Search Results (1,816)

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

Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Background/Objectives: Rest–activity rhythm (RAR) disturbances can contribute to aging and dementia via metabolic dysregulation. Hydroxycholesterol (OH) is thought to mediate the link between hypercholesterolemia and neurodegeneration. This study compared sleep and RAR parameters between amnestic mild cognitive impairment (aMCI) patients and normal controls (NCs), and examined their associations with plasma 27-OH levels, reflecting peripheral cholesterol metabolism. Methods In total, 18 aMCI patients (76.6 ± 6.1 years) and 21 NCs (70.4 ± 6.7 years) underwent five-day actigraphy and dim light melatonin onset assessment. Plasma 27-OH levels were measured via high-performance liquid chromatography-mass spectrometry. Generalized linear models (GLMs) were used to analyze the relationships between sleep, RAR, and 27-OH levels. Results: The aMCI group had significantly lower 27-OH levels and 27-OH/total cholesterol ratios (p < 0.05). GLM revealed that longer sleep onset latency (SOL) was associated with higher 27-OH levels in aMCI, distinguishing them from NCs. Additionally, in aMCI, longer SOL, lower sleep efficiency (SE), and higher fragmentation index (FI) were associated with an increased 27-OH/total cholesterol ratio (p < 0.05). Higher relative amplitude of RAR was linked to lower 27-OH levels across groups (p < 0.01), but RAR parameters showed no significant association with the 27-OH/total cholesterol ratio. Sleep disturbances, including prolonged SOL, reduced SE, and increased FI, were associated with altered peripheral cholesterol oxygenation in aMCI. Conclusions: Greater RAR amplitude correlated with lower 27-OH levels, regardless of cognitive status. These findings suggest that peripheral cholesterol oxygenation in aMCI is related to both sleep disturbances and circadian rhythm dysregulation, highlighting their role in cholesterol metabolism and neurodegeneration. Full article

Fungi, from saprophytes to pathogens, face predictable daily fluctuations in light, temperature, humidity, and nutrient availability. To cope, they have evolved an internal circadian clock that confers a major adaptive advantage. This review critically synthesizes current knowledge on the molecular architecture and physiological relevance of fungal circadian systems, moving beyond the canonical Neurospora crassa model to explore the broader phylogenetic diversity of timekeeping mechanisms. We examine the core transcription-translation feedback loop (TTFL) centered on the FREQUENCY/WHITE COLLAR (FRQ/WCC) system and contrast it with divergent and non-canonical oscillators, including the metabolic rhythms of yeasts and the universally conserved peroxiredoxin (PRX) oxidation cycles. A central theme is the clock’s role in gating cellular defenses against oxidative, osmotic, and nutritional stress, enabling fungi to anticipate and withstand environmental insults through proactive regulation. We provide a detailed analysis of chrono-pathogenesis, where the circadian control of virulence factors aligns fungal attacks with windows of host vulnerability, with a focus on experimental evidence from pathogens like Botrytis cinerea, Fusarium oxysporum, and Magnaporthe oryzae. The review explores the downstream pathways—including transcriptional cascades, post-translational modifications, and epigenetic regulation—that translate temporal signals into physiological outputs such as developmental rhythms in conidiation and hyphal branching. Finally, we highlight critical knowledge gaps, particularly in understudied phyla like Basidiomycota, and discuss future research directions. This includes the exploration of novel clock architectures and the emerging, though speculative, hypothesis of “chrono-therapeutics”—interventions designed to disrupt fungal clocks—as a forward-looking concept for managing fungal infections. Full article

Introduction: Breakfast has emerged as a critical factor in preventing cardiovascular diseases, driven not only by its nutritional content but also by its alignment with circadian rhythms. However, gaps remain in the literature regarding its clinical impact and thematic evolution. Objective: To characterize the global scientific output on the relationship between breakfast quality and cardiovascular health through a systematic bibliometric analysis. Methodology: The PRISMA 2020 protocol was applied to select 1436 original articles indexed in Scopus and Web of Science (1957–2025). Bibliometric tools, including R (v4.4.2) and VOSviewer (v1.6.19) were used to map productivity, impact, collaboration networks, and emerging thematic areas. Results: Scientific output has grown exponentially since 2000. The most influential journals are the American Journal of Clinical Nutrition, Nutrients, and Diabetes Care. The United States, United Kingdom, and Japan lead in publication volume and citations, with increasing participation from Latin American countries. Thematic trends have shifted from traditional clinical markers to innovative approaches such as chrononutrition, digital health, and personalized nutrition. However, methodological gaps persist, including a predominance of observational studies and an underrepresentation of vulnerable populations. Conclusions: Breakfast is a dietary practice with profound implications for cardiometabolic health. This study provides a comprehensive overview of scientific literature, highlighting both advancements and challenges. Strengthening international collaboration networks, standardizing definitions of a healthy breakfast, and promoting evidence-based interventions in school, clinical, and community settings are recommended. Full article

