生物钟基因与心血管疾病

几乎各种生物的生理、生化和行为过程中都表现出一定的昼夜节律变化。昼夜节律生物钟(circa dianclock)就是设定并调控机体出现这种昼夜周期的系统,是一种以近似24h为周期的振荡器(oscilla tor);是机体为了更好地适应环境,在进化过程中自然选择作用下获得的[1]。该生物钟与昼-夜变换同步,使得机体不仅能适应由于地球自转带来的昼夜中的明暗变化,也能够适应地轴相对于太阳倾斜角度发生变化引起的昼夜长短变化。很早就已发现动物植物的生理行为呈现昼夜节律,但直到上世纪中期才发现该节律由内在的昼夜节律生物钟所控制[2]。1生物钟基因对果蝇…     

光照周期对生物钟基因表达的调控

所有生物在环境条件呈昼夜节律性(24h)变化的环境中生存，它们体内的生物钟将感受到的外界变化信息，经过中央振荡器(central oscmator)整合以后，以神经冲动或激素信号的形式作用于靶器官，产生生理与行为活动的昼夜变化，其昼夜节律性表达对维持生物钟的周期性活动来说是必需的。     

生物钟紊乱与相关疾病关系的研究进展

生物钟又称生物节律,是生物体内周期性波动的行为和生理现象,近年来对生物钟产生和同步的分子机制的研究日益深入.研究表明,生物钟的周期性变化与生物体的某些疾病(如失眠、癌症、抑郁症、阿尔茨海默氏病等)息息相关.所以,对生物钟与相关疾病的关系的研究有重要的意义.本文就国内外有关生物钟的生理机制及生物钟相关疾病的研究综述如下,以期为更好地研究生物钟的生理机制及防治相关疾病提供理论依据.     

血尿酸与骨质疏松症相关性的研究进展

骨质疏松症是骨骼系统最常见的慢性代谢性疾病,其特征是骨密度降低和骨骼微结构退化。嘌呤代谢失调所引起的高尿酸血症是一种代谢异常综合征,近些年来其患病率有了明显增长,而且逐渐呈现出年轻化的发展趋势。国内外学者对骨质疏松与尿酸之间相关性的研究较多,研究结果表明两者之间具有相关性,但因混杂因素较多,对两者间具体的、 确切的关系仍有争议。本文对血尿酸与骨质疏松症的相关性作一综述。     

肠道菌群失调与生物钟紊乱的相关性

<正>正常人体肠道内寄生着种类繁多、数量庞大的微生物,以细菌为主,统称为肠道菌群。据统计其种类大于1 000种,总数高达1014,是人体细胞总和的10倍[1]。正常情况下,肠道内的微生物与宿主相互依存彼此制约,共同维持动态的生物平衡。一旦外界环境或内在平衡受到破坏,肠道菌群种类、数量及比例等发生改变,造成肠道内菌群失调[2]。研究发     

昼夜节律性生物钟的分子调节机制

哺乳动物昼夜节律性生物钟由下丘脑视交叉上核 (SCN)内的“中枢起搏点”来调节控制 ,其机制是单个细胞水平的一个分子自动调节环路 ,包含转录、翻译及蛋白产物入核负反馈抑制核内转录过程。SCN的主控振动机制有其自身的周期性以及周期的持续性并能够通过特定途径感受光信号的输入 ,作出反应进而适应外界环境的变化。SCN这种节律性机制的“输出”是通过细胞之间信号的整合 ,再将最终的“指令”传递至全身。     

哺乳动物的生物钟分子机制研究进展

生物体内存在着内源性生物钟，调控着机体生命活动和生理功能。近来哺乳动物的生物钟机制的研究取得重大进展，已深入到分子水平。包括几种生物钟相关基因的分离鉴定，明确了这些基因及其蛋白质产物的功能，它们构成的自主调节的转录和翻译反馈环，是生物钟运转的分子机制。另外，哺乳动物体外培养的外周组织也存在着近日节律，这为生物节律的深入研究提供了重要线索。     

生物钟基因Timeless及与肿瘤关系的研究进展

生物钟基因的功能不仅局限于调节生物节律,更与细胞内DNA的修复、细胞的增殖等一系列过程相关联,Timeless是生物钟基因成员之一,对Timeless基因的研究起步较晚.近年来研究发现生物钟基因在多种肿瘤中普遍存在表达异常,而对Timeless研究较少.     

