The impact of melatonin on pediatric populations has not yet been widely researched. This narrative review is intended to summarize the current literature regarding the efficacy and safety of melatonin for children and potential pitfalls in its clinical use, in order to assist pediatric practitioners in making evidence-based recommendations that serve the best interests of their patients and families.

A literature review of melatonin in the pediatric population was conducted using PubMed search terms: melatonin, pediatrics, child/adolescent.

Melatonin use in the pediatric population world-wide has increased significantly over the past several decades. While a number of studies, largely in children with neurodevelopmental disorders with insomnia, have suggested that melatonin is generally safe and well-tolerated, a similar body of evidence is overall lacking for typically developing children and prospective studies regarding long-term adverse events are lacking. In addition, recent studies have raised concerns regarding the variable content of melatonin in over-the-counter products, as well as safety issues relating to accidental ingestions.

Due to a number of concerns regarding inappropriate use, lack of efficacy and safety data across pediatric populations and variability in actual content, melatonin should be used with caution in children and only under medical supervision.

Pain is a significant global public health issue that can interfere with daily activities, sleep, and interpersonal relationships when it becomes chronic or worsens, ultimately impairing quality of life. Despite ongoing efforts, the efficacy of pain treatments in improving outcomes for patients remains limited. At present, the challenge lies in developing a personalized care and management plan that helps to maintain patient activity levels and effectively manages pain. Neuropathic pain is a chronic condition resulting from damage to the somatosensory nervous system, significantly impacting quality of life. It is partly thought to be caused by inflammation and oxidative stress, and clinical research has suggested a link between this condition and diet. However, these links are not yet well understood and require further investigation to evaluate the pathways involved in neuropathic pain. Specifically, the question remains whether supplementation with dietary antioxidants, such as melatonin, could serve as a potential adjunctive treatment for neuropathic pain modulation. Melatonin, primarily secreted by the pineal gland but also produced by other systems such as the digestive system, is known for its anti-inflammatory, antioxidant, and anti-aging properties. It is found in various fruits and vegetables, and its presence alongside other polyphenols in these foods may enhance melatonin intake and contribute to improved health. The aim of this review is to provide an overview of neuropathic pain and examine the potential role of melatonin as an adjunctive treatment in a neuro-nutritional approach to pain management.

During the process of sperm cryopreservation, the overproduction of reactive oxygen species (ROS) triggers oxidative stress thereby leading to a reduction in sperm motility and quality. Therefore, it is a feasible strategy to mitigate oxidative damage during cryopreservation by adding antioxidants to freezing media.

In this study, we explored the potential of melatonin to protect sperm from oxidative stress-induced damage by evaluating sperm-related parameters after thawing through self-assembly with a hyaluronic acid-bilirubin conjugate into nanoparticles (M@HBn).

The optimized M@HBn exhibited uniform spherical morphology with average particle size of 112.57   ±   9.8 nm, PDI of 0.22   ±   0.02, a surface potential of  - 0.43   ±   1.02 mV and entrapment efficiency of 85.1   ±   4.6%. The addition of 5 μM M@HBn demonstrated a notable enhancement in frozen-thawed human spermatozoa viability, motility, and DNA integrity by scavenging ROS. Additionally, the use of M@HBn supplementation in freezing medium resulted in the most mitochondrial stability and total viability as compared to the other groups.

These findings suggest that M@HBn have the potential to serve as a novel drug delivery platform for protecting spermatozoa against from cryodamage while enhancing the quality of cryopreserved sperm and the bioavailability of melatonin.

It is well accepted that attention deficit hyperactivity disorder (ADHD) is in part driven by dysfunction in the monoaminergic neurotransmitter system, but both the extent of dysfunction and possible therapeutic avenues presented by serotonergic neurotransmission is frequently overlooked. As such, we present key evidence for dysfunction in serotonergic transmission, as seen from biochemical, genetic and pharmacological perspectives. An overall deficit in serotonin availability is a common theme throughout the literature, thus this review aims to explore possible dysfunctions in the serotonin synthesis pathway which result in this reduced bioavailability, and investigate whether such dysfunctions could be loci of change in ADHD. We have identified several steps in transmission, namely the conversion of tryptophan to 5-hydroxytryptophan and its use of cofactor tetrahydrobiopterin, which could present promising avenues for development of novel clinical interventions for ADHD.

The indoleamine hormone, melatonin, is produced in the pineal gland and has an essential role in many physiological functions. The pineal gland is considered to be the most important organ for producing melatonin. Nevertheless, it is important to point out that the eye is also capable of producing melatonin, and has its own circadian rhythm in producing this hormone. Melatonin is mainly produced by a subpopulation of photoreceptors in a diurnal rhythm. Numerous in vitro and in vivo studies have shown the beneficial effects of melatonin in eye-related disorders. These diseases primarily affect retinal cells, highlighting the therapeutic potential of melatonin, especially in the retina. Melatonin's ability to regulate oxidative stress response pathways and modulate the expression of antioxidant genes makes it a promising candidate for mitigating retinal cell damage. Moreover, melatonin can modulate inflammatory pathways such as NF-кB and further reduce retinal damage, as well as affecting programmed cell death such as apoptosis and autophagy in retinal cells. Therefore, the goal of this review is to explore the ways in which melatonin protects retinal cells from damage and ischemia. We discuss the mechanisms involved in order to gain valuable understanding of the possible therapeutic applications of melatonin in protection of retinal cells and treatment of retinal disorders.

Glutamate-induced neurotoxicity can be attenuated via paracrine mechanisms involving mesenchymal stem cells (MSCs). Conditioned medium (CM) from dental MSCs stimulates neuroprotective effects through trophic factors, and melatonin is a known enhancer of the efficacy of conditional media. Here, we investigated the protective effect of CM derived from stem cells from the apical papilla (SCAPs), supplemented without and with melatonin CM (SCAP-CM and Mel-CM), against glutamate-induced PC12 cell apoptosis via the inhibition of intracellular calcium influx and reactive oxygen species (ROS) production. The results showed that CM effectively reduced glutamate-induced intracellular calcium ion concentration, ROS production, and LDH levels in PC12 cells, elevated mitochondrial membrane potential, and inhibited Bax and Cytochrome c protein expression while increasing Bcl-2 protein expression. Moreover, CM significantly reduced the expression of caspase-9 and caspase-3 to inhibit glutamate-induced PC12 cell apoptosis. Notably, Mel-CM outperformed SCAP-CM in all aspects. This study demonstrates that melatonin can enhance the paracrine effects of stem cells and that Mel-CM mediates neuroprotection by inhibiting neuronal cell damage and apoptosis induced by glutamate-induced neurotoxicity.