Background: Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. Methods: High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues. Results: Nearly 10% of mature miRNAs showed a daily rhythm in expression. A peak of miRNAs’ levels was in most cases observed during the first half of the D phase of the LD cycle. The highest amplitude was detected in expression of miR-150-5p and miR-142-3p. In the L phase of the LD cycle, the maximum in miR-30d-5p expression was detected. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during the D phase influence apoptosis, angiogenesis, the immune system, and EGF and TGF-beta signaling. Rhythm in miR-150-5p, miR-142-3p, and miR-30d-5p expression was confirmed by real-time PCR. Oncogenes bcl2 and myb and clock gene cry1 were identified as miR-150-5p targets. miR-150-5p administration promoted camptothecin-induced apoptosis. Expression of myb showed a rhythmic profile in DLD1 cells with inverted acrophase with respect to miR-150-5p. miR-150-5p was decreased in cancer compared to adjacent tissue in CRC patients. Decrease in miR-150-5p was age dependent. Older patients with lower expression of miR-150-5p and higher expression of cry1 showed worse survival in comparison with younger patients. Conclusions: miRNA signaling differs between the L and D phases of the LD cycle. miR-150-5p, targeting myb, bcl2, and cry1, can influence CRC progression in a phase-dependent manner. Full article

Sleep is crucial to overall health and plays a significant role in skin function. While the circadian rhythm has been extensively researched for its impact on the body’s optimal functioning, the skin also possesses an independent circadian system that serves many important functions. Sleep disruptions or deprivation can significantly affect skin conditions, by compromising the skin barrier and impairing processes such as collagen production, cellular repair, and wound healing. Given the commonality of sleep disturbances, it is crucial to understand the connection between sleep, circadian regulation, and skin health. This is particularly important in understudied populations, such as those with occupational sleep disruption and individuals with hormone-related conditions like PCOS and menopause. Bidirectional relationships have been established between sleep and several inflammatory skin conditions, including atopic dermatitis, psoriasis, rosacea, and hidradenitis suppurativa. While acne is influenced by sleep, the reverse relationship, how acne affects sleep quality, has not been well established. Chronic sleep disruption can increase cortisol levels and oxidative stress, both of which contribute to skin aging and the progression of autoimmune skin conditions, including systemic lupus erythematosus. As sleep is a modifiable risk factor, it is crucial to consider therapeutic options and interventions to prevent or alleviate skin conditions. This review discusses various therapeutic approaches, including melatonin, L-Theanine, Magnesium-L-threonate, Inositol, Cinnamomi cortex, nervous system regulation, and proper sleep hygiene. These therapeutic options have been studied for their impact on sleep, and importantly, several have been evaluated for their utility as adjuncts for treating skin conditions. Overall, the relationship between sleep and skin health is clear, and incorporating sleep-focused therapeutic interventions offers potential to improve both sleep quality and skin health in individuals with a variety of skin conditions. 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

Obesity is a multifactorial condition that influences metabolic, endocrine, inflammatory, circadian, and behavioral systems. These disruptions can adversely affect the initiation of lactogenesis II—the critical process marking the onset of copious milk secretion following childbirth. In mothers with obesity, prolonged inflammation within the mammary gland, a blunted hormonal response (notably of prolactin), altered progesterone and estrogen dynamics, high leptin levels, and misaligned circadian rhythms contribute significantly to delayed lactogenesis. In addition, mechanical difficulties and psychological factors further hinder effective breastfeeding. This report synthesizes evidence from human epidemiological studies and animal models that elucidate the diverse mechanisms linking maternal obesity to delayed lactogenesis. We review the role of obesity-associated inflammatory mediators in impairing mammary tissue remodeling, the endocrine aberrations that impair lactogenic signaling, the consequences of circadian disruption on hormonal rhythmicity, and the behavioral influences that challenge effective breastfeeding. Finally, we discuss the clinical implications of these findings and propose future research directions targeting endocrine modulation, anti-inflammatory therapy, circadian interventions, and enhanced lactation support strategies for mothers with obesity. Full article

Time-restricted eating (TRE), a dietary strategy that aligns food intake with circadian rhythms, has emerged as a promising non-pharmacological approach for improving glycemic control in patients with type 2 diabetes. This systematic review and meta-analysis evaluated the effects of TRE on glycemic outcomes by analyzing eight randomized controlled trials involving 312 participants with type 2 diabetes or impaired fasting glucose. Meta-analyses of six eligible studies demonstrated that TRE significantly reduced fasting glucose (mean difference [MD]: −0.74 mmol/L; 95% CI: −1.13 to −0.36) and glycated hemoglobin (ΔHbA1c) (MD: −0.11%; 95% CI: −0.15 to −0.07) and increased time in range (TIR) for blood glucose (MD: +10.51%; 95% CI: 6.81 to 14.21). Improvements in fasting glucose and HbA1c were modest but consistent, while the increase in TIR showed no between-study heterogeneity, suggesting a robust and reproducible benefit of TRE on glycemic stability. These findings support the clinical feasibility and effectiveness of TRE as a dietary intervention in diabetes management. However, further high-quality trials with standardized protocols and longer follow-up are needed to confirm long-term efficacy and inform guidelines. Full article

