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Molecular Research in Circadian Rhythm and Cellular Synchrony

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 17997

Special Issue Editor


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Guest Editor
School of Sport and Health Sciences, University of Central Lancashire, Preston PR1 2HE, UK
Interests: metabolic syndrome; insulin resistance; obesity; tyep-2 diabetes; metabolic inflammation; chrononutrition; molecular nutrition
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Special Issue Information

Dear Colleagues,

The circadian clock coordinates biochemical, physiological, and behavioural processes in every living organism. As Albert Einstein said, "The only reason for time is so that everything doesn't happen at once", the internal timekeeping mechanisms operate at the cell, organ/tissue and organism levels ensure temporal separation of the molecular events.

An essential outcome of the circadian regulatory process is achieving cellular synchrony that influences the collective outcome of the cellular response. The cellular response to a variety of stimuli is more efficient in a population of synchronized than asynchronized cells. It may be hypothesized that any inefficiency of managing oxidative stresses and inflammatory responses, the two hallmarks of most non-communicable diseases, underly the phenomenon of cellular asynchrony.

The mammalian circadian clock's three distinct hierarchical levels (the central clock in the suprachiasmatic centre, the peripheral clocks of organs/tissues and the clock gene system at the cell level) enable constant interaction with the environmental cues (zeitgebers). While the role of photic zeitgebers in setting the biological rhythm is widely investigated, non-photic zeitgebers, particularly the dietary ingredients (nutrients and non-nutrients), has just started to unfurl.

Dietary polyphenols are powerful zeitgebers that can directly influence the circadian clock system (regulation of the clock genes) and/or indirectly (via gut microflora). Understanding the bi-directional interaction between dietary ingredients and central and peripheral clocks and clock genes may pave the way for developing novel strategies for preventing, managing, and treating non-communicable diseases.

This Special Issue of Molecular Sciences will showcase original research on the regulation of the mammalian circadian clock by various zeitgebers, including dietary bioactive molecules in the context of non-communicable disease models.

Topics of interest to this Special Issue include but are not limited to:
1. The interaction of the master clock, peripheral clock and clock genes with the nutrient and non-nutrients bioactive molecules
2. Nutraceuticals (polyphenols), the metabolites and gut microbiome in the regulation of circadian clock system, cellular synchrony and molecular entrainment
3. Regulation of cell synchrony in different biological models by various stimuli including hormonal (melatonin, cortisol), nutritional, xenobiotics, drugs, toxins etc.
4. Molecular pathways of clock gene in energy homeostasis, satiety and hunger-energy mechanisms, insulin resistance and diabetes, neurodegenerative diseases, ageing and cancers.
5. Biomarkers for the assessment of the state of circadian rhythm at the three hierarchical levels

In addition, review articles on the exploration of pharmacological and nutritional approaches targeting the circadian clock for the prevention and treatment of non-communicable disease are also welcomed.

Dr. Bojlul Bahar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • circadian clock
  • cell synchrony
  • bioactive
  • polyphenol
  • oxidative stress
  • metabolic syndrome

Published Papers (6 papers)

