Regular Circadian Rhythm Research Articles

Melatonin modulates lipopolysaccharides-induced inflammatory response and maintains circadian rhythm associated with histone H3 acetylation in bovine mammary epithelial cells

Lipopolysaccharides (LPS) can disrupt the barrier function of mammary epithelial cells, leading to mastitis. The protective effects of melatonin (MT) have been demonstrated against various infections, but the underlying mechanism remains unclear in LPS-induced bovine mastitis. This study, therefore, aimed to investigate the modulatory effect of melatonin (MT) on LPS-induced inflammation in bovine mammary epithelial cells (BMECs), its influence on the disruption of circadian rhythms triggered by this inflammation, and the potential underlying molecular mechanisms. BMECs extracted from lactating cows underwent one of 4 treatments in triplicates for 12 h simultaneously: Control (CON), LPS (exposed to LPS at 1 μg/mL), MT (exposed to MT at 40 μmol/L), or LPS + MT (LMT, exposed to both LPS at 1 μg/mL and MT at 40 μmol/L). The flow cytometry results demonstrated that MT reduced the ratios of cells in the G0/G1 phase but increased those in the G2/M phase (P < 0.05). Additionally, MT inhibited p65 phosphorylation levels, leading to a decreased cellular inflammatory response (P < 0.05). Treatment with MT elevated the acetylation levels of histone H3 in BMECs compared to the LPS treatment (P < 0.05). The circadian rhythm analysis revealed a significant increase in the gene expression levels of BMAL1, PER1, CRY1, and CRY2 at the 12 h mark in LMT compared to the LPS treatment (P < 0.05). Additionally, this study assessed the fluctuations in clock-related genes PER2 and CLOCK over 24 h under various treatment conditions. The results demonstrated that BMECs exposed to LMT treatment exhibited a significant increase in the expression levels of CLOCK and PER2 genes from 4 to 24 h in comparison to the LPS treatment (P < 0.05). Moreover, cells in the LMT treatment displayed a more regular circadian rhythm cycle compared to those in the LPS treatment. Overall, the data suggest that MT could alleviate the inflammatory response in BMECs by upregulating histone H3 acetylation, thereby maintaining the physiological circadian rhythm of BMECs.

(057) Influence of Circadian Disruption on Erectile Function in Chronic Jet-Lagged Young Rats

Abstract Introduction Sleep is crucial during the developing stage of one’s life and has been associated with physical activity. However, as the number of 24-hour stores such as convenience stores and supermarkets have increased, along with increased internet usage, people have developed the habit of staying up late, resulting in sleep deprivation due to disruption in the light-dark cycle. Jet lag is widely used in animal models for inducing irregular circadian rhythms. Chronic jet lagged model animals are known to develop a variety of disorders. Objective To investigate the influences of chronic jet lag on erectile function in rats in order to elucidate the effects of irregular circadian rhythms on future sexual function. Methods 4-week-old rats underwent randomly assigned to remain either under the control light/dark cycle (Cont group) or under chronic light/dark shift schedule to simulate the conditions of chronic jet lag (CJL group). The shift-lag protocol consisted of 8 h light/dark phase advances repeated every 3 days for 4 weeks. Erectile function was examined at 1, 2, and 4 weeks post CJL treatment. After 4 weeks of CJL treatment, the rats were returned to control light/dark cycle for 4 and 8 weeks, as CJL(4w)+Rest(4w) group and CJL(4w)+Rest(8w) group, and erectile function was examined correspondingly. Erectile function was tested using intracavernous pharmacotherapy (ICP) measurements, and endothelial function was tested through an isometric tension study. Western blot analysis was used to assess the levels of endothelial nitric oxide (eNOS) and phosphorylated eNOS (p-eNOS). Additionally, mRNA expressions of clock genes (Bmal1 and Cry 1) and growth factors (TGF-β1 and ICAM-1) were tested using real-time PCR. Results The ICP/MAP ratio was significantly lower in the CJL group (0.35 ± 0.05) at 4 weeks than in the control group (0.66 ± 0.05) (P &amp;lt; 0.05). CJL group exhibited significantly lower testosterone levels, Bmal1, Cry 1, TGF-β1, and ICAM-1 expression, and p-eNOS and cGMP levels. The ICP/MAP ratio in the CJL(4w)+Rest(4w) group (0.47 ± 0.06) was lower than that in the control group (P &amp;lt; 0.01) whereas the ratio in the CJL(4w)+Rest(8w) group (0.81 ± 0.03) was similar to that in the control group (P &amp;gt; 0.05). Conclusions In this study, chronic jet lagged (4 weeks) rats exhibited a decreased ICP/MAP ratio, reduced testosterone level, and decreased p-eNOS expression, indicating the development of erectile dysfunction (ED). Upon 8 weeks of normal light/dark shift schedule, erectile function was recovered. This study suggests that irregular circadian rhythms induced by repeated jet lag, especially in childhood, may affect the production of sex hormones and erectile function in the future. Therefore, it is necessary for children to follow a regular circadian rhythm and healthy lifestyle. Disclosure No.

