• Clinical Nutrition Research
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• 제12권1호
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• pp.7-20
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• 2023

Creating a complex balance between dietary composition, circadian rhythm, and the hemostasis control of energy is important for managing diseases. Therefore, we aimed to determine the interaction between cryptochrome circadian clocks 1 polymorphism and energy-adjusted dietary inflammatory index (E-DII) on high-sensitivity C-reactive protein in women with central obesity. This cross-sectional study recruited 220 Iranian women aged 18-45 with central obesity. The 147-item semi-quantitative food frequency questionnaire was used to assess the dietary intakes, and the E-DII score was calculated. Anthropometric and biochemical measurements were determined. By polymerase chain response-restricted length polymorphism method, cryptochrome circadian clocks 1 polymorphism was assigned. Participants were categorized into three groups based on the E-DII score, then categorized according to cryptochrome circadian clocks 1 genotypes. The mean and standard deviation of age, BMI, and high-sensitivity C-reactive protein (hs-CRP) were 35.61 ± 9.57 years, 30.97 ± 4.16 kg/m², and 4.82 ± 5.16 mg/dL, respectively. The interaction of the CG genotype and E-DII score had a significant association with higher hs-CRP level compared to GG genotype as the reference group (β, 1.19; 95% CI, 0.11-2.27; p value, 0.03). There was a marginally significant association between the interaction of the CC genotype and the E-DII score with higher hs-CRP level compared to the GG genotype as the reference group (β, 0.85; 95% CI, -0.15 to 1.86; p value, 0.05). There is probably positive interaction between CG, CC genotypes of cryptochrome circadian clocks 1, and E-DII score on the high-sensitivity C-reactive protein level in women with central obesity.

• 생명과학회지
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• 제28권8호
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• pp.985-991
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• 2018

생물시계(Biological clock)는 생명체에서 나타나는 반복되는 자율적인 리듬을 말하며, 단일세포는 물론 다세포 생명체의 기본적인 대사와 이에 따른 표현형과 행동을 직접적으로 조절하고 있다. 이러한 생물시계는 동면 리듬, 수면 리듬, 심장박동 리듬 및 짝짓기 노래 리듬 등 매우 다양하며, 24시간 이상의 주기를 infradian rhythm, 24시간 주기를 circadian rhythm, 24시간 이내의 짧은 주기를 ultradian rhythm으로 구분한다. 효모 Saccharomyces cerevisiae는 최소 5종 이상의 반복되는 자율적인 리듬이 알려져 있으며, 이중 일부는 생체시계로 인식되고 있다. 본 리뷰에서는 Saccharomyces cerevisiae의 glycolytic oscillation (T= 1~30분), cell cycle-dependent oscillation (T= 2~16 시간), ultradian metabolic oscillation (T= 15~50분), yeast colony oscillation (T= 수 시간) 및 circadian oscillation (T= 24시간)에 대한 연구 결과를 제시하고, 특히 ultradian metabolic oscillation의 특징, 집단 동조인자(population synchronizer), 동조인자의 조절 기작 및 효모 생물시계의 대사공학 분야의 이용성을 제시하여 효모를 이용한 동적 대사조절 및 생물시계 연구가 가능함을 제시하였다.

• Molecules and Cells
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• 제28권2호
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• pp.75-80
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• 2009

The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease. At the same time, metabolic processes feed back into the circadian clock, affecting clock gene expression and timing of behaviour. In this review, we summarize the experimental evidence for this bimodal interaction, with a focus on the molecular mechanisms mediating this exchange, and outline the implications for clock-based and metabolic diseases.

• Animal cells and systems
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• 제16권1호
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• pp.1-10
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• 2012

Most living organisms synchronize their physiological and behavioral activities with the daily changes in the environment using intrinsic time-keeping systems called circadian clocks. In mammals, the key molecular features of the internal clock are transcription- and translational-based negative feedback loops, in which clock-specific transcription factors activate the periodic expression of their own repressors, thereby generating the circadian rhythms. CLOCK and BMAL1, the basic helix-loop-helix (bHLH)/PAS transcription factors, constitute the positive limb of the molecular clock oscillator. Recent investigations have shown that various levels of posttranslational regulation work in concert with CLOCK/BMAL1 in mediating circadian and cellular stimuli to control and reset the circadian rhythmicity. Here we review how the CLOCK and BMAL1 activities are regulated by intracellular distribution, posttranslational modification, and the recruitment of various epigenetic regulators in response to circadian and cellular signaling pathways.

