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Introduction: Cortisol rhythm disruptions predict early mortality in renal, colorectal, lung, and metastatic breast cancer. In head and neck cancer (HNC), various cortisol indices are known to correlate with adverse psychological and biological (e.g., inflammatory) outcomes, but links to mortality have yet to be demonstrated. We hypothesize that the prognostic value of diurnal cortisol aberrations will hold in HNC. Prior work leads us to predict that flattened or elevated diurnal cortisol profiles will be associated with elevations of serum inflammatory and tumor-promoting cytokines in this population, and that these immune markers would themselves predict poor progression-free survival. Method: We prospectively recruited a pilot sample of HNC patients (N=40) at a multidisciplinary HNC clinic. Most patients presented with late-stage oral/oropharyngeal cancer, were older than 50, male, and subsequently received combined-modality (surgery and/or radiotherapy with or without chemotherapy) treatment with curative intent. Saliva was collected twice daily for six days to assess diurnal slope, mean, waking, and evening cortisol levels. Serum was assayed for an exploratory panel of inflammatory and tumor-promoting cytokines. Two years post study-entry, disease progression and survivorship status were abstracted from medical records. Bivariate correlations, linear regressions, and Cox Proportional Hazards models tested hypotheses. Results: Elevations of evening cortisol and diurnal mean levels were each associated with shorter progression-free survival (evening: Hazard Ratio [HR]=1.848, 95% Confidence Interval [CI]=1.057-3.230, p=.031; diurnal mean: HR=2.662, 95% CI=1.115-6.355, p=.027). Bivariate correlations revealed that higher levels of the serum inflammatory marker interferon (IFN)-γ were linked with elevated evening (r=.405, p=.014) and mean (r=.459, p=.004) cortisol. Higher expression of IFN-γ also predicted poorer progression-free survival (HR=4.671, 95% CI=1.409-15.484, p=.012). Discussion: Elevated evening and diurnal mean cortisol were both prognostic; suggesting cortisol secretion is both dysregulated and elevated among patients who subsequently experienced accelerated disease progression. These exploratory data from 40 HNC patients mirror relationships between cortisol and survival identified among patients with numerous other tumor types. This pilot study highlights the need for research on effects of cortisol rhythm disruption among HNC patients. Future research in larger samples should also examine the role of inflammatory and tumor-promoting factors–both systemically and within the tumor microenvironment–as potential mediators of cortisol rhythm disruption. [ABSTRACT FROM AUTHOR]

Circadian rhythm disruption is a universal phenomenon that is associated with a combination of internal and external factors, with internal factors referring to disturbances in the intrinsic regulatory mechanisms of sleep-wake behavior, and external factors including changes in sleep habits, severe sleep deprivation, shift work, social jet lag, prolonged exposure to nighttime light, and late nighttime eating. Shift work, as a common occupational factor, can lead to disruption of the central/ peripheral biological clock which regulates the expression of almost the entire genome, and the disruption of the biological clock can lead to genetic variants, hormonal secretion abnormalities, insulin resistance, oxidative stress, and systemic inflammation, which are risk factors for obesity. In the context of rapid advancement of global economy and industrialization, the prevalence of simple obesity in the traditional cognitive category is increasing in a linear trend, while the incidence of abdominal obesity, which is closely related to metabolic disorders, is also showing an increasing trend. In recent years, the mechanism of circadian rhythm disorder and obesity associated with shift work has attracted much attention, and this article summarized the latest research progress, aiming to provide a basis for the prevention and treatment of obesity caused by circadian rhythm disruption due to shift work.

Abstract The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth’s magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth’s rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.

• AD is the most common neurodegenerative disease and associated with sleep problems. • Abnormal accumulation of Aβ and hyperphosphorylated tau are key contributors to AD. • Circadian rhythm and neuronal oscillation disorders is associated with AD pathology. • Sleep disorders worsen Aβ and tau pathology and cause severe neuroinflammation. Alzheimer's disease (AD) is the most prevalent dementia, pathologically featuring abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, while sleep, divided into rapid eye movement sleep (REM) and nonrapid eye movement sleep (NREM), plays a key role in consolidating social and spatial memory. Emerging evidence has revealed that sleep disorders such as circadian disturbances and disruption of neuronal rhythm activity are considered as both candidate risks and consequence of AD, suggesting a bidirectional relationship between sleep and AD. This review will firstly grasp basic knowledge of AD pathogenesis, then highlight macrostructural and microstructural alteration of sleep along with AD progression, explain the interaction between accumulation of Aβ and hyperphosphorylated tau, which are two critical neuropathological processes of AD, as well as neuroinflammation and sleep, and finally introduce several methods of sleep enhancement as strategies to reduce AD-associated neuropathology. Although theories about the bidirectional relationship and relevant therapeutic methods in mice have been well developed in recent years, the knowledge in human is still limited. More studies on how to effectively ameliorate AD pathology in patients by sleep enhancement and what specific roles of sleep play in AD are needed. [ABSTRACT FROM AUTHOR]

Sleep is a vital biological function that significantly influences overall health. While sleep deprivation (SD) and circadian rhythm disruption are known to negatively impact various organs, their specific effects on kidney function remain understudied. This study aimed to investigate the impact of chronic partial sleep deprivation and circadian rhythm disruption on renal function in rats, providing insights into the relationship between sleep disturbances and kidney health. A total of 40 male Wistar rats were divided into five groups: a control group, a group with circadian rhythm disruption (CIR), a group with sleep deprivation during the light phase (SD-AM), a group with sleep deprivation during the dark phase (SD-PM), and a group with combined sleep deprivation and circadian rhythm disruption (SD-CIR). Sleep deprivation was induced using a specialized machine, depriving rats of sleep for 4 h daily, while circadian rhythm disruption was achieved through a 3.5-h light/dark cycle. After four weeks, kidney tissues and blood samples were collected for histological and biochemical analyses. The results showed that all experimental groups exhibited reduced water intake, with the CIR and SD-CIR groups also showing significantly lower food intake and reduced weight gain compared to controls. Oxidative stress markers revealed increased serum malondialdehyde (MDA) levels in the SD-PM and SD-CIR groups. Despite these metabolic and oxidative changes, histological examination of the kidneys revealed no significant alterations in renal structure or function across the groups. This study highlights the negative effects of chronic partial sleep deprivation and circadian rhythm disruption on feeding behavior, weight gain, and oxidative stress in rats. However, these interventions did not significantly alter renal structure or function. Further research is needed to explore the physiological mechanisms underlying these findings and the potential long-term effects of sleep disturbances on kidney health.

