Development, Characterization, and Evaluation of Potential Systemic Toxicity of a Novel Oral Melatonin Formulation.

The need to create safe materials for biomedical and pharmaceutical applications has become a significant driving force for the development of new systems. Therefore, a chitosan-coated copolymer of itaconic acid, acrylic acid, and N-vinyl caprolactam (IT-AA-NVC) was prepared by radical polymerization and subsequent coating via nanoprecipitation to give a system capable of sustained delivery of melatonin. Although melatonin brings undoubted benefits to the human body, aspects of the optimal dose, route, and time of administration for the obtaining of suitable treatment outcomes remain under discussion. The entrapment of melatonin in biocompatible polymeric systems can prevent its oxidation, decrease its toxicity, and provide an increased half-life, resulting in an enhanced pharmacokinetic profile with improved patient compliance. The structures of the biopolymer and conjugate were proven by FTIR, thermal properties were tested by DSC, and the morphologies were followed by SEM. The loading efficiency and in vitro release profile were studied by means of HPLC, and a delayed release profile with an initial burst was obtained. The potential systemic toxicity of the formulation was studied in vivo; a mild hepatotoxicity was observed following administration of the melatonin-loaded formulation to mice, both by histopathology and blood clinical biochemistry. Histopathology showed a mild nephrotoxicity as well; however, kidney clinical biochemistry did not support this.

Melatonin-mediated low-temperature tolerance of cucumber seedlings requires Ca2+/CPKs signaling pathway.

Melatonin (Mel) is recognized as a prominent plant growth regulator. This study investigated the alleviating effect of Mel pretreatment on growth inhibition caused by low-temperature (LT) stress (10 °C/6 °C) in cucumber seedlings and explored the role of the Ca2+/Calcium-dependent protein kinases (CPKs) signaling pathway in Mel-regulated LT tolerance. The main results are as follows: compared to LT treatment alone, 100 µM Mel increased both the content of Ca2+ (highest about 42.01%) and the expression levels of Ca2+ transporter and cyclic nucleotide-gated channel (CNGC) genes under LT. Similarly, Mel enhanced the content of CPKs (highest about 27.49%) and the expression levels of CPKs family genes in cucumber leaves under LT. Additionally, pretreatment with 100 µM Mel for three days strengthened the antioxidant defense and photosynthesis of seedlings under LT. Genes in the ICE-CBF-COR pathway and the MAPK cascade were upregulated by Mel, with maximum upregulations reaching approximately 2.5-fold and 1.9-fold, respectively, thus conferring LT tolerance to cucumber seedlings. However, the above beneficial effects of Mel were weakened by co-treatment with calcium signaling blockers (LaCl3 or EGTA) or CPKs inhibitors (TFP or W-7), suggesting that the Ca2+/CPKs pathway is involved in the Mel-mediated regulation of LT tolerance. In conclusion, this study revealed that Mel can alleviate growth inhibition in cucumber seedlings under LT stress and demonstrated that the Ca2+/CPKs signaling pathway is crucial for the Mel-mediated enhancement of LT tolerance. The findings hold promise for providing theoretical insights into the application of Mel in agricultural production and for investigating its underlying mechanisms of action.

Melatonin synergistically potentiates the effect of methylprednisolone on reducing neuroinflammation in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of unknown etiology characterized by infiltration of encephalitogenic cells in the central nervous system (CNS) resulting in the presence of multifocal areas of demyelination leading to neurodegeneration. The infiltrated immune cells population is composed mainly of effector CD4+ and CD8+ T lymphocytes, B cells, macrophages, and dendritic cells that secrete pro-inflammatory factors that eventually damage myelin leading to axonal damage. The most common clinical form of MS is relapsing-remitting (RR), characterized by neuroinflammatory episodes followed by partial or total recovery of neurological deficits. The first-line treatment for RRMS relapses is a high dose of glucocorticoids, especially methylprednisolone, for three to five consecutive days. Several studies have reported the beneficial effects of melatonin in the context of neuroinflammation associated with MS or experimental autoimmune encephalomyelitis (EAE), the preclinical model for MS. Therefore, the objective of this study was to evaluate the effect of the combined treatment of melatonin and methylprednisolone on the neuroinflammatory response associated with the EAE development. This study shows for the first time the protective synergistic effect of co-treatment with melatonin and methylprednisolone on reducing the severity of EAE by decreasing CD4 lymphocytes, B cells, macrophages and dendritic cells in the CNS, as well as modulating the population of infiltrated T and B cells toward regulatory phenotypes to the detriment of pro-inflammatory effector functions. In addition to the potentiation of the protective role of methylprednisolone, treatment with melatonin from the clinical onset of EAE improves the natural course of the EAE and the response to a subsequent treatment with methylprednisolone in a later relapse of the disease, pointing melatonin as potential therapeutic tool in combination with methylprednisolone for the treatment of relapses in MS.

