Melatonin Synthesis Research Articles

Hydrogen peroxide mediates melatonin-induced chilling tolerance in cucumber seedlings.

MT mitigates chilling damage by enhancing antioxidant system and photosystem activities, and cold-responsive genes expression in cucumbers. H2O2 may act as a downstream signaling molecule in the MT-induced chilling tolerance. Melatonin (MT) and hydrogen peroxide (H2O2) are important endogenous signaling molecules that play multifaceted roles in plant responses to abiotic stress. However, the interactive mechanism by which MT and H2O2 regulate chilling tolerance remains unclear. Here we found that MT exhibited a positive regulatory effect on the chilling tolerance of cucumbers, with an optimum concentration of 100µM. MT markedly enhanced RBOH1 mRNA expression, activity and endogenous H2O2 accumulation in cucumber seedlings. However, 1.0mM H2O2 had no significant effect on mRNA levels of TDC and ASMT, the key genes for MT synthesis, and endogenous MT content. Both MT and H2O2 significantly decreased malondialdehyde (MDA), electrolyte leakage (EL) and chilling injury index (CI) by activating the antioxidant system, thereby alleviating chilling damage in cucumber seedlings. MT and H2O2 improved photosynthetic carbon assimilation, which was primarily attributed to an increase in activity, mRNA expression, and protein levels of RuBPCase and RCA. Meanwhile, MT and H2O2 induced the photoprotection for both PSII and PSI by enhancing the QA's electron transport capacity and elevating protein levels of the photosystems. Moreover, MT and H2O2 significantly upregulated the expression of cold response genes. MT-induced chilling tolerance was attenuated by N', N'-dimethylthiourea (DMTU), a H2O2 specific scavenger. Whereas, the MT synthesis inhibitor (p-chlorophenylalanine, p-CPA) did not influence H2O2-induced chilling tolerance. The positive regulation of MT on the antioxidant system, photosynthesis and cold response gene levels were significantly attenuated in RBOH1-RNAi plants compared with WT plants. These findings suggest that H2O2 may functions as a downstream signaling molecule in MT-induced chilling tolerance in cucumber plants.

The Physiological and Pharmacological Roles of Melatonin and Pregabalin

Melatonin and pregabalin are two important compounds that are broadly used in the fields of physiological and medicinal sciences. Melatonin is a primary hormone mainly secreted by the pineal gland and plays an important role in regulating circadian rhythms, sleep-wake cycles, and neuroimmune processes. Its strong antioxidant anti-inflammatory and anti-apoptotic properties have protected it against a wide range of diseases, from cancer to neurological disorders. In this study, the synthesis of melatonin will be widely studied, mainly regarding its role in regulating circadian rhythms and sleep, and its possible therapeutic use in treating neurological diseases and inflammation-related disorders. Pregabalin is an analog of the neurotransmitter gamma-aminobutyric acid (GABA), with anticonvulsant, analgesic, and anxiolytic actions. Clinical practice has widely utilized it because studies indicate that it is useful in treating a variety of conditions: fibromyalgia, epilepsy, neuropathic pain, and generalized anxiety disorder. This article reviews aspects of the pharmacokinetics of pregabalin, its useful functions in pain treatment, and its impact on calcium channel regulation. The review also discusses indications of pregabalin in therapy, along with its possible side effects. This review article aims to consider the molecular processes underlying the activities of melatonin and pregabalin and their therapeutic potential for the management of sleep disorders, inflammation, and neurological diseases to future use of these compounds clinically.

Integrative DNA methylome and transcriptome analysis illuminate leaf phenotype alterations in tetraploid citrus