Simple Summary: Circadian rhythms manipulate various physiological functions to help organisms adapt to environmental variations in a 24 h cycle. However, there are very few studies identifying key sensitive genes linking disrupted circadian rhythms to the progression of Alzheimer's disease (AD), especially elucidating the important role of the key genes at the epigenetic molecular level. Thus, the present study constructed a disrupted circadian rhythm model for accelerated progression of AD, and the results showed increased cellular oxidative stresses, reduced antioxidant capacities, and damage to neuronal cells and brain function in model mice. Then, an increase in RNA m6A levels in mice's brains due to disturbed circadian rhythms was observed, and the special m6A methylation site of the Hif3α gene is 3632 was proven to be involved. This leads us to propose a potential mechanism for the observed malignant progression of AD. Last but not the least, protein expression of KDM3A and TGF -β1 decreased as HIF3A expression increased, indicating that the three co-existing factors might affect disease progression caused by disrupted circadian rhythms. Disrupted circadian rhythms are associated with the onset of chronic diseases and impairments, including cancer, diabetes, and hypertension. However, whether circadian disruptions accelerate the progression of Alzheimer's disease and the respective pathway remains unclear. In this study, we constructed animal models using male C57BL/6N and APP/PS1 mice. Irregular illumination during sleeping hours was administered to the mice in our intervention groups to consistently disrupt their circadian rhythms. The impact of the intervention was evaluated through body weight tracking, cerebral index determination, histopathological staining, and biochemical marker analysis. Transcriptomic sequencing identified critical genes, with the data subsequently validated using RNA m6A detection and site analysis. The evaluations revealed that circadian disruptions impaired normal weight gain, liver and kidney functions, neuronal cells, and overall brain function. Transcriptomic sequencing data revealed a trend of elevating expression of Hif3α mRNA in the intervention groups. Further analysis of specific gene sites revealed that m6A methylation of the Hif3α gene at m6A site 3632 primarily drove the observed variations in HIF3A protein expression in our model. Furthermore, the expression of proteins in PC12 cells, N2a cells, and mice brains validated that an increase in HIF3A expression decreased KDM3A and TGF-β1 protein expression. Our study reveals a hitherto unknown pathway through which the disruption of circadian rhythms, by triggering m6A methylation at m6A site 3632 in the Hif3α gene, leads to the initiation and acceleration of AD. These findings provide valuable insights and guidelines for treating AD patients and enhancing caregiving by professionals. [ABSTRACT FROM AUTHOR]

Circadian rhythms are essential regulators of a multitude of physiological and behavioral processes, such as the metabolism and function of the liver. Circadian rhythms are crucial to liver homeostasis, as the liver is a key metabolic organ accountable for the systemic equilibrium of the body. Circadian rhythm disruption alone is sufficient to cause liver cancer through the maintenance of hepatic metabolic disorder. Although there is evidence linking CRD to hepatocarcinogenesis, the precise cellular and molecular mechanisms that underlie the circadian crosstalk that leads to hepatocellular carcinoma remain unknown. The expression of CRD-related genes in HCC was investigated in this study via bulk RNA transcriptomic analysis and single-cell sequencing. Dysregulated CRD-related genes are predominantly found in hepatocytes and fibroblasts, according to the findings. By using a combination of single-cell RNA sequencing and bulk RNA sequencing analyses, the dysregulated CRD-related genes ADAMTS13, BIRC5, IGFBP3, MARCO, MT2A, NNMT, and PGLYRP2 were identified. The survival analysis using the Kaplan–Meier method revealed a significant correlation between the expression levels of BIRC5 and IGFBP3 and the survival of patients diagnosed with HCC. [ABSTRACT FROM AUTHOR]

IntroductionCortisol rhythm disruptions predict early mortality in renal, colorectal, lung, and metastatic breast cancer. In head and neck cancer (HNC), various cortisol indices are known to correlate with adverse psychological and biological (e.g., inflammatory) outcomes, but links to mortality have yet to be demonstrated. We hypothesize that the prognostic value of diurnal cortisol aberrations will hold in HNC. Prior work leads us to predict that flattened or elevated diurnal cortisol profiles will be associated with elevations of serum inflammatory and tumor-promoting cytokines in this population, and that these immune markers would themselves predict poor progression-free survival.MethodWe prospectively recruited a pilot sample of HNC patients (N=40) at a multidisciplinary HNC clinic. Most patients presented with late-stage oral/oropharyngeal cancer, were older than 50, male, and subsequently received combined-modality (surgery and/or radiotherapy with or without chemotherapy) treatment with curative intent. Saliva was collected twice daily for six days to assess diurnal slope, mean, waking, and evening cortisol levels. Serum was assayed for an exploratory panel of inflammatory and tumor-promoting cytokines. Two years post study-entry, disease progression and survivorship status were abstracted from medical records. Bivariate correlations, linear regressions, and Cox Proportional Hazards models tested hypotheses.ResultsElevations of evening cortisol and diurnal mean levels were each associated with shorter progression-free survival (evening: Hazard Ratio [HR]=1.848, 95% Confidence Interval [CI]=1.057-3.230, p=.031; diurnal mean: HR=2.662, 95% CI=1.115-6.355, p=.027). Bivariate correlations revealed that higher levels of the serum inflammatory marker interferon (IFN)-γ were linked with elevated evening (r=.405, p=.014) and mean (r=.459, p=.004) cortisol. Higher expression of IFN-γ also predicted poorer progression-free survival (HR=4.671, 95% CI=1.409-15.484, p=.012).DiscussionElevated evening and diurnal mean cortisol were both prognostic; suggesting cortisol secretion is both dysregulated and elevated among patients who subsequently experienced accelerated disease progression. These exploratory data from 40 HNC patients mirror relationships between cortisol and survival identified among patients with numerous other tumor types. This pilot study highlights the need for research on effects of cortisol rhythm disruption among HNC patients. Future research in larger samples should also examine the role of inflammatory and tumor-promoting factors–both systemically and within the tumor microenvironment–as potential mediators of cortisol rhythm disruption.