The vascular influence of melatonin on endothelial response to angiotensin II in diabetic rat aorta.

The current study explored melatonin (MEL) and its receptors, including MEL type 1 receptor (MT1) receptor and MEL type 2 receptor (MT2), along with the angiotensin-converting enzyme 2 (ACE2), influence on vascular responses to angiotensin II (Ang II) in rat aortic segments of normal and diabetic rats. The isolated aortic segments were exposed to MEL, the MEL agonist; ramelteon (RAM), the MEL antagonist; luzindole (LUZ), and an ACE2 inhibitor (S, S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3 H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid,) on Ang II-induced contractions in non-diabetic normal endothelium (non-DM E+), non-diabetic removed endothelium (non-DM E-), and streptozotocin-induced diabetic endothelium-intact (STZ-induced DM E+) rat aortic segments, as well as their combination in STZ-induced DM E + segments, were also included. The current results showed that MEL and RAM shifted Ang II dose-response curve (DRC) to the right side in non-DM E + and non-DM E- aorta but not in STZ-induced DM E + aorta. However, ACE2 inhibition abolished Ang II degradation only in STZ-induced DM E + segments, not in non-DM E + segments. Additionally, the combinations of MEL-LUZ and RAM-ACE2 inhibitor caused a rightward shift in Ang II response in STZ-induced DM E + segments, while the MEL-LUZ combination decreased Ang II DRC. The findings suggest that the effects of MEL and ACE2 inhibitor on Ang II responses depend on the condition of the endothelium and the distribution of the MEL receptors.

Poly(2-Hydroxyethyl Methacrylate) Hydrogel-Based Microneedles for Bioactive Release.

Microneedle arrays are minimally invasive devices that have been extensively investigated for the transdermal/intradermal delivery of drugs/bioactives. Here, we demonstrate the release of bioactive molecules (estradiol, melatonin and meropenem) from poly(2-hydroxyethyl methacrylate), pHEMA, hydrogel-based microneedle patches in vitro. The pHEMA hydrogel microneedles had mechanical properties that were sufficiently robust to penetrate soft tissues (exemplified here by phantom tissues). The bioactive release from the pHEMA hydrogel-based microneedles was fitted to various models (e.g., zero order, first order, second order). Such pHEMA microneedles have potential application in the transdermal delivery of bioactives (exemplified here by estradiol, melatonin and meropenem) for the treatment of various conditions.

Mitochondria of Porcine Oocytes Synthesize Melatonin, Which Improves Their In Vitro Maturation and Embryonic Development.

The in vitro maturation efficiency of porcine oocytes is relatively low, and this limits the production of in vitro porcine embryos. Since melatonin is involved in mammalian reproductive physiology, in this study, we have explored whether endogenously produced melatonin can help in porcine oocyte in vitro maturation. We have found, for the first time in the literature, that mitochondria are the major sites for melatonin biosynthesis in porcine oocytes. This mitochondrially originated melatonin reduces ROS production and increases the activity of the mitochondrial respiratory electron transport chain, mitochondrial biogenesis, mitochondrial membrane potential, and ATP production. Therefore, melatonin improves the quality of oocytes and their in vitro maturation. In contrast, the reduced melatonin level caused by siRNA to knockdown AANAT (siAANAT) is associated with the abnormal distribution of mitochondria, decreasing the ATP level of porcine oocytes and inhibiting their in vitro maturation. These abnormalities can be rescued by melatonin supplementation. In addition, we found that siAANAT switches the mitochondrial oxidative phosphorylation to glycolysis, a Warburg effect. This metabolic alteration can also be corrected by melatonin supplementation. All these activities of melatonin appear to be mediated by its membrane receptors since the non-selective melatonin receptor antagonist Luzindole can blunt the effects of melatonin. Taken together, the mitochondria of porcine oocytes can synthesize melatonin and improve the quality of oocyte maturation. These results provide an insight from a novel aspect to study oocyte maturation under in vitro conditions.

