Clocks & Sleep, Volume 7, Issue 3 (September 2025) – 9 articles

The circadian clock is a self-sustaining oscillator with a period of approximately 24 h, enabling organisms to anticipate daily recurring events, such as sunrise and sunset. Since the circadian period is not exactly 24 h and the environmental day length varies throughout the year, the clock must be periodically reset to align an organism’s physiology with the natural light/dark cycle. This synchronization, known as entrainment, is primarily regulated by nocturnal light, which can be replicated in laboratory settings using a 15 min light pulse (LP) and by assessing locomotor activity. An LP during the early part of the dark phase delays the onset of locomotor activity, resulting in a phase delay, whereas an LP in the late dark phase advances activity onset, causing a phase advance. The clock gene Period 2 (Per2) plays a key role in this process. To investigate its contributions, we examined the effects of Per2 deletion in neurons versus astrocytes using glia-specific GPer2 (Per2/GfapCre) knockout (KO) and neuronal-specific NPer2KO (Per2/NesCre) mice. All groups were subjected to Aschoff type II protocol, where an LP was applied at ZT14 or ZT22 and the animals were released into constant darkness. As control, no LP was applied. Phase shift, period, amplitude, total activity count, and rhythm instability were assessed. Our findings revealed that mice lacking Per2 in neurons (NPer2) exhibited smaller phase delays and larger phase advances compared to control animals. In contrast, mice with Per2 deletion specifically in glial cells including astrocytes (GPer2) displayed normal clock resetting. Interestingly, the absence of Per2 in either of the cell types resulted in a shorter circadian period compared to control animals. These results suggest that astrocytic Per2 is important for maintaining the circadian period but is not required for phase adaptation to light stimuli. Full article

Burnout syndrome is characterized mainly by three criteria (emotional exhaustion, depersonalization, and low personal accomplishment), and further exacerbated by night shift work, with profound implications for individual and societal well-being. The Maslach Burnout Inventory survey applied to 97 medical care professionals (with day and night work) revealed different scores for these criteria. Blood metabolic profiles were obtained by UHPLC-QTOF-ESI⁺-MS untargeted metabolomics and multivariate statistics using the Metaboanalyst 6.0 platform. The Partial Least Squares Discrimination scores and VIP values, Random Forest graphs, and Heatmaps, based on 99 identified metabolites, were complemented with Biomarker Analysis (AUC ranking) and Pathway Analysis of metabolic networks. The data obtained reflected the biochemical implications of night shift work and correlated with each criterion’s burnout scores. Four main metabolic pathways with important consequences in burnout were affected, namely lipid metabolism, especially steroid hormone synthesis and cortisol, the energetic mitochondrial metabolism involving acylated carnitines, fatty acids, and phospholipids as well polar metabolites’ metabolism, e.g., catecholamines (noradrenaline, acetyl serotonin), and some amino acids (tryptophan, tyrosine, aspartate, arginine, valine, lysine). These metabolic profiles suggest potential strategies for managing burnout levels in healthcare professionals, based on validated criteria, including night shift work management. Full article

Morningness-eveningness is usually assessed as either a trait or a state using either a morning–evening preference scale or sleep timing reported for free days, respectively. These assessments were implemented in numerous studies exploring the associations between morningness-eveningness and health, mood, and sleep problems. Evening types almost always had more problems than morning types. We examined these associations in university students with conflicting results of trait and state assessments of morningness-eveningness and tried to confirm their chronotype using a multidimensional chronotyping approach that recognizes four types other than morning and evening (lethargic, vigilant, napping, and afternoon). The conflicting trait and state assessments of morningness-eveningness were found in 141 of 1582 students. Multidimensional chronotyping supported morningness of morning types with late weekend sleep timing, and the associations with health, mood, and sleep problems resembled the associations of other morning types (i.e., these associations persisted despite late sleep timing). In contrast, evening types with early weekend sleep timing were more likely classified as lethargic or napping types rather than evening types. They did not resemble evening types in their associations with health, mood, and sleep problems (i.e., early sleep timing did not change these associations). Model-based simulations of the sleep–wake cycles of students with conflicting trait and state assessments suggested that their bedtimes cannot be solely determined by their biological clocks. On weekdays or weekends, mind-bedtime procrastination can lead to missing the bedtime signal from their biological clocks (i.e., self-deprivation of sleep or, in other words, voluntary prolongation of the wake phase of the sleep–wake cycle). Full article