Postoperative cognitive dysfunction (POCD) is a neurological disorder characterized by the emergence of cognitive impairment after surgery. A growing body of literature suggests that the onset of POCD is closely tied to circadian rhythm disruption (CRD). Circadian rhythms are patterns of behavioral and physiological change that repeat themselves at approximately, but not exactly, every 24 h. They are entrained to the 24 h day by the daily light--dark cycle. Postoperative CRD affects cognitive function likely by disrupting sleep architecture, which in turn provokes a host of pathological processes including neuroinflammation, blood--brain barrier disturbances, and glymphatic pathway dysfunction. Therefore, to address the pathogenesis of POCD it is first necessary to correct the dysregulated circadian rhythms that often occur in surgical patients. This narrative review summarizes the evidence for CRD as a key contributor to POCD and concludes with a brief discussion of how circadian-effective hospital lighting can be employed to re-entrain stable and robust circadian rhythms in surgical patients. [ABSTRACT FROM AUTHOR]

The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic. [ABSTRACT FROM AUTHOR]

It is widely accepted that circadian rhythm disruption caused short- or long-term adverse effects on health. Although many previous studies have focused on exploration of the molecular mechanisms, there is no rapid, convenient, and non-invasive method to reveal the influence on health after circadian rhythm disruption. Here, we performed a high-resolution mass spectrometry-based data-independent acquisition (DIA) quantitative urinary proteomic approach in order to explore whether urine could reveal stress changes to those brought about by circadian rhythm disruption after sleep deprivation. After sleep deprivation, the subjects showed a significant increase in both systolic and diastolic blood pressure compared with routine sleep. More than 2000 proteins were quantified and they contained specific proteins for various organs throughout the body. And a total of 177 significantly up-regulated proteins and 68 significantly down-regulated proteins were obtained after sleep deprivation. These differentially expressed proteins (DEPs) were associated with multiple organs and pathways, which reflected widespread influences of sleep deprivation. Besides, machine learning identified a panel of five DEPs (CD300A, SCAMP3, TXN2, EFEMP1, and MYH11) that can effectively discriminate circadian rhythm disruption. Taken together, our results validate the value of urinary proteome in predicting and diagnosing the changes by circadian rhythm disruption. [ABSTRACT FROM AUTHOR]

Social jet lag (SJL) is a misalignment between sleep and wake times on workdays and free days. SJL leads to chronic circadian rhythm disruption and may affect nearly 70% of the general population, leading to increased risk for cardiometabolic diseases. This study investigated the effects of SJL on metabolic health, exercise performance, and exercise-induced skeletal muscle adaptations in mice. Ten-week-old C57BL/6J mice (n = 40) were allocated to four groups: control sedentary (CON-SED), control exercise (CON-EX), social jet lag sedentary (SJL-SED), and social jet lag exercise (SJL-EX). CON mice were housed under a 12:12-h light-dark cycle. SJL was simulated by implementing a 4-h phase delay for 3 days to simulate "weekends," followed by a 4-h phase advance back to "weekdays," for 6 wk. EX mice had free access to a running wheel. Graded exercise tests (GXTs) and glucose tolerance tests (GTTs) were performed at baseline and after intervention to monitor the effects of exercise and social jet lag on cardiorespiratory and metabolic health, respectively. SJL led to alterations in activity and running patterns and clock gene expression in skeletal muscle and decreased average running distance (P < 0.05). SJL-SED mice gained significantly more weight compared with CON-SED and SJL-EX mice (P < 0.01). SJL impaired fasting blood glucose and glucose tolerance compared with CON mice (P < 0.05), which was partially restored by exercise in SJL-EX mice. SJL also blunted improvements in exercise performance and mitochondrial content in the quadriceps. These data suggest that SJL blunted some cardiometabolic adaptations to exercise and that proper circadian hygiene is necessary for maintaining health and performance. NEW & NOTEWORTHY: In mice, disrupting circadian rhythms with social jet lag for 6 wk caused significant weight gain, higher fasting blood glucose, and impaired glucose tolerance compared with control. Voluntary exercise in mice experiencing social jet lag prevented weight gain, though the mice still experienced increased fasting blood glucose and impaired exercise performance compared with trained mice not experiencing social jet lag. Social jet lag seems to be a potent circadian rhythm disruptor that impacts exercise-induced training adaptations. [ABSTRACT FROM AUTHOR]

The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.

Postoperative cognitive dysfunction (POCD) is a neurological disorder characterized by the emergence of cognitive impairment after surgery. A growing body of literature suggests that the onset of POCD is closely tied to circadian rhythm disruption (CRD). Circadian rhythms are patterns of behavioral and physiological change that repeat themselves at approximately, but not exactly, every 24 h. They are entrained to the 24 h day by the daily light–dark cycle. Postoperative CRD affects cognitive function likely by disrupting sleep architecture, which in turn provokes a host of pathological processes including neuroinflammation, blood–brain barrier disturbances, and glymphatic pathway dysfunction. Therefore, to address the pathogenesis of POCD it is first necessary to correct the dysregulated circadian rhythms that often occur in surgical patients. This narrative review summarizes the evidence for CRD as a key contributor to POCD and concludes with a brief discussion of how circadian-effective hospital lighting can be employed to re-entrain stable and robust circadian rhythms in surgical patients.

Artificial light at night (ALAN) is a pervasive circadian rhythm disruptor. Exposure to ALAN is associated with detrimental effects on physiology and behavior, including disrupted metabolism, immune function, endocrine function, and pain behavior. Given the detrimental effects of ALAN and other circadian rhythm disruptors on pain, we sought to understand how ALAN may alter the progression and severity of diabetic neuropathy. To do this, we used a previously reported high-fat diet and streptozotocin injection protocol to induce a type II diabetic phenotype in ~8 week old female and male mice and then exposed the mice to either control or ALAN lighting conditions in 14:10 h light-dark cycles for 4 weeks. Male mice housed in control conditions exhibited reduced responsiveness to cold pain; in contrast, ALAN blunted this effect in male mice. ALAN exposure also elevated blood glucose and altered body mass loss in male mice. These effects were not present in female mice. The results of this study highlight the need to consider and study ALAN exposure and sex as a biological variable as risk factors in the treatment and mitigation of pain. [ABSTRACT FROM AUTHOR]