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Research

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15 pages, 1467 KiB  
Article
Disruption of the Expression of the Placental Clock and Melatonin Genes in Preeclampsia
by Aïssatou Bailo Diallo, Benjamin Coiffard, Raoul Desbriere, Maria Katsogiannou, Xavier Donato, Florence Bretelle, Soraya Mezouar and Jean-Louis Mege
Int. J. Mol. Sci. 2023, 24(3), 2363; https://doi.org/10.3390/ijms24032363 - 25 Jan 2023
Cited by 5 | Viewed by 1917
Abstract
Circadian rhythms have been described in numerous tissues of living organisms and are necessary for homeostasis. The understanding of their role in normal and pathological pregnancy is only just emerging. It has been established that clock genes are expressed in the placenta of [...] Read more.
Circadian rhythms have been described in numerous tissues of living organisms and are necessary for homeostasis. The understanding of their role in normal and pathological pregnancy is only just emerging. It has been established that clock genes are expressed in the placenta of animals and humans, but the rhythmicity of placenta immune cells is not known. Macrophages from healthy placenta of women at term were isolated and the expression of clock genes BMAL1, CLOCK, PER2, CRY2, and NR1D1 was assessed by qRT-PCR every 4 h over 24 h. Raw data were treated with cosinor analysis to evaluate the significance of the oscillations. Placental macrophages exhibited significant circadian expression of clock genes but one third of placental macrophages lost clock gene rhythmicity; the clock gene oscillations were restored by co-culture with trophoblasts. We wondered if melatonin, a key hormone regulating circadian rhythm, was involved in the oscillations of placental cells. We showed that macrophages and trophoblasts produced melatonin and expressed MT2 receptor. In women who developed preeclampsia during pregnancy, circadian oscillations of placental macrophages were lost and could not be rescued by coculture with trophoblasts from healthy women. Moreover, production and oscillations of melatonin were altered in preeclamptic macrophages. For the first time to our knowledge, this study shows circadian rhythms and melatonin production by placental macrophages. It also shows that preeclampsia is associated with a disruption of the circadian rhythm of placental cells. These results represent a new scientific breakthrough that may contribute to the prevention and treatment of obstetrical pathologies. Full article
(This article belongs to the Special Issue Molecular Research in Circadian Rhythm and Cellular Synchrony)
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15 pages, 28804 KiB  
Article
Per1/Per2 knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis
by Ruyi He, Shijie Zhang, Jiale Yu, Xiaojie Yu, Jian Wang, Yi Qiu, Wenting Zhou, Fangyi Wang, Feng Ren and Zhiguo Liu
Int. J. Mol. Sci. 2022, 23(21), 12962; https://doi.org/10.3390/ijms232112962 - 26 Oct 2022
Cited by 4 | Viewed by 2000
Abstract
Disturbances in circadian rhythms are known to affect immune functions. However, the long-term impact of abnormal circadian rhythms on the immune-related functions of the spleen are poorly understood. Hence, we aimed to investigate the immune-related functions of spleen in Per1/Per2 double-knockout (DKO) and [...] Read more.
Disturbances in circadian rhythms are known to affect immune functions. However, the long-term impact of abnormal circadian rhythms on the immune-related functions of the spleen are poorly understood. Hence, we aimed to investigate the immune-related functions of spleen in Per1/Per2 double-knockout (DKO) and wild-type (WT) mice aged 4, 9, and 14 months. Compared to the WT mice, the DKO mice had smaller spleen white pulp (WP) and lymphocyte germinal area, as well as fewer immune cells with age—these differences were especially clear. The spleen lymphocyte mortality, malondialdehyde (MDA) levels, reactive oxygen species (ROS) levels, and ferritin-binding receptor (TFR1) levels were significantly higher in the 14-month-old DKO mice than in WT mice of the same age. Transcriptome analysis showed that most of the differentially expressed mRNAs were enriched in DNA damage repair-related pathways. In DKO mice, spleen cells showed up-regulation of pro-ferroptosis genes, such as Cd36,Atm, and Acsl4, and down-regulation of anti-ferroptosis genes, such as GPX4. We found that long-term abnormalities in the circadian rhythm can induce DNA damage and ferroptosis in mouse spleen. Full article
(This article belongs to the Special Issue Molecular Research in Circadian Rhythm and Cellular Synchrony)
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14 pages, 2634 KiB  
Article
Per1/Per2 Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice
by Qinrui Liu, Hu Wang, Hualin Wang, Na Li, Ruyi He and Zhiguo Liu
Int. J. Mol. Sci. 2022, 23(13), 7399; https://doi.org/10.3390/ijms23137399 - 2 Jul 2022
Cited by 5 | Viewed by 2295
Abstract
Circadian rhythm disorders caused by genetic or environmental factors lead to decreased male fertility but the mechanisms are poorly understood. The current study reports that the mechanism of Per1/Per2 Double knockout (DKO) reduced the reproductive capacity of elderly male mice. The sperm motility [...] Read more.
Circadian rhythm disorders caused by genetic or environmental factors lead to decreased male fertility but the mechanisms are poorly understood. The current study reports that the mechanism of Per1/Per2 Double knockout (DKO) reduced the reproductive capacity of elderly male mice. The sperm motility and spermatogenic capacity of male DKO mice were weak. Hormone-targeted metabolomics showed reduced plasma levels of free testosterone in DKO male mice compared with WT male mice. Transcriptomic analysis of testicular tissue showed the down-regulation of testosterone synthesis-related enzymes (Cyp11a1, Cyp17a1, Hsd17b3, Hsd3b1, and Star) in the steroid hormone synthesis pathway. Spermatogenesis genes, Tubd1 and Pafah1b were down-regulated, influencing tubulin dynamics and leading to impaired motility. Seleno-compound metabolic loci, Scly and Sephs2, were up-regulated and Slc7a11 and Selenop were down-regulated. Western-blotting showed that steroid acute regulatory protein (StAR) and p-CREB, PKA and AC1 were reduced in testicular tissue of DKO mice compared to WT. Therefore, Per1/Per2 disruption reduced testosterone synthesis and sperm motility by affecting the PKA-StAR pathway, leading to decreased fertility. Full article
(This article belongs to the Special Issue Molecular Research in Circadian Rhythm and Cellular Synchrony)
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Review