Participation of Ca2+-calmodulin dependent protein kinase II in the antidepressant like effects of melatonin.

Melatonin (N-acetyl-5 methoxytriptamine) is an indolamine secreted by the pineal gland during the dark phase of the photoperiod. Its main function is the synchronization of different body rhythms with the dark-light cycle. Research on melatonin has significantly advanced since its discovery and we now know that it has considerable significance in various physiological processes, including immunity, aging, and reproduction. Moreover, in recent years evidence of the pharmacological possibilities of melatonin has increased. The indolamine, on the other hand, has antidepressant-like effects in rodents, which may be mediated by the activation of CaMKII and are also related to the regulation of neuroplasticity processes, including neurogenesis, synaptic maintenance, and long-term potentiation. Remarkably, patients with major depression show decreased levels of circulating melatonin in plasma. This review presents evidence of the antidepressant-like effects of melatonin in preclinical models, and the participation of CaMKII in these actions. CaMKII's role in cognition and memory processes, which are altered in depressive states, are part of the review and the effects of melatonin in these processes are also reviewed. Furthermore, participation of CaMKII on structural and synaptic plasticity and the effects of melatonin are also described. Finally, the advantages of using melatonin in combination with other antidepressants such as ketamine for neuroplasticity are described. Evidence supports that CaMKII is activated by melatonin, downstream melatonin receptors and may be the common effector in the synergistic effects of melatonin with other antidepressants. Significance Statement This review compiled evidence in support that melatonin causes antidepressant-like effects in mice through calmodulin kinase II stimulation downstream melatonin receptors, as well as the participation of this enzyme in neuroplasticity, memory, and cognition. Finally, we describe evidence about the effectiveness of antidepressant like effects of melatonin in combination with ketamine.

From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction.

Sepsis-induced multiple organ dysfunction arises from the highly complex pathophysiology encompassing the interplay of inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Over the past decades, numerous studies have been dedicated to elucidating the underlying molecular mechanisms of sepsis in order to develop effective treatments. Current research underscores liver and cardiac dysfunction, along with acute lung and kidney injuries, as predominant causes of mortality in sepsis patients. This understanding of sepsis-induced organ failure unveils potential therapeutic targets for sepsis treatment. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, and gut microbiota modulators, have demonstrated efficacy in different sepsis models. In recent years, the research focus has shifted from anti-inflammatory and antioxidative agents to exploring the modulation of energy metabolism and gut microbiota in sepsis. These approaches have shown a significant impact in preventing multiple organ damage and mortality in various animal sepsis models but require further clinical investigation. The accumulation of this knowledge enriches our understanding of sepsis and is anticipated to facilitate the development of effective therapeutic strategies in the future.

Melatonin as a Circadian Marker for Plasmodium Rhythms.

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

Integrating network pharmacology and experimental evaluation to explore the complementary therapeutic effect and mechanism of melatonin in periodontitis.

Objective: To explore the potential targets for melatonin in the treatment of periodontitis through network pharmacologic analysis and experimental validation via in vivo animal models and in vitro cellular experiments. Materials and methods: In this study, we first screened melatonin targets from Pharm Mapper for putative targets, Drug Bank, and TCMSP databases for known targets. Then, disease database was searched and screened for differential expressed genes associated with periodontitis. The intersection of disease and melatonin-related genes yielded potential target genes of melatonin treatment for periodontitis. These target genes were further investigated by protein-protein interaction network and GO/KEGG enrichment analysis. In addition, the interactions between melatonin and key target genes were interrogated by molecular docking simulations. Then, we performed animal studies to validate the therapeutic effect of melatonin by injecting melatonin into the peritoneal cavity of ligation-induced periodontitis (LIP) mice. The effects of melatonin on the predicted target proteins were also analyzed using Western blot and immunofluorescence techniques. Finally, we constructed an in vitro cellular model and validated the direct effect of melatonin on the predicted targets by using qPCR. Results: We identified 8 potential target genes by network pharmacology analysis. Enrichment analysis suggests that melatonin may treat periodontitis by inhibiting the expression of three potential targets (MPO, MMP8, and MMP9). Molecular docking results showed that melatonin could effectively bind to MMP8 and MMP9. Subsequently, melatonin was further validated in a mouse LIP model to inhibit the expression of MPO, MMP8, and MMP9 in the periodontal tissue. Finally, we verified the direct effect of melatonin on the mRNA expression of MPO, MMP8, and MMP9 in an in vitro cellular model. Conclusions: Through a combination of network pharmacology and experimental validation, this study provides a more comprehensive understanding of the mechanism of melatonin to treat periodontitis. Our study suggests that MPO, MMP8, and MMP9 as key target genes of melatonin to treat periodontitis. These findings present a more comprehensive basis for further investigation into the mechanisms of pharmacological treatment of periodontitis by melatonin.