Circadian Genes and Economic Traits in Livestock Animals

Circadian rhythms are oscillators of endogenous autonomic activity in all living organisms and regulate economic traits such as reproduction, milk characteristics and growth performance in farm animals. These rhythms are directly or indirectly controlled by the circadian clock in a 24-hour cycle. It has evolved as an adaptive system for living organisms in a cyclical natural environment. A regular circadian rhythm can be associated with good health, well-being, strong immunity, and high economic characteristics. The interaction between circadian rhythmicity and the physiology of farm animals is becoming an important focus of animal science. Understanding the circadian genes (CLOCK, BMAL, PER1, PER2, CRY1, CRY2) and actions regulating circadian oscillation in farm animals is important to improve management and increase economic traits. The study aimed to summarise the research on the effects of circadian rhythm genes on productivity and to highlight the importance of this topic

Physical activity influences adherence to pharmacological treatments in patients with severe mental disorders: results from the multicentric, randomized controlled LIFESTYLE trial.

Introduction: Poor adherence to pharmacological treatment is frequent in people with severe mental disorders and it often causes lack of effectiveness of many psychotropic drugs. Thus, efforts should be made to improve adherence to pharmacological treatments in patients with these disorders. Methods: In this paper, based on the LIFESTYLE randomized, controlled multicentric trial, we aim to: 1) assess the level of adherence in a real-world sample of patients with severe mental disorders; 2) evaluate differences in treatment adherence according to patients' socio-demographic and clinical characteristics; 3) evaluate the impact of an innovative psychosocial intervention, on patients' adherence to treatments. The Lifestyle Psychosocial Group Intervention consists of group sessions, focused on different lifestyle behaviours, including healthy diet; physical activity; smoking habits; medication adherence; risky behaviours; and regular circadian rhythms. At end of each session a 20-min moderate physical activity is performed by the whole group. Results: The sample consists of 402 patients, mainly female (57.1%, N = 229), with a mean age of 45.6years (±11.8). Less than 40% of patients reported a good adherence to pharmacological treatments. Adherence to treatments was not influenced by gender, age, diagnosis and duration of illness. At the end of the intervention, patients receiving the experimental intervention reported a significant improvement in the levels of adherence to treatments (T0: 35.8% vs. T3: 47.6%, p < 0.005). Patients practicing moderate physical activity reported a two-point improvement in the levels of adherence [odds ratio (OR): 1,542; 95% confidence intervals (CI): 1,157-2,055; p < 0.001], even after controlling for several confounding factors. Discussion: The experimental lifestyle intervention, which can be easily implemented in the routine clinical practice of mental health centres, was effective in improving adherence to pharmacological treatments.

G protein-coupled receptor 55 activated by palmitoylethanolamide is associated with the development of nocturia associated with circadian rhythm disorders

