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Tan, Dun-Xian, i Rüdiger Hardeland. "The Reserve/Maximum Capacity of Melatonin’s Synthetic Function for the Potential Dimorphism of Melatonin Production and Its Biological Significance in Mammals". Molecules 26, nr 23 (2.12.2021): 7302. http://dx.doi.org/10.3390/molecules26237302.
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In this article, we attempt to classify a potential dimorphism of melatonin production. Thus, a new concept of “reserve or maximum capacity of melatonin synthetic function” is introduced to explain the subtle dimorphism of melatonin production in mammals. Considering ASMT/ASMTL genes in the pseudoautosomal region of sex chromosomes with high prevalence of mutation in males, as well as the sex bias of the mitochondria in which melatonin is synthesized, we hypothesize the existence of a dimorphism in melatonin production to favor females, which are assumed to possess a higher reserve capacity for melatonin synthesis than males. Under physiological conditions, this subtle dimorphism is masked by the fact that cells or tissues only need baseline melatonin production, which can be accomplished without exploiting the full potential of melatonin’s synthetic capacity. This capacity is believed to exceed the already remarkable nocturnal increase as observed within the circadian cycle. However, during aging or under stressful conditions, the reserve capacity of melatonin’s synthetic function is required to be activated to produce sufficiently high levels of melatonin for protective purposes. Females seem to possess a higher reserve/maximum capacity for producing more melatonin than males. Thus, this dimorphism of melatonin production becomes manifest and detectable under these conditions. The biological significance of the reserve/maximum capacity of melatonin’s synthetic function is to improve the recovery rate of organisms from injury, to increase resistance to pathogen infection, and even to enhance their chances of survival by maximizing melatonin production under stressful conditions. The higher reserve/maximum capacity of melatonin synthesis in females may also contribute to the dimorphism in longevity, favoring females in mammals.
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Wang, Tong-Hong, Chuen Hsueh, Chin-Chuan Chen, Wan-Syuan Li, Chau-Ting Yeh, Jang-Hau Lian, Junn-Liang Chang i Chi-Yuan Chen. "Melatonin Inhibits the Progression of Hepatocellular Carcinoma through MicroRNA Let7i-3p Mediated RAF1 Reduction". International Journal of Molecular Sciences 19, nr 9 (10.09.2018): 2687. http://dx.doi.org/10.3390/ijms19092687.
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Melatonin is the main pineal hormone that relays light/dark-cycle information to the circadian system. Recent studies have examined the intrinsic antitumor activity of melatonin in various cancers, including hepatocellular carcinoma (HCC), the primary life-threatening malignancy in both sexes in Taiwan. However, the detailed regulatory mechanisms underlying melatonin’s anti-HCC activity remain incompletely understood. Here, we investigated the mechanisms by which the anti-HCC activity of melatonin is regulated. Human hepatoma cell lines were treated with 1 and 2 mM melatonin, and functional assays were used to dissect melatonin’s antitumor effect in HCC; small-RNA sequencing was performed to identify the microRNAs (miRNAs) involved in the anti-HCC activity of melatonin; and quantitative RT-PCR and Western blotting were used to elucidate how miRNAs regulate melatonin-mediated HCC suppression. Melatonin treatment at both doses strongly inhibited the proliferation, migration and invasion capacities of Huh7 and HepG2 cell lines, and melatonin treatment markedly induced the expression of the miRNA let7i-3p in cells. Notably, transfection of cells with a let7i-3p mimic drastically reduced RAF1 expression and activation of mitogen-activated protein kinase signaling downstream from RAF1, and rescue-assay results demonstrated that melatonin inhibited HCC progression by modulating let7i-3p-mediated RAF1 suppression. Our findings support the view that melatonin treatment holds considerable promise as a therapy for HCC.
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Maitra, Sayantan, Debanjan Bhattacharya, Stabak Das i Subhrajit Bhattacharya. "Melatonin and its anti-glioma functions: a comprehensive review". Reviews in the Neurosciences 30, nr 5 (26.07.2019): 527–41. http://dx.doi.org/10.1515/revneuro-2018-0041.
