Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug–drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.     

Long-term cyclic oxidation behavior of uncoated and coated RE108 and IN939 at 980 and 870 °C

Very long-term cyclic oxidation behavior of Re108 and In939 with and without a protective coating was evaluated at 980 and 870 °C, respectively. Re108 and In939 without a protective coating began to show a rapid weight loss at 3000 h due to scale spallation, indicating the need for an oxidation protective coating for longer than thousands of hours of oxidative life. NiAl-base coatings of a vapor phase aluminide (VPA), a pack aluminide (CODEP), and a slurry paint aluminide (SERMALOY J) were applied on Re108 and In939. The VPA and CODEP on Re108 and all three coatings on In939 showed excellent cyclic oxidation resistance out to 10,000 h. Coated alloys were annealed in an inert atmosphere to determine the loss of Al from the coating into the alloy substrate through diffusion. The Al loss from the coating through diffusion was twice as great as the Al loss through oxidation after 10,000 h of cyclic exposure. The oxidation life of VPA-coated Re108 was estimated by calculating the amount of Al initially available for protective oxidation and the amount of Al lost through oxidation and diffusion.     

Polyvinylphosphonic acid copolymer hydrogels prepared with amide and ester type crosslinkers

Crosslinked hydrogels made of poly(vinylphosphonic acid‐co‐N,N′‐methylenebisacrylamide) (P(VPA‐co‐MBAA)) and poly(vinylphosphonic acid‐co‐ethyleneglycol diacrylate) (P(VPA‐co‐EGDA)) were prepared by using precipitation polymerization in water medium. A comparison research was made between the resultant hydrogels containing different loads of vinylphosphonic acid segments when N,N′‐methylenebisacrylamide (MBAA) or ethyleneglycol diacrylate (EGDA) were used as comonomers. Morphological observations indicated that the resultant copolymer appeared as a fine powder at low VPA loadings and strongly aggregated at the high loadings; especially, a copolymer containing 63 mol % of VPA segments in P(VPA‐co‐MBAA) was observed to have a flake‐shaped appearance in its aggregated morphology. The resultant copolymer powders were characterized using FTIR spectroscopy and titrimetric analysis. Also, monomer reactivity ratios, r₁ and r₂, of VPA and MBAA or EGDA were estimated as 0.06 and 0.98 for VPA and MBAA and 0.05 and 1.82 for VPA and EGDA, respectively. This suggested that a large distribution of MBAA and EGDA was present in the resultant copolymer powders. Their crosslinked PVPA structure presented hydrogel properties having high water uptakes and an absorption mechanism independent from pH of bulk solution. The evidence showed that high VPA loadings could strongly interacted through hydrogen bonds between neighbor VPA segments even in the presence of water. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

基于802.16e的信道估计算法研究

常用的空时译码方法在很大程度上依赖于准确的信道状态信息,使得信道估计成为正确进行空时编码译码的先决条件。结合虚拟导频的设计和时频二维多项式拟合算法,研究了一种适用于快速移动场景下的虚拟导频信道估计算法。该算法能够利用时频二维信道信息的相关性,对信道进行拟合,从而提升信道估计的性能。分别在车载60km以及车载120km信道模式下进行仿真,结果表明,较现有的信道估计算法,在快速移动场景下虚拟导频信道估计算法具有更好的均方误差性能。     

数据仓库中多视图环境下的联机维护

数据仓库的视图联机维护是指数数据仓库中的实体化视图实时地与信息源中的数据库仑保持一致,同时不影响前端用户对数据仓库的正常使用。为了解决多视图环境中视图联机维护与下钻查询的一致性问题,文中在数据仓库体系结构中引入了“基库”模型,并提出了相应的视图维护算法３ＶＰＡ。     

Alterations in Tau Protein Level and Phosphorylation State in the Brain of the Autistic-Like Rats Induced by Prenatal Exposure to Valproic Acid

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficient social interaction and communication besides repetitive, stereotyped behaviours. A characteristic feature of ASD is altered dendritic spine density and morphology associated with synaptic plasticity disturbances. Since microtubules (MTs) regulate dendritic spine morphology and play an important role in spine development and plasticity the aim of the present study was to investigate the alterations in the content of neuronal α/β-tubulin and Tau protein level as well as phosphorylation state in the valproic acid (VPA)-induced rat model of autism. Our results indicated that maternal exposure to VPA induces: (1) decrease the level of α/β-tubulin along with Tau accumulation in the hippocampus and cerebral cortex; (2) excessive Tau phosphorylation and activation of Tau-kinases: CDK5, ERK1/2, and p70S6K in the cerebral cortex; (3) up-regulation of mTOR kinase-dependent signalling in the hippocampus and cerebral cortex of adolescent rat offspring. Moreover, immunohistochemical staining showed histopathological changes in neurons (chromatolysis) in both analysed brain structures of rats prenatally exposed to VPA. The observed changes in Tau protein together with an excessive decrease in α/β-tubulin level may suggest destabilization and thus dysfunction of the MT cytoskeleton network, which in consequence may lead to the disturbance in synaptic plasticity and the development of autistic-like behaviours.     

Untargeted LC-MS/MS Metabolomics Study on the MCF-7 Cell Line in the Presence of Valproic Acid

To target breast cancer (BC), epigenetic modulation could be a promising therapy strategy due to its role in the genesis, growth, and metastases of BC. Valproic acid (VPA) is a well-known histone deacetylase inhibitor (HDACi), which due to its epigenetic focus needs to be studied in depth to understand the effects it might elicit in BC cells. The aim of this work is to contribute to exploring the complete pharmacological mechanism of VPA in killing cancer cells using MCF-7. LC-MS/MS metabolomics studies were applied to MCF-7 treated with VPA. The results show that VPA promote cell death by altering metabolic pathways principally pentose phosphate pathway (PPP) and 2′deoxy-α-D-ribose-1-phosphate degradation related with metabolites that decrease cell proliferation and cell growth, interfere with energy sources and enhance reactive oxygen species (ROS) levels. We even suggest that mechanisms such as ferropoptosis could be involved due to deregulation of L-cysteine. These results suggest that VPA has different pharmacological mechanisms in killing cancer cells including apoptotic and nonapoptotic mechanisms, and due to the broad impact that HDACis have in cells, metabolomic approaches are a great source of information to generate new insights for this type of molecule.