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Objectives: Diabetes mellitus is a metabolic condition with hyperglycemia. Literature has shown a correlation between poor sleep quality and duration with an increased incidence of insomnia in diabetic individuals. The goal of this study was to determine the magnesium and potassium supplementation effect among diabetic individuals with insomnia., Methods: A randomized controlled trial (single blind) was conducted on 320 patients with diabetes; after 2 months of follow-up, 290 patients completed the trial. The Insomnia Severity Index (ISI) was used to assess the severity and duration of insomnia, before and after the trial. Tablets containing supplements were prepared: placebo (T1), magnesium (Mg, T2), potassium (K, T3), and a combination of Mg and K (T4). Melatonin and cortisol (sleep hormones) were measured from blood (serum) using an enzyme-linked immunosorbent assay (ELISA), before and after the trial., Results: The study included 93 (32.1%) male and 197 (67.9%) female participants. According to the analysis, there was a significant association between the treatment groups and ISI after the trial (post-trial), p = 0.0001. Analysis showed that there was significant association between pre- and post-serum cortisol levels in treatment groups 2, 3, and 4 (T2, T3, and T4) as p -values are 0.001, 0.001, and 0.001 respectively. Similar findings were observed for serum melatonin., Conclusions: The study revealed that magnesium, potassium, and magnesium and potassium combined had a significant effect on serum cortisol and melatonin levels (sleep hormones). In addition, supplementation significantly decreased the severity of insomnia among patients with diabetes by improving sleep duration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khalid, Bashir, Mehboob, Anwar, Ali, Hashim, Waseem and Basharat.)

Background: Melatonin, a hormone found in various bodily fluids and cells, is known for its potent antioxidative, anti-apoptotic, and endocrine regulatory properties. This study aimed to analyze melatonin levels in patients with diminished ovarian reserve (DOR) and its impact on embryo quality., Methods: We enrolled 85 women who were undergoing in vitro fertilization or intracytoplasmic sperm injection procedures, including normal ovarian reserve (NOR, n = 27), pathological DOR (DOR-Path, n = 25), and physiological DOR (DOR-Phy, n = 33). Melatonin levels in patient serum and follicular fluid were assessed using ELISA, and correlations between melatonin levels and indicators of embryo quality were examined., Results: Our findings indicate that melatonin levels in the follicular fluid and basal serum of the DOR-Path and DOR-Phy groups were lower compared to the NOR group (P < 0.05). However, no significant differences in melatonin levels were found between the DOR-Path and DOR-Phy groups (P > 0.05). Additionally, the concentration of melatonin in the follicular fluid of the NOR group was significantly higher than in their serum (P < 0.001). Lastly, a significant correlation was discovered between melatonin levels in serum and follicular fluid and parameters of ovarian reserve and embryonic development (P < 0.05)., Conclusions: Melatonin levels in DOR patients may impact embryo quality, offering insights into potential DOR pathogenesis and opportunities to enhance treatment outcomes in these patients., (© 2024. The Author(s).)

Migraine, a complex disorder, is characterized by recurrent headache episodes. The production of melatonin in the pineal gland, which is crucial for controlling circadian rhythms and sleep-wake cycles, is altered in various conditions, including neurological disorders such as migraine. Recent studies underscore the significance of serum melatonin levels in patients with chronic and episodic migraine, the focus of this study. This case‒control study, conducted from September 2017 to June 2020 in Tehran, Iran, selected potential participants aged 18-65 years from a headache clinic at Sina Hospital (affiliated with Tehran University of Medical Sciences). Both episodic migraine and chronic migraine were diagnosed following the diagnostic criteria in the International Classification of Headache Disorders' third edition. Melatonin levels were measured according to the instructions of the ELISA kits. There were significant differences in the frequency of headache days and the duration of abortive medication usage between the two groups (P value < 0.001). Besides, analysis revealed significantly lower serum melatonin levels in patients with episodic ((80.45-45.06) 72.83) and chronic migraine ((154.34-63.34) 70.38, P value < 0.001) than in healthy controls (281.25-160.86) 280). Although no considerable differences were found between episodic and chronic migraine patients, the current study demonstrated that serum melatonin levels were substantially greater in healthy controls than in patients with migraine., (© 2024. The Author(s).)

This study aimed to determine the relationship between melatonin hormone levels, sleep, and factors affecting sleep, psychological resilience, and depression in nurses working with a shift work system. Conducted between February 5-12, 2021, at the Training and Research Hospital in Ağrı province, the descriptive study included 41 night shift nurses and 35 day shift nurses, totaling 76 participants. Blood samples for melatonin analysis were collected and data were gathered using the Sociodemographic Information Form, Epworth Sleepiness Scale, Sleep Disorder Scale Short Form, Brief Psychological Resilience Scale, and Beck Depression Scale Short Form. Melatonin analysis was performed using the ELISA method. Statistical significance was set at p < 0.05. Results showed that sleep disorders were present in all nurses with <7 h of daily sleep. Factors such as the use of sleeping pills, marital status, age, and gender affected sleep disorders. Mean scores for melatonin levels were 67.82 ± 40.20 for night shift nurses and 68.08 ± 39.62 for day shift nurses, with no significant difference between shifts. Similarly, no significant differences were found in daytime sleepiness (7.49 ± 4.47 vs. 7.51 ± 4.65), sleep disturbance (24.71 ± 7.33 vs. 25.23 ± 6.64), psychological resilience (18.42 ± 4.19 vs. 17.89 ± 4.74), or depression (3.22 ± 2.60 vs. 3.49 ± 3.35). Nurses exhibited mild sleep disturbances, low depression tendencies, and moderate psychological resilience. Increased daytime sleepiness and sleep disorders correlated with higher depression tendencies and lower psychological resilience. Hospital management and education units are recommended to conduct interventions on sleep quality, depression, and psychological resilience to raise awareness among nurses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Melatonin is an antioxidant and anti-inflammatory agent that modulates the immune system by scavenging free radicals, reducing the upregulation of pro-inflammatory cytokines, and reducing transendothelial cell migration. Therefore, melatonin may play a role in regulating multiple sclerosis (MS) disease activity. However, little is known about how melatonin supplementation effects individuals with MS., Objective: Determine if there was a dose-dependent elevation in urine and serum melatonin concentrations. Determine if melatonin supplementation had an impact on patient reported outcomes., Methods: This was a randomized, dose-blinded exploratory study. Adults (age 18-65) with relapsing forms of multiple sclerosis (RMS) treated with a stable dose of oral disease modifying therapy for at least 6 months were randomized into melatonin 3 mg or 5 mg daily. Urinary and serum melatonin levels and modified fatigue impact scale (MFIS), multiple sclerosis impact scale (MSIS-29), and Pittsburgh sleep quality index (PSQI), patient determined disease steps (PDDS) and performance scales (PS) were measured at baseline, 3, 6, and 12 months. Urinary and serum melatonin analyses was performed to estimate mean concentrations and their differences between treatment arms over time by a repeated measures linear mixed model. The model included treatment, assessment time, and treatment × time interaction., Results: Thirty patients, randomized 1:1, were analyzed in an intent to treat population. Twenty-three completed the study. The repeated measures linear mixed model analysis of all timepoints revealed higher melatonin concentrations in patients on 5 mg compared to 3 mg melatonin for both urinary 6-SMT (p = 0.03) and serum melatonin (p = 0.04). MFIS, MSIS-29, PSQI, and PDSS-PS scores did not significantly change from baseline to month 12. No significant differences in these measures were seen between the two doses. Five patients stopped melatonin (three on 5 mg and two on 3 mg) due to adverse events, including one patient who developed focal spongiotic dermatitis. One patient experienced three consecutive serious adverse events that were unrelated to melatonin supplementation., Conclusions: The 5 mg melatonin supplementation group had higher concentrations of urinary 6-SMT and serum melatonin compared to the 3 mg group over 12 months of treatment. There was a correlation between 6-SMT and serum melatonin concentrations. This suggests that measuring serum melatonin is a reliable alternative to measuring urinary 6-SMT. However, no differences in clinical benefit between the two dosage groups were demonstrated in the patient reported outcomes., Trial Registration Number: NCT03498131., Competing Interests: Declaration of competing interest KS - Consulting and speaking honoraria from Biogen, Bristol Myers Squibb, EMD Serono, Janssen, Roche, Sanofi Genzyme, and TG Therapeutics. Research support from Sanofi Genzyme and Roche Genentech. SC - Research Support from AbbVie, Biogen, Bristol Myers Squibb, EMDSerono, Novartis, Roche Genentech, and Sanofi Genzyme. Consulting and speaking honoraria from Biogen, Bristol Myers Squibb, & EMDSerono. TGF, HM, and CC- no conflicts of interest to report., (Copyright © 2024. Published by Elsevier B.V.)