生物钟与肠道微环境、肠道免疫系统之间关系的研究进展

生物钟可以通过影响真核生物体内基因转录、改变生物氧化还原状态等方式保证机体每天进行正常的生长代谢节律波动,人体内的生物钟还能够调控肠道免疫细胞的增殖、分化及分泌功能.生物钟紊乱时会降低机体肠道免疫系统的抗病能力进而引起局部肠道黏膜损害或部分肠道炎症的发生.由大量微生物菌群组成的肠道微环境参与机体肠道黏膜保护、能量传递及营养代谢等生理过程,微环境发生改变时也会引起肠道病理性炎症反应.昼夜节律性改变也会改变正常的肠道微生态环境,使益生菌群数量下降并激活条件致病菌,产生大量有害代谢物质引起肠道炎症反应.生物钟、肠道菌群、肠道免疫系统之间存在着一定关系,但是它们之间的联系目前并不明确.明确生物钟、肠道微环境、肠道免疫防御、炎症性肠道疾病之间关系,从而探讨肠道疾病可能的发病机制,为炎症性肠道疾病治疗途径提供新的思路治疗途径提供新的思路.     

A silent polymorphism in the PER1 gene associates with extreme diurnal preference in humans

The three PERIOD proteins form a major negative feedback component of the molecular mechanism governing the periodicity of the vertebrate circadian clock. Genetic variations within the human PER2 and PER3 genes have been linked with diurnal preference and disorders of sleep timing. We screened the coding region of PER1, as well as the 5′- and 3′-untranslated regions and the promoter region, for polymorphisms. The T2434C polymorphism in exon 18, a synonymous substitution, associated with extreme diurnal preference. The C allele was more frequent in subjects with extreme morning preference (frequency = 0.24) than in subjects with extreme evening preference (frequency = 0.12). No significant association was observed between either allele and delayed sleep phase syndrome. This polymorphism may have a direct effect on RNA translatability, or be in linkage disequilibrium with another polymorphism which affects PER1 expression at the DNA, RNA, or protein level. This is the first reported association between a PER1 polymorphism and extreme diurnal preference. Functionally important polymorphisms in PER1 are rare, which may indicate that it is subject to more stringent selection pressure than the other PER genes.     

Epidemiological and genetic overlap among biological aging clocks: New challenges in biogerontology

Estimators of biological age (BA) – defined as the hypothetical underlying age of an organism – have attracted more and more attention in the last years, especially after the advent of new algorithms based on machine learning and genetic markers. While different aging clocks reportedly predict mortality in the general population, very little is known on their overlap. Here we review the evidence reported so far to support the existence of a partial overlap among different BA acceleration estimators, both from an epidemiological and a genetic perspective. On the epidemiological side, we review evidence supporting shared and independent influence on mortality risk of different aging clocks - including telomere length, brain, blood and epigenetic aging – and provide an overview of how an important exposure like diet may affect the different aging systems. On the genetic side, we apply linkage disequilibrium score regression analyses to support the existence of partly shared genomic overlap among these aging clocks. Through multivariate analysis of published genetic associations with these clocks, we also identified the most associated variants, genes, and pathways, which may affect common mechanisms underlying biological aging of different systems within the body. Based on our analyses, the most implicated pathways were involved in inflammation, lipid and carbohydrate metabolism, suggesting them as potential molecular targets for future anti-aging interventions. Overall, this review is meant as a contribution to the knowledge on the overlap of aging clocks, trying to clarify their shared biological basis and epidemiological implications.     

骨质疏松症动物模型的构建及实验方法研究进展

骨质疏松症是一种全身性骨代谢病,由多种因素引起,其特点是骨量、骨密度和骨组织的显微结构恶化,骨脆性增强和易发生骨折.骨质疏松症已严重威胁人类健康,最终将导致患者日常活动减少,生活质量降低,死亡率增加.针对不同的研究对象,选择一个正确、理想的动物骨质疏松的模型和实验方法以尽可能再现人类骨质疏松的状态,是开展动物实验的关键...     