Whole-genome duplication (WGD) in plants triggers profound morphological and physiological changes, with DNA modification being a key epigenetic factor that helps neo-polyploids overcome challenges and gain adaptive advantages. Tetraploids were previously mined from diploid citrus seedlings, showing enhanced environmental adaptability and potential as rootstocks. These tetraploids exhibited increased leaf and cell wall thickness compared to their diploid counterparts. To explore the impact of WGD, transcriptomic and whole-genome bisulfite sequencing (WGBS) were conducted on two pairs of citrus tetraploids and their diploid controls, revealing significant molecular changes. Notably, tetraploid citrus displayed lower CG methylation levels in gene and transposable element (TE) bodies relative to diploids. Differentially methylated genes (DMGs) between tetraploids and diploids were primarily associated with immune stress, organ development, metabolic pathways, and secondary metabolism. In Trifoliate orange (Poncirus trifoliata L. Raf.) and Ziyang Xiangcheng (Citrus junos Sieb. ex Tanaka), only 150 and 58 differentially expressed genes (DEGs) were identified, respectively, with enrichment in critical cellular processes such as cell wall synthesis, plastid development, and pathways modulating chloroplasts and plasma membranes. A total of 70 genes showed both differential methylation and expression, including ACN1, Nac036, and ASMT1, which are involved in stomatal development, leaf morphology, and melatonin synthesis, respectively, offering insight into the regulatory mechanisms of phenotype alterations after polyploidization. These findings reveal the epigenetic modifications in polyploid citrus and highlight the role of polyploidization-induced methylation in driving phenotypic changes.

Gut Bacterial Metabolites from Tryptophan and Phenylalanine Induce Melatonin Synthesis and Extend Sleep Duration in Mice.

The human gut microbiota significantly influences various physiological systems, including immune, nervous, and metabolic systems. Recent studies suggest that gut microbiota may affect sleep quality with certain bacteria and metabolites being linked to sleep patterns. However, the underlying chemical signaling pathway remains unclear. In this study, we investigated the effect of four gut bacteria-derived metabolites, tryptamine (1), indolokine A5 (2), 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE, 3), and phenethylamine (PEA, 4), on sleep characteristics in mice and melatonin biosynthesis pathways in zebrafish. Their sleep-promoting effects were evaluated in a pentobarbital-induced sleep mouse model, revealing significant increases in sleep duration and blood melatonin levels, particularly with ITE (3) and PEA (4). Further tests in zebrafish embryos showed that ITE (3) and PEA (4) increased the expression of genes for melatonin biosynthesis (Aanat1, Aanat2, Tph1a, and Hiomt) in a concentration-dependent manner, indicating their potential as therapeutic agents for sleep disorders.

Postnatal Development of the Circadian Rhythmicity of Human Pineal Melatonin Synthesis and Secretion (Systematic Review).

Introduction: According to current knowledge, at birth, the pineal gland and melatonin receptors are already present and the suprachiasmatic nucleus is largely functional, and noradrenaline, the key pineal transmitter, can be detected in the early foetal period. It is still unclear why the pineal gland is not able to start its own pulsatile synthesis and secretion of melatonin in the first months of life, and as a result, infants during this time are dependent on an external supply of melatonin. Method: The causes and consequences of this physiological melatonin deficiency in human infancy are examined in a systematic review of the literature, in which 40 of 115 initially selected publications were evaluated in detail. The references of these studies were checked for relevant studies on this topic. References from previous reviews by the author were taken into account. Results: The development and differentiation of the pineal gland, the pinealocytes, as the site of melatonin synthesis, and the development and synaptic coupling of the associated predominantly noradrenergic neural pathways and vessels and the associated Lhx4 homebox only occurs during the first year of life. Discussion: The resulting physiological melatonin deficiency is associated with sleep disorders, infant colic, and increased crying in babies. Intervention studies indicate that this deficiency should be compensated for through breastfeeding, the administration of nonpooled donor milk, or through industrially produced chrononutrition made from nonpooled cow's milk with melatonin-poor day milk and melatonin-rich night milk.

Functional Characterization of the Ciliate Stylonychia lemnae Serotonin N-Acetyltransferase, a Pivotal Enzyme in Melatonin Biosynthesis and Its Overexpression Leads to Peroxidizing Herbicide Tolerance in Rice.

