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Melatonin, sleep disturbance and cancer risk
Abstract
The pineal hormone melatonin is involved in the circadian regulation and facilitation of sleep, the inhibition of cancer development and growth, and the enhancement of immune function. Individuals, such as night shift workers, who are exposed to light at night on a regular basis experience biological rhythm (i.e., circadian) disruption including circadian phase shifts, nocturnal melatonin suppression, and sleep disturbances. Additionally, these individuals are not only immune suppressed, but they are also at an increased risk of developing a number of different types of cancer. There is a reciprocal interaction and regulation between sleep and the immune system quite independent of melatonin. Sleep disturbances can lead to immune suppression and a shift to the predominance in cancer-stimulatory cytokines. Some studies suggest that a shortened duration of nocturnal sleep is associated with a higher risk of breast cancer development. The relative individual contributions of sleep disturbance, circadian disruption due to light at night exposure, and related impairments of melatonin production and immune function to the initiation and promotion of cancer in high-risk individuals such as night shift workers are unknown. The mutual reinforcement of interacting circadian rhythms of melatonin production, the sleep/wake cycle and immune function may indicate a new role for undisturbed, high quality sleep, and perhaps even more importantly, uninterrupted darkness, as a previously unappreciated endogenous mechanism of cancer prevention.
... [2][3][4][5]. Several pathways may exist through which sleep traits may have downstream effects on the risk of lung cancer (6,7). Proposed mechanisms linking sleep and lung cancer include melatonin pathophysiology, physiologic changes in cellular function, and suppressed immune function (6,7). ...
... Several pathways may exist through which sleep traits may have downstream effects on the risk of lung cancer (6,7). Proposed mechanisms linking sleep and lung cancer include melatonin pathophysiology, physiologic changes in cellular function, and suppressed immune function (6,7). However, limited studies have examined these proposed associations, with inconsistent results (5,(8)(9)(10)(11)(12)(13)(14)(15). ...
... Furthermore, suggestive positive associations were observed for insomnia symptoms and short sleep duration on lung cancer risk. Plausible biologic mechanisms linking insomnia to lung cancer risk include altered immune function and secretion of melatonin (6). Further studies are needed to elucidate the relationships between sleep duration and insomnia on lung carcinogenesis and to better understand the possible molecular mechanisms. ...
Background:
Relationships between sleep duration, chronotype, insomnia and lung cancer risk have not been comprehensively examined. Inter-relations between sleep traits on the risk of lung cancer have not been assessed. We aimed to examine sleep traits with lung cancer risk.
Methods:
Participants were recruited between 2006 - 2010 and followed through November 30th, 2020. We included 382,966 participants (3,664 incident lung cancer) in analysis. Cox proportional hazards models estimated hazards ratios (HR) and 95% confidence intervals (CI) for associations between sleep duration, chronotype, and insomnia symptoms and lung cancer risk. Joint effects analyses were examined between sleep duration and three traits (chronotype,insomnia,daytime napping). Non-linear associations between sleep duration and lung cancer risk were assessed in restricted cubic spline analysis.
Results:
Longer sleep (>8 hours) was positively associated with lung cancer risk compared with normal sleep duration (7-8 hours; HR=1.22; 95% CI: 1.10, 1.36). Frequent insomnia symptoms increased the risk of lung cancer compared with never/rarely experiencing symptoms (HR= 1.16; 95% CI: 1.05, 1.28). Joint effects between sleep duration and chronotype, and sleep duration and insomnia symptoms were observed. In analysis excluding participants reporting shift work at baseline, evening chronotypes ('slight', 'definite') were at a greater risk of lung cancer compared with definite morning chronotype (HR=1.17; 95% CI: 1.06, 1.28 and HR=1.37; 95% CI: 1.21, 1.54, respectively).
Conclusions:
Sleep traits such as long sleep duration, frequent insomnia symptoms, and definite evening chronotype may be risk factors for lung cancer. Joint effects should be further investigated.
Impact:
Sleep traits may be risk factors of lung cancer.
... Indeed, shorter hours of sleep are reported to be associated with several health conditions, from cardiovascular disease to diabetes and cancer [33]. Short sleep duration can indeed negatively influence several homeostatic systems, possibly resulting in procarcinogen effects on stem cells [34,35]. Moreover, the bidirectional relationship between psychological disorders and sleep is well known. ...
... On the other hand, long sleep duration (commonly referred as >8-9 h of sleep) also seems to act negatively on health, and could be a symptom of major depression. Once sleep exceeds 8/9 h, metabolism takes a direction that results in an increased level of carcinogenic factors [35,41]. The association between long sleep duration and GI cancers has been explained as potentially confounded by low SES, low physical activity, and additional comorbidities. ...
The association between sleep and stress and cancer is underinvestigated. We evaluated these factors in association with gastric cancer (GC). Five case-control studies from the Stomach Cancer Pooling (StoP) Project were included. We calculated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for sleep duration and stress level in association with GC through multiple logistic regression models adjusted for several lifestyle factors. The analysis included 1293 cases and 4439 controls, 215 cardia and 919 noncardia GC, and 353 diffuse and 619 intestinal types. Sleep duration of ≥9 h was associated with GC (OR =1.57, 95% CI = 1.23–2.00) compared to 8 h. This was confirmed when stratifying by subsite (noncardia OR = 1.59, 95% CI = 1.22–2.08, and cardia OR = 1.63, 95% CI = 0.97–2.72) and histological type (diffuse OR = 1.65, 95% CI = 1.14–2.40 and intestinal OR = 1.24, 95% CI = 0.91–1.67). Stress was associated with GC (OR = 1.33, 95% CI = 1.18–1.50, continuous). This relationship was selectively related to noncardia GC (OR = 1.28, 95% 1.12–1.46, continuous). The risk of diffuse (OR = 1.32, 95% CI = 1.11–1.58) and intestinal type (OR = 1.23, 95% CI = 1.07–1.42) were higher when stress was reported. Results for the association between increasing level of stress and GC were heterogeneous by smoking and socioeconomic status (p for heterogeneity = 0.02 and <0.001, respectively). In conclusion, long sleep duration (≥9 h) was associated with GC and its subtype categories. Stress linearly increased the risk of GC and was related to noncardia GC.
... While all of the positive benefits of sleep have yet to be proven, it is generally accepted that sleep is necessary to restore and maintain physiological homeostasis after waking periods by removing waste through the glymphatic system, initiating and maintaining macromolecule biosynthesis, maintaining prophylactic cells, and regulating metabolic functions and energy balance [8,9]. The literature is clear that a healthy amount of sleep is essential for daily function as well as the prevention and treatment of chronic health conditions, especially cancer [10]. Patients with cancer have a higher-than-normal incidence of sleep disturbance; a problem that can continue for up to 9 years after entering remission [11]. ...
... For example, the preoptic area of the hypothalamus and thalamus coordinate sleep and waking states, while further sleep regulation and induction are influenced by melatonin secreted from the pineal gland [24]. This provides time-of-day information to all cells and serves as a biomarker of the central biological clock [10]. The hypothalamus and the adjacent neuron groups of the basal forebrain regulate sleep duration by producing GABA. ...
Sleep disturbance can occur when sleep centers of the brain, regions that are responsible for coordinating and generating healthy amounts of sleep, are disrupted by glioma growth or surgical resection. Several disorders cause disruptions to the average duration, quality, or patterns of sleep, resulting in sleep disturbance. It is unknown whether specific sleep disorders can be reliably correlated with glioma growth, but there are sufficient numbers of case reports to suggest that a connection is possible. In this manuscript, these case reports and retrospective chart reviews are considered in the context of the current primary literature on sleep disturbance and glioma diagnosis to identify a new and useful connection which warrants further systematic and scientific examination in preclinical animal models. Confirmation of the relationship between disruption of the sleep centers in the brain and glioma location could have significant implications for diagnostics, treatment, monitoring of metastasis/recurrence, and end-of-life considerations.
... Concretely, excess ALAN strongly interferes with the light from celestial bodies, making it problematic for astronomical instruments to seize them accurately [20]. Long-term exposure to inappropriate ALAN will induce diversiform physical and mental diseases and even endanger personal safety [2,[21][22][23][24][25][26][27]. Not only humans but also other organisms on Earth suffer from ALAN, as evidenced by the decay of biodiversity and the disruption of life rhythms [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. ...
... Studies also have shown that the threshold of lighting intensity affecting human physiology is so low that only one lux may disrupt circadian rhythms [21,91,92]. Physiologically, when exposed to excessive blue light from outdoor lighting or indoor displays, the eyes may suffer from accidental retinal damage due to oxidative stress [22] and may even lead to reduced levels of melatonin, leading to daily rhythm phase shifts, which increases the incidence of some diseases, including but not limited to vision loss, metabolic disorders, diabetes, obesity, coronary heart disease, tumors, and even cancer [23,[93][94][95][96][97][98][99][100]. Psychologically, the altered circadian rhythms triggered by the light environment may lead to alertness, rapid heart rate, sleep disturbances, mood disorders, and other derived problems such as depression, irritability, fatigue, and anxiety [25,26,101]. ...
With the rapid development of the global economy, the over-expansion of outdoor artificial light at night (ALAN) in cities has led to increasingly severe light pollution worldwide. More and more studies have paid attention to the problem of light pollution, but there is still a lack of systematic literature review on nighttime light pollution in terms of research progress, hotspots, and its evolutions. For this purpose, this study firstly analyzed current research actuality and trends about nighttime light pollution via a comprehensive retrospect of pertinent literature and summarized the adverse effects and monitoring technologies of light pollution by VOSviewer-based keyword co-occurrence technique. Additionally, the study explored the variation tendency of nighttime light pollution in typical countries from 2013 to 2021 based on remote-sensing data and further proposed management suggestions to protect the nighttime environment. The results indicate that the research popularity of nighttime light pollution has been increasing recently, especially after the opening of diversified remote-sensing data in 2012; the main research topics are dominated by adverse effects and monitoring technologies, where the latter is represented by ground survey and remote-sensing observation; the total levels of ALAN intensity are relatively high in most developed countries, but the mean and per capita values are decreasing, and the above phenomenon in developing countries show the opposite trend. This study expects to integrate the literature analysis method and remote-sensing data to demonstrate the research status and variation trends of nighttime light pollution systematically so as to provide scientific references for the assessment and management of the nighttime light environment.
... Melatonin is usually secreted during the night in the absence of light, and is essential for the regulation of sleep patterns and wake cycles. Decreased levels of melatonin that can be caused by light-and temperature-related stress conditions have been connected to development of human breast cancer xenografts and rat hepatomas, immunosuppression, and sleep disturbance [34,35]. On top of this, sleep disturbance on its own can lead to an increased production of cancer-stimulatory cytokines [35]. ...
... Decreased levels of melatonin that can be caused by light-and temperature-related stress conditions have been connected to development of human breast cancer xenografts and rat hepatomas, immunosuppression, and sleep disturbance [34,35]. On top of this, sleep disturbance on its own can lead to an increased production of cancer-stimulatory cytokines [35]. Although there are no specific associations between the development of cancer in sleep deprived individuals due to low secretion of melatonin and installation of cancer, studies have shown that melatonin is able to impair malignant cell proliferation and also initiate apoptosis [33]. ...
Hypoxia is the main cause and effect of a large number of diseases, including the most recent one facing the world, the coronavirus disease (COVID-19). Hypoxia is divided into short-term, long-term, and periodic, it can be the result of diseases, climate change, or living and traveling in the high mountain regions of the world. Since each type of hypoxia can be a cause and a consequence of various physiological changes, the methods for modeling these hypoxias are also different. There are many techniques for modeling hypoxia under experimental conditions. The most common animal for modeling hypoxia is a rat. Hypoxia models (hypoxia simulations) in rats are a tool to study the effect of various conditions on the oxygen supply of the body. These models can provide a necessary information to understand hypoxia and also provide effective treatment, highlighting the importance of various reactions of the body to hypoxia. The main parameters when choosing a model should be reproducibility and the goal that the scientist wants to achieve. Hypoxia in rats can be reproduced both ways exogenously and endogenously. The reason for writing this review was the aim to systematize the models of rats available in the literature in order to facilitate their selection by scientists. The relative strengths and limitations of each model need to be identified and understood in order to evaluate the information obtained from these models and extrapolate these results to humans to develop the necessary generalizations. Despite these problems, animal models have been and remain vital to understanding the mechanisms involved in the development and progression of hypoxia. The eligibility criteria for the selected studies was a comprehensive review of the methods and results obtained from the studies. This made it possible to make generalizations and give recommendations on the application of these methods. The review will assist scientists in choosing an appropriate hypoxia simulation method, as well as assist in interpreting the results obtained with these methods.
... In addition to its central role in the regulation of sleep and wake cycles, melatonin is involved in the modulation of the immune system, tumor growth inhibition and anti-aging processes. Several mechanisms have been proposed to link sleep disturbances and circadian rhythm disruption with cancer development and growth, including melatonin physiopathology, immune suppression, and cancerstimulatory cytokines activation [4,5]. ...
... The biologic mechanisms underlying the potential association between sleep disorders and incidence of cancer are complex. Sleep deprivation could result in immune suppression, activate cancer-stimulatory cytokines and finally promotes cancer [4,5]. In contrast, long sleep duration could indicate ill-health, which could in turn increase cancer incidence [10]. ...
