Search Results (377)

In humans, the master circadian clock, present in the suprachiasmatic nucleus, plays an important role in controlling life-sustaining functions. The development of the circadian clock begins in the fetal period and is almost completed during infancy to early childhood, based on the developmental program that is influenced by the mother’s daily rhythms and, after birth, with the addition of information from the daily life environment. It is known that circadian rhythms are deeply related not only to the balance of a child’s mental and physical development but also to maintaining mental and physical health throughout one’s life. However, it has been suggested that various health problems in the future at any age may be caused by the occurrence of circadian disturbances transmitted by the mother during the fetal period. This phenomenon can be said to support the so-called DOHaD theory, and the involvement of the mother in the maturation of appropriate and stable circadian rhythms cannot be ignored. We consider the problems and countermeasures during the fetal and infant periods, which are important for the formation of circadian clocks. Full article

Disruption of circadian rhythms by abnormal light exposure and reduced melatonin secretion has been linked to heightened pain sensitivity and opioid tolerance. This study evaluated how environmental light manipulation and exogenous melatonin supplementation influence pain perception and morphine tolerance in a rat model of neuropathic pain induced by partial sciatic nerve transection (PSNT). Rats were exposed to constant darkness, constant light, or a 12 h/12 h light–dark cycle for one week before PSNT surgery. Behavioral assays and continuous intrathecal (i.t.) infusion of morphine, melatonin, or their combination were conducted over a 7-day period beginning immediately after PSNT. On Day 7, after discontinued drugs infusion, an acute intrathecal morphine challenge (15 µg, i.t.) was administered to assess tolerance expression. Constant light suppressed melatonin levels, exacerbated pain behaviors, and accelerated morphine tolerance. In contrast, circadian-aligned lighting preserved melatonin rhythms and mitigated these effects. Melatonin co-infusion attenuated morphine tolerance and enhanced morphine analgesia. Reduced pro-inflammatory cytokine expression and increase anti-inflammatory cytokine IL-10 level and suppressed astrocyte activation were also observed by melatonin co-infusion during morphine tolerance induction. These findings highlight the potential of melatonin and circadian regulation in improving opioid efficacy and reduced morphine tolerance in managing neuropathic pain. Full article

Measurement of nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, non-invasive, simple, and safe method for assessing airway inflammation. It serves as a complementary tool to other methods for evaluating airway diseases. However, little is known about the typical NO levels in healthy individuals, including individual differences and the influence of measurement timing. Therefore, this study classified measurement times into four periods and statistically analyzed NO levels in healthy individuals. The mean values among groups were compared using repeated measures ANOVA on six participants. The analysis showed large individual variations in NO levels, resulting in no significant difference (p = 0.29). Notably, greater fluctuations were observed in the morning. These findings align with previous studies suggesting the influence of circadian rhythms and the redundancy of repeated measurements. This study highlights the need to consider timing and individual variability when using FeNO as a physiological marker in healthy populations. Full article

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

Tonsils are secondary lymphoid organs that play a crucial role in the immunological response, with B cells being a major component involved in both innate and adaptive immunity. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and obstructive sleep apnea syndrome (OSAS) are both common pediatric conditions involving tonsillar pathology. In both syndromes, the molecular pathways dysregulated in tonsillar B cells are still to be understood. The study aimed to unravel and compare the proteomic profiles of tonsillar CD19+ B cells isolated from pediatric patients with PFAPA (n = 6) and OSAS (n = 6) to identify disease-specific molecular signatures. B cells were isolated from the tonsillar tissue using magnetic microbeads (with a purity of 93.50%). Proteomic analysis was performed by nanoLC-MS/MS with both data-dependent (DDA) and data-independent acquisition (DIA) methods, followed by comprehensive bioinformatic analysis. By merging DDA and DIA datasets, a total of 18.078 unique proteins were identified. Differential expression analysis revealed 83 proteins increased and 49 proteins decreased in OSAS B cells compared to PFAPA B cells (fold change ≥ 1.5 or ≤0.6, p < 0.05). Distinct pathway enrichments were highlighted, including alterations in the regulation of PTEN gene transcription, circadian gene expression, inflammasome pathways (IPAF and AIM2), and the metabolism of angiotensinogen to angiotensin. Specific proteins such as p53, Hdac3, RPTOR, MED1, Caspase-1, Cathepsin D, Chymase, and TLR2 (validated by WB) were shown to be differentially expressed. These findings reveal distinct proteomic signatures in tonsillar B cells from patients with PFAPA and OSAS, offering novel insights into the pathophysiology and potential avenues for biomarker discovery. Full article

