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The Importance of Molecular Circadian Rhythms in Health and Disease
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The Importance of Molecular Circadian Rhythms in Health and Disease

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

Deadline for manuscript submissions: 20 December 2025 | Viewed by 3298

Special Issue Editors

Dr. Telma Quintela

E-Mail Website
Guest Editor
CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
Interests: circadian rhythm; blood-cerebrospinal fluid barrier; drug delivery; chronotherapy
Special Issues, Collections and Topics in MDPI journals
Dr. Diana Rita Barata Costa

E-Mail Website
Guest Editor
CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
Interests: circadian rhythm; nanoformulations; drug delivery; chronotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

A variety of an organism’s behaviors and physiological and biochemical processes occur across a span of 24 hours. A diverse range of species developed an internal time keeping system that allows the organisms to better adapt to daily variations, known as the biological clock system. On a molecular level, this clock, present in almost every tissue in mammals, is based on an autoregulatory transcription–translation feedback loop comprising clock genes/proteins. From sleep–wake cycles to hormone secretion or even foraging and activity schedules, many biological functions are associated with this scale of rhythmicity. Recently, it has been recognized that circadian rhythms play important roles in both daily physiological processes and disease mechanisms, namely cancer and neurodegenerative disorders. In fact, the dysfunction or misalignment of the circadian clock can increase the risk of disease and influence treatment responses.

Thus, this Special Issue will focus on elucidating body clocks and clock dysregulation. In addition, it intends to highlight novel findings on molecular clock manipulation in order to prevent and treat diseases.

Dr. Telma Quintela
Dr. Diana Rita Barata Costa
Guest Editors

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

  • molecular clock
  • circadian dysfunction
  • health
  • chronotherapy
  • circadian rhythms

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Published Papers (3 papers)

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22 pages, 1990 KiB  
Article
Circadian-Tuned Peptide Drug/Gene Co-Delivery Nanocomplexes to Enhance Glioblastoma Targeting and Transfection
by Ana R. Neves, Eric Vivès, Prisca Boisguérin, Telma Quintela and Diana Costa
Int. J. Mol. Sci. 2025, 26(13), 6130; https://doi.org/10.3390/ijms26136130 - 26 Jun 2025
Viewed by 221
Abstract
Glioblastoma is the most prevalent and aggressive form of brain malignancy. Actual treatments face several challenges due to its high aggressiveness and poor prognosis. The chemotherapeutic agent temozolomide (TMZ) has limited therapeutic efficacy, and mutations in the tumour protein p53 gene (TP53 [...] Read more.
Glioblastoma is the most prevalent and aggressive form of brain malignancy. Actual treatments face several challenges due to its high aggressiveness and poor prognosis. The chemotherapeutic agent temozolomide (TMZ) has limited therapeutic efficacy, and mutations in the tumour protein p53 gene (TP53) have been associated with treatment resistance. Thus, this study aimed to explore an innovative therapeutic strategy to enhance treatment efficacy of GBM. Previously, our team had developed a WRAP5 cell-penetrating peptide (CPP) functionalized with a transferrin receptor ligand (Tf) for the targeted delivery of TMZ and a p53-encoding plasmid to glioma cells. Our research had elucidated the circadian oscillations of the clock genes in the U87 glioma cells by employing two different computational models and observed that T16 and T8 time points revealed the highest circadian activity for Bmal1 and Per2 genes, respectively. Similar analysis was conducted for the transferrin receptor, which revealed that T7 and T8 were the key time points for its expression. A confocal microscopy study indicated the highest intracellular uptake of complexes and p53 mRNA expression at T8, the time point with the highest Per2 and transferrin receptor expression. Following mRNA analysis, the evaluation of p53 levels confirmed transcriptional changes at the protein level, and that T16 appears to be a favourable time point for enhancing therapeutic efficacy in U87 glioblastoma cells. These findings suggested that synchronizing the complexes’ administration with the biological clock of GBM cells may significantly improve glioblastoma therapeutics. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
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Review

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22 pages, 332 KiB  
Review
Circadian Disruption and Sleep Disorders in Astronauts: A Review of Multi-Disciplinary Interventions for Long-Duration Space Missions
by Hongjie Zong, Yifei Fei and Ningang Liu
Int. J. Mol. Sci. 2025, 26(11), 5179; https://doi.org/10.3390/ijms26115179 - 28 May 2025
Viewed by 566
Abstract
As humanity advances into deep space exploration, astronauts on long-duration missions face significant challenges posed by circadian rhythm disruptions and sleep disorders, which arise from extreme environmental stressors such as microgravity, ionizing radiation, and operational workload. These disruptions not only compromise physiological and [...] Read more.
As humanity advances into deep space exploration, astronauts on long-duration missions face significant challenges posed by circadian rhythm disruptions and sleep disorders, which arise from extreme environmental stressors such as microgravity, ionizing radiation, and operational workload. These disruptions not only compromise physiological and psychological health but also impair cognitive function and mission-critical performance. In this review, we summarized established countermeasures encompassing pharmacological interventions, light-based circadian regulation, and work–rest schedule optimization alongside innovative approaches such as gut microbiota modulation and traditional Chinese medicine. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
31 pages, 1937 KiB  
Review
Chrononutrition: Potential, Challenges, and Application in Managing Obesity
by Siti Aisyah Fuad, Rehna Paula Ginting and Min-Woo Lee
Int. J. Mol. Sci. 2025, 26(11), 5116; https://doi.org/10.3390/ijms26115116 - 26 May 2025
Viewed by 1340
Abstract
The circadian clock orchestrates nearly every aspect of physiology, aligning metabolic processes with environmental cues, such as light and food intake. While the central pacemaker in the suprachiasmatic nucleus synchronizes peripheral clocks across key metabolic tissue, feeding behavior emerges as the dominant cue [...] Read more.
The circadian clock orchestrates nearly every aspect of physiology, aligning metabolic processes with environmental cues, such as light and food intake. While the central pacemaker in the suprachiasmatic nucleus synchronizes peripheral clocks across key metabolic tissue, feeding behavior emerges as the dominant cue for peripheral clock alignment. This interaction reveals a crucial link between circadian biology and metabolism. Disruption of these processes, whether from shift work, irregular eating patterns or lifestyle misalignment, has been strongly associated with metabolic disorders, including obesity, insulin resistance and cardiometabolic diseases. Within the field of chrononutrition, strategies, such as time-restricted feeding (TRF), have gained attention for their potential to restore circadian alignment and improve metabolic health. However, translational gaps persist, as most mechanistic insights are derived from nocturnal murine models, limiting their applicability to diurnal human physiology. Moreover, human studies are confounded by interindividual variability in chronotype, behavioral patterns, and dietary compliance. This review explores the molecular underpinnings of zeitgeber signals and critically assesses the translational barriers to implementing chrononutrition across species. By integrating insights from both preclinical and clinical research, we aim to refine the potential of circadian-based dietary interventions for metabolic disease prevention and personalized nutrition. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
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