AimsBladder function is regulated by clock genes and dysregulation of circadian bladder function can cause nocturia. The blood concentration of palmitoylethanolamide (PEA), a fatty acid metabolite, changes with circadian rhythm. Clock gene abnormalities demonstrate the highest PEA levels during the sleep phase. PEA is a GPR55 agonist that influences urination; therefore, increased PEA during the sleep phase may cause nocturia. Herein, we investigated the function of GPR55 to evaluate the relationship between GPR55 and nocturia that evoked higher PEA during the sleep phase in patients with circadian rhythm disorders. Main methodsMale C57BL/6 mice were used. GPR55 localization was evaluated by immunofluorescence staining, qRT-PCR, and western blotting. Variations in PEA-induced intracellular Ca2+ concentrations were measured in primary cultured mouse urothelial cells (UCs) using Ca2+ imaging. PEA-induced NGF and PGI2 release in UCs was measured by ELISA. The micturition reflex pathway after PEA administration was evaluated using immunofluorescence staining. Key findingsGPR55 was predominant in the UC layer. PEA induced release of Ca2+ from the endoplasmic reticulum into the UC cytoplasm. ELISA and immunofluorescence staining revealed that NGF and PGI2 were released from bladder UCs, stimulated the pontine micturition center in mice, and induced nocturia. SignificanceThe loss of regular circadian metabolizing rhythm in fatty acids causes higher blood PEA levels during the sleep phase. Binding of PEA to GPR55 in UC may activate the downstream processes of the micturition reflex, leading to nocturia. These findings suggest a new mechanism for nocturia and its potential as a therapeutic target.

Circadian clock disruption in autoimmune thyroiditis.

A vicious cycle between circadian disruption and escalating immune responses has been described in diverse inflammatory disease. The current study aimed to explore the role of circadian clock disruption in autoimmune thyroiditis (AIT). Thirty AIT patients and 30 controls were enrolled and biopsied for thyroid tissues. Alterations of core clock genes expression in AIT thyroid tissues, and its association with serum and tissue inflammatory biomarkers were assessed. For animal studies, C57BL/6J mice administered with porcine thyroglobulin or PBS (as control) combined with adjuvants were sacrificed at four time points to investigate the circadian characteristic of experimental autoimmune thyroiditis (EAT). Light shift (LS) conditions were used to explore the influence of external circadian disturbance on EAT. The expression of clock genes BMAL1 and PER2 was significantly reduced in thyroid tissues from AIT patients and was negatively correlated to levels of thyroid peroxidase antibodies. In mouse models, diurnal fluctuations of proinflammatory cytokines were demonstrated, and further exposing mice to LS led to overproduction of TNF-α, IFN-γ, and anti-thyroglobulin antibodies. Circadian analysis revealed significant oscillations of Bmal1, Clock, Per2, Cry1, Ror, and Rev-erb, which was broadly disturbed in EAT, LS, and EAT + LS groups. This study demonstrates that expression pattern of clock genes was disrupted in AIT thyroid, and chronic circadian disruption may aggravate the inflammatory responses in AIT. Whether maintaining a regular circadian rhythm can alleviate autoimmune thyroid diseases warrants further research.

The Metastatic Spread of Breast Cancer Accelerates during Sleep: How the Study Design can Affect the Results.

Metastasis is the most common event that determines survival in patients with breast cancer. The benefits of appropriate sleep in enhancing cancer patients' prognosis have been demonstrated. Likewise, emerging evidence has noted the positive impacts of regular circadian rhythm on cancer survival. Proper sleep and regular circadian rhythm can help to improve the cancer prognosis by enhancing the immune system. Besides, circadian rhythm disruption can assist cancer progression by promoting systemic inflammation. However, a recent study by Diamantopoulou et al. titled "The Metastatic Spread of Breast Cancer Accelerates during Sleep" demonstrated that sleep can aggravate breast cancer metastasis. This article outlines how the study design can affect this controversy.

Circadian Rhythm Changes in Healthy Aging and Mild Cognitive Impairment.

Disruptions in circadian rhythms can occur in healthy aging; however, these changes are more severe and pervasive in individuals with age-related and neurodegenerative diseases, such as dementia. Circadian rhythm alterations are also present in preclinical stages of dementia, for example, in patients with mild cognitive impairments (MCI); thus, providing a unique window of opportunity for early intervention in neurodegenerative disorders. Nonetheless, there is a lack of studies examining the association between relevant changes in circadian rhythms and their relationship with cognitive dysfunctions in MCI individuals. In this review, circadian system alterations occurring in MCI patients are examined compared to healthy aging individuals while also considering their association with MCI neurocognitive alterations. The main findings are that abnormal circadian changes in rest-activity, core body temperature, melatonin, and cortisol rhythms appear in the MCI stage and that these circadian rhythm disruptions are associated with some of the neurocognitive deficits observed in MCI patients. In addition, preliminary evidence indicates that interventions aimed at restoring regular circadian rhythms may prevent or halt the progress of neurodegenerative diseases and mitigate their related cognitive impairments. Future longitudinal studies with repeated follow-up assessments are needed to establish the translational potential of these findings in clinical practice.

