硒蛋白M敲除在褪黑素拮抗镍诱导的小鼠心脏细胞凋亡和内质网应激中的作用（英文）

本研究旨在研究硒蛋白M(SelM)在由镍诱导的小鼠心脏内质网应激和细胞凋亡中的作用,并探索褪黑素的解毒作用。在对雄性野生型(WT)和SelM敲除型(KO)C57BL/6J小鼠腹腔注射氯化镍(NiCl₂)和/或褪黑素21天后,我们发现NiCl2能诱发WT和SelM KO小鼠心脏的微观结构和超微结构的变化,并通过丙二醛(MDA)含量和总抗氧化能力(T-AOC)下降证明这些变化是由氧化应激、内质网应激和细胞凋亡引起的。同时,我们观察到与内质网应激(激活转录因子4(ATF4)、肌醇需要酶1(IRE1)、c-Jun N-端激酶(JNK)和C/EBP同源蛋白(CHOP))和细胞凋亡(B细胞淋巴瘤2型蛋白(Bcl-2)、Bcl-2相关蛋白X(Bax)、半胱氨酸-天冬氨酸蛋白酶3(Caspase-3)、Caspase-9和Caspase-12)相关基因的信使RNA(mRNA)和蛋白表达的变化。值得注意的是,这种损伤在SelM KO小鼠中更严重。此外,褪黑素减轻了WT小鼠由NiCl₂引起的心脏损伤,但对SelM KO小鼠的心脏却不能产生良好的保护作用。综上所述...     

组蛋白去乙酰化酶（HDAC）抑制剂西达本胺联合维奈托克通过下调MYC、BCL2和TP53的表达协同抑制弥漫性大B细胞淋巴瘤的生长（英文）

目的：探讨表观遗传学组蛋白去乙酰化酶(HDAC)抑制剂西达本胺与BCL2抑制剂维奈托克的联合对弥漫性大B细胞淋巴瘤(DLBCL)生长的影响及相关机制。创新点：本研究首次探索了将西达本胺和维奈托克联合作用于MYC⁺/BCL2⁺DLBCL,使用二代测序(NGS)开创性地从表观遗传学和基因蛋白层面探讨这种联合用药的效果及作用机制。方法：利用生物信息学技术分析表观遗传学HDAC基因与BCL2基因之间的相关性;体外应用DHL细胞株DB(MYC/BCL2重排)和DEL细胞株SUDHL-4(MYC、BCL2表达)分别进行单药和联合用药处理,通过CCK-8法检测细胞活力,流式细胞术检测细胞凋亡和周期,RNA测序和蛋白质印迹(westernblot)检测MYC、BCL2、TP53等相关基因的m RNA水平及蛋白的表达;体内建立DLBCL异种移植小鼠模型进行单药和联合用药治疗,分析并评价药物治疗后皮下瘤的大小和病理切片。结论：西达本胺与维奈托克协同抑制DLBCL的生长,通过调控表观遗传的改变,沉默MYC、TP53的表达,降低抗凋亡蛋白BCL2表达以及增加促凋亡蛋...     

Epigenetics recording varied environment and complex cell events represents the origin of cellular aging

Journal of Zhejiang University-SCIENCE B - Although a relationship between epigenetics and aging phenotypic changes has been established, a theoretical explanation of the intrinsic connection...     

从市场营销环境的视角谈我国老龄产业发展问题

随着科学技术的进步和人民生活水平的提高、人口平均寿命的延长,我国正迎来一个前所未有的"银发浪潮".如何适应未来人口发展趋势,大力发展老龄产业,是值得各级人民政府、企事业单位和社会各界高度关注、重视和思考的问题.针对目前老龄产业发展面临的困难与问题,本文提出五点思考,即提高对老龄产业的认识,抓好相关法规政策落实;因地制宜制定优惠政策、多方参与发展老龄产业;加强部门间的协调与配合,形成发展老龄产业的合力;切实转变营销服务观念,不断拓展老年消费市场;做强做大做优老龄产业,努力实现又好又快发展.     

DNA-damage response network at the crossroads of cell-cycle checkpoints,cellular senescence and apoptosis

Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities. Cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms. Apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death. The intimate link between the cell cycle, cellular senescence, apoptosis regulation, cancer development and tumor responses to cancer treatment has become eminently apparent. Extensive research on tumor suppressor genes, oncogenes, the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways, referred to as the DNA-damage response network, are tied to cell proliferation, cell-cycle arrest, cellular senescence and apoptosis. DNA-damage responses are complex, involving ＂sensor＂ proteins that sense the damage, and transmit signals to ＂transducer＂ proteins, which, in turn, convey the signals to numerous ＂effector＂ proteins implicated in specific cellular pathways, including DNA repair mechanisms, cell-cycle checkpoints, cellular senescence and apoptosis. The Bcl-2 family of proteins stands among ＂the mos＂t crucial regula＂tors of apop＂tosis and performs vi＂tal func＂tions in deciding whether a cell will live or die after cancer chemotherapy and irradiation. In addition, several studies have now revealed that members of the Bcl-2 family also interface with the cell cycle, DNA repair/recombination and cellular senescence, effects that are generally distinct from their function in apoptosis. In this review, we report progress in understanding the molecular networks that regulate cell-cycle checkpoints, cellular senescence and apoptosis after DNA damage, and discuss the influence of some Bcl-2 family members on cell-cycle checkpoint regulation.     

Molecular modeling study of the effect of base methylation on internal interactions and motions in DNA and implication to B-Z conformation change

1. Introduction Experimental studies have shown that a DNA molecule with alternating pyrimidine-purine sequence can adopt a left-handed, double-helical Z-DNA conformation [1,2]. Such structural changes of DNA occur as a consequence of environmental conditions such as at salt concentration above 4 mol/L NaCl [1,2] or through certain chemical modification such as methylation [1] or bromination [2,3] of bases at physiological conditions. These structural changes and chemical modifications …     

Review:DNA-damage response network at the crossroads of cell-cycle checkpoints, cellular senescence and apoptosis

Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities. Cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms. Apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death. The intimate link between the cell cycle, cellular senes- cence, apoptosis regulation, cancer development and tumor responses to cancer treatment has become eminently apparent. Extensive research on tumor suppressor genes, oncogenes, the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways, referred to as the DNA-damage response network, are tied to cell proliferation, cell-cycle arrest, cellular senescence and apoptosis. DNA-damage responses are complex, involving “sensor” proteins that sense the damage, and transmit signals to “transducer” proteins, which, in turn, convey the signals to numerous “effector” proteins implicated in specific cellular pathways, including DNA repair mechanisms, cell-cycle checkpoints, cellular senescence and apoptosis. The Bcl-2 family of proteins stands among the most crucial regulators of apoptosis and performs vital functions in deciding whether a cell will live or die after cancer chemotherapy and irradiation. In addition, several studies have now revealed that members of the Bcl-2 family also interface with the cell cycle, DNA repair/recombination and cellular senescence, effects that are generally distinct from their function in apoptosis. In this review, we report progress in understanding the molecular networks that regulate cell-cycle checkpoints, cellular senescence and apoptosis after DNA damage, and discuss the influence of some Bcl-2 family members on cell-cycle checkpoint regulation.