Circadian rhythms (CRs) are 24-hour periodic oscillations governed by an endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN), which organizes the physiology and behavior of organisms. Circadian rhythm disruption (CRD) is also indicative of the aging process. In mammals, melatonin is primarily synthesized in the pineal gland and participates in a variety of multifaceted intracellular signaling networks and has been shown to synchronize CRs. Endogenous melatonin synthesis and its release tend to decrease progressively with advancing age. Older individuals experience frequent CR disruption, which hastens the process of aging. A profound understanding of the relationship between CRs and aging has the potential to improve existing treatments and facilitate development of novel chronotherapies that target age-related disorders. This review article aims to examine the circadian regulatory mechanisms in which melatonin plays a key role in signaling. We describe the basic architecture of the molecular circadian clock and its functional decline with age in detail. Furthermore, we discuss the role of melatonin in regulation of the circadian pacemaker and redox homeostasis during aging. Moreover, we also discuss the protective effect of exogenous melatonin supplementation in age-dependent CR disruption, which sheds light on this pleiotropic molecule and how it can be used as an effective chronotherapeutic medicine. [ABSTRACT FROM AUTHOR]

Artificial light at night (ALAN) is a pervasive circadian rhythm disruptor. Exposure to ALAN is associated with detrimental effects on physiology and behavior, including disrupted metabolism, immune function, endocrine function, and pain behavior. Given the detrimental effects of ALAN and other circadian rhythm disruptors on pain, we sought to understand how ALAN may alter the progression and severity of diabetic neuropathy. To do this, we used a previously reported high-fat diet and streptozotocin injection protocol to induce a type II diabetic phenotype in ∼8 week old female and male mice and then exposed the mice to either control or ALAN lighting conditions in 14:10 h light-dark cycles for 4 weeks. Male mice housed in control conditions exhibited reduced responsiveness to cold pain; in contrast, ALAN blunted this effect in male mice. ALAN exposure also elevated blood glucose and altered body mass loss in male mice. These effects were not present in female mice. The results of this study highlight the need to consider and study ALAN exposure and sex as a biological variable as risk factors in the treatment and mitigation of pain.

The neurovascular system forms the interface between the tissue of the central nervous system (CNS) and circulating blood. It plays a critical role in regulating movement of ions, small molecules, and cellular regulators into and out of brain tissue and in sustaining brain health. The neurovascular unit (NVU), the cells that form the structural and functional link between cells of the brain and the vasculature, maintains the blood-brain interface (BBI), controls cerebral blood flow, and surveils for injury. The neurovascular system is dynamic; it undergoes tight regulation of biochemical and cellular interactions to balance and support brain function. Development of an intrinsic circadian clock enables the NVU to anticipate rhythmic changes in brain activity and body physiology that occur over the day-night cycle. The development of circadian neurovascular function involves multiple cell types. We address the functional aspects of the circadian clock in the components of the NVU and their effects in regulating neurovascular physiology, including BBI permeability, cerebral blood flow, and inflammation. Disrupting the circadian clock impairs a number of physiological processes associated with the NVU, many of which are correlated with an increased risk of dysfunction and disease. Consequently, understanding the cell biology and physiology of the NVU is critical to diminishing consequences of impaired neurovascular function, including cerebral bleeding and neurodegeneration. [ABSTRACT FROM AUTHOR]

Abstract Background Little is known about the link between solar activity and variations in melatonin. In this study, we investigated if melatonin's major urinary metabolite, urinary 6-sulfatoxymelatonin (aMT6s), is lowest under periods of intense solar activity. Methods We investigated associations between high-energy solar particle events [Coronal Mass Ejection (CME) mass, speed and energy] on creatinine-adjusted aMT6s (aMT6sr) concentrations in 140 patients with chronic obstructive pulmonary disease (COPD) using up to four seasonal urine samples (n = 440). Mixed effect models with a random intercept for each subject were used to estimate associations, including effect modification attributable to diabetes, obesity, and reduced pulmonary function. Results Higher values of CME were associated with reduced aMT6sr concentrations, with stronger associations in patients with diabetes. An interquartile range (IQR) increase in natural log CMEspeed averaged through two days before urine collection was associated with a reduction of 9.3% aMT6sr (95%CI: − 17.1%, − 0.8%) in aMT6sr. There was a greater reduction in aMT6sr in patients with diabetes (− 24.5%; 95%CI: − 35.9%, − 11.6%). In patients without diabetes there was no meaningful association (− 2.2%; 95%CI: − 12%, 8.4%). There were similar associations with CMEenergy and CMEmass. There was no effect modification attributable to reduced pulmonary function or obesity. Conclusions This is the first study in patients with COPD to demonstrate strong detrimental impact of high-energy solar particle events on aMT6sr, with greater associations in patients with diabetes. Since melatonin is an anti-oxidant, it is possible that adverse effects of intense solar activity may be attributable to a reduction in circulating melatonin and that patients with both COPD and diabetes may be more susceptible.

The neurovascular system forms the interface between the tissue of the central nervous system (CNS) and circulating blood. It plays a critical role in regulating movement of ions, small molecules, and cellular regulators into and out of brain tissue and in sustaining brain health. The neurovascular unit (NVU), the cells that form the structural and functional link between cells of the brain and the vasculature, maintains the blood–brain interface (BBI), controls cerebral blood flow, and surveils for injury. The neurovascular system is dynamic; it undergoes tight regulation of biochemical and cellular interactions to balance and support brain function. Development of an intrinsic circadian clock enables the NVU to anticipate rhythmic changes in brain activity and body physiology that occur over the day-night cycle. The development of circadian neurovascular function involves multiple cell types. We address the functional aspects of the circadian clock in the components of the NVU and their effects in regulating neurovascular physiology, including BBI permeability, cerebral blood flow, and inflammation. Disrupting the circadian clock impairs a number of physiological processes associated with the NVU, many of which are correlated with an increased risk of dysfunction and disease. Consequently, understanding the cell biology and physiology of the NVU is critical to diminishing consequences of impaired neurovascular function, including cerebral bleeding and neurodegeneration.