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18 pages, 1112 KiB  
Review
Hair Follicles as a Critical Model for Monitoring the Circadian Clock
by Li-Ping Liu, Meng-Huan Li and Yun-Wen Zheng
Int. J. Mol. Sci. 2023, 24(3), 2407; https://doi.org/10.3390/ijms24032407 - 26 Jan 2023
Cited by 7 | Viewed by 3000
Abstract
Clock (circadian) genes are heterogeneously expressed in hair follicles (HFs). The genes can be modulated by both the central circadian system and some extrinsic factors, such as light and thyroid hormones. These circadian genes participate in the regulation of several physiological processes of [...] Read more.
Clock (circadian) genes are heterogeneously expressed in hair follicles (HFs). The genes can be modulated by both the central circadian system and some extrinsic factors, such as light and thyroid hormones. These circadian genes participate in the regulation of several physiological processes of HFs, including hair growth and pigmentation. On the other hand, because peripheral circadian genes are synchronized with the central clock, HFs could provide a noninvasive and practical method for monitoring and evaluating multiple circadian-rhythm-related conditions and disorders among humans, including day and night shifts, sleep–wake disorders, physical activities, energy metabolism, and aging. However, due to the complexity of circadian biology, understanding how intrinsic oscillation operates using peripheral tissues only may be insufficient. Combining HF sampling with multidimensional assays such as detection of body temperature, blood samples, or certain validated questionnaires may be helpful in improving HF applications. Thus, HFs can serve as a critical model for monitoring the circadian clock and can help provide an understanding of the potential mechanisms of circadian-rhythm-related conditions; furthermore, chronotherapy could support personalized treatment scheduling based on the gene expression profile expressed in HFs. Full article
(This article belongs to the Special Issue Molecular Research in Circadian Rhythm and Cellular Synchrony)
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31 pages, 852 KiB  
Review
Role of Omega-3 Fatty Acids as Non-Photic Zeitgebers and Circadian Clock Synchronizers
by Ana Checa-Ros and Luis D’Marco
Int. J. Mol. Sci. 2022, 23(20), 12162; https://doi.org/10.3390/ijms232012162 - 12 Oct 2022
Cited by 4 | Viewed by 2912
Abstract
Omega-3 fatty acids (ω-3 FAs) are well-known for their actions on immune/inflammatory and neurological pathways, functions that are also under circadian clock regulation. The daily photoperiod represents the primary circadian synchronizer (‘zeitgeber’), although diverse studies have pointed towards an influence of dietary FAs [...] Read more.
Omega-3 fatty acids (ω-3 FAs) are well-known for their actions on immune/inflammatory and neurological pathways, functions that are also under circadian clock regulation. The daily photoperiod represents the primary circadian synchronizer (‘zeitgeber’), although diverse studies have pointed towards an influence of dietary FAs on the biological clock. A comprehensive literature review was conducted following predefined selection criteria with the aim of updating the evidence on the molecular mechanisms behind circadian rhythm regulation by ω-3 FAs. We collected preclinical and clinical studies, systematic reviews, and metanalyses focused on the effect of ω-3 FAs on circadian rhythms. Twenty animal (conducted on rodents and piglets) and human trials and one observational study providing evidence on the regulation of neurological, inflammatory/immune, metabolic, reproductive, cardiovascular, and biochemical processes by ω-3 FAs via clock genes were discussed. The evidence suggests that ω-3 FAs may serve as non-photic zeitgebers and prove therapeutically beneficial for circadian disruption-related pathologies. Future work should focus on the role of clock genes as a target for the therapeutic use of ω-3 FAs in inflammatory and neurological disorders, as well as on the bidirectional association between the molecular clock and ω-3 FAs. Full article
(This article belongs to the Special Issue Molecular Research in Circadian Rhythm and Cellular Synchrony)
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24 pages, 1588 KiB  
Review
A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer’s Disease
by Xuemin Peng, Rongping Fan, Lei Xie, Xiaoli Shi, Kun Dong, Shujun Zhang, Jing Tao, Weijie Xu, Delin Ma, Juan Chen and Yan Yang
Int. J. Mol. Sci. 2022, 23(1), 504; https://doi.org/10.3390/ijms23010504 - 3 Jan 2022
Cited by 25 | Viewed by 4653
Abstract
Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer’s disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we [...] Read more.
Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer’s disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we review the relationship among circadian rhythm disruption, T2DM and AD, and suggest that the occurrence and progression of T2DM and AD may in part be associated with circadian disruption. Then, we summarize the promising therapeutic strategies targeting circadian dysfunction for T2DM and AD, including pharmacological treatment such as melatonin, orexin, and circadian molecules, as well as non-pharmacological treatments like light therapy, feeding behavior, and exercise. Full article
(This article belongs to the Special Issue Molecular Research in Circadian Rhythm and Cellular Synchrony)
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