Elucidating the role of exogenous melatonin in mitigating alkaline stress in soybeans across different growth stages: a transcriptomic and metabolomic approach.

BACKGROUND: Soybean (Glycine max), a vital grain and oilseed crop, serves as a primary source of plant protein and oil. Soil salinization poses a significant threat to soybean planting, highlighting the urgency to improve soybean resilience and adaptability to saline stress. Melatonin, recently identified as a key plant growth regulator, plays crucial roles in plant growth, development, and responses to environmental stress. However, the potential of melatonin to mitigate alkali stress in soybeans and the underlying mechanisms remain unclear. RESULTS: This study investigated the effects of exogenous melatonin on the soybean cultivar Zhonghuang 13 under alkaline stress. We employed physiological, biochemical, transcriptomic, and metabolomic analyses throughout both vegetative and pod-filling growth stages. Our findings demonstrate that melatonin significantly counteracts the detrimental effects of alkaline stress on soybean plants, promoting plant growth, photosynthesis, and antioxidant capacity. Transcriptomic analysis during both growth stages under alkaline stress, with and without melatonin treatment, identified 2,834 and 549 differentially expressed genes, respectively. These genes may play a vital role in regulating plant adaptation to abiotic stress. Notably, analysis of phytohormone biosynthesis pathways revealed altered expression of key genes, particularly in the ARF (auxin response factor), AUX/IAA (auxin/indole-3-acetic acid), and GH3 (Gretchen Hagen 3) families, during the early stress response. Metabolomic analysis during the pod-filling stage identified highly expressed metabolites responding to melatonin application, such as uteolin-7-O-(2''-O-rhamnosyl)rutinoside and Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside, which helped alleviate the damage caused by alkali stress. Furthermore, we identified 183 differentially expressed transcription factors, potentially playing a critical role in regulating plant adaptation to abiotic stress. Among these, the gene SoyZH13_04G073701 is particularly noteworthy as it regulates the key differentially expressed metabolite, the terpene metabolite Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. WGCNA analysis identified this gene (SoyZH13_04G073701) as a hub gene, positively regulating the crucial differentially expressed metabolite of terpenoids, Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. Our findings provide novel insights into how exogenous melatonin alleviates alkali stress in soybeans at different reproductive stages. CONCLUSIONS: Integrating transcriptomic and metabolomic approaches, our study elucidates the mechanisms by which exogenous melatonin ameliorates the inhibitory effects of alkaline stress on soybean growth and development. This occurs through modulation of biosynthesis pathways for key compounds, including terpenes, flavonoids, and phenolics. Our findings provide initial mechanistic insights into how melatonin mitigates alkaline stress in soybeans, offering a foundation for molecular breeding strategies to enhance salt-alkali tolerance in this crop.

The Effect Mechanism of N6-adenosine Methylation (m6A) in Melatonin Regulated LPS-induced Colon Inflammation.

Colon inflammation is characterized by disturbances in the intestinal microbiota and inflammation. Melatonin (Mel) can improve colon inflammation. However, the underlying mechanism remains unclear. Recent studies suggest that m6A methylation modification may play an important role in inflammatory responses. This study aimed to explore the effects of melatonin and LPS-mediated m6A methylation on colon inflammation. Our study found that melatonin inhibits M1 macrophages, activates M2 macrophages, inhibit the secretion of pro-inflammatory factors, maintain colon homeostasis and improves colon inflammation through MTNR1B. In addition, the increased methylation level of m6A is associated with the occurrence of colon inflammation, and melatonin can also reduce the level of colon methylation to improve colon inflammation. Among them, the main methylated protein METTL3 can be inhibited by melatonin through MTNR1B. In a word, melatonin regulates m6A methylation by improving abnormal METTL3 protein level to reshape the microflora and activate macrophages to improve colon inflammation, mainly through MTNR1B.

Rational modification of melatonin for broad-spectrum antifungal agents discovery.