Background: Little is known about the link between solar activity and variations in melatonin. In this study, we investigated if melatonin's major urinary metabolite, urinary 6-sulfatoxymelatonin (aMT6s), is lowest under periods of intense solar activity. Methods: We investigated associations between high-energy solar particle events [Coronal Mass Ejection (CME) mass, speed and energy] on creatinine-adjusted aMT6s (aMT6sr) concentrations in 140 patients with chronic obstructive pulmonary disease (COPD) using up to four seasonal urine samples (n = 440). Mixed effect models with a random intercept for each subject were used to estimate associations, including effect modification attributable to diabetes, obesity, and reduced pulmonary function. Results: Higher values of CME were associated with reduced aMT6sr concentrations, with stronger associations in patients with diabetes. An interquartile range (IQR) increase in natural log CMEspeed averaged through two days before urine collection was associated with a reduction of 9.3% aMT6sr (95%CI: − 17.1%, − 0.8%) in aMT6sr. There was a greater reduction in aMT6sr in patients with diabetes (− 24.5%; 95%CI: − 35.9%, − 11.6%). In patients without diabetes there was no meaningful association (− 2.2%; 95%CI: − 12%, 8.4%). There were similar associations with CMEenergy and CMEmass. There was no effect modification attributable to reduced pulmonary function or obesity. Conclusions: This is the first study in patients with COPD to demonstrate strong detrimental impact of high-energy solar particle events on aMT6sr, with greater associations in patients with diabetes. Since melatonin is an anti-oxidant, it is possible that adverse effects of intense solar activity may be attributable to a reduction in circulating melatonin and that patients with both COPD and diabetes may be more susceptible. [ABSTRACT FROM AUTHOR]

We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process. [ABSTRACT FROM AUTHOR]

Abstract Artificial light has been increasingly in use for the past 70 years. The aberrant light exposure and round‐the‐clock nature of work lead to the disruption of biological clock. Circadian rhythm disruption (CRD) contributes to multiple metabolic and neurodegenerative diseases. However, its effect on vision is not understood. Moreover, the mammalian retina possesses an autonomous clock that could be reset with light exposure. We evaluated the impact of CRD on retinal morphology, physiology, and vision after housing mice in a disruption inducing shorter light/dark cycle (L10:D10). Interestingly, the mice under L10:D10 exhibited three different entrainment behaviors; “entrained,” “free‐running,” and “zigzagging.” These behavior groups under CRD exhibited reduced visual acuity, retinal thinning, and a decrease in the number of photoreceptors. Intriguingly, the electroretinogram response was decreased only in the mice exhibiting “entrained” behavior. The retinal proteome showed distinct changes with each entrainment behavior, and there was a dysfunctional oxidative stress‐antioxidant mechanism. These results demonstrate that CRD alters entrainment behavior and leads to visual dysfunction in mice. Our studies uniquely show the effect of entrainment behavior on retinal physiology. Our data have broader implications in understanding and mitigating the impact of CRD on vision and its potential role in the etiology of retinal diseases.

Pain behavior and the systems that mediate opioid analgesia and opioid reward processing display circadian rhythms. Moreover, the pain system and opioid processing systems, including the mesolimbic reward circuitry, reciprocally interact with the circadian system. Recent work has demonstrated the disruptive relationship among these three systems. Disruption of circadian rhythms can exacerbate pain behavior and modulate opioid processing, and pain and opioids can influence circadian rhythms. This review highlights evidence demonstrating the relationship among the circadian, pain, and opioid systems. Evidence of how disruption of one of these systems can lead to reciprocal disruptions of the other is then reviewed. Finally, we discuss the interconnected nature of these systems to emphasize the importance of their interactions in therapeutic contexts. [ABSTRACT FROM AUTHOR]

Circadian rhythm disruption (CRD) is a potential risk factor for developing Alzheimer's disease (AD). However, the mechanistic link between CRD and AD is still not fully understood. CRD may lead to intestinal barrier impairment. Several studies in animals and humans suggest a connection between gut microbiota disturbance, intestinal barrier damage and neurodegenerative diseases. In this study, we investigated the effect of CRD on cognition in mice and explored the role of intestinal barrier and inflammatory responses in this process. CRD modulates the composition of gut microbiota, impairs intestinal barrier integrity, and induces both peripheral and central inflammation and cognitive impairment in mice. Rifaximin, a non‐absorbable antibiotic which modulates the gut microbial composition and increases intestinal barrier integrity, effectively suppresses inflammatory responses, and rescues cognitive impairment induced by CRD. Furthermore, the impairment in hippocampal neurogenesis, tau hyperphosphorylation, and loss in synaptic proteins in CRD mice is also reversed by Rifaximin. These data identify that the impaired intestinal barrier integrity related to gut microbiota disturbance plays a key role in CRD‐induced inflammatory responses and cognitive impairments in mice, and Rifaximin is effective in preventing CRD‐induced cognitive deficit through protecting the gut barrier and ameliorating neuroinflammation. [ABSTRACT FROM AUTHOR]

Pain behavior and the systems that mediate opioid analgesia and opioid reward processing display circadian rhythms. Moreover, the pain system and opioid processing systems, including the mesolimbic reward circuitry, reciprocally interact with the circadian system. Recent work has demonstrated the disruptive relationship among these three systems. Disruption of circadian rhythms can exacerbate pain behavior and modulate opioid processing, and pain and opioids can influence circadian rhythms. This review highlights evidence demonstrating the relationship among the circadian, pain, and opioid systems. Evidence of how disruption of one of these systems can lead to reciprocal disruptions of the other is then reviewed. Finally, we discuss the interconnected nature of these systems to emphasize the importance of their interactions in therapeutic contexts.

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape—for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading malignancy in females and flight attendants seem to have an elevated risk for it. This paper synthesizes the current evidence on the association of occupational exposure to cosmic radiation and circadian rhythm disruption and breast cancer risk in this population. Objective: We conducted a systematic review and meta-analysis to investigate occupational exposures and their role in breast cancer (BC) risk among female flight attendants (FFAs). Methods: We systematically searched PubMed and EMBASE and included all observational studies reporting on the outcome BC incidence among FFAs. The exposures of interest were cosmic radiation and circadian rhythm disruption. Study quality was assessed using the Newcastle-Ottawa Scale. Results: Nine studies met the inclusion criteria, of which four were included in the meta-analysis for BC incidence (pooled standardized incidence ratio, 1.43; 95% confidence interval, 1.32 to 1.54). Three studies suggested a possible association between BC and cosmic radiation, whereas none found an association with circadian rhythm disruption. Conclusion: Neither exposure to cosmic radiation nor circadian rhythm disruption seems to explain the elevated risk of BC among flight attendants. Further studies reporting individual information on occupational exposures are needed. [ABSTRACT FROM AUTHOR]