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Abstract Melatonin (N-acetyl-5-methoxytryptamine) is a naturally synthesized hormone secreted from the pineal gland in a variety of animals and is primarily involved in the regulation of the circadian rhythm, which is the natural cycle controlling sleep in organisms. Melatonin acts on specific receptors and has an important role in overall energy metabolism. This review encompasses several aspects of melatonin activity, such as synthesis, source, structure, distribution, function, signaling and its role in normal physiology. The review highlights the cellular signaling and messenger systems involved in melatonin’s action on the body and their wider implications, the distribution and diverse action of different melatonin receptors in specific areas of the brain, and the pharmacological agonists and antagonists that have specific action on these melatonin receptors. This review also incorporates the antitumor effects of melatonin in considerable detail, emphasizing on melatonin’s role as an adjuvant therapeutic agent in glioma treatment. We conclude that the diminishing levels of melatonin have significant debilitating effects on normal physiology and can also be associated with malignant conditions such as glioma. Based on the review of the available evidence, our study provides a broad platform for a better understanding of the specific roles of melatonin and serves as a starting point for further investigation into the therapeutic effect of melatonin in glioma as an adjuvant therapeutic agent.
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Moretti, Enrico, Gaia Favero, Luigi Fabrizio Rodella i Rita Rezzani. "Melatonin’s Antineoplastic Potential Against Glioblastoma". Cells 9, nr 3 (3.03.2020): 599. http://dx.doi.org/10.3390/cells9030599.
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Glioblastoma (GBM) is one of the most intransigent and aggressive brain tumors, and its treatment is extremely challenging and ineffective. To improve patients’ expectancy and quality of life, new therapeutic approaches were investigated. Melatonin is an endogenous indoleamine with an incredible variety of properties. Due to evidence demonstrating melatonin’s activity against several cancer hallmarks, there is growing interest in its use for preventing and treating cancer. In this review, we report on the potential effects of melatonin, alone or in combination with anticancer drugs, against GBM. We also summarize melatonin targets and/or the intracellular pathways involved. Moreover, we describe melatonin’s epigenetic activity responsible for its antineoplastic effects. To date, there are too few clinical studies (involving a small number of patients) investigating the antineoplastic effects of melatonin against GBM. Nevertheless, these studies described improvement of GBM patients’ quality of life and did not show significant adverse effects. In this review, we also report on studies regarding melatonin-like molecules with the tumor-suppressive properties of melatonin together with implemented pharmacokinetics. Melatonin effects and mechanisms of action against GBM require more research attention due to the unquestionably high potential of this multitasking indoleamine in clinical practice.
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Fernandez-Gil, Beatriz I., Andrea Otamendi-Lopez, Alexandra Bechtle, Carla A. Vazquez-Ramos, Neda Qosja, Paola Suarez-Meade, Rachel Sarabia-Estrada i in. "Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma". Cells 11, nr 21 (2.11.2022): 3467. http://dx.doi.org/10.3390/cells11213467.
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Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin’s functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin’s cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.
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Văn Thoại, Phạm, i Nguyen Hai Nam. "Design and Synthesis of Sustain-Acting Melatonin Prodrugs". Journal of Chemistry 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/684760.
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Twelve melatonin amide prodrugs aiming at prolonging the action of melatoninin vivoby improving its half-life were designed and synthesized. Using an 80% human plasma model, it was found that the aliphatic amide derivatives were relatively stable and melatonin release from these compounds was not sufficient with melatonin release percentage. After 4-hour incubation with 80% human plasma, the melatonin release percentage achieved only approximately less than 20%. In contrast, the -succinyl and -glutaroylmelatonin derivatives (compounds11and12, resp.) were found to release melatonin in much higher rates. After 3-hour incubation in 80% human plasma, the melatonin release rates from11and12were found to be 67.3 and 75.6%, respectively. From these results, the -succinyl and -glutaroylmelatonin derivatives (compounds11and12) could be promising as sustained release prodrugs of melatonin.