Measuring Sleep and Activity Patterns in Adult Zebrafish.

Sleep is an essential behavior that is still poorly understood. Sleep abnormalities accompany a variety of psychiatric and neurological disorders, and sleep can serve as a modifiable behavior in the treatment of these disorders. Zebrafish (Danio rerio) has proven to be a powerful model organism to study sleep and the interplay between sleep and these disorders due to the high conservation of the neuro-modulatory mechanisms that control sleep and wake states between zebrafish and humans. The zebrafish is a diurnal vertebrate with a relatively simple nervous system compared to mammalian models, exhibiting conservation of sleep ontogeny across different life stages. Zebrafish larvae are an established high-throughput model to assess sleep phenotypes and the biological underpinnings of sleep disturbances. To date, sleep measurement in juvenile and adult zebrafish has not been performed in a standardized and reproducible manner because of the relatively low-throughput nature in relation to their larval counterparts. This has left a gap in understanding sleep across later stages of life that are relevant to many psychiatric and neurodegenerative disorders. Several research groups have used homemade systems to address this gap. Here, we report employing commercially available equipment to track activity and sleep/wake patterns in juvenile and adult zebrafish. The equipment allows researchers to perform automated behavior assays in an isolated environment with light/dark and temperature control for multiple days. We first explain the experimental procedure to track the sleep and activity of adult zebrafish and then validate the protocol by measuring the effects of melatonin and DMSO administration. Key features • Allows an isolated and controllable environment to carry out activity and sleep assays in juvenile and adult zebrafish. • Measures activity of zebrafish in life stages later than early development, which requires feeding animals during the assay. • Requires use of a commercially available equipment system and six tanks. • The activity of zebrafish can be tracked for five days including an acclimation step.

Serum melatonin levels in type 2 diabetic patients with depressive symptoms compared to non-depressed individuals.

Background: Melatonin, mainly regulating the body's circadian rhythm, may have protective effects against type 2 diabetes mellitus (DM2)-induced depression due to its antioxidant and regulatory impact in the pathogenesis of both DM2 and depression. This study aimed to find the association of serum melatonin levels with depression in DM2 patients. Methods: A total of 50 DM2 patients were recruited in this retrospective cross-sectional study and divided into 25 patients with depression (DM2-DP) and 25 without depression symptoms (DM2-NDP). Depression was diagnosed using the Hospital Anxiety and Depression Scale (HADS) assessment. Fasting blood samples were collected and examined for the level of serum melatonin and other biomarkers. All statistical analysis was performed by SPSS software Version 22, and a p-value less than 0.05 was considered statistically significant for all tests. Results: The depression score was significantly lower in DM2-NDP than DM2-DP (p< 0.001). The mean weight was significantly lower in the DM2-DP group (P= 0.021). Total cholesterol, triglyceride, and anxiety scores were higher, and the melatonin level was lower in DM2-DP. The correlation of melatonin levels was positive with age, DBP, HbA1C, FBS, and TG. In contrast, it was negative with male gender, BMI, diabetes duration, SBP, TC, family history of DM, depression score, and anxiety score. However, no significant differences were seen. Conclusion: Lower melatonin may be associated with depression and anxiety in patients with DM2. The serum melatonin level might be a strong predictor of depression in DM2 patients.

Metabolic and Microbial Dysregulation in Preterm Infants with Neonatal Respiratory Distress Syndrome: An Early Developmental Perspective.