Background: Prematurity-related brain injury is a common and serious complication that has long-term effects on the survival and development of affected infants. Currently, the roles of certain biomarkers such as the protein hydrolysis product SBDP145, melatonin, soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), high mobility group box 1 protein (HMGB1), and hypoxia-inducible factor 1-alpha (HIF-1α) in prematurity-related brain injury remain not fully elucidated. Our study aims to assess the significance of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in preterm infants with brain injury., Methods: 135 preterm infants admitted to our hospital from January 2020 to February 2022 were selected and divided into 78 cases in a prematurity-associated brain injury group, and 57 cases in another group of preterm infants without brain injury or other diseases according to the magnetic resonance imaging results. The levels of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in the two groups were analyzed. The serum concentrations of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in newborns with different severity of ventricular hemorrhage were observed, and the levels of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in those with different severity of white matter brain injury were compared., Results: The levels of SBDP145, sLOX-1, HMGB1 and HIF-1α were significantly higher in the preterm combined brain injury group than in the preterm group, and melatonin levels were significantly lower than in the preterm group(P < 0.05). The levels of SBDP145, sLOX-1, HMGB1 and HIF-1α were higher in the moderate to severe group and melatonin levels were lower in the mild group of newborns with ventricular hemorrhage (P < 0.05). The levels of SBDP145, sLOX-1, HMGB1 and HIF-1α were higher in the moderate-severe group and melatonin levels were lower in the mild group in newborns with cerebral white matter injury (P < 0.05). The independent variables were SBDP145, melatonin, sLOX-1, HMGB1, HIF-1α, and the dependent variable was the prognosis of neonates with brain injury. Univariate logistic regression analysis and multivariate logistic regression analysis were performed. The results showed that the influencing factors of newborns with brain injury were SBDP145, melatonin, sLOX-1, HMGB1, HIF-1α., Conclusion: The levels of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α were highly expressed in preterm newborns with brain injury, and the levels were higher when the condition of the newborns was more severe. These findings suggest the potential clinical utility of these biomarkers in predicting and monitoring brain injury in preterm infants, which could aid in early intervention and improve long-term outcomes., (© 2024. The Author(s).)

Background: Biological synchronized rhythmicity is a critical physiological process. The lack of synchronized rhythms, mainly those showing a circadian basis, like sleep, the heart rate (HR) and arterial blood pressure (BP), often leads to several organic challenges, usually associated with adverse outcomes., Objectives: The aim of the study was to investigate whether the intensive care unit (ICU) environment favors clock genes and cardiorespiratory changes., Material and Methods: A total of 22 critically ill patients (16 males; 72.73%) with a mean age of 60.82 ±20.07 years and well-established cardiovascular conditions were selected from ICU. Blood samples were obtained, and total RNA was isolated and reverse-transcribed into complementary DNA (cDNA). A quantitative polymerase chain reaction (qPCR) was performed to assess the target gene expression levels. The urinary concentration levels of melatonin (MEL) were assessed. The heart rate, BP (systolic - SBP, diastolic - DBP and mean - MBP) and the oxygen saturation (SpO2) levels were assessed as continuous variables., Results: The urinary MEL and Brain and muscle Arnt-like protein-1 (BMAL1) levels were shown to have a non-linear relationship with HR (coefficient (coef): 2.318, p = 0.032; coef: 2.722, p = 0.006, respectively) and SBP (coef: 1.000, p = 0.008; coef: 2.000, p = 0.037, respectively), with an explanatory power of up to 50.3% and 39.7% of the HR and SBP variability, respectively. Melatonin, but not BMAL1, was also shown to have a non-linear relationship with MBP (coef: 1.000, p = 0.007), with an explanatory power of up to 31.3% regarding the MBP variability. The HR and SBP oscillatory dynamics was shown to be related to changes in the genetic expression of BMAL1 and the urinary MEL concentrations. To a lower degree, MEL also impacted the variation of MBP., Conclusions: Our results suggest that not only are circadian functional matrices crucial for the dynamics of vital parameters in critically ill patients, but also that routinely assessed cardiovascular parameters like HR and BP may constitute important markers for the circadian timing system function. These parameters are easy to assess and have a relevant prognostic value regarding recovery outcomes, as well as the morbidity and mortality rates in ICU.

Background: Two main types of galenic formulation, immediate release and prolonged release, have been developed to optimize melatonin bioavailability. We recently described the kinetic profile of a prolonged-release form generating a peak of plasma melatonin 1 h (T max ) after intake, followed by a prolonged decay over time. We have developed a new oral form of melatonin with the aim of producing a melatonin peak several hours after intake., Objective: The objective is to investigate melatonin bioavailability after administration of this new delayed-release form (DR form)., Methods: In this single-centre open-label study, 12 healthy male volunteers received one tablet of the DR form containing 1.9 mg melatonin, 10 mg zinc and 200 mg lemon balm extract (Melissa officinalis L aerial parts). Blood samples were collected for 12 h, beginning at 8:00 am. Plasma concentrations of melatonin and 6-sulfatoxymelatonin (6-SMT), the main hepatic melatonin metabolite, were determined by radioimmunoassay., Results: A progressive increase in plasma melatonin concentrations was observed from 20 min and a peak about 3 h after intake (C max 740 ± 824 pg/mL; T max 179 ± 60 min). Concentrations remained high between 140 and 220 min, the concentration remaining physiologically significant (over 100 pg/mL) up to 7 h after intake. The DR form was well tolerated., Conclusions: The melatonin release profile was consistent with what was anticipated for the DR form. The DR form generated a 2 h delayed T max compared with a prolonged-release form previously evaluated. This suggests that the DR form is suitable for the treatment of certain sleep disorders such as short sleep duration or early awakening., Trial Registry: Registration number: NCT05419466., (© 2024. The Author(s).)

Objective: To investigate the early prediction value of transcranial Doppler ultrasound (TCD) combined with serum melatonin level for delayed cerebral ischemia (DCI) caused by subarachnoid hemorrhage (SAH)., Methods: This paper is a prospective study. A total of 120 patients with SAH treated were included. The patients were divided into the DCI group (40 cases) and non-DCI group (80 cases) according to whether DCI occurred 14 days after SAH (DCI usually occurs 4 to 14 d after bleeding). Baseline data, serum melatonin level, and TCD test results within 24 hours after admission were compared between the 2 groups. Multivariate logistic analysis was used to analyze the factors affecting the occurrence of DCI after SAH. The value of serum melatonin level, middle cerebral artery mean blood flow velocity (MBFV) and their combination in predicting DCI in SAH patients was evaluated., Results: Univariate analysis showed that there were statistically significant differences in the proportion of Fisher grade, Hunt-Hess grade, serum melatonin level, middle cerebral artery systolic blood flow velocity (Vs), MBFV and pulse index (PI) between the 2 groups ( P <0.05). Serum melatonin levels, middle cerebral artery Vs, MBFV, and PI in the DCI group were higher than those in non-DCI group. Logistic regression (LR) analysis showed that serum melatonin level (OR=1.796, 95% CI: 1.575-4.123) and middle cerebral artery MBFV (OR=3.279, 95% CI: 2.112-4.720] were the influencing factors for DCI in SAH patients ( P <0.05)., Conclusion: Middle cerebral artery MBFV and serum melatonin levels were higher in patients with SAH complicated with DCI, and the combination of the 2 could provide a reference for early clinical prediction of DCI in patients with aneurysmal subarachnoid hemorrhage (aSAH)., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Goat bucks are seasonal breeders that show variation in sperm quality, endogenous melatonin (MLT), and presumably in the expression of MLT receptors on the sperm throughout the year, which may modify sperm freezability. The aim of this study was to determine whether sperm freezability is associated with (i) endogenous melatonin levels in seminal plasma and (ii) the expression of sperm plasma membrane melatonin receptors (MT1, MT2). To evaluate this, spermatozoa from seven Saanen goat bucks were cryopreserved throughout the year in Mexico using a standard freezing protocol. Seminal plasma MLT concentrations were determined by ELISA and the expression and localization of MT1 and MT2 were detected by immunocytochemistry and confirmed by western blotting. The recovery rate of progressive motility after thawing was higher in spring than autumn and winter; in contrast, the F pattern (CTC assay) was higher in winter than in the other seasons. A proportional increase in the AR pattern (CTC assay) was smaller in winter than in the other seasons and the proportion of sperm showing high plasma membrane fluidity was higher in spring than in summer and autumn. The seminal plasma MLT concentrations showed no significant interseasonal differences. The MT1 receptor was immunolocalised at the apical region of the sperm head, while MT2 was mainly localised in the neck. The relative expression of MLT receptors showed significant differences between summer and winter for all bands, except at 75 kDa of MT2. In conclusion, there was an association between the relative expression of MT1 and MT2 receptors throughout the year and sperm freezability in goat bucks in México. Post-thaw sperm quality is enhanced in semen samples collected during breeding season., Competing Interests: Declaration of competing interest none., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Intestinal barrier dysfunction and systemic inflammation are common in obstructive sleep apnoea (OSA). We aimed to investigate the role of melatonin, an anti-inflammatory mediator, in mediating the relationships between OSA, intestinal barrier dysfunction and systemic inflammation., Methods: Two hundred and thirty-five male participants who complained with sleep problems and underwent whole night polysomnography at our sleep centre between 2017 and 2018 were enrolled. Polysomnographic data, anthropometric measurements and biochemical indicators were collected. Serum melatonin, intestinal barrier function biomarker zonula occludens-1 (ZO-1) and inflammatory biomarkers C-reactive protein (CRP) with lipopolysaccharide (LPS) were detected. Spearman's correlation analysis assessed the correlations between sleep parameters, melatonin and biomarkers (ZO-1, LPS and CRP). Mediation analysis explored the effect of OSA on intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients., Results: As OSA severity increased, serum melatonin decreased, whereas ZO-1, LPS and CRP increased. Spearman's correlation analysis showed that serum melatonin was significantly negatively correlated with ZO-1 ( r  = -0.19, p  < .05) and LPS ( r  = -0.20, p  < .05) in the moderate-OSA group; serum melatonin was significantly negatively correlated with ZO-1 ( r  = -0.46, p  < .01), LPS ( r  = -0.35, p  < .01) and CPR ( r  = -0.30, p  < .05) in the severe-OSA group. Mediation analyses showed melatonin explain 36.12% and 35.38% of the effect of apnoea-hypopnea index (AHI) on ZO-1 and LPS in moderate to severe OSA patients., Conclusions: Our study revealed that melatonin may be involved in mediating intestinal barrier dysfunction and systemic inflammation in moderate-to-severe OSA patients.

