Exogenous melatonin enhances the continuous cropping tolerance of Tartary buckwheat (Fagopyrum tataricum) by regulating the antioxidant defense system.

The yield of Tartary buckwheat is significantly affected by continuous cropping. Melatonin plays a crucial role in plant defense mechanisms against abiotic stresses. However, the relationship between melatonin and continuous cropping tolerance remains unclear. This study aimed to analyze the physiological mechanism of melatonin in enhancing the continuous cropping tolerance (abiotic stress) of Tartary buckwheat. A field experiment was conducted on Tartary buckwheat cultivar Jinqiao 2 under continuous cropping with five melatonin application rates, 0 (Control), 10, 50, 100, and 200 µmol L-1, applied during the early budding stage. The chlorophyll content, antioxidant enzyme activity, osmolyte and auxin (IAA) contents, root activity, rhizosphere soil nutrient content, and agronomic traits of Tartary buckwheat initially increased and then decreased with an increase in the concentration of exogenous melatonin application, with the best effects observed at 100 µmol L-1. Compared with the Control treatment, the 100 µmol L-1 treatment decreased the contents of malondialdehyde, superoxide anion free radical, and abscisic acid (ABA) by an average of 28.79%, 27.08%, and 31.64%, respectively. Exogenous melatonin treatment significantly increased the yield of Tartary buckwheat under continuous cropping. Plants treated with 10, 50, 100, and 200 µM respectively had 1.88, 2.01, 2.20, and 1.78 times higher yield than those of the Control treatment. In summary, melatonin treatment, particularly 100 µmol L-1, enhanced the continuous cropping tolerance of Tartary buckwheat by increasing antioxidant capacity and osmotica content, coordinating endogenous ABA and IAA content levels, and delaying senescence, ultimately increasing yield.

Melatonin facilitates oocyte growth in goats and mice through increased nutrient reserves and enhanced mitochondrial function.

Oogenesis involves two phases: initial volumetric growth driven by nutrient accumulation and subsequent nuclear maturation. While melatonin (MLT) has been employed as a supplement to enhance the quality of fully grown oocytes during nuclear maturation phase, its impact on oocyte growth remains poorly studied. Here, we provide in vivo evidence demonstrating that follicle-stimulating hormone increases MLT content in ovary. Administration of MLT improves oocyte growth and quality in mice and goats by enhancing nutrient reserves and mitochondrial function. Conversely, MLT-deficient mice have smaller oocytes and dysfunctional mitochondria. Exploring the clinical implications of MLT in promoting oocyte growth, we observe that a brief 2-day MLT treatment enhances oocyte quality and reproductive performance in older mice. These findings highlight the role of MLT in regulating oocyte growth and provide a specific treatment window for optimizing oocyte quality and reproductive performance in female animals.

Clock protein LHY targets SNAT1 and negatively regulates the biosynthesis of melatonin in Hypericum perforatum.

Hypericum perforatum, also known as "natural fluoxetine," is a commonly used herbal remedy for treating depression. It is unclear whether melatonin in plants regulated by the endogenous circadian clock system is like in vertebrates. In this work, we found that the melatonin signal and melatonin biosynthesis gene, serotonin N-acetyltransferase HpSNAT1, oscillates in a 24-hour cycle in H. perforatum. First, we constructed a yeast complementary DNA library of H. perforatum and found a clock protein HpLHY that can directly bind to the HpSNAT1 promoter. Second, it was confirmed that HpLHY inhibits the expression of HpSNAT1 by targeting the Evening Element. Last, it indicated that HpLHY-overexpressing plants had reduced levels of melatonin in 12-hour light/12-hour dark cycle photoperiod, while loss-of-function mutants exhibited high levels, but this rhythm seems to disappear as well. The results revealed the regulatory role of LHY in melatonin biosynthesis, which may make an important contribution to the field of melatonin synthesis regulation.

A Protocol to Determine Circadian Phase by At-Home Salivary Dim Light Melatonin Onset Assessment.

