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31.
32.
Jinling Zhang Wenbao Wang Yanzhao Tian Liwei Ma Lin Zhou Hao Sun Yukun Ma Huiling Hou Xiaoli Wang Jin Ye Xiaobo Wang 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1299
To discover new lead compounds with anti-tumour activities, in the present study, natural diosgenin was hybridised with the reported benzoic acid mustard pharmacophore. The in vitro cytotoxicity of the resulting newly synthesised hybrids (8–10, 14a–14f, and 15a–15f) was then evaluated in three tumour cells (HepG2, MCF-7, and HeLa) as well as normal GES-1 cells. Among them, 14f possessed the most potential anti-proliferative activity against HepG2 cells, with an IC50 value of 2.26 µM, which was 14.4-fold higher than that of diosgenin (IC50 = 32.63 µM). Furthermore, it showed weak cytotoxicity against GES-1 cells (IC50 > 100 µM), thus exhibiting good antiproliferative selectivity between normal and tumour cells. Moreover, 14f could induce G0/G1 arrest and apoptosis of HepG2 cells. From a mechanistic perspective, 14f regulated cell cycle-related proteins (CDK2, CDK4, CDK6, cyclin D1 and cyclin E1) as well mitochondrial apoptosis pathway-related proteins (Bax, Bcl-2, caspase 9, and caspase 3). These findings suggested that hybrid 14f serves as a promising anti-hepatoma lead compound that deserves further research. 相似文献
33.
Alzheimer’s disease (AD) involves the neurotoxic self-assembly of a 40 and 42 residue peptide, Amyloid-β (Aβ). Inherited early-onset AD can be caused by single point mutations within the Aβ sequence, including Arctic (E22G) and Italian (E22K) familial mutants. These mutations are heterozygous, resulting in an equal proportion of the WT and mutant Aβ isoform expression. It is therefore important to understand how these mixtures of Aβ isoforms interact with each other and influence the kinetics and morphology of their assembly into oligomers and fibrils. Using small amounts of nucleating fibril seeds, here, we systematically monitored the kinetics of fibril formation, comparing self-seeding with cross-seeding behavior of a range of isoform mixtures of Aβ42 and Aβ40. We confirm that Aβ40(WT) does not readily cross-seed Aβ42(WT) fibril formation. In contrast, fibril formation of Aβ40(Arctic) is hugely accelerated by Aβ42(WT) fibrils, causing an eight-fold reduction in the lag-time to fibrillization. We propose that cross-seeding between the more abundant Aβ40(Arctic) and Aβ42(WT) may be important for driving early-onset AD and will propagate fibril morphology as indicated by fibril twist periodicity. This kinetic behavior is not emulated by the Italian mutant, where minimal cross-seeding is observed. In addition, we studied the cross-seeding behavior of a C-terminal-amidated Aβ42 analog to probe the coulombic charge interplay between Glu22/Asp23/Lys28 and the C-terminal carboxylate. Overall, these studies highlight the role of cross-seeding between WT and mutant Aβ40/42 isoforms, which can impact the rate and structure of fibril assembly. 相似文献
34.
本文对洈水水库鳡鱼的生长及其利用进行了分析研究,结果表明:1.该种鱼生长快,高速生长时间长,可连续5年每年生长6kg以上;2.雌、雄鱼体长与体重生长分别适合Von.Bertalanffy的生长公式:L=L_∞(1-e-k(t-t·))和W=W_∞(1-e-k(t-t·))~3;3.雌鱼体重生长速度快于雄鱼,体长生长无明显差别;4.建议大中型水体中的鳡鱼与其它鱼类群落体重之比控制在3—5%为宜。 相似文献
35.
同型半胱氨酸对大鼠血管平滑肌细胞增殖的作用 总被引:11,自引:0,他引:11
血中同型半胱氨酸(homocysteine,HCY)浓度的升高已成为动脉粥样硬化发生的一个独立危险因子.为进一步阐明HCY促进血管平滑肌细胞(vascularsmoothmusclecels,VSMCs)增殖,从而引起动脉粥样硬化发生的机理.本实验采用细胞计数、3H-TdR参入、细胞周期分析、Northern杂交方法证明,一定剂量的HCY可促进离体培养的WKY大鼠血管平滑肌细胞增殖,使其DNA合成增加,细胞周期中S期细胞所占比例增加43%,并促进c-myc与c-fos原癌基因mRNA表达增加.提示HCY可能通过促进VSMCs增殖而诱发动脉粥样硬化 相似文献
36.
Response of physiologic metabolism and cell structures in mango fruit to exogenous methyl salicylate under low-temperature stress 总被引:2,自引:0,他引:2
We explored the effects of exogenous methyl salicylate (MeSA) on the development of chilling injury symptom, and the structure and composition of the pericarp, in mango ( Mangifera indica L. cv. 'Red 6') fruit under low-temperature stress using histochemical analysis and scanning electron microscopy together with Fourier transform infrared (FTIR) analysis. The results indicated that chilling injury symptom was remarkably limited in the fruit treated with MeSA at 0.1 m M as compared to the 5°C control, demonstrating the positive effects of MeSA in reducing chilling injury of mango fruit in low-temperature storage. In MeSA-treated fruit, the pericarp wax surface showed many cracks, and exocarp cells exhibited normal separation. The cell wall of exocarp contained lower amounts of pectic substances, aliphatics and phenolics in MeSA-treated fruit. In addition, MeSA-treated fruit contained more esterified substances and less carboxylate and carboxyl substances. Our work revealed the importance of MeSA in enhancing fruit tolerance to low-temperature stress and suggested a contribution of cellular structure and composition to this effect, which has not been reported previously. 相似文献
37.