Melatonin (MTN) is a neuro-hormone released from the pineal gland. MTN secretion is regulated by different neuronal circuits, including the retinohypothalamic tract and suprachiasmatic nucleus (SCN), which are affected by light. MTN is neuroprotective in various neurodegenerative diseases, including Parkinson's disease (PD). MTN circulating level is highly blunted in PD. However, the underlying causes were not fully clarified. Thus, the present review aims to discuss the potential causes of blunted MTN levels in PD. Distortion of MTN circadian rhythmicity in PD patients causies extreme daytime sleepiness. The underlying mechanism for blunted MTN response may be due to reduction for light exposure, impairment of retinal light transmission, degeneration of circadian pacemaker and dysautonomia. In conclusion, degeneration of SCN and associated neurodegeneration together with neuroinflammation and activation of NF-κB and NLRP3 inflammasome, induce dysregulation of MTN secretion. Therefore, low serum MTN level reflects PD severity and could be potential biomarkers. Preclinical and clinical studies are suggested to clarify the underlying causes of low MTN in PD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To explore the effects of Du Meridian moxibustion combined with ear acupuncture on clinical symptoms and serum neurotransmitters in patients with coronary heart disease and insomnia. This study is a retrospective study. From June 2021 to May 2023, 116 patients with coronary heart disease and insomnia treated at our hospital were selected as subjects. They were divided into 2 groups according to the treatment. The control group received treatment with alprazolam, while the experimental group received Du Meridian moxibustion combined with ear acupuncture in addition to alprazolam treatment. The efficacy of the 2 groups was compared, and the levels of cardiac function indicators, serum melatonin, leptin, and neurotransmitters were measured. The total effectiveness rate in the experimental group was 93.10% (with a cure rate of 36.21%, a significant improvement rate of 41.38%, and an effective rate of 15.52%), which was significantly higher than the 79.31% in the control group (with a cure rate of 24.14%, a significant improvement rate of 32.76%, and an effective rate of 22.41%) (P < .05). Both groups exhibited an increase in left ventricular ejection fraction, stroke volume, and cardiac output after treatment compared to before treatment. Additionally, left ventricular end-systolic diameter decreased after treatment compared to before treatment, but the cardiac function was compared between the 2 groups after treatment (P > .05). In both groups, serum melatonin and serotonin (5-HT) levels increased after treatment compared to before treatment, while serum leptin, dopamine, and glutamate levels decreased after treatment compared to before treatment. Furthermore, the experimental group had higher serum melatonin, 5-HT, and gamma-aminobutyric acid levels compared to the control group, and lower serum leptin, dopamine, and glutamate levels compared to the control group (P < .05). The serum traditional Chinese medicine syndrome score and Pittsburgh sleep quality index score of the 2 groups decreased after treatment, and the experimental group was lower than the conventional group (P < .05). The combination of Du Meridian acupuncture with ear acupuncture in the treatment of insomnia in coronary heart disease can regulate the expression of serum melatonin, leptin, and neurotransmitters, alleviate symptoms, and improve therapeutic efficacy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Type 2 diabetes mellitus is a metabolic disorder that causes chronic high blood sugar levels, and diabetic patients are more susceptible to infections. American cutaneous leishmaniasis is an infectious disease caused by a parasite that affects the skin and mucous membranes, leading to one or multiple ulcerative lesions. Chronic inflammation and functional changes in various organs and systems, including the immune system, are the primary causes of both diseases. Melatonin, an essential immunomodulatory, antioxidant, and neuroprotective agent, can benefit many immunological processes and infectious diseases, including leishmaniasis. Although, limited reports are available on diabetic patients with leishmaniasis. The literature suggests that melatonin may play a promising role in inflammatory disorders. This study was designed to assess melatonin levels and inflammatory mediators in diabetic patients affected by leishmaniasis. Blood samples from 25 individuals were analyzed and divided into four groups: a control group (without any diseases), a Leishmania-positive group, patients with type 2 diabetes mellitus, and patients with a combination of both diseases. This study measured the serum levels of melatonin through ELISA, while IL-4 and TNF-α were measured using flow cytometry, and C-reactive protein was measured through turbidimetry. This study found that patients with leishmaniasis significantly increased TNF-α and decreased melatonin levels. However, the group of diabetic patients with leishmaniasis showed higher melatonin levels than the control group. These observations suggest that TNF-α may influence melatonin production in patients with American cutaneous leishmaniasis, potentially contributing to the inflammatory characteristics of both diseases.

Background: There are increased indications that physical activity timing, irrespective of intensity, impacts insomnia and circadian clock function. Here, we describe the rationale and design of a randomized cross-over study, called ON TIME, to examine the effects of (changing) physical activity timing on insomnia severity and on multiple exploratory outcomes that are linked to circadian clock function., Methods: We will conduct a randomized cross-over trial in 40 healthy older adults (aged 65 to 75 years) with subclinical or clinical insomnia (Insomnia Severity Index (ISI) scores of ≥ 10) from the Dutch municipality of Leiden and surroundings. Participants will undergo 3 intervention periods (14 days each) consecutively: one sedentary period and two periods of increased physical activity (one period with morning activity and one period with evening activity). The intervention periods are separated by a wash-out period of 1 week. In both active intervention arms, participants will follow coached or uncoached outdoor physical exercise sessions comprising endurance, strength, and flexibility exercises for 14 days. The primary outcome is change in insomnia severity as measured by the ISI. Additional exploratory outcomes include multiple components of objective sleep quality measured with tri-axial accelerometry and subjective sleep quality assessed by questionnaires as well as dim light melatonin onset and 24-h rhythms in heart rate, heart rate variability, breathing rate, oxygen saturation, mood, and objective emotional arousal and stress. Additionally, we will collect diary data on eating patterns (timing and composition). Finally, fasting blood samples will be collected at baseline and after each intervention period for measurements of biomarkers of metabolic and physiological functioning and expression of genes involved in regulation of the biological clock., Discussion: We anticipate that this study will make a significant contribution to the limited knowledge on the effect of physical activity timing. Optimizing physical activity timing has the potential to augment the health benefits of increased physical exercise in the aging population., Trial Registration: Trial was approved by the Medical Ethics Committee Leiden, The Hague, Delft, The Netherlands (June, 2023). The trial was registered in the CCMO-register https://www.toetsingonline.nl/to/ccmo&#95;search.nsf/Searchform?OpenForm under study ID NL82335.058.22 and named ("Ouderen op tijd in beweging" or in English "Older adults exercising on time"). At time of manuscript submission, the trial was additionally registered at ClinicalTrials.gov under study ID: NL82335.058.22 and is awaiting approval., (© 2024. The Author(s).)

We analyzed plasma melatonin levels in different groups of preterm newborns without hypoxia and their relationship with several perinatal variables like gestational age or neonatal pain. Prospective cohort study of preterm newborns (PTNB) without perinatal hypoxia, Apgar > 6 at 5 min, and oxygen needs on the third day of life. We compared melatonin levels at day 3 of life in different groups of non-hypoxic preterm infants (Student's t-tests, Mann-Whitney U, and chi 2 ) and analyzed the relationship of melatonin with GA, birth weight, neonatal pain (Premature Infant Pain Profile (PIPP) scale), caffeine treatment, parenteral nutrition, or the development of free radical diseases (correlation study, linear regression) and factors associated with moderate/intense pain and free radical diseases (logistic regression analysis). Sixty-one preterm infants with gestational age (GA) of 30.7 ± 2.0 weeks with no oxygen requirements at day 3 of life were studied with plasma melatonin levels of 33.8 ± 12.01 pg/ml. Preterm infants weighing < 1250 g at birth had lower plasma melatonin levels (p = 0.05). Preterm infants with moderate or severe pain (PPIPP > 5) have lower melatonin levels (p = 0.01), and being preterm with PIPP > 5 is associated with lower plasma melatonin levels (p = 0.03). Being very preterm (GA < 32 GS), having low weight for gestational age (LWGA), receiving caffeine treatment, or requiring parenteral nutrition did not modify melatonin levels in non-hypoxic preterm infants (p = NS). Melatonin on day 3 of life in non-hypoxic preterm infants is not associated with later development of free radical diseases (BPD, sepsis, ROP, HIV, NEC)., Conclusion: We observed that preterm infants with moderate to severe pain have lower melatonin levels. These findings are relevant because they reinforce the findings of other authors that melatonin supplementation decreases pain and oxidative stress in painful procedures in premature infants. Further studies are needed to evaluate whether melatonin could be used as an analgesic in painful procedures in preterm infants., Trial Registration: Trial registration was not required since this was an observational study., What Is Known: • Melatonin is a potent antioxidant and free radical scavenger in newborns under stress conditions: hypoxia, acidosis, hypotension, painful procedures, or parenteral nutrition. • Pain stimulates the production of melatonin. • Various studies conclude that melatonin administration decreases pain during the neonatal period., What Is New: • Non-hypoxic preterm infants with moderate to severe pain (PIPP>5) have lower levels of melatonin. • Administration of caffeine and treatment with parenteral nutrition do not modify melatonin levels in non-hypoxic preterm infants., (© 2024. The Author(s).)

