Aim:To explore the potential biomarkers of lymphoma .Methods:Ultra high performance liquid chroma-tography-Q Exactive orbit trap high-resolution mass spectrometry was applied to process the plasma samples of 12 lymphoma patients as well as 12 healthy volunteers .Orthogonal to partial least squares discriminant analysis was performed to identify the differences in metabolic profiles between the two groups and further to select potential biomarkers related to lymphoma . Results:A significant distinction in the metabolic profiles between lymphoma patients and healthy volunteers was yielded by multivariate statistical analysis and 8metabolites were found .Compared with healthy controls , the contents of aspartic acid and 4-pyridoxate were significantly higher in plasma of lymphoma patients (P<0.05), while the contents of L-α-glyc-erophosphorylcholine ,linoleic acid ,decanoyl carnitine ,phenylalany-lphenylalanine ,taurine and threonic acid were obviously lower(P<0.05).Conclusion:The 8 metabolites found via metabonomics might be potential biomarkers associated to lym-phoma.

Objective To screen the interaction of lysine specific demethylase 1( LSD1 ) and Rabdosia extracts. Methods In pH 7. 4 buffer,the interaction of LSD1 and Rabdosia extracts(JD160 and JD284)was detected by cyclic voltam-metry under different conditions. Results When changing extract concentration and scan rate respectively,the peak current of extract showed good linear relationship with the extract concentration and scan rate. In pH 7. 40 buffer,no peak current of LSD1 appeared,while the peak current of extract appeared,and the electrochemical behavior was typically irreversible. When adding LSD1 into the extract gradually,the peak current obviously decreased,and there was a negative shift in the oxidation peak of ex-tracts. Conclusion Both JD160 and JD284 can be combined with LSD1 to generate non - electric complexes,which led to a de-crease in the free drug concentration in the solutions. From changes to the reduction and oxidation currents,it can be concluded that the inhibition of JD160 against LSD1 is reversible,whereas JD284 is irreversible.

Ethnopharmacological relevance: Flavokawain A, the major chalcone in kava extracts, was served as beverages for informal social occasions and traditional ceremonials in most South Pacific islands. It exhibited strong antiproliferative and apoptotic effects against human prostate and urinary bladder cancer cells.Aim of the study: The current study was purposed to investigate the interaction between Flavokawain A and Cytochrome P450, including the inhibitory effects of Flavokawain A on predominant CYP450 isotypes and further clarified the inhibitory mechanism of FM on CYP450 enzymes. Besides, study about identifying the key CYP450 isotypes responsible for the metabolism of FKA was also performed.Materials and methods: In this study, probe-based assays with rat liver microsome system were used to characterize the inhibitory effects of FICA. Molecular docking study was performed to further explore the binding site of WA on CYP450 isoforms. In addition, chemical inhibition experiments using specific inhibitors (a-naphthoflavone, quinidine, sulfamethoxazde, ketoconazole, omeprazole) were performed to clarify the individual CYP450 isoform that are responsible for the metabolism of FICA.Results: FM showed significant inhibition on CYP1A2, CYP2D1, CYP2C6 and CYP3A2 activities with IC50 values of 102.23, 20.39, 69.95, 60.22 mu mol/L, respectively. The inhibition model was competitive, mixed inhibition, uncompetitive, and noncompetitive for CYP1A2, CYP2D1, CYP2C6 and CYP3A2 enzymes. Molecular docking study indicated the ligand-binding conformation of FKA in the active site of CYP450 isoforms. The chemical inhibition experiments showed that the metabolic clearance rate of Flavokawain A decreased to 19.84%, 50.38%, and 67.02% of the control in the presence of ketoconazole, sulfamethoxazde and a-naphthoflavone.Conclusion: The study showed that Flavokawain A has varying inhibitory effect on CYP450 enzymes and CYP3A2 was the principal CYP isoform contributing to the metabolism of Flavokawain A. Besides, CYP2C6 and CYP1A2 isoforms also play important roles in the metabolism of FKA. Our results provided a basis for better understanding the biotransformation of FICA and prediction of drug-drug interaction of FICA. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

目的:观察冬凌草提取物KYBNZ-1I对口腔鳞状细胞癌细胞Tca8113增殖的抑制作用,并探讨其可能机制.方法:采用MTT法检测0.5、1.0、2.0、4.0、8.0 mg/L的KYBNZ-1I分别作用24、48、72 h对Tea8113细胞增殖的抑制作用.分别采用流式细胞仪及Western blot检测0.0、1.0、2.0、3.0 mg/L的KYBNZ-1I作用48 h Tca8113细胞的周期分布、凋亡情况及CyclinD1、CyclinB1、Cdc-2蛋白的表达.结果:KYBNZ-1I对Tca8113细胞增殖有抑制作用,该作用呈剂量和时间依赖性(F剂量=133.991,F时间=22.526,P＜ 0.05).与对照组比较,1.0、2.0、3.0 mg/L的KYBNZ-1I作用48 h后G2/M期细胞增多,并可诱导细胞凋亡,呈剂量依赖性(F=108.465、212.353,P＜0.05);随药物剂量的升高,CyclinD1蛋白的表达水平下降(F=45.288,P＜0.001),CyclinB1、Cdc-2蛋白的表达水平升高(F=21.273、19.228,P＜0.05).结论:KYBNZ-1I对Tca8113细胞增殖有抑制作用,可将细胞阻滞于G2/M期并诱导细胞凋亡,其作用机制可能与KYBNZ-1I抑制CyclinD1蛋白的表达、提高CyclinB1和Cdc-2蛋白的表达有关.

目的:研究叶黄素对结肠癌HT29细胞的增殖抑制作用及可能的机制.方法:用不同浓度的叶黄素(20、40、80、160 mg/L)和空白对照组(0 mg/L)干预处理培养的HT29细胞24、48、72 h,采用SRB法检测其对该细胞的增殖抑制作用;流式细胞仪检测细胞周期;Hoechst33342/PI荧光染色法检测细胞凋亡;Western blot检测磷酸化ERK(phosphorylation of ERK,p-ERK)、磷酸化p38(phosphorylation of p38,p-p38)蛋白表达水平的变化.结果:叶黄素能抑制HT29细胞增殖,且有明显的剂量和时间依赖性.流式细胞仪检测细胞周期结果显示,叶黄素(80 mg/L)干预处理HT29细胞48 h后,G0/G1期细胞由58.67％增加至63.23％,且随药物浓度增加,G0/G1期细胞显著增加,当叶黄素浓度为160mg/L时,G0/G1期细胞增加至70.81％,表明叶黄素可将HT29细胞阻滞在G0/G1期;Hoechst33342/PI荧光染色法检测细胞凋亡结果显示,叶黄素可诱导HT29细胞凋亡;Western blot检测结果显示叶黄素可下调p-ERK、上调p-p38蛋白的表达,有浓度依赖性(P＜0.01).结论:叶黄素可显著抑制HT29细胞的增殖并诱导其凋亡,使细胞周期阻滞在G0/G1期;下调p-ERK蛋白、上调p-p38蛋白的表达可能是其诱导细胞凋亡的重要机制.