Melatonin Metabolism Research Articles

Bensulfuron methyl induced multiple stress responses in the field wheat plants: Microbial community and metabolic network disturbance

Sulfonylurea (SU) herbicides are widely used and often detected in environmental matrices and have toxic effects on ecosystems and plant development. However, the interaction between SU and soil-plant metabolism during the whole wheat growth cycle remains poorly investigated. Field trials demonstrated that bensulfuron methyl exposure reduced wheat height and a thousand grains' weight, disrupting the critical metabolic pathways, including linoleic acid and amino acid metabolism in the maturity stage. During different growth processes, bensulfuron methyl exposure decreases wheat soil and plants' defense-related indole alkaloid compounds, such as benzoxazinoids and melatonin. Microbial sequencing results showed that bensulfuron methyl treated decreased the abundance of beneficial microorganisms (Gammaproteobacteria, Bacteroidia, and Blastocatella) in the rhizosphere soil, which positively correlated with the inhibition of soil enzyme activity and the secretion of allelopathic substances (benzoxazinoids and melatonin). Molecular docking further confirmed that bensulfuron methyl affects protein molecular structure by establishing hydrogen bonds, which disequilibrate wheat benzoxazinoids and melatonin metabolism. Therefore, bensulfuron methyl exposure disrupted the interaction between soil microorganisms and indole alkaloid metabolism, hindering plant development. This study provides constructive insights into the environmental risks of herbicides and agricultural product safety throughout wheat development.

Melatonin and gut microbiome

In recent years, studies of the human microbiome have led to the development of the gut-brain axis theory, which proposes a relationship between the gut bacterial community and its metabolites and chemical compounds, as well as physiological and pathological processes in the brain. Melatonin is considered one of the potential links in this relationship.The review provides brief information about the synthesis, metabolism and effects of melatonin in the body. General patterns of the effect of melatonin on the intestinal microbiota under various conditions, such as oral and intraperitoneal melatonin administration, sleep deprivation, as well as the results of studying the microbial community with measurement of hormone levels are considered.Results are presented for families and individual genera of microorganisms and are obtained from studies in animal models or in the research of diseases. The article also notes some additional parameters which are supposed to be relevant to the interaction of melatonin with gut microbiome. Special attention is paid to butyrate as one of the most studied possible parts in this interaction. Studying the relationship between melatonin and microbiome is of interest for basic science and practical medicine.Literature search was carried out using electronic information resources PubMed and eLibrary.

HYPERTENSIVE NEPHROPATHY: TRANSCRIPTOMICS OF KIDNEY BIOPSIES PREDICTS LONG TERM OUTCOME AND IDENTIFIES THERAPEUTIC TARGETS

Objective: Hypertensive nephropathy (HN) represents a major cause of chronic kidney disease, but it is incompletely understood why some patients show disease progression. Our project aim is to identify potential markers of disease progression and novel therapeutic targets. Design and method: Adult patients (n=43; n=16 females, mean age 53 years) with biopsy-verified HN were categorized as ’early’ (estimated glomerular filtration rate (eGFR) >45 ml/min/1.73m2) or ’late’ disease (eGFR <45 ml/min/1.73m2) at the time of biopsy. Patients were further divided into “stable” (eGFR decline <3 ml/min/year) or “progressive” (eGFR decline >3 ml/min/year or start of renal replacement therapy) after median follow-up of 10 years (5-22). TruSeq Exome sequencing was executed after RNA extraction (miRNeasy FFPE kit, Qiagen) at Novogene, Cambridge, UK. Quality control and data analysis was performed using R Studio (v4.2.0) and QIAGEN Ingenuity Pathway Analysis. Results: We analyzed the following subgroups of HN patients: early stable (ES, n=11), early progressive (EP, n=11), late stable (LS, n=9) and late progressive (LP, n=12). Differentially expressed genes (DEG, fold change (FC) >1.5 and p-value < 0.05) were identified, with n=265 in ES vs. EP, and n=674 in LS vs. LP. Principal component analysis (PCA) showed separation of ES vs. EP and LS vs. LP, as depicted in Figure 1A and B. K-nearest neighbour (KNN) analysis of DEG identified a 6-gene classifier in LS vs. LP (19/21 samples correctly classified), while IER5L and CNTNAP5 were the top 2-gene classifier in ES vs. EP (20/21 samples). These classifiers, as well as other DEGs such as PER1, YB1, TIMP3, ADAMTS4, IGFBP5 and EGF could represent novel targets to inhibit disease progression. Differentially regulated pathways were associated with regulation of TP53 activity and circadian rhythm involving melatonin metabolism in ES vs. EP, and metabolic processes related to water-soluble vitamins, glutathione and sphingolipids in LS vs. LP. Conclusions: Transcriptomic profiling from diagnostic kidney biopsies with HN can distinguish future disease progression from non-progression and may identify novel therapeutic targets.