Introduction: The reproductive system is tightly regulated by environmental and physiological signals. Melatonin, known as the hormone of darkness, plays a crucial role in regulating both the circadian and reproductive systems in mammals. Hypothyroidism is a key endocrine disorder that harms the reproductive system. Despite many studies on melatonin's effects on the reproductive system, there is conflicting information regarding melatonin synthesis modulation in hypothyroidism. The objective of this study was to investigate the modulation of plasma melatonin levels and gene expression of Aanat and Asmt in the pineal gland and gonads of rats with hypothyroidism at different times of the day., Methods: Female and male Wistar rats were divided into control and hypothyroid groups. Hypothyroidism was induced using propylthiouracil (PTU) for 15 days, rats were euthanized six hours after lights on (ZT6), before lights off (ZT11.5), and six hours after lights off (ZT18). Free thyroxine (FT4) and melatonin were quantified in plasma, and gene expressions of melatonin synthesizing enzymes ( Aanat and Asmt ) were measured in pineal and sexual organs (testis and ovary). Also, morphological analysis was performed in sexual organs., Results: The results reveal some disparities between the sexes. Hypothyroidism reduced antral and primary follicles in the ovary, and reduced the weight of testis, epididymis, and prostate. In relation to gene expression, we observed a reduction in Aanat expression in the pineal gland during the light phase (ZT6), and in males, this reduction occurred during the dark phase (ZT18). Regarding Asmt expression, there was a decrease in females also during the dark phase (ZT18). In the gonads, there was an increase in expression in both sexes at ZT11.5. Additionally, it was interesting to observe the association between FT4 levels and Asmt expression in the gonads., Conclusions: This study showed that acute hypothyroidism can affect components of the melatonergic system in gonads, particularly gene expression of melatonin synthesis enzymes ( Aanat and Asmt ) contributing to changes in reproduction organs during disease progression. These findings enhance our understanding of melatonin synthesis in the reproductive system during hypothyroidism, showing distinct responses in male and female rats, and suggest that hypothyroidism affects the circadian rhythmicity of melatonin synthesis in a sex-dependent manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Paiva, Mondes, Brandão, Sant’Anna, Freire dos Santos, Fighera, Santos, Markus, Fernandes, Silva and Tamura.)

Objective: Melatonin plays a role in many biological and physiological events. There are studies in the literature relating melatonin levels to many psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder. We aimed to investigate the relationship between serum melatonin levels with the Beck Depression Inventory and the Beck Scale for Suicidal Ideation in suicide patients., Methods: The study was conducted prospectively with volunteer patients aged 20-50 years who were admitted to the emergency department after a suicide attempt. The social and occupational status, educational levels, marital status, and stressor factors of patients were questioned. Beck Depression Inventory and Beck Scale for Suicidal Ideation were applied to each patient included in the study. Blood melatonin levels were evaluated using the enzyme-linked immunosorbent assay method. The data were analyzed with the SPSS 23.00 statistical program. Descriptive values were expressed by the number of cases (n), percentage (%), median (interquartile range), and mean±standard deviation. The Kolmogorov-Smirnov test was used to assess the distribution of continuous variables, and the Pearson or Spearman correlation test was used to assess the relationship between disease severity and melatonin level. A value of p<0.05 was considered statistically significant., Results: No statistically significant correlation was found between melatonin level and the Beck Depression Inventory score (r=-0.098, p=0.44). However, a statistically weak, inverse, and significant correlation was discovered between melatonin levels and the Beck Scale for Suicidal Ideation score (r=-0.465, p=0.00)., Conclusion: According to our results, it was determined that there was a significant negative relationship between melatonin level and the Beck Scale for Suicidal Ideation scoring.

Acute pancreatitis (AP), a severe inflammatory condition affecting the pancreas requires investigation into its predictors. Melatonin, a compound with anti-inflammatory and antioxidant properties, has shown promise in managing AP. Additionally, the gut microbiota, a community of microorganisms residing in the intestines has been linked to AP development. This study aims to explore the correlation between melatonin and gut microbiota in predicting AP severity. This study involved 199 participants, with 99 diagnosed with AP and 100 serving as healthy controls. The AP patients were categorized into 2 groups based on the severity of their condition: mild AP (MAP) and severe AP (SAP). Serum melatonin levels were measured on Days 1, 3, and 5 of hospitalization, and gut microbiota composition was examined via 16S rRNA gene sequencing. Other parameters were evaluated, such as the Acute Physiology and Chronic Health Evaluation (APACHE) score, Ranson, and Acute Gastrointestinal Injury (AGI) scores. Melatonin levels were significantly lower in subjects with severe AP compared those with mild AP (18.2 ng/mL vs 32.2 ng/mL, P = .001), and melatonin levels decreased significantly in patients with AP on Days 3 and 5. The study also revealed that individuals with AP exhibited a significantly altered gut microbiota composition compared to control individuals, with a lower Shannon index and higher Simpson index. The AUCs for Simpson index and F/B ratio were significantly higher than those for other biomarkers, indicating that these gut microbiota markers may also be useful for AP prediction. The study proposes that there is a relationship between melatonin levels and the dynamics of gut microbiota profiles in relation to the severity of AP. As a result, the severity of the disease can be assessed by assessing the levels of serum melatonin and gut microbiota profiles., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients. Methods: One hundred twenty-six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C-reactive protein (CRP), Interleukin 6 (IL-6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and the Epidemiological Research Center Depression Scale (CES-D), respectively. Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF-A and CES-D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF-A and CES-D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients. Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM-associated executive impairment and depression status., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Shuai He et al.)

Chronic disruption of circadian rhythms by night shift work is associated with an increased breast cancer risk. However, little is known about the impact of night shift on peripheral circadian genes (CGs) and circadian-controlled genes (CCGs) associated with breast cancer. Hence, we assessed central clock markers (melatonin and cortisol) in plasma, and peripheral CGs (PER1, PER2, PER3, and BMAL1) and CCGs (ESR1 and ESR2) in peripheral blood mononuclear cells (PBMCs). In day shift nurses (n = 12), 24-h rhythms of cortisol and melatonin were aligned with day shift-oriented light/dark schedules. The mRNA expression of PER2, PER3, BMAL1, and ESR2 showed 24-h rhythms with peak values in the morning. In contrast, night shift nurses (n = 10) lost 24-h rhythmicity of cortisol with a suppressed morning surge but retained normal rhythmic patterns of melatonin, leading to misalignment between cortisol and melatonin. Moreover, night shift nurses showed disruption of rhythmic expressions of PER2, PER3, BMAL1, and ESR2 genes, resulting in an impaired inverse correlation between PER2 and BMAL1 compared to day shift nurses. The observed trends of disrupted circadian markers were recapitulated in additional day (n = 20) and night (n = 19) shift nurses by measurement at early night and midnight time points. Taken together, this study demonstrated the misalignment of cortisol and melatonin, associated disruption of PER2 and ESR2 circadian expressions, and internal misalignment in peripheral circadian network in night shift nurses. Morning plasma cortisol and PER2, BMAL1, and ESR2 expressions in PBMCs may therefore be useful biomarkers of circadian disruption in shift workers., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common respiratory disease with potential lethality. At present, the commonly used treatment method is continuous positive airway pressure ventilation, but with the prolongation of the course of the disease, the effect of single ventilation on the improvement of oxidative stress levels is not good. Lipoic acid is a commonly used antioxidant in clinics. In this paper, lipoic acid combined with continuous positive airway pressure ventilation is used to explore whether it has a better therapeutic effect on patients., Aim: To probe into the clinical efficacy of lipoic acid combined with continuous positive airway pressure ventilation in the therapy of OSAHS., Methods: 82 patients with OSAHS who were cured in our hospital from March 2021 to September 2022 were prospectively collected as subjects. Based on different treatment methods, patients were grouped into a control group (43 cases) and an observation group (39 cases). The control group was treated with continuous positive airway pressure (CPAP), and the observation group was treated with lipoic acid based on control group. The therapeutic effects were measured by apnea hypopnea index (AHI), oxygen saturation (SpO2), mean oxygen saturation (MSpO2), serum malondialdehyde (MDA), superoxide dismutase (SOD), hypoxia inducible factor-1α (HIF-1α) levels, peripheral blood γ-aminobutyric acid, melatonin levels., Results: The clinical effectiveness of the observation group was better (P < 0.05). After treatment, AHI, the levels of MDA and HIF-1α in the observation group were lower and SpO 2 , MSpO 2 and the level of SOD, γ- aminobutyric acid, and melatonin were higher than those in the control group (P < 0.05). The levels of γ- aminobutyric acid and melatonin were negatively correlated with the severity of symptoms, ESS, and AIS scores (P < 0.05)., Conclusions: The clinical effect of lipoic acid combined with CPAP in the treatment of OSAHS is better, and it has a positive effect on the levels of γ-aminobutyric acid and melatonin in peripheral blood. Lipoic acid was added to the original method for treatment, and the therapeutic effect was greatly improved., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Western sand lance, Ammodytes japonicus , is known to have an estivation period, in which they cease feeding and stay in the sand from early summer to late autumn, followed by gonadal maturation. During the feeding period prior to estivation, they swim in daytime and spend the night in the sand. Before they start swimming, they show a typical behavior of head-exposing from the sand, which is likely to be related to foraging and predation avoidance. Our previous study revealed that melatonin regulates such diel behavior of this species. To elucidate the mechanisms of behavioral regulation throughout the life cycle of this sand lance, the present study examined the changes in behavior and melatonin secretion toward the estivation period. Both head-exposing and swimming behaviors were frequently observed at the transition period toward estivation. On the other hand, occurrence of these behaviors was suppressed just before entering estivation. Subsequently, it was found that plasma melatonin concentration was about three times higher at night than in daytime in the non-estivation period, while it was retained at high levels throughout the day in the estivation period. These results indicate that diurnal swimming behavior of sand lance from the feeding to estivation periods is associated with the daily cycle of melatonin secretion.