Serotonin N-acetyltransferase (SNAT) is a pivotal enzyme for melatonin biosynthesis in all living organisms. It catalyzes the conversion of serotonin to N-acetylserotonin (NAS) or 5-methoxytrypytamine (5-MT) to melatonin. In contrast to animal- and plant-specific SNAT genes, a novel clade of archaeal SNAT genes has recently been reported. In this study, we identified homologues of archaeal SNAT genes in ciliates and dinoflagellates, but no animal- or plant-specific SNAT homologues. Archaeal SNAT homologue from the ciliate Stylonychia lemnae was annotated as a putative N-acetyltransferase. To determine whether the putative S. lemnae SNAT (SlSNAT) exhibits SNAT enzyme activity, we chemically synthesized and expressed the full-length SlSNAT coding sequence (CDS) in Escherichia coli, from which the recombinant SlSNAT protein was purified by Ni2+ affinity column chromatography. The recombinant SlSNAT exhibited SNAT enzyme activity toward serotonin (Km = 776 µM) and 5-MT (Km = 246 µM) as substrates. Furthermore, SlSNAT-overexpressing (SlSNAT-OE) transgenic rice plants showed higher levels of melatonin synthesis than wild-type controls. The SlSNAT-OE rice plants exhibited delayed leaf senescence and tolerance against treatment with the reactive oxygen species (ROS)-inducing herbicide butafenacil by decreasing hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels, suggesting that melatonin alleviates ROS production in vivo.

AANAT kinetics of CoASH-targeted electrophiles of tryptamine and related analogs

Arylalkylamine N-acetyltransferase (AANAT) catalyzes the rate-limiting step in melatonin synthesis and is a potential target for disorders involving melatonin overproduction, such as seasonal affective disorder. Previously described AANAT inhibitor bromoacetyltryptamine (BAT) and benzothiophenes analogs were reported to react with CoASH to form potent bisubstrate inhibitors through AANAT’s alkyltransferase function, which is secondary to its role as an acetyltransferase. We replaced the bromoacetyl group in BAT with various Michael acceptors to mitigate possible off-target activity of its bromoacetyl group. Additionally, we modified the length of the carbon linker between the Michael acceptor and indole bicycle of tryptamine to determine its effect on potency. An AANAT enzymatic assay showed a two-carbon linker present in BAT was optimal, while none of the new warheads had activity. Kinetic analysis indicated that these Michael acceptors reacted with CoASH much slower than BAT and not within the timeframe of our enzymatic assay. Additionally, we confirmed earlier reports that the acetyltransferase function of AANAT follows an ordered bi bi mechanism in which AcCoA binds before serotonin. In contrast, BAT’s alkyltransferase kinetics revealed a bi uni mechanism in which BAT binds to AANAT before CoASH. Our model combines both functions of AANAT into one kinetic mechanism.

Protective role of melatonin against radiation-induced disruptions in behavior rhythm of zebrafish (danio rerio)

Ionizing radiation, as an increasingly serious environmental pollutant, has aroused widespread public concern. Melatonin, as an indole heterocyclic compound, is known to have anti-inflammatory and antioxidant effects. However, few studies have considered the comprehensive impact of melatonin on radiation damage. In this study, we used zebrafish as experimental materials and employed methods such as acridine orange staining, enzyme-linked immunosorbent assay (ELISA), video tracking for automated behavior analysis, microscope imaging, and real-time fluorescence quantitative analysis. Zebrafish embryos at 2 h post-fertilization (hpf) were treated under four different experimental conditions to assess their growth, development, and metabolic consequences. Our findings indicate that 0.10 Gy gamma radiation significantly augments body length, eye area, spine width, and tail fin length in zebrafish, along with a marked increase in oxidative stress (P < 0.05). Moreover, it enhances cumulative swimming distance, time, and average speed, suggesting elevated activity levels. We observed circadian rhythm phase shifts, peak increases, and cycle shortening, accompanied by abnormal expression of genes pivotal to biological rhythms, exercise, melatonin synthesis, apoptosis/anti-apoptosis, and oxidation/antioxidant balance. The inclusion of melatonin (1 × 10-5 mol/L MLT) ameliorated these radiation-induced anomalies, while its independent effect on zebrafish was negligible. Melatonin can regulate oxidative stress responses, hinders apoptosis responses, and reprogramming the expression of rhythm-related genes in zebrafish embryos after reprogramming radiation stimulation. Overall, our research highlights melatonin's critical role in countering the biological damage inflicted by gamma radiation, proposing its potential as a therapeutic agent in radiation protection.

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.