Hepatotoxicity of pyrazinamide, an antituberculosis drug, limits its therapeutic use and oxidative stress has been implicated in this toxicity. This study investigated the protective effects of adenosine triphosphate (ATP), thiamine pyrophosphate (TPP), melatonin, and Liv-52, which have previously been shown antioxidant activities, on pyrazinamide-induced hepatotoxicity.

36 albino Wistar male rats were divided into randomized six groups; healthy (HG), pyrazinamide (PZG), ATP + pyrazinamide (APZG), TPP + pyrazinamide (TPZG), melatonin + pyrazinamide (MPZG) and Liv-52 + pyrazinamide (LPZG) groups. ATP 4 mg/kg and TPP 25 mg/kg were administered intraperitoneally (IP). Melatonin 10 mg/kg and Liv-52 20 mg/kg were given orally. One hour after administration of ATP, TPP, melatonin, and Liv-52, 250 mg/kg pyrazinamide was applied orally to all rats except HG group. The treatment was repeated (1 × 1) for 4 weeks. Then, blood samples were taken for determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Immediately after, the rats were euthanized with thiopental sodium (50 mg/kg, IP), and the livers were removed. The tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) also hydropic degeneration, necrosis, and apoptosis (caspase 3) were examined.One-Way ANOVA was used in biochemical analyses and Tukey test was used as post-hoc. For histopathological and immunohistochemical analysis, the Kruskal-Wallis test was used and Dunn's test as a post-hoc.

Pyrazinamide increased MDA land decreased tGSH, SOD, and CAT levels in liver tissues (p < 0.001). It also increased serum ALT and AST activities and caused severe hydropic degeneration and necrosis in liver tissue (p < 0.001). ATP, TPP, melatonin, and Liv-52 significantly prevented the biochemical and histopathological changes induced by pyrazinamide (p < 0.05). On the other hand, Liv-52 was more successful than other potential protectors in protecting liver tissue from pyrazinamide damage (p < 0.05).

ATP, TPP, melatonin, and Liv-52 can be used to protect liver tissue from pyrazinamide-induced hepatotoxicity in rats.

The hormone melatonin (MEL), primarily acknowledged for its role in regulating circadian rhythms, has demonstrated itself to be a complicated molecule with significant implications for vascular physiology. Melatonin exerts extensive physiological effects directly via the MEL receptor type 1 (MT1R) and the MEL receptor type 2 (MT2R), as well as indirectly through the improvement of antioxidant vascular tone.

This review aims to analyse the intricate relationships between MEL and the renin-angiotensin system (RAS) in the vascular attenuation of non-diabetic (non-DM) and diabetic (DM) contexts. Alterations in the expression of RAS components and their dysregulation are prevalent in diabetes. Melatonin exhibits vasoprotective advantages in non-diabetic conditions. In the context of DM, vascular problrms such as vascular endothelial dysfunction (VED), hypertension, and atherosclerosis result from the dysregulation of MEL-RAS interactions. Comprehending the actions of MEL on RAS components in diabetes vasculature is essential for formulating tailored pharmaceutical therapy methods.

This review consolidates existing knowledge regarding the vascular effects of MEL in relation to RAS activation, emphasising its potential role as a modulating factor for angiotensin 1-8 (Ang 1-8), angiotensin-converting enzyme 2 (ACE2), and angiotensin 1-7 (Ang 1-7) in the management of vascular complications associated with DM.

Vitamin D is associated with sleep quality and duration, but it is unclear whether vitamin D status influences sleep variability. Therefore, we sought to determine whether vitamin D status was associated with sleep variability in healthy adults. We assessed objective sleep, including timing and duration standard deviation (SD) using the Philips Actiwatch Spectrum and subjective sleep quality using the Pittsburgh Sleep Quality Index (PSQI) in 130 adults. We measured plasma 25(OH)D concentration to assess vitamin D. We used one-way ANOVAs and Kruskal-Wallis tests to compare sleep in participants characterized as vitamin D deficient (<20 ng/mL), insufficient (21-29 ng/mL), and sufficient (>30ng/mL). We used covariate-adjusted linear regression to assess associations between vitamin D status and sleep metrics. We compared differences in "low" and "high" sleep variability based on vitamin D status using the Chi-squared test. There was an effect of vitamin D status on sleep timing SD (Kruskal-Wallis, P = 0.021) and sleep duration SD (Kruskal-Wallis, P < 0.001). There was an inverse association between vitamin D status with sleep duration SD (after covariate adjustment R2 = 0.267, P < 0.001, deficient vs. sufficient P = 0.050, insufficient vs. sufficient P = 0.022). There was no effect of vitamin D status on objective sleep duration, efficiency, or PSQI scores (P > 0.05). We did not observe differences in "low" and "high" sleep timing SD based on vitamin D status (χ2 = 5.43, P = 0.066), but we did for sleep duration SD (χ2 = 22.4, P < 0.001). Our data indicate that individuals with poor vitamin D status exhibit greater objective sleep variability. Clinical Trial Registry: https://www.clinicaltrials.gov/; Unique identifiers NCT04334135, NCT04244604, and NCT04576338.NEW & NOTEWORTHY Our findings reveal that individuals with lower circulating vitamin D concentrations experience greater sleep variability compared with those with higher circulating concentrations. This supports the growing body of evidence suggesting an important link between vitamin D status and sleep health.