... In addition to its central role in the regulation of sleep and wake cycles, melatonin is involved in the modulation of the immune system, tumor growth inhibition and anti-aging processes. Several mechanisms have been proposed to link sleep disturbances and circadian rhythm disruption with cancer development and growth, including melatonin physiopathology, immune suppression, and cancer-stimulatory cytokines activation [4,5]. ...
... The biologic mechanisms underlying the potential association between sleep disorders and incidence of cancer are complex. Sleep deprivation could result in immune suppression, activate cancer-stimulatory cytokines and finally promotes cancer [4,5]. In contrast, long sleep duration could indicate ill-health, which could in turn increase cancer incidence [10]. ...
Circadian rhythm disruption due to night shift work and/or sleep disorders is associated with negative health outcomes including cancer. There is only scant evidence of an association with lung cancer, unlike breast and prostate cancer. We explore the role of sleep disorders and night shift work in lung cancer risk among women in a population-based case-control study, including 716 lung cancer cases and 758 controls. Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with sleep duration per day (<7 h, 7–7.9 h, ≥8 h), a summary index of sleep disorders, chronotype, and night shift work exposure metrics. When compared to women with an average sleep duration of 7–7.9 h per day, the OR was 1.39 (95% CI 1.04–1.86) in long sleepers (≥8 h) and 1.16 (95% CI 0.86–1.56) in short sleepers (<7 h). Overall, lung cancer was not associated with the sleep disorder index, nor with night shift work, regardless of the duration of night work or the frequency of night shifts. However, elevated OR associated with the sleep disorder index were found in the subgroup of current smokers. The U-shaped association of lung cancer with sleep duration was more particularly pronounced among women who worked at night ≥5 years. Our findings suggested that sleep patterns are associated with lung cancer risk in women with a potential modifying effect by night shift work duration or tobacco smoking.
... The exposure assessments used in these studies are not always comparable among them, and studies did not always take into account cancer aggressiveness or other circadian disturbance parameters, such as chronotype or night shift work, which further complicates the conclusions that can be drawn. Biological mechanisms underlying the potential association between sleep disorders and incidence of cancer include: a dysregulation of the production of melatonin which is known to inhibit cancer cell proliferation (Gilad, 1998, Joo S, 2009), a decrease of immune system and the activation of cancerstimulatory cytokines (Blask 2009), a systemic inflammation with increases in levels of C-Reactive Protein (CRP) and Interleukine-6 (IL6) (Irwin et al. 2016) or disruption and promotion of the activity of neuroendocrine stress systems (Meerlo et al. 2008). ...
... It has been showed that men with sleep problems had lower morning levels of urinary 6-sulfatoxymelatonin, a major metabolite of melatonin, which has been associated with increased risk of advanced prostate cancer (Sigurdardottir et al. 2015). Another hypothesis is that sleep deprivation can also lead to immune suppression, activate cancer-stimulatory cytokines and finally promotes cancer (Blask 2009;Faraut et al. 2013). In contrast, long sleep duration could be a marker of ill-health, rather than a direct effect in cancer risk (Cappuccio 2010). ...
Background:
Sleep disturbances have been singled out for their implication in the risk of several cancer sites. However, results for prostate cancer are still inconsistent.
Methods:
We used data from the EPICAP study, a French population-based case-control study including 819 incident prostate cancer cases and 879 controls frequency matched by age. Detailed information on sleep duration on work/free days, and sleep medication over lifetime was collected.
Results:
Sleep duration and sleep deprivation were not associated with prostate cancer, whatever the aggressiveness of prostate cancer. However, sleep deprivation was associated with an increased prostate cancer risk among men with an evening chronotype (OR= 1.96, 95% CI 1.04-3.70). We also observed an increased risk of prostate cancer with higher duration of sleep medication use (p for trend= 0.008). This association with long duration of sleep medication use (≥10 years) was more pronounced among men who worked at night 15 years or more (OR= 3.84, 95% CI 1.30-11.4) and among non-users of non-steroid anti-inflammatory drug (NSAID) (OR = 2.08, 95% CI 1.15-3.75).
Conclusions:
Our results suggested that chronotype, night work, or NSAID use could modify the association between sleep disorders and prostate cancer occurrence needing further investigations to go further.
Impact:
EPICAP is the first study which investigates several sleep indicators taking into account potential effect modifiers. If our findings were confirmed, we could identify subgroups of men at higher risk of PCa that may be accessible to preventive measures.
... In recent years, sleep disorders are emerging environmental factors that influence the risk of BC 11-14 and are co-morbid with the MS. The association between sleep and BC may be explained by misalignment of the molecular clock circadian rhythm that decreases melatonin secretion, an oncostatic agent and estrogen suppressor [15][16][17] and by altering the regulation of glucose tolerance and insulin-sensitivity 18,19 . Sleep problems or bad sleep quality increase after BC diagnosis and treatment and are more common in BRCA1/2 mutation carriers compared to general population 20 . ...
... The sum of the seven components returns a final score from 0 to 21, with lower scores indicating a better sleep quality. The cut-off value of 5 divides participants into good sleepers (0-5) from bad sleepers (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). In addition, the numbers of hours spent in bed and sleeping and the sleep efficiency can be obtained from the questionnaire 38,40 . ...
The aim of the present study is to explore the potential association between sleep quality and physical activity (PA) in women carriers of BRCA1/2 mutations. 63 women completed the Pittsburgh Sleep Quality Index (PSQI) and Godin Shepard Leisure-Time Physical Activity Questionnaire (GSL-TPAQ) and were included in the present cross-sectional analysis. Globally, women showed a PSQI score of 7.0 ± 3.6 and a GSL-TPAQ score of 22.8 ± 18.3. Good sleepers (PSQI score ≤ 5) showed significantly higher PA levels compared to bad sleepers (PSQI score > 5). Women in the higher tertile of GSL-TPAQ total score (≥ 27 METs/week) have a prevalence ratio (PR) of being a good sleeper of 2.85 (1.25–6.52, 95% confidence intervals) compared to women in the lower tertile (≤ 11 METs/week). These results were consistent in BRCA1 and BRCA2 women. Considering each single question of PA intensity, the PR of being a good sleeper by unit of increase of MET/week was higher and significant in women engaged in strenuous and moderate intensity PA. These results suggests a direct association between PA and sleep quality in women carriers of BRCA mutations.
... Artificial light at night is of major concern to the epidemiologist and oncologist based on its implication in cancer of breast in females and prostate cancer in males (Haim and Portnov, 2014; Al-Naggar and Anil, 2016; Garcia-Saenz et al., Haim et al., 2019). [1][2][3][4] The consequences and negative impact of exposure to light reported was directly linked to its ability to suppress melatonin (Falchi et al., 2011;Haim and Zubidat, 2015), [5,6] an ubiquitous hormone known to play vital roles in the survival of animals due to its activity in combating oxygen radicals (Blask, 2009;Reiter et al., 2011 andGuerrero et al., 2013). [7][8][9] Melatonin is responsible for various physiological processes (Barrenetxe et al., 2004;Golan et al., 2018) [10][11] in the body and any alteration in its activity could be detrimental to the body. ...
... [1][2][3][4] The consequences and negative impact of exposure to light reported was directly linked to its ability to suppress melatonin (Falchi et al., 2011;Haim and Zubidat, 2015), [5,6] an ubiquitous hormone known to play vital roles in the survival of animals due to its activity in combating oxygen radicals (Blask, 2009;Reiter et al., 2011 andGuerrero et al., 2013). [7][8][9] Melatonin is responsible for various physiological processes (Barrenetxe et al., 2004;Golan et al., 2018) [10][11] in the body and any alteration in its activity could be detrimental to the body. Moreover, previous studies focus mostly on the effect of white light on the activity of melatonin (Haim and Portnov, 2014) [1] but recent studies have shown that all the light spectra have the potential to suppress melatonin, this time with respect to the light intensity (Zubidat et al., 2011;Haim et al., 2019). ...
Artificial light at night is considered as environmental stressor depending largely on the spectra. Haematological parameters have been used as bio-indicator of stress when animals are subjected to unfavourable environmental condition. Hence this study evaluated the effect of various spectra of light on the haematology of albino rats. Day old rats were exposed to blue (BL), green (GL), yellow (YL), red (RL) and white (WL) lights at night while darkness (DD) and ambient light (CL) served as control. Compact florescent bulbs were used and light intensity maintained at 300 lux. At days 35, 63, 91 and 126, six rats per treatment and per sex were euthanized. Blood was collected and analysed for haematocrit (Hct), haemoglobin (Hb) and red blood cells (RBC). At d35 and d63, Hct and Hb and RBC were significantly (p < 0.05) low in male and female rats exposed to coloured light. Hct and Hb recorded in the male rats exposed to green light and female rats exposed to blue and green lights were lower than the normal physiological range for rats at these ages bracket. Further exposure to light at d91 and d126 showed no negative effects on blood parameters. Linear regression showed significant increase in the blood parameter with time on exposure to coloured light which together signifies adaptation. Exposure to light of high energy (BL and GL) and WL during prepubertal could be detrimental. Normal day and night light cycle provided the optimum environmental lighting condition for adequate homeostatic of the blood in rats.
... Possible reasons for this race-based discrepant finding are that Asians have lower melatonin levels compared to Caucasians (70,71), and Asians have a different sleep pattern characterized by more naps during the day and shorter sleeping duration at night (72). Several plausible mechanisms have been proposed to explain associations between short sleep duration and cancer risk (73,74). First, short sleep duration is associated with decreased levels of melatonin, which plays a role in suppressing the initiation of tumorigenesis and inhibiting cancer cell proliferation (73,74). ...
... Several plausible mechanisms have been proposed to explain associations between short sleep duration and cancer risk (73,74). First, short sleep duration is associated with decreased levels of melatonin, which plays a role in suppressing the initiation of tumorigenesis and inhibiting cancer cell proliferation (73,74). Second, short sleep duration may lead to suppression of immune system and alter cytokine production, which can increase cancer risk (75,76). ...
Current literature has identified relationships among sleep, nutrition, and diet-related chronic diseases; however, knowledge about how sleep influences diet-related diseases is lacking in dietetics practice. This narrative review briefly explains sleep physiology and outlines the relationships between sleep duration and quality and common nutrition-related diseases, including obesity, diabetes, cardiovascular disease, obstructive sleep apnea, and cancer. Additionally, the review discusses how sleep influences wound healing and pregnancy outcomes and why hospitalized patients are likely to experience sleep problems. Plausible mechanisms explaining the relationships between sleep and disease are presented. Finally, commonly used sleep assessment tools and interventions are reviewed. Given the importance of sleep to health, dietitians should not only be aware of the role sleep plays in disease development and prevention but also assess sleep when feasible and refer patients and clients who are at high risk for sleep problems to a sleep clinic or community program that can address sleep issues.
Teaching points:
• • Sleep duration and quality influence risk and outcomes of common nutrition-related diseases.
• • Sleep health evaluation is a missing piece in dietetic practice.
• • There are easy-to-use, validated tools that dietitians can use to screen for sleep problems in order to refer patients and clients to sleep experts.
... Several studies found that administration of antipsychotic drugs such as haloperidol or fluvoxamine can induce CRSD such as DSWPD [ [ 14,15,16,17,18,19,20 ]. Modern living styles characterized by nocturnal living patterns, shift-time work, and working in offices with little variation in illumination throughout the day and night may also induce disorders in biological rhythm. ...
... Therefore, continuous exposure to nighttime illumination from digital media devices may be a risk factor to developing sleep or sleep/wake circadian disorders. It is well-established in the sleep literature that targeted exposure to bright ALAN can delay sleep onset and melatonin secretion [ 14,15,16,23,24 ], and therefore is considered an effective treatment for circadian rhythms sleep disorders [ 25,26 ]. In our opinion, extended exposure to light from digital screens at night is in practice a form of unintended "light therapy" that affects the circadian clock and its derivatives and consequently influences sleep capacity and quality. ...
Circadian rhythm sleep disorders (CRSD) are a group of sleep disorders characterized by a de-synchronization between a person’s biological clock and the environmental 24-h schedule. There are six main types of CRSD, namely, advanced sleep phase syndrome (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm (ISWR), free running disorder (FRD), shift work type (SWD), and jet lag disorder (JLD). Physiological data and genetic studies in patients with CRSDs suggest that these disorders result from abnormal functioning of the circadian rhythm system. The diagnosis of CRSD is based on clinical interview and sleep log diaries and/or actigraphic monitoring under a free condition schedule. Bright-light therapy and melatonin administration have proved to be the most effective treatments for CRSD. Difficulties in daytime functioning are one of the prominent characteristics of CRSDs. Individuals with CRSDs frequently fail to adjust to the normal accepted hours of activity. It is common that the daytime functional difficulties that accompany CRSDs are misinterpreted as symptoms of psychopathology or daily dysfunction. CRSDs are under-recognized and frequently misdiagnosed, and therefore treated as psychological, psychiatric, and/or sleep disorders. Recognition and awareness of the characterization of these disorders should improve the diagnosis and treatment of these patients.KeywordsCircadian rhythm sleep disordersInsomniaHypersomniaDepression
... Melatonin is a hormone released from the pineal gland, usually at night. It has many roles in the human body, regulating circadian and sleep/wake cycles and enhancing sleep (Blask 2009). Melatonin can be found in many fruits (e.g., grapes and berries), vegetables (e.g., tomato), seeds (e.g., black and white mustard), cereals, and nuts (e.g., pistachio) (Meng, et al. 2017). ...