GnRH protective effects against long-term potentiation impairment induced by AANAT-siRNA

There is an interplay between the gonadotropin-releasing hormone (GnRH) and melatoninergic systems. The key enzyme of melatonin synthesis (arylalkylamine N-acetyltransferase, AANAT), and GnRH receptors are expressed in the hippocampus. While it has been shown that hippocampal AANAT enzyme activity is necessary for proper hippocampal cognitive function, their role in long-term potentiation (LTP) induction is not fully understood. In current study, the impact of GnRH on LTP induction was investigated, while hippocampal melatonin synthesis had been inhibited. The melatonin synthesis was inhibited by AANAT-siRNA administration, and LTP was induced using in vivo field potential electrophysiological recording.Animals were divided into 5 groups: Intact, vehicle, siRNA, GnRH and siRNA+GnRH. All animals, except intact group, experienced the stereotaxic surgery and intra-hippocampal cannulation to receive vehicle agent, AANAT siRNA (0.5 μg/hip), GnRH (1 ng/rat), and AANAT siRNA+GnRH. The recognition memory was assessed by Novel object recognition test. The field potential electrophysiology experiment was conducted by stimulating the Schaffer collateral pathway, and LTP induction was carried out through high-frequency stimulation (HFS). After recording, animals' brain was isolated and quickly frozen for further hippocampal melatonin levels measurement by LC-MS and AANAT mRNA levels by qRT-PCR.GnRH injection in the hippocampus increased local AANAT-mRNA expression and melatonin levels. GnRH-treated animals displayed higher LTP amplitude compared to intact, vehicle and siRNA groups. While the reduction in hippocampal melatonin levels by AANAT-siRNA inhibited LTP and impaired recognition memory, the GnRH prevented these adverse effects. The data suggests that GnRH have protective effects against AANAT-siRNA-induced LTP decline. The protective mechanism at least partially, may be related to the increased expression of local AANAT-mRNA.

A comparison of the potential of melatonin and tryptophan to ameliorate CCl4-induced hepatic and renal toxicity in Wistar rats

CCl4 causes oxidative injury, fatty degeneration, fibrosis of the liver, renal failure, and even hepatocellular and renal carcinoma. Certain substances have the potential to neutralize the harmful effects of CCl4, so it will lead to numerous beneficial effects. Melatonin (MEL) is a powerful antioxidant that regulates circadian rhythm and has beneficial effects on organism; tryptophan (TRP) is its precursor necessary for the synthesis of MEL. The aim of the current study was to determine whether MEL and TRP, have protective effects during subchronic application of CCl4 to the liver and kidneys. Results suggest that CCl4 led to decrease of total proteins, albumins, globulins, erythrocytes, hemoglobin, and hematocrit; and increase of creatinine, AST, ALT values, and leukocytes. MEL and TRP both showing protective effects on regulation of serum proteins, albumins, globulins, A/G, AST, ALT, and creatinine levels. TRP had been shown to have potential in regulation of disbalanced hematological parameters caused by CCl4. TRP had beneficial effects on hepatocyte morphology in term of beaded chromatin and preserved cell morphology. Overall, oral supplementation of TRP had better protective effects on liver/kidneys compared to MEL.

The effects of artificial light at night on spider brains.

Artificial light at night (ALAN) is an increasingly pervasive pollutant that alters animal behaviour and physiology, with cascading impacts on development and survival. Recent evidence links exposure to ALAN with neural damage, potentially due to its action on melatonin synthesis, a powerful antioxidant. However, these data are scarce and taxonomically limited. Here, we used micro-CT to test the effects of short-term ALAN exposure on brain volumes in the Australian garden orb-weaving spider (Hortophora biapicata), a species commonly found in urban areas and, specifically, around street lights. We found that short-term ALAN exposure was linked to reductions in the volumes of brain structures in the primary eye visual pathway, potentially as a consequence of oxidative stress or plastic shifts in neural investment. Although the effects of ALAN were subtle, they provided new insights into potential mechanisms underpinning the behavioural and physiological impacts of ALAN in this important urban predator.