Periodontal ligament stem cells (PDLSCs) bring new hope to patients with poor periodontium recovery and impaired regeneration. However, the complex inflammatory microenvironment continually inhibits stem cell function and hinders stem cell therapy effectiveness. Melatonin is a naturally occurring neurohormone that participates in the regulation of a large spectrum of biological functions. We investigated the effect of melatonin on periodontium regeneration both in vitro and in vivo. The results showed that melatonin promoted periodontitis recovery and enhanced the osteogenesis of inflamed PDLSCs (Inf-PDLSCs) depending on concentrations. Further mechanistic exploration indicated that autophagy activation played a significant role in enhancing the osteogenic differentiation of Inf-PDLSCs after melatonin treatment. Additionally, melatonin-induced upregulation of TEME110 participated in the initiation of autophagy activation and enhancement of osteogenesis in Inf-PDLSCs. Collectively, the results of our study provide evidence that melatonin-mediated osteogenesis of Inf-PDLSCs is important for periodontal tissue regeneration. Moreover, melatonin as a therapeutic drug for periodontitis treatment deserves further investigation.

(1) Background: Hair growth can function as an indicator of an animal's health and nutritional status, furnishing a valuable means for early diagnosis and timely modifications to management practices, and is influenced by hormones, the immune system, and the levels of minerals within the animal's body. (2) Methods: In this study, a total of 81 yaks were selected and divided into three groups according to their ages (1-2 years, 3-4 years, 5-6 years), and the concentrations of melatonin, dihydrotestosterone, IgA, IgG, and IgM in their blood serum and the levels of Ca, Mg, Zn, Fe, and P in both their blood serum and hair were detected. (3) Results: The levels of melatonin and dihydrotestosterone in yaks aged 1-2 years were significantly higher than those of other age groups (p < 0.001). In addition, the concentration of melatonin in male yaks was markedly greater than that in female yaks (p < 0.05). When it came to immunoglobulins, the IgA level in 1-2-year-old yaks was strikingly higher than those in yaks aged 3-4 years and 5-6 years (p < 0.05). In terms of mineral elements, the concentrations of calcium, magnesium, zinc, and iron in the blood serum of 1-2-year-old and 5-6-year-old yaks were significantly elevated compared to those in 3-4-year-old yaks. However, there was no notable difference between the 1-2-year-old and 5-6-year-old groups. The correlation analysis showed that there was a significant correlation between DHT and the levels of melatonin and IgA in yaks. Additionally, a significant correlation was observed between IgA and IgG, as well as between IgA and the levels of Fe, Mg, and Ca. It is likely that they jointly regulate the hair growth and immune processes of yaks. (4) Conclusions: There are positive correlations among melatonin, dihydrotestosterone, and IgA in the blood serum and the content of Fe and Mg in the hair to varying degrees, implying these indicators may jointly regulate yak hair growth and immune status. These research findings provide data support for applied research into evaluating the overall health status of yaks through the growth status of hair or by measuring the mineral content in hair in a non-invasive way.

Sodium arsenite (SA), NaAsO2, is among the most hazardous toxicants, and wide use and presence of this toxicant leads to a severe environmental threat. Exposure to SA is associated with many health concerns, such as the prevalence of cancer and diabetes mellitus type 2 (DMT2). Many studies suggest that SA induces inflammation and biochemical impairments through different mechanisms, including increasing oxidative stress and altering vital genes such as biochemical and anti-inflammatory. Recent studies on melatonin (MLT), a harmless hormone secreted in the body generally for induction of sleepiness, find many beneficial and positive effects. Mitigating different harms and toxicities through different mechanisms, such as antioxidant properties, anti-inflammatory effects, and critical gene regulation, is essential. Due to these findings, this study aimed to evaluate the hypothesis that MLT may ameliorate pancreatic damage caused by exposure to SA.

Forty-eight adult healthy male wistar rats aged 7-8 weeks were divided into eight for this research. Group 1 did not receive any intervention. Group 2 received 10 mg/kg/day MLT through intraperitoneal (IP) injection. Groups 3, 4, and 5 received 1.5 (1/10 LD50), 5 (1/3 LD50), and 7.5 (1/2 LD50) mg/kg SA, respectively. Groups 6, 7, and 8 were given 1.5 (1/10 LD50), 5 (1/3 LD50), and 7.5 (1/2 LD50) mg/kg of SA along with 10 mg/kg/day MLT, respectively, during the last ten days of the experiment. After 28 days of the experiment, the blood and tissue samples of the pancreas were removed for biochemical and pathological examination.

MLT attenuates SA toxicity by reducing oxidative stress biomarkers and inflammation markers. Moreover, MLT improves SA exposure's biochemical and functional damages by regulating related genes and pathways.

MLT poses protective and preventive effects on the pancreas against exposure to SA. However, MLT's therapeutic and beneficial impacts have great potential for further investigation.

The therapeutic value of pregabalin in managing various pathological states, such as sleep, anxiety, and bipolar disorders, fibromyalgia, epilepsy, and others, cannot be overstated. Nevertheless, the gonadotoxicity of this drug remains a concern. In contrast, melatonin, an endogenous hormone, is known for its beneficial effects on reproductive tissues following various insults. Thus, this study aimed to examine the impact of melatonin on male Wistar rats exposed to pregabalin.

A total of sixty male Wistar rats, weighing between 120 and 140 g, were randomly assigned to six groups, with each group consisting of ten rats. The control group was given 0.5 ml of normal saline orally, whereas melatonin was administered alone at 10 mg/kg/BW, and pregabalin was delivered at low and high doses of 150 and 300 mg/kg/BW orally, respectively. At the specified dosages, rats were also treated simultaneously with low and high doses of pregabalin in combination with melatonin. All treatments lasted for 56 days. Biomarkers were assayed in the testicular and epididymal tissues, while hormones were assayed in the serum.

Pregabalin treatment resulted in notable decreases in the percentage body weight change, testicular weight, relative testicular weight, FSH, LH, testosterone, 3β-HSD, 17β-HSD, SOD, catalase, and GSH, as compared to the control group. However, these effects were mitigated in the groups administered melatonin in conjunction with pregabalin. Pregabalin treatment also caused significant elevations in lactate, pyruvate, LDH, GGT, MDA, caspase, IL-1β, NF-κB, and TNF-α, and distorted testicular histoarchitecture, but these effects were blunted in the group co-administered with pregabalin and melatonin. The histological findings paralleled the biochemical assays.

Conclusively, melatonin has a protective effect against pregabalin-induced gonadotoxicity through anti-oxidative, anti-inflammatory, anti-apoptotic, enzymatic, and hormonal regulatory mechanisms.