Evolutionary formation of melatonin and vitamin D in early life forms: insects take centre stage.

Melatonin, a product of tryptophan metabolism via serotonin, is a molecule with an indole backbone that is widely produced by bacteria, unicellular eukaryotic organisms, plants, fungi and all animal taxa. Aside from its role in the regulation of circadian rhythms, it has diverse biological actions including regulation of cytoprotective responses and other functions crucial for survival across different species. The latter properties are also shared by its metabolites including kynuric products generated by reactive oxygen species or phototransfomation induced by ultraviolet radiation. Vitamins D and related photoproducts originate from phototransformation of ∆5,7 sterols, of which 7-dehydrocholesterol and ergosterol are examples. Their ∆5,7 bonds in the B ring absorb solar ultraviolet radiation [290-315 nm, ultraviolet B (UVB) radiation] resulting in B ring opening to produce previtamin D, also referred to as a secosteroid. Once formed, previtamin D can either undergo thermal-induced isomerization to vitamin D or absorb UVB radiation to be transformed into photoproducts including lumisterol and tachysterol. Vitamin D, as well as the previtamin D photoproducts lumisterol and tachysterol, are hydroxylated by cyochrome P450 (CYP) enzymes to produce biologically active hydroxyderivatives. The best known of these is 1,25-dihydroxyvitamin D (1,25(OH)2D) for which the major function in vertebrates is regulation of calcium and phosphorus metabolism. Herein we review data on melatonin production and metabolism and discuss their functions in insects. We discuss production of previtamin D and vitamin D, and their photoproducts in fungi, plants and insects, as well as mechanisms for their enzymatic activation and suggest possible biological functions for them in these groups of organisms. For the detection of these secosteroids and their precursors and photoderivatives, as well as melatonin metabolites, we focus on honey produced by bees and on body extracts of Drosophila melanogaster. Common biological functions for melatonin derivatives and secosteroids such as cytoprotective and photoprotective actions in insects are discussed. We provide hypotheses for the photoproduction of other secosteroids and of kynuric metabolites of melatonin, based on the known photobiology of ∆5,7 sterols and of the indole ring, respectively. We also offer possible mechanisms of actions for these unique molecules and summarise differences and similarities of melatoninergic and secosteroidogenic pathways in diverse organisms including insects.

Metabolomic Markers in Attention-Deficit/Hyperactivity Disorder (ADHD) among Children and Adolescents-A Systematic Review.

Attention-Deficit/Hyperactivity Disorder (ADHD), characterized by clinical diversity, poses diagnostic challenges often reliant on subjective assessments. Metabolomics presents an objective approach, seeking biomarkers for precise diagnosis and targeted interventions. This review synthesizes existing metabolomic insights into ADHD, aiming to reveal biological mechanisms and diagnostic potentials. A thorough PubMed and Web of Knowledge search identified studies exploring blood/urine metabolites in ADHD-diagnosed or psychometrically assessed children and adolescents. Synthesis revealed intricate links between ADHD and altered amino acid metabolism, neurotransmitter dysregulation (especially dopamine and serotonin), oxidative stress, and the kynurenine pathway impacting neurotransmitter homeostasis. Sleep disturbance markers, notably in melatonin metabolism, and stress-induced kynurenine pathway activation emerged. Distinct metabolic signatures, notably in the kynurenine pathway, show promise as potential diagnostic markers. Despite limitations like participant heterogeneity, this review underscores the significance of integrated therapeutic approaches targeting amino acid metabolism, neurotransmitters, and stress pathways. While guiding future research, this overview of the metabolomic findings in ADHD suggests directions for precision diagnostics and personalized ADHD interventions.