骨质疏松症对松质骨骨小梁应力与微损伤关系的影响

目的应用显微CT和微有限元分析评估微损伤、微骨折骨小梁的应力、应变,探讨骨质疏松症对骨小梁应力和微损伤、微骨折之间关系的影响。方法通过显微CT扫描健康和骨质疏松人体髋臼松质骨,构建松质骨块三维微有限元模型,在无摩擦的位移边界条件下模拟松质骨块的单轴压缩实验,通过非线性微有限元分析得到在不同表观应变下骨小梁的应力、应变、微损伤和微骨折。结果 0.05%~0.50%表观应变下,健康和骨质疏松松质骨未损伤骨小梁的应力在50 MPa以下,微损伤骨小梁应力在110 MPa以上。健康松质骨骨小梁的平均应力相对较高,骨质疏松松质骨骨小梁最高应力值相对较高。健康和骨质疏松松质骨骨小梁均出现微损伤,健康松质骨骨小梁微损伤较多,骨质疏松骨骨小梁出现微骨折。结论在表观小应变范围内,健康松质骨骨小梁能承受更高的应力,出现较多的微损伤,而骨质疏松松质骨高应力骨小梁群内出现微骨折。     

Control of behavioral circadian rhythms for nesting and wheel running in mice

In Experiment 1 a circadian rhythm for nest-building behavior is demonstrated in 10 males from a genetically heterogeneous stock of Mus musculus. In Experiment 2, this circadian rhythm in nesting and that for wheel running activity were monitored simultaneously in an additional sample of five males from the same stock. Under a 16:8 LD photoperiod, mice displayed a 24-hr periodicity for both behaviors but a phase difference in peak behavioral intensities of approximately two and one-half hours. After ten days of exposure to constant light both rhythms persisted, but with no detectable difference in phase. The altered phase relationship under constant light suggests a difference in control of the circadian periodicities of these two behaviors. In Experiment 3, 5 additional males were subjected to a 10-hr shift in photoperiod to further examine control of these rhythms as well as those in food and water consumption. All four circadian rhythms re-entrained within four days. Thus, their entrainment mechanisms are functionally similar in spite of the differences in control suggested in Experiment 2.     

老年骨质疏松机制及股骨转子间骨折治疗的研究进展

骨质疏松症是一种以脆性骨折为显著表现的全身性、代谢性骨骼系统疾病。其发病原因包括多种因素,根据目前的流行病学研究,骨质疏松及相关性骨折的发病率会继续增加。本文主要关注老年骨质疏松的机制、涉及相关基因、信号传递方面的基础研究及其继发股骨粗隆间骨折的临床治疗的进展。成骨细胞通过Wnt信号通路,促进成骨细胞活化。骨细胞通过产生前列腺素E2,促进细胞核因子κB受体激活蛋白(RANK)与细胞核因子κB受体激活蛋白配体(RANKL)结合,促进破骨细胞分化及其对骨的吸收。而成骨细胞则阻碍上述过程。丝裂原活化蛋白激酶信号通路中的ERK1/2通路、JNK通路、P38通路与骨质疏松的治疗有关。生长激素和胰岛素样生长因子通过JAK-STAT信号通路,保持成骨细胞和破骨细胞稳定维持骨量,若两者之间的关系破坏,则会出现骨质疏松。基于上述基础研究,临床上出现了更多的抗骨质疏松药物。在手术治疗方面,传统动力髋螺钉、解剖型钢板、Gamma钉、股骨近端髓内钉的地位继续下降,股骨近端防旋髓内钉(PFNA)及其改型PFNA-Ⅱ的发明和使用,坚持了科学的髓内固定,增加了对于股骨颈骨质的充填、提高了把持力、抗旋力和纵行加压,成为目前老年骨质疏松性粗隆间骨折临床治疗的首选。对于部分患者,髋关节置换也成为首次治疗或者补救性治疗的方法,虽然有较多缺点,但可提高手术疗效,早期下地。