Natural products, known for their environmental safety, are regarded as a significant basis for the modification and advancement of fungicides. Melatonin, as a low-cost natural indole, exhibits diverse biological functions, including antifungal activity. However, its potential as an antifungal agent has not been fully explored. In this study, a series of melatonin derivatives targeting the mitogen-activated protein kinase (Mps1) protein of fungal pathogens were synthesized based on properties of melatonin, among which the trifluoromethyl-substituted derivative Mt-23 exhibited antifungal activity against seven plant pathogenic fungi, and effectively reduced the severity of crop diseases, including rice blast, Fusarium head blight of wheat and gray mold of tomato. In particular, its EC50 (5.4 µM) against the rice blast fungus Magnaporthe oryzae is only one-fourth that of isoprothiolane (22 µM), a commercial fungicide. Comparative analyzes revealed that Mt-23 simultaneously targets the conserved protein kinase Mps1 and lipid protein Cap20. Surface plasmon resonance assays showed that Mt-23 directly binds to Mps1 and Cap20. In this study, we provide a strategy for developing antifungal agents by modifying melatonin, and the resultant melatonin derivative Mt-23 is a commercially valuable, eco-friendly and broad-spectrum antifungal agent to combat crop disease.

Melatonin alleviates myocardial dysfunction through inhibition of endothelial-to-mesenchymal transition via the NF-κB pathway.

Endothelial-to-mesenchymal transition (EndMT) is a complex biological process of cellular transdifferentiation by which endothelial cells (ECs) lose their characteristics and acquire mesenchymal properties, leading to cardiovascular remodeling and complications in the adult cardiovascular diseases environment. Melatonin is involved in numerous physiological and pathological processes, including aging, and has anti-inflammatory and antioxidant activities. This molecule is an effective therapeutic candidate for preventing oxidative stress, regulating endothelial function, and maintaining the EndMT balance to provide cardiovascular protection. Although recent studies have documented improved cardiac function by melatonin, the mechanism of action of melatonin on EndMT remains unclear. The present study investigated the effects of melatonin on induced EndMT by transforming growth factor-ß2/interleukin-1ß in both in vivo and in vitro models. The results revealed that melatonin reduced the migratory ability and reactive oxygen species levels of the cells and ameliorated mitochondrial dysfunction in vitro. Our findings indicate that melatonin prevents endothelial dysfunction and inhibits EndMT by activating related pathways, including nuclear factor kappa B and Smad. We also demonstrated that this molecule plays a crucial role in restoring cardiac function by regulating the EndMT process in the ischemic myocardial condition, both in vessel organoids and myocardial infarction (MI) animal models. In conclusion, melatonin is a promising agent that attenuates EC dysfunction and ameliorates cardiac damage compromising the EndMT process after MI.

Impact of exogenous melatonin foliar application on physiology and fruit quality of wine grapes (Vitis vinifera) under salt stress.

Soil salinisation is an important abiotic stress faced in grape cultivating, leading to weakened plant vigour and reduced fruit quality. Melatonin as a novel hormone has shown positive exogenous application value. Therefore, this study used wine grape (Vitis vinifera ) 'Pinot Noir' as a test material to investigate the changes of foliar spraying with different concentrations of melatonin on the physiology and fruit quality of wine grapes in a field under simulated salt stress (200mmolL-1 NaCl). The results showed that foliar spraying of melatonin significantly increased the intercellular CO2 concentration, maximum photochemical quantum yield of PSII, relative chlorophyll and ascorbic acid content of the leaves, as well as the single spike weight, 100-grain weight, transverse and longitudinal diameters, malic acid, α-amino nitrogen and ammonia content of fruits, and decreased the initial fluorescence value of leaves, ascorbate peroxidase activity, glutathione content, fruit transverse to longitudinal ratio and tartaric acid content of plants under salt stress. Results of the comprehensive evaluation of the affiliation function indicated that 100µmolL-1 melatonin treatment had the best effect on reducing salt stress in grapes. In summary, melatonin application could enhance the salt tolerance of grapes by improving the photosynthetic capacity of grape plants under salt stress and promoting fruit development and quality formation, and these results provide new insights into the involvement of melatonin in the improvement of salt tolerance in crop, as well as some theoretical basis for the development and industrialisation of stress-resistant cultivation techniques for wine grapes.

A new method based on melatonin-mediated seed germination to quickly remove pesticide residues and improve the nutritional quality of contaminated grains.