Sleep quality and its effects have become a public concern over the last few years. While the prevalence of sleep disorders was increasing, several studies have linked diet and physical activity as a cause of it. Indeed, many people complain about their sleeping problems without considering their lifestyle as a cause. This leads the efforts to focus on these principal factors and find their specific effect. The study aims to map out the research on the effect of nutrition and physical activity on sleep quality. The literature search was conducted in electronic libraries and databases related to nutrition and medical literature – Google Scholar, PubMed, and ScienceDirect– using relevant selected keywords. Article inclusion and selection were made by excluding duplicates, analyzing titles and abstracts, and reviewing the articles’ full text. This review included 61 articles. This literature study reinforces the importance of researching sleep and the lifestyle contributors to poor sleep, such as physical activity and nutrition.
... It is reported that insomnia constitutes a common health concern, with an estimated incidence ranging from 5 to 50% (Morin and Jarrin 2022), which is associated with a number of negative consequences such as hypertension (Jarrin et al. 2018), cardiac events (Zhong et al. 2023), mood/anxiety disorders (Palagini et al. 2022), and cancer (Blask 2009). In addition, our bodies require appropriate sleep duration to perform regular physiological, cognitive and psychological processes, and excessive or insufficient sleep length can be harmful to our health (Diekelmann and Born 2010). ...
Recently, polycyclic aromatic hydrocarbons (PAHs) were found to be linked to various diseases. The current study’s objective was to explore whether or not there was a relation between PAH exposure and poor sleep pattern. We evaluated nine urine PAH metabolites as exposures in our cross-sectional research based on the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Logistic regression, restricted cubic spline regression (RCS) model, weighted quantile sum (WQS) regression, subgroup analysis, and mediation analysis were used to assess the associations between PAH metabolism and poor sleep pattern risk. After controlling for all confounding variables, several primary PAH metabolites, namely 1-hydroxynapthalene (1-NAP, OR 1.32, 95% CI 1.04–1.68), 2-hydroxyfluorene (2-FLU, OR 1.34, 95% CI 1.05–1.71), 1-hydroxyphenanthrene (1-PHE, OR 1.30, 95% CI 1.03–1.64), 9-hydroxyfluorene (9-FLU, OR 1.38, 95% CI 1.09–1.74), and ∑PAHs (OR 1.33, 95% CI 1.05–1.69), compared to the bottom tertile, were associated with increased risk of poor sleep pattern. The WQS regression analysis showed that 9-FLU and 1-NAP comprised the two most important factors related to poor sleep pattern. Mediation analysis revealed that inflammation acted as a mediator between PAHs and the prevalence of poor sleep pattern. In conclusion, exposure to PAHs may be associated with poor sleep pattern. Inflammation is a mediator of the effects of PAH exposure on poor sleep pattern.
... One of the consequences of light pollution is the negative impact it has on mammal animals [6,7], insects [8,9] and human health. Studies have shown a link between light pollution, disturbed human biorhythms, and increased numbers of patients with certain cancers, particularly breast and colon cancer [10,11]. It is shown that the proportion of patients with direct exposure to artificial light from unsuitable lighting systems is higher if they are exposed to it during typical sleep times and/or when working night shifts. ...
... Pineal gland-secreted melatonin during darkness maintains the circadian clock resulting in sleep stimulation and its regulation [113][114][115]. Reportedly, disruption in melatonin expression could also result in reduced immune response, sleep disturbance, and cancer [116]. Advancing age-dependent reduction of melatonin levels occurs mainly due to calcification of the pineal gland [117,118]. ...
Abstract
Increasing incidences of insomnia in adults, as well as the aging population, have been reported for their negative impact on the quality of life. Insomnia episodes may be associated with neurocognitive, musculoskeletal, cardiovascular, gastrointestinal, renal, hepatic, and metabolic disorders. Epidemiological evidence also revealed the association of insomnia with oncologic and asthmatic complications, which has been indicated as bidirectional. Two therapeutic approaches including cognitive behavioral therapy (CBT) and drugs-based therapies are being practiced for a long time. However, the adverse events associated with drugs limit their wide and long-term application. Further, Traditional Chinese medicine, acupressure, and pulsed magnetic field therapy may also provide therapeutic relief. Notably, the recently introduced cryotherapy has been demonstrated as a potential candidate for insomnia which could reduce pain, by suppressing oxidative stress and inflammation. It seems that the synergistic therapeutic approach of cryotherapy and the above-mentioned approaches might offer promising prospects to further improve efficacy and safety. Considering these facts, this perspective presents a comprehensive summary of recent advances in pathological aetiologies of insomnia including COVID-19, and its therapeutic management with a greater emphasis on cryotherapy.
Key words
insomnia / cognitive behavioral therapy / whole-body cryotherapy / traditional chinese medicine / pulsed magnetic field therapy / acupressure
... 15 Moreover, sleep disturbance can lead to immuno-suppression and augment the release of cancer-stimulatory cytokines. 16 Furthermore, a strong regulatory effect may augment metastatic stages in cancer along with sleep deprivation. In the current work, the overall response rate (ORR) (including either complete or partial response) was higher as compared to patient data from the MONALEESA-2 trial. ...
... Light at night for prolonged night-shift work, e.g. working night shift for several years, has been associated with numerous adverse health outcomes, including obesity, cardiovascular problems, and cancer [1][2][3][4][5][6][7][8][9]. Mechanisms contributing to these consequences are related to the disruption of circadian rhythms, e.g. the sleep-wake cycle and the melatonin secretion. ...
In industrialized countries with their 24-h societies humans are increasingly exposed to light at night. More and more people are working at night or in evening shifts in times when the circadian system expects darkness to function smoothly. On one hand, light at night is necessary for work and safety reasons, on the other side it can lead to negative health consequences. In this study we investigate the research question, if it is possible to design the spectral and spatial features of a lighting installation for night shift workers to minimize the melatonin suppression and at the same time to support acute alertness. This paper focuses on the applied method because it is an ongoing study and results are planned to become available from late summer 2022 on. The results can be used to derive
recommendations for health-promoting lighting during the night shift, for example for control centers, control rooms or similar workplaces.
... For example, shift workers are at higher risk of developing cancer, metabolic syndrome, immune system dysfunction, and mental health disorders (45,551). Melatonin rhythm disruption can disinhibit cancer cell growth factors, lower immune function (42), and drive resistance to hormonal therapy for breast cancer (115). The enduring emergence of strong evidence from preclinical animal studies and retrospective human findings linking circadian disruption and cancer, led the World Health Organization to designate shift work as a class 2a probable carcinogen (in the same category as ultraviolet radiation) in 2007 (134). ...
Circadian rhythms are endogenously generated, daily patterns of behavior and physiology that are essential for optimal health and disease prevention. Disruptions to circadian timing are associated with a host of maladies, including metabolic disease and obesity, diabetes, heart disease, cancer, and mental health disturbances. The circadian timing system is hierarchically organized, with a master circadian clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks throughout the CNS and periphery. The SCN receives light information via a direct retinal pathway, synchronizing the master clock to environmental time. At the cellular level, circadian rhythms are ubiquitous, with rhythms generated by interlocking, autoregulatory transcription-translation feedback loops. At the level of the SCN, tight cellular coupling maintains rhythms even in the absence of environmental input. The SCN, in turn, communicates timing information via the autonomic nervous system and hormonal signaling. This signaling couples individual cellular oscillators at the tissue level in extra-SCN brain loci and the periphery and synchronizes subordinate clocks to external time. In the modern world, circadian disruption is widespread due to limited exposure to sunlight during the day, exposure to artificial light at night, and widespread use of light-emitting electronic devices, likely contributing to an increase in the prevalence, and the progression, of a host of disease states. The present overview focuses on the circadian control of endocrine secretions, the significance of rhythms within key endocrine axes for typical, homeostatic functioning, and implications for health and disease when dysregulated. © 2022 American Physiological Society. Compr Physiol 12: 1-30, 2022.
... Prevalence or incidence rates of several cancers were considered, with breast cancer (BC) in women and prostate cancer (PC) in men as the most frequent types of cancers evaluated. Evidence from animal studies and limited epidemiology on night-shift work suggests that hormone-dependent cancers are especially affected by circadian disruption likely due to the potential role of melatonin as a modulator of cell proliferation [43,44]. ...
Exposure to artificial light at night (ALAN) has been associated with disruption of the circadian system, which has been pointed out to have detrimental effects on health. Exposure to outdoor ALAN is very frequent in industrialised countries due to nocturnal light pollution and the relevant involvement of the total workforce in shift work and night work. Ecological and epidemiologic studies highlight the association between exposure to ALAN and several diseases, mainly obesity and cancer. More recently, also indoor ALAN exposure has been investigated. Among several multifactorial mechanisms linking ALAN exposure and health risks, suppression of melatonin secretion plays a pivotal role leading to alterations in circadian rhythm patterns, that are detrimental in terms of appetite regulation, and dysfunctions in metabolic signalling and cell growth in cancer. In addition, gut dysbiosis, inflammation, hypovitaminosis D, imbalance in cytokine secretion and levels are responsible for the multiple relationship linking circadian dysregulation due to ALAN exposure and obesity, and cancer. Therefore, the current manuscript summarises human and basic studies pointing out the impact of ALAN exposure on health, mostly focusing on obesity and cancer. Based on extant evidence, prevention strategies for obesity and cancer should be prompted, targeting exposure to ALAN.
... Several potential mechanisms may explain the relationship between sleep duration and mortality. Previous studies have showed that, sleep restriction could influence the endocrine and metabolic system, such as decreased the levels of testosterone and melatonin (23,24), reduced level of leptin, and elevated level of ghrelin (25,26), which may be implicated with mortality (27)(28)(29)(30). The mechanisms for extreme long sleep duration and mortality are considered more indeterminate. ...
To clarify the association of sleep duration with all-cause and cardiovascular mortality, and further estimate the population attributable fraction (PAF) for the 10-year risk of cardiovascular disease (CVD) due to inappropriate sleep duration among US adults, we included data of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014 by linkage to the National Death Index until December 31, 2015 in a prospective design. Cox proportional hazards models were used for multivariate longitudinal analyses. The Pooled Cohort Equations methods was adopted to calculate the predicted 10-year CVD risk. In the current study, sleep <5 h or longer than 9 h per day were significantly associated with elevated risks of all-cause mortality, and the multivariable-adjusted HRs across categories were 1.40 (95% CI, 1.14–1.71), 1.12 (95% CI, 0.91–1.38), 1 (reference), 1.35 (95% CI, 1.12–1.63), and 1.74 (95% CI, 1.42–2.12). Similarly, the HRs of cardiovascular mortality across categories were 1.66 (95% CI, 1.02–2.72), 1.15 (95% CI, 0.77–1.73), 1 (reference), 1.55 (95% CI, 1.05–2.29), and 1.81 (95% CI, 1.09–3.02). Under a causal–effect assumption, we estimated that 187 000 CVD events (PAF 1.8%, 0.9% to 2.3%) were attributable to short sleep duration and 947 000 CVD events (PAF 9.2%, 6.4% to 11.6%) were attributable to long sleep duration from 2018 to 2028. This study informed the potential benefit of optimizing the sleep duration for the primary prevention of CVD in a contemporary population.
... In addition to exposure in the home or at workplaces (particularly due to shift work), streetlights and light-emitting diodes (LEDs), particularly on the screens of televisions, computers, and mobile phones, are increasingly pervasive sources of ALAN in society. In the past two decades, several epidemiological studies have demonstrated that ALAN exposure has detrimental impacts on sleep and sleeping behaviour [18,20,[22][23][24]. While the majority of existing ALAN studies were primarily focused on sleep, some recent studies have demonstrated that ALAN is also associated with other physiological and behavioural functions. ...
Artificial light at night (ALAN) exposure is associated with the disruption of human circadian processes. Through numerous pathophysiological mechanisms such as melatonin dysregulation, it is hypothesised that ALAN exposure is involved in asthma and allergy, mental illness, and cancer outcomes. There are numerous existing studies considering these relationships; however, a critical appraisal of available evidence on health outcomes has not been completed. Due to the prevalence of ALAN exposure and these outcomes in society it is critical that current evidence of their association is understood. Therefore, this systematic scoping review will aim to assess the association between ALAN exposure and asthma and allergy, mental health, and cancer outcomes. This systematic scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We will search bibliographic databases, registries, and references. We will include studies that have described potential sources of ALAN exposure (such as shift work or indoor and outdoor exposure to artificial light); have demonstrated associations with either allergic conditions (including asthma), mental health, or cancer-related outcomes; and are published in English in peer-reviewed journals. We will conduct a comprehensive literature search, title and abstract screening, full-text review, and data collection and analysis for each outcome separately.
... Such sleep-related characteristics of patients with cancer reduce immune functioning (Firth et al., 2017a) and elicit changes in carbohydrate metabolism and endocrine function (Spiegel et al., 1999). Further, they slow their recovery and exacerbate the disorder (Blask, 2009). Increased pain sensitivity (Sateia and Lang, 2008), fatigue, depression levels (Donovan and Jacobsen, 2007), and reduced quality of life (Simon and Vonkorff, 1997) also frequently arise due to sleeprelated problems. ...
Objective:
This pilot study aimed to evaluate the efficacy of a digital cognitive behavioral therapy (dCBT) in patients with cancer experiencing sleep problems.