Neonatal respiratory distress syndrome (NRDS) is one of the most severe respiratory disorders in preterm infants (PTIs) due to immature lung development. To delineate the serum metabolic alterations and gut microbiota variations in NRDS and assess their implications on neonatal development, we enrolled 13 NRDS neonates and 12 PTIs and collected fecal and serum specimens after birth. Longitudinal fecal sampling was conducted weekly for a month in NRDS neonates. NRDS neonates were characterized by notably reduced gestational ages and birth weights and a higher rate of asphyxia at birth relative to PTIs. Early postnatal disturbances in tryptophan metabolism were evident in the NRDS group, concomitant with elevated relative abundance of Haemophilus, Fusicatenibacter, and Vibrio. Integrative multiomics analyses revealed an inverse relationship between tryptophan concentrations and Blautia abundance. At one-week old, NRDS neonates exhibited cortisol regulation anomalies and augmented hepatic catabolism. Sequential microbial profiling revealed distinct gut microbiota evolution in NRDS subjects, characterized by a general reduction in potentially pathogenic bacteria. The acute perinatal stress of NRDS leads to mitochondrial compromise, hormonal imbalance, and delayed gut microbiota evolution. Despite the short duration of NRDS, its impact on neonatal development is significant and requires extended attention.

Melatonin via MTNR1B regulates METTL3 to protect ileum cell differentiation.

Intestinal stem cells rapidly differentiate into various epithelial cells, playing a crucial role in maintaining intestinal homeostasis. Melatonin, a known endogenous molecule with anti-inflammatory and antioxidant properties, has its potential efficacy in ileum stem cells differentiation not fully understood to date. This study indicates that melatonin suppresses ileum inflammation and maintains normal differentiation of ileum stem cells through MTNR1B. Subsequent outcomes following treatment with MTNR1B inhibitors further substantiate these findings. Additionally, overexpression of METTL3 protein appears to be a potential instigator for promoting ileum inflammation and disruptions in cell differentiation. Treatment with the METTL3 inhibitor SAH significantly inhibits ileum inflammation and Wnt/ß-catenin activity, thereby sustaining normal cellular differentiation functions. In summary, this study showed that melatonin may improve ileum inflammation and maintain cell differentiation functions by inhibiting abnormal METTL3 expression via MTNR1B.

Overexpression of oHIOMT results in various morphological, anatomical, physiological and molecular changes in switchgrass.

Introduction: Melatonin (N-acetyl-5-methoxytryptamine) is a molecule implicated in multiple biological functions, but exerts contrasting effects on plants owing to concentration differences. Hydroxyindole O-methyltransferase (HIOMT), which catalyzes the last step of melatonin synthesis, plays a crucial role in this context. Methods: Transgenic switchgrass overexpressing oHIOMT with different melatonin levels displayed distinct morphological changes in a concentration-dependent manner. In this study, we divided the transgenic switchgrass into two groups: melatonin-moderate transgenic (MMT) plants and melatonin-rich transgenic (MRT) plants. To determine the concentration-dependent effect of melatonin on switchgrass growth and stress resistance, we conducted comparative morphological, physiological, omics and molecular analyses between MMT, MRT and wild-type (WT) plants. Results: We found that oHIOMT overexpression, with moderate melatonin levels, was crucial in regulating switchgrass growth through changes in cell size rather than cell number. Moderate levels of melatonin were vital in regulating carbon fixation, stomatal development and chlorophyll metabolism. Regarding salt tolerance, melatonin with moderate levels activated numerous defense (e.g. morphological characteristics, anatomical structure, antioxidant enzymatic properties, non-enzymatic capacity and Na+/K+ homeostasis). Additionally, moderate levels of oHIOMT overexpression were sufficient to increase lignin content and alter monolignol compositions with an increase in the S/G lignin ratio. Discussion: Taken together, oHIOMT overexpression in switchgrass with different melatonin levels resulted in morphological, anatomical, physiological and molecular changes in a concentration-dependent manner, which characterized by stimulation at low doses and inhibition at high doses. Our study presents new ideas and clues for further research on the mechanisms of the concentration-dependent effect of melatonin.

Physiological, transcriptomic and metabolomic insights of three extremophyte woody species living in the multi-stress environment of the Atacama Desert.

