Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes

Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.     

Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice

Introduction

Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals.

Results

Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots.

Conclusions

We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis.     

Beta-carotene affects gene expression in lungs of male and female <Emphasis Type="Italic">Bcmo1</Emphasis><Superscript>−/−</Superscript> mice in opposite directions

Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1 ^−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1 ^−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1 ^−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1 ^−/− mice, which had, unlike wild-type (Bcmo1 ^+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice.     

Protecting the boundary: the sentinel role of host defense peptides in the skin

The skin is our primary shield against microbial pathogens and has evolved innate and adaptive strategies to enhance immunity in response to injury or microbial insult. The study of antimicrobial peptide (AMP) production in mammalian skin has revealed several of the elegant strategies that AMPs use to prevent infection. AMPs are inducible by both infection and injury and protect the host by directly killing pathogens and/or acting as multifunctional effector molecules that trigger cellular responses to aid in the anti-infective and repair response. Depending on the specific AMP, these molecules can influence cytokine production, cell migration, cell proliferation, differentiation, angiogenesis and wound healing. Abnormal production of AMPs has been associated with the pathogenesis of several cutaneous diseases and plays a role in determining a patient’s susceptibility to pathogens. This review will discuss current research on the regulation and function of AMPs in the skin and in skin disorders.     

法锥条件下非凸规划的非内点同伦方法

利用不可行的内点同伦方法(CHIIP)求解非凸规划问题的KKT点. 证明了当非凸规划问题的可行域满足法锥条件时, 跟踪同伦方程产生的同伦曲线可得到非凸规划问题的KKT点, 且该算法具有全局收敛性.     

混合约束非凸规划拟锥条件下的同伦方法

使用同伦算法研究混合约束的非凸非线性规划问题. 当规划问题为混合约束（带有等式约束）时, 可行域变成一个边界区域, 并没有内点. 通过对可行域定义新的拟锥条件, 给出相应同伦方程, 并证明此同伦算法在此拟锥条件下具有全局收敛性.     

东濮凹陷胡庆地区原油地球化学特征与油源分析

研究东濮凹陷胡庆地区原油地球化学特征及其来源.利用有机地球化学分析方法,对原油与烃源岩进行饱和烃色谱、饱和烃与芳烃色谱-质谱分析,剖析了两者的分子地球化学特征及油源.研究表明:胡庆地区发育3类原油,第一类原油具有极高伽马蜡烷,质量色谱图中甾烷呈"L"形特征,来自第二台阶的沙一段烃源岩,在沙一段储层中富集形成自生自储常温...     

湘西更新世哺乳动物化石痕迹考察研究

目的 考察湘西土家族苗族自治州古丈县断龙乡猛虎洞更新世哺乳动物群骨化石断裂痕迹的状态与原因,探索湘西地区古人类活动的遗迹.方法 观测哺乳动物群骨化石断裂痕迹剖面的形态结构,以区别食肉类动物群的咬痕与人类打造的印迹.结果 经40件东方剑齿象、中国犀、鹿等残骨化石标本断裂痕迹剖面的观测,发现有部分骨化石断裂剖面圆钝,似啮齿动物的咬痕,但大部分骨化石断端剖面呈锥形切削改造,有的双面削刮呈锐利器型,有的存在明显打击或铲刮的 “印记”,初步认为属早期人类制作骨器的遗迹.结论 结合地理环境和地学结构分析,猛虎洞可能属晚更新世(10～5)万年前旧石器人类穴居的营地或系同生代古脊椎动物的遗址.     

碱激发胶凝材料的碳化性能研究进展

碱激发胶凝材料作为新型绿色建筑材料,在促进工业固体废料的循环使用、减少CO2气体排放等方面有着突出的优势,近几年针对这种材料耐久性能的研究越发受到重视,碳化作为影响耐久性能的关键因素,也需要进一步的研究。从碳化机理、碳化速率、碳化影响以及抗碳化性能改善方面总结了碱激发胶凝材料碳化性能研究现状,概述了目前碳化领域研究所取得的成果和面临的困难。基于已有成果,提出了研究建议,以期为碱激发混凝土的发展和推广应用提供参考。     

Effects of Hydrophilic Monomer Types and Level on Polystyrene-Acrylate/montmorillonite Nanocomposite Made by Emulsion Polymerization

1 Results Nanocomposite has attracted more and more interest all over the world.Polystyrene (PS) is a commercialized and mass-productive polymer,continuous research efforts have been devoted to the development of polystyrene/montmorillonite (PS/MMT) nanocomposites[1-2].But the polarity of styrene (St) is too small to intercalate the space between the clay layers.The polarity of hydrophilic monomer is so strong that it can intercalate the MMT easily,the intercalated smectic clays maybe exfoliated by usin...