Chronobiology International最新文献

The objective of this study was to unveil the interplay between circadian rhythms (CR) and hypertensive nephropathy (HTN) by investigating genes, pathways, and molecular functions and the correlation between CR and HTN's immune landscape through bioinformatic approaches. Key genes associated with CR in HTN were screened through an integrated analysis of GEO data, employing consensus clustering and machine learning approaches (Generalized Linear Models (GLM), Random Forest (RF), and Support Vector Machine (SVM)). CIBERSORT, ESTIMATE and ssGSEA algorithm were used to assess the infiltration of immune cells between HTN and control groups and in three distinct CR phenotypes of HTN. Functional analyses including GO and KEGG were conducted to elucidate the underlying mechanisms. The DGIdb website is utilized for predicting potential effective therapeutic drugs targeting CR genes closely linked to HTN. We obtained 45 differentially expressed CR-related genes and these genes are mainly involving signaling pathways such as rhythmic process, circadian rhythm and TGF-beta signaling pathway. Three CR related genes (CCL5, ATF3 and NR4A1) were identified to construct a diagnostic model and have a good performance in diagnosis of HTN and patients with HTN were clustered into three subgroups by consensus clustering according to these genes. Analysis of immune infiltration revealed immune heterogeneity between HTN patients and controls and between the three key CR-related gene clusters of patients with HTN. Furthermore, three CR related genes clusters revealing distinct ESTIMATE Score, Immune Score, Stromal Score heterogeneity with p value < 0.05. Meanwhile, spearman analysis showed CCL5 has a strong correlation different immune cells infiltration, especially NK activated cells (p < 0.001), ATF3 has a correlation with NK resting cells (p = 0.029) and NR4A1 has the most significant correlation with activated T CD4 memory cells infiltration (p = 0.020). The potential therapeutic drug predictions for three CR genes indicate that ATF3 and NR4A1 may harbor potential effective treatment options. Our findings suggest an association between circadian rhythm disruption and altered immune landscape in HTN, highlighting the potential role of CR-related genes in disease heterogeneity. The genes CCL5, ATF3, and NR4A1-which are implicated in circadian regulatory networks - may serve as candidate biomarkers and provide new directions for diagnostic and therapeutic strategies in HTN. Further experimental validation is required to confirm their functional roles and clinical significance .

Insomnia, a prevalent sleep disorder, affects 6-10% of the global population and causes significant functional impairments. Chronotype, individual diurnal preferences, influences health outcomes and varies by sex. However, evidence on sex-specific chronotype distribution and its relationship with insomnia in Asian populations remains limited. This study aimed to examine how chronotype is distributed differently between men and women, and to explore its relationship with insomnia symptoms using nationwide population-based data from Korea. We analyzed data from 2,838 participants aged 20-59 years from the baseline assessment phase of the Circannual Change in Headache and Sleep Study. The Morningness-Eveningness Questionnaire was administered to assess chronotype, while insomnia symptoms were estimated using the Insomnia Severity Index. Covariates included sociodemographic factors, depression, employment, smoking and alcohol consumption, body mass index, and average sleep duration. Women reported a higher prevalence of insomnia symptoms than men (14.5% vs. 11.7%, p = 0.027) and were more likely to be evening types (26.4% vs. 20.6%, p < 0.001), whereas men were more likely to be morning types (11.2% vs. 7.0%, p < 0.001). These sex-specific differences in chronotype distribution were consistently observed across individuals in their 30s to 60s. Across chronotype groups, the prevalence of insomnia symptoms was lowest in morning types (4.7%) and highest in evening types (18.4%, p < 0.001). In adjusted analyses, morning type was significantly associated with reduced odds of insomnia (OR = 0.47, 95% CI = 0.22-0.98), whereas evening type was not significantly associated with insomnia risk. Stratified analyses suggested a stronger protective effect of morning type among women, although the chronotype-by-sex interaction term did not reach statistical significance. This nationwide Korean study found that women tended to be evening type, whereas men were more frequently morning type. Morning type was also linked to a lower risk of insomnia symptoms in the overall population, with the association being more pronounced in women. Together, these findings confirm sex-specific differences in chronotype distribution in Korea and demonstrate the independent protective effect of morning type against insomnia.