Not applicable.

Engineered extracellular vesicles play an increasingly important role in the treatment of spinal cord injury. In order to prepare more effective engineered extracellular vesicles, we biologically modified M2 microglia. Angiopep-2 (Ang2) is an oligopeptide that can target the blood-brain barrier. Through single-cell sequencing and immunofluorescence experiments, we confirmed that the expression of LRP-1, the targeted receptor of Ang2, was elevated after spinal cord injury. Subsequently, we integrated the Ang2 peptide segment into M2 microglia to obtain Ang2-EVs, which could successfully target the site of spinal cord injury. However, in order to improve the function of Ang2-EVs, we pretreated M2 microglia with melatonin, which has anti-inflammatory effects, to obtain M-Ang2-EVs. The results of single-nucleus sequencing of the mouse spinal cord verified that neurons and OPCs gradually transformed into subtypes related to nerve repair functions after treatment with M-Ang2-EVs. This is consistent with the sequencing and enrichment analysis of miRNAs contained in M-Ang2-EVs. We further verified through experiments that M-Ang2-EVs can promote microglia/macrophages to phagocytose sphingomyelin, promote axon remyelination and axon elongation, and maintain the integrity of the blood-spinal barrier. Since Ang2 can also target the blood-brain barrier, we found that M-Ang2-EVs can also reduce brain inflammation that results from spinal cord injury. Our study applied the Angiopep-2 peptide to spinal cord injury to enhance the targeting of injured cells, and successfully construct engineered extracellular vesicles that can target the spinal cord injury site and the brain.

Skin health is impacted by a wide range of intrinsic and extrinsic factors (J Dermatol Sci, 2017, 85, 152), including those that impact circadian rhythm, such as sleep disruption (Textbook of Aging Skin, 2016), UV (Biomed Aging Pathol, 2013, 3, 161) and blue light (Int J Cosmet Sci, 2019, 41, 558). Disruption of the skin's endogenous circadian balance, even by a consistently late bedtime, has deleterious effects on multiple measurements of skin health, including hydration, skin barrier protection, microbiome counts and skin regeneration, among others (Clin Cosmet Investig Dermatol, 2022, 15, 1051). Skin repair processes occur at night and help to maintain important aspects of skin health (FEBS Lett, 2021, 595, 2413). Interest is increasing in the development of topical products that help restore proper circadian function. This study demonstrates that a proprietary topical formulation regulates new and established gene and protein biomarkers of circadian entrainment and circadian rhythm, demonstrating the product's potential to maintain appropriate dermal diurnal balance.

The stress response maintains the homeostasis of the body's internal environment and normal physiological activities, involving several neuroendocrine systems, such as the HPA axis, the HPG axis, the endocannabinoid system, and the melatonin system. However, studies on the intricate interactions among the four neuroendocrine systems are lacking, and it is not clear how these interactions are affected by demographic variables. The aim of this study was to investigate the network characteristics of hormonal networks comprising nine hormones from four neuroendocrine systems and how they were affected by demographic variables.

252 healthy current students were recruited from Southeast University, China. The concentrations of nine hormones in their hair were measured by LC/MS methods, and hormonal network was constructed. Network analysis was used to characterize the interrelationships between hormones or neuroendocrine systems, central hormones, bridge hormones, hormonal network characteristics, and their changes in response to demographic variables.

Complex interactions between the HPA axis, the HPG axis, the ECS and the melatonin system formed a sparse and stable network, with cortisol and cortisone being the central hormones and melatonin as the bridge hormone. Demographic variables did not affect the overall characteristics of the network or the central hormone, but a number of specific connections in the network changed and the bridge hormones became cortisone and progesterone.

The interactions between the four stress-related neuroendocrine systems were relatively stable and were centered and initiated by the HPA axis. Demographic variables did not affect the overall structure of the network, but influenced local features of the network, such as edge weights and bridge centrality.

Bipolar disorder (BD) is a significant neuropsychiatric condition characterized by marked psychological mood disturbances. Despite extensive research on the symptomatology of BD, the mechanisms underlying its development and presentation remain unknown. Consequently, potential treatments are limited, and existing medications often cause significant side effects, leading to treatment discontinuation. Dopamine (DA) has been implicated in behavioral regulation, reward systems, and mood, highlighting the importance of the dopaminergic system in BD. Elevated levels of DA and tyrosine hydroxylase are associated with the onset of manic episodes, whereas reduced levels are linked to the depressive phase. Additionally, endogenous melatonin (MEL) levels are considerably lower in patients with BD. When administered as a treatment, exogenous MEL and MEL agonists improve behavioral characteristics and significantly modulate DA-related pathophysiological pathways in BD, with minimal adverse effects achieved through MEL receptor activation. Moreover, MEL and MEL agonists offer neuroprotection by promoting physiological homeostasis during disruption. The aim of this review is to investigate and propose MEL receptors as potential novel therapeutic targets for BD. This review seeks to analyze the role of MEL and its agonists in modulating dopamine-related pathophysiological pathways, improving behavioral outcomes, and providing neuroprotection with minimal side effects.

To review causes, risk factors, and consequences of sleep disruption in critically ill patients; evaluate the role of nonpharmacological and pharmacological therapies for management of sleep in the intensive care unit (ICU); and discuss the role of pharmacists in implementation of sleep bundles.

Critically ill patients often have disrupted sleep and circadian rhythm alterations that cause anxiety, stress, and traumatic memories. This can be caused by factors such as critical illness, environmental factors, mechanical ventilation, and medications. Methods to evaluate sleep, including polysomnography and questionnaires, have limitations that should be considered. Multicomponent sleep bundles with a focus on nonpharmacological therapy aiming to reduce nocturnal noise, light, and unnecessary patient care may improve sleep disorders in critically ill patients. While pharmacological agents are often used to facilitate sleep in critically ill patients, evidence supporting their use is often of low quality, which limits use to patients who have sleep disruption refractory to nonpharmacological therapy. Dedicated interprofessional teams are needed for implementation of sleep bundles in the ICU. Extensive pharmacotherapeutic training and participation in daily patient care rounds make pharmacists vital members of the team who can help with all components of the bundle. This narrative review discusses evidence for elements of the multicomponent sleep bundle and provides guidance on how pharmacists can help with implementation of nonpharmacological therapies and management of neuroactive medications to facilitate sleep.