Internal circadian phase assessment is increasingly acknowledged as a critical clinical tool for the diagnosis, monitoring, and treatment of circadian rhythm sleep-wake disorders and for investigating circadian timing in other medical disorders. The widespread use of in-laboratory circadian phase assessments in routine practice has been limited, most likely because circadian phase assessment is not required by formal diagnostic nosologies, and is not generally covered by insurance. At-home assessment of salivary dim light melatonin onset (DLMO, a validated circadian phase marker) is an increasingly accepted approach to assess circadian phase. This approach may help meet the increased demand for assessments and has the advantages of lower cost and greater patient convenience. We reviewed the literature describing at-home salivary DLMO assessment methods and identified factors deemed to be important to successful implementation. Here, we provide specific protocol recommendations for conducting at-home salivary DLMO assessments to facilitate a standardized approach for clinical and research purposes. Key factors include control of lighting, sampling rate, and timing, and measures of patient compliance. We include findings from implementation of an optimization algorithm to determine the most efficient number and timing of samples in patients with Delayed Sleep-Wake Phase Disorder. We also provide recommendations for assay methods and interpretation. Providing definitive criteria for each factor, along with detailed instructions for protocol implementation, will enable more widespread adoption of at-home circadian phase assessments as a standardized clinical diagnostic, monitoring, and treatment tool.

LncRNA018392 promotes the proliferation of Liaoning cashmere goat skin fibroblasts by upregulating CSF1R through binding to SPI1.

BACKGROUND: Liaoning cashmere goat is recognized as a valuable genetic resource breed, with restrictions on genetic outflow in China. Hair follicle development in the cashmere goat is influenced by melatonin and long non-coding RNAs (lncRNAs). However, the role of lncRNAs in facilitating melatonin-promoted cashmere growth remains poorly understood. Previous studies have identified a new lncRNA, lncRNA018392, which is involved in the melatonin-promoted proliferation of cashmere skin fibroblasts. METHOD: Flow cytometry and CCK-8 assays confirmed that silencing lncRNA018392 negates the effects of melatonin on cell proliferation, and that proliferation was reduced when the gene CSF1R, located near lncRNA018392, was inhibited. Further investigation using a dual-luciferase reporter assay showed that lncRNA018392 could positively regulate the promoter of CSF1R. RESULTS: Results from RNA-binding protein immunoprecipitation (RIP) and chromatin immunoprecipitation sequencing (ChIP-Seq) revealed that lncRNA018392 interacts with the transcription factor SPI1, with CSF1R being a downstream target gene regulated by SPI1. This interaction was confirmed by ChIP-PCR, which demonstrated SPI1's binding to CSF1R. CONCLUSIONS: This study found that the melatonin-responsive lncRNA018392 accelerates the cell cycle and promotes cell proliferation by recruiting SPI1 to upregulate the expression of the neighboring gene CSF1R. These findings provide a theoretical foundation for elucidating the molecular mechanisms of cashmere growth and for the molecular breeding of cashmere goats.

Melatonin Priming Promotes Crop Seed Germination and Seedling Establishment Under Flooding Stress by Mediating ABA, GA, and ROS Cascades.

Both seed germination and subsequent seedling establishment are key checkpoints during the life cycle of seed plants, yet flooding stress markedly inhibits both processes, leading to economic losses from agricultural production. Here, we report that melatonin (MT) seed priming treatment enhances the performance of seeds from several crops, including soybean, wheat, maize, and alfalfa, under flooding stress. Transcriptome analysis revealed that MT priming promotes seed germination and seedling establishment associated with changes in abscisic acid (ABA), gibberellin (GA), and reactive oxygen species (ROS) biosynthesis and signaling pathways. Real-time quantitative RT-PCR (qRT-PCR) analysis confirmed that MT priming increases the expression levels of GA biosynthesis genes, ABA catabolism genes, and ROS biosynthesis genes while decreasing the expression of positive ABA regulatory genes. Further, measurements of ABA and GA concentrations are consistent with these trends. Following MT priming, quantification of ROS metabolism-related enzyme activities and the concentrations of H2O2 and superoxide anions (O2 -) after MT priming were consistent with the results of transcriptome analysis and qRT-PCR. Finally, exogenous application of GA, fluridone (an ABA biosynthesis inhibitor), or H2O2 partially rescued the poor germination of non-primed seeds under flooding stress. Collectively, this study uncovers the application and molecular mechanisms underlying MT priming in modulating crop seed vigor under flooding stress.

YTHDF3 Regulates the Degradation and Stability of m6A-Enriched Transcripts to Facilitate the Progression of Castration-Resistant Prostate Cancer.