Aims/hypothesis: The aim of this study was to explore whether diabetic retinopathy is associated with alterations of the circadian system, and to examine the role of reduced intrinsically photosensitive retinal ganglion cell (ipRGC) function., Methods: Participants with type 2 diabetes, with diabetic retinopathy (n=14) and without diabetic retinopathy (n=9) underwent 24 h blood sampling for melatonin and cortisol under controlled laboratory conditions. ipRGC function was inferred from the post-illumination pupil response (PIPR). Habitual sleep duration, efficiency and variability were assessed by actigraphy., Results: Participants with diabetic retinopathy compared to participants without diabetic retinopathy had smaller PIPR (p=0.007), lower 24 h serum melatonin output (p=0.042) and greater day-to-day sleep variability (p=0.012). By contrast, 24 h cortisol profiles, sleep duration and efficiency were similar in both groups. Six individuals with diabetic retinopathy had no detectable dim-light melatonin onset. PIPR correlated with 24 h mean melatonin levels (r=0.555, p=0.007)., Conclusions/interpretation: ipRCG dysfunction in diabetic retinopathy is associated with disruptions of the 24 h melatonin rhythm, suggesting circadian dysregulation in diabetic retinopathy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This article discusses data showing that mammals, including humans, have two sources of melatonin that exhibit different functions. The best-known source of melatonin, herein referred to as Source #1, is the pineal gland. In this organ, melatonin production is circadian with maximal synthesis and release into the blood and cerebrospinal fluid occurring during the night. Of the total amount of melatonin produced in mammals, we speculate that less than 5% is synthesized by the pineal gland. The melatonin rhythm has the primary function of influencing the circadian clock at the level of the suprachiasmatic nucleus (the CSF melatonin) and the clockwork in all peripheral organs (the blood melatonin) via receptor-mediated actions. A second source of melatonin (Source # 2) is from multiple tissues throughout the body, probably being synthesized in the mitochondria of these cells. This constitutes the bulk of the melatonin produced in mammals and is concerned with metabolic regulation. This review emphasizes the action of melatonin from peripheral sources in determining re-dox homeostasis, but it has other critical metabolic effects as well. Extrapineal melatonin synthesis does not exhibit a circadian rhythm and it is not released into the blood but acts locally in its cell of origin and possibly in a paracrine matter on adjacent cells. The factors that control/influence melatonin synthesis at extrapineal sites are unknown. We propose that the concentration of melatonin in these cells is determined by the subcellular redox state and that melatonin synthesis may be inducible under stressful conditions as in plant cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Reiter, Sharma, Tan, Chuffa, da Silva, Slominski, Steinbrink and Kleszczynski.)

Background and Objectives : The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to progressive health complications. Melatonin can act on adipose tissue mass, promoting its reduction and influencing inflammation, reducing IL-6 and releasing IL-10, pro- and anti-inflammatory markers, respectively. However, the role of melatonin regarding such parameters under the context of hypoestrogenism remains unknown. The aim of this study was to determine the effect of 12 weeks of hypoestrogenism and melatonin on white adipose tissue mass and circulating levels of IL-6, IL-10, TGF-β-1, and leukotriene C4 (LTC4). Materials and Methods : The animals (Wistar rats with sixteen weeks of age at the beginning of the experiment) under hypoestrogenism were submitted to the surgical technique of bilateral ovariectomy. The animals received melatonin (10 mg·kg -1 ) or vehicles by orogastric gavage every day for 12 weeks and administration occurred systematically 1 h after the beginning of the dark period. White adipose tissue (perigonadal, peritoneal, and subcutaneous) was collected for mass recording, while blood was collected for the serum determination of IL-6, IL-10, TGF-β-1, and LTC4. Results : Hypoestrogenism increased the perigonadal and subcutaneous mass and IL-6 levels. Melatonin kept hypoestrogenic animals in physiological conditions similar to the control group and increased thymus tissue mass. Conclusions : Hypoestrogenism appears to have a negative impact on white adipose tissue mass and IL-6 and although melatonin commonly exerts a significant effect in preventing these changes, this study did not have a sufficiently negative impact caused by hypoestrogenism for melatonin to promote certain benefits.

Objective: Endogenous melatonin is produced from tryptophan which is an essential amino acid. Besides its role in the regulation of sleep patterns, melatonin has anti-inflammatory effects. In this case-control study, we aimed to compare tryptophan and melatonin levels and their relationship with the inflammatory response, specifically serum interleukin-1, interleukin-6, and c-reactive protein levels following major abdominal surgery in patients with food restriction and who receive parenteral nutritional therapy., Methods: We enrolled 40 patients between the ages of 18 and 65 years in the study. We collected blood and urine samples 48 h before the operation and on postoperative days 1, 3, and 5., Results and Conclusion: The tryptophan levels in the experimental group were higher than in the control group but failed to reach any statistical difference. Melatonin levels were increased in both groups following the surgery compared with preoperative levels. The increase in the experimental group was statistically different 3 days after the surgery. The difference in the level of interleukin-1 between the control and the experimental groups was greatest on postoperative day 3. On postoperative day 3, the interleukin-6 level in the treatment group was slightly higher than in the control group. We did not find any difference in the levels of c-reactive protein between the groups. As a result, the levels of tryptophan and melatonin were increased in the parenteral nutrition group, irrespective of the postoperative inflammatory response.

Melatonin (N-acetyl-5 methoxytryptamine) is an indolic neurohormone that modulates a variety of physiological functions due to its antioxidant, anti-inflammatory, and immunoregulatory properties. Therefore, the purpose of this study was to critically review the effects of melatonin supplementation in sports performance and circulating biomarkers related to the health status of highly trained athletes. Data were obtained by performing searches in the following three bibliography databases: Web of Science, PubMed, and Scopus. The terms used were "Highly Trained Athletes", "Melatonin", and "Sports Performance", "Health Biomarkers" using "Humans" as a filter. The search update was carried out in February 2024 from original articles published with a controlled trial design. The PRISMA rules, the modified McMaster critical review form for quantitative studies, the PEDro scale, and the Cochrane risk of bias were applied. According to the inclusion and exclusion criteria, 21 articles were selected out of 294 references. The dose of melatonin supplemented in the trials ranged between 5 mg to 100 mg administered before or after exercise. The outcomes showed improvements in antioxidant status and inflammatory response and reversed liver damage and muscle damage. Moderate effects on modulating glycemia, total cholesterol, triglycerides, and creatinine were reported. Promising data were found regarding the potential benefits of melatonin in hematological biomarkers, hormonal responses, and sports performance. Therefore, the true efficiency of melatonin to directly improve sports performance remains to be assessed. Nevertheless, an indirect effect of melatonin supplementation in sports performance could be evaluated through improvements in health biomarkers.

Background/aim: The aim of this study was to investigate the effect of phototherapy treatment on serum melatonin levels in term newborn infants., Material and Methods: This study was planned as a single-center, prospective, observational, case-control study. Term infants (gestation week ≥37 weeks) who received at least 6 h of phototherapy due to jaundice constitute the phototherapy group, while the term infants without jaundice and who were exclusively breastfed constitute the control group. Melatonin levels were examined by taking blood samples from babies in both groups at 02:00 at night. Melatonin values were compared between groups. The effect of phototherapy on serum melatonin levels was investigated. The relationship between the duration of phototherapy and maximum serum bilirubin values on melatonin values was investigated., Results: Seventy term infants (64.3% girls) were included in the study. Mean gestational week was 38.3 ± 1.1 weeks, mean birth weight was 3295 ± 434 g. There was no statistically significant difference between the phototherapy group and the control group in terms of sex, type of delivery, gestational week, birth weight, height, and head circumference (all p > 0.05). Serum melatonin level was 20.3 ± 5.9 pg/mL (range: 8.7-36.6 pg/mL) in the phototherapy group and 19.9 ± 4.38 pg/mL (range: 9.9-26.3 pg/mL) in the control group. There was no significant difference between the two groups in terms of serum melatonin levels (p = 0.155). The mean total bilirubin value was 17.65 ± 1.48 mg/dL, and the average duration of phototherapy application was 13.94 ± 7.64 h in the babies in the phototherapy group. No correlation was found between the duration of phototherapy application and serum melatonin levels (p = 0.791)., Conclusion: It was determined that there was no significant difference in serum melatonin levels in term newborn babies who received phototherapy for at least 6 h due to jaundice. No correlation was found between the duration of phototherapy application and the serum melatonin level of the maximum bilirubin values., Competing Interests: Conflict of interest: All authors declare that they have no conflicts of interest that may have affected the conduct or presentation of the research., (© TÜBİTAK.)