Background/Objectives: The COVID-19 pandemic has caused sickness and death among many health care workers. However, the apparent resistance of health care workers to SARS-CoV-2 infection despite their high-risk work environment remains unclear. To investigate if inflammation and circadian disruption contribute to resistance or diminished susceptibility to the SARS-CoV-2 virus, we retrospectively evaluated a cohort of volunteer hospital nurses (VHNs). Methods: A total of 246 apparently healthy VHNs (mean age 37.4 ± 5.9 years) who had received the BNT162b2 mRNA vaccine were asked to report their sleep quality, according to the Pittsburgh Sleep Quality Index, and number of SARS-CoV-2 infections during the observational study period (from the end of December 2020 to April 2025). The expression of inflammation-associated mediators and circadian transcription factors in peripheral blood mononuclear cells, as well as sleep quality, were examined. Results: Our findings revealed no anthropometric, biochemical, or inflammation-associated parameters but demonstrated significantly greater levels of NFE2L2, also known as nuclear factor erythroid-derived 2-like 2 (NFR2), gene expression in peripheral blood mononuclear cells among VHNs who had never been infected with SARS-CoV-2 (n = 97) than in VHNs with only one (n = 119) or with two or more (n = 35) prior SARS-CoV-2 infections (p < 0.01). This result was confirmed through one-to-one propensity score matching (p < 0.01). Moreover, NRF2 gene expression was not associated with the number of COVID-19 vaccinations (p = 0.598). Finally, NRF2 gene expression was higher among participants who reported better sleep quality (p < 0.01). Conclusions: Our findings suggest possible interactions among NRF2 gene expression, protection against SARS-CoV-2 infection, and the modulation of COVID-19 vaccination efficacy. Full article

Salivary cortisol is widely used to assess stress and circadian rhythms, yet its control variables in neonates, particularly regarding postnatal age, remain poorly understood. To elucidate age-specific effects of clinical variables on cortisol levels, 91 neonates with a mean (standard deviation) gestational age of 34.2 (3.8) weeks and postnatal age of 38.3 (35.4) days were categorised into Early, Medium, and Late groups by quartiles (days 10 and 56). Interactions with postnatal age were evaluated by comparing Early-to-Medium or Early-to-Late differences in regression coefficients between independent variables and cortisol levels. In the whole cohort, maternal hypertensive disorders of pregnancy and morning sampling were associated with reduced cortisol levels (both p = 0.001). Mean regression coefficients (95% CI) between variables and cortisol levels were as follows: for postconceptional age, Early, −0.102 (−0.215, 0.010) and Late, 0.065 (−0.203, 0.332) (p = 0.035); for feeding duration, Early, 0.796 (−0.134, 1.727) and Late, −0.702 (−2.778, 1.376) (p = 0.010); for time elapsed since feeding, Early, −0.748 (−1.275, −0.221) and Late, −0.071 (−1.230, 1.088) (p = 0.036); and for blood lactate, Early, 0.086 (0.048 to 0.124), Medium, 0.022 (−0.063, 0.108), and Late, −0.018 (−0.106, 0.070) (p = 0.008 and <0.001 vs. Medium and Late, respectively). The influence of postconceptional age, oral feeding, and anaerobic metabolism on salivary cortisol levels was observed during the birth transition period but not beyond 10 days of life. Given the age-specific dependence of cortisol levels on clinical variables, including postconceptional age, feeding, and oxygen metabolism, caution is warranted when interpreting findings from studies on salivary cortisol in newborn infants. Full article