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Campos, Luciana Aparecida, Ovidiu Constantin Baltatu, Sergio Senar, Rym Ghimouz, Eman Alefishat i José Cipolla-Neto. "Multiplatform-Integrated Identification of Melatonin Targets for a Triad of Psychosocial-Sleep/Circadian-Cardiometabolic Disorders". International Journal of Molecular Sciences 24, nr 1 (3.01.2023): 860. http://dx.doi.org/10.3390/ijms24010860.
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Several psychosocial, sleep/circadian, and cardiometabolic disorders have intricately interconnected pathologies involving melatonin disruption. Therefore, we hypothesize that melatonin could be a therapeutic target for treating potential comorbid diseases associated with this triad of psychosocial-sleep/circadian-cardiometabolic disorders. We investigated melatonin’s target prediction and tractability for this triad of disorders. The melatonin’s target prediction for the proposed psychosocial-sleep/circadian-cardiometabolic disorder triad was investigated using databases from Europe PMC, ChEMBL, Open Targets Genetics, Phenodigm, and PheWAS. The association scores for melatonin receptors MT1 and MT2 with this disorder triad were explored for evidence of target–disease predictions. The potential of melatonin as a tractable target in managing the disorder triad was investigated using supervised machine learning to identify melatonin activities in cardiovascular, neuronal, and metabolic assays at the cell, tissue, and organism levels in a curated ChEMBL database. Target–disease visualization was done by graphs created using “igraph” library-based scripts and displayed using the Gephi ForceAtlas algorithm. The combined Europe PMC (data type: text mining), ChEMBL (data type: drugs), Open Targets Genetics Portal (data type: genetic associations), PhenoDigm (data type: animal models), and PheWAS (data type: genetic associations) databases yielded types and varying levels of evidence for melatonin-disease triad correlations. Of the investigated databases, 235 association scores of melatonin receptors with the targeted diseases were greater than 0.2; to classify the evidence per disease class: 37% listed psychosocial disorders, 9% sleep/circadian disorders, and 54% cardiometabolic disorders. Using supervised machine learning, 546 cardiovascular, neuronal, or metabolic experimental assays with predicted or measured melatonin activity scores were identified in the ChEMBL curated database. Of 248 registered trials, 144 phase I to IV trials for melatonin or agonists have been completed, of which 33.3% were for psychosocial disorders, 59.7% were for sleep/circadian disorders, and 6.9% were for cardiometabolic disorders. Melatonin’s druggability was evidenced by evaluating target prediction and tractability for the triad of psychosocial-sleep/circadian-cardiometabolic disorders. While melatonin research and development in sleep/circadian and psychosocial disorders is more advanced, as evidenced by melatonin association scores, substantial evidence on melatonin discovery in cardiovascular and metabolic disorders supports continued R&D in cardiometabolic disorders, as evidenced by melatonin activity scores. A multiplatform analysis provided an integrative assessment of the target–disease investigations that may justify further translational research.
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Chakraborty, Souradipta, Razia Khatoon, Aindrila Chattopadhyay i Debasish Bandyopadhyay. "Emerging role of melatonin in the alleviation of ischemic heart disease: A comprehensive review". INDIAN JOURNAL OF PHYSIOLOGY AND ALLIED SCIENCES 75, nr 04 (31.12.2023): 5–12. http://dx.doi.org/10.55184/ijpas.v75i04.139.