Sleep bundles are necessary for patients in the ICU, and dedicated interprofessional teams that include pharmacists are vital for successful creation and implementation.

Although circadian rhythms have been shown to influence some neuromuscular performance tasks, the time-of-day effect on team sports performance athletes remains equivocal. This study aimed to examine the existing evidence concerning diurnal variations in neuromuscular performance in professional and semi-professional team sports athletes using a meta-analytic approach.

A literature search was conducted through three different databases: PubMed, SportDiscus and Web of Science. Article selection was made based on the following inclusion criteria: team sports athletes, professional or semi-professional athletes, neuromuscular performance, testing protocols and time-of-day testing times. Neuromuscular performance parameters such vertical jump capacity (i.e., squat and countermovement jump), agility and isometric strength were included in the analysis. Testing protocols that specifically assessed these parameters across morning (AM) and late afternoon/evening (PM) periods were considered were extracted from the selected studies.

Ten studies met the inclusion criteria for qualitative synthesis and five for quantitative synthesis. Meta-analysis indicated lower countermovement jump in the AM compared to with PM (mean difference, -1.44; 95% CI -2.80 to -0.08; p = 0.04) and higher agility performance (mean difference 0.42; 95% CI 0.09-0.74; p = 0.01) in PM comparing with AM. No differences were reported in isometric strength and squat jump performance (p > 0.05).

Neuromuscular performance is higher in the late afternoon or early evening compared to morning schedules in team sport athletes. Hence, time-of-day variations need to be considered when evaluating neuromuscular performance in professional and semi-professional team sports athletes.

Dex is a drug commonly used as an immunosuppressive and anti-inflammatory agent in humans and animals. GCs have a profound impact on melatonin expression and biological rhythm. However, the effect of chronic exposure to Dex on melatonin secretion and biological clock gene expression in ruminants is still unclear. Ten goats were randomly divided into two groups: the control group was injected with saline, and the Dex-treated group was intramuscularly injected daily for 21 d with 0.2 mg/kg Dex. The rhythm of melatonin secretion in the plasma was disturbed in the Dex group, and the plasma and colon levels of melatonin were lower in the Dex group compared to the control group (p < 0.05). Dex leads to a significant decrease in the expression of Arylalkylamine N-acetyltransferase (AANAT), a key melatonin synthase, in the pineal gland and colon. Detecting intestinal leakage-related indices showed that diamine oxidase (DAO) and lipopolysaccharide (LPS) content increased significantly in the Dex group (p < 0.05). We also detected genes associated with biological rhythms in the plasma. In the control group, the five tested genes showed circadian rhythms, but the circadian rhythms of Clock, Cry1, Cry2, and Per2 were abolished or blunted by the Dex (p < 0.05). Protein levels of CLOCK and BMAL1 in the colon changed significantly (p < 0.05). In conclusion, the above experimental results show that chronic exposure to Dex leads to the disorder of the circadian rhythms of melatonin secretion and clock genes.

This study evaluated the influence of melatonin supplementation on tissue's response of endodontic sealers in Wistar rats.

Forty-eight rats received subcutaneous implants of four polyethylene tubes: one empty (control) and three filled with endodontic sealers (AH Plus, Endofill and Sealapex). Half of the animals were supplemented with melatonin (ME) and the remaining treated with water (WA) for 15 days before the implantation until euthanasia, forming the groups: control-WA, AH Plus-WA, Endofill-WA, Sealapex-WA, Control-ME, AH Plus-ME, Endofill-ME and Sealapex-ME. After 5, 15 and 30 days, (n = 8) tubes were removed and evaluated in H&E., immunohistochemistry, PSR, VK and POL. The results were statistically analyzed (p < 0.05).

In animals treated with water, Endofill-WA evoked more intense inflammatory infiltrate compared to AH Plus-WA and Control-WA in a 30-day period (p < 0.05). In animals supplemented with melatonin, there was any difference among endodontic sealers' response in any period of analysis (p > 0.05). Comparing the individual response of each sealer, over a 30-day period, Endofill-ME and Sealapex-ME showed less inflammatory infiltrate compared to Endofill-WA and Sealapex-WA, respectively (p < 0.05). Immunostaining for IL-6 and TNF-α was less intense for all groups in animals supplemented with melatonin, in most periods, except for the Endofill sealer (p < 0.05). Furthermore, Endofill-ME at 5 days and AH-Plus-ME at 30 days showed a higher percentage of mature collagen fibers compared to the Endofill-WA and AH Plus-WA, respectively (p < 0.05). Positive structures for von Kossa staining and birefringent to polarized light were observed only for Sealapex-WA and Sealapex-ME in all periods.

It can be concluded that melatonin influences the tissue response to endodontic sealers, modulating the inflammatory and reparative process.

Light is a crucial factor influencing sleep arousal patterns. This meta-analysis investigates the efficacy of light therapy (LT) for insomnia treatment.

Five electronic databases were independently searched by two reviewers until August 2024. The literature screening focused specifically on populations with insomnia complaints treated by LT. Weighted Mean Difference (WMD) and 95% Confidence Interval (CI) were used as statistical tools, while the Cochrane Risk of Bias tool version 2 (RoB 2) was employed to assess the quality of evidence. A total of 10 randomized controlled trials (RCTs) were analyzed.

The results demonstrated that LT showed statistically significant improvements in subjective sleep quality, as evidenced by a reduction in Pittsburgh sleep quality scale (PSQI) scores by -2.89 (95% CI = -4.80 to -0.97) and Insomnia severity index (ISI) scores by -2.16 (95% CI = -4.23 to -0.08) post-intervention. Additionally, actigraphy revealed a statistically significant increase in total sleep time (TST) by 16.78 min (95% CI = 0.67 to 32.89) and a decrease in wake after sleep onset (WASO) by -12.91 min (95% CI = -25.62 to -0.20) by LT.

The preliminary results of the study suggest that LT has some efficacy in improving sleep quality in insomnia. However, it needs to be validated in future clinical trials with larger samples.

