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Crosstalk between Circadian Rhythm and Diseases 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 11681

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Special Issue Editor

Dr. Fuyuki Sato

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Guest Editor

Department of Diagnostic Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka Prefecture 411-8777, Japan
Interests: crosstalk between circadian rhythm and tumor progression; pathological analysis in human and mouse tissues; functional analysis of DEC1 and DEC2 in tumor progression; molecular pathways of DEC1 and DEC2; crosstalk between basic and clinical research, involving clock genes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Circadian rhythm is dominantly regulated by clock genes. Recent evidence suggests that the clock genes CLOCK, BMAL1/2, DEC1/2, PER1/2/3, and CRY1/2 play important roles in tumor progression, metabolism, immune responses, and sleep disorders by regulating apoptosis-related factors, cell cycle regulators, and inflammatory factors. On the other hand, various kinds of stress, such as hypoxia, inflammation, and anti-tumor drugs, affect the expression of clock genes. Therefore, clock genes have multiple functions in vivo that are associated with various kinds of diseases. Our aim is to improve the understanding of crosstalk between circadian rhythms, clock genes, and diseases to allow the development of strategies to overcome diseases, involving clock gene abnormalities. We encourage the submission of original articles and reviews involving circadian rhythm/clock genes and diseases.

Topics include, but are not limited to the following:

Relevant circadian rhythm/clock genes and diseases
Molecular pathways of clock genes, involving tumor progression, metabolism, inflammation, etc.
Functional analyses of clock genes in mouse models

You may choose our Joint Special Issue in Clocks & Sleep.

Dr. Fuyuki Sato
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 rhythm
clock genes
tumor progression
metabolism
immune response
inflammation
molecular pathway

Published Papers (4 papers)

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Research

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15 pages, 4024 KiB

Open AccessArticle

Sex- and Neuropsychiatric-Dependent Circadian Alterations in Daily Voluntary Physical Activity Engagement and Patterns in Aged 3xTg-AD Mice

by Daniel Alveal-Mellado, Lidia Castillo-Mariqueo and Lydia Giménez-Llort

Int. J. Mol. Sci. 2022, 23(22), 13671; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213671 - 08 Nov 2022

Viewed by 1204

Abstract

Alzheimer’s disease (AD) patients suffer from circadian rhythm alterations affecting their daily physical activity patterns with less willingness to perform a voluntary exercise. In preclinical studies, there is no clarity on whether animal models of AD can replicate these impairments. Here, we provide a proof of concept of the performance and behavioral effects of four weeks of voluntary wheel running (VWR) in a group of 14-month-old male and female 3xTg-AD mice at advanced stages of AD and the daily variance (behavioral circadian rhythmicity) of VWR associated with sex and their neuropsychiatric-like phenotype. Higher levels of horizontal exploration in the open field (OF) test were found in mice submitted to exercise. A linear mixed effect model showed significant sex-dependent differences in the VWR activity performed on the first night of follow-up, with high-NIBI males running less than high-NIBI females. Thus, an influence of NPS-like symptoms on the circadian patterns of VWR may account for such differences. In addition, males remained more active than females during diurnal periods. We hypothesize that this increment in energy expenditure during resting periods may be related to hyperactive behavior, similar to that observed in humans’ exacerbated agitation or sundowning behavior. These findings support the usage of the 3xTg-AD mouse as a reliable model for studying circadian rhythm alterations in AD and, at the translational level, the importance of tailored and individualized physical activity programs in clinical settings. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases 2.0)

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20 pages, 4335 KiB

Open AccessArticle

SOX2 Regulates Neuronal Differentiation of the Suprachiasmatic Nucleus

by Arthur H. Cheng, Samuel W. Fung, Sara Hegazi, Osama Hasan Mustafa Hasan Abdalla and Hai-Ying Mary Cheng

Int. J. Mol. Sci. 2022, 23(1), 229; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010229 - 26 Dec 2021