RNA N6-methyladenosine (m6A) readers mediate cancer progression. However, the functional role and potential mechanisms of the m6A readers in prostate cancer tumorigenicity remain to be elucidated. In this study, we demonstrate that YTHDF3 expression is elevated in castration-resistant prostate cancer (CRPC) and positively correlated to high grade, bone metastasis and poor survival. YTHDF3 expression promoted CRPC cell proliferation, epithelial to mesenchymal transition (EMT) and tumour progression. Mechanistically, YTHDF3 promoted the RNA degradation of SPOP and NXK3.1 but stabilized RNA expressions of TWIST1 and SNAI2 dependent on m6A to facilitate cell proliferation and EMT. Additionally, YTHDF3 expression enhanced AKT activity via degrading SPOP in an m6A-dependent manner. Importantly, we found that melatonin can compete with m6A to occupy the m6A-binding cage of YTHDF3, leading to inhibition of YTHFD3 and its target expressions as well as CRPC tumour growth. Our findings uncover an essential role of YTHDF3 in the progression of CRPC and highlight the role of melatonin in anti-CRPC activity.

KARS Mutations Impair Brain Myelination by Inducing Oligodendrocyte Deficiency: One Potential Mechanism and Improvement by Melatonin.

It is very crucial to investigate key molecules that are involved in myelination to gain an understanding of brain development and injury. We have reported for the first time that pathogenic variants p.R477H and p.P505S in KARS, which encodes lysyl-tRNA synthetase (LysRS), cause leukoencephalopathy with progressive cognitive impairment in humans. The role and action mechanisms of KARS in brain myelination during development are unknown. Here, we first generated Kars knock-in mouse models through the CRISPR-Cas9 system. Kars knock-in mice displayed significant cognitive deficits. These mice also showed significantly reduced myelin density and content, as well as significantly decreased myelin thickness during development. In addition, Kars mutations significantly induced oligodendrocyte differentiation arrest and reduction in the brain white matter of mice. Mechanically, oligodendrocytes' significantly imbalanced expression of differentiation regulators and increased capase-3-mediated apoptosis were observed in the brain white matter of Kars knock-in mice. Furthermore, Kars mutations significantly reduced the aminoacylation and steady-state level of mitochondrial tRNALys and decreased the protein expression of subunits of oxidative phosphorylation complexes in the brain white matter. Kars knock-in mice showed decreased activity of complex IV and significantly reduced ATP production and increased reactive oxygen species in the brain white matter. Significantly increased percentages of abnormal mitochondria and mitochondrion area were observed in the oligodendrocytes of Kars knock-in mouse brain. Finally, melatonin (a mitochondrion protectant) significantly attenuated mitochondrion and oligodendrocyte deficiency in the brain white matter of KarsR504H/P532S mice. The mice treated with melatonin also showed significantly restored myelination and cognitive function. Our study first establishes Kars knock-in mammal models of leukoencephalopathy and cognitive impairment and indicates important roles of KARS in the regulation of mitochondria, oligodendrocyte differentiation and survival, and myelination during brain development and application prospects of melatonin in KARS (or even aaRS)-related diseases.

Melatonin targets the paraventricular thalamus to promote non-rapid eye movement sleep in C3H/HeJ mice.

Melatonin (MLT) is an important circadian signal for sleep regulation, but the neural circuitries underlying the sleep-promoting effects of MLT are poorly understood. The paraventricular thalamus (PVT) is a critical thalamic area for wakefulness control and expresses MLT receptors, raising a possibility that PVT neurons may mediate the sleep-promoting effects of MLT. Here, we found that MLT receptors were densely expressed on PVT neurons and exhibited circadian-dependent variations in C3H/HeJ mice. Application of exogenous MLT decreased the excitability of PVT neurons, resulting in hyperpolarization of membrane potential and reduction of action potential firing. MLT also inhibited the spontaneous activity of PVT neurons at both population and single-neuron levels in freely behaving mice. Furthermore, pharmacological manipulations revealed that local infusion of exogeneous MLT into the PVT promoted non-rapid eye movement (NREM) sleep and increased NREM sleep duration, whereas MLT receptor antagonists decreased NREM sleep. Moreover, we found that selectively knocking down endogenous MLT receptors in the PVT decreased NREM sleep and correspondingly increased wakefulness, with particular changes shortly after the onset of the dark or light phase. Taken together, these results demonstrate that PVT is an important target of MLT for promoting NREM sleep.