Methods:
A total of 57 participants aged 25-65 years (6M/51F with a mean of 42.80 years and a standard deviation of 14.15 years) were randomly assigned to three groups-21 participants to a dCBT program (HARUToday Sleep), 20 participants to an app-based attentional control program (HARUCard Sleep), and 16 participants to a waitlist control group-and evaluated offline before and after the program completion. Of the 57 participants, there were a total of 45 study completers, 15 participants in each group. The dependent variables were sleep quality scores, measured by the Pittsburgh Sleep Quality Index (PSQI) and health-related quality of life scores, measured using the Short-Form 36 (SF-36), and attentional bias scores from a dot-probe computer task.
Results:
For both the intention-to-treat (N = 57) and study-completers analyses (N = 45, 15 for each group), a significant increase supported by a large effect size was found in the quality of sleep score of the HARUToday Sleep group compared to both the app-based attentional control and the waitlist control group. However, no significant changes were found in the quality of life and attentional bias scores.
Conclusion:
Our results suggest that the HARUToday Sleep app has the potential to serve as an intervention module to enhance the sleep quality of patients with cancer experiencing sleep problems.
... Existing literature have established the effects of physical activity (1,2), screen time (3,4), and sleep duration (5,6) on the depression status of both, adolescent and adult populations. Moreover, previous studies revealed that unhealthy time use activities (e.g., excessive sedentary time, inadequate sleep duration) were risk predictors of physiological diseases, including cardiovascular diseases (7)(8)(9), hypertension (10,11), and cancers (12)(13)(14). Based on plentiful existing evidence, the World Health Organization (WHO) and other health institutes proposed updated time use guidelines to direct people's daily activities for substantial health benefits (15)(16)(17)(18). ...
Background
To date, the relationship between diverse time use behaviors and depression status among emerging adults have not been disentangled in the literature. Therefore, if and how the time displacement mechanism activates depressive symptoms among emerging adults remains unclear.
Methods
To fill this gap in the literature, we employed a network analysis to make estimations. The emerging adult sample ( N = 1,811) was collected by the Guizhou Population Health Cohort Study. Time use behaviors were measured by an adaption of the self-administered International Physical Activity Questionnaire, and depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9).
Results
The results revealed that the time displacement mechanism of emerging adults differed from that of adolescents. Sleep duration was not crowded out by other activities, while the time spent on computer use was found to be negatively related to time spent on heavy work activities. Moreover, computer use behavior triggered three depressive symptoms (“Anhedonia,” “Guilt,” and “Motor”), but inhibited “Suicide.” The results of the directed acyclic graph revealed that females and heavy drinkers were at risk of depression.
Limitations
The study sample was confined to only one province, which may limit its generalizability. The cross-sectional design impeded the ability to draw causal inferences.
Conclusion
Our results enhance the current understanding of the internal mechanism of how time use behaviors influence depressive symptoms among emerging adults.
... Nocturnal melatonin secretion can persists in constant darkness, but exposure to light during the nighttime can suppress the release of the hormone into the bloodstream (25). The endogenous activity of the central clock results in melatonin production, so suppression of melatonin can lead to stimulation of cancer development (27). The possibility of chronotherapy and melatonin supplementation can be applied as a new platform to enhance the efficacy of chemotherapy drugs through precise time-dependent administration (28). ...
The circadian system is an innate clock mechanism that governs biological processes on a near 24-hour cycle. Circadian rhythm disruption (i.e., misalignment of circadian rhythms), which results from the lack of synchrony between the master circadian clock located in the suprachiasmatic nuclei (SCN) and the environment (i.e., exposure to day light) or the master clock and the peripheral clocks, has been associated with increased risk of and unfavorable cancer outcomes. Growing evidence supports the link between circadian disruption and increased prevalence and mortality of genitourinary cancers (GU) including prostate, bladder, and renal cancer. The circadian system also plays an essential role on the timely implementation of chronopharmacological treatments, such as melatonin and chronotherapy, to reduce tumor progression, improve therapeutic response and reduce negative therapy side effects. The potential benefits of the manipulating circadian rhythms in the clinical setting of GU cancer detection and treatment remain to be exploited. In this review, we discuss the current evidence on the influence of circadian rhythms on (disease) cancer development and hope to elucidate the unmet clinical need of defining the extensive involvement of the circadian system in predicting risk for GU cancer development and alleviating the burden of implementing anti-cancer therapies.
... [16,17] Melatonin, or sleep hormone, is primarily released by the brain in response to darkness and helps regulate the body's sleep-wake cycle. [18] To the best of our knowledge, no study has been conducted and published on the comparative effects of eye masks and music on anxiety levels and hemodynamic indices of patients undergoing coronary angiography. The present study was thus conducted to examine the comparative effects of eye masks and music on anxiety levels and hemodynamic indices of patients undergoing coronary angiography. ...
Context: Anxiety is common among patients undergoing coronary angiography.
Aims: The aim of this study was to examine the comparative effects of eye masks and music on anxiety levels and hemodynamic indices of patients undergoing coronary angiography.
Setting and Design: This is a single-blind randomized clinical trial conducted on 300 patients undergoing coronary angiography.
Materials and Methods: Patients were recruited using convenience sampling and then randomly allocated to one of the four groups. Ten minutes before the coronary angiography, baseline anxiety levels were measured using the state-trait anxiety inventory. Patients' hemodynamic indices were also measured and recorded immediately before they entered the cath-lab operating room, as soon as, they were in bed in the cath-lab operating room, 5 min after the start of coronary angiography, and immediately and 20 min after the completion of coronary angiography. Anxiety levels were measured again 20 min after coronary angiography.
Statistical Analysis Used: All statistical analyses were conducted using SPSS 22 Software. Mean and SD indices were used. The normality of both overt and covert anxiety variables was confirmed using Kolmogorov–Smirnov test. The presence of intervening variables was examined using analysis of variance, the final analysis was performed using analysis of covariance. For all analyses, a P < 0.05 was considered to be statistically significant.
Results: The mean scores on overt and covert anxiety decreased after intervention. A statistically significant difference was observed among the four groups on overt and covert anxiety (P < 0.001). Compared to before coronary angiography (P < 0.001) and routine care only group (P < 0.001), hemodynamic indices had a decreasing trend during coronary angiography in the intervention groups.
Conclusion: The results of the present study revealed that nonverbal, relaxing, and classical music significantly reduced anxiety and hemodynamic indices of patients undergoing coronary angiography. Future studies should examine the effectiveness of other music genres on anxiety and hemodynamic indices in patients undergoing coronary angiography.
... The influence of neuro-endocrine signals on proliferation of immune cells or the last effector mechanism as production of antibodies or the activity of cytotoxic cells were estimated in previous studies (13,14), Each of the main stress system hypothalamo pituitary adrenal(HPA) axis and the sympathetic nervous system(SNS), during nocturnal sleep period their activity inhibited, associated with suppression in cortisol and catecholamines in circulation (13,15), In normal nocturnal sleep cytokine production will support towards type1 dominance and therefore reinforce proinflammatory activity and showed that the nocturnal prevalence of type1 cytokines shifted towards type2 cytokines by acute experimental sleep deprivation that's mean sleep leads to direct suppression of IL-10 production as anti-inflammatory cytokines (16). The pituitary growth hormone (GH), prolactin and the pineal hormone melatonin that responsible about cell growth, differentiation and restoration that's during sleep show an increase in their blood levels (17), that promote activation of immune cells and enhance production of pro-inflammatory cytokines as interleukin IL-12,tumor necrotic factor alpha TNF-α (18)(19)(20). Where these proinflammatory cytokines found to be peak throughout nocturnal sleep (21,22). ...
Sleep is a naturally, restorative process, characterized by altered consciousness. Normal sleep and circadian system act as important physiological regulator on immune functions, these regulation mediated by neurotransmitters, hormones and cytokines signals which support relation between the immune system and central nervous system. Various immune parameters in peripheral circulation show Diurnal changes over the day, these changes under effect of the 2 main stress systems, the sympathetic nervous system(SNS) and the hypothalamo pituitary adrenal (HPA) axis, changes occurring in immune parameters over the 24-h during the sleep-wake cycle categorized to nocturnal Proinflammatory and daytime anti-inflammatory activity. In addition to its effects on cognitive function, compelling evidence links sleep loss to alterations in the neuroendocrine, immune and inflammatory systems. sleep deprivation either in partial sleep deprivation or total sleep deprivation as a stressful status enhances the adrenergic tons that affects innate and adaptive immunity, with increasing susceptibility to infections and immune-related diseases. Several studies have shown negative effects of sleep deprivation on all functions of the body and its effect on the immune system this review aims to explain the changes occurring in immune parameters and inflammatory cytokines over the 24-h during the normal sleep-wake cycle and during sleep disturbance and benefit of sleep recovery(napping) to recede these physiological changes that resulting from sleep deprivation. ÖZET Uyku değişen bilinç durumlarıyla karakterize onarıcı ve doğal bir süreçtir. Uyku ve sirkadiyen sistem bağışıklık sistemi fonksiyonları üzerinde güçlü bir düzenleyici etkiye sahiptir. Bu etki bağışıklık sistemi ve merkezi sinir sistemi arasındaki ilişkiyi destekleyen nörotransmitterler, hormonlar ve sitokinler aracılığıyla oluşturulur. Çeşitli bağışıklık sistemi parametreleri gün içerisinde kan dolaşımında diurnal değişiklikler göstermektedir. Bu değişiklikler hipotalamus-hipofiz-adrenal (HPA) aks ve sempatik sinir sisteminin (SNS) kontrolündedir. Gün boyunca uyku-uyanıklık döngüsünde, bağışıklık sistemi parametrelerinde gerçekleşen değişiklikler, gece pro-inflamatuar etki gündüz ise anti-inflamatuar etki olarak ortaya çıkmaktadır. Uyku eksikliği bilişsel işlev üzerindeki etkilerine ek olarak, nöroendokrin, bağışıklık ve inflamatuar sistemdeki değişikliklere de yol açmaktadır. Kısmi ya da tam uyku yoksunluğu stresli bir durum olarak sempatik tonusu arttırmasıyla doğal ve kazanılmış bağışıklığı etkilemektedir. Bu durum enfeksiyonlara yatkınlığa ve bağışıklık sistemiyle ilişkili hastalıklarda artışa sebep olmaktadır. Çeşitli araştırmalar, uyku yoksunluğunun vücudun tüm işlevleri üzerindeki olumsuz etkilerini ve bağışıklık sistemi üzerindeki etkilerini göstermiştir. Bu derleme gün içerisinde normal uyku-uyanıklık dönemi ya da uyku bozukluğu sırasında, bağışıklık sistemi parametreleri ve inflamatuar sitokinlerdeki değişiklikleri; uyku açığını kapatmak için yapılan toparlanma uykusunun, uyku yoksunluğunun sebep olduğu fizyolojik değişiklikleri geriletme üzerindeki faydalarını açıklamayı amaçlamaktadır.
... The influence of neuro-endocrine signals on proliferation of immune cells or the last effector mechanism as production of antibodies or the activity of cytotoxic cells were estimated in previous studies (13,14), Each of the main stress system hypothalamo pituitary adrenal(HPA) axis and the sympathetic nervous system(SNS), during nocturnal sleep period their activity inhibited, associated with suppression in cortisol and catecholamines in circulation (13,15), In normal nocturnal sleep cytokine production will support towards type1 dominance and therefore reinforce proinflammatory activity and showed that the nocturnal prevalence of type1 cytokines shifted towards type2 cytokines by acute experimental sleep deprivation that's mean sleep leads to direct suppression of IL-10 production as anti-inflammatory cytokines (16). The pituitary growth hormone (GH), prolactin and the pineal hormone melatonin that responsible about cell growth, differentiation and restoration that's during sleep show an increase in their blood levels (17), that promote activation of immune cells and enhance production of pro-inflammatory cytokines as interleukin IL-12,tumor necrotic factor alpha TNF-α (18)(19)(20). Where these proinflammatory cytokines found to be peak throughout nocturnal sleep (21,22). ...
