Polo-like kinases play an essential role in the ordered execution of mitotic events and 4 mammalian PLK family members have been identified. Accumulating evidence indicates that PLK1 is an attractive target for anticancer drugs. In this paper, a series of beta-carboline derivatives were synthesized and three compounds, DH281, DH285 and DH287, were identified as potent new PLK inhibitors. We employed various biochemical and cellular approaches to determine the effects of these compounds on the activity of PLK1 and other mitotic kinases and on cell cycle progression. We found that these three compounds could selectively inhibit the kinase activity of purified PLK1, PLK2 and PLK3 in vitro. They show strong antitumor activity against a number of cancer cell lines with relatively low micromolar IC(50)s, but are relatively less toxic to non-cancer cells (MRC5). Moreover, these compounds could induce obvious accumulation of HeLa cells in G(2)/M and S phases and trigger apoptosis. Although MRC5 cells show clear S-phase arrest after treatment with these compounds, the G2/M arrest and apoptosis are less insignificant, indicating the distinct sensitivity between normal and cancer cells. We also found that HeLa cells treated with these drugs exhibit monopolar spindles and increased Wee1 protein levels, the characteristics of cells treated with PLK1 inhibitors. Together, these results demonstrate that DH281, DH285 and DH287 beta-carboline compounds are new PLK inhibitors with potential for cancer treatment.

OBJECTIVE:To detect the anti-tumor activity and molecular mechanisms of 4-[2-(3-Methyl-thiophen-2-yl)-thiazol-4-yl]-benzene-1,2-dio(MTBD) as inhibitor of Aurora-B kinase.METHODS:The anti-tumor activity was detected by MTT assay.ELISA assay was performed to test the inhibition of purified recombinant human Aurora-B kinase.Flow cytometry analysis was used to analysis the cell cycle treated with MTBD.The relative mRNA expression level of Hela cells treated with MTBD was detected by real time PCR.RESULTS:MTBD could inhibit the growth of tumor cells,such as Hela,HepG2 and A549,and its IC50 was(1.03±2.23),(1.72±3.78) and(2.01±1.23) μmol/L respectively;MTBD could induce S phase and G2/M phase arrest and apoptosis in Hela cells.MTBD could also inhibited the activity of Aurora-B kinase and its IC50 was(1.70±2.02) μmol/L.But the H3(Ser10) phosphorylation increased treated with MTBD.RT-PCR analysis showed that MTBD could increase the mRNA expression level of p21 and p53 and decrease the level of CDK2,Cyclin A1 and pCNA.CONCLUSIONS:MTBD can inhibit the proliferation of tumor cells.MTBD can induce cell cycle arrest and apopsis through several cell cycle events but not Aurora-B kinase.

Objective:To find potential small-molecular Aurora-B kinase inhibitors through high throughput screening(HTS)using budding yeast cells.Method:Wild-type yeast cells and ipl1-321 temperature sensitive mutant were used toscreen the potential Aurora -B kinase inhibitors and in vitro biochemical assay was performed to test the inhibition of candidates on purified recombinant human Aurora-B kinase.The anti-tumor activity was detected by MTT assay.Flow cytometry analysis was used to analysis the cell cycle treated with compound.Result:There were twelve compounds and five microbial fermentation could inhibite the growth of ipl1-321 temperature sensitive mutant more dramatically than wild-type yeast cells.In which the inhibition of seven compounds on purified recombinant human Aurora-B kinase was more than 50%with 10μg · ml~(-1),and IC_(50)of three compounds were 10.253,1.826 and 2.054μmol · L~(-1).respectively These three compounds inhibit the growth of Hela,HepG2 and HCT116 cells,and the IC_(50)of them were 4.255, 15.326 and 1.032μmol · L~(-1)respectively on Hel cells,and IC_(50)of them were 5.387,17.465 and 1.725μm ol · L~(-1)respectively on HepG2 cells,and the IC_(50)of them were 5.380,8.528 and 2.029μm ol · L~(-1)respectively on HCT116 cells.And three compounds inhibited purified recombinant human Aurora-B kinase in vitro.Eleventh compound could induce the G2/M phase arrest in HCT116 cells.Conclusion:Several compounds and fermentation are determined as new inhibitor of Aurora-B through HTS using wild-type yeast cells and jpl1-321 temperature sensitive mutant.

冬虫夏草是临床常用名贵中药之一,具有补肾益肺、纳气平喘、止血化痰的功效,与人参、鹿茸并为三大补品.有特殊的药用价值.临床用于治疗阳痿、腰膝酸痛,久虚咳喘,痨咳咯血等症.因资源稀少,价格昂贵,消费者购买到货真价实、物有所值的冬虫夏草,是每个人的愿望.并要掌握它的应用方法与鉴别才能发挥更好的治疗效果.

中草药抗病毒的作用机理主要是抑制或者直接杀灭病毒、保护正常的细胞和组织、调节机体免疫功能来加强自身抗病毒能力等.现将抗病毒中药及其有效成分与作用机制综述如下.

Objective:To study the clinic effect of Danshen and Naloxone on hypoxic-ischemic en-cephulapathy(HIE)in newborn.Methods:120 cases with HIE from three hospitals were divided into twogroups.60 cases as obaeming group were treated by Danshen and Naloxone and the rest 60 cases as controlgroup were treated by cytidine 5-diphosphchuline(CDPC).SOD,MDA,brain CT,NBNA marks after birthwere taken as index to evaluate.Results:SOD,MDA,brain CT and NBNA marks in observing groups werebetter than that in control groups.There were great difference between two groups(P0.05).Conclusion:Itis very effective to use Danshen and Naloxone in treating HIE in newborn.

目的观察下乳涌泉散对因不良情绪致乳汁不足产妇的催乳效果。方法将产后1个月内,因不良情绪致乳汁不足的产妇106例随机分为治疗组和对照组。治疗组服用下乳涌泉散,对照组服用谷维素、维生素 B 1 ,两组均给予心理疏导和精神鼓励支持。观察两组产妇3 d、5 d后的泌乳量。结果两组产妇3 d、5 d后的泌乳情况有显著性差异(P<0.01)。结论对不良情绪引起的乳量不足或无乳,服用下乳涌泉散有明显的促进乳汁分泌。