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Melatonin, a circardian biomolecule exerts cardioprotective effects through its ability to directly scavenge free radicals and to indirectly act as an antioxidant. It has biological functions such as anti-apoptosis, anti-inflammation, antioxidant activity, mitochondrial protection, and controlling the production of cytokines by target cells. Melatonin also showed blood pressure lowering, normalising lipid profiles, and anti-inflammatory characteristics. Melatonin plays critical roles in averting oxidative stress, enhancing autophagic cell repair, modulating immunological and inflammatory responses, improving mitochondrial function, and reducing endoplasmic reticulum stress in cardiomyocytes. The absence of these cardioprotective properties due to low melatonin levels may be linked to an array of cardiovascular diseases, including ischemic heart disease. As a result, administration of melatonin is anticipated to have a clinically important role in the management of ischemic heart disease; an assertion backed by melatonin's low toxicity and high safety. Therefore, the evidence gathered in this review should provide comprehensive information on melatonin's effect in cardioprotection and, perhaps, contribute to the planning of future experimental studies.
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Min, Seung Hyun, Gabriella Gobbi i Luca Posa. "Melatonin and its Receptors". McGill Science Undergraduate Research Journal 12, nr 1 (9.04.2017): 38–43. http://dx.doi.org/10.26443/msurj.v12i1.43.
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Background: Melatonin (5-methoxy-N-acetyltryptamine) is a hormone that has numerous physiological functions. Synthesized and released during nighttime, melatonin exerts its physiological effects in a circadian manner. Melatonin acts by binding to its different types of receptors. The purpose of this systematic review is to summarize recent findings about melatonin, its receptors, and the differential functionalities of the most characterized melatonin receptors MT1 and MT2. Methods: We searched PubMed and Google Scholar for studies that reported melatonin receptor subtypes, their differential functionalities, biochemical structures, signal transductions, and various functions of melatonin such as pain, sleep, temperature, and antioxidative effects. We chose seventy articles for this systematic review. Summary: These studies highlight melatonin’s range of physiological functions and the differential functionalities of the melatonin receptors MT1 and MT2; they characterize the receptors’ signal transduction cascades and their biochemical structures. More studies assessing melatonin receptors’ functions would help patients with disorders in sleep, pain, and circadian rhythm.
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S, Ghosh. "Roles of Melatonin and Phyto-Melatoninas an Anti-Cancer Molecule: An Evolutionary Perspective". Journal of Natural & Ayurvedic Medicine 5, nr 3 (13.07.2021): 1–8. http://dx.doi.org/10.23880/jonam-16000316.
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Etymologically, melatonin (N-acetyl-5-methoxytryptamine) can be traced back to the origin of life. The first origin of melatonin was detected in cyano-bacteria. As considering the endosymbiont hypothesis, cyanobacteria were engulfed by the animal and plant cells. Later on, these bacteria performed the roles of mitochondria and chloroplastids in animals and plant cells respectively. Inner matrices of these organelles are having melatonin and probable function of this intra-organelle melatonin is to protect the organelles from the detrimental effects from free radicals (Reactive Oxygen Species; ROSs and Reactive Nitrogen Species; RNSs). In higher animals, melatonin is synthesized and secreted by the pineal gland mainly during the night, since light exposure suppresses its production. Other than pineal gland, melatonin is secreted from several different organs like retina, gastro-intestinal tract. The secretion of this hormone is regulated by several environmental factors like photo-period, temperature, humidity etc. Melatonin can exert its function either by as a free molecule or by its membrane bound receptors MT1 and MT2 respectively. Modulations of melatonin receptors results in stimulation of apoptosis, regulation of pro-survival signaling, inhibition on angiogenesis, metastasis, and induction of epigenetic alteration. Melatonin could also be utilized as adjuvant of cancer therapies, through reinforcing the therapeutic effects and reducing the side effects of chemotherapies or radiation. Melatonin could be an excellent candidate for prevention and treatment of several cancers, such as breast cancer, prostate cancer, gastric cancer and colorectal cancer. This review summarized the anticancer efficacy of melatonin, based on the results of epidemiological, experimental and clinical studies.