Aims: We evaluated endogenous melatonin levels in the acute phase of cerebral infarction and explored the impact of possible changes in melatonin levels on the prognosis of patients., Methods: This study recruited acute ischemic stroke (AIS) patients from the Department of the Second Affiliated Hospital of Soochow University between December 2019 and June 2021, along with healthy control subjects. Salivary melatonin samples were collected from each participant between 7 pm and 10 pm, and fasting plasma was collected the following morning to measure the levels of inflammatory markers. The prognosis was assessed through follow-up three months after discharge. The relationship between melatonin levels and plasma inflammatory markers was assessed, followed by an analysis of the effect of melatonin levels on patient prognosis., Results: The study enrolled a total of 160 participants, including 120 AIS patients aged 50 years or older (61.7% male) and 40 age-matched controls (55.0% male). The AIS group exhibited lower salivary melatonin levels at 19 (P = 0.002), 20 (P < 0.001), 21 (P < 0.001), and 22 (P < 0.001) o'clock, and the average melatonin level was also lower (P < 0.001). Logistic regression analysis models indicated an association between low melatonin levels and poor prognosis. Salivary melatonin levels demonstrated good predictive ability for the prognosis of AIS patients., Conclusion: Melatonin levels were lower in AIS patients compared to controls. In addition, lower melatonin levels were associated with a poorer prognosis among AIS patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Posttranscriptional mechanisms are increasingly recognized as important contributors to the formation of hyperexcitable networks in epilepsy. Messenger RNA (mRNA) polyadenylation is a key regulatory mechanism governing protein expression by enhancing mRNA stability and translation. Previous studies have shown large-scale changes in mRNA polyadenylation in the hippocampus of mice during epilepsy development. The cytoplasmic polyadenylation element-binding protein CPEB4 was found to drive epilepsy-induced poly(A) tail changes, and mice lacking CPEB4 develop a more severe seizure and epilepsy phenotype. The mechanisms controlling CPEB4 function and the downstream pathways that influence the recurrence of spontaneous seizures in epilepsy remain poorly understood., Methods: Status epilepticus was induced in wild-type and CPEB4-deficient male mice via an intra-amygdala microinjection of kainic acid. CLOCK binding to the CPEB4 promoter was analyzed via chromatin immunoprecipitation assay and melatonin levels via high-performance liquid chromatography in plasma., Results: Here, we show increased binding of CLOCK to recognition sites in the CPEB4 promoter region during status epilepticus in mice and increased Cpeb4 mRNA levels in N2A cells overexpressing CLOCK. Bioinformatic analysis of CPEB4-dependent genes undergoing changes in their poly(A) tail during epilepsy found that genes involved in the regulation of circadian rhythms are particularly enriched. Clock transcripts displayed a longer poly(A) tail length in the hippocampus of mice post-status epilepticus and during epilepsy. Moreover, CLOCK expression was increased in the hippocampus in mice post-status epilepticus and during epilepsy, and in resected hippocampus and cortex of patients with drug-resistant temporal lobe epilepsy. Furthermore, CPEB4 is required for CLOCK expression after status epilepticus, with lower levels in CPEB4-deficient compared to wild-type mice. Last, CPEB4-deficient mice showed altered circadian function, including altered melatonin blood levels and altered clustering of spontaneous seizures during the day., Significance: Our results reveal a new positive transcriptional-translational feedback loop involving CPEB4 and CLOCK, which may contribute to the regulation of the sleep-wake cycle during epilepsy., (© 2023 International League Against Epilepsy.)

Objective: We tested whether the concurrence of food intake and elevated concentrations of endogenous melatonin, as occurs with late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin receptor-1B gene (MTNR1B)., Research Design and Methods: In a Spanish natural late-eating population, a randomized, crossover study was performed. Each participant (n = 845) underwent two evening 2-h 75-g oral glucose tolerance tests following an 8-h fast: an early condition scheduled 4 h prior to habitual bedtime ("early dinner timing") and a late condition scheduled 1 h prior to habitual bedtime ("late dinner timing"), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses between early and late dinner timing were determined using incremental area under the curve (AUC) calculated by the trapezoidal method., Results: Melatonin serum levels were 3.5-fold higher in the late versus early condition, with late dinner timing resulting in 6.7% lower insulin AUC and 8.3% higher glucose AUC. The effect of late eating impairing glucose tolerance was stronger in the MTNR1B G-allele carriers than in noncarriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (P for interaction, Pint glucose area under the curve = 0.009, Pint corrected insulin response = 0.022, and Pint disposition index = 0.018)., Conclusions: Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impairs glucose tolerance, especially in MTNR1B G-risk allele carriers, attributable to insulin secretion defects., (© 2022 by the American Diabetes Association.)

While studies suggest that light and feeding patterns can reset circadian rhythms in various metabolites, whether these shifts follow a predictable pattern is unknown. We describe the first phase response curves (PRC) for lipids and hepatic proteins in response to combined light and food stimuli. The timing of plasma rhythms was assessed by constant routine before and after exposure to a combined 6.5-hour blue light exposure and standard meal schedule, which was systematically varied by ~20° between in0000dividuals. We find that the rhythms shift according to a PRC, with generally greater shifts for lipids and liver proteins than for melatonin. PRC timing varies relative to the stimulus, with albumin and triglyceride PRCs peaking at a time similar to melatonin whereas the cholesterol and high-density lipoprotein PRCs are offset by ~12 h. These data have important implications for treating circadian misalignment in shiftworkers who consume meals and are exposed to light around the clock., (© 2022. The Author(s).)

Introduction: Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role., Objective: The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin., Methods: A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge., Results: At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group (52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group (36.48 ± 33.85 pg/mL vs. 89.97 ± 52.01 pg/mL)., Conclusions: Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration . This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Lucia Marseglia et al.)

Background: Sleep deprivation (SD) often leads to complex detrimental consequences, though the mechanisms underlying these dysfunctional effects remain largely unknown. We investigated whether the right stellate ganglion block in rats can improve the spatial learning and memory dysfunction induced by sleep deprivation by alleviating the damage of hippocampus in rats., Methods: Sixty four male Sprague Dawley rats were randomly divided into four groups: Control, SD (sleep deprivation), SGB (stellate ganglion block) and SGB + SD (stellate ganglion block+ sleep deprivation) (n = 16). The SGB and SD + SGB groups were subjected to right stellate ganglion block through posterior approach method once per day. SD and SD + SGB groups were treated with modified multi-platform water environment method for 96 h sleep deprivation in rats and their body weights were analyzed. Histopathological changes of hippocampal neurons in rats and the expression of Caspase-3 in hippocampus of rats was detected by western blotting. ELISA was used to detect the content of IL-6, IL-1 in hippocampus and serum melatonin levels., Results: Compared with the group SD, the spatial learning and memory function of the group SD + SGB was improved, the weight loss was alleviated, the pathological damage of the hippocampus was reduced and the expression of IL-6, IL-1β and Caspase-3 in the hippocampus was decreased. The content of rat serum melatonin was also increased., Conclusions: The right stellate ganglion block can improve the spatial learning and memory dysfunction of rats with sleep deprivation, and the underlying mechanism may be related to alleviating the apoptosis and inflammation of hippocampus of rats with sleep deprivation., (© 2021. The Author(s).)

Lip, oral cavity, and pharyngeal cancers (LOCP) constitute a group of rare neoplasms with unfavorable prognosis. So far, not much is known about the role of vitamin D and oxidative stress in the pathogenesis of LOCP in the European population. The aim of the study was to determine the concentrations of vitamin D, osteopontin, melatonin, and malondialdehyde (MDA) as markers of oxidative stress and/or inflammation, as well as the activities of antioxidant enzymes in the course of LOCP. The vitamin D, melatonin, and osteopontin concentrations in blood serum, the MDA levels in erythrocytes and blood plasma, and the activities of superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GPx) in erythrocytes were measured in blood samples taken from 25 LOCP patients of middle age (YCG), 20 LOCP elderly patients (OCG), and 25 healthy middle-aged volunteers. In both cancer groups, decreases in vitamin D and CAT, as well as increases in osteopontin and blood plasma MDA, were observed. An increase in GPx activity in YCG and a decrease in melatonin level in OCG were found. The results indicate the vitamin D deficiency and disturbed oxidant-antioxidant homeostasis in LOCP patients. Osteopontin seems to be associated with LOCP carcinogenesis and requires further research., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Jarosław Nuszkiewicz et al.)