Sleep is a naturally, restorative process, characterized by altered consciousness. Normal sleep and circadian system act as important physiological regulator on immune functions, these regulation mediated by neurotransmitters, hormones and cytokines signals which support relation between the immune system and central nervous system. Various immune parameters in peripheral circulation show Diurnal changes over the day, these changes under effect of the 2 main stress systems, the sympathetic nervous system(SNS) and the hypothalamo pituitary adrenal (HPA) axis, changes occurring in immune parameters over the 24-h during the sleep-wake cycle categorized to nocturnal Proinflammatory and daytime anti-inflammatory activity. In addition to its effects on cognitive function, compelling evidence links sleep loss to alterations in the neuroendocrine, immune and inflammatory systems. sleep deprivation either in partial sleep deprivation or total sleep deprivation as a stressful status enhances the adrenergic tons that affects innate and adaptive immunity, with increasing susceptibility to infections and immune-related diseases. Several studies have shown negative effects of sleep deprivation on all functions of the body and its effect on the immune system this review aims to explain the changes occurring in immune parameters and inflammatory cytokines over the 24-h during the normal sleep-wake cycle and during sleep disturbance and benefit of sleep recovery(napping) to recede these physiological changes that resulting from sleep deprivation. ÖZET Uyku değişen bilinç durumlarıyla karakterize onarıcı ve doğal bir süreçtir. Uyku ve sirkadiyen sistem bağışıklık sistemi fonksiyonları üzerinde güçlü bir düzenleyici etkiye sahiptir. Bu etki bağışıklık sistemi ve merkezi sinir sistemi arasındaki ilişkiyi destekleyen nörotransmitterler, hormonlar ve sitokinler aracılığıyla oluşturulur. Çeşitli bağışıklık sistemi parametreleri gün içerisinde kan dolaşımında diurnal değişiklikler göstermektedir. Bu değişiklikler hipotalamus-hipofiz-adrenal (HPA) aks ve sempatik sinir sisteminin (SNS) kontrolündedir. Gün boyunca uyku-uyanıklık döngüsünde, bağışıklık sistemi parametrelerinde gerçekleşen değişiklikler, gece pro-inflamatuar etki gündüz ise anti-inflamatuar etki olarak ortaya çıkmaktadır. Uyku eksikliği bilişsel işlev üzerindeki etkilerine ek olarak, nöroendokrin, bağışıklık ve inflamatuar sistemdeki değişikliklere de yol açmaktadır. Kısmi ya da tam uyku yoksunluğu stresli bir durum olarak sempatik tonusu arttırmasıyla doğal ve kazanılmış bağışıklığı etkilemektedir. Bu durum enfeksiyonlara yatkınlığa ve bağışıklık sistemiyle ilişkili hastalıklarda artışa sebep olmaktadır. Çeşitli araştırmalar, uyku yoksunluğunun vücudun tüm işlevleri üzerindeki olumsuz etkilerini ve bağışıklık sistemi üzerindeki etkilerini göstermiştir. Bu derleme gün içerisinde normal uyku-uyanıklık dönemi ya da uyku bozukluğu sırasında, bağışıklık sistemi parametreleri ve inflamatuar sitokinlerdeki değişiklikleri; uyku açığını kapatmak için yapılan toparlanma uykusunun, uyku yoksunluğunun sebep olduğu fizyolojik değişiklikleri geriletme üzerindeki faydalarını açıklamayı amaçlamaktadır.
Background
Studies of sleep and prostate cancer are almost entirely based on self-report, with limited research using actigraphy. Our goal was to evaluate actigraphy-measured sleep and prostate cancer and to expand on findings from prior studies of self-reported sleep.
Methods
We prospectively examined 34 260 men without a history of prostate cancer in the UK Biobank. Sleep characteristics were measured over 7 days using actigraphy. We calculated sleep duration, onset, midpoint, wake-up time, social jetlag (difference in weekend-weekday sleep midpoints), sleep efficiency (percentage of time spent asleep between onset and wake-up time), and wakefulness after sleep onset. Cox proportional hazards models were used to estimate covariate-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs).
Results
Over 7.6 years, 1152 men were diagnosed with prostate cancer. Sleep duration was not associated with prostate cancer risk. Sleep midpoint earlier than 4:00 am was not associated with prostate cancer risk, though sleep midpoint of 5:00 am or later was suggestively associated with lower prostate cancer risk but had limited precision (earlier than 4:00 am vs 4:00-4:59 am HR = 1.00, 95% CI = 0.87 to 1.16; 5:00 am or later vs 4:00-4:59 am HR = 0.79, 95% CI = 0.57 to 1.10). Social jetlag was not associated with greater prostate cancer risk (1 to <2 hours vs <1 hour HR = 1.06, 95% CI = 0.89 to 1.25; ≥2 hours vs <1 hour HR = 0.90, 95% CI = 0.65 to 1.26). Compared with men who averaged less than 30 minutes of wakefulness after sleep onset per day, men with 60 minutes or more had a higher risk of prostate cancer (HR = 1.20, 95% CI = 1.00 to 1.43).
Conclusions
Of the sleep characteristics studied, higher wakefulness after sleep onset—a measure of poor sleep quality—was associated with greater prostate cancer risk. Replication of our findings between wakefulness after sleep onset and prostate cancer are warranted.
Sleep is one of the most important aspects of the normal functioning of the brain and the entire organism. Research into the different ways in which sleep can be disrupted as well as the various consequences of sleep disruption have gained much attention recently. Here we explore the ways in which a single pathology (a malignant brain disease) can affect the sleeping patterns of a person. We also explore the various well-known consequences of sleep disruption, both local and systemic. Our goal is to show how this often overlooked pathology is crucial in the understanding of many common pathologies.KeywordsDisrupted sleepMalignant brain tumors
Background:
The relationship between sleep duration and cancer in China remains inconclusive. The authors investigated the association between sleep duration and cancer from both static and dynamic perspectives.
Methods:
This study was based on the China Health and Retirement Longitudinal Study. We first tested the hazard ratios (HRs) with 95% confidence intervals (CIs) between baseline sleep duration and incident cancer using Cox proportional hazards regression analysis. Sleep duration trajectories from 2011 to 2015 were identified using group-based trajectory modeling to examine the subsequent risk of incident cancer from 2015 to 2018 using Cox proportional hazards regression model.
Results:
The risk of incident cancer increased by 69% (HR, 1.69; 95% CI, 1.19-2.39) in individuals who slept for <7 h per day (vs. 7 to ≤8 h), 41% (HR, 1.41; 95% CI, 1.01-1.95) in those who slept for <6 h per night (vs. 6 to ≤8 h), and 60% (HR, 1.60; 95% CI, 1.01-2.55) in those who did not take any naps during the day (vs. >60 min). Stratified by sex and body mass index, the risk of cancer was evident among women with night sleep of <6 h (vs. 6-8 h). However, the duration of <7 h of total sleep among men and overweight individuals was associated with cancer risk. Moreover, individuals with a short night sleep duration but no napping had a higher risk of cancer. Furthermore, cancer risk was only observed in individuals with short stable trajectory of night sleep (HR, 2.01; 95% CI, 1.07-3.80) and among women with short stable trajectory of total sleep (HR, 2.26; 95% CI, 1.13-4.52).
Conclusions:
Cancer incidence risk was observed in participants with sleep duration of <7 h and among women with short stable sleep trajectory. Short nights and total sleep duration were both associated with a high risk of incident cancer, but varied by sex. Interestingly, cancer risk was restricted to women with short stable sleep trajectory.
Plain language summary:
This study showed that short nights and total sleep duration were associated with a high risk of cancer incidence in middle-aged and elderly Chinese population, with implications for early effective cancer prevention. Habitual sleep is a modifiable and dynamic lifestyle behavior, and long-term short sleep trajectories among women can predict cancer outcomes. Future studies should examine the association between the trajectory of sleep parameters based on objective measures and specific cancer types.
Background:
The all-cause and cause-specific mortality risk associated with sleep latencies in the general adult population is unknown. We aimed to investigate the association of habitual prolonged sleep latency with long-term all-cause and cause-specific mortality in adults.
Methods:
The Korean Genome and Epidemiology Study (KoGES) is a population-based prospective cohort study comprising community-dwelling men and women aged 40-69 years from Ansan, South Korea. The cohort was studied bi-annually from April 17, 2003, to Dec 15, 2020, and the current analysis included all individuals who completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire between April 17, 2003, and Feb 23, 2005. The final study population comprised 3757 participants. Data were analysed from Aug 1, 2021, to May 31, 2022. The main exposure was sleep latency groups based on the PSQI questionnaire: fell asleep in 15 min or less, fell asleep in 16-30 min, occasional prolonged sleep latency (fell asleep in >30 min once or twice a week in the past month) and habitual prolonged sleep latency (fell asleep in >60 min more than once a week or fell asleep in >30 min ≥3 times a week, or both) in the past month at baseline. Outcomes were all-cause and cause-specific (cancer, cardiovascular disease, and other causes) mortality reported during the 18-year study period. Cox proportional hazards regression models were used to examine the prospective relationship between sleep latency and all-cause mortality, and competing risk analyses were done to investigate the association of sleep latency with cause-specific mortality.
Findings:
During a median follow-up of 16·7 years (IQR 16·3-17·4), 226 deaths were reported. After adjusting for demographic characteristics, physical characteristics, lifestyle factors, chronic conditions, and sleep variables, self-reported habitual prolonged sleep latency was associated with an increased risk of all-cause mortality (hazard ratio [HR] 2·22, 95% CI 1·38-3·57) compared to the reference group (those who fell asleep in 16-30 min). In the fully adjusted model, habitual prolonged sleep latency was associated with a more than doubled risk of dying from cancer compared to the reference group (HR 2·74, 95% CI 1·29-5·82). No significant association was observed between habitual prolonged sleep latency and deaths from cardiovascular disease and other causes.
Interpretation:
In this population-based prospective cohort study, habitual prolonged sleep latency was independently associated with an increased risk of all-cause and cancer-specific mortality in adults (independently of demographic characteristics, lifestyle factors, chronic morbidities, and other sleep variables). Although further studies are warranted to investigate the causality of the relationship, strategies or interventions to prevent habitual prolonged sleep latencies might enhance longevity in the general adult population.
Funding:
Korea Centers for Disease Control and Prevention.
Background:
We sought to assess the influences of sleep duration, sleep adequacy, and daytime sleepiness on survival outcomes among Stage III colon cancer patients.
Methods:
We conducted a prospective observational study of 1175 Stage III colon cancer patients enrolled in the CALGB/SWOG 80702 randomised adjuvant chemotherapy trial who completed a self-reported questionnaire on dietary and lifestyle habits 14-16 months post-randomisation. The primary endpoint was disease-free survival (DFS), and secondary was overall survival (OS). Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary and lifestyle factors.
Results:
Patients sleeping ≥9 h-relative to 7 h-experienced a worse hazard ratio (HR) of 1.62 (95% confidence interval (CI), 1.01-2.58) for DFS. In addition, those sleeping the least (≤5 h) or the most (≥ 9 h) experienced worse HRs for OS of 2.14 (95% CI, 1.14-4.03) and 2.34 (95% CI, 1.26-4.33), respectively. Self-reported sleep adequacy and daytime sleepiness showed no significant correlations with outcomes.
Conclusions:
Among resected Stage III colon cancer patients who received uniform treatment and follow-up within a nationwide randomised clinical trial, very long and very short sleep durations were significantly associated with increased mortality. Interventions targeting optimising sleep health among indicated colon cancer patients may be an important method by which more comprehensive care can be delivered.
Trial registration:
ClinicalTrials.gov Identifier: NCT01150045.
According to estimates, more than 800 mushroom species have been confirmed to possess various pharmacological properties. While the primary research focus has been on immunomodulatory and, more recently, on direct antitumor effects, many other therapeutic properties have also become important research subjects. Systems biology approaches, which include various omics methods coupled with bioinformatics, have begun to enter the field of medicinal mushroom research. Proteomics is a well-established hypothesis-generating discipline focused on the systemic study of proteins, used in discovering new pathways and processes resulting from physiological and pathological states or pharmacological interventions. It is particularly powerful in new potential therapeutic target discovery of “druggable proteins” or disease biomarkers of prognostic or therapeutic significance. Despite challenges in proteomics’ extensive data analysis and interpretation, proteomics remains indispensable for the detailed understanding and characterization of pharmacological effects.In comparison with genomics, proteomics generates more accurate data since several protein products may result from only one gene. This results from differential splicing and more than 200 posttranslational modifications, which affect protein function, stability, protein-protein, and other interactions. This chapter provides a current overview of proteomic research on medicinal mushrooms concerning anticancer, immunomodulatory, antidiabetic, hypolipidemic, antiatherosclerotic, hepatoprotective, and neuroprotective properties.KeywordsAnticancerAntidiabeticHepatoprotectiveHypolipidemicMedicinal mushroomsNeuroprotectiveProteomics
Background:
Insufficient or disrupted sleep increases the risk of cardiovascular disease, including atherosclerosis. However, we know little about the molecular mechanisms by which sleep modulates atherogenesis. This study aimed to explore the potential role of circulating exosomes in endothelial inflammation and atherogenesis under sleep deprivation status and the molecular mechanisms involved.
Methods:
Circulating exosomes were isolated from the plasma of volunteers with or without sleep deprivation and mice subjected to 12-week sleep deprivation or control littermates. miRNA array was performed to determine changes in miRNA expression in circulating exosomes.
Results:
Although the total circulating exosome levels did not change significantly, the isolated plasma exosomes from sleep-deprived mice or human were a potent inducer of endothelial inflammation and atherogenesis. Through profiling and functional analysis of the global microRNA in the exosomes, we found miR-182-5p is a key exosomal cargo that mediates the proinflammatory effects of exosomes by upregulation of MYD88 and activation of NF-ĸB/NLRP3 pathway in endothelial cells. Moreover, sleep deprivation or the reduction of melatonin directly decreased the synthesis of miR-182-5p and led to the accumulation of reactive oxygen species in small intestinal epithelium.
Conclusions:
The findings illustrate an important role for circulating exosomes in distant communications, suggesting a new mechanism underlying the link between sleep disorder and cardiovascular disease.