In the present study, we attempted to use melatonin combined with germination treatment to remove pesticide residues from contaminated grains. High levels of pesticide residues were detected in soybean seeds after soaking with chlorothalonil (10 mM) and malathion (1 mM) for 2 hours. Treatment with 50 µM melatonin for 5 days completely removed the pesticide residues, while in the control group, only 61-71% of pesticide residues were removed from soybean sprouts. Compared with the control, melatonin treatment for 7 days further increased the content of ascorbic acid (by 48-66%), total phenolics (by 52-68%), isoflavones (by 22-34%), the total antioxidant capacity (by 37-40%), and the accumulated levels of unsaturated fatty acids (C18:1, C18:2, and C18:3) (by 17-30%) in soybean sprouts. Moreover, melatonin treatment further increased the accumulation of ten components of phenols and isoflavones in soybean sprouts relative to those in the control. The ability of melatonin to accelerate the degradation of pesticide residues and promote the accumulation of antioxidant metabolites might be related to its ability to trigger the glutathione detoxification system in soybean sprouts. Melatonin promoted glutathione synthesis (by 49-139%) and elevated the activities of glutathione-S-transferase (by 24-78%) and glutathione reductase (by 38-61%). In summary, we report a new method in which combined treatment by melatonin and germination rapidly degrades pesticide residues in contaminated grains and improves the nutritional quality of food.

Melatonin improves maternal sleep deprivation-induced learning and memory impairment, inflammation, and synaptic dysfunction in murine male adult offspring.

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.

Seeds Priming with Melatonin Improves Root Hydraulic Conductivity of Wheat Varieties under Drought, Salinity, and Combined Stress.

Drought and salinity stress reduce root hydraulic conductivity of plant seedlings, and melatonin application positively mitigates stress-induced damage. However, the underlying effect of melatonin priming on root hydraulic conductivity of seedlings under drought-salinity combined remains greatly unclear. In the current report, we investigated the influence of seeds of three wheat lines' 12 h priming with 100 µM of melatonin on root hydraulic conductivity (Lpr) and relevant physiological indicators of seedlings under PEG, NaCl, and PEG + NaCl combined stress. A previous study found that the combined PEG and NaCl stress remarkably reduced the Lpr of three wheat varieties, and its value could not be detected. Melatonin priming mitigated the adverse effects of combined PEG + NaCl stress on Lpr of H4399, Y1212, and X19 to 0.0071 mL·h-1·MPa-1, 0.2477 mL·h-1·MPa-1, and 0.4444 mL·h-1·MPa-1, respectively, by modulating translation levels of aquaporin genes and contributed root elongation and seedlings growth. The root length of H4399, Y1212, and X19 was increased by 129.07%, 141.64%, and 497.58%, respectively, after seeds pre-treatment with melatonin under PEG + NaCl combined stress. Melatonin -priming appreciably regulated antioxidant enzyme activities, reduced accumulation of osmotic regulators, decreased levels of malondialdehyde (MDA), and increased K+ content in stems and root of H4399, Y1212, and X19 under PEG + NaCl stress. The path investigation displayed that seeds primed with melatonin altered the modification of the path relationship between Lpr and leaf area under stress. The present study suggested that melatonin priming was a strategy as regards the enhancement of root hydraulic conductivity under PEG, NaCl, and PEG + NaCl stress, which efficiently enhanced wheat resistant to drought-salinity stress.

Crosstalk between melatonin and nitric oxide restrains Cadmium-induced oxidative stress and enhances vinblastine biosynthesis in Catharanthus roseus (L) G Don.

KEY MESSAGE: Nitric oxide functions downstream of the melatonin in adjusting Cd-induced osmotic and oxidative stresses, upregulating the transcription of D4H and DAT genes, and increasing total alkaloid and vincristine contents. A few studies have investigated the relationship between melatonin (MT) and nitric oxide (NO) in regulating defensive responses. However, it is still unclear how MT and NO interact to regulate the biosynthesis of alkaloids and vincristine in leaves of Catharanthus roseus (L.) G. Don under Cd stress. Therefore, this context was explored in the present study. Results showed that Cd toxicity (200 µM) induced oxidative stress, decreased biomass, Chl a, and Chl b content, and increased the content of total alkaloid and vinblastine in the leaves. Application of both MT (100 µM) and sodium nitroprusside (200 µM SNP, as NO donor) enhanced endogenous NO content and accordingly increased metal tolerance index, the content of total alkaloid and vinblastine. It also upregulated the transcription of two respective genes (D4H and DAT) under non-stress and Cd stress conditions. Moreover, the MT and SNP treatments reduced the content of H2O2 and malondialdehyde, increased the activities of superoxide dismutase and ascorbate peroxidase, enhanced proline accumulation, and improved relative water content in leaves of Cd-exposed plants. The scavenging NO by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy l-3-oxide (cPTIO) averted the effects of MT on the content of total alkaloid and vinblastine and antioxidative responses. Still, the effects conferred by NO on attributes mentioned above were not significantly impaired by p-chlorophenylalanine (p-CPA as an inhibitor of MT biosynthesis). These findings and multivariate analyses indicate that MT motivated terpenoid indole alkaloid biosynthesis and mitigated Cd-induced oxidative stress in the leaves of periwinkle in a NO-dependent manner.