Night shift work (NSW), has been associated with adverse health outcomes in women, including increased risks of metabolic disorders, cardiovascular diseases, and reproductive dysfunctions. However, the specific effects of NSW during the climacteric period remain underexplored. This narrative review aimed to examine original studies evaluating the health impacts of NSW on women in their climacteric, with a focus on menopausal timing, hormonal balance, and related symptoms. Relevant studies published in PubMed, Embase, and Scopus were reviewed in January 2025. Of 664 articles screened, 15 met the inclusion criteria. Results indicate that NSW may lead to circadian rhythm disruption, which in turn affects hormonal regulation, the timing of menopause, and the intensity of climacteric symptoms. Prolonged exposure to night shift work appears to increase the risk of metabolic and cardiovascular conditions, and certain cancers. These findings underscore the need to consider NSW as a potential modifiable risk factor for adverse health outcomes during midlife in women. They also highlight the importance of developing targeted occupational health policies and workplace interventions to mitigate these risks and promote healthier aging and quality of life. Full article

Background: Frozen shoulder (FS) is a common musculoskeletal condition with significant socioeconomic impact. Despite its prevalence, the condition lacks a definitive understanding and universally effective treatment approach. Objective: To evaluate the effects of an intervention combining manual therapy, conventional exercises, and strategies to improve sleep quality and circadian rhythm on recovery and biomarkers in patients with FS. Methods: A single-blind, randomized, controlled trial was conducted with 34 participants divided into control and experimental groups (n = 17 each). Both groups received manual therapy and conventional exercises, while the experimental group (EG) also received sleep and circadian rhythm optimization instructions. Biomarkers (fasting glucose, insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA) index, leptin, triglycerides, total cholesterol, HDL cholesterol, uric acid, CRP, IL-1β, IL-6, IL-17, IL-10, IL-33, HMGB1, and TNF-α) and functional outcomes (SPADI, ROM, and PSQI) were assessed pre- and post-intervention. Results: After six weeks, the EG showed significant improvements in IL-10 levels (mean change: 2.5 pg/mL vs. 0.5 pg/mL in the control group (CG), p = 0.03), IL-6 reduction (−1.8 pg/mL vs. −0.4 pg/mL, p = 0.02), and HOMA index (−0.8 vs. −0.2, p = 0.04). ROM improved by 20 degrees in the EG versus 10 degrees in the CG (p = 0.01), SPADI scores decreased by 25 points versus 15 points (p = 0.03), and PSQI improved by 4 points compared to 2 points (p = 0.05). Conclusion: The integration of sleep quality and circadian rhythm optimization into conventional rehabilitation significantly enhances recovery, particularly IL-10 modulation, but these did not translate into superior clinical improvements within the study period. Further long-term studies are needed to confirm whether early biological effects lead to sustained functional recovery in FS patients. Full article

Among various plants, corn is the primary host damaged by Spodoptera frugiperda J. E. Smith (Lepidoptera: Noctuidae). After long-term regional colonization, its larvae feed on sweet waxy corn and fresh corn for extended periods. A question arises: Does long-term feeding on different corn varieties affect their rhythms? Currently, there are no reports addressing these issues. To facilitate the formulation of effective prevention and control measures, Zhengdan 958 and Zhenghuangnuo were selected as representative varieties of normal and sweet waxy corn, respectively, for laboratory experiments. S. frugiperda were fed the leaves of these two corn types over nine consecutive generations, thereby establishing distinct S. frugiperda strains associated with each corn variety. Additionally, a strain fed an artificial diet served as the control group. Through a comparative analysis of the emergence, movement, nutritional foraging, dormancy, mating, and oviposition behaviors of adult fall armyworms from different populations, differences in the six behavioral peak times among the strains were identified. RT-qPCR analysis indicated significant differences in the expression levels of four circadian clock genes across different populations and tissues of the fall armyworm. Feeding on different host plants influenced the expression of circadian clock genes and their associated behavioral rhythms. Our study showed that sweet corn is more conducive to pupation, mating, and oviposition. Because of these differences in adult insect rhythms, sweet corn may have an impact on the reproduction of fall armyworms in the Huang–Huai–Hai corn-planting region. Full article