The incidence of early puberty in children has been increasing. It has been suspected that both genetic and various environmental factors such as nutrition and hormonal exposure could influence the mechanisms underlying the earlier onset of puberty. Interestingly, several previous studies have reported a strong connection between sleep and puberty. Specifically, it was discovered that luteinizing hormone (LH), a potential marker for the onset of puberty, was increased during the deep sleep period. Furthermore, a high prevalence of early puberty was observed in patients with sleep disorders, especially in those experiencing narcolepsy. In this review article, findings related to the association between sleep disturbance and early puberty have been comprehensively summarized. Any contrary findings are also included and discussed. Advances in the knowledge surrounding sleep disturbance have led to a greater understanding of a correlation between early puberty and sleep disorder and provide alternative therapeutic options for the treatment of central precocious puberty in the future.

Sleep deficiency is a common problem in the hospital setting. Contributing factors include preexisting medical conditions, illness severity, the hospital environment, and treatment-related effects. Hospitalized patients are particularly vulnerable to the negative health effects of sleep deficiency that impact multiple organ systems. Objective sleep measurement is difficult to achieve in the hospital setting, posing a barrier to linking improvements in hospital outcomes with sleep promotion protocols. Key next steps in hospital sleep promotion include improvement in sleep measurement techniques and harmonization of study protocols and outcomes to strengthen existing evidence and facilitate data interpretation across studies.

We aim to investigate the relationship between individuals' perceptions of their neighbourhood environment and early menarche.

This was a retrospective cohort study of 7,486 girls of Ethiopia, India, South Korea, the United Kingdom (UK), and the United States (US), born in 1997-2011 was analysed. Early menarche was defined as being below the 10th to 20th percentiles in each cohort, considering the varying distributions across countries. Perceived neighbourhood environments were assessed based on the responses for neighbourhood pollution, safety, and recreational facilities. We calculated the relative risk (RR) of early menarche for unfavourable environment.

The mean age at menarche was lowest in South Korea (10.6 years) and highest in Ethiopia (13.7 years). Unfavourable environment was associated with higher risk of early menarche overall (RR = 1.34, 95% confidence interval [CI]:1.09-1.65) and each country (3.03, 95% CI: 1.15-7.96 in Ethiopia; 1.99, 95% CI: 0.97-4.10 in India, 1.23, 95% CI: 0.67-2.27 in Korea; 1.26, 95% CI: 0.96-1.64 in the UK). Specifically, pollution (1.29, 95% CI: 1.03-1.62) and low safety (1.19, 95% CI: 1.60-1.88) were associated with early menarche.

Our finding highlights the potential role of perceived neighbourhood environment in the timing of puberty.

Melatonin, the primary hormone secreted by the pineal gland, regulates central and peripheral oscillators and adapts the internal environment to the external one through MT1 and MT2 receptors. The authors present a case of 16-year-old male intentionally overdosed on 900mg of melatonin (180 tablets) and 10 tablets of 0.5mg alprazolam. Admitted to the emergency department, he was extremely drowsy and minimally responsive with a Glasgow coma scale score of 8/15. Vital signs were stable, and no renal or liver dysfunction was noted. Elevated total leucocyte count and positive benzodiazepine urine test were observed. Gastric lavage was performed, and toxicology reports showed blood alprazolam levels at 0.15 mg/litre eight hours post-overdose. The patient regained consciousness 32 hours post-ingestion and was transferred to the psychiatry unit. This case underscores the increasing abuse of melatonin due to its easy availability and lack of regulation. Although melatonin has a low toxicity potential, side effects and interactions with other drugs can be severe. Supportive measures and vital sign control are crucial in overdose treatment.

Light exposure triggers a range of physiological and behavioural responses that can improve and challenge health and well-being. Insights from laboratory studies have recently culminated in standards and guidelines for measuring and assessing healthy light exposure, and recommendations for healthy light levels. Implicit to laboratory paradigms is a simplistic input-output relationship between light and its effects on physiology. This simplified approach ignores that humans actively shape their light exposure through behaviour. This article presents a novel framework that conceptualises light exposure as an individual behaviour to meet specific, person-based needs. Key to healthy light exposure is shaping behaviour, beyond shaping technology.

Metabolomics research provides a clearer understanding of an organism's metabolic state and enables a more accurate representation of its functional performance. This study aimed to investigate changes in the metabolome of lung tissues resulting from prenatal exposure to polystyrene microplastics (PS-MPs) and to understand the underlying mechanisms of lung damage in rat offspring. We conducted metabolomic analyses of lung tissue from seven-day-old rat pups exposed to prenatal PS-MPs. Our findings revealed that prenatal exposure to PS-MPs led to significantly increased oxidative stress in lung tissues, characterized by notable imbalances in nucleic acid metabolism and altered profiles of specific amino acids. Furthermore, we evaluated the therapeutic effects of melatonin treatment on lung function in 120-day-old offspring and found that melatonin treatment significantly improved lung function and histologic change in the affected offspring. This study provides valuable biological insights into the mechanisms underlying lung damage caused by prenatal PS-MPs exposure. Future studies should focus on validating the results of animal experiments in humans, exploring additional therapeutic mechanisms of melatonin, and developing suitable protocols for clinical use.

Melatonin (MLT) is a hormone that exists in all living organisms, including bacteria, yeast, fungi, animals, and plants, many of which are ingested daily in the diet. However, the exact concentrations of melatonin in each of the foods and the effect on health of the intake of foods rich in MLT are not known. Therefore, the aim of this review was to gather the available information on the melatonin content of different foods and to evaluate the effect that this hormone has on different pathologies. The amount of MLT may vary depending on the variety, origin, heat treatment, processing, and analysis technique, among other factors. Dietary interventions with foods rich in MLT report health benefits, but there is no evidence that hormone is partially responsible for the clinical improvement. Therefore, it is necessary to evaluate the MLT content in more foods, as well as the effect that cooking/processing has on the amount of MLT, to estimate its total intake in a typical diet and better explore its potential impact on the health.