Progress in researches on the effect of artificial light at night on infertility

Infertility is a serious social and public health problem, and the causes of infertility are also the focus of many researchers in recent years. Since the invention of the electric light, people's exposure to night light has increased rapidly, and the adverse effects on human health have also begun to enter the vision of researchers. Studies have shown that artificial lighting at night can affect the circadian rhythm of organisms and the secretion of melatonin (melatonin), and regular circadian rhythms and sufficient melatonin are conducive to successful reproduction. This article reviews the current research status of the effects of artificial lighting at night on infertility in recent years, which provides a new direction for researchers to study the influencing factors of infertility.

Lactation Associated Genes Revealed in Holstein Dairy Cows by Weighted Gene Co-Expression Network Analysis (WGCNA).

Simple SummaryWeighted gene coexpression network analysis (WGCNA) is a novel approach that can quickly analyze the relationships between genes and traits. In the past few years, studies on the gene expression changes of dairy cow mammary glands were only based on transcriptome comparisons between two lactation stages. Few studies focused on the relationships between gene expression of the dairy mammary gland and lactation stage or milk composition in a lactation cycle. In this study, we detected milk yield and composition in a lactation cycle. For the first time, we constructed a gene coexpression network using WGCNA on the basis of 18 gene expression profiles during six stages of a lactation cycle by transcriptome sequencing, generating 10 specific modules. Genes in each module were performed with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Module–trait relationship analysis showed a series of potential candidates related to milk yield and composition. The current study provides an important theoretical basis for the further molecular breeding of dairy cows. Weighted gene coexpression network analysis (WGCNA) is a novel approach that can quickly analyze the relationships between genes and traits. In this study, the milk yield, lactose, fat, and protein of Holstein dairy cows were detected in a lactation cycle. Meanwhile, a total of 18 gene expression profiles were detected using mammary glands from six lactation stages (day 7 to calving, −7 d; day 30 post-calving, 30 d; day 90 post-calving, 90 d; day 180 post-calving, 180 d; day 270 post-calving, 270 d; day 315 post-calving, 315 d). On the basis of the 18 profiles, WGCNA identified for the first time 10 significant modules that may be related to lactation stage, milk yield, and the main milk composition content. Genes in the 10 significant modules were examined with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results revealed that the galactose metabolism pathway was a potential candidate for milk yield and milk lactose synthesis. In −7 d, ion transportation was more frequent and cell proliferation related terms became active. In late lactation, the suppressor of cytokine signaling 3 (SOCS3) might play a role in apoptosis. The sphingolipid signaling pathway was a potential candidate for milk fat synthesis. Dairy cows at 315 d were in a period of cell proliferation. Another notable phenomenon was that nonlactating dairy cows had a more regular circadian rhythm after a cycle of lactation. The results provide an important theoretical basis for the further molecular breeding of dairy cows.

Benefits and Risks of Melatonin in Hepatic and Pancreatic Disorders; A Review of Clinical Evidences.

Melatonin is the “clock factor” produced from the pineal gland dominating regular circadian rhythm in mammalians. It is an indoleamine with potent multifunctional pharmacological effects, both receptor dependent and non-receptor dependent effects, including antioxidant and anti-inflammatory activities. The aim of this review is to summarize clinical evidence related to melatonin’s effectiveness in the treatment of liver and pancreas diseases. Databases including PubMed, Scopus, and Cochran Library were searched up to November 2020.Finally, this review has summarized up-to-date clinical evidence to investigate the efficacy and safety of melatonin for the management of liver and pancreas diseases. Melatonin has been demonstrated to have beneficial effects on the management of Non-alcoholic fatty liver disease (NAFLD), sleep disturbance of cirrhotic patients, prevention of drug/poison induced liver toxicity,and prevention of post endoscopic retrograde cholangiopancreatography pancreatitis (PEP);more data is needed to recommend melatonin administration in the treatment of mentioned disorders.