Background: In systemic sclerosis (SSc), endothelial dysfunction, inflammation, and reduced nitric oxide levels may disrupt circadian blood pressure (BP) regulation. There are studies showing that inflammatory and certain other cells in diseases like SSc exhibit diurnal rhythms. In our study, we examined the effect of SSc on BP. In particular, the frequency of the non-dipper pattern (lack of nighttime BP reduction) in SSc patients has not been adequately investigated. The aim of this study was to evaluate the 24 h BP profile in SSc patients and to compare the frequency of the non-dipper pattern with that of the non-scleroderma group. Additionally, the identification of disrupted circadian BP patterns in SSc patients aims to contribute to the development of personalized, time-sensitive BP monitoring strategies in the future and to support the applicability of personalized medicine in this context. Methods: A total of 31 SSc patients diagnosed according to the 2013 ACR/EULAR classification criteria and 30 age- and sex-matched individuals without SSc were included in this prospective study. BP changes between day and night were evaluated by measuring BP every 30 min with a 24 h ambulatory blood pressure monitoring (ABPM) device. The non-dipper pattern was defined as a decrease in BP of less than 10% during the night compared to the day. To better assess BP fluctuations during the night, nighttime measurements were divided into two time periods: first, 24:00–04:00, and then 04:00–08:00. Additionally, laboratory and clinical parameters and SSc subtypes were compared between the groups. Results: The ABPM findings were compared between the groups with and without SSc. The non-dipper pattern was significantly more common in the SSc group at all time intervals. The non-dipper pattern was observed in 25.8% of the non-SSc group and 83.9% of SSc patients (p < 0.001). In the period between 24:00 and 04:00, the prevalence was 25.8% in the control group and 71.0% in SSc patients (p < 0.001), and between 04:00 and 08:00, it was 35.5% in the control group and 80.6% in SSc patients (p < 0.001). No significant difference was found in non-dipper patterns between individuals with diffuse and limited cutaneous forms of systemic sclerosis. Conclusions: The non-dipper BP pattern is significantly more common in patients with SSc, indicating the disruption of the circadian rhythm affecting BP. Analysis performed by dividing the night into specific time periods revealed that this deterioration continued throughout the night. The findings highlight the importance of circadian BP monitoring in SSc patients and may contribute to future risk stratification and treatment strategies. Circadian BP analysis in SSc may help to develop strategies that are personalized for these patients and tailored to their physiological rhythm. Full article

Rhythms, regulated by core clock genes like the period (per) gene family, are crucial for maintaining physiological processes in animals. In teleost fish, including channel catfish (Ictalurus punctatus), these genes have evolved distinct functions. However, the evolutionary characteristics and functional roles of period genes, particularly in response to environmental cues such as feeding, remain unclear. This study aimed to investigate the evolutionary divergence and functional specialization of the period gene family in channel catfish, with a focus on feeding-induced rhythmicity. Four period genes, Ipper1b, Ipper2, Ipper2l, and Ipper3, were identified in channel catfish. Phylogenetic analysis revealed distinct evolutionary paths for these genes, with Ipper2l forming a separate clade from Ipper2. Tissue-specific expression analysis showed differential expression of period genes across tissues, with Ipper1b exhibiting the highest expression in the intestine and Ipper2 being predominantly expressed in the liver. Statistical analysis confirmed significant differences in the expression levels between tissues (p < 0.05), supporting the tissue-specific roles of these genes. Notably, under strict feeding schedules, we observed significant modulation of rhythmic expression in both the brain and liver, with a notable shift in the peak expression times and amplitude changes aligned with the feeding time. These results suggest that feeding serves as a critical Zeitgeber, entraining circadian rhythms in key tissues and potentially enhancing metabolic efficiency. These results demonstrated that feeding schedules play a key role in modulating circadian gene expression in channel catfish. This study provides insights into the evolutionary divergence and functional roles of the period gene family in channel catfish, showing how feeding schedules modulate circadian gene expression in the brain and liver. These findings have potential applications in optimizing feeding strategies for improving fish health and growth in aquaculture. Full article