Melatonin mitigates drought stress by increasing sucrose synthesis and suppressing abscisic acid biosynthesis in tomato seedlings.

The increasing prevalence of drought events poses a major challenge for upcoming crop production. Melatonin is a tiny indolic tonic substance with fascinating regulatory functions in plants. While plants can respond in several ways to alleviate drought stress, the processes underpinning stress sensing and signaling are poorly understood. Hereafter, the objectives of this investigation were to explore the putative functions of melatonin in the regulation of sugar metabolism and abscisic acid biosynthesis in drought-stressed tomato seedlings. Melatonin (100 µM) and/or water were foliar sprayed, followed by the plants being imposed to drought stress for 14 days. Drought stress significantly decreased biomass accumulation, inhibited photosynthetic activity, and stimulated senescence-associated gene 12 (SAG12) expression. Melatonin treatment effectively reversed drought-induced growth retardation as evidenced by increased leaf pigment and water balance and restricted abscisic acid (ABA) accumulation. Sugar accumulation, particularly sucrose content, was higher in drought-imposed seedlings, possibly owing to higher transcription levels of sucrose non-fermenting 1-related protein kinase 2 (SnKR2.2) and ABA-responsive element binding factors 2 (AREB2). Melatonin addition further uplifted the sucrose content, which coincided with increased activity of sucrose synthase (SS, 130%), sucrose phosphate synthase (SPS, 137%), starch degradation encoding enzyme ß-amylase (BAM, 40%) and α-amylase (AMY, 59%) activity and upregulated their encoding BAM1(10.3 folds) and AMY3 (8.1 folds) genes expression at day 14 relative to the control. Under water deficit conditions, melatonin supplementation decreased the ABA content (24%) and its biosynthesis gene expressions. Additionally, sugar transporter subfamily genes SUT1 and SUT4 expression were upregulated by the addition of melatonin. Collectively, our findings illustrate that melatonin enhances drought tolerance in tomato seedlings by stimulating sugar metabolism and negatively regulating ABA synthesis.

METHIONINE SULFOXIDE REDUCTASE A AND NEUROTRANSMISSION ENZYMES IN AUTISM SPECTRUM DISORDER AND DYSTOCIA RELATED AUTISTICS.

Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme that repairs the oxidation of methionine residues in proteins and free methionine in autism spectrum disorder (ASD). The present study aimed to assess the level of MsrA and neurotransmission enzymes in ASD individuals. Results confirmed that ASD associated with significant (P<0.05) reduction of MsrA and modulated mission enzymes. The role of MsrA as repair enzyme should be taken into account for study the activity of brain enzymes and proteins in ASD including ASMT that has a role in melatonin problems production in ASD due to higher AANAT level. The influence of MsrA also should be studied with MAT in mice to give more evidence.

Melatonin alleviates UV-B stress and enhances phenolic biosynthesis in rosemary (Rosmarinus officinalis) callus.

Although used in in vitro culture to boost secondary metabolite production, UV-B radiation can seriously affect plant growth if not properly dosed. Rosemary callus can be used as an important source of effective ingredients in the food and medicine industry. To balance the positive and negative effects of UV-B on rosmary callus, this study investigated the effects of melatonin on rosemary callus under UV-B radiation. The results showed that melatonin improved rosemary callus growth, with fresh weight and dry weight increased by 15.81% and 8.30%, respectively. The addition of 100 µM melatonin increased antioxidant enzyme activity and NO content in rosemary callus. At the same time, melatonin also significantly reduced membrane lipid damage and H2O2 accumulation in rosemary callus under UV-B stress, with malondialdehyde (MDA) and H2O2 contents reduced by 13.03% and 14.55%, respectively. In addition, melatonin increased the total phenol and rosmarinic acid contents in rosemary callus by 19% and 54%, respectively. Melatonin significantly improved the antioxidant activity of the extracts from rosemary callus. These results suggest that exogenous melatonin can alleviate the adverse effects of UV-B stress on rosemary callus by promoting NO accumulation while further enhancing phenolic accumulation and biological activity.

Blunted Melatonin Circadian Rhythm in Parkinson's Disease: Express Bewilderment.