Short communication: An alternative pathway for melatonin synthesis in the skin of European flounder (Platichthys flesus)

The classic melatonin biosynthesis pathway (Mel; N-acetyl-5-methoxytryptamine) involves two consecutive enzymatic steps that are decisive in hormone production: conversion of serotonin (5-hydroxytryptamine; 5-HT) to N-acetylserotonin (NAS) and the methylation of the last compound to Mel. This pathway requires the activity of the enzymes: the first is of the category of N-acetyltransferases (AANAT, SNAT, or NAT) and the second is N-acetylserotonin O-methyltransferase (ASMT; also known as HIOMT). However, quite recently, new information has been provided on the possibility of an alternative Mel synthesis pathway; it would include a two-step action by these enzymes, but in reverse order, where ASMT (or ASMTL, the enzyme related to ASMT) methylates 5-HT to 5-methoxytryptamine (5-MT), and then the last compound is acetylated by an enzyme of the category of N-acetyltransferases to Mel. In our study on the activity of enzymes in the Mel biosynthesis pathway in flounder skin, we have found an increase in 5-MT level, as a result of the increase in 5-HT concentration, which is followed by a growing concentration of Mel. However, we have not found any increase in Mel concentration, despite an increase in NAS in the samples. Our data strongly suggest an alternative way of Mel production in flounder skin in which 5-HT is first methylated to 5-MT, which is then acetylated to Mel.

Revealing the Effects of Zinc Sulphate Treatment on Melatonin Synthesis and Regulatory Gene Expression in Germinating Hull-Less Barley through Transcriptomic Analysis.

This study investigated the transcriptomic mechanisms underlying melatonin accumulation and the enhancement of salt tolerance in hull-less barley seeds subjected to zinc sulphate stress. Following zinc sulphate treatment, hull-less barley seeds demonstrated increased melatonin accumulation and improved salt tolerance. Through transcriptome analysis, the study compared gene expression alterations in seeds (using the first letter of seed, this group is marked as 'S'), seeds treated with pure water (as the control group, is marked as 'C'), and germinated seeds exposed to varying concentrations of zinc sulphate (0.2 mM and 0.8 mM, the first letter of zinc sulphate, 'Z', is used to mark groups 'Z1' and 'Z2'). The analysis revealed that 8176, 759, and 622 differentially expressed genes (DEGs) were identified in the three comparison groups S.vs.C, C.vs.Z1, and C.vs.Z2, respectively. Most of the DEGs were closely associated with biological processes, including oxidative-stress response, secondary metabolite biosynthesis, and plant hormone signaling. Notably, zinc sulphate stress influenced the expression levels of Tryptophan decarboxylase 1 (TDC1), Acetylserotonin O-methyltransferase 1 (ASMT1), and Serotonin N-acetyltransferase 2 (SNAT2), which are key genes involved in melatonin synthesis. Furthermore, the expression changes of genes such as Probable WRKY transcription factor 75 (WRKY75) and Ethylene-responsive transcription factor ERF13 (EFR13) exhibited a strong correlation with fluctuations in melatonin content. These findings contribute to our understanding of the mechanisms underlying melatonin enrichment in response to zinc sulphate stress.

Genome-Wide Identification of Caffeic Acid O-Methyltransferase Gene Family in Medicago truncatula: MtCOMT13-Mediated Salt and Drought Tolerance Enhancement

Legumes are important grains and forages, providing high-quality proteins, vitamins, and micronutrients to humans and animals. Medicago truncatula is a close relative of alfalfa (Medicago sativa). Caffeic acid O-methyltransferase (COMT), a key gene that is identified to be essential for melatonin synthesis, plays a significant role in plant growth, development, and abiotic stress responses. However, a systematic study on the COMT gene family in M. truncatula has still not been reported. In this study, 63 MtCOMT genes were identified and categorized into three groups. Gene structure and conserved motif analyses revealed the relative conservation of closely clustered MtCOMTs within each group. Duplicated events in MtCOMT members were identified, and segmental duplication was the main mean. Cis-acting element prediction revealed the involvement of MtCOMTs in growth and development and response to light, stress, and plant hormones. RNA-seq data analysis showed that 57 MtCOMTs varied under salt and drought stresses. The RT-qPCR expression patterns showed that MtCOMT9, MtCOMT13, MtCOMT22, MtCOMT24, MtCOMT43, and MtCOMT46 were related to salt and drought responses in M. truncatula. Additionally, Arabidopsis thaliana overexpressing MtCOMT13 displayed superior plant growth phenotypes and enhanced tolerance to salt and drought stresses through higher photosynthetic parameters and activities of antioxidant enzymes, which indicated that MtCOMT13 played an important role in positively regulating plant salt and drought tolerance. These findings contribute to an improved understanding of MtCOMTs’ roles in abiotic stress responses in M. truncatula, providing an important theoretical basis and genetic resource for legume species resistance breeding in the future.