Melatonin ameliorates 10-hydroxycamptothecin-induced oxidative stress and apoptosis via autophagy-regulated p62/Keap1/Nrf2 pathway in mouse testicular cells.

10-Hydroxycamptothecin (HCPT) is a widely used clinical anticancer drug but has a significant side effect profile. Melatonin has a beneficial impact on the chemotherapy of different cancer cells and reproductive processes, but the effect and underlying molecular mechanism of melatonin's involvement in the HCPT-induced side effects in cells, especially in the testicular cells, are poorly understood. In this study, we found that melatonin therapy significantly restored HCPT-induced testicular cell damage and did not affect the antitumor effect of HCPT. Further analysis found that melatonin therapy suppressed HCPT-induced DNA damage associated with ataxia-telangiectasia mutated- and Rad3-related and CHK1 phosphorylation levels in the testis. Changes in apoptosis-associated protein levels (Bax, Bcl-2, p53, and Cleaved caspase-3) and in reactive oxygen species-associated proteins (Nrf2 and Keap1) and index (malondialdehyde and glutathione) suggested that melatonin treatment relieved HCPT-induced cell apoptosis and oxidative damage, respectively. Mechanistically, melatonin-activated autophagy proteins (ATG7, Beclin1, and LC3bII/I) may induce p62-dependent autophagy to degrade Keap1, eliciting Nrf2 from Keap1-Nrf2 interaction to promote antioxidant enzyme expression such as HO-1, which would salvage HCPT-induced ROS production and mitochondrial dysfunction. Collectively, this study reveals that melatonin therapy may protect testicular cells from HCPT-induced damage via the activation of autophagy, which alleviates oxidative stress, mitochondrial dysfunction, and cell apoptosis.

Melatonin/Sericin Wound Healing Patches: Implications for Melanoma Therapy.

Melatonin and sericin exhibit antioxidant properties and may be useful in topical wound healing patches by maintaining redox balance, cell integrity, and regulating the inflammatory response. In human skin, melatonin suppresses damage caused by ultraviolet radiation (UVR) which involves numerous mechanisms associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and enhancing apoptosis. Sericin is a protein mainly composed of glycine, serine, aspartic acid, and threonine amino acids removed from the silkworm cocoon (particularly Bombyx mori and other species). It is of interest because of its biodegradability, anti-oxidative, and anti-bacterial properties. Sericin inhibits tyrosinase activity and promotes cell proliferation that can be supportive and useful in melanoma treatment. In recent years, wound healing patches containing sericin and melatonin individually have attracted significant attention by the scientific community. In this review, we summarize the state of innovation of such patches during 2021-2023. To date, melatonin/sericin-polymer patches for application in post-operational wound healing treatment has been only sparingly investigated and it is an imperative to consider these materials as a promising approach targeting for skin tissue engineering or regenerative dermatology.