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.

Exploring the association between melatonin and nicotine dependence (Review).

Due to the addictive qualities of tobacco products and the compulsive craving and dependence associated with their use, nicotine dependence continues to be a serious public health concern on a global scale. Despite awareness of the associated health risks, nicotine addiction contributes to numerous acute and chronic medical conditions, including cardiovascular disease, respiratory disorders and cancer. The nocturnal secretion of pineal melatonin, known as the 'hormone of darkness', influences circadian rhythms and is implicated in addiction­related behaviors. Melatonin receptors are found throughout the brain, influencing dopaminergic neurotransmission and potentially attenuating nicotine­seeking behavior. Additionally, the antioxidant properties of melatonin may mitigate oxidative stress from chronic nicotine exposure, reducing cellular damage and lowering the risk of nicotine­related health issues. In addition to its effects on circadian rhythmicity, melatonin acting via specific neural receptors influences sleep and mood, and provides neuroprotection. Disruptions in melatonin signaling may contribute to sleep disturbances and mood disorders, highlighting the potential therapeutic role of melatonin in addiction and psychiatric conditions. Melatonin may influence neurotransmitter systems involved in addiction, such as the dopaminergic, glutamatergic, serotonergic and endogenous opioid systems. Preclinical studies suggest the potential of melatonin in modulating reward processing, attenuating drug­induced hyperactivity and reducing opioid withdrawal symptoms. Chronotherapeutic approaches targeting circadian rhythms and melatonin signaling show promise in smoking cessation interventions. Melatonin supplementation during periods of heightened nicotine cravings may alleviate withdrawal symptoms and reduce the reinforcing effects of nicotine. Further research is required however, to examine the molecular mechanisms underlying the melatonin­nicotine association and the optimization of therapeutic interventions. Challenges include variability in individual responses to melatonin, optimal dosing regimens and identifying biomarkers of treatment response. Understanding these complexities could lead to personalized treatment strategies and improve smoking cessation outcomes.

Melatonin-Nitric Oxide Crosstalk in Plants and the Prospects of NOMela as a Nitric Oxide Donor.

Melatonin regulates vital physiological processes in animals, such as the circadian cycle, sleep, locomotion, body temperature, food intake, and sexual and immune responses. In plants, melatonin modulates seed germination, longevity, circadian cycle, photoperiodicity, flowering, leaf senescence, postharvest fruit storage, and resistance against biotic and abiotic stresses. In plants, the effect of melatonin is mediated by various regulatory elements of the redox network, including RNS and ROS. Similarly, the radical gas NO mediates various physiological processes, like seed germination, flowering, leaf senescence, and stress responses. The biosynthesis of both melatonin and NO takes place in mitochondria and chloroplasts. Hence, both melatonin and nitric oxide are key signaling molecules governing their biological pathways independently. However, there are instances when these pathways cross each other and the two molecules interact with each other, resulting in the formation of N-nitrosomelatonin or NOMela, which is a nitrosated form of melatonin, discovered recently and with promising roles in plant development. The interaction between NO and melatonin is highly complex, and, although a handful of studies reporting these interactions have been published, the exact molecular mechanisms governing them and the prospects of NOMela as a NO donor have just started to be unraveled. Here, we review NO and melatonin production as well as RNS-melatonin interaction under normal and stressful conditions. Furthermore, for the first time, we provide highly sensitive, ozone-chemiluminescence-based comparative measurements of the nitric oxide content, as well as NO-release kinetics between NOMela and the commonly used NO donors CySNO and GSNO.

Melatonin and Seasonal Synchrony in Mammals.

In mammals, seasonal opportunities and challenges are anticipated through programmed changes in physiology and behavior. Appropriate anticipatory timing depends on synchronization to the external solar year, achieved through the use of day length (photoperiod) as a synchronizing signal. In mammals, nocturnal production of melatonin by the pineal gland is the key hormonal mediator of photoperiodic change, exerting its effects via the hypothalamopituitary axis. In this review/perspective, we consider the key developments during the history of research into the seasonal synchronizer effect of melatonin, highlighting the role that the pars tuberalis-tanycyte module plays in this process. We go on to consider downstream pathways, which include discrete hypothalamic neuronal populations. Neurons that express the neuropeptides kisspeptin and (Arg)(Phe)-related peptide-3 (RFRP-3) govern seasonal reproductive function while neurons that express somatostatin may be involved in seasonal metabolic adaptations. Finally, we identify several outstanding questions, which need to be addressed to provide a much thorough understanding of the deep impact of melatonin upon seasonal synchronization.