Purpose : To explore the role of outdoor light exposure by estimating ocular sun exposure measured by Conjunctival Ultraviolet Autofluorescence (CUVAF) imaging and serum melatonin levels in myopes and non-myopes. Materials & Methods : Age and sex matched emmetropes and myopes (60 each) aged 10-25 years participated. Those with a history of ocular surgery or any ocular or systemic co-morbidity were excluded. Socio-demographic parameters, sun exposure questionnaires, indoor and outdoor activity profile, morning serum melatonin levels, sleep pattern, degree of myopia, ocular biometry and area of CUVAF on ultraviolet photography were noted and analyzed. Results : Mean age of myopes (18 ± 4.5 years) and emmetropes (18.5 ± 4 years) was similar ( P = .523). Serum melatonin levels were significantly higher ( P = .001) among myopes (89.45 pg/ml) as compared to emmetropes (52.83 pg/ml). Lifetime sun exposure was significantly lower in myopes than emmetropes ( P = .0003). Area of CUVAF was inversely related to degree of myopia ( P < .0001). Day time sleepiness was greater in myopes (51.7%) than emmetropes (15%) ( P < .0001). There was a positive correlation between serum melatonin levels and axial length among myopes (correlation coefficient = 0.27; P = .03). Age and gender had no association with serum melatonin levels. Conclusion : This study demonstrates an inverse relationship between serum melatonin levels and degree of CUVAF in myopes. A novel link between serum melatonin, axial length and outdoor sun exposure is highlighted in the current study.

We studied the effect of constant illumination on the effects of administration of arginine vasopressin (AVP), one of the most important regulators of the key adaptive hypothalamic-pituitary-adrenal (HPA) axis under basal conditions and during stress, as well as on the circadian rhythm of activity of HPA axis and the pineal gland in laboratory primates. In young adult female rhesus monkeys exposed to constant illumination for 7 weeks, the rise in the concentration of ACTH and cortisol in response to administration of AVP was markedly reduced in comparison with both the basal period and with the control group of animals. In addition, a destructive effect of constant lighting on circadian rhythm of cortisol secretion was observed in the absence of significant circadian changes in melatonin secretion. The inhibitory effect of constant illumination on the function of the HPA axis under basal conditions and under conditions of its activation can reduce the body's adaptive abilities., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH., Materials and Methods: Daytime (from 11:00 am to 05:00 pm) melatonin levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from 30 patients on the day of aSAH onset (d 0 ) and in five pre-defined time intervals during the early (d 1-4 ), critical (d 5-8 , d 9-12 , d 13-15 ) and late (d 16-21 ) phase. Perioperative daytime melatonin levels determined in 30 patients who underwent elective open aortic surgery served as a control for the acute effects of surgical treatment on melatonin homeostasis., Results: There was no difference between serum melatonin levels measured in the control patients and on the day of aSAH onset (p = 0.664). However, aSAH was associated with a sustained up-regulation that started during the critical phase (d 9-12 ) and progressed to the late phase (d 16-21 ), during which almost 80% of the patients reached daytime melatonin levels above 5 pg/ml. In addition, subgroup analyses revealed higher melatonin levels on d 5-8 in patients with a poor clinical status on admission (p = 0.031), patients with anterior communicating artery aneurysms (p = 0.040) and patients without an external ventricular drain (p = 0.018), possibly pointing to a role of hypothalamic dysfunction., Conclusion: Our observations in a small cohort of patients provide first evidence for a delayed up-regulation of circulatory daytime melatonin levels after aSAH and a role of aneurysm location for higher levels during the critical phase. These findings are discussed in terms of previous results about stress-induced melatonin production and the role of hypothalamic and brainstem involvement for melatonin levels after aSAH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Intermittent light (IML) pulses are more efficient per minute of exposure than continuous exposure in resetting the phase of the human circadian pacemaker. We assessed the spectral sensitivity in phase resetting, melatonin suppression and alertness induced by IML pulses. Twelve healthy young adults (6 females; mean age ± SD = 25.4 ± 3.6 years) were exposed to six monochromatic light pulses (2.8 × 10 13 photons/cm 2 /s) over a 6.5 h window during the biological night. Six participants (3F) received 6 × 15-minute 460 nm (blue) pulses and six participants received 6 × 2-minute 555 nm (green) light pulses. Results were compared to historical data in 16 individuals who received continuous 460 nm (n = 8) or 555 nm (n = 8) light exposure using an identical protocol. As expected, long duration continuous 460 nm light exposure induced the largest total phase delay shifts, but intermittent 555 nm light induced the largest phase delay shifts per minute of the photic stimulus. Melatonin suppression was significantly higher under continuous light exposure compared to intermittent exposure patterns, and for 460 nm versus 555 nm exposure (under both light patterns). These data extend prior work showing a non-linear relationship between light exposure duration and phase resetting responses and illustrate the potential role of light wavelength, and therefore photoreceptor recruitment, in mediating these responses., (Copyright © 2021. Published by Elsevier Inc.)

Background/aim: This study aimed to analyze the serum melatonin levels and changes in sleep patterns in pediatric patients with coronavirus disease 2019 (COVID-19)., Materials and Methods: This study was designed as a descriptive, cross-sectional study. Serum melatonin levels and sleep parameters of children with the diagnosis of COVID-19 who had mild and moderate disease (i.e., COVID-19 group) were compared with those of children admitted with non-COVID-19 nonspecific upper respiratory tract infection (i.e., control group). The sleep disturbance scale for children (SDSC) questionnaire was applied to the participants› primary caregivers to analyze their sleep patterns at present and six months before symptom onset and to investigate the impact of COVID-19 on sleep patterns., Results: The entire study cohort consisted of 106 patients. The COVID-19 group included 80 patients, while the control group consisted of 26 patients. The mean serum melatonin levels were 136.72 pg/mL and 172.63 pg/mL in the COVID-19 and control groups, respectively (p = 0.16). There was no significant difference between the groups in terms of 6 subcategories of the SDSC questionnaire regarding the present time and 6 months before symptom onset. The total SDSC scores were also similar in two different evaluation time points described above (p = 0.99), Conclusions: We conclude that COVID-19 did not impact the sleep parameters of children. Serum melatonin levels of all patients were higher than the reference range; however, they were higher in the non-COVID-19 patient group than the COVID-19 group. Since serum melatonin levels were higher than the reference values in children with COVID-19, and this disease is significantly less morbid in children, melatonin may have protective effects against COVID-19., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

The aim of this study was to identify the effects of melatonin on acute gouty inflammation and to investigate the underlying mechanisms. We found significantly lower serum melatonin levels in gout patients in the acute phase than in those in the remission phase or in normal individuals. The mRNA expression of melatonin receptor 2 (MT2) was also lower in gout patients than in normal individuals. To verify the in-vivo role of melatonin, a gouty arthritis model was established by intraarticular injection of monosodium urate (MSU, 1 mg) crystals into the paws of C57BL/6 mice. Joint inflammation in the mouse model was evaluated by measuring the thickness of the right paw/left paw, and the inflammation index was determined by examining infiltrating neutrophils with haematoxylin and eosin (H&E) staining. Melatonin was found to reduce both paw thickness and the inflammation index in the mouse model, and melatonin also reduced the mRNA levels of interleukin-1 beta (IL-1β), IL-6 and NLR family pyrin domain containing 3 (NLRP3) inflammasome. To mimic gouty inflammation in vitro, mouse peritoneal macrophages were stimulated with lipopolysaccharides (LPS) plus MSU. Melatonin was revealed to reduce IL-1β secretion by stimulated macrophages. The mRNA expression levels of IL-1β and IL-6 were also inhibited by melatonin. Western blot analysis showed that the expression of NLRP3, caspase-1 and pro-IL-1β was also inhibited by melatonin. In conclusion, our study demonstrated that melatonin alleviated gouty inflammation in vivo and in vitro, and the underlying mechanism may involve inhibiting the assembly of the NLRP3 inflammasome., (© 2021. Huazhong University of Science and Technology.)

