Circadian Clocks

昼夜节律时钟
  • 文章类型: Journal Article
    肺腺癌是世界上最常见的原发性肺癌,识别遗传标记对于预测肺腺癌的预后和改善治疗结果至关重要。众所周知,昼夜节律的改变与较高的癌症风险有关。此外,昼夜节律在人体中起着调节作用。因此,研究癌症患者昼夜节律的变化对于优化治疗至关重要。基因表达数据和临床数据来源于TCGA数据库,我们确定了与生物钟相关的基因。我们使用获得的TCGA-LUAD数据集来建立模型,其他647例肺腺癌患者的数据来自两个GEO数据集,用于外部验证。构建了昼夜节律相关基因的风险评分模型,基于8个遗传显著基因的鉴定。根据ROC分析,风险模型在预测训练折叠期肺腺癌患者的总体生存时间方面表现出很高的准确性,以及外部数据集。本研究成功构建了肺腺癌预后风险模型,利用昼夜节律作为其基础。该模型证明了预测疾病结果的可靠能力,从而进一步指导肺腺癌的相关机制,将行为疗法与治疗相结合,优化治疗决策。
    Lung adenocarcinoma is the most common primary lung cancer seen in the world, and identifying genetic markers is essential for predicting the prognosis of lung adenocarcinoma and improving treatment outcomes. It is well known that alterations in circadian rhythms are associated with a higher risk of cancer. Moreover, circadian rhythms play a regulatory role in the human body. Therefore, studying the changes in circadian rhythms in cancer patients is crucial for optimizing treatment. The gene expression data and clinical data were sourced from TCGA database, and we identified the circadian clock-related genes. We used the obtained TCGA-LUAD data set to build the model, and the other 647 lung adenocarcinoma patients\' data were collected from two GEO data sets for external verification. A risk score model for circadian clock-related genes was constructed, based on the identification of 8 genetically significant genes. Based on ROC analyses, the risk model demonstrated a high level of accuracy in predicting the overall survival times of lung adenocarcinoma patients in training folds, as well as external data sets. This study has successfully constructed a risk model for lung adenocarcinoma prognosis, utilizing circadian rhythm as its foundation. This model demonstrates a dependable capacity to forecast the outcome of the disease, which can further guide the relevant mechanism of lung adenocarcinoma and combine behavioral therapy with treatment to optimize treatment decision-making.
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  • 文章类型: Journal Article
    昼夜节律是整个生物体中普遍存在的特征。越来越多的证据表明,由于基因突变或环境因素导致的昼夜节律功能障碍有助于多种疾病的发生和发展。眼表的生理稳态,像任何其他组织或器官一样,也是由昼夜节律精心策划的。在这次审查中,我们总结了哺乳动物眼表的分子钟和时钟控制基因的表达。基于这些基因的昼夜节律表达,我们总结了哺乳动物眼表细胞生物学活动的昼夜振荡。此外,我们评估了在眼表中夹带昼夜节律振荡器的因素。最后,我们进一步讨论了昼夜节律与眼部健康密切相关的最新进展。简而言之,这篇综述旨在综合以往的研究,以帮助理解眼表昼夜节律的重要性,以及基于昼夜节律的干预策略恢复眼表稳态的可能机会。
    Circadian rhythms are a ubiquitous feature throughout the organism. Accumulating evidence suggests that the dysfunction of circadian rhythms due to genetic mutations or environmental factors contributes to the genesis and progress of multiple diseases. The physiological homeostasis of the ocular surface, like any other tissue or organ, is also orchestrated by circadian rhythms. In this review, we summarize the molecular clocks and the expression of clock-controlled genes in the mammalian ocular surface. Based on the circadian expression of these genes, we conclude the diurnal oscillations of cellular biological activities in the mammalian ocular surface. Moreover, we evaluate the factors entraining circadian oscillators in the ocular surface. Finally, we further discuss the latest development of the close correlation between circadian rhythms and ocular health. Briefly, this review aimed to synthesize the previous studies to aid in understanding the importance of circadian rhythms in the ocular surface and the possible opportunities for circadian rhythm-based interventional strategies to restore the homeostasis of the ocular surface.
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  • 文章类型: Journal Article
    昼夜节律在调节各种生理过程中起着至关重要的作用,包括特定的免疫功能,增强身体有效应对威胁的预测和反应能力。然而,关于昼夜节律对骨免疫学影响的研究仍然有限。我们的研究发现,昼夜节律破坏通过减少骨髓中的Treg细胞数量而导致骨量损失。此外,我们观察到血清IL-10细胞因子水平显着下降在时差小鼠。在我们目前的调查中,我们探讨了IL-10的抗破骨细胞作用,发现IL-10以剂量依赖性方式抑制RANKL诱导的破骨细胞生成.我们的发现表明,昼夜节律破坏下Tregs的抗破骨细胞特性降低是由IL-10细胞因子产生介导的。此外,我们的发现提示,IL-10或丁酸可能逆转时差反应个体的骨量丢失.