Engineering a GPCR-based yeast biosensor for a highly sensitive melatonin detection from fermented beverages.

Melatonin is a multifunctional molecule with diverse biological roles that holds great value as a health-promoting bioactive molecule in any food product and yeast's ability to produce it has been extensively demonstrated in the last decade. However, its quantification presents costly analytical challenges due to the usual low concentrations found as the result of yeast metabolism. This study addresses these analytical challenges by optimizing a yeast biosensor based on G protein-coupled receptors (GPCR) for melatonin detection and quantitation. Strategic genetic modifications were employed to significantly enhance its sensitivity and fluorescent signal output, making it suitable for detection of yeast-produced melatonin. The optimized biosensor demonstrated significantly improved sensitivity and fluorescence, enabling the screening of 101 yeast strains and the detection of melatonin in various wine samples. This biosensor's efficacy in quantifying melatonin in yeast growth media underscores its utility in exploring melatonin production dynamics and potential applications in functional food development. This study provides a new analytical approach that allows a rapid and cost-effective melatonin analysis to reach deeper insights into the bioactivity of melatonin in fermented products and its implications for human health. These findings highlight the broader potential of biosensor technology in streamlining analytical processes in fermentation science.

Melatonin Receptor Expression in Primary Uveal Melanoma.

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.

The Physiological Impact of Melatonin, Its Effect on the Course of Diseases and Their Therapy and the Effect of Magnetic Fields on Melatonin Secretion-Potential Common Pathways of Influence.

Melatonin is a relic, due to its millions-of-years-old presence in chemical reactions, found in evolutionarily diverse organisms. It has a multidirectional biological function. It controls diurnal rhythms, redox homeostasis, intestinal motor functions, mitochondrial biogenesis and fetal development and has antioxidant effects. It also has analgesic and therapeutic effects. The purpose of this paper is to describe the role of melatonin in vital processes occurring in interaction with the environment, with particular reference to various magnetic fields ubiquitous in the life of animate matter, especially radio frequency/extra low frequency (RF/ELF EMF) and static magnetic fields. The most important part of this article is to describe the potential effects of magnetic fields on melatonin secretion and the resulting possible health effects. Melatonin in some cases positively amplifies the electromagnetic signal, intensifying health effects, such as neurogenesis, analgesic effects or lowering blood pressure. In other cases, it is a stimulus that inhibits the processes of destruction and aggravation of lesions. Sometimes, however, in contrast to the beneficial effects of electromagnetic fields in therapy, they intensify pathogenic effects, as in multiple sclerosis by intensifying the inflammatory process.

Bioactive Peptides in Dairy Milk: Highlighting the Role of Melatonin.

Melatonin, an endogenous indolamine derived from tryptophan, is primarily synthesized by the pineal gland in mammals and regulated by a complex neural system. Its release follows a circadian rhythm, which is crucial for regulating physiological processes in response to light-dark cycles in both humans and animals. In this review, we report that the presence of this hormone in bovine milk, with significant differences in concentration between daytime and nighttime milking, has increased interest in milk as a natural source of bioactive molecules. Melatonin lowers cortisol levels at night, reduces body temperature and blood pressure, coinciding with decreased alertness and performance, acts as an antioxidant and anti-inflammatory agent, modulates the immune system, offers neuroprotective benefits, and supports gastrointestinal health by scavenging free radicals and reducing oxidative stress in dairy cows. Many factors influence the release of melatonin, such as the intensity of artificial lighting during nighttime milking, the frequency of milkings, milk yield, and genetic differences between animals. Nocturnal milking under low-intensity light boosts melatonin, potentially reducing oxidative damage and mastitis risk. Additionally, ultra-high temperature (UHT) treatment does not significantly affect the melatonin content in milk. However, further research on its stability during milk processing and storage is crucial for ensuring product efficacy. In some countries, nighttime milk with naturally elevated melatonin content is already commercialized as a natural aid for sleep. Thus, naturally melatonin-rich milk may be a promising alternative to synthetic supplements for promoting better sleep and overall well-being.