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Onaolapo, O. J., A. Y. Onaolapo, O. A. Olowe, M. O. Udoh, D. O. Udoh i I. T. Nathaniel. "Melatonin and Melatonergic Influence on Neuronal Transcription Factors: Implications for the Development of Novel Therapies for Neurodegenerative Disorders". Current Neuropharmacology 18, nr 7 (28.07.2020): 563–77. http://dx.doi.org/10.2174/1570159x18666191230114339.
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Melatonin is a multifunctional signalling molecule that is secreted by the mammalian pineal gland, and also found in a number of organisms including plants and bacteria. Research has continued to uncover an ever-increasing number of processes in which melatonin is known to play crucial roles in mammals. Amongst these functions is its contribution to cell multiplication, differentiation and survival in the brain. Experimental studies show that melatonin can achieve these functions by influencing transcription factors which control neuronal and glial gene expression. Since neuronal survival and differentiation are processes that are important determinants of the pathogenesis, course and outcome of neurodegenerative disorders; the known and potential influences of melatonin on neuronal and glial transcription factors are worthy of constant examination. In this review, relevant scientific literature on the role of melatonin in preventing or altering the course and outcome of neurodegenerative disorders, by focusing on melatonin’s influence on transcription factors is examined. A number of transcription factors whose functions can be influenced by melatonin in neurodegenerative disease models have also been highlighted. Finally, the therapeutic implications of melatonin’s influences have also been discussed and the potential limitations to its applications have been highlighted.
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Guerra-Librero, Ana, Beatriz I. Fernandez-Gil, Javier Florido, Laura Martinez-Ruiz, César Rodríguez-Santana, Ying-Qiang Shen, José M. García-Verdugo i in. "Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function". Antioxidants 10, nr 4 (14.04.2021): 603. http://dx.doi.org/10.3390/antiox10040603.
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Metabolic reprogramming, which is characteristic of cancer cells that rapidly adapt to the hypoxic microenvironment and is crucial for tumor growth and metastasis, is recognized as one of the major mechanisms underlying therapeutic resistance. Mitochondria, which are directly involved in metabolic reprogramming, are used to design novel mitochondria-targeted anticancer agents. Despite being targeted by melatonin, the functional role of mitochondria in melatonin’s oncostatic activity remains unclear. In this study, we aim to investigate the role of melatonin in mitochondrial metabolism and its functional consequences in head and neck cancer. We analyzed the effects of melatonin on head and neck squamous cell carcinoma (HNSCC) cell lines (Cal-27 and SCC-9), which were treated with 100, 500, and 1500 µM of melatonin for 1, 3, and 5 days, and found a connection between a change of metabolism following melatonin treatment and its effects on mitochondria. Our results demonstrate that melatonin induces a shift to an aerobic mitochondrial metabolism that is associated with changes in mitochondrial morphology, function, fusion, and fission in HNSCC. We found that melatonin increases oxidative phosphorylation (OXPHOS) and inhibits glycolysis in HNSCC, resulting in increased ROS production, apoptosis, and mitophagy, and decreased cell proliferation. Our findings highlight new molecular pathways involved in melatonin’s oncostatic activity, suggesting that it could act as an adjuvant agent in a potential therapy for cancer patients. We also found that high doses of melatonin, such as those used in this study for its cytotoxic impact on HNSCC cells, might lead to additional effects through melatonin receptors.
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Givler, Donald, Amy Givler, Patrick M. Luther, Danielle M. Wenger, Shahab Ahmadzadeh, Sahar Shekoohi, Amber N. Edinoff i in. "Chronic Administration of Melatonin: Physiological and Clinical Considerations". Neurology International 15, nr 1 (15.03.2023): 518–33. http://dx.doi.org/10.3390/neurolint15010031.