    Circadian rhythms play a crucial role in regulating various physiological processes, including specific immune functions that enhance the body\'s ability to anticipate and respond to threats effectively. However, research on the impact of circadian rhythms on osteoimmunology remains limited. Our study uncovered that circadian disruption leads to bone mass loss by reducing the population of Treg cells in the bone marrow. Furthermore, we observed a significant decrease in serum IL-10 cytokine levels in jet lagged mice. In our current investigation, we explored the anti-osteoclastogenic effects of IL-10 and found that IL-10 inhibits RANKL-induced osteoclastogenesis in a dose-dependent manner. Our findings suggest that the diminished anti-osteoclastogenic properties of Tregs under circadian disruption are mediated by IL-10 cytokine production. Moreover, our discoveries propose that administration of IL-10 or butyrate could potentially reverse bone mass loss in individuals experiencing jet lag.
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  • 文章类型: Journal Article
    昼夜节律在大约24小时的周期内调节生理过程,它们的破坏与各种疾病有关。炎症可能扰乱昼夜节律,尽管这些相互作用尚不清楚。这项研究检查了腹膜内注射脂多糖(LPS)引起的全身性炎症是否可以改变中枢和外周昼夜节律和昼夜神经免疫动力学。将小鼠随机分为两组:盐水对照组和LPS组。测定下丘脑昼夜节律基因和炎症因子的昼夜表达,海马体,还有肝脏.还评估了小胶质细胞的昼夜动态行为。我们的结果表明,LPS扰乱了下丘脑的昼夜节律基因振荡,海马体,还有肝脏.此外,LPS诱导的全身性炎症可引发神经炎症并扰乱海马小胶质细胞的昼夜动态行为。这些发现揭示了炎症和昼夜节律紊乱之间的复杂联系,强调它们在神经退行性疾病中的重要性。
    Circadian rhythms regulate physiological processes in approximately 24 h cycles, and their disruption is associated with various diseases. Inflammation may perturb circadian rhythms, though these interactions remain unclear. This study examined whether systemic inflammation induced by an intraperitoneal injection of lipopolysaccharide (LPS) could alter central and peripheral circadian rhythms and diurnal neuroimmune dynamics. Mice were randomly assigned to two groups: the saline control group and the LPS group. The diurnal expression of circadian clock genes and inflammatory cytokines were measured in the hypothalamus, hippocampus, and liver. Diurnal dynamic behaviors of microglia were also assessed. Our results revealed that the LPS perturbed circadian gene oscillations in the hypothalamus, hippocampus, and liver. Furthermore, systemic inflammation induced by the LPS could trigger neuroinflammation and perturb the diurnal dynamic behavior of microglia in the hippocampus. These findings shed light on the intricate link between inflammation and circadian disruption, underscoring their significance in relation to neurodegenerative diseases.
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  • 文章类型: Journal Article
    表观遗传调节对昼夜节律很重要。在以往的研究中,在周期(每个)基因座发现了多个组蛋白修饰。然而,这些研究大多不是在时钟神经元中进行的。在我们的屏幕上,我们发现CoREST突变通过影响Per转录导致昼夜节律缺陷。根据以前的研究,我们假设CoREST通过调节Per位点的多个组蛋白修饰来调节昼夜节律。遗传和物理相互作用实验支持这些调节关系。此外,通过时钟神经元的组织特异性染色质免疫沉淀试验,我们发现CoREST突变导致Per基因座相应组蛋白修饰的时间依赖性变化。最后,我们提出了一个模型,表明CoREST复合体在昼夜节律调节中的作用.这项研究揭示了特定于时钟神经元的Per基因座组蛋白修饰的动态变化。重要的是,它提供了对表观遗传因素在昼夜节律动态基因表达变化调节中的作用的见解。
    Epigenetic regulation is important for circadian rhythm. In previous studies, multiple histone modifications were found at the Period (Per) locus. However, most of these studies were not conducted in clock neurons. In our screen, we found that a CoREST mutation resulted in defects in circadian rhythm by affecting Per transcription. Based on previous studies, we hypothesized that CoREST regulates circadian rhythm by regulating multiple histone modifiers at the Per locus. Genetic and physical interaction experiments supported these regulatory relationships. Moreover, through tissue-specific chromatin immunoprecipitation assays in clock neurons, we found that the CoREST mutation led to time-dependent changes in corresponding histone modifications at the Per locus. Finally, we proposed a model indicating the role of the CoREST complex in the regulation of circadian rhythm. This study revealed the dynamic changes of histone modifications at the Per locus specifically in clock neurons. Importantly, it provides insights into the role of epigenetic factors in the regulation of dynamic gene expression changes in circadian rhythm.