The circadian rhythm plays a crucial role in regulating biological processes, and its disruption is linked to various health issues. Identifying small molecules that influence the circadian period is essential for developing targeted therapies. This study explores the use of evolutionary optimization techniques to enhance the classification of these molecules. We applied a genetic algorithm to optimize feature selection and classification performance. Several tree-based learning classification algorithms (Decision Trees, Extra Trees, Random Forest, XGBoost) and a distance-based classifier (kNN) were employed. Their performance was evaluated using accuracy and F1-score, while considering their generalization ability with a validation set. The findings demonstrate that the proposed genetic algorithm improves classification accuracy and reduces overfitting compared to baseline models. Additionally, the use of variance in accuracy as a penalty factor may enhance the model’s reliability for real-world applications. Our study confirms that evolutionary optimization is an effective strategy for classifying small molecules regulating the circadian rhythm. The proposed approach not only improves predictive performance but also ensures a more robust model. Full article

Schizophrenia is a psychiatric disorder characterized by positive, negative, and cognitive symptoms. MK-801, an N-methyl-D-aspartate receptor antagonist, has been used to induce schizophrenia-like behaviors in animal models. Here, we employed IntelliCage, an automated system used for tracking behavior, to assess schizophrenia-like behaviors in MK-801-treated mice under semi-naturalistic conditions. Mice that had been treated with MK-801 for 2 weeks were analyzed for locomotion, emotional, and cognitive functions. Repeated MK-801-treated mice exhibited transient hyperactivity in a novel environment, without significant changes in overall circadian activity. Sucrose preference remained intact, suggesting preserved reward sensitivity. However, less time spent in the corner during the early phase of the competition test indicated reduced competitive behavior for limited water rewards. In the behavioral flexibility test, repeated MK-801-treated mice showed impaired reversal learning, suggesting reduced cognitive flexibility, although the acquisition of initial place discrimination was comparable to that observed in control mice. These behavioral impairments parallel core symptoms of schizophrenia, particularly in the social and cognitive domains. Our findings demonstrate the utility of IntelliCage in detecting behavioral phenotypes over prolonged periods in group-housed settings. This study provides an ecologically valid platform for assessing schizophrenia-like behaviors and may facilitate the development of translationally relevant therapeutic interventions. Full article

Daytime-restricted feeding (TRF) exerts outstanding effects on circadian physiology, nutrient utilization, and energy metabolism. Limiting feeding access to two hours during the daytime (12:00–14:00 h) for three weeks promotes food-anticipatory activity (FAA). FAA encompasses not only behaviors related to meal expectations but also includes diurnal fluctuations in liver metabolic responses, including distinct redox handling. Hepatic microarray profiles of genes associated with redox response processes were analyzed at three crucial time points: at the beginning of the light period or before FAA (08:00 h), during the expression of FAA (11:00 h), and after feeding (14:00 h). Data on fasting and nutrient processing were integrated, whereas circadian implications were extrapolated by comparing the TRF transcriptional output with a one-day fasting group. Transcripts of redox reactions, such as reactive oxygen species (ROS) generation, antioxidant defenses, NAD⁺/NADH equilibrium, and glutathione, hydrogen peroxide (H₂O₂), arginine, nitric oxide (NO), and hydrogen sulfide (H₂S) metabolism, were analyzed. Results showed a decline in antioxidant defenses at 08:00 h, followed by a burst of pro-oxidant reactions, preparation of glutathione metabolism factors, and a tendency to decrease H₂O₂ and increase NO and H₂S during the FAA. Most of the findings observed during the FAA were absent in response to one-day fasting. Hence, TRF involves concerted and sequential responses in liver pro-oxidant and antioxidant reactions, facilitating a redox-related circadian control that optimizes the metabolic utilization of nutrients, which differs from a response to a simple fast-feed cycle. Full article