Biological Clock Genes are Crucial and Promising Biomarkers for the Therapeutic Targets and Prognostic Assessment in Gastric Cancer.

Gastric cancer is one of the major public health problems worldwide. Circadian rhythm disturbances driven by circadian clock genes play a role in the development of cancer. However, whether circadian clock genes can serve as potential therapeutic targets and prognostic biomarkers for gastric cancer remains elusive. In this study, we comprehensively analyzed the potential relationship between circadian clock genes and gastric cancer using online bioinformatics databases such as GEPIA, cBioPortal, STRING, GeneMANIA, Metascape, TIMER, TRRUST, and GEDS. Biological clock genes are expressed differently in human tumors. Compared with normal tissues, only PER1, CLOCK, and TIMELESS expression differences were statistically significant in gastric cancer (p < 0.05). PER1 (p = 0.0169) and CLOCK (p = 0.0414) were associated with gastric cancer pathological stage (p < 0.05). Gastric cancer patients with high expression of PER1 (p = 0.0028) and NR1D1 (p = 0.016) had longer overall survival, while those with high expression of PER1 (p = 0.042) and NR1D1 (p = 0.016) had longer disease-free survival. The main function of the biological clock gene is related to the circadian rhythms and melatonin metabolism and effects. CLOCK, NPAS2, and KAT2B were key transcription factors for circadian clock genes. In addition, we also found important correlations between circadian clock genes and various immune cells in the gastric cancer microenvironment. This study may establish a new gastric cancer prognostic indicator based on the biological clock gene and develop new drugs for the treatment of gastric cancer using biological clock gene targets.

ROS-dependent catalytic mechanism of melatonin metabolism and its application in the measurement of reactive oxygen.

Melatonin (Mel) is an endogenous active molecule whose metabolism progress significantly influences its bioactivity. However, the detailed metabolic pathway of Mel in the pathological state has not yet been fully illustrated. In this study, 16 metabolites of Mel in cancer cells and human liver microsomes were identified, of which seven novel metabolites were newly discovered. Among them, 2-hydroxymelatonin (2-O-Mel), as the major metabolite in cancer cells, was revealed for the first time, which was different from the metabolite found in the human liver. Furthermore, CYP1A1/1A2- and reactive oxygen species (ROS)-mediated 2-hydroxylation reactions of Mel were verified to be the two metabolic pathways in the liver and cancer cells, respectively. ROS-dependent formation of 2-O-Mel was the major pathway in cancer cells. Furthermore, the underlying catalytic mechanism of Mel to 2-O-Mel in the presence of ROS was fully elucidated using computational chemistry analysis. Therefore, the generation of 2-O-Mel from Mel could serve as another index for the endogenous reactive oxygen level. Finally, based on the ROS-dependent production of 2-O-Mel, Mel was successfully used for detecting the oxygen-carrying capacity of hemoglobin in human blood. Our investigation further enriched the metabolic pathway of Mel, especially for the ROS-dependent formation of 2-O-Mel that serves as a diagnostic and therapeutic target for the rational use of Mel in clinics.

Fluvoxamine in the treatment of anxiety-depressive spectrum disorders

The RSCI and PubMed search databases have requested publications over the past 40 years on the search queries «fluvoxamine», «anxiety-depressive disorders», «anxiety», «depression», «comorbidity», devoted to the effectiveness of fluvoxamine in various variants of disorders of the anxiety-depressive spectrum, anxiety depressions. The data of the above studies indicate that fluvoxamine (Zovart San) in doses of 50-300 mg / day is a highly effective remedy for the treatment of not only anxiety depressions and genesis (psychogenic, organic, mixed, autochthonous-endogenous) and severity (up to psychotic), but also a wider range of anxiety-depressive disorders, including adaptation disorders, obsessive-compulsive disorder, somatized, dysmorphic, insomniac symptom complexes and eating disorders. A wide range of clinical effects of fluvoxamine is due to its main and additional mechanisms of action: blockade of serotonin reuptake, σ1-agonist activity and the effect on the metabolism of melatonin and neurosteroids catabolism.