Re-Setting the Circadian Clock Using Exercise against Sarcopenia.

Sarcopenia is defined as the involuntary loss of skeletal muscle mass and function with aging and is associated with several adverse health outcomes. Recently, the disruption of regular circadian rhythms, due to shift work or nocturnal lifestyle, is emerging as a novel deleterious factor for the development of sarcopenia. The underlying mechanisms responsible for circadian disruption-induced sarcopenia include molecular circadian clock and mitochondrial function associated with the regulation of circadian rhythms. Exercise is a potent modulator of skeletal muscle metabolism and is considered to be a crucial preventative and therapeutic intervention strategy for sarcopenia. Moreover, emerging evidence shows that exercise, acting as a zeitgeber (time cue) of the skeletal muscle clock, can be an efficacious tool for re-setting the clock in sarcopenia. In this review, we provide the evidence of the impact of circadian disruption on skeletal muscle loss resulting in sarcopenia. Furthermore, we highlight the importance of exercise timing (i.e., scheduled physical activity) as a novel therapeutic strategy to target circadian disruption in skeletal muscle.

Relationship between Sleep Duration, Sun Exposure, and Serum 25-Hydroxyvitamin D Status: A Cross-sectional Study

Normal-range sleep duration is an important factor for general health and metabolism, and insufficient or excessive sleep is associated with chronic metabolic disease. Among the many factors that affect sleep duration, sun exposure plays an important role in maintaining regular circadian rhythm and is also involved in the production and activation of 25-hydroxyvitamin D [25(OH)D], which regulates various functions in the body. However, 25(OH)D is available through food and various nutritional supplements without sun exposure, so it is important to find out the complex relationship among sun exposure, vitamin D status, and sleep duration. The relationship between sun exposure, vitamin D status, and sleep duration was analyzed in the nationwide survey and examination of 25,534 study populations, after adjusting for demographic characteristics, physical characteristics, lifestyle status, and socio-demographic variables. Vitamin D status alone did not show the relationship with sleep duration, although there were statistical relationships in the various factors including sun exposure with sleep duration. There was a statistical difference in 25(OH)D according to sleep duration, only in low sun exposure group. Subjects with low sun exposure and excessive sleep duration comparatively lower 25(OH)D than those with normal-range sleep, even after adjustment for potentially confounding factors. Individuals with limited exposure to sunlight should maintain adequate vitamin D status to have an appropriate sleep duration for health.

Circadian rhythm disruption is associated with an increased risk of sarcopenia: a nationwide population-based study in Korea

Reduced sleep quality is associated with an increased risk of sarcopenia. However, the potential effects of disturbing the regular circadian rhythm, as occurs with shift work, on the risk of sarcopenia have not been established. Data from 9105 workers from the 2008–2011 Korean National Health and Nutrition Examination Survey were analyzed. Sarcopenia, measured by dual-energy X-ray absorptiometry, was defined as one standard deviation below the mean of the appendicular skeletal muscle/body mass index value of a young reference group. Compared to the group that had never experienced shift work, the odds ratio (OR) for sarcopenia with a 95% confidence interval (95% CI) for the shift work group was 1.7 (1.5–1.9); the association remained even after adjusting for confounding variables, including age, sex, total fat mass, insulin resistance profile, smoking, alcohol intake, diet, and physical activity. The results of the subgroup analysis indicated that the highest risk of sarcopenia was among workers engaging in shift work with an irregular schedule (OR 1.8, 95% CI 1.3–2.4). Disruption of circadian rhythm by shift work was associated with increased risk of sarcopenia. Intervention strategies are needed to prevent sarcopenia in shift workers.

Therapeutic role of melatonin in migraine prophylaxis: A systematic review.