Exposure to air pollution or lack of physical activity (PA) increases the risk of insomnia. However, evidence on joint exposure to air pollutants is limited, and the interaction of joint air pollutants and PA on insomnia is unknown. This prospective cohort study included 40,315 participants with related data from the UK Biobank, which recruited participants from 2006 to 2010. Insomnia was assessed by self-reported symptoms. The annual average air pollutant concentrations of particulate matter (PM2.5, PM10), nitrogen oxides (NO2, NOX), sulfur dioxide (SO2) and carbon monoxide (CO) were calculated based on participants' addresses. We applied a weighted Cox regression model to evaluate the correlation between air pollutants and insomnia and newly proposed an air pollution score to assess joint air pollutants effect using a weighted concentration summation after obtaining the weights of each pollutant in the Weighted-quantile sum regression. With a median follow-up of 8.7 years, 8511 participants developed insomnia. For each 10 μg/m³ increase in NO2, NOX, PM10, SO2, the average hazard ratios (AHRs) and 95% confidence interval (CI) of insomnia were 1.10 (1.06, 1.14), 1.06 (1.04, 1.08), 1.35 (1.25, 1.45) and 2.58 (2.31, 2.89), respectively; For each 5 μg/m³ increase in PM2.5 and each 1 mg/m³ increase in CO, the corresponding AHRs (95%CI) were 1.27 (1.21, 1.34) and 1.83 (1.10, 3.04), respectively. The AHR (95%CI) for insomnia associated with per interquartile range (IQR) increase in air pollution scores were 1.20 (1.15, 1.23). In addition, potential interactions were examined by setting cross-product terms of air pollution score with PA in the models. We observed an interaction between air pollution scores and PA (P = 0.032). The associations between joint air pollutants and insomnia were attenuated among participants with higher PA. Our study provides evidence on developing strategies for improving healthy sleep by promoting PA and reducing air pollution.
em>Islam is a universal religion. Not only governs the relationship between servant and God but also regulates the relationship with fellow beings. Among the teachings of Islam that governs the relationship with the creatures is how the adherents of Islam set to be considerate of the environment, ie, how should humans maintain balance of nature and not ruin it. The use of water and energi, including matters governed by Islam through the Qur'an and the instructions Prophet Sallallaahu 'alaihi wasallam. Instructions regarding the procedure of which the Prophet made ablution, bathing, brushing teeth closely related to water conservation, while the doctrine of fasting, to walk to the mosque, turn off a light during sleep so strongly associated with the doctrine of the conservation of energy. By following the Sunnah of a Moslem not only to be rewarded, but also contribute to the conservation of natural resources whose benefits will be felt by all mankind</em
Sleep, accounting for roughly one-third of a person’s life, plays an important role in human health. Despite the close association between sleep patterns and medical diseases proven by several studies, it has been neglected in recent years. Presently, all societies are facing the most challenging health-threatening disease, cancer. Among all cancer types, gastrointestinal (GI) cancers, especially colorectal type, seem to be one of the most relevant to an individual’s lifestyle; thus, they can be prevented by modifying behaviors most of the time. Previous studies have shown that disruption of the 24-h sleep–wake cycle increases the chance of colorectal cancer, which can be due to exposure to artificial light at night and some complex genetic and hormone-mediated mechanisms. There has also been some evidence showing the possible associations between other aspects of sleep such as sleep duration or some sleep disorders and GI cancer risk. This review brings some information together and presents a detailed discussion of the possible role of sleep patterns in GI malignancy initiation.
Dependency on digital devices resulting in an ever-increasing daily screen time has subsequently also been the cause of several adverse effects on physical and mental or psychological health. Constant exposure to devices like smartphones, personal computers, and television can severely affect mental health- increase stress and anxiety, for example, and cause various sleep issues in both children as well as adults. Risk factors for obesity and cardiovascular disorders, including hypertension, poor regulation of stress, low HDL cholesterol, and insulin resistance are among the physical health repercussions we see. The psychological health effects comprise suicidal tendencies and symptoms of depression which are associated with digital device dependency, screen-time-induced poor sleep quality, and content-influenced negativity. Oftentimes it can cause the induction of a state of hyper-arousal, increase stress hormones, desynchronize the body clock or the circadian cycle, alter brain chemistry and create a drag on mental energy and development. With a focus on brain development in children and detrimental effects in both adults and children, this research article goes on to explore the various aspects of screen addiction and excessive screen exposure.
Background: Whether sleep quality and duration-combination assessed from multiple domains are strongly associated with mortality risk in older adults remains unelucidated. We aimed to clarify these relationships.
Methods: We enrolled 7,668 older (age ≥65) Japanese adults in the Kyoto-Kameoka prospective cohort study who provided valid responses to the Pittsburgh Sleep Quality Index (PSQI) in a mail-in survey. Sleep quality and duration were classified into six groups using previously validated PSQI: short sleep duration (SSD: <360 min/day)/sleep disturbance (SD: ≥5.5 PSQI points), n=701; SSD/non-sleep disturbance (NSD: <5.5 PSQI points), n=100; optimal sleep duration (OSD: 360-480 min/day)/NSD, n=1863; OSD/SD, n=2113; long sleep duration (LSD: >480 min/day)/NSD, n=1972; LSD/SD, n=919. Mortality data were collected from February 15, 2012, to November 30, 2016. We evaluated the relationship between all-cause mortality risk and sleep quality and duration-combination using a multivariable Cox proportional hazards model that included baseline covariates.
Results: The median follow-up period was 4.75 years (34,826 person-years), with a total of 616 deaths. After adjusting for confounders, compared with other groups, SSD/SD and LSD/SD had the highest hazard ratio (HR) of mortality [SSD/SD: HR, 1.56 (95% confidence interval [CI]: 1.10-2.19); SSD/NSD: HR, 1.27 (95%CI: 0.47-3.48); OSD/NSD: reference; OSD/SD: HR, 1.20 (95%CI: 0.91-1.59); LSD/NSD: HR, 1.35 (95%CI: 1.03-1.77); LSD/SD: HR, 1.83 (95%CI: 1.37-2.45)]. However, mortality risk was not associated with the interaction between sleep quality and duration.
Conclusions: Older adults with sleep disturbances involving SSD and LSD have a strong positive association with mortality risk, suggesting an additive effect between sleep quality and duration.
Extracellular vesicles (EVs) are emerging as key players in intercellular communication. Few studies have focused on EV levels in subjects with sleep disorders. Here, we aimed to explore the role of acute sleep deprivation on the quantity and functionality of circulating EVs, and their tissue distribution. EVs were isolated by ultracentrifugation from the plasma of volunteers and animals undergoing one night of sleep deprivation. Arterio‐venous shunt, FeCl3 thrombus test and thrombin‐induced platelet aggregation assay were conducted to evaluate the in vivo and in vitro bioactivity of small EVs. Western blotting was performed to measure the expression of EV proteins. The fate and distribution of circulating small EVs were determined by intravital imaging. We found that one night of sleep deprivation triggers release of small EVs into the circulation in both healthy individuals and animals. Injection of sleep deprivation‐liberated small EVs into animals increased thrombus formation and weight in thrombosis models. Also, sleep deprivation‐liberated small EVs promoted platelet aggregation induced by thrombin. Mechanistically, sleep deprivation increased the levels of HMGB1 protein in small EVs, which play important roles in platelet activation. Furthermore, we found sleep deprivation‐liberated small EVs are more readily localize in the liver. These data suggested that one night of sleep deprivation is a stress for small EV release, and small EVs released here may increase the risk of thrombosis. Further, small EVs may be implicated in long distance signalling during sleep deprivation‐mediated adaptation processes.
The goal of this work was to see how melatonin affected Bax and Bcl‐2 expression, as well as apoptosis and autophagy, in MCF‐7 and MDA‐MB‐231 breast cancer cell lines, which have distinct hormonal sensitivities.
In this study, to investigate the IC50 value of melatonin, varied melatonin concentrations were administered to MCF‐7 and MDA‐MB‐231 breast cancer cell lines. Moreover, cytotoxic activities were analyzed through MTT analysis. Five subgroups were created for both cell lines: control, IC50‐MeL, hIC50‐MeL, DMSO1, and DMSO2. To evaluate the apoptotic effect of melatonin, immunofluorescence staining methods of TUNEL, Bax, and Bcl‐2 were used, and to examine the effects of autophagy, immunofluorescence staining methods of Beclin‐1, LC3, and p62 were used.
In vitro results revealed upregulation of the expression of TUNEL and Bax in both MCF‐7 and MDA‐MB‐231 cell lines regarding dose and time, but downregulation of Bcl‐2 expression. Moreover, autophagy results were consistent with in vitro apoptosis results in both MCF‐7 and MDA‐MB‐231 cell lines. We determined that the expressions of the autophagy markers Beclin‐1, LC3, and p62 were increased. Our findings indicate that treatment of breast cancer cells with melatonin increased the inhibitory effect of melatonin on cell growth through both apoptosis and autophagy in vitro.
Consequently, it was concluded that melatonin might adjust the expression balance of markers that have a role in cell death mechanisms and significantly promote these mechanisms. Therefore, melatonin can inhibit the growth of breast cancer cells by inducing cell death.
Background: Liver cancer is a major cause of morbidity and mortality in Japan and worldwide, that can be prevented by controlling its risk factors. On the other hand, daytime napping is a common behavior, especially among older adults, that was related in previous literature to unfavorable health conditions, including cancer. Thus, investigating whether daytime napping could be associated with liver cancer risk for possible preventive interventions and identifying populations at risk to personalize such interventions are essential. We, therefore, used the framework of predictive, preventive, and personalized medicine to study the association between daytime napping and liver cancer risk among the general population of Japan.
Methods: In this prospective cohort study, data of 51,185 participants, aged 40-79 years, and registered in the Japan Collaborative Cohort Study (JACC Study) were analyzed. Incident cases of liver cancer were diagnosed using cancer registries, hospital records, and death certificates. Daytime napping was assessed using the JACC baseline self-administered questionnaire. We used the Cox regression to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs) of incident liver cancer among participants in the age categories of the 40s, 50s, 60s, and 70s who reported daytime napping compared with their counterparts who did not.
Results: Within 669,734 person-years of follow-up, 341 participants developed liver cancer. Daytime napping was associated with the increased risk of liver cancer among participants who were in their 60s and 70s of age after adjusting for sex: HRs (95% CIs) 1.88 (1.35, 2.61) and 1.96 (1.18, 3.26), lifestyle and medical history: 1.76 (1.27, 2.47) and 1.82 (1.07, 3.09), and history of liver diseases: 1.66 (1.18, 2.34) and 1.72 (1.01, 2.94), respectively. No associations were detected among participants from the 40s and 50s age groups. The association did not significantly differ between men and women (p- interaction= 0.775). Sensitivity analyses by excluding participants with a positive history of liver disease and those who reported short or long sleep duration did not materially affect the results.
Conclusions: Daytime napping was associated with the increased risk of liver cancer among Japanese older adults. For liver cancer risk prevention, older adults should be advised against daytime napping.
Sleep duration is emerging as an important modifiable risk factor for morbidity and mortality. We assessed the association between sleep duration and cancer incidence and mortality among Japanese adults using data from six population-based cohorts with 271 694 participants. During a total follow-up period of about 5.9 million person-years, we identified 40 751 incident cancer cases and 18 323 cancer deaths. We computed study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models and pooled the estimates using random-effects meta-analysis. Sleep duration of ≥ 10 h (vs. 7 h) was associated with increased risk of cancer incidence among women (HR 1.19, 95% CI 1.02-1.38), but not men, and increased risk of cancer mortality among men (HR 1.18, 95% CI 1.00-1.39) and women (HR 1.44, 95% CI 1.20-1.73). Sleep duration of ≤ 5 h (vs. 7 h) was not associated with cancer incidence and mortality. However, among post-menopausal women, sleep durations of both ≤ 5 h and ≥ 10 h (vs. 7 h) were associated with an increased risk of cancer mortality. Among Japanese adults, sleep duration of ≥ 10 h is associated with increased risk of cancer incidence and mortality among women and cancer mortality among men.
Background: Evidence on the variability of associations between sleep duration and incident disability according to the presence or absence of sleep complaints is limited.This study assessed the associations between sleep durations and disability incidence stratified by the presence or absence of sleep complaints.
Methods: A total of 3,896 community-dwelling Japanese adults aged ≥65 years were observed for 37 months after the self-reporting of sleep duration and sleep complaints. Disability incidence was defined by the certification of needed support/long-term care according to the public long-term care insurance. A proportional hazards model was fitted to examine the association of sleep duration with incident disability according to the presence or absence of fatigue on awakening. Missing values of covariates were estimated using multiple imputations.
Results: Long sleep duration was associated significantly with incident disability regardless of the presence or absence of fatigue on awakening; the age- and sex-adjusted hazard ratios were 1.62 (95% Confidence Interval, 1.02–2.56) and 1.35 (1.04–1.75), respectively. The elevated risks of long sleep durations without complaints disappeared after an adjustment for impairments of functional health, while that of long sleep duration with complaints disappeared after an adjustment for medical histories, especially stroke history.
Conclusion: Long sleep duration was associated with disability incidence among community-dwelling older persons. The domains of health accounting for the association differed by the presence or absence of sleep complaints.
Background:
It is unclear which psychological factors (stressors, emotional correlates, and psychophysiological markers) induce cancer risk. This currently limits the potential for prevention strategies.
Purpose:
The aim of this review is to bring forth evidence of stress as a determinant of cancer risk from a public health perspective, written for a broad public of practitioners and scientists.
Methods:
Based on a semisystematic literature search, the impact of different aspects/types of stress and the potential physiological and behavioral pathways are summarized, while highlighting further research, public health and clinical implications.
Results:
Between 2007 and 2020, 65 case-control or cohort studies have been identified. Apart from overall cancer (N = 24), 12 cancer types have been associated with psychological stress with most for breast (N = 21), colorectal (N = 11) and lung/prostate/pancreas cancer (N = 8 each). Although the evidence regarding the mechanisms is still scarce, cancer development in relation to stress might be due to interacting and combined effects of different stress(or) types, but such interaction has not really been tested yet. The path from stress towards cancer incidence consists of a biological pathway with endocrinology and immunology as well as stress-induced behavioral pathways, including smoking, alcoholism, sleep disruption, an unhealthy diet, and low physical activity together with the related phenomenon of obesity.