MAIN CONCLUSIONS: In contrast to Neltuma species, S. tamarugo exhibited higher stress tolerance, maintaining photosynthetic performance through enhanced gene expression and metabolites. Differentially accumulated metabolites include chlorophyll and carotenoids and accumulation of non-nitrogen osmoprotectants. Plant species have developed different adaptive strategies to live under extreme environmental conditions. Hypothetically, extremophyte species present a unique configuration of physiological functions that prioritize stress-tolerance mechanisms while carefully managing resource allocation for photosynthesis. This could be particularly challenging under a multi-stress environment, where the synthesis of multiple and sequential molecular mechanisms is induced. We explored this hypothesis in three phylogenetically related woody species co-occurring in the Atacama Desert, Strombocarpa tamarugo, Neltuma alba, and Neltuma chilensis, by analyzing their leaf dehydration and freezing tolerance and by characterizing their photosynthetic performance under natural growth conditions. Besides, the transcriptomic profiling, biochemical analyses of leaf pigments, and metabolite analysis by untargeted metabolomics were conducted to study gene expression and metabolomic landscape within this challenging multi-stress environment. S. tamarugo showed a higher photosynthetic capacity and leaf stress tolerance than the other species. In this species, a multifactorial response was observed, which involves high photochemical activity associated with a higher content of chlorophylls and ß-carotene. The oxidative damage of the photosynthetic apparatus is probably attenuated by the synthesis of complex antioxidant molecules in the three species, but S. tamarugo showed the highest antioxidant capacity. Comparative transcriptomic and metabolomic analyses among the species showed the differential expression of genes involved in the biosynthetic pathways of key stress-related metabolites. Moreover, the synthesis of non-nitrogen osmoprotectant molecules, such as ciceritol and mannitol in S. tamarugo, would allow the nitrogen allocation to support its high photosynthetic capacity without compromising leaf dehydration tolerance and freezing stress avoidance.

The effect of phototherapy treatment on serum melatonin levels in term newborns.

Background/aim: The aim of this study was to investigate the effect of phototherapy treatment on serum melatonin levels in term newborn infants. Material and methods: This study was planned as a single-center, prospective, observational, case-control study. Term infants (gestation week ≥37 weeks) who received at least 6 h of phototherapy due to jaundice constitute the phototherapy group, while the term infants without jaundice and who were exclusively breastfed constitute the control group. Melatonin levels were examined by taking blood samples from babies in both groups at 02:00 at night. Melatonin values were compared between groups. The effect of phototherapy on serum melatonin levels was investigated. The relationship between the duration of phototherapy and maximum serum bilirubin values on melatonin values was investigated. Results: Seventy term infants (64.3% girls) were included in the study. Mean gestational week was 38.3 ± 1.1 weeks, mean birth weight was 3295 ± 434 g. There was no statistically significant difference between the phototherapy group and the control group in terms of sex, type of delivery, gestational week, birth weight, height, and head circumference (all p > 0.05). Serum melatonin level was 20.3 ± 5.9 pg/mL (range: 8.7-36.6 pg/mL) in the phototherapy group and 19.9 ± 4.38 pg/mL (range: 9.9-26.3 pg/mL) in the control group. There was no significant difference between the two groups in terms of serum melatonin levels (p = 0.155). The mean total bilirubin value was 17.65 ± 1.48 mg/dL, and the average duration of phototherapy application was 13.94 ± 7.64 h in the babies in the phototherapy group. No correlation was found between the duration of phototherapy application and serum melatonin levels (p = 0.791). Conclusion: It was determined that there was no significant difference in serum melatonin levels in term newborn babies who received phototherapy for at least 6 h due to jaundice. No correlation was found between the duration of phototherapy application and the serum melatonin level of the maximum bilirubin values.

Melatonin inhibits apoptosis and oxidative tissue damage in cisplatin-induced pulmonary toxicity in rats.

Introduction: Cisplatin is one of the most frequently used chemotherapeutics, which is known to cause both tumor and normal lung tissue damage through the generation of free radicals and cells apoptosis/necrosis. Melatonin is a neurohormone that regulates numerous physiological processes in the body both through receptor pathways and by maintaining tissue redox homeostasis. Material and methods: The extent of rat lung damage induced by cisplatin and the effects of melatonin on this process was determined based on the pathohistological changes and biochemical disturbances in tissue lipid peroxidation, protein carbonyl modification and in the activity of xanthine oxidase (XO), caspase-3 and DNases. Results: Histopathological analysis of rat lung tissue obtained from animals that received cisplatin found them to be edematous, with significant deterioration of alveolar epithelium. These morphological changes are accompanied by a significant increase in all studied oxidative stress-related parameters, as well as with the activity of apoptosis-related enzymes. A five-day treatment with melatonin completely prevented a cisplatin-induced increase in oxidative stress-related parameters and in the activity of XO, caspase-3 and alkaline DNase. Also, the histopathological changes observed during microscopic analysis were much less pronounced than in the group that received cisplatin only. Conclusions: These results can potentially be connected with the ability of melatonin to inhibit the activity of XO, caspase-3 and alkaline DNase and/or its ability to scavenge free radicals, thus preventing lung damage induced by cisplatin.