Anxiety and depressive symptoms are prevalent among adolescents. Social jetlag has been recognized as a potential risk factor for mental health issues. However, the mechanisms underlying social jetlag and mental health remain unclear. This study aims to investigate the associations of social jetlag with anxiety and depressive symptoms in adolescents. The mediating effects of sleep quality and self-control on these associations were also examined. A cross-sectional study was conducted. In total, 633 adolescents completed an online survey. Social jetlag, sleep quality, self-control, anxiety, and depressive symptoms were assessed using the Munich Chronotype Questionnaire, Pittsburgh Sleep Quality Index, Dual-Mode of Self-Control Scale, Self-rating Anxiety Scale, and Center for Epidemiological Studies Depression Scale, respectively. Multiple linear regression and mediation analyses were performed. The results show that female adolescents experienced higher levels of social jetlag, poorer sleep quality, lower self-control, more severe anxiety and depressive symptoms than male adolescents. Social jetlag was a significant predictor of sleep quality, self-control, anxiety, and depressive symptoms. Notably, sleep quality and self-control had a chain-mediating effect on the associations of social jetlag with anxiety and depressive symptoms in Chinese adolescents. These findings provide evidence for the development of targeted interventions to improve the mental health of adolescents. Reducing social jetlag and improving sleep quality and self-control may be relevant for mitigating anxiety and depressive symptoms.

This study investigated predictors of psychomotor vigilance recovery across a six-day inter-tour rest period separating two consecutive duty tours in a sample of career firefighters. Thirty-five firefighters [M age: 38 yrs (SD = 9.2 yrs)] took psychomotor vigilance task (PVT) tests at the beginning of a six-day recovery period and after beginning their next tour; each tour consisted of five, non-consecutive, 24-hour shifts. During the recovery period, subjects wore a wrist-worn actigraph (Actiwatch-2) and completed a sleep diary. Mixed analysis of covariance was employed to test whether change in psychomotor vigilance occurred as a function of time and recovery sleep. Results  indicated that firefighters with longer sleep periods during recovery had relatively stable psychomotor vigilance at both testing time points. In contrast, firefighters with shorter recovery sleep periods had worse psychomotor vigilance at the end of the tour, followed by substantial improvement after the recovery interval. Significant improvements in number of lapses, mean reciprocal reaction time, median reaction time, fastest 10% reaction times, and slowest 10% reaction times were observed across both groups. These findings underscore the restorative impact of off-duty recovery sleep on attentional performance in firefighters.

The relationship between chronotype and physical activity (PA) is of significant interest due to the well-established connection between PA and numerous health issues, including obesity. While previous research has yielded mixed results, most studies suggest that an individual's PA level is influenced by their chronotype, with morning types generally exhibiting higher PA levels. In the current investigation, we conducted a secondary analysis of actigraphy data, focusing exclusively on the wellrested sleep week collected in the parent protocol. Research-grade actigraphy devices were used to record PA, sampling data every 30 s. We report PA levels for all 7 d and across all waking hours. Contrary to previous findings, our results show no significant differences in average PA levels among intermediate, morning, and evening chronotypes. Given the critical role of PA in overall health and its link to obesity, identifying potential chronotype-related risks should inform decision-making processes, health policies, and practices. Our findings highlight the need for further research to better understand the relationship between chronotype and PA, particularly in the context of controlled sleep schedules and in specific age groups.

Ifosfamide (IFO), developed in the 1970 s as a cyclophosphamide analog, is a cytotoxic alkylating agent of the oxazaphosphorine family. Despite its efficacy in sarcomas and germ-cell tumors, its clinical use remains limited by toxicities, particularly encephalopathy, for which no preventive or curative strategy exists. While cyclophosphamide has been extensively investigated in chronotherapy, IFO chronotolerance remains underexplored. This study aimed to determine circadian variation in IFO toxicity in mice. A total of 180 male Swiss Albino mice (8-10 weeks, ≈25 g) were synchronized for 3 weeks to a 12:12 light - dark cycle and housed in two separate rooms with inverted schedules to allow exploration of six circadian dosing times (1, 5, 9, 13, 17, and 21 HALO; Hours After Light Onset). LD₅₀ was determined by regression analysis of mortality rates at increasing doses (400-750 mg/kg). Survival, survival time, body weight, and rectal temperature were assessed following a single intraperitoneal LD₅₀ dose (520 mg/kg). The estimated LD₅₀ was 520 mg/kg (95% CI: 495-545; χ²=14.8, df=1, p < 0.001; R²=0.92). Circadian variation in survival was highly significant (p < 0.0001). The highest tolerance occurred at 13 HALO (72% survival, mean survival 12.2 d, minimal weight loss and hypothermia), whereas the lowest tolerance was observed at 9 HALO (22% survival, mean survival 7.6 d, maximal weight loss and hypothermia). A secondary peak of tolerance was detected at 1 HALO (64% survival). Rectal temperature rhythms confirmed proper circadian entrainment at baseline, but IFO administration induced marked desynchronization at toxic dosing times. IFO toxicity follows a bimodal circadian pattern, with a major tolerance peak at 13 HALO and a secondary peak at 1 HALO. Translational extrapolation suggests that 13 HALO in mice corresponds to early morning (≈06:00h) in humans, indicating that morning administration may represent the safest therapeutic window for IFO.