Conclusion:
Not only the stress but also the stress-induced lifestyle should be targeted for cancer prevention and treatment. Future research should include a more diverse spectrum of cancer types (not only hormonal related like breast cancer) and of stress measures while also considering behavioral covariates.
Background:
Melatonin shows potential oncostatic action, and light exposure during night suppresses melatonin production. There is little information, however, about the direct effect of night work on the risk of cancer. We investigated the effect of night work in breast cancer.
Methods:
We examined the relationship between breast cancer and working on rotating night shifts during 10 years of follow-up in 78 562 women from the Nurses' Health Study. Information was ascertained in 1988 about the total number of years during which the nurses had worked rotating night shifts with at least three nights per month. From June 1988 through May 1998, we documented 2441 incident breast cancer cases. Logistic regression models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for confounding variables and breast cancer risk factors. All statistical tests were two-sided.
Results:
We observed a moderate increase in breast cancer risk among the women who worked 1-14 years or 15-29 years on rotating night shifts (multivariate adjusted RR = 1.08 [95% CI = 0.99 to 1.18] and RR = 1.08 [95% CI = 0.90 to 1.30], respectively). The risk was further increased among women who worked 30 or more years on the night shift (RR = 1.36; 95% CI = 1.04 to 1.78). The test for trend was statistically significant (P =.02).
Conclusions:
Women who work on rotating night shifts with at least three nights per month, in addition to days and evenings in that month, appear to have a moderately increased risk of breast cancer after extended periods of working rotating night shifts.
The present study investigated the temporal structure of sleep propensity during 48 hours using an ultrashort 7-min sleep/13-min wake cycle. Eight subjects were tested under two experimental conditions of either attempting sleep, or resisting sleep after a monitored night in the laboratory. Electrophysiological recordings were carried out during the 7-min trials. The temporal structure and the overall level of sleepiness of the 48-hour sleep propensity functions calculated from the amount of total sleep in each trial revealed a high within-subjects stability. This was found both across the two days of the study within conditions, and across conditions. Also, diurnal levels of sleepiness were systematically related to nocturnal sleep parameters. Subjects having short nocturnal sleep latencies and higher sleep efficiencies slept more during the day. It is proposed that the structure and level of the sleep propensity function can be used to characterize individuals along two dimensions of somnotypology: "morningness-eveningness" and "sleepy-alert."
The human circadian pacemaker modulates our desire and ability to fall asleep at different times of day. To study this circadian component of sleep tendency, we have analyzed the sleep-wake patterns recorded from 15 free-running subjects in whom the sleep-wake cycle spontaneously desynchronized from the circadian rhythm of body temperature. The analysis indicates that the distribution of sleep onsets during free run is bimodal, with one peak at the temperature trough and, contrary to previous reports, a second peak 9-10 h later. Furthermore, there are two consistent zones in the circadian temperature cycle during which normal subjects rarely fall asleep. We hypothesize that this bimodal rhythm of sleep tendency, revealed under free-running conditions, maintains the same fixed phase relation to the circadian temperature cycle during 24-h entrainment. This would imply that normally entrained individuals should experience a peak of sleep tendency in the midafternoon and a zone of minimal sleep tendency approximately 1-3 h before habitual bedtime. Our temporal isolation data thereby account quantitatively for the timing of the afternoon siesta and suggest that malfunctions of the phasing of the circadian pacemaker may underlie the insomnia associated with sleep-scheduling disorders.
The goal of this study was to examine the effect of rotating three-shift work on the circadian distribution of dietary intake and to investigate the relationships between displaced eating and nutritional status variables [blood lipids, blood glucose, body mass index (BMI)].
Dietary data were collected by 147 replicate 24-h dietary recalls from 22 male industrial workers in rotating three-shift work. The intakes of energy and nutrients were estimated by the use of a nutrient data base. The BMI was calculated, and blood glucose, serum triglycerides, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol were measured once.
The dietary intakes of energy, protein, total fat, saturated fat, total carbohydrates, sucrose, and dietary fiber did not differ between 24-h periods but did differ between work shifts and were lowest during the night. Correlation analyses between dietary intakes and nutritional status parameters showed that those who redistributed their eating most to the night shift had higher levels of serum total cholesterol and LDL and a higher LDL:HDL ratio; 63% of the LDL cholesterol level was explained by carbohydrate intake during night shifts. In contrast, the total intake for whole 24-h periods or across entire shift cycles was not related to serum variables or BMI.
Dietary intake is lower during night shifts (34-37% of 24-h intake of various nutrients) than during morning shifts (43-47%) and afternoon shifts (47-59%). The redistribution of food intake to the night may be associated with metabolic disturbances in lipid metabolism.
In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.
In this study, we used the "ultrashort sleep-wake paradigm" (7/13), which measures sleep propensity three times an hour for 29 h, from 0700 to 1200 the next day, on 6 healthy male subjects concomitantly with melatonin plasma level. Melatonin was measured once an hour during the morning and early afternoon of the first day and three times an hour from 1600 to 1000 the following morning. Rectal temperature was measured continuously for four subjects. Subjects underwent the 7/13 paradigm three times, and in all three sessions consistent phase relationships were found between the nocturnal onset of melatonin secretion and opening of the nocturnal sleep gate; also, there was an inverse relationship between melatonin and core body temperature and an almost perfect out-of-phase relationship between sleep propensity and temperature, with the temperature peak falling precisely in the middle of the "forbidden zone" for sleep, i.e., the early evening nadir in sleepiness. On the basis of these phase relationships and previous findings from our laboratory on the effects of exogenous melatonin on the sleep propensity function, we conclude that melatonin participates in sleep-wake regulation in humans.
Cytokines and hormones, including interleukin-1, tumor necrosis factor, growth hormone-releasing hormone, vasoactive intestinal polypeptide and prolactin, are involved in sleep regulation. These substances enhance sleep, inhibition of them inhibits sleep, and their brain levels vary with sleep. This knowledge helps our understanding of the humoral regulation of sleep.
Although the neuroendocrine system has immunomodulating potential, studies examining the relationship between stress, immunity and infection have, until recently, largely been the preserve of behavioural psychologists. Over the last decade, however, immunologists have begun to increasingly appreciate that neuroendocrine-immune interactions hold the key to understanding the complex behaviour of the immune system in vivo. The nervous, endocrine and immune systems communicate bidirectionally via shared messenger molecules variously called neurotransmitters, cytokines or hormones. Their classification as neurotransmitters, cytokines or hormones is more serendipity than a true reflection of their sphere of influence. Rather than these systems being discrete entities we would propose that they constitute, in reality, a single higher-order entity. This paper reviews current knowledge of neuroendocrine-immune interaction and uses the example of T-cell subset differentiation to show the previously under-appreciated importance of neuroendocrine influences in the regulation of immune function and, in particular, Th1/Th2 balance and diurnal variation there of.
Light exposure was measured in 30 permanent night nurses to determine if specific light/dark profiles could be associated with a better circadian adaptation. Circadian adaptation was defined as a significant shift in the timing of the episode of melatonin secretion into the daytime. Light exposure was continuously recorded with ambulatory wrist monitors for 56 h, including 3 consecutive nights of work. Participants were then admitted to the laboratory for 24 h where urine was collected every 2 h under dim light for the determination of 6-sulphatoxymelatonin concentration. Cosinor analysis was used to estimate the phase position of the episode of melatonin secretion. Five participants showed a circadian adaptation by phase delay ("delayed participants") and 3 participants showed a circadian adaptation by phase advance ("advanced participants"). The other 22 participants had a timing of melatonin secretion typical of day-oriented people ("nonshifters"). There was no significant difference between the 3 groups for total light exposure or for bright light exposure in the morning when traveling home. However, the 24-h profiles of light exposure were very distinctive. The timing of the main sleep episode was associated with the timing of light exposure. Delayed participants, however, slept in darker bedrooms, and this had a major impact on their profile of light/dark exposure. Delayed and advanced participants scored as evening and morning types, respectively, on a morningness-eveningness scale. This observation suggests that circadian phase prior to night work may contribute to the initial step toward circadian adaptation, later reinforced by specific patterns of light exposure.
Melatonin, as a new member of an expanding group of regulatory factors that control cell proliferation and loss, is the only known chronobiotic, hormonal regulator of neoplastic cell growth. At physiological circulating concentrations, this indoleamine is cytostatic and inhibits cancer cell proliferation in vitro via specific cell cycle effects. At pharmacological concentrations, melatonin exhibits cytotoxic activity in cancer cells. At both physiological and pharmacological concentrations, melatonin acts as a differentiating agent in some cancer cells and lowers their invasive and metastatic status through alterations in adhesion molecules and maintenance of gap junctional intercellular communication. In other cancer cell types, melatonin, either alone or in combination with other agents, induces apoptotic cell death. Biochemical and molecular mechanisms of melatonin's oncostatic action may include regulation of estrogen receptor expression and transactivation, calcium/calmodulin activity, protein kinase C activity, cytoskeletal architecture and function, intracellular redox status, melatonin receptor-mediated signal transduction cascades, and fatty acid transport and metabolism. A major mechanism mediating melatonin's circadian stage-dependent tumor growth inhibitory action is the suppression of epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) activity. This occurs via melatonin receptor-mediated blockade of tumor linoleic acid uptake and its conversion to 13-hydroxyoctadecadienoic acid (13-HODE) which normally activates EGFR/MAPK mitogenic signaling. This represents a potentially unifying model for the chronobiological inhibitory regulation of cancer growth by melatonin in the maintenance of the host/cancer balance. It also provides the first biological explanation of melatonin-induced enhancement of the efficacy and reduced toxicity of chemo- and radiotherapy in cancer patients.
Because night work is becoming more prevalent, we studied whether feeding at different times of a 24-h period would elicit different metabolic responses and whether dietary macronutrient composition would affect these responses. Seven men (26-43 y, 19.9-26.6 kg/m(2)) consumed two isocaloric diets, in a crossover design. The diets were a high carbohydrate (HC) diet [65 energy % (E%) carbohydrates, 20E% fat] and a high fat (HF) diet (40E% carbohydrates, 45E% fat). After a 6-d diet-adjustment period, the men were kept awake for 24 h and the food (continuation of respective diet) was provided as six isocaloric meals (i.e., every 4 h). Energy and substrate turnover, heart rate, mean arterial pressure (MAP), blood glucose, triacylglycerol (TAG), nonesterified fatty acid (NEFA) and glycerol were measured throughout the 24-h period. Significantly higher energy expenditure and NEFA concentration, and lower blood glucose and TAG concentrations were observed when the men consumed the HF diet than when they consumed the HC diet. Significant circadian patterns were seen in body and skin temperature (nadir, 0400-0500 h). When the men consumed the HF diet, significant circadian patterns were seen in fat oxidation (nadir, 0800-1200 h; plateau, 1200-0800 h), heat release (nadir, 0800-1200 h; plateau, 1600-0800 h), heart rate (nadir, 0000 h), blood glucose (nadir, 0800-1200 h; peak, 0000-0400 h), NEFA (nadir, 0800-1200 h; peak, 1200-2000 h) and TAG (nadir, 0800-1200 h; peak, 0400-0800 h) concentrations. Energy expenditure, carbohydrate oxidation, MAP and glycerol concentration did not display circadian patterns. Unequal variances eradicated most circadian effects in the HC-diet data. The increased TAG concentration in response to feeding at 0400 h might be involved in the higher TAG concentrations seen in shift workers. Distinct macronutrient/circadian-dependent postprandial responses were seen in most studied variables.
The effects of shift work on physiological function through disruption of circadian rhythms are well described. However, shift work can also be associated with specific pathological disorders. This article reviews the evidence for a relationship between specific medical disorders and working at night or on shift systems. The strongest evidence exists for an association with peptic ulcer disease, coronary heart disease and compromised pregnancy outcome.
Exposure to light at night suppresses the physiologic production of melatonin, a hormone that has antiproliferative effects
on intestinal cancers. Although observational studies have associated night-shift work with an increased risk of breast cancer,
the effect of night-shift work on the risk of other cancers is not known. We prospectively examined the relationship between
working rotating night shifts and the risk of colorectal cancers among female participants in the Nurses’ Health Study. We
documented 602 incident cases of colorectal cancer among 78 586 women who were followed up from 1988 through 1998. Compared
with women who never worked rotating night shifts, women who worked 1–14 years or 15 years or more on rotating night shifts
had multivariate relative risks of colorectal cancer of 1.00 (95% confidence interval [CI] = 0.84 to 1.19) and 1.35 (95% CI
= 1.03 to 1.77), respectively (Ptrend = .04). These data suggest that working a rotating night shift at least three nights per month for 15 or more years may increase
the risk of colorectal cancer in women.
In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.
In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.
Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light ⁄ dark cycle via the suprachiasmatic nucleus. Pinealocytes function as
‘neuroendocrine transducers’ to secrete melatonin during the dark phase of the light ⁄ dark cycle and, consequently, melatonin is often called the ‘hormone of darkness’. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the
‘time of day’ and ‘time of year’ (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body’s chronological pacemaker or ‘Zeitgeber’. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence
other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions,
melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin’s cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immuneenhancing
and oncostatic properties. Its ‘chronobiotic’ properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder. Melatonin acting as an ‘internal sleep facilitator’ promotes sleep, and melatonin’s sleep-facilitating properties have been found to be useful for treating insomnia symptoms
in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin’s role as a ‘photoperiodic molecule’ in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under
investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body’s physiological functions.