BackgroundMelatonin is the “clock factor” generated from pineal gland dominating regular circadian rhythm in humans. Migraine is one of the most severe and debilitating primary headache disorders. Thus far, many diseases have been found to associate with melatonin, including the migraine. Therefore, melatonin's therapeutic potential for migraine is drawing attention.ObjectivesThe aim of this study is to offer a systematic review of extant data of melatonin in migraine prophylaxis and to provide clinical implications and specific recommendations for future studies.Data sources and study methodsA systematic research was conducted in September 2018 by using PubMed and Google Scholar databases to search for science literature published after 1988.ResultsIn all, 7 eligible articles were identified, including 4 randomized controlled studies and 3 observational studies. Due to high heterogeneities and limited number of studies, meta-analysis was not feasible, and only systematic review was performed. The results show that present evidence cannot claim melatonin's effectiveness according to the conflicting outcomes; however, the two negative outcomes of melatonin not different from placebo and melatonin inferior to amitriptyline are possible under-powering because of methodological, pharmacological, and therapeutic shortcomings. Observational studies also support melatonin's efficacy in migraine. As a result, melatonin is very likely to benefit migraine in prophylaxis and may have a similar effectiveness to other main preventive medications. Immediate-release melatonin 3 mg was established as effective, melatonin receptor agonist (Agomelatine) 25 mg and prolonged-release melatonin 4 mg were observed efficacious in observational studies. Melatonin displayed ineffective in the 2-month trial; thus, 3 months or more may be an enough duration for migraine therapy. Despite melatonin being generally safe, emerging literature is illustrating that a few severe adverse effects can be caused by melatonin, for example, liver injuries, reproductive system dysfunctions, and detrimental immunostimulation.ConclusionsMelatonin is very likely to be a promising alternative for migraine prophylaxis. Current literature examining melatonin's efficacy in migraine prevention is growing, but still limited. Future studies of perfect design in methodology, pharmacology, and therapeutics are needed to achieve a deeper awareness of melatonin's role in migraine as well as more studies to explore the safety issues of melatonin medicine.

Chronodisruption and Obesity

BACKGROUND: Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders.CONTENT:Regularly alternating periods of light and darkness, such as normally occur with the rising and the setting of the sun, are essential for the maintenance of undisturbed circadian rhythms in all organisms including humans. The light-dark environment, as detected by specialized photoreceptors in the retinas, impacts the endogenous circadian clock in the anterior hypothalamus, the suprachiasmatic nuclei. These nuclei, via both neural and humoral signals, communicate with cells throughout the organism to establish regular circadian rhythms. The introduction of artificial sources of light roughly 150 years ago has significantly undermined the naturally occurring light-dark environment and, likewise, has disturbed circadian rhythms since light is now available at unusual times, i.e., at night. Light at night is known to cause circadian disruption and melatonin suppression. Many potentially pathophysiological consequences of these artificial light-mediated changes, include cancer, cardiovascular diseases, insomnia, metabolic syndrome, diabetes, and cognitive disorders may be aggravated by the increased exposure to light at night, which is inevitable in well-developed societies that have undergone extensive electrification.SUMMARY: Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding, calorie restriction and intermittent fasting, provide a time cue and reset the circadian clock and lead to better health. In contrast, high-fat diet leads to disrupted circadian expression of metabolic factors and obesity.KEYWORDS: obesity, circadian clock, metabolism, chronodisruption

Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology

Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on the peripheral reproductive organs. Likewise, numerous investigations have documented that stable circadian rhythms are also helpful in maintaining reproductive health. The relationship of melatonin and circadian rhythmicity to maternal and fetal health is summarized in this review. Databases were searched for the related published English literature up to 15 May 2013. The search terms used in various combinations included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress and free radicals. The results of the studies uncovered are summarized herein. Both melatonin and circadian rhythms impact reproduction, especially during pregnancy. Melatonin is a multifaceted molecule with direct free radical scavenging and indirect antioxidant activities. Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress. The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction. This may contribute to pre-eclampsia and other disorders which often complicate pregnancy. Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals. Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei. Optimal circadian rhythmicity in the mother is important since her circadian clock, either directly or indirectly via the melatonin rhythm, programs the developing master oscillator of the fetus. Experimental studies have shown that disturbed maternal circadian rhythms, referred to as chronodisruption, and perturbed melatonin cycles have negative consequences for the maturing fetal oscillators, which may lead to psychological and behavioral problems in the newborn. To optimize regular circadian rhythms and prevent disturbances of the melatonin cycle during pregnancy, shift work and bright light exposure at night should be avoided, especially during the last trimester of pregnancy. Finally, melatonin synergizes with oxytocin to promote delivery of the fetus. Since blood melatonin levels are normally highest during the dark period, the propensity of childbirth to occur at night may relate to the high levels of melatonin at this time which work in concert with oxytocin to enhance the strength of uterine contractions. A number of conclusions naturally evolve from the data summarized in this review: (i) melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis; (ii) circadian clock genes, which are components of all cells including those in the peripheral reproductive organs, have important roles in reproductive and organismal (fetal and maternal) physiology; (iii) due to the potent antioxidant actions of melatonin, coupled with its virtual absence of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia, intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc. (iv) the propensity for parturition to occur at night may relate to the synergism between the nocturnal increase in melatonin and oxytocin.