• BMB Reports
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• 제48권12호
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• pp.677-684
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• 2015

Cardiovascular function is regulated by the rhythmicity of circadian, infradian and ultradian clocks. Specific time scales of different cell types drive their functions: circadian gene regulation at hours scale, activation-inactivation cycles of ion channels at millisecond scales, the heart's beating rate at hundreds of millisecond scales, and low frequency autonomic signaling at cycles of tens of seconds. Heart rate and rhythm are modulated by a hierarchical clock system: autonomic signaling from the brain releases neurotransmitters from the vagus and sympathetic nerves to the heart's pacemaker cells and activate receptors on the cell. These receptors activating ultradian clock functions embedded within pacemaker cells include sarcoplasmic reticulum rhythmic spontaneous Ca²⁺ cycling, rhythmic ion channel current activation and inactivation, and rhythmic oscillatory mitochondria ATP production. Here we summarize the evidence that intrinsic pacemaker cell mechanisms are the end effector of the hierarchical brain-heart circadian clock system.

• 대한의생명과학회지
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• 제11권4호
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• pp.493-501
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• 2005

Circadian rhythms, time on a scale of about 24 hours, are present in a number of organisms including animals, plants, and bacteria. The control of the biochemical, physiological and behavioral processes is regulated by endogenous clocks in the suprachiasmatic nucleus (SCN). At the core of this timing mechanism is molecular machinery that are present both in the brain and in the peripheral tissues throughout the body, and even in a single cultured cell. In this study, we performed two-dimensional gel electrophoresis to figure out any correlation between protein expression patterns and the requirement of two canonical clock proteins, either mPER1 or mPER2, by comparing global protein expression profiles in livers from wildtype or mPer1/mPer2 double mutant mice. We could identify several differentially expressed protein candidates with respect to time and genotypes. Further analysis of these candidate proteins in detail in vivo will lead us to the better understanding of how circadian clock functions in mammals.

• Molecules and Cells
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• 제40권7호
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• pp.450-456
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• 2017

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-$erb{\alpha}$ induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

• Molecules and Cells
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• 제42권4호
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• pp.301-312
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• 2019

Post-transcriptional regulation underlies the circadian control of gene expression and animal behaviors. However, the role of mRNA surveillance via the nonsense-mediated mRNA decay (NMD) pathway in circadian rhythms remains elusive. Here, we report that Drosophila NMD pathway acts in a subset of circadian pacemaker neurons to maintain robust 24 h rhythms of free-running locomotor activity. RNA interference-mediated depletion of key NMD factors in timeless-expressing clock cells decreased the amplitude of circadian locomotor behaviors. Transgenic manipulation of the NMD pathway in clock neurons expressing a neuropeptide PIGMENT-DISPERSING FACTOR (PDF) was sufficient to dampen or lengthen free-running locomotor rhythms. Confocal imaging of a transgenic NMD reporter revealed that arrhythmic Clock mutants exhibited stronger NMD activity in PDF-expressing neurons than wild-type. We further found that hypomorphic mutations in Suppressor with morphogenetic effect on genitalia 5 (Smg5) or Smg6 impaired circadian behaviors. These NMD mutants normally developed PDF-expressing clock neurons and displayed daily oscillations in the transcript levels of core clock genes. By contrast, the loss of Smg5 or Smg6 function affected the relative transcript levels of cAMP response element-binding protein B (CrebB) in an isoform-specific manner. Moreover, the overexpression of a transcriptional repressor form of CrebB rescued free-running locomotor rhythms in Smg5-depleted flies. These data demonstrate that CrebB is a rate-limiting substrate of the genetic NMD pathway important for the behavioral output of circadian clocks in Drosophila.

• Clinical and Experimental Reproductive Medicine
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• 제46권2호
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• pp.76-86
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• 2019

Objective: This study was performed to explore the possibility that each oocyte and its surrounding cumulus cells might have different genetic expression patterns that could affect human reproduction. Methods: Differential gene expression analysis was performed for 10 clusters of cumulus cells obtained from 10 cumulus-oocyte complexes from 10 patients. Same procedures related to oocyte maturation, microinjection, and microarray analyses were performed for each group of cumulus cells. Two differential gene expression analyses were performed: one for the outcome of clinical pregnancy and one for the outcome of live birth. Results: Significant genes resulting from these analyses were selected and the top 20 affected pathways in each group were analyzed. Circadian entrainment is determined to be the most affected pathway for clinical pregnancy, and proteoglycans in cancer pathway is the most affected pathway for live birth. Circadian entrainment is also amongst the 12 pathways that are found to be in top 20 affected pathways for both outcomes, and has both lowest p-value and highest number of times found count. Conclusion: Although further confirmatory studies are necessary, findings of this study suggest that these pathways, especially circadian entrainment in cumulus cells, may be essential for embryo development and pregnancy.