In this paper, the epidemiology of breast cancer will be discussed, followed by a brief description of the effect of electric fields on melatonin and the relation of melatonin to mammary cancer in rats. Finally, there will be a consideration of factors such as alcohol that affect melatonin and their relation to breast cancer risk. 55 refs.
Purpose. The purpose of this review is to inform both scientists and clinicians about the increase in cancer incidence throughout the Western World and to discuss environmental influences in cancer aetiology, in order to stimulate thoughts about plausible aetiological mechanisms and possible preventative measures. Design. Literature review. Materials and methods. This review was conducted by searching biomedical databases such as PubMed and Medline. Further research to obtain cancer incidence data involved accessing UK cancer registries, major cancer charities and government statistical records from the Office of National Statistics, the Department of Health, and the Department of Environment, Food and Rural Affairs. Results. Cancer incidence rates have increased in the Western World and this increased incidence affects the whole age spectrum. Epidemiological studies have provided some evidence of an association between exposure to environmental contaminants such as organochlorines and increased cancer risk. However, many epidemiological studies have been inconclusive. Similar reviews concerning environmental influences in cancer aetiology concluded that exposures to carcinogenic or endocrine‐disrupting chemicals exist at concentrations too low or have carcinogenic potential too weak to be considered a major factor in cancer aetiology. However, animal and in vitro studies together with epidemiological evidence discussed in this review would dispute that claim; even if healthy adults are not at risk, it would seem that the developing foetus, infant, child and young adults are at risk. In addition, studies discussed in this review show that low oestrogenic potency cannot be used as a marker of the capability of a chemical to cause oestrogenic responses and endocrine disruption. Genetic polymorphisms, which can predispose people to cancer, may interact with environmental contaminants such as organochlorines and endocrine disrupters, thus providing a modifying effect. Prevention measures have hitherto predominately centred on tobacco smoking cessation and diet education. Anecdotal evidence from practising physicians in pre‐industrial and traditional living societies, i.e. Canadian Inuits and Brazilian Indians suggests malignant disease was rare. A relatively new theory other than the somatic mutation theory has been proposed, the main premise being that carcinogenesis is a problem of tissue organization, comparable with organogenesis. Conclusions. It is feasible that chemical environmental contaminants, in particular synthetic pesticides and organochlorines with endocrine‐disrupting properties, could be major factors in cancer aetiology, particularly for hormone‐dependent malignancies, such as breast, testicular and prostate cancers. Animal and in vitro studies provide good evidence of a feasible mechanism whereby environmentally relevant levels of organochlorines and substances of low oestrogenic potency can cause endocrine disruption and consequently malignant disease. In addition, low oestrogenic potency should not be used as a marker of the capability of a chemical to cause oestrogenic responses and endocrine disruption. Preventative measures other than education about tobacco, diet and the promotion of physical activity should be considered. Moreover, it seems to be the most vulnerable members of society: the developing foetus, the developing child and adolescent and the genetically predisposed, who are at risk of developing cancer following involuntary exposure to environmental contaminants. This may be an appropriate time for governments to adopt the precautionary principle until substances to which members of society are involuntarily exposed are proved safe from long‐term, low‐level effects on human health. The World Health Organization estimates that between 1 and 5% of malignant disease in developed countries is attributable to environmental factors: it is possible that this figure may be underestimated. Anecdotal evidence suggests that cancer may be a disease of industrialization. Further research into the tissue organization field theory may be warranted, as some forms of pre‐malignant states are attributed to dysorganogenesis, for example an undescended testis.
The circadian pacemaker regulates the timing, structure and consolidation of human sleep. The extent to which this pacemaker affects electroencephalographic (EEG) activity during sleep remains unclear.
To investigate this, a total of 1.22 million power spectra were computed from EEGs recorded in seven men (total, 146 sleep episodes; 9 h 20 min each) who participated in a one‐month‐long protocol in which the sleep–wake cycle was desynchronized from the rhythm of plasma melatonin, which is driven by the circadian pacemaker.
In rapid eye movement (REM) sleep a small circadian variation in EEG activity was observed. The nadir of the circadian rhythm of α‐activity (8.25–10.5 Hz) coincided with the end of the interval during which plasma melatonin values were high, i.e. close to the crest of the REM sleep rhythm.
In non‐REM sleep, variation in EEG activity between 0.25 and 11.5Hz was primarily dependent on prior sleep time and only slightly affected by circadian phase, such that the lowest values coincided with the phase of melatonin secretion.
In the frequency range of sleep spindles, high‐amplitude circadian rhythms with opposite phase positions relative to the melatonin rhythm were observed. Low‐frequency sleep spindle activity (12.25–13.0 Hz) reached its crest and high‐frequency sleep spindle activity (14.25–15.5Hz) reached its nadir when sleep coincided with the phase of melatonin secretion.
These data indicate that the circadian pacemaker induces changes in EEG activity during REM and non‐REM sleep. The changes in non‐REM sleep EEG spectra are dissimilar from the spectral changes induced by sleep deprivation and exhibit a close temporal association with the melatonin rhythm and the endogenous circadian phase of sleep consolidation.
Life in industrialized societies is primarily life inside buildings. Illumination from electric lighting in the built environment is quite different from solar radiation in intensity, spectral content, and timing during the 24-hour daily period. Humans evolved over millions of years with the day–night pattern of solar radiation as the primary circadian cue. This pattern maintained a 24-hour rhythm of melatonin release, as well as a host of other physiological rhythms including the sleep–wake cycle. Electric lighting in the built environment is generally more than sufficient for visual performance, but may be inappropriate for the maintenance of normal neuroendocrine rhythms in humans; e.g., insufficient during the day and too much at night. Lighting standards and engineering stress visual performance, whereas circadian function is not currently emphasized. The molecular biological research on the circadian clock and on mechanisms of phototransduction makes it clear that light for vision and light for circadian function are not identical systems. In particular, if electric lighting as currently employed contributes to `circadian disruption' it may be an important cause of `endocrine disruption' and thereby contribute to a high risk of breast cancer in industrialized societies.
Shift work, in particular night work, can have a negative impact on health and well-being of workers as it can cause: (a) disturbances of the normal circadian rhythms of the psychophysiological functions, beginning with the sleep/wake cycle; (b) interferences with work performance and efficiency over the 24 hour span, with consequent errors and accidents; (c) difficulties in maintaining the usual relationships both at family and social level, with consequent negative influences on marital relations, care of children and social contacts; (d) deterioration of health that can be manifested in disturbances of sleeping and eating habits and, in the long run, in more severe disorders that deal prevalently with the gastrointestinal (colitis, gastroduodenitis and peptic ulcer), neuro-psychic (chronic fatigue, anxiety, depression) and, probably, cardiovascular (hypertension, ischemic heart diseases) functions. Besides, shift and night work may have more specific adverse effects on women's health both in relation to their particular hormonal and reproductive function, and their family roles. It has been estimated that about 20% of all workers have to leave shift work in a very short time because of serious disturbances; those remaining in shift work show different levels of (mal)adaptation and (in)tolerance, that can become more or less manifest in different times, and with different intensity. In fact, the effects of such stress condition can vary widely among the shift workers in relation to many ‘intervening variables’ concerning both individual factors (e.g. age, personality traits, physiological characteristics), as well as working situations (e.g. work loads, shift schedules) and social conditions (e.g. number and age of children, housing, commuting).
Results of a photoperiod experiment show that human sleep can be unconsolidated and polyphasic, like the sleep of other animals. When normal individuals were transferred from a conventional 16-h photoperiod to an experimental 10-h photo-period, their sleep episodes expanded and usually divided into two symmetrical bouts, several hours in duration, with a 1-3 h waking interval between them. The durations of nocturnal melatonin secretion and of the nocturnal phase of rising sleepiness (measured in a constant routine protocol) also expanded, indicating that the timing of internal processes that control sleep and melatonin, such as circadian rhythms, had been modified by the change in photoperiod. Previous work suggests that the experimental results could be simulated with dual-oscillators, entrained separately to dawn and dusk, or with a two-process model, having a lowered threshold for sleep-onset during the scotoperiod.
(1) Evidence has been presented, based on measurement of melatonin by radioimmunoassay in 12 healthy males, that the urinary excretion of melatonin follows a circadian pattern in humans during sleep deprivation when the subjects are exposed to light. (2) Melatonin excretion increased with increased sleep deprivation. (3) Melatonin excretion during recovery sleep did not differ from that during base line sleep. (4) Melatonin excretion did not react to psychosocial stress at trough times (as adrenaline did). (5) Self-rated fatigue and body temperature exhibited a circadian variation. (6) Peak fatigue and trough body temperature coincided temporally with the peak of melatonin excretion.
Interleukin-6 (IL-6) is a recently characterized pleiotropic cytokine with antitumor activity. We investigated the production of IL-6 by renal cell cancer (RCC) and the growth effects of IL-6 on RCC. Using immunoperoxidase staining, cytoplasmic IL-6 was detected in four of four renal tumor lines and in tumor cells from freshly nephrectomized RCC. We found that IL-6 mRNA was expressed at basal culture conditions by seven of ten RCC tumor lines tested. Biologically active IL-6, as measured by the B9 assay, was produced by all ten RCC tumor lines. The addition of tumor necrosis factor alpha (TNF alpha) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P less than 0.05). The combination of interferon gamma IFN gamma and TNF alpha further enhanced the augmented IL-6 mRNA accumulation seen with TNF alpha alone (P less than 0.05). TNF alpha also significantly stimulated the production of biologically active IL-6 (P less than 0.01). Furthermore, IFN gamma and TNF alpha were found to enhance IL-6 bioactivity synergistically (P less than 0.05). The growth effects of IL-6 on RCC were also investigated in two experimental systems: IL-6 was found to stimulate proliferative responses in six of six RCC tumor lines as measured by thymidine-uptake assays; however, only one of six tumor lines displayed an increase in proliferative response of greater than 21% (113%). The growth effect of IL-6 was further tested in clonogenic assays. One of the tumor lines tested displayed an enhanced growth response of up to 200%. We conclude that IL-6 is produced by RCC; this production is enhanced by TNF alpha with synergistic effects seen with IFN gamma at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines.
Three experiments which utilized an ultrashort sleep-waking cycle were conducted to investigate the 24 h structure of sleepiness after 1 night of sleep deprivation under 2 experimental conditions: instructing subjects to attempt to fall asleep or instructing subjects to attempt to resist sleep. Six subjects participated in experiment 1. At 19.00 h they started a 13 min waking-7 min sleep attempt, or 13 min waking-7 min resisting sleep, until 19.00 h on the next day. Eight subjects were tested in a similar way in experiment 2, which started at 07.00 h after a night of sleep deprivation and lasted for 24 h. Eight subjects were similarly tested in experiment 3 which started at 11.00 h after a night of sleep deprivation and lasted for 36 h until 23.00 h on the next day. The results showed that in spite of the significant between-group differences in total sleep, the temporal structure of sleepiness was very similar in the 3 experiments. In each there was a bimodal distribution of sleepiness: a major nocturnal sleepiness crest and a secondary mid-afternoon sleepiness peak. These were separated by a 'forbidden zone' for sleep centred at around 20.00-22.00 h. The onset of the nocturnal sleep period (the sleep gate) was found to be a discrete event occurring as an 'all or none' phenomenon. Its timing was stable over a 2 week period, and independent of the specific experimental demands; there were no significant differences between the AS and RS conditions with respect to total sleep time or any of the sleep stages. These results, which demonstrate structured variations in sleepiness across the nycthemeron are discussed in the light of the recent modelling of sleep along homeostatic principles.
It is the purpose of this paper to present the hypothesis that use of electric power may increase risk of breast cancer. The hypothesis is based on experimental evidence that shows an effect of light and extremely low frequency electric and/or magnetic (ELF) fields on pineal melatonin production, and on the relationship of melatonin to mammary carcinogenesis. A brief discussion of the epidemiology of breast cancer will be followed by a description of the experimental foundation for the hypothesis. 20 references, 1 figure.
Plasma melatonin concentrations were determined over a period of 24 hours in 20 women with clinical stage I or II breast cancer. In ten of the patients, whose tumors were estrogen receptor positive, the nocturnal increase in plasma melatonin was much lower than that observed in eight control subjects. Women with the lowest peak concentration of melatonin had tumors with the highest concentrations of estrogen receptors. A significant correlation was found between the peak plasma melatonin concentration and the tumor estrogen receptor concentration in 19 of the patients. These data suggest that low nocturnal melatonin concentrations may indicate the presence of estrogen receptor positive breast cancer and could conceivably have etiologic significance.
The sleep patterns of 8 normal subjects living in a winter-type photoperiod (10 h light and 14 h darkness; LD 10:14) for 4 weeks were characterized by the presence of periods of spontaneous wakefulness alternating with periods of spontaneous sleep. Transitions from sleep to wakefulness occurred much more frequently out of REM sleep than out of NREM sleep (P < 0.002). REM periods that terminated in wakefulness showed shorter REM durations (P < 0.0005) and higher REM densities (P < 0.0005) than REM periods that did not terminate in wakefulness. The authors discuss these results in terms of a possible relationship between REM density and arousal level. The higher REM density preceding wakefulness and the increased number of REM periods terminating in spontaneous awakenings could reflect an enhanced level of a brain arousing process, resulting from reduced sleep pressure in the extended nights.