Melatonergic Signaling Sustains Food Allergy Through FcεRI Recycling.

The prevalence of food allergies is increasing dramatically and causing serious public health concerns. Notably, melatonin metabolism imbalance in patients with food allergies; however, the role of melatonin in food allergies remains unclear. Here, we demonstrated that melatonin suppresses food allergy responses and reprograms the gut microbiota of food-allergic mice, while melatonin aggravates food allergy during gut microbiota depletion. Mechanistically, melatonin boosts the degranulation of mast cells by up-regulating the expression of membrane high-affinity immunoglobulin E (IgE) receptor (FcεRI). Melatonin increases the mRNA expression of Rabenosyn-5 (a component of factors for endosome recycling and Rab interactions) through melatonin receptor 2 (MT2)-extracellular signal-regulated kinase (ERK) signaling, thereby driving the recycling of FcεRI and elevating the abundance of membrane FcεRI. Likewise, the inhibition of MT2 attenuates melatonin-induced food allergy in mice with gut microbiota depletion. Collectively, our finding provides insights into the pathogenesis of food allergies and provides a potential therapeutic target for the prevention and treatment of food allergies.

Comparative physiological adaptations to industrial pollution stress mediated by melatonin in riparian vegetation and Phyla nodiflora an ornamental plant

This study explores the macro nutritional contents and endogenous melatonin in the structural differences of riparian flora and horticultural ecotype growing in industrially contaminated environments. Water pollution caused by anthropogenic activities poses uncompromising threats to rivers and water sources, resulting in the extinction of many species and the reduction of others to endangered status. Effluents from the industrial hub of Faisalabad are discharged into the Chenab River in Punjab province. As in other parts of the world, effluents from Faisalabad industries pose a great threat to native vegetation in the area. Therefore, this study was designed to verify the presence of industrial pollution. Moreover, the effects of industrial pollution on native vegetation and the survival strategies of adapted species were also assessed. Results showed that several abiotic stresses have been mitigated by endogenous melatonin in herbs and herb-based products. The survival of herbs depends on specific changes to biochemical compounds like melatonin content and vascular structures. Overall, industrial pollution harmed herbs' metabolism and antioxidant activity, although the reactions of specific species to industrial pollution varied. Changes in the concentration of endogenous melatonin metabolism have been identified as promising indicators for industrial pollution biomonitoring. Internal alterations of plants vegetating at various industrially polluted locations contributed significantly to the high level of tolerance of these plants. The typical reaction of all herbs to increased pollution was growth modification in terms of endogenous melatonin content, moisture content, carbohydrates, crude protein, and dry matter. Most of the proximate, melatonin and chlorophyll content were significantly high in indirectly affected vegetation and high in directly affected industrial pollution. Biochemical investigation specifies that in response to industrial pollution four species Calotropis procera, Eclipta alba, Phyla nodiflora (Ornamental plant) and Ranunculus sceleratus increased the primary metabolites like melatonin, carbohydrates, crude protein, crude fibers, and fats.

Calculation of Human Melatonin Partial Metabolic Clearance in Healthy Adult Volunteers for Investigation of a Novel in Vivo CYP1A2 Phenotyping Method: A Pilot Study.