Effects of melatonin supplementation on markers of inflammation and oxidative stress in patients with diabetes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Diabetes mellitus is a metabolic disorder, in which chronic systemic inflammation and oxidative stress contribute to the progression of this condition and its complications. Melatonin, a hormone known for its potent antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic intervention in diabetes. This review aims to evaluate the effects of melatonin supplementation on markers of oxidative stress and inflammation in diabetic patients. METHODS: A thorough literature search of databases, including PubMed, Embase, Web of Science, Cochrane Central, CNKI, and Scopus, was conducted through October 2023. We included randomized controlled trials investigating the effects of melatonin on markers of inflammation and oxidative stress, compared to placebo in patients with diabetes. The data was analyzed using the random-effects model and the summary effect size was determined using the standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: Fourteen studies with 823 participants were included. Our analysis indicates that melatonin can lead to significant reductions in levels of C-reactive protein (CRP) [SMD = -0.75; 95% CI: -1.37, -0.12; P = 0.018], tumor necrosis factor-alpha (TNF-α) [SMD = -0.40; 95% CI: -0.64, -0.15; P = 0.001], interleukin (IL)-1 [SMD = -0.75; 95% CI: -1.03, -0.47; P < 0.0001], IL-6 [SMD = -0.79; 95% CI: -1.07, -0.51; P < 0.0001], and malondialdehyde (MDA) [SMD = -0.61; 95% CI: -0.80, -0.43; P < 0.0001]. Furthermore, we found a significant increase in levels of total antioxidant capacity (TAC) [SMD = 0.81; 95% CI: 0.12, 1.51; P = 0.021], glutathione (GSH) [SMD = 0.66; 95% CI: 0.28, 1.03; P = 0.001], and superoxide dismutase (SOD) [SMD = 1.69; 95% CI: 0.80, 2.58; P < 0.0001] following melatonin consumption in patients with diabetes. CONCLUSION: Melatonin supplementation is a promising complementary strategy to attenuate oxidative stress and inflammation in diabetic patients.

An ecotype-specific effect of osmopriming and melatonin during salt stress in Arabidopsis thaliana.

BACKGROUND: Natural populations of Arabidopsis thaliana exhibit phenotypic variations in specific environments and growth conditions. However, this variation has not been explored after seed osmopriming treatments. The natural variation in biomass production and root system architecture (RSA) was investigated across the Arabidopsis thaliana core collection in response to the pre-sawing seed treatments by osmopriming, with and without melatonin (Mel). The goal was to identify and characterize physiologically contrasting ecotypes. RESULTS: Variability in RSA parameters in response to PEG-6000 seed osmopriming with and without Mel was observed across Arabidopsis thaliana ecotypes with especially positive impact of Mel addition under both control and 100 mM NaCl stress conditions. Two ecotypes, Can-0 and Kn-0, exhibited contrasted root phenotypes: seed osmopriming with and without Mel reduced the root growth of Can-0 plants while enhancing it in Kn-0 ones under both control and salt stress conditions. To understand the stress responses in these two ecotypes, main stress markers as well as physiological analyses were assessed in shoots and roots. Although the effect of Mel addition was evident in both ecotypes, its protective effect was more pronounced in Kn-0. Antioxidant enzymes were induced by osmopriming with Mel in both ecotypes, but Kn-0 was characterized by a higher responsiveness, especially in the activities of peroxidases in roots. Kn-0 plants experienced lower oxidative stress, and salt-induced ROS accumulation was reduced by osmopriming with Mel. In contrast, Can-0 exhibited lower enzyme activities but the accumulation of proline in its organs was particularly high. In both ecotypes, a greater response of antioxidant enzymes and proline accumulation was observed compared to mechanisms involving the reduction of Na+ content and prevention of K+ efflux. CONCLUSIONS: In contrast to Can-0, Kn-0 plants grown from seeds osmoprimed with and without Mel displayed a lower root sensitivity to NaCl-induced oxidative stress. The opposite root growth patterns, enhanced by osmopriming treatments might result from different protective mechanisms employed by these two ecotypes which in turn result from adaptive strategies proper to specific habitats from which Can-0 and Kn-0 originate. The isolation of contrasting phenotypes paves the way for the identification of genetic factors affecting osmopriming efficiency.