流行性出血热地鼠肾细胞灭活疫苗人体试用细胞免疫反应观察 总被引:2,自引:0,他引:2
观察了20位志愿者在接种试验性流行性出血热(EHF)地鼠肾细胞(GHKC)双价灭活疫苗后的细胞免疫反应,并以其体液免疫反应作对照观察。用淋巴细胞转化试验测定细胞免疫水平。结果首针疫苗接种后42天和56天,特异性刺激指数(SSI)和非特异性刺激指数(NSI)均较免疫前显著增高(P_(SSI)<0.001;P_(NSI)<0.02),免疫后SSI累计阳转率为100%,NSI累计阳转率为60%,免疫后6个月二者均降低至正常水平。免疫后56天测定抗体,荧光抗体阳转率为100%;微量感染性中和试验表明,针对家鼠型病毒L99株中和抗体阳转率为95%,而针对野鼠型病毒JR株阳转率为65%。 相似文献
38.
Zhiyi Liu Zilu Tian Kuan Cao Bin Zhang Quan Wen Xinyu Zhou Weibin Yang Tao Wang Hengliang Shi Renhao Wang 《Journal of cellular and molecular medicine》2019,23(1):70-82
The tumour susceptibility gene 101 (TSG101) is reported to play important roles in the development and progression of several human cancers. However, its potential roles and underlined mechanisms in human hepatocellular carcinoma (HCC) are still needed to be further clarified. In the present study, we reported that knock down of TSG101 suppressed the proliferation, migration and invasion of HCC cells, while overexpression of TSG101 facilitated them. Molecularly, the results revealed that knock down of TSG101 significantly decreased the cell cycle related regulatory factor p53 and p21. In another point, knock down of TSG101 also obviously decreased the level of metallopeptidase inhibitor TIMP1 (Tissue inhibitors of metalloproteinases 1), which results in inhibition of MMP2, MMP7 and MMP9. In contrast, overexpression of TSG101 had opposite effects. The iTRAQ proteomics analysis identified that oncogenic protein PEG10 (Paternally expressed gene 10) might be a potential downstream target of TSG101. Further investigation showed that TSG101 interacted with PEG10 and protected it from proteasomal degradation thereby regulating the expression of p53, p21 and MMPs. Finally, we found that both TSG101 and PEG10 proteins are up‐regulated and presented a direct correlation in HCC patients. In conclusion, these results suggest that TSG101 is up‐regulated in human HCC patients, which may accelerate the proliferation, migration and invasion of HCC cells through regulating PEG10. 相似文献
39.
Xiao-yu Chu Jian Tian Ning-feng Wu Yun-liu Fan 《Applied microbiology and biotechnology》2010,88(1):125-131
OPHC2, a methyl parathion hydrolase (MPH) from Pseudomonas pseudoalcaligenes C2-1 (CGMCC 1150), can degrade a wide range of organophosphate pesticides. Compared with other MPHs, OPHC2 exhibits high
thermostability. Its thermostability mechanism, however, remains unknown. In the present study, sequence analysis demonstrated
that two cysteines (Cys110 and Cys146) exist in OPHC2, but not in other MPHs. The three-dimensional structural model of OPHC2
performed by computer-assisted homology modelling revealed a potential stacking network with residues Cys110 and Cys146, which
probably formed an intramolecular disulfide bond. Furthermore, both sodium dodecyl sulphate-polyacrylamide gel electrophoresis
and thiol-titration analyses indicated that OPHC2 contains a disulfide bond. Substitution of the disulfide bond-forming cysteines
with alanine, leucine or methionine residues substantially decreased the thermostability of OPHC2, suggesting that disulfide
bond formation affects conformational stability. These results, combined with three-dimensional structural modelling, demonstrated
that the formation of a C110-C146 disulfide bond may stabilise the conformation of OPHC2, contributing to its thermostability. 相似文献
40.
基于变权模型的舟山群岛生态安全预警 总被引:4,自引:0,他引:4
生态安全预警是生态安全研究的重要内容,对维护区域生态安全具有重要的指示意义.本文以浙江省舟山群岛为例,基于驱动力、压力、状态、影响、响应(DPSIR)框架模型构建了生态安全预警指标体系,使用变权模型对2000-2012年舟山市生态安全的预警等级进行测度,并使用马尔科夫预测方法对2013-2018年生态安全警情进行了预测.结果表明:变权模型能够有效地满足舟山群岛生态安全动态预警研究需要;2000-2012年,舟山群岛生态安全预警指数由0.286波动上升至0.484,警度等级从“重警”演变为“中警”,指示灯由“橙灯”演化为“黄灯”;2013-2018年,舟山群岛生态安全预警等级预测结果为“中警”,指示灯为“黄灯”.研究结果可为维护舟山群岛生态安全提供参考. 相似文献