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  • 文章类型: Journal Article
    超级Afrotheria的Sirenians是第一批从陆地过渡到水的哺乳动物,并且是唯一的食草海洋哺乳动物。这里,我们产生了一个染色体水平的儒艮(Dugongdugon)基因组。将我们的组装与其他非洲基因组进行比较,揭示了Sirenians可能对水生生物进行分子适应,包括日常活动模式(昼夜节律)的变化以及通过碘化物转运蛋白NIS(SLC5A5)及其共同转运蛋白的变化介导的对高碘植物饮食的耐受性。功能性体外测定证实西伦氨基酸取代改变昼夜节律时钟蛋白PER2和NIS的性质。Sirenians显示了鲸类动物的外皮系统(皮肤及其附属物)基因的趋同回归的证据。我们的分析还发现了在现代环境中可能适应不良的基因丢失,包括Sirenian冷应激综合征的候选基因(KCNK18),可能在日常活动模式的进化转变过程中丢失。来自9个澳大利亚地点和功能上已灭绝的冲绳人口的基因组确认并确定了约10.7万年前在澳大利亚东海岸发生的遗传断裂,并提供了相关生态型的证据。并强调需要对全世界儒艮种群的全基因组重新测序数据进行保护和基因管理。
    Sirenians of the superorder Afrotheria were the first mammals to transition from land to water and are the only herbivorous marine mammals. Here, we generated a chromosome-level dugong (Dugong dugon) genome. A comparison of our assembly with other afrotherian genomes reveals possible molecular adaptations to aquatic life by sirenians, including a shift in daily activity patterns (circadian clock) and tolerance to a high-iodine plant diet mediated through changes in the iodide transporter NIS (SLC5A5) and its co-transporters. Functional in vitro assays confirm that sirenian amino acid substitutions alter the properties of the circadian clock protein PER2 and NIS. Sirenians show evidence of convergent regression of integumentary system (skin and its appendages) genes with cetaceans. Our analysis also uncovers gene losses that may be maladaptive in a modern environment, including a candidate gene (KCNK18) for sirenian cold stress syndrome likely lost during their evolutionary shift in daily activity patterns. Genomes from nine Australian locations and the functionally extinct Okinawan population confirm and date a genetic break ~10.7 thousand years ago on the Australian east coast and provide evidence of an associated ecotype, and highlight the need for whole-genome resequencing data from dugong populations worldwide for conservation and genetic management.
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  • 文章类型: Journal Article
    人体内的生理过程在大约24小时的周期中被调节,称为昼夜节律。适应环境变化。骨节律在骨骼发育中起关键作用,新陈代谢,矿化,和重塑过程。骨节律表现出细胞特异性,骨骼中的不同细胞显示各种时钟基因的表达。多种环境因素,包括光,喂养,锻炼,和温度,通过交感神经系统和各种激素影响骨骼昼夜节律。骨骼昼夜节律的破坏有助于骨骼疾病的发作,例如骨质疏松症,骨关节炎和骨骼发育不全。相反,当针对骨细胞的昼夜节律时,这些骨骼疾病可以得到有效治疗,包括时钟基因和药物靶标的节律表达。在这次审查中,我们描述了各种骨细胞生理活动中独特的昼夜节律。然后,我们总结了使骨骼昼夜节律与潜在机制同步的因素。根据审查,我们旨在全面了解骨骼昼夜节律,并总结骨骼疾病的新预防和治疗策略。
    Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.
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  • 文章类型: Journal Article
    组织特异性是影响许多生物过程的器官的基本属性。包括衰老和长寿,并且受生物钟的调节。然而,受昼夜节律影响的组织特异性和其他组织特异性之间的区别仍然知之甚少.这里,利用小鼠昼夜节律的多组学数据,我们发现约35%的组织特异性基因直接受到昼夜节律调节的影响.这些受昼夜节律影响的组织特异性基因具有较高的表达水平,并且与肝细胞中的代谢有关。它们还在长读段测序数据中表现出特定特征。值得注意的是,这些基因在基因水平和网络模块水平上都与衰老和寿命有关。这些基因的表达在热量限制喂养方案的反应中振荡,已被证明可以促进长寿。此外,衰老和长寿基因在各种昼夜节律紊乱中被破坏。我们的研究表明,受昼夜节律影响的组织特异性的调节对于理解在基因组水平上调节衰老和寿命的昼夜节律机制至关重要。
    Tissue specificity is a fundamental property of an organ that affects numerous biological processes, including aging and longevity, and is regulated by the circadian clock. However, the distinction between circadian-affected tissue specificity and other tissue specificities remains poorly understood. Here, using multi-omics data on circadian rhythms in mice, we discovered that approximately 35% of tissue-specific genes are directly affected by circadian regulation. These circadian-affected tissue-specific genes have higher expression levels and are associated with metabolism in hepatocytes. They also exhibit specific features in long-reads sequencing data. Notably, these genes are associated with aging and longevity at both the gene level and at the network module level. The expression of these genes oscillates in response to caloric restricted feeding regimens, which have been demonstrated to promote longevity. In addition, aging and longevity genes are disrupted in various circadian disorders. Our study indicates that the modulation of circadian-affected tissue specificity is essential for understanding the circadian mechanisms that regulate aging and longevity at the genomic level.