Exogenous melatonin promotes the differentiation of secondary hair follicles in Cashmere goats, thereby improving cashmere production. MicroRNAs (miRNAs) play a crucial role in regulating post-transcriptional gene expression and influence hair follicle growth. However, the mechanism through which melatonin regulates hair follicle development via miRNA mediation remains unclear. In this study, we used RNA-seq to identify differentially expressed (DE) miRNAs during melatonin-induced growth of secondary hair follicles in inner Mongolian Cashmere goats. In total, 170 DE miRNAs were identified. Enrichment analysis revealed that the target genes of these DE miRNAs were related to biological processes such as protein modification; cytoskeletal components; and the Notch, Wnt, and MAPK signaling pathways. The miRNA-mRNA regulatory network suggested that the DE miRNA chi-let-7d-5p negatively regulates WNT2 expression. Mechanistic studies revealed that melatonin promotes the proliferation of DP cells in Cashmere goats via the chi-let-7d-5p/WNT2 axis.

Phytanic acid (PA) (3,7,11,15-tetramethylhexadecanoic acid) is a methyl-branched fatty acid that enters the body through food consumption, primarily through red meat, dairy products, and fatty marine foods. The metabolic byproduct of phytol is PA, which is then oxidized by the ruminal microbiota and some marine species. The first methyl group at the 3-position prevents the β-oxidation of branched-chain fatty acid (BCFA). Instead, α-oxidation of PA results in the production of pristanic acid (2,10,14-tetramethylpentadecanoic acid) with CO2. This fatty acid (FA) builds up in individuals with certain peroxisomal disorders and is historically linked to neurological impairment. It also causes oxidative stress in synaptosomes, as demonstrated by an increase in the production of reactive oxygen species (ROS), which is a sign of oxidative stress. This review concludes that the nutraceuticals (melatonin, piperine, quercetin, curcumin, resveratrol, epigallocatechin-3-gallate (EGCG), coenzyme Q10, ω-3 FA) can reduce oxidative stress and enhanced the activity of mitochondria. Furthermore, the use of nutraceuticals completely reversed the neurotoxic effects of PA on NO level and membrane potential. Additionally, the review further emphasizes the urgent need for more research into dairy-derived BCFAs and their impact on human health.

The blood-brain barrier and the blood-cerebrospinal fluid barrier separate the blood from brain tissue and cerebrospinal fluid. These brain barriers are important to maintain homeostasis and complex functions by protecting the brain from xenobiotics and harmful endogenous compounds. The disruption of brain barriers is a characteristic of neurologic diseases. Melatonin is a lipophilic hormone that is mainly produced by the pineal gland. The blood-brain barrier and the blood-cerebrospinal fluid barriers are melatonin-binding sites. Among the several melatonin actions, the most characteristic one is the regulation of sleep-wake cycles, melatonin has anti-inflammatory and antioxidant properties. Since brain barriers disruption can arise from inflammation and oxidative stress, knowing the influence of melatonin on the integrity of brain barriers is extremely important. Therefore, the objective of this review is to gather and discuss the available literature about the regulation of brain barriers by melatonin.

Previous studies have indicated a complex interplay between the nitric oxide (NO) pain signaling pathways and hormonal signaling pathways in the body. This article delineates the role of nitric oxide signaling in neuropathic and inflammatory pain generation and subsequently discusses how the neuroendocrine system is involved in pain generation. Hormonal systems including the hypothalamic-pituitary axis (HPA) generation of cortisol, the renin-angiotensin-aldosterone system, calcitonin, melatonin, and sex hormones could potentially contribute to the generation of nitric oxide involved in the sensation of pain. Further research is necessary to clarify this relationship and may reveal therapeutic targets involving NO signaling that alleviate neuropathic and inflammatory pain.

Consequences of the disease produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to an urgent search for preventive and therapeutic strategies. Besides drug treatments, proposals have been made for supplementation with biomolecules possessing immunomodulatory and antioxidant properties. The objective of this study was to review published evidence on the clinical usefulness of supplementation with vitamin D, antioxidant vitamins (vitamin A, vitamin E, and vitamin C), melatonin, lactoferrin and natural products found in food (curcumin, luteolin, ginger, allicin, magnesium and zinc) as supplements in SARS-CoV-2 infection. In general, supplementation of conventional treatments with these biomolecules has been found to improve the clinical symptoms and severity of the coronavirus disease (COVID-19), with some indications of a preventive effect. In conclusion, these compounds may assist in preventing and/or improving the symptoms of COVID-19. Nevertheless, only limited evidence is available, and findings have been inconsistent. Further investigations are needed to verify the therapeutic potential of these supplements.

Burnout among healthcare workers has been extensively studied since its initial recognition in 1960, with its defining characteristics established by Maslach in 1982. The syndrome, characterized by emotional exhaustion, depersonalization, and low personal accomplishment, is exacerbated by work-related stress and has profound implications for individual and societal well-being.

A review of the literature, including PubMed searches and analyses of risk factors and protective measures, was conducted to assess the prevalence, impacts, and biomarkers associated with burnout among healthcare workers. Various instruments for evaluating burnout were examined, including the widely used Maslach Burnout Inventory, alongside specific tools tailored to different occupational populations.

Healthcare workers, particularly physicians, exhibit significantly higher rates of burnout compared to the general population. Factors such as night shifts, workload, and exposure to biohazards contribute to elevated burnout risk. Biomarkers like cortisol, melatonin, and thyroid hormones have been linked to burnout, highlighting physiological implications.

Burnout poses significant challenges to healthcare systems globally, impacting patient care, worker retention, and overall well-being. Identifying and addressing risk factors while promoting protective factors such as resilience and social support are crucial in mitigating burnout. Further research into prevention strategies and biomarker monitoring is warranted to support the mental and physical health of healthcare workers.

Cluster headache (CH) is a common primary headache that severely impacts patients' quality of life, characterized by recurrent, severe, unilateral headaches often centered around the eyes, temples, or forehead. Distinguishing CH from other headache disorders is challenging, and its pathogenesis remains unclear. Notably, patients with CH often experience high levels of depression and suicidal tendencies, necessitating increased clinical attention. This comprehensive assessment combines various reports and the latest scientific literature to evaluate the current state of CH research. It covers epidemiology, population characteristics, predisposing factors, and treatment strategies. Additionally, we provide strategic insights into the holistic management of CH, which involves continuous, individualized care throughout the prevention, treatment, and rehabilitation stages. Recent advances in the field have revealed new insights into the pathophysiology of CH. While these findings are still evolving, they offer a more detailed understanding of the neurobiological mechanisms underlying this disorder. This growing body of knowledge, alongside ongoing research efforts, promises to lead to the development of more targeted and effective treatments in the future.