Worsening adolescent mental health is a significant social issue. Although dreams may reflect one’s mental state, few studies have focused on adolescents. Therefore, this study investigated the relationship between dream content and mental health, specifically anxiety disorder and depressive symptoms, among Japanese adolescents. This cross-sectional study obtained data on gender, grade, age, lifestyle habits, weekday sleep duration, anxiety disorder symptoms, depressive symptoms, and dreams from Japanese high school students. The data were analyzed via multiple logistic regression analyses. The prevalence of anxiety and depressive symptoms increased with the frequency of “rumination at bedtime”, “memory of dreams”, “emotional carryover”, and “awakening by frightening”, “unpleasant”, “film-like”, “fantastical”, and “recurring” dreams. However, this was not the case for “pleasant dreams”. Furthermore, “rumination at bedtime” (anxiety disorder symptoms: adjusted odds ratio: 10.60; 95% confidence interval: 5.92–18.97; depressive symptoms: 8.79, 5.58–13.87) and “unpleasant dreams” (anxiety disorder symptoms: 5.25, 2.86–9.64; depressive symptoms: 10.13, 5.57–18.44) exhibited particularly high odds ratios. “Rumination at bedtime” and “unpleasant dreams” may serve as early indicators of declining mental health. School- and parent-led interventions aimed at improving mental well-being may help prevent the progression or exacerbation of anxiety and depressive symptoms among adolescents. Full article

Circadian rhythms (CRs) are a key biological system regulating physiological processes such as metabolism, cell growth, DNA repair, and immunity, adapting to environmental changes like the light/dark cycle. Governed by internal clocks, it modulates gene expression through feedback loops involving Clock Genes (CGs), with the cycle initiated by CLOCK–BMAL1 and NPAS2–BMAL1 heterodimers. Disruptions in circadian rhythms have been linked to diseases including metabolic disorders, neurodegeneration, and cancer. CIPC (CLOCK-interacting pacemaker) has been studied as a negative regulator of the CLOCK–BMAL1 complex, focusing on its role in cancer, particularly leukemias. Public datasets and bioinformatics tools were used to examine CIPC gene expression in healthy patients and acute myeloid leukemia (AML) samples. Our analysis revealed significant overexpression of CIPC in AML compared to healthy tissues (p < 0.0001 ****). Additionally, survival analysis indicated significant differences in overall survival based on CIPC expression, with a log-rank test p-value = 0.014, suggesting that CIPC expression may affect overall patient survival. Altered CIPC expression may contribute to leukemogenesis by inhibiting circadian genes, which are often disrupted in leukemia. Furthermore, CIPC interacts with oncogenic pathways, including the MAPK/ERK pathway, which is essential for cell proliferation. Additional studies are needed to validate these findings and explore the detailed role of CIPC in cancer development. Full article

Background. Sleep disorders are a group of conditions that disrupt normal sleep patterns and are among the most common clinical challenges faced today. An innovative device that employs nanotechnology to deliver beneficial effects on the human body is the Taopatch^® (Tao Technologies, Vedelago, Italy). This study aims to assess the effectiveness of such nanotechnology-based devices in improving sleep quality. Methods. This study included only female participants, as a review of the literature indicated that sleep disorders are more prevalent in women than in men. A total of 30 subjects (with a mean age of 44.8 ± 3.44 years) were randomly divided into two groups: an experimental group and a control group. Sleep quality was evaluated three times throughout the study for each participant using the Pittsburgh Sleep Quality Index (PSQI). The Taopatch^® devices were applied using a specialized pillow. Results. The experimental group showed significantly better sleep quality (p < 0.001) compared to the control group. Conclusions. Our findings suggest that the application of the Taopatch^® has a positive impact on sleep quality by optimizing posture, aligning the cervical spine, and promoting muscle relaxation. This device uses advanced nanotechnology to enhance various physiological functions, contributing to better overall well-being. Full article