Background: Numerous symptoms of bipolar disorder are regulated by the circadian rhythm. Because of this association it is assumed that disruption of the circadian rhythm may be part of the pathomechanism of bipolar disorder. Objectives: A comparison and subsequent critical discussion of the current data situation on chronobiological aspects of bipolar disorder are presented. Methods: A narrative literature search was carried out and the main findings are presented in a summarized form. Results: There are a large number of animal and human studies investigating the connection between disorders of the circadian rhythm and bipolar disorder. Especially chronotype, the environmental factor light and sleep disorders seem to be associated with the development of bipolar disorder. Conclusions: The neurobiology of bipolar disorder shows numerous chronobiological aspects. There is evidence for a direct connection of disruption of the circadian rhythm and development and progression of bipolar disorder; however, at present there is no proof for the specificity of these findings for bipolar disorder. Future studies should consolidate the evidence on the impact of disorders of the circadian rhythm on the pathomechanism of bipolar disorder. [ABSTRACT FROM AUTHOR]

Objectives Epidemiological observations indicate that female flight attendants are exposed to some reproductive and endocrine system disturbances. The aim of the study was to determine the incidence of hyperprolactinemia among female flight attendants, and to identify factors affecting the secretion of prolactin in female flight attendants working within 1 time zone as well as on long-distance flights. Material and Methods The cross-sectional study covered 103 women aged 23–46 years. The study group (I) was divided into 2 subgroups: subgroup Ia comprising female flight attendants flying within 1 flight zone, and subgroup Ib composed of female flight attendants working on long-distance flights. The control group (II) included women of reproductive age who sought medical assistance due to marital infertility in whom the male factor was found to be responsible for problems with conception in the course of the diagnostic process. The assessment included: age, the body mass index, menstrual cycle regularity, the length of service, the frequency of flying, the prolactin, estradiol and progesterone concentrations, and the result of endometrial biopsy. Descriptive and inferential statistics methods were used to compile the data. Results The incidence of hyperprolactinemia in the female flight attendants (46%) was significantly higher than in the control group (9%), p < 0.001. Differences between subgroups Ia and Ib regarding individual concentrations were not statistically significant (p = 0.425). Hyperprolactinemia among the female flight attendants working ≥15 years is present slightly more often than in those working 0.05). No significant difference was revealed in the secretion of prolactin between the study participants spending 0.05). Conclusions Hyperprolactinemia is more common in female flight attendants than in the general population. High values of prolactin concentration in flight attendants are rarely manifested in clinical symptoms. The frequency of flying and the length of service do not affect the development of hyperprolactinemia or the mean prolactin concentration. Int J Occup Med Environ Health. 2021;34(3):351–61

Artificial light has been increasingly in use for the past 70 years. The aberrant light exposure and round‐the‐clock nature of work lead to the disruption of biological clock. Circadian rhythm disruption (CRD) contributes to multiple metabolic and neurodegenerative diseases. However, its effect on vision is not understood. Moreover, the mammalian retina possesses an autonomous clock that could be reset with light exposure. We evaluated the impact of CRD on retinal morphology, physiology, and vision after housing mice in a disruption inducing shorter light/dark cycle (L10:D10). Interestingly, the mice under L10:D10 exhibited three different entrainment behaviors; "entrained," "free‐running," and "zigzagging." These behavior groups under CRD exhibited reduced visual acuity, retinal thinning, and a decrease in the number of photoreceptors. Intriguingly, the electroretinogram response was decreased only in the mice exhibiting "entrained" behavior. The retinal proteome showed distinct changes with each entrainment behavior, and there was a dysfunctional oxidative stress‐antioxidant mechanism. These results demonstrate that CRD alters entrainment behavior and leads to visual dysfunction in mice. Our studies uniquely show the effect of entrainment behavior on retinal physiology. Our data have broader implications in understanding and mitigating the impact of CRD on vision and its potential role in the etiology of retinal diseases. [ABSTRACT FROM AUTHOR]

Circadian rhythm disruption is detrimental and results in adverse health consequences. We used a multi-omics profiling approach to investigate the effects of Cyclocarya paliurus flavonoid (CPF)-enriched diets on gut microbiota, metabolites, and hypothalamus clock genes in mice with induced circadian rhythm disruption. It was observed that CPF supplementation altered the specific composition and function of gut microbiota and metabolites induced by circadian rhythm disruption. Analysis showed that the abundance of Akkermansia increased, while the abundance of Clostridiales and Ruminiclostridium displayed a significant downward trend after the CPF intervention. Correlation analysis also revealed that these gut microbes had certain correlations with the metabolites, suggesting that CPFs help the intestinal microbiota to repair the intestinal environment and modulate the release of some beneficial metabolites. Notably, single-cell RNA-seq revealed that CPF supplementation significantly regulated the expression of genes associated with circadian rhythm, myelination, and neurodegenerative diseases. Altogether, these findings highlight that CPFs may represent a promising dietary therapeutic strategy for treating circadian rhythm disruption. [ABSTRACT FROM AUTHOR]