Melatonin Enhances Neural Differentiation of Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ASCs) are adult multipotent stem cells, able to differentiate toward neural elements other than cells of mesodermal lineage. The aim of this research was to test ASC neural differentiation using melatonin combined with conditioned media (CM) from glial cells. Isolated from the lipoaspirate of healthy donors, ASCs were expanded in a basal growth medium before undergoing neural differentiation procedures. For this purpose, CM obtained from olfactory ensheathing cells and from Schwann cells were used. In some samples, 1 µM of melatonin was added. After 1 and 7 days of culture, cells were studied using immunocytochemistry and flow cytometry to evaluate neural marker expression (Nestin, MAP2, Synapsin I, GFAP) under different conditions. The results confirmed that a successful neural differentiation was achieved by glial CM, whereas the addition of melatonin alone did not induce appreciable changes. When melatonin was combined with CM, ASC neural differentiation was enhanced, as demonstrated by a further improvement of neuronal marker expression, whereas glial differentiation was attenuated. A dynamic modulation was also observed, testing the expression of melatonin receptors. In conclusion, our data suggest that melatonin's neurogenic differentiation ability can be usefully exploited to obtain neuronal-like differentiated ASCs for potential therapeutic strategies.

Melatonin-Mediated Molecular Responses in Plants: Enhancing Stress Tolerance and Mitigating Environmental Challenges in Cereal Crop Production.

Cereal crops are crucial for global food security; however, they are susceptible to various environmental stresses that significantly hamper their productivity. In response, melatonin has emerged as a promising regulator, offering potential benefits for stress tolerance and crop growth. This review explores the effects of melatonin on maize, sorghum, millet, rice, barley, and wheat, aiming to enhance their resilience to stress. The application of melatonin has shown promising outcomes, improving water use efficiency and reducing transpiration rates in millet under drought stress conditions. Furthermore, it enhances the salinity and heavy metal tolerance of millet by regulating the activity of stress-responsive genes. Similarly, melatonin application in sorghum enhances its resistance to high temperatures, low humidity, and nutrient deficiency, potentially involving the modulation of antioxidant defense and aspects related to photosynthetic genes. Melatonin also exerts protective effects against drought, salinity, heavy metal, extreme temperatures, and waterlogging stresses in maize, wheat, rice, and barley crops by decreasing reactive oxygen species (ROS) production through regulating the antioxidant defense system. The molecular reactions of melatonin upregulated photosynthesis, antioxidant defense mechanisms, the metabolic pathway, and genes and downregulated stress susceptibility genes. In conclusion, melatonin serves as a versatile tool in cereal crops, bolstering stress resistance and promoting sustainable development. Further investigations are warranted to elucidate the underlying molecular mechanisms and refine application techniques to fully harness the potential role of melatonin in cereal crop production systems.

Localized surface plasmon resonance and atomic force microscopy study of model lipid membranes and their interactions with amyloid and melatonin.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain. The toxicity of amyloid to neuronal cell surfaces arises from interactions between small intermediate aggregates, namely amyloid oligomers, and the cell membrane. The nature of these interactions changes with age and disease progression. In our previous work, we demonstrated that both membrane composition and nanoscale structure play crucial roles in amyloid toxicity, and that membrane models mimicking healthy neuron were less affected by amyloid than model membranes mimicking AD neuronal membranes. This understanding introduces the possibility of modifying membrane properties with membrane-active molecules, such as melatonin, to protect them from amyloid-induced damage. In this study, we employed atomic force microscopy and localized surface plasmon resonance to investigate the protective effects of melatonin. We utilized synthetic lipid membranes that mimic the neuronal cellular membrane at various stages of AD and explored their interactions with amyloid-ß(1-42) in the presence of melatonin. Our findings reveal that the early diseased membrane model is particularly vulnerable to amyloid binding and subsequent damage. However, melatonin exerts its most potent protective effect on this early-stage membrane. These results suggest that melatonin could act at the membrane level to alleviate amyloid toxicity, offering the most protection during the initial stages of AD.

THE EFFECT OF MELATONIN ON THE SERUM LEVEL OF INTERLEUKIN 31 IN HERPESVIRUS SKIN DISEASES ON THE BACKGROUND OF HIV.