Melatonin, noted for its anti-cancer properties in various malignancies, including cutaneous melanoma, shows promise in Uveal melanoma (UM) treatment. This study aimed to evaluate melatonin receptor expression in primary UM and its association with UM-related mortality and prognostic factors. Immunohistochemical analysis of 47 primary UM tissues showed low expression of melatonin receptor 1A (MTNR1A) and melatonin receptor 1B (MTNR1B), with MTNR1A significantly higher in patients who succumbed to UM. Analysis of TCGA data from 80 UM patients revealed RNA expression for MTNR1A, retinoic acid-related orphan receptor alpha (RORα), and N-ribosyldihydronicotinamide:quinone oxidoreductase (NQO2), but not MTNR1B or G protein-coupled receptor 50 (GPR50). Higher MTNR1A RNA levels were observed in patients with a BRCA1 Associated Protein 1 (BAP1) mutation, and higher NQO2 RNA levels were noted in patients with the epithelioid tumor cell type. However, Kaplan-Meier analysis did not show distinct survival probabilities based on receptor expression. This study concludes that UM clinical samples express melatonin receptors, suggesting a potential mechanism for melatonin's anti-cancer effects. Despite finding higher MTNR1A expression in patients who died of UM, no survival differences were observed.

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.

Melatonin, a pineal gland hormone closely associated with the circadian rhythm, has been trending over the past years as an over-the-counter medication to aid with sleep disturbances. Although generally believed to be safe, recent studies show negative inotropic and chronotropic effects on the heart rate and blood pressure in humans. Several studies suggested that melatonin induces cardiac vagal tone and affects heart rate and mean arterial pressure. Limited literature is currently available on the effects of melatonin beyond its sleep function. We present a case of a healthy 22-year-old male who visited the emergency department reporting palpitations and dizziness following the ingestion of 20 mg of melatonin. Subsequent examinations revealed marked bradycardia. Fortunately, the patient experienced spontaneous resolution of the bradycardia without necessitating intervention after a few hours of observation, and he was observed and discharged.

The age-related alterations in pituitary function, including changes in prolactin (PRL) production contributes to the systemic susceptibility to age-related diseases. Our previous research has shown the involvement of Nrg1 in regulating the expression and secretion of PRL. However, the precise role of Nrg1 in mitigating the senescence of pituitary lactotrophs and the underlying mechanisms are yet to be comprehended. Here, data from the GEPIA database was used to evaluate the association between transient receptor potential cation channel subfamily M member 8 (TRPM8) and PRL in normal human pituitary tissues, followed by immunofluorescence verification using a human pituitary tissue microarray. TRPM8 levels showed a significant positive association with PRL expression in normal human pituitary tissues, and both TRPM8 and PRL levels declined during aging, suggesting that TRPM8 may regulate pituitary aging by affecting PRL production. It was also found that treatment with exogenous neuregulin 1 (Nrg1) markedly delayed the senescence of GH3 cells (rat lactotroph cell line) generated by D-galactose (D-gal). In addition, melatonin reduced the levels of senescence-related markers in senescent pituitary cells by promoting Nrg1 / ErbB4 signaling, stimulating PRL expression and secretion. Further investigation showed that Nrg1 attenuated senescence in pituitary cells by increasing TRPM8 expression. Downregulation of TRPM8 activation eliminated Nrg1-mediated amelioration of pituitary cell senescence. These findings demonstrate the critical function of Nrg1 / ErbB signaling in delaying pituitary lactotroph cell senescence and enhancing PRL production via promoting TRPM8 expression under the modulation of melatonin.

Previous studies have demonstrated that the hippocampus, a crucial region for memory and cognitive functions, is particularly vulnerable to adverse effects of exposure to heavy metals. Nickel (Ni) is a neurotoxic agent that, primarily induces oxidative stress, a process known to contribute to cellular damage, which consequently affects neurological functions. The antioxidant properties of melatonin are a promising option for preventing the adverse effects of Ni, especially by protecting cells against oxidative stress and related damage. In our investigation of the potential neuroprotective effects of melatonin against Ni-induced neurotoxicity, we chose to administer melatonin through intraperitoneal injection in rats following an intrahippocampal injection of Ni into the left hippocampus. This approach allows us a targeted investigation into the influence of melatonin on the neurotoxic effects of Ni, particularly within the crucial context of the hippocampus. In the present study, we demonstrated that melatonin efficiency reduced lactate dehydrogenase level, and preserved antioxidant enzyme activities in Ni-exposed hippocampal tissue. It also mitigated the decline in superoxide dismutase and catalase activities. On the other hand, melatonin could act directly by reducing reactive oxygen species Ni-induced overproduction. Taking to gather these two potential mechanisms of action could be responsible for the adverse effect of Ni on the behavioral alteration observed in our study. This study provides significant insights into the potential of melatonin to mitigate the detrimental effects of Ni on the brain, particularly into the hippocampal region, suggesting its possible implications for the treatment of neurological disorders related to Ni exposure.

Plasmodium, a digenetic parasite, requires a host and a vector for its life cycle completion. Most Plasmodium species display circadian rhythmicity during their intraerythrocytic cycle within the host, aiding in immune evasion. This rhythmicity, however, diminishes in in vitro cultures, highlighting the importance of host-derived signals for synchronizing the parasite's asexual cycle. Studies indicate a species-specific internal clock in Plasmodium, dependent on these host signals. Melatonin, a hormone the pineal gland produces under circadian regulation, impacts various physiological functions and is extensively reviewed as the primary circadian marker affecting parasite rhythms. Research suggests that melatonin facilitates synchronization through the PLC-IP3 signaling pathway, activating phospholipase C, which triggers intracellular calcium release and gene expression modulation. This evidence strongly supports the role of melatonin as a key circadian marker for parasite synchronization, presenting new possibilities for targeting the melatonin pathway when developing novel therapeutic approaches.