Circadian phenotype (i.e. chronotype) may affect athletic performance across different times of day, but its role in team sports is underexplored. The aim of this study was to assess the impact of chronotype on neuromuscular performance in male volleyball players. Forty-six male volleyball players (age: 26.8 ± 7.9 years) completed the Morningness-Eveningness Questionnaire and were classified as morning-type (n = 12), intermediate-type (n = 15) or evening-type (n = 19). Then, in a randomized and cross-over design, participants completed a neuromuscular test battery comprising vertical jumps (squat jump, countermovement jump, spike jump), spike tests (standing and jump spike), agility (modified T-test), isometric handgrip strength, and dynamic balance; performed in the morning (8:00-10:00 AM) and the evening (18:00-20:00). No significant circadian phenotype by time-of-day interaction was found (p = 0.133-0.743, η_p² = 0.09-0.14). However, time-of-day effect was found in squat jump, countermovement jump, spike jump, standing spike test, and non-dominant handgrip strength (p = 0.001-0.046, η_p² = 0.09-0.41), observing an evening improvement in performance ranging from 1.8% to 3.0% (p = 0.001-0.035, d = 0.47-1.16). circadian phenotype had limited impact on neuromuscular performance while diurnal variation enhanced evening performance with a significant role in vertical jump ability and spike velocity among male volleyball players.

Chronotype, which reflects an individual's preference for activity and sleep timing, has been associated with various chronic conditions, particularly the evening chronotype. Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that collectively increase the risk of developing type 2 diabetes mellitus and cardiovascular diseases. Previous studies on chronotype and MetS have been inconsistent, and none has explored the longitudinal association between MetS and its components. Therefore, this study investigated these associations in middle-aged Japanese civil servants. We analyzed 2231 non-rotating, non-night shift workers (aged 29-69, 71.6% male) from the Aichi Workers' Cohort Study who participated in surveys in 2018 (baseline) and 2022 and were free of MetS at baseline. Participants were classified into morning, evening, or intermediate chronotypes using the shortened Morningness - Eveningness Questionnaire. MetS was defined according to the harmonized criteria for Japanese, based on waist circumference (≥85 cm for men and ≥90 cm for women), triglycerides, HDL cholesterol, blood pressure, and blood sugar levels. Over 4 y, 232 participants (10.4%) developed MetS, with a cumulative incidence rate of 9.9% in morning, 17.6% in evening, and 9.5% in intermediate types. Logistic regression analysis adjusted for sex, age, educational background, occupation, leisure-time physical activity, alcohol intake, sleep duration, smoking status, snoring, night-time awakening, sleep medication use, working hours, breakfast eating habit, and medication use for diabetes, hypertension, and dislipdemia, revealed that the evening type individuals had a significantly higher risk of MetS (OR: 2.30, 95% CI: 1.48-3.57) compared to intermediate types. In conclusion, evening chronotype was independently associated with a higher risk of developing MetS in middle-aged Japanese civil servants.

In Japan, irregular sleep patterns due to modern work styles have been linked to poor mental health. Prior studies relied mostly on subjective reports, limiting accuracy. We examined associations between daily sleep variability and depressive symptoms to explore how these factors are related in real-world occupational settings. The study involved 32 adults without physical or psychiatric disorders, insomnia, or shift-duty history who followed a Monday-to-Friday work schedule. Sleep was monitored at home for one week by a wearable electroencephalograph, and sleep indices were calculated. Questionnaires (Pittsburgh Sleep Quality Index [PSQI] and Beck Depression Inventory-II [BDI] were used to assess sleep and mental health. Bedtime, wake-up time, and time in bed were all delayed or extended before holidays. On holidays, light sleep duration increased significantly, and sleep latency was significantly prolonged. Greater bedtime variability was significantly associated with BDI. Median sleep time and rapid eye movement sleep duration were related to PSQI. Sleep disturbances were associated with variability in median sleep time, sleep efficiency, and mean light sleep. Absolute social jetlag related to PSQI and daytime dysfunction. These findings suggest that regular sleep patterns are crucial in occupational settings.

Social jet lag (SJL), i.e. the misalignment between internal biological clocks and social schedules, can negatively impact health. Traditional SJL, defined as the difference in mid-sleep time between workdays and free days, may overestimate misalignment, especially in individuals who extend sleep on free days to offset workday sleep deficits. To refine this measurement, Jankowski proposed sleep-corrected social jet lag (SJLsc), which accounts for variations in sleep duration between workdays and free days. Building on this work, we propose a practical extension of the SJLsc framework that applies a unified rule across seven sleep patterns. Utilizing data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES), we illustrated a step-by-step method for calculating SJLsc. We found that 3.2% of participants were classified into different SJLsc categories (0-< 1.0 h, 1.0-< 2.0 h, and ≥2.0 h) depending on whether Jankowski's method or our approach was used. Continuous SJLsc values from both methods showed high concordance (Spearman's ρ = 0.94). Our approach offers a simple and transparent rule that can be applied consistently across diverse sleep patterns.