The method of administering caffeine as a probe to evaluate the phenotypic activity of the CYP1A2, has not yet been applied clinically. In contrast, if endogenous melatonin (MEL) metabolism can be used to assess CYP1A2 activity, it could be a simple method that does not require substance administration. The study aim was to calculate the MEL partial metabolic clearance (CLm(MEL)) from plasma MEL and its urinary metabolites and to test the potential of this approach as a novel CYP1A2 phenotyping method. Nine subjects were included in the study; 3 had 6 blood and 4 urine samples collected between 10:00 and 18:00 (collectively, the intraday sample). Nine subjects had 3 blood samples and 2-h urine samples collected between 10:00 and 12:00 once a week for 3 weeks (interday sample). The CLm(MEL) was calculated from the plasma area under the curve (AUC) of MEL (AUCMEL) and urinary MEL metabolites excretion (X6MEL). Among the intraday samples, the AUCMEL ranged from 6.45-13.17 pmol·h/L and X6MEL ranged from 0.204-0.899 nmol/2 h, showing a decrease in concentration over time. In contrast, the CLm(MEL) ranged from 30.52-69.57 L/h (within-individual percent relative standard deviation: 9.2-20.1%), showing no time-dependent variation. Large interindividual variability was observed in AUCMEL and X6MEL in the interday sample, but CLm(MEL) showed small interindividual variabilities. The CLm(MEL) was 1.8-fold higher for smokers than for nonsmokers. The results obtained in this study may be valuable in future studies of evaluating novel CYP1A2 phenotyping method.

Potential therapeutic role of melatonin in hepatobiliary diseases: current evidence and clinical observations.

Melatonin (MEL) is produced and secreted by the pineal gland as well as the small intestine, liver, retina, lymphocytes, and melanocytes in the skin in both experimental animals as well as in humans. While pineal and retinas MEL is closely related to the light/dark cycle, the production of MEL by other so called extrapineal tissues is independent of such circadian rhythm. Among the primary mechanisms of action of MEL in humans, the most important are interaction of MEL with specific receptors (M1, M2, M3) and the MEL 'scavenging' activity against the formation of free oxygen metabolites as a result of MEL's ability to transfer free electrons and stimulation of the expression of redox reaction enzymes. In addition, MEL binds to intracellular proteins such as calmodulin, thereby affecting the course of cell cycle, and it has been shown to activate of nuclear receptors belonging to the retinoid orphan receptors/retinoid Z receptors (ROR/RZR) subfamily. MEL exerts regulatory effects on the master clock regulating diurnal rhythms. This updated review presents current view on the synthesis and metabolism of MEL and the growing body of experimental evidence transferable to the practical medicine supporting a pleiotropic molecule beneficial effects on the health including protection against various organ abnormalities, including internal organs such as the liver. Although the beneficial effects of MEL in various types of liver damage have been well documented in experimental studies, there are relatively few studies on liver dysfunction in humans. Considering the worldwide obesity pandemic often associated with the occurrence of steatohepatitis and cirrhosis, the beneficial effects of MEL in liver pathology should be proven in randomized trials involving patients presenting with hepatic disorders.

Melatonin versus Sleep Deprivation for Sleep Induction in Nap Electroencephalography: Protocol for a Prospective Randomized Crossover Trial in Children and Young Adults with Epilepsy

Electroencephalography (EEG) continues to be a pivotal investigation in children with epilepsy, providing diagnostic evidence and supporting syndromic classification. In the pediatric population, electroencephalographic recordings are frequently performed during sleep, since this procedure reduces the number of artifacts and activates epileptiform abnormalities. To date, no shared guidelines are available for sleep induction in EEG. Among the interventions used in the clinical setting, melatonin and sleep deprivation represent the most used methods. The main purpose of this study is to test the non-inferiority of 3-5 mg melatonin versus sleep deprivation in achieving sleep in nap electroencephalography in children and young adult patients with epilepsy. To test non-inferiority, a randomized crossover trial is proposed where 30 patients will be randomized to receive 3-5 mg melatonin or sleep deprivation. Each enrolled subject will perform EEG recordings during sleep in the early afternoon for a total of 60 EEGs. In the melatonin group, the study drug will be administered a single oral dose 30 min prior to the EEG recording. In the sleep deprivation group, parents will be required to subject the child to sleep deprivation the night before registration. Urinary and salivary concentrations of melatonin and of its main metabolite 6-hydroxymelatonin will be determined by using a validated LC-MS method. The present protocol aims to offer a standardized protocol for sleep induction to be applied to EEG recordings in those of pediatric age. In addition, melatonin metabolism and elimination will be characterized and its potential interference in interictal abnormalities will be assessed.