Psychosomatic disorder may be related to circadian rhythms in physically healthy students

Students suffering from subjective psychosomatic disorder often have basic lifestyle problems. We examined 30 healthy students aged 21–22 years old. Salivary samples were collected from the subjects at home five times per day (20:00, 24:00, 04:00, 08:00 and 12:00 h). We assessed melatonin secretion patterns by fluorescence enzyme immunoassay and cortisol secretion by ELISA. We assigned the subjects to regular, semi-regular and irregular circadian rhythm groups based on whether melatonin secretion was high until midnight. A self-assessment questionnaire addressing psychosomatic disorder was completed by the same students. The subjects rated their psychosomatic symptoms twice per day (08:00 and 20:00 h). The irregular group showed lower cortisol awakening response, but high cortisol concentrations at 12:00 h; this group also reported more subjective health complaints related to psychosomatic stress compared with the regular group. Our findings suggest that psychosomatic disorder is associated with circadian rhythms in Japanese students.

Quantifying Collective Attention from Tweet Stream

Online social media are increasingly facilitating our social interactions, thereby making available a massive “digital fossil” of human behavior. Discovering and quantifying distinct patterns using these data is important for studying social behavior, although the rapid time-variant nature and large volumes of these data make this task difficult and challenging. In this study, we focused on the emergence of “collective attention” on Twitter, a popular social networking service. We propose a simple method for detecting and measuring the collective attention evoked by various types of events. This method exploits the fact that tweeting activity exhibits a burst-like increase and an irregular oscillation when a particular real-world event occurs; otherwise, it follows regular circadian rhythms. The difference between regular and irregular states in the tweet stream was measured using the Jensen-Shannon divergence, which corresponds to the intensity of collective attention. We then associated irregular incidents with their corresponding events that attracted the attention and elicited responses from large numbers of people, based on the popularity and the enhancement of key terms in posted messages or “tweets.” Next, we demonstrate the effectiveness of this method using a large dataset that contained approximately 490 million Japanese tweets by over 400,000 users, in which we identified 60 cases of collective attentions, including one related to the Tohoku-oki earthquake. “Retweet” networks were also investigated to understand collective attention in terms of social interactions. This simple method provides a retrospective summary of collective attention, thereby contributing to the fundamental understanding of social behavior in the digital era.

직장온·멜라토닌·코티졸 분석을 통한 노년기 여성의 의복 착용 쾌적성 평가

This study examines the wearing comfort of elderly women through a physiological analysis based on rectal temperature and biochemical analysis with salivary melatonin and cortisol. This study was conducted on 7 elderly women aged 65 or over. Two kinds of clothing ensemble (control and prototype) were used as experimental clothing. The control clothing was a general clothing ensemble and the prototype clothing lowered clothing pressure by adding an extra gap. The experimental schedule included daily living activities with randomly assigned experimental clothing. Rectal temperature was constantly measured every 5 minutes during the experiment and saliva samples for melatonin and cortisol were collected twice per day before and after sleep. The rectal temperature was lower for the prototype than the control throughout the experiment, and its circadian rhythm was prompt and clear in prototype. In addition, melatonin was secreted more but cortisol was secreted less when the subjects wore the prototype clothing. With these results, we assumed that regular circadian rhythm and low level of stress might be caused by wearing prototype clothing that lowered clothing pressure. The results demonstrate the necessity to develop clothing that considers body changes in elderly women.