Background: Circadian rhythm disturbance is common postoperatively in older patients with hip fractures, which may contribute to the development of postoperative delirium (POD). As a reliable biomarker of endogenous circadian rhythms, melatonin regulates the sleep-wake cycle and environmental adaptation, and its secretory rhythm may be modified by anaesthesia and surgery. This study compared the impact of subarachnoid anaesthesia (SA) and general anaesthesia (GA), on the peak of melatonin secretion (primary outcome), the circadian rhythm of melatonin, cortisol and sleep, and the POD incidence (secondary outcome)., Methods: In this prospective cohort observational study, hip fracture surgery patients were enrolled and assigned to receive either SA or GA. Postoperative plasma melatonin and cortisol levels were dynamically measured every six hours on seven time-points, and the circadian rhythm parameters including mesor, amplitude, and acrophase were calculated. Subjective and objective sleep assessments were performed by sleep diaries and sleep trackers, respectively. The Confusion Assessment Method was used twice daily by a specific geriatrician to screen for POD occurrence., Findings: In a cohort of 138 patients who underwent hip fracture surgery, the circadian rhythm disruption of the patients in the GA group (n=69) was greater than the SA group (n=69). Compared with SA, GA provided the lower peak concentration, mesor, and amplitude of melatonin secretion on postoperative day 1 (p < 0.05). Patients in the GA group experienced higher awakenings, more sleep deprivation, and poor sleep quality on surgery day (p < 0.05). A proportion of 12 patients in the SA group (17.4%) and 24 patients in the GA group (34.8%) experienced POD (p = 0.020)., Interpretation: These results suggest that SA may be superior to GA in elderly patients undergoing hip fracture surgery as SA is associated with less impairment of the melatonin rhythm and sleep patterns, and fewer POD occurrences., Funding: The study was supported by the National Natural Science Foundation of China (81971012, 81873726, 81901095, 81701052, and 81801070), Key Clinical Projects of Peking University Third Hospital (BYSYZD2019027), and Peking University "Clinical Medicine plus X" Youth Project (PKU2020LCXQ016)., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Time-Restricted Eating is an eating pattern based on the circadian rhythm which limits daily food intake (usually to ≤12 h/day), unique in that no overt restriction is imposed on the quality, nor quantity, of food intake. This paper aimed to examine the effects of two patterns of TRE, traditional TRE, and Ramadan fasting, on two markers of circadian rhythm, cortisol and melatonin. PubMed and Web of Science were searched up to December 2020 for studies examining the effects of time restricted eating on cortisol and melatonin. Fourteen studies met our inclusion criteria. All Ramadan papers found statistically significant decrease in melatonin ( p < 0.05) during Ramadan. Two out of the three Ramadan papers noted an abolishing of the circadian rhythm of cortisol ( p < 0.05). The non-Ramadan TRE papers did not examine melatonin, and cortisol changes were mixed. In studies comparing TRE to control diets, Stratton et al. found increased cortisol levels in the non-TRE fasting group ( p = 0.0018) and McAllister et al. noted no difference. Dinner-skipping resulted in significantly reduced evening cortisol and non-significantly raised morning cortisol. Conversely, breakfast skipping resulted in significantly reduced morning cortisol. This blunting indicates a dysfunctional HPA axis, and may be associated with poor cardio-metabolic outcomes. There is a paucity of research examining the effects of TRE on cortisol and melatonin. The contrasting effect of dinner and breakfast-skipping should be further examined to ascertain whether timing the feeding window indeed has an impact on circadian rhythmicity.

Ethnopharmacological Relevance: The tea made with the fruits of Luffa operculata (L.) Cogn. (Cucurbitaceae; EBN) is popularly used as abortive., Aim of the Study: The present work aimed at accessing how the exposition of female Wistar rats to 1.0 mg/kg of EBN (experimental group, EG), or distilled water (control group, CG), by gavage, at gestational days (GD) 17-21 interfered with the reproductive performance, and with dams' behavior after weaning., Materials and Methods: At post-natal day 2 (PND2), the number of male and female pups was evaluated, as well as their weight. After weaning (PND21), dams were euthanized, and their liver and kidneys were removed for histological and biochemical analyses, while the blood was used in the evaluation of cytokines IL-1α, IL-1β, IL-6 and TNF-α, corticosterone, adrenocorticotrophic hormone, melatonin, AST, ALT and creatinine levels., Results and Discussion: Dams that were treated with EBN showed an anxiety-like behavior, weight loss at the end of gestation and weight gain at weaning, accompanied with a significant decrease in pro-inflammatory cytokines and in the melatonin level. No significant histological or biochemical alterations have occurred in the liver or kidneys. The number of female pups was significantly higher in the EG. The male pups showed weight gain at PND60., Conclusion: The presence of cucurbitacins is probably involved in the dysregulations that were found, due to their polycyclic steroid triterpene structure., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The inflammatory response is a complex process that relies on interactions among multiple endocrine and immune modulators. Studies incorporating time-related and integrative endocrine and immune responses to an immune challenge might shed light on the characterization of the phases of the inflammatory response in anurans. The present study investigated time-related changes (1, 3, 6, and 18 h post-challenge) in plasma corticosterone (CORT), melatonin (MEL) and testosterone (T) levels, phagocytosis percentage (PP), plasma bacterial killing ability (BKA), and neutrophil to lymphocyte ratio (NLR) following a lipopolysaccharide (LPS) immune challenge in Rhinella diptycha toads. Our results showed the response to LPS injection was characterized by increased CORT, PP, BKA, and NLR, with a concomitant decrease in plasma MEL and T. Increased CORT was more pronounced at 6 and 18 h, while increased NLR was observed only 18 h post-LPS injection. Meanwhile, plasma MEL and T decreased independently of the time post-LPS injection. Additionally, toads in better body condition showed higher BKA and PP in the LPS-treated group, regardless of the time postinjection. Our results show that toads (R. diptycha) were sensitive to the LPS challenge, mounting an inflammatory response, which started quickly (after 1 h) and developed over time and was influenced by body condition. These results demonstrate a time-related hormonal and immune variation as a consistent pattern of activation of the immune system, as well as of hypothalamic-pituitary-adrenal/interrenal and immune-pineal axes following an immune challenge more deeply studied in mammals, suggesting the evolutionary conservation of the regulatory mechanisms for tetrapod vertebrates., (© 2021 Wiley Periodicals LLC.)

Melatonin's role in circadian rhythm is well documented, as are its' anti-oxidant, oncostatic and anti-inflammatory properties. Poor sleep quality has been associated as a potential risk factor for several malignancies, including head and neck cancers. The purpose of this study is to determine salivary melatonin (MLT) levels in oral squamous cell carcinoma (OSCC) patients, compare the salivary MLT levels with those in healthy individuals and compare the salivary and serum levels in OSCC patients. Furthermore, the aim is to investigate the potential relationship between sleep quality and salivary MLT levels in OSCC patients. Unstimulated (UWS) and stimulated (SWS) whole saliva was sampled from patients with T1N0M0 and T2N0M0 OSCC (N = 34) and 33 sex and age matched healthy subjects. Serum samples were taken from 11 OSCC patients. Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI) questionnaire. Melatonin levels in UWS and SWS were significantly higher in the OSCC group. Sleep quality was significantly lower in patients with OSCC (P = 0.0001). ROC analysis was found to be significant (P < 0.001) in evaluating MLT concentration limit in diagnosing OSCC. The expected relationship between sleep quality and salivary MLT levels in OSCC patients was not observed. Our results suggest salivary MLT as a potential biomarker that might facilitate non-invasive detection of early stage OSCC.

Shift workers are mostly suffered from the disruption of circadian rhythm and health problems. In this study, we designed proper light environment to maintain stable circadian rhythm, cognitive performance, and mood status of shift workers. We used five-channel light-emitting diodes to build up the dynamic daylight-like light environment. The illuminance, correlated color temperature, and circadian action factor of light were tunable in the ranges of 226 to 678 lx, 2680 to 7314 K, and 0.32 to 0.96 throughout the day (5:30 to 19:40). During the nighttime, these parameters maintained about 200 lx, 2700 K, and 0.32, respectively. In this light environment, three subjects had engaged in shift work for 38 consecutive days. We measured plasma melatonin, activity counts, continuous performance tests, and visual analogue scale on mood to assess the rhythm, cognitive performance, and mood of subjects. After 38-day shift work, the subjects' peak melatonin concentration increased significantly. Their physiological and behavioral rhythms maintained stable. Their cognitive performance improved significantly after night work, compared with that before night work. Their mood status had no significant change during the 38-day shift work. These results indicated that the light environment was beneficial to maintain circadian rhythm, cognitive performance and mood status during long-term shift work in closed environment.

Objectives: Exercise can improve both health and mood. Some beneficial effects of exercise are attributed to endocrine status. This study aims to evaluate the effect of eight weeks of basketball training on melatonin, serotonin, and hematologic parameters in basketball players., Methods: The experimental group was selected form 34 healthy young boys, aged between 13 and 16 years old. The participants were randomly assigned to the control group (n=17) and the exercise group (n=17). The exercise program consisted of 2 h/day aerobic activity of basketball training in 5 days a week for 8 weeks. Venous blood was taken on the day before experiment (pre-exercise) and on the day following the last exercise (post-exercise) and hormone levels were detected by ELISA., Results: Serotonin and melatonin levels significantly increased in the post-exercise group compared to the other groups (p<0.05). Exercise caused increase in WBC, RBC, HCT and Hb levels (p<0.05) while did not alter PLT, MCH, and PCT levels (p>0.05). This study indicates that an eight weeks-long regular aerobic exercise increased melatonin and serotonin levels, and also altered some hematological parameters., Conclusions: In conclusion, it is believed that improvement in levels of serotonin, melatonin, and hematological parameters after eight weeks of regular basketball training in basketball players could be attributed to beneficial effects of exercise. Investigation in other branches of sports and in different gender and age groups would make contribution into exercise physiology and training science., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: The purpose of this study was to characterize the metabolomic profiles of shift workers and day workers and to discover the effect of shift work on workers' metabolic health., Methods: A total of 824 participants aged 25 to 55 years were recruited, and 485 (275 shift workers and 210 day workers) completed the study. The mean age of the shift workers was 37.32 (5.53) years old, and that of day workers was 36.50 (7.83) years old. Serum and salivary samples were collected for the detection of key biochemical indicators (melatonin, cholesterol, and low-density lipoprotein cholesterol) and for metabolome profile analyses., Results: Compared with female day workers, female shift workers had a higher BMI, waist circumference, and hip circumference. Correspondingly, we identified 76 significant metabolites (false discovery rate < 0.05) in shift workers, including L-tryptophan, acylcarnitines, and several fatty acids. Three pathways that presented significant differences were biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and ubiquinone and other terpenoid-quinone biosynthesis., Conclusions: Compared with day workers, shift workers were more prone to weight gain and central obesity and were at a higher risk for impaired lipid metabolism with disrupted circadian rhythms., (© 2021 The Obesity Society.)