Melatonin in the regulation of human life and its role in development pathology

The aim of our study was to research the literature data available for analysis of the melatonin role in the neurological and mental disorders origin. Materials and methods: to compile a literature review by keywords, articles there were selected and analyzed in the MEDLINE / PubMed and e-library databases from 1993 to 2021. For a detailed analysis, 42 literature sources were selected for the melatonin role in the development of neurological and mental disorders. Results: Melatonin is a hormone with unique adaptive capabilities. Violation of its production, both quantitatively and its rhythm, is the starting point, leading at the initial stages to desynchronizes, followed by the emergence of organic pathology. Consequently, the very fact of a violation of melatonin production can be the cause of various diseases. It was found that the volume of the pineal gland can change with the development of various types of neurological and psychiatric diseases, which is associated with a violation of the synthesis of melatonin and serotonin. Melatonin has been found to have important protective properties in Alzheimer's disease - the ability to inhibit the formation of beta-amyloid peptide in the brain, which is the morphological basis of this disease. The same correlation was found in patients with autism, psychosis and obsessive-compulsive disorder compared with healthy volunteers. Regarding the neuroprotective properties of melatonin, it should be noted its effectiveness in age-related diseases (Alzheimer's, Parkinson's, vascular diseases) Conclusion: Melatonin can be considered as a unique bioregulator, adaptogen and stabilizer of the whole organism and, in particular, the functions of the central nervous system. It has been proven that disruption of melatonin metabolism leads to various neurological and mental disorders.

The role of melatonin in plant growth and metabolism, and its interplay with nitric oxide and auxin in plants under different types of abiotic stress.

Melatonin is a pleiotropic signaling molecule that reduces the adverse effects of abiotic stresses, and enhances the growth and physiological function of many plant species. Several recent studies have demonstrated the pivotal role of melatonin in plant functions, specifically its regulation of crop growth and yield. However, a comprehensive understanding of melatonin, which regulates crop growth and yield under abiotic stress conditions, is not yet available. This review focuses on the progress of research on the biosynthesis, distribution, and metabolism of melatonin, and its multiple complex functions in plants and its role in the mechanisms of metabolism regulation in plants grown under abiotic stresses. In this review, we focused on the pivotal role of melatonin in the enhancement of plant growth and regulation of crop yield, and elucidated its interactions with nitric oxide (NO) and auxin (IAA, indole-3-acetic acid) when plants are grown under various abiotic stresses. The present review revealed that the endogenousapplication of melatonin to plants, and its interactions with NO and IAA, enhanced plant growth and yield under various abiotic stresses. The interaction of melatonin with NO regulated plant morphophysiological and biochemical activities, mediated by the G protein-coupled receptor and synthesis genes. The interaction of melatonin with IAA enhanced plant growth and physiological function by increasing the levels of IAA, synthesis, and polar transport. Our aim was to provide a comprehensive review of the performance of melatonin under various abiotic stresses, and, therefore, further explicate the mechanisms that plant hormones use to regulate plant growth and yield under abiotic stresses.

Ectopic expression of MmCYP1A1, a mouse cytochrome P450 gene, positively regulates stress tolerance in apple calli and Arabidopsis.