The human circadian rhythm is connected to the body’s endogenous clock and can influence people’s natural sleeping habits as well as a variety of other biological functions. According to research, various electric light sources in interior locations can disrupt the human circadian rhythm. Many psychological studies, on the other hand, reveal that different colors can have varied connections with and a variety of effects on people’s emotions. In this study, the effects of light source attributes and interior space paint color on human circadian rhythm were studied using 24 distinct computer simulations. Simulations were performed using the ALFA plugin for Rhinoceros 6 on an unfurnished bedroom 3D model at night. Results suggest that cooler hues, such as blue, appear to have an unfavorable effect on human circadian rhythm at night, especially when utilized in spaces that are used in the evening, which contradicts what psychologists and interior designers advocate in terms of the soothing mood and nature of the color. Furthermore, the effects of Correlated Color Temperature (CCT) and the intensity of a light source might be significant in minimizing melanopic lux to prevent melatonin suppression at night. These insights are significant for interior designers, architects, and lighting professionals aiming to create healthier living environments by carefully selecting lighting and color schemes that support circadian health. Incorporating these considerations into design practices can help mitigate adverse effects on sleep and overall well-being, ultimately contributing to improved occupant comfort and health. Full article

Modern life, characterized by constant exposure to artificial light from electronic devices, such as light-emitting diodes (LEDs), disrupts the natural circadian rhythm and induces important metabolic changes. The impact of blue light exposure on male and female rat’s onset of puberty, hormonal and biochemical parameters was assessed by comparison between the four study groups: the control group (CTRL) maintained under normal light conditions, the group exposed to blue light from a mobile phone (MP), the group subjected to blue light from a computer screen (PC), and the group exposed to blue light from an LED lamp (LED). Both female and male rats exposed to PC and LED failed to thrive, with a significantly lower body weight intake than the CTRL group. All three distinct sources of blue light interfered with the cyclicity of the estrous cycle in female rats. A marked decrease in the number of complete estrous cycles and the highest incidence of incomplete cycles were noticed in the LED group. Elevated ALT, AST, glucose, and insulin levels were influenced in a gender-specific manner, and depending on the source of emitted light. Prolonged blue light exposure induces significant metabolic disruptions and possesses important future research potential in identifying explicit pathways regarding this environmental stressor. Full article

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article

Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by excess body weight, hyperandrogenism, hyperglycemia, and insulin resistance often resulting in hirsutism and infertility. Dietary strategies have been shown to ameliorate metabolic disturbances, hormonal imbalances, and inflammation associated with PCOS. Recent evidence indicates that intermittent fasting (IF) could effectively enhance health outcomes and regulate circadian rhythm; however, its impact on PCOS remain unclear. Objective: Therefore, this systematic review and meta-analysis aims to examine the effect of IF on women diagnosed with PCOS. Methods: Comprehensive research was conducted across three major databases including PubMed, Scopus, and Web of Science without date restrictions. Meta-analysis was performed using Cochrane Review Manager Version 5.4 software. Results: Five studies fulfilled the inclusion criteria. IF significantly reduced body weight (MD = −4.25 kg, 95% CI: −7.71, −0.79; p = 0.02), BMI (MD = −2.05 kg/m², 95% CI: −3.26, −0.85; p = 0.0008), fasting blood glucose (FBG; MD = −2.86 mg/dL, 95% CI: −4.83, −0.89; p = 0.004), fasting blood insulin (FBI; MD = −3.17 μU/mL, 95% CI: −5.18, −1.16; p = 0.002), insulin resistance (HOMA-IR; MD = −0.94, 95% CI: −1.39, −0.50; p < 0.0001), triglycerides (TG; MD = −40.71 mg/dL, 95% CI: −61.53, −19.90; p = 0.0001), dehydroepiandrosterone sulfate (DHEA-S; MD = −33.21 μg/dL, 95% CI: −57.29, −9.13; p = 0.007), free androgen index (FAI; MD = −1.61%, 95% CI: −2.76, −0.45; p = 0.006), and C-reactive protein (CRP; MD = −2.00 mg/L, 95% CI: −3.15, −0.85; p = 0.006), while increasing sex hormone-binding globulin (SHBG; SMD = 0.50, 95% CI: 0.22, 0.77; p = 0.004). No significant changes were observed in waist-to-hip ratio (WHR), total cholesterol (TC), LDL, HDL, total testosterone (TT), or anti-Mullerian hormone (AMH). Conclusions: IF represents a promising strategy for improving weight and metabolic, hormonal, and inflammatory profiles in women with PCOS. However, the existing evidence remains preliminary, necessitating further robust studies to substantiate these findings. Full article