Introduction: For patients in intensive care units, the Richards–Campbell Sleep Questionnaire (RCSQ) seems to be a useful tool for assessing sleep quality. However, its application in the Moroccan medical context could be limited due to the lack of a dialectal Arabic version for Morocco. This study’s objective was to translate and validate the RCSQ into Arabic for Moroccan speakers. Patients and methods: For this investigation, a cross-sectional design was adopted. The RCSQ was translated and validated into Arabic for Morocco in accordance with the recommendations. For every scale, psychometric properties were computed. The Cronbach’s α coefficient was utilized to evaluate the internal consistency of multi-item measures. Results: The study involved 224 patients, whose mean age was 47 ± 18.3 years. The RCSQ’s internal consistency, or Cronbach’s alpha, was computed, and all dimensions showed good reliability over the 0.92 (0.894–0.983) level. The items demonstrated good reliability and validity, with correlation values larger than 0.4, according to the data. Conclusion: The RCSQ translated into Arabic for Morocco appears to have good psychometric qualities, making it useful for assessing the quality of sleep of patients in intensive care units within Moroccan healthcare settings. Full article

Chronobiotics represent a pharmacologically diverse group of substances, encompassing both experimental compounds and those utilized in clinical practice, which possess the capacity to modulate the parameters of circadian rhythms. These substances influence fluctuations in various physiological and biochemical processes, including the expression of core “clock” genes in model organisms and cell cultures, as well as the expression of clock-controlled genes. Despite their chemical heterogeneity, chronobiotics share the common ability to alter circadian dynamics. The concept of chronobiotic drugs has been recognized for over five decades, dating back to the discovery and detailed clinical characterization of the hormone melatonin. However, the field remains fragmented, lacking a unified classification system for these pharmacological agents. The current categorizations include natural chrononutrients, synthetic targeted circadian rhythm modulators, hypnotics, and chronobiotic hormones, yet no comprehensive repository of knowledge on chronobiotics exists. Addressing this gap, the development of the world’s first curated and continuously updated database of chronobiotic drugs—circadian rhythm modulators—accessible via the global Internet, represents a critical and timely objective for the fields of chronobiology, chronomedicine, and pharmacoinformatics/bioinformatics. The primary objective of this study is to construct a relational database, ChronobioticsDB, utilizing the Django framework and PostGreSQL as the database management system. The database will be accessible through a dedicated web interface and will be filled in with data on chronobiotics extracted and manually annotated from PubMed, Google Scholar, Scopus, and Web of Science articles. Each entry in the database will comprise a detailed compound card, featuring links to primary data sources, a molecular structure image, the compound’s chemical formula in machine-readable SMILES format, and its name according to IUPAC nomenclature. To enhance the depth and accuracy of the information, the database will be synchronized with external repositories such as ChemSpider, DrugBank, Chembl, ChEBI, Engage, UniProt, and PubChem. This integration will ensure the inclusion of up-to-date and comprehensive data on each chronobiotic. Furthermore, the biological and pharmacological relevance of the database will be augmented through synchronization with additional resources, including the FDA. In cases of overlapping data, compound cards will highlight the unique properties of each chronobiotic, thereby providing a robust and multifaceted resource for researchers and practitioners in the field. Full article

Sleep is an essential part of everyday life and disturbed sleep can produce numerous deleterious effects on the body. An especially prevalent and detrimental subset of sleep disturbances are sleep disturbances that occur in patients during the postoperative period. To better understand these disorders and how to treat them, a literature search was conducted to identify and consolidate recent advancements in this field. This narrative review discusses the structure of a typical night of sleep and the causes, effects, and treatment strategies of Postoperative Sleep Disturbances (PSDs). Factors that contribute to the development of PSDs have been identified at all stages of the surgical process, including the preoperative, intraoperative, and postoperative timepoints. Exposure to these factors can accumulate during each step and may decrease the quality of sleep postoperatively. The development of PSDs has been found to affect multiple systems throughout the body and can ultimately lead to poorer recovery times and increased postoperative mortality. As a result, multiple therapeutic approaches are being investigated for their role in reducing the prevalence of these disorders. This has revealed promising interventions throughout the surgical process, such as preoperative nerve blocks, intraoperative infusions, and postoperative behavioral interventions. However, despite these successful findings, work still needs to be completed to optimize these techniques and generalize intervention strategies. Full article