Partners in health and disease: pineal gland and purinergic signalling.

In mammal's pineal glands, ATP interacts with the high-affinity P2Y1 and the low-affinity P2X7 receptors. ATP released from sympathetic nerve terminals potentiates noradrenaline-induced serotonin N-acetyltransferase (Snat) transcription, N-acetylserotonin (NAS), and melatonin (MLT) synthesis. Circulating melatonin impairs the expression of adhesion molecules in endothelial cells, blocking the migration of leukocytes. Acute defence response induced by pathogen- and danger/damage-associated molecular patterns (PAMPs and DAMPs) triggers the NF-κB pathway in pinealocytes and blocks the transcription of Snat. Therefore, the darkness hormone is not released, and neutrophils and monocytes migrate to the lesion sites. ATP released in high amounts from apoptotic and death cells was considered a DAMP, and the blockage of P2X7 receptors was tested as a new class of drugs for treating brain damage. However, this is not a simple equation. High ATP injected in a lateral ventricle blocked MLT, but not NAS, synthesis as it impairs the transcription of acetyl serotonin N-methyltransferase. NAS is released in the plasma and the cerebral spinal fluid. NAS also blocks the rolling and adhesion of leukocytes to endothelial cells. Otherwise, it is metabolised specifically in each brain area to provide the requested concentration of MLT as a neuroprotector. As observed in physiological conditions, high extracellular ATP, different from the other DAMPs, reports the environmental light/dark cycle rhythm because NAS substitutes MLT as the nocturnal chemical indicator, the darkness hormone. Thus, blocking the P2X7R should not be considered a universal therapy for improving acute strokes, as MLT and ATP are partners in health and disease.

SlTDC modulates photosynthesis of senescent leaves in tomato

Melatonin (MT) is a key regulator in plants’ response to leaf senescence induced by aging or various abiotic stresses. Here, we demonstrated that darkness and leaf aging enhance endogenous MT levels by upregulating key genes involved in MT synthesis. Additionally, exogenous MT application significantly mitigated leaf senescence induced by darkness and leaf aging in tomato plants, leading to higher chlorophyll content and maximum photochemical efficiency (Fv/Fm) compared to the control. Using Solanum lycopersicum L. tryptophan decarboxylase (SlTDC)-overexpressed and -knockout transgenic tomato seedlings, we found that SlTDC overexpression increased endogenous MT content and suppressed mRNA levels of chlorophyll degradation-related genes: pheophorbide a oxygenase (PAO), pheophytinase (PPH), and non-yellow coloring1 like (NOL). Furthermore, SlTDC overexpression alleviated photosystem II complex (PSII) photoinhibition, increased ribulose-1,5-bisphosphate carboxylase (Rubisco) and Rubisco activase (RCA) activities and mRNA levels, and maintained higher photosynthetic efficiency in leaves under darkness and in leaves aged over 35 d compared to wild-type plants. Conversely, SlTDC knockout accelerated darkness- or leaf aging-induced leaf senescence in tomatoes. Our findings suggest that MT application or SlTDC overexpression can effectively alleviate leaf senescence by regulating photosynthesis in tomato plants.

КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ СУТОЧНОГО МОНИТОРИРОВАНИЯ АРТЕРИАЛЬНОГО ДАВЛЕНИЯ И ЦИРКАДНОГО СИНТЕЗА МЕЛАТОНИНА В ПРОГНОЗИРОВАНИИ СИНДРОМА ОБСТРУКТИВНОГО АПНОЭ СНА У ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ I-II СТЕПЕНИ

Objective. To study the role of 24-hour ambulatory blood pressure monitoring (ABPM) and circadian melatonin (MT) synthesis in predicting obstructive sleep apnea syndrome (OSAS) in patients with grade 1-2 arterial hypertension (AH) and to reveal the relationship between the study findings. Material and methods. 67 patients aged 50.0 (41.0; 56.0) having grade 1-2 AH were examined and divided into 2 groups in regard to the complex of clinical and instrumental research methods: Group 1 – 25 patients having AH and Group – 45 patients having AH associated with OSAS. 24-hour ABPM, anthropometric measurements, and respiratory monitoring were performed. MT levels were evaluated by the content of its metabolite 6-sulfatoxymelatonin (6-COMT) in the urine. Results It has been found that according to ABPM diastolic blood pressure variability during the day was ≥12 mm Hg and had high sensitivity (74.1%) and specificity (91.7%) for predicting the OSAS in patients with hypertension receiving standard antihypertensive therapy. The characteristic feature of the daily MT production in patients with AH in combination with OSAS is an increase in the level of 6-SOMT in daily urine (p=0.031) and its daily portion (p=0.037), correlating with the severity of OSAS (r=0.43; p=0.00065 and r=0.40; p=0.00079, respectively) and independent of the grade of AH (p&gt;0.05). Conclusion. The obtained results allow us to recommend the use of ABPM as a screening, low-cost study to predict OSAS in patients with grade 1-2 AH. The identified changes in the daily rhythm of MT synthesis weakly correlate with the severity of OSAS and the degree of hypertension.

Multifaceted Roles of Melatonin in Sleep Disorders

Hormone protein melatonin helps regulate the sleep–wake cycle or circadian rhythm, making it a critical substance in sleep regulation. Melatonin synthesis mainly occurs in the epiphysis of the pineal gland, although extra-pineal melatonin has been observed in other sites of the body, such as salivary glands, the gastrointestinal tract, the placenta and breast milk. Over the years, research into melatonin has shown that it has multiple roles in sleep disorders, revealing its mechanisms of action, clinical implications and therapeutic performance. In this paper, we review recent findings on the role of melatonin in sleep disorders which include insomnia, delayed sleep phase disorder (DSPD), jet lag, and shift work sleep disorder (SWSD). In addition, we report results where melatonin agonists and novel therapeutic targets have been designed and utilized to manipulate the melatonin receptors. This paper helps delineate melatonin’s role in sleep disorders from the literature, and clarify new perspectives for prevention and treatment of human health.

Melatonin-Induced Chromium Tolerance Requires Hydrogen Sulfide Signaling in Maize.

Both melatonin and hydrogen sulfide (H2S) mitigate chromium (Cr) toxicity in plants, but the specific interaction between melatonin and H2S in Cr detoxification remains unclear. In this study, the interaction between melatonin and H2S in Cr detoxification was elucidated by measuring cell wall polysaccharide metabolism and antioxidant enzyme activity in maize. The findings revealed that exposure to Cr stress (100 μM K2Cr2O7) resulted in the upregulation of L-/D-cysteine desulfhydrase (LCD/DCD) gene expression, leading to a 77.8% and 27.3% increase in endogenous H2S levels in maize leaves and roots, respectively. Similarly, the endogenous melatonin system is activated in response to Cr stress. We found that melatonin had a significant impact on the relative expression of LCD/DCD, leading to a 103.3% and 116.7% increase in endogenous H2S levels in maize leaves and roots, respectively. In contrast, NaHS had minimal effects on the relative mRNA expression of serotonin-Nacetyltransferase (SNAT) and endogenous melatonin levels. The production of H2S induced by melatonin is accompanied by an increase in Cr tolerance, as evidenced by elevated gene expression, elevated cell wall polysaccharide content, increased pectin methylesterase activity, and improved antioxidant enzyme activity. The scavenging of H2S decreases the melatonin-induced Cr tolerance, while the inhibitor of melatonin synthesis, p-chlorophenylalanine (p-CPA), has minimal impact on H2S-induced Cr tolerance. In conclusion, our findings suggest that H2S serves as a downstream signaling molecule involved in melatonin-induced Cr tolerance in maize.