Background & Aims: Gut microbiota have been reported to be sensitive to circadian rhythms and host lipometabolism, respectively. Although melatonin-mediated beneficial efforts on many physiological sites have been revealed, the regulatory actions of oral melatonin on the communication between gut microbiota and host are still not clear. Angiopoietin-like 4 (ANGPTL4) has been shown to be strongly responsible for the regulation of systemic lipid metabolism. Herein, we identified that oral melatonin improved lipid dysmetabolism in ileum and epididymal white adipose tissue (eWAT) via gut microbiota and ileac ANGPTL4. Methods: Analyses of jet-lag (JL) mice, JL mice with oral melatonin administration (JL+MT), and the control for mRNA and protein expression regarding lipid uptake and accumulation in ileum and eWAT were made. Gut microbiome sequencing and experimental validation of target strains were included. Functional analysis of key factors/pathways in the various rodent models, including the depletion of gut microbiota, mono-colonization of Escherichia coli, and other genetic intervention was made. Analyses of transcriptional regulation and effects of melatonin on E coli-derived lipopolysaccharide (LPS) in vitro were made. Results: JL mice have a higher level of ileal lipid uptake, fat accumulation in eWAT, and lower level of circulating ANGPTL4 in comparison with the control mice. JL mice also showed a significantly higher abundance of E coli and LPS than the control mice. Conversely, oral melatonin supplementation remarkably reversed these phenotypes. The test of depletion of gut microbiota further demonstrated that oral melatonin-mediated improvements on lipometabolism in JL mice were dependent on the presence of gut microbiota. By mono-colonization of E coli, LPS has been determined to trigger these changes similar to JL. Furthermore, we found that LPS served as a pivotal link that contributed to activating toll-like receptor 4 (TLR4)/signal transducer and activator of transcription 3 (STAT3_/REV-ERBα) signaling to up-regulate nuclear factor interleukin-3-regulated protein (NFIL3) expression, resulting in increased lipid uptake in ileum. In MODE-K cells, the activation of NFIL3 has further been shown to inhibit ANGPTL4 transcription, which is closely associated with lipid uptake and transport in peripheral tissues. Finally, we confirmed that melatonin inhibited LPS via repressing the expression of LpxC in E coli. Conclusions: Overall, oral melatonin decreased the quantity of E coli-generated LPS, which alleviated NFIL3-induced transcriptional inhibition of ANGPTL4 through TLR4/IL-22/STAT3 signaling in ileum, thereby resulting in the amelioration of ileal lipid intake and lower fat accumulation in eWAT. These results address a novel regulation of oral melatonin originating from gut microbiota to host distal tissues, suggesting that microbe-generated metabolites are potential therapies for melatonin-mediated improvement of circadian rhythm disruption and related metabolic syndrome.

Background: Chronic jet lag (CJL)‐induced circadian rhythm disruption (CRD) is positively correlated with an increased risk of allergic diseases. However, little is known about the mechanism involved in allergic rhinitis (AR). Methods: Aberrant light/dark cycles‐induced CRD mice were randomly divided into negative control (NC) group, AR group, CRD+NC group, and CRD+AR group (n = 8/group). After ovalbumin (OVA) challenge, nasal symptom scores were recorded. The expression of Occludin and ZO‐1 in both nasal mucosa and lung tissues was detected by reverse transcription–quantitative polymerase chain reaction (RT‐PCR) and immunohistochemical staining. The level of OVA–specific immunoglobulin E (sIgE) and T‐helper (Th)‐related cytokines in the plasma was measured by enzyme‐linked immunosorbent assay (ELISA), and the proportion of Th1, Th2, Th17, and regulatory T cell (Treg) in splenocytes was evaluated by flow cytometry. Results: The nasal symptom score in the CRD+AR group was significantly higher than those in the AR group with respect to eosinophil infiltration, mast cell degranulation, and goblet cell hyperplasia. The expression of ZO‐1 and Occludin in the nasal mucosa and lung tissues in the CRD+AR group were significantly lower than those in the AR group. Furthermore, Th2 and Th17 cell counts from splenocytes and OVA‐sIgE, interleukin 4 (IL‐4), IL‐6, IL‐13, and IL‐17A levels in plasma were significantly increased in the CRD+AR group than in the AR group, whereas Th1 and Treg cell count and interferon γ (IFN‐γ) level were significantly decreased in the CRD+AR group. Conclusion: CRD experimentally mimicked CJL in human activities, could exacerbate local and systemic allergic reactions in AR mice, partially through decreasing Occludin and ZO‐1 level in the respiratory mucosa and increasing Th2‐like immune response in splenocytes. [ABSTRACT FROM AUTHOR]

The goal of this review is to provide a perspective on the nature and importance of the relationship between the circadian and pain systems. We provide: 1) An overview of the circadian and pain systems, 2) a review of direct and correlative evidence that demonstrates diurnal and circadian rhythms within the pain system; 3) a perspective highlighting the need to consider the role of a proposed feedback loop of circadian rhythm disruption and maladaptive pain; 4) a perspective on the nature of the relationship between circadian rhythms and pain. In summary, we propose that there is no single locus responsible for producing the circadian rhythms of the pain system. Instead, circadian rhythms of pain are a complex result of the distributed rhythms present throughout the pain system, especially those of the descending pain modulatory system, and the rhythms of the systems with which it interacts, including the opioid, endocrine, and immune systems. [ABSTRACT FROM AUTHOR]

Human circadian rhythm refers to the intrinsic ∼24-h oscillation that regulates biological processes to adapt to environments. Disruption of rhythmicity causes mitochondrial dysfunction, changes metabolism, and is associated with neurodegenerative diseases and mental disorders. By employing cellular respiration analyses and mitochondrial membrane potential characterization, we confirmed that donepezil, a sigma-1 receptor agonist, restored mitochondrial function in neuronal cells with induced-circadian rhythm disruption (CRD). This protective effect was elicited by boosting oxidative respiration and increasing mitochondrial membrane potentials. Furthermore, donepezil treatment reinstated rhythmicity of core clock genes. Our findings suggest a novel countermeasure for treating CRD-related neurodegeneration and mental disorders. • Donepezil, a sigma-1 receptor agonist, helps ameliorate mitochondrial dysfunction caused by circadian rhythm disruption (CRD). • Donepezil helps restore rhythmicity of core clock gene expression in neurons. • Sigma-1 receptor ligands as a potential countermeasure for treating CRD-related neuronal dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: Epidemiological observations indicate that female flight attendants are exposed to some reproductive and endocrine system disturbances. The aim of the study was to determine the incidence of hyperprolactinemia among female flight attendants, and to identify factors affecting the secretion of prolactin in female flight attendants working within 1 time zone as well as on long-distance flights.Material and Methods: The cross-sectional study covered 103 women aged 23-46 years. The study group (I) was divided into 2 subgroups: subgroup Ia comprising female flight attendants flying within 1 flight zone, and subgroup Ib composed of female flight attendants working on long-distance flights. The control group (II) included women of reproductive age who sought medical assistance due to marital infertility in whom the male factor was found to be responsible for problems with conception in the course of the diagnostic process. The assessment included: age, the body mass index, menstrual cycle regularity, the length of service, the frequency of flying, the prolactin, estradiol and progesterone concentrations, and the result of endometrial biopsy. Descriptive and inferential statistics methods were used to compile the data.Results: The incidence of hyperprolactinemia in the female flight attendants (46%) was significantly higher than in the control group (9%), p < 0.001. Differences between subgroups Ia and Ib regarding individual concentrations were not statistically significant (p = 0.425). Hyperprolactinemia among the female flight attendants working ≥15 years is present slightly more often than in those working <15 years: 46% vs. 45% (p > 0.05). No significant difference was revealed in the secretion of prolactin between the study participants spending <60 h/month flying and those spending ≥60 h/month flying (p > 0.05).Conclusions: Hyperprolactinemia is more common in female flight attendants than in the general population. High values of prolactin concentration in flight attendants are rarely manifested in clinical symptoms. The frequency of flying and the length of service do not affect the development of hyperprolactinemia or the mean prolactin concentration. Int J Occup Med Environ Health. 2021;34(3):351-61. [ABSTRACT FROM AUTHOR]