The immune system of the skin is the first line of defense against various infections, on the other hand, its strategic location as a key barrier between external and internal environment makes the skin an important tool for maintaining homeostasis, so dermatological lesions are often a manifestation of various pathological conditions. Thus, herpesvirus skin diseases, which are the result of reactivation of a latent infection and occur against the background of human immunodeficiency, may be the first manifestation of HIV. Active study of melatonin in recent years in the dermatological field is associated with interest in its biological action, which extends to the skin due to the melatoninergic system, and promising prospects for the development of new treatments. The aim of this study was to investigate the effect of melatonin on the serum levels of interleukin 31 in herpesvirus skin diseases on the background of HIV. The current study selected 40 HIV patients who had an acute herpesvirus infection caused by HSV-1, HSV-2, VZV, EBV, and HHV-8 were selected. Patients were divided into two groups: group I consisted of patients receiving antiretroviral therapy, valaciclovir in standard therapeutic doses and melatonin as immunomodulatory therapy. Patients in the melatonin group received two melatonin tablet, 3 mg for 14 days, 6 mg daily (two doses of 3 mg). Group II included patients who received antiretroviral therapy in combination with valaciclovir. Serum levels of IL-31 were measured before and after 14 days of therapeutic intervention. The mean serum level of IL-31 was significantly lower in the melatonin group (p˂0.05). Also, in both groups, serum levels of IL-31 showed a significant increase compared to the indicator of the norm. The results of this study showed that melatonin administration could modify inflammatory cytokines secretion such as IL-31. Given the low toxicity of melatonin and its ability to reduce side effects and increase the efficiency of therapeutic agents, its use may be important and significant in combined therapy in combination with highly active antiretroviral therapy.

Exogenous melatonin delays leaves senescence and enhances saline and alkaline stress tolerance in grape seedlings.

Saline and alkaline stress is one of the major abiotic stresses facing agricultural production, which severely inhibits the growth and yield of plant. The application of plant growth regulators can effectively prevent crop yield reduction caused by saline and alkaline stress. Exogenous melatonin (MT) can act as a signaling molecule involved in the regulation of a variety of physiological processes in plants, has been found to play a key role in enhancing the improvement of plant tolerance to abiotic stresses. However, the effects of exogenous MT on saline and alkaline tolerance of table grape seedlings and its mechanism have not been clarified. The aim of this study was to investigate the role of exogenous MT on morphological and physiological growth of table grape seedlings (Vitis vinifera L.) under saline and alkaline stress. The results showed that saline and alkaline stress resulted in yellowing and wilting of grape leaves and a decrease in chlorophyll content, whereas the application of exogenous MT alleviated the degradation of chlorophyll in grape seedling leaves caused by saline and alkaline stress and promoted the accumulation of soluble sugars and proline content. In addition, exogenous MT increased the activity of antioxidant enzymes, which resulted in the scavenging of reactive oxygen species (ROS) generated by saline and alkaline stress. In conclusion, exogenous MT was involved in the tolerance of grape seedlings to saline and alkaline stress, and enhanced the saline and alkaline resistance of grape seedlings to promote the growth and development of the grape industry in saline and alkaline areas.

Metabolome and Transcriptome Analysis Revealed the Pivotal Role of Exogenous Melatonin in Enhancing Salt Tolerance in Vitis vinifera L.

Vitis vinifera L. possesses high economic value, but its growth and yield are seriously affected by salt stress. Though melatonin (MT) has been widely reported to enhance tolerance towards abiotic stresses in plants, the regulatory role melatonin plays in resisting salt tolerance in grapevines has scarcely been studied. Here, we observed the phenotypes under the treatment of different melatonin concentrations, and then transcriptome and metabolome analyses were performed. A total of 457 metabolites were detected in CK- and MT-treated cell cultures at 1 WAT (week after treatment) and 4 WATs. Exogenous melatonin treatment significantly increased the endogenous melatonin content while down-regulating the flavonoid content. To be specific, the melatonin content was obviously up-regulated, while the contents of more than a dozen flavonoids were down-regulated. Auxin response genes and melatonin synthesis-related genes were regulated by the exogenous melatonin treatment. WGCNA (weighted gene coexpression network analysis) identified key salt-responsive genes; they were directly or indirectly involved in melatonin synthesis and auxin response. The synergistic effect of salt and melatonin treatment was investigated by transcriptome analysis, providing additional evidence for the stress-alleviating properties of melatonin through auxin-related pathways. The present study explored the impact of exogenous melatonin on grapevines' ability to adapt to salt stress and provided novel insights into enhancing their tolerance to salt stress.

A Clinical, Pharmacological, and Formulation Evaluation of Melatonin in the Treatment of Ocular Disorders-A Systematic Review.

Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.

Impact of Melatonin Supplementation on Sports Performance and Circulating Biomarkers in Highly Trained Athletes: A Systematic Review of Randomized Controlled Trials.

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