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  • 文章类型: Journal Article
    由于地球的自转,自然环境表现出接近24小时的明暗昼夜周期。为了适应这种能量摄入模式,生物体在很长一段时间内形成了24小时有节奏的昼夜循环,被称为昼夜节律,或生物钟。随着生物钟研究的逐步推进,越来越明显的是,昼夜节律的中断与2型糖尿病(T2D)的发生密切相关。为了进一步了解T2D和生物钟的研究进展,本文综述了生物钟与糖代谢的相关性,并分析了其潜在的作用机制。基于此,我们讨论了导致昼夜节律紊乱的潜在因素及其对发展为T2D的风险的影响,旨在为今后T2D的防治探索新的可能的干预措施。在明暗的昼夜节律下,为了适应这种变化,人体形成一个涉及多种基因的内部生物钟,蛋白质和其他分子。主要机制是以CLOCK/BMAL1异源二聚体为中心的转录-翻译反馈环。构成此环的重要生物钟基因的表达可以调节T2DM相关血糖性状如葡萄糖摄取,脂肪代谢,各种外周组织和器官的胰岛素分泌/胰高血糖素分泌和敏感性。此外,睡眠,光,昼夜节律下的饮食因素也影响着T2DM的发生。
    Due to the Earth\'s rotation, the natural environment exhibits a light-dark diurnal cycle close to 24 hours. To adapt to this energy intake pattern, organisms have developed a 24-hour rhythmic diurnal cycle over long periods, known as the circadian rhythm, or biological clock. With the gradual advancement of research on the biological clock, it has become increasingly evident that disruptions in the circadian rhythm are closely associated with the occurrence of type 2 diabetes (T2D). To further understand the progress of research on T2D and the biological clock, this paper reviews the correlation between the biological clock and glucose metabolism and analyzes its potential mechanisms. Based on this, we discuss the potential factors contributing to circadian rhythm disruption and their impact on the risk of developing T2D, aiming to explore new possible intervention measures for the prevention and treatment of T2D in the future. Under the light-dark circadian rhythm, in order to adapt to this change, the human body forms an internal biological clock involving a variety of genes, proteins and other molecules. The main mechanism is the transcription-translation feedback loop centered on the CLOCK/BMAL1 heterodimer. The expression of important circadian clock genes that constitute this loop can regulate T2DM-related blood glucose traits such as glucose uptake, fat metabolism, insulin secretion/glucagon secretion and sensitivity in various peripheral tissues and organs. In addition, sleep, light, and dietary factors under circadian rhythms also affect the occurrence of T2DM.
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  • 文章类型: Journal Article
    昼夜节律振荡系统在协调大多数生物体的代谢中起着关键作用。遗传效应的扰动和昼夜节律的失调导致昼夜节律功能障碍和代谢紊乱的迹象。进食-禁食周期可以作用于周围的生物钟,绕过光周期。因此,限时饮食(TRE)可以通过调整饮食节奏来改善代谢健康,通过在不同组织水平上重新编程昼夜节律基因组和代谢程序或重塑肠道微生物群实现的过程,与组学技术允许可视化的监管过程。这里,我们回顾了代谢昼夜节律调节的最新进展,重点关注TRE在挽救昼夜节律功能障碍和代谢紊乱以及肠道微生物群之间的贡献方面的潜在应用,并总结了组学技术的意义。
    Circadian oscillatory system plays a key role in coordinating the metabolism of most organisms. Perturbation of genetic effects and misalignment of circadian rhythms result in circadian dysfunction and signs of metabolic disorders. The eating-fasting cycle can act on the peripheral circadian clocks, bypassing the photoperiod. Therefore, time-restricted eating (TRE) can improve metabolic health by adjusting eating rhythms, a process achieved through reprogramming of circadian genomes and metabolic programs at different tissue levels or remodeling of the intestinal microbiota, with omics technology allowing visualization of the regulatory processes. Here, we review recent advances in circadian regulation of metabolism, focus on the potential application of TRE for rescuing circadian dysfunction and metabolic disorders with the contribution of intestinal microbiota in between, and summarize the significance of omics technology.
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