Long‐term subjection to shift work increases the risk of cancer. The purpose of the present study was to explore the mechanism by which chronic circadian disruption impairs natural killer (NK) cell immunosurveillance. Mice were subjected to light‐dark reverse every 4 days for 12 weeks to disrupt normal circadian rhythm. NK cell development and function were evaluated by flow cytometry. The mRNA and protein levels of period 1 (per1) and per2 were suppressed, while circadian locomotor output cycle kaput (CLOCK) was increased in the shifted mice, indicating successful generation of the circadian rhythm disruption mouse model. Chronic shift‐lag promoted NK cell ageing, which is likely due to the reduction in Ly49 family receptor expression in shifted NK. We further studied the effects of circadian rhythm disruption on NK cell function. Chronic shift‐lag inhibited NK cell secretion of granular CD107a and interferon gamma. Moreover, chronic shift‐lag attenuated the clearance of MHC‐I–deficient tumour cells by NK cells in vivo and promoted lung metastasis of B16F10 melanomas. Furthermore, chronic shift‐lag reduced NK cell killing function, which may be due to the suppression of Eomes transcription factor expression, which inhibiting the transcription of CD122. In conclusion, our findings suggest that chronic circadian disruption attenuates NK cell cytolytic activity by decreasing the expression of CD122. [ABSTRACT FROM AUTHOR]

Today, daylight saving time is observed in nearly 80 countries around the world, including the European Union, the USA, Canada, and Russia. The benefits of daylight saving time in energy management have been questioned since it was first introduced during World War I and the latest research has led to varying results. Meanwhile, adverse effects of seasonal time shifts on human biology have been postulated and the European Union is planning to abandon the biannual clock change completely. Medical studies have revealed a correlation of seasonal time shifts with increased incidences of several diseases including stroke, myocardial infarction, and unipolar depressive episodes. Moreover, studies in mice have provided convincing evidence, that circadian rhythm disruption may be involved in the pathogenesis of inflammatory bowel diseases, mainly by disturbing the intestinal barrier integrity. Here, we present previously unpublished data from a large German cohort indicating a correlation of seasonal clock changes and medical leaves due to ulcerative colitis and Crohn's disease. Furthermore, we discuss the health risks of clock changes and the current attempts on reforming daylight saving time from a medical perspective.

Background: Benign prostatic hyperplasia (BPH) is the most common urologic disease in aging males, affecting 50% of men over 50 and up to 80% of men over 80 years old. Its negative impact on health-related quality of life implores further investigation into its risk factors and strategies for effective management. Although the exact molecular mechanisms underlying pathophysiological onset of BPH are poorly defined, the current hypothesized contributors to BPH and lower urinary tract symptoms (LUTS) include aging, inflammation, metabolic syndrome, and hormonal changes. These processes are indirectly influenced by circadian rhythm disruption. In this article, we review the recent evidence on the potential association of light changes/circadian rhythm disruption and the onset of BPH and impact on treatment., Methods: A narrative literature review was conducted using PubMed and Google Scholar to identify supporting evidence. The articles referenced ranged from 1975 to 2023., Results: A clear relationship between BPH/LUTS and circadian rhythm disruption is yet to be established. However, common mediators influence both diseases, including proinflammatory states, metabolic syndrome, and hormonal regulation that can be asserted to circadian disruption. Some studies have identified a possible relationship between general LUTS and sleep disturbance, but little research has been done on the medical management of these diseases and how circadian rhythm disruption further affects treatment outcomes., Conclusions: There is evidence to implicate a relationship between BPH/LUTS and circadian rhythm disruptions. However, there is scarce literature on potential specific link in medical management of the disease and treatment outcomes with circadian rhythm disruption. Further study is warranted to provide BPH patients with insights into circadian rhythm directed appropriate interventions., (© 2023 Wiley Periodicals LLC.)

Circadian timekeeping mechanisms and cell cycle regulation share thematic biological principles in responding to signals, repairing cellular damage, coordinating metabolism, and allocating cellular resources for optimal function. Recent studies show interactions between cell cycle regulators and circadian clock components, offering insights into potential cancer treatment approaches. Understanding circadian control of metabolism informs timing for therapies to reduce adverse effects and enhance treatment efficacy. Circadian adaptability to lifestyle factors, such as activity, sleep, and nutrition sheds light on their impact on cancer. Leveraging circadian regulatory mechanisms for cancer prevention and care is vital, as most risk stems from modifiable lifestyles. Monitoring circadian factors aids risk assessment and targeted interventions across the cancer care continuum., Competing Interests: Declaration of Interests S.P. is the author of the books The Circadian Code and The Circadian Diabetes Code. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Night-shift work involving disruption of circadian rhythms has been associated with breast cancer risk. A role in prostate cancer is also suspected, but evidence is limited. We investigated the association between night-shift work and prostate cancer incidence in the Prostate Cancer and Environment Study (PROtEuS), a population-based case-control study conducted in 2005–2012 in Montreal, Quebec, Canada. Participants were 1,904 prostate cancer cases (432 high-grade cancers) and 1,965 population controls. Detailed work schedules for each job held for at least 2 years (n = 15,724) were elicited in face-to-face interviews. Night-shift work was defined as having ever worked ≥3 hours between midnight and 5:00 am ≥3 nights/month for ≥1 year. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between night-shift work and prostate cancer, adjusting for age, ancestry, and education. No association was found between overall prostate cancer and night-shift work metrics, including ever exposure, duration, intensity, cumulative exposure, rotating shifts, and early-morning shifts. For none of the exposure indices was there evidence of heterogeneity in odds ratios between low- and high-grade cancers. Sensitivity analyses restricting exposures to ≥7 nights/month or considering screening history yielded similar results. Our findings lend no support for a major role of night-shift work in prostate cancer development. [ABSTRACT FROM AUTHOR]