Cited by 2 | Viewed by 3491

Abstract

In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment to the environmental light/dark cycle. The neurons that comprise the SCN are anatomically and functionally heterogeneous, but despite their physiological importance, little is known about the pathways that guide their specification and differentiation. Here, we report that the stem/progenitor cell transcription factor, Sex determining region Y-box 2 (Sox2), is required in the embryonic SCN to control the expression of SCN-enriched neuropeptides and transcription factors. Ablation of Sox2 in the developing SCN leads to downregulation of circadian neuropeptides as early as embryonic day (E) 15.5, followed by a decrease in the expression of two transcription factors involved in SCN development, Lhx1 and Six6, in neonates. Thymidine analog-retention assays revealed that Sox2 deficiency contributed to reduced survival of SCN neurons during the postnatal period of cell clearance, but did not affect progenitor cell proliferation or SCN specification. Our results identify SOX2 as an essential transcription factor for the proper differentiation and survival of neurons within the developing SCN. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases 2.0)

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Figure 1

13 pages, 3550 KiB

Open AccessArticle

Expression Patterns of Clock Gene mRNAs and Clock Proteins in Human Psoriatic Skin Samples

by Viktória Németh, Szabina Horváth, Ágnes Kinyó, Rolland Gyulai and Zsuzsanna Lengyel

Int. J. Mol. Sci. 2022, 23(1), 121; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010121 - 23 Dec 2021

Cited by 7 | Viewed by 3116

Abstract

Psoriasis is a systemic inflammatory skin disorder that can be associated with sleep disturbance and negatively influence the daily rhythm. The link between the pathomechanism of psoriasis and the circadian rhythm has been suggested by several previous studies. However, there are insufficient data on altered clock mechanisms in psoriasis to prove these theories. Therefore, we investigated the expression of the core clock genes in human psoriatic lesional and non-lesional skin and in human adult low calcium temperature (HaCaT) keratinocytes after stimulation with pro-inflammatory cytokines. Furthermore, we examined the clock proteins in skin biopsies from psoriatic patients by immunohistochemistry. We found that the clock gene transcripts were elevated in psoriatic lesions, especially in non-lesional psoriatic areas, except for rev-erbα, which was consistently downregulated in the psoriatic samples. In addition, the REV-ERBα protein showed a different epidermal distribution in non-lesional skin than in healthy skin. In cytokine-treated HaCaT cells, changes in the amplitude of the bmal1, cry1, rev-erbα and per1 mRNA oscillation were observed, especially after TNFα stimulation. In conclusion, in our study a perturbation of clock gene transcripts was observed in uninvolved and lesional psoriatic areas compared to healthy skin. These alterations may serve as therapeutic targets and facilitate the development of chronotherapeutic strategies in the future. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases 2.0)

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Review

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24 pages, 12871 KiB

Open AccessReview

Death of a Protein: The Role of E3 Ubiquitin Ligases in Circadian Rhythms of Mice and Flies

by Osama Hasan Mustafa Hasan Abdalla, Brittany Mascarenhas and Hai-Ying Mary Cheng

Int. J. Mol. Sci. 2022, 23(18), 10569; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810569 - 12 Sep 2022

Cited by 2 | Viewed by 3050

Abstract

Circadian clocks evolved to enable organisms to anticipate and prepare for periodic environmental changes driven by the day–night cycle. This internal timekeeping mechanism is built on autoregulatory transcription–translation feedback loops that control the rhythmic expression of core clock genes and their protein products. The levels of clock proteins rise and ebb throughout a 24-h period through their rhythmic synthesis and destruction. In the ubiquitin–proteasome system, the process of polyubiquitination, or the covalent attachment of a ubiquitin chain, marks a protein for degradation by the 26S proteasome. The process is regulated by E3 ubiquitin ligases, which recognize specific substrates for ubiquitination. In this review, we summarize the roles that known E3 ubiquitin ligases play in the circadian clocks of two popular model organisms: mice and fruit flies. We also discuss emerging evidence that implicates the N-degron pathway, an alternative proteolytic system, in the regulation of circadian rhythms. We conclude the review with our perspectives on the potential for the proteolytic and non-proteolytic functions of E3 ubiquitin ligases within the circadian clock system. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases 2.0)

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