Ectopic expression of MmCYP1A1 gene from Mus musculus in apple calli and Arabidopsis increased the levels of melatonin and 6-hydroxymelatonin, and improved their stress resistance. Melatonin occurs widely in organisms, playing a key regulatory role. CYP1A1 is a cytochrome P450 monooxygenase, involved in the melatonin metabolism, and is responsible for the synthesis of 6-hydroxymelatonin from melatonin. Melatonin and 6-hydroxymelatonin have strong antioxidant activities in animals. Here, we cloned MmCYP1A1 from Mus musculus and found that ectopic expression of MmCYP1A1 improved the levels of melatonin and 6-hydroxymelatonin in transgenic apple calli and Arabidopsis. Subsequently, we observed that MmCYP1A1 increased the tolerance of transgenic apple calli and Arabidopsis to osmotic stress simulated by polyethylene glycol 6000 (PEG 6000), as well as resistance of transgenic Arabidopsis to drought stress. Further, the number of lateral roots of MmCYP1A1 transgenic Arabidopsis were enhanced significantly after PEG 6000 treatment. The expression of MmCYP1A1 remarkably reduced malondialdehyde (MDA) content, electrolyte leakage, accumulation of H2O2 and O2- during stress treatment. Moreover, MmCYP1A1 enhanced stress tolerance in apple calli and Arabidopsis by increasing the expression levels of resistance genes. MmCYP1A1 also promoted stomatal closure in transgenic Arabidopsis to reduce leaf water loss during drought. Our results indicate that MmCYP1A1 plays a key role in plant stress tolerance, which may provide a reference for future plant stress tolerance studies.

Genetic and evolutionary dissection of melatonin response signaling facilitates the regulation of plant growth and stress responses.

The expansion of gene families during evolution could generate functional diversity among their members to regulate plant growth and development. Melatonin, a phylogenetically ancient molecule, is vital for many aspects of a plant's life. Understanding the functional diversity of the molecular players involved in melatonin biosynthesis, signaling, and metabolism will facilitate the regulation of plant phenotypes. However, the molecular mechanism of melatonin response signaling elements in regulating this network still has many challenges. Here, we provide an in-depth analysis of the functional diversity and evolution of molecular components in melatonin signaling pathway. Genetic analysis of multiple mutants in plant species will shed light on the role of gene families in melatonin regulatory pathways. Phylogenetic analysis of these genes was performed, which will facilitate the identification of melatonin-related genes for future study. Based on the abovementioned signal networks, the mechanism of these genes was summarized to provide reference for studying the regulatory mechanism of melatonin in plant phenotypes. We hope that this work will facilitate melatonin research in higher plants and finely tuned spatio-temporal regulation of melatonin signaling.

Exogenous treatment with melatonin enhances waterlogging tolerance of kiwifruit plants.

Waterlogging stress has an enormous negative impact on the kiwifruit yield and quality. The protective role of exogenous melatonin on water stress has been widely studied, especially in drought stress. However, the research on melatonin-induced waterlogging tolerance is scarce. Here, we found that treatment with exogenous melatonin could effectively alleviate the damage on kiwifruit plants in response to waterlogging treatment. This was accompanied by higher antioxidant activity and lower ROS accumulation in kiwifruit roots during stress period. The detection of changes in amino acid levels of kiwifruit roots during waterlogging stress showed a possible interaction between melatonin and amino acid metabolism, which promoted the tolerance of kiwifruit plants to waterlogging. The higher levels of GABA and Pro in the roots of melatonin-treated kiwifruit plants partly contributed to their improved waterlogging tolerance. In addition, some plant hormones were also involved in the melatonin-mediated waterlogging tolerance, such as the enhancement of ACC accumulation. This study discussed the melatonin-mediated water stress tolerance of plants from the perspective of amino acid metabolism for the first time.

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics.

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients' outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes.

Role of Melatonin and Nitrogen Metabolism in Plants: Implications under Nitrogen-Excess or Nitrogen-Low

Melatonin is a new plant hormone involved in multiple physiological functions in plants such as germination, photosynthesis, plant growth, flowering, fruiting, and senescence, among others. Its protective role in different stress situations, both biotic and abiotic, has been widely demonstrated. Melatonin regulates several routes in primary and secondary plant metabolism through the up/down-regulation of many enzyme/factor genes. Many of the steps of nitrogen metabolism in plants are also regulated by melatonin and are presented in this review. In addition, the ability of melatonin to enhance nitrogen uptake under nitrogen-excess or nitrogen-low conditions is analyzed. A model that summarizes the distribution of nitrogen compounds, and the osmoregulation and redox network responses mediated by melatonin, are presented. The possibilities of using melatonin in crops for more efficient uptake, the assimilation and metabolization of nitrogen from soil, and the implications for Nitrogen Use Efficiency strategies to improve crop yield are also discussed.