapk1 (ERK) and Mapk14 (MAPK p38) had more cross-interactions with other genes and revealed an increase in expression by 8.14- and 11.84-fold, respectively during the combinatorial treatment by curcumin and MMC when compared with the control. Moreover, curcumin can synergistically improve tumoricidal effect of MMC in another human breast cancer MDA-MB-231 cells. Apoptosis was significantly induced by the combinatorial treatment (p < 0.05) and significantly inhibited by ERK inhibitor (PD98059) in MCF-7 cells (p < 0.05). The synergistic effect of combinatorial treatment by curcumin and MMC on the induction of apoptosis in breast cancer cells may be via the ERK pathway.     

稀土磁性纳米微球Dy:Fe_3O_4@PHEMA-Tb的载药性研究

以稀土磁性纳米微球Dy:Fe3O4@PHEMA-Tb为载体材料,丝裂霉素C(MMC)为模型药物,在一定条件下制备了具有生物相容性、低毒性等特点的稀土磁性药物微球(MMC-PHEMA-FMPMs).通过正交实验设计考察了制备MMC-PHEMA-FMPMs工艺条件对磁性微球的载药量和包封率的影响,用高效液相色谱(HPLC)测定稀土磁性药物微球的载药量和包封率,固体永磁铁测试稀土磁性药物微球的体外磁响应性.结果表明,稀土磁性纳米微球具有较高的载药量和包封率,体外药物释放受pH影响较大,磁响应性显著,是靶向给药的良好载体.     

葛根素的抗氧化活性研究

目的研究检测葛根素的抗氧化性。方法设6.25、12.5、25和50μg/m L 4个剂量组,葛根素和丝裂霉素C(mitomycin C,MMC)采用前处理、同时处理和后处理3种方式处理小鼠淋巴瘤细胞L5178Y。处理结束后采用试剂盒法检测细胞丙二醛(malondialdehyde,MDA)含量,超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性。结果 MMC组的MDA含量明显高于溶剂对照组(P0.05),SOD和GSH-Px的活性低于溶剂对照组(P0.05)。在3种处理方式下,与MMC组比较,葛根素4个剂量组的MDA含量均低于MMC组(P0.05),差异有统计学意义。同时葛根素所有剂量组的SOD和GSH-Px的活性随着剂量升高而增强,与MMC组比较差异有统计学意义(P0.05)。结论葛根素具有较好的抗氧化性,具有较好的开发应用前景。     

Novel carboxymethyl derivatives of chitin and chitosan materials and their biomedical applications

Chitin and chitosan are natural biopolymers that are non-toxic, biodegradable and biocompatible. In the last decade, chitin and chitosan derivatives have garnered significant interest in the biomedical and biopharmaceutical research fields with applications as biomaterials for tissue engineering and wound healing and as excipients for drug delivery. Introducing small chemical groups to the chitin or chitosan structure, such as alkyl or carboxymethyl groups, can drastically increase the solubility of chitin and chitosan at neutral and alkaline pH values without affecting their characteristics; substitution with carboxyl groups can yield polymers with polyampholytic properties. Carboxymethyl derivatives of chitin and chitosan have shown promise for adsorbing metal ions, as drug delivery systems, in wound healing, as anti-microbial agents, in tissue engineering, as components in cosmetics and food and for anti-tumor activities. This review will focus on the preparative methods and applications of carboxymethyl and succinyl derivatives of chitin and chitosan with particular emphasis on their uses as materials for biomedical applications.     

RecA and RecB: probing complexes of DNA repair proteins with mitomycin C in live Escherichia coli with single-molecule sensitivity

The RecA protein and RecBCD complex are key bacterial components for the maintenance and repair of DNA. RecBCD is a helicase-nuclease that uses homologous recombination to resolve double-stranded DNA breaks. It also facilitates coating of single-stranded DNA with RecA to form RecA filaments, a vital step in the double-stranded break DNA repair pathway. However, questions remain about the mechanistic roles of RecA and RecBCD in live cells. Here, we use millisecond super-resolved fluorescence microscopy to pinpoint the spatial localization of fluorescent reporters of RecA or RecB at physiological levels of expression in individual live Escherichia coli cells. By introducing the DNA cross-linker mitomycin C, we induce DNA damage and quantify the resulting steady state changes in stoichiometry, cellular protein copy number and molecular mobilities of RecA and RecB. We find that both proteins accumulate in molecular hotspots to effect repair, resulting in RecA stoichiometries equivalent to several hundred molecules that assemble largely in dimeric subunits before DNA damage, but form periodic subunits of approximately 3–4 molecules within mature filaments of several thousand molecules. Unexpectedly, we find that the physiologically predominant forms of RecB are not only rapidly diffusing monomers, but slowly diffusing dimers.