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Background: Exogenous melatonin is commonly used to treat insomnia, other sleep problems, and numerous medical illnesses, including Alzheimer’s disease, autism spectrum disorder, and mild cognitive impairment in adults and children. There is evolving information regarding issues with the use of chronic melatonin. Methods: The present investigation was a narrative review. Results: Melatonin usage has risen dramatically in recent years. Many countries only allow melatonin prescriptions. In the United States (U.S.), it is classified as a dietary supplement accessible over the counter and can be derived from animals, microorganisms, or, most commonly, made synthetically. No regulatory agency oversees its manufacturing or sale in the U.S. melatonin concentration of marketed preparations varies widely between product labels and manufacturers. Melatonin’s ability to induce sleep is detectable. However, it is modest for most people. Sleep length appears to be less important in sustained-release preparations. The optimal dosage is unknown, and routinely used amounts vary substantially. Melatonin’s short-term negative effects are minimal, resolve at medicine cessation, and do not usually prevent usage overall. Much research on long-term melatonin administration has found no difference between exogenous melatonin and placebo in terms of long-term negative effects. Conclusion: Melatonin at low to moderate dosages (approximately 5–6 mg daily or less) appears safe. Long-term usage appears to benefit certain patient populations, such as those with autism spectrum disorder. Studies investigating potential benefits in reducing cognitive decline and increased longevity are ongoing. However, it is widely agreed that the long-term effects of taking exogenous melatonin have been insufficiently studied and warrant additional investigation.
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Chen, Zhongyi, Chu Chang Chua, Jinping Gao, Ronald C. Hamdy i Balvin H. L. Chua. "Protective effect of melatonin on myocardial infarction". American Journal of Physiology-Heart and Circulatory Physiology 284, nr 5 (1.05.2003): H1618—H1624. http://dx.doi.org/10.1152/ajpheart.00874.2002.
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The dose- and time dependence of melatonin and the effective window of melatonin administration were determined in a mouse model of myocardial infarction. When mouse hearts were subjected to 60 min of occlusion of the left anterior descending artery (LAD) followed by 4 h of reperfusion, melatonin pretreatment for 30 min significantly reduced the infarct size/risk area. The most effective dose was found to be 150 μg/kg intraperitoneally, and the effective period of protection lasted up to 2 h after melatonin administration. Melatonin administration 45 min after LAD ligation or right before reperfusion was as effective as administration 30 min before ligation; however, melatonin administered after the release of occlusion was not protective. Melatonin's effect was still present in mice deficient for the Mel1a melatonin receptor. 8-Methoxy-2-propionamidotetralin, a melatonin receptor agonist with no antioxidant activity, offered no protection, suggesting a lack of involvement of melatonin receptors. Finally, the effects of melatonin were similar in rats and mice. Our results demonstrate that melatonin is an effective cardioprotective agent when administered either before or during coronary occlusion at a very low dose.
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Lalanne, Sébastien, Claire Fougerou-Leurent, George M. Anderson, Carmen M. Schroder, Tali Nir, Sylvie Chokron, Richard Delorme i in. "Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder". International Journal of Molecular Sciences 22, nr 3 (2.02.2021): 1490. http://dx.doi.org/10.3390/ijms22031490.
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The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin’s effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.
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Mondes, Pedro Henrique de Lima, i Eduardo Koji Tamura. "Melatonina em Animais de Companhia: uma Revisão de Literatura". Ensaios e Ciência C Biológicas Agrárias e da Saúde 25, nr 5-esp (14.03.2022): 671–81. http://dx.doi.org/10.17921/1415-6938.2021v25n5-espp671-681.
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A melatonina, N-acetil-5-metoxi-triptamina, é uma indolamina que possui diversas ações no organismo, desde regulação de ritmos circadianos, modulação do sistema imune, indutor do sono em determinas espécies e até eliminação de radicais livres. O objetivo desta revisão foi descrever o histórico, a síntese, os mecanismos de ação e os efeitos da melatonina, além de descrever trabalhos que utilizaram a melatonina em patologias associadas aos animais domésticos, em especial, nos cães e nos gatos. Esta revisão pode ser classificada como integrativa, com metodologia que consistiu em selecionar artigos das plataformas online como PubMed e Google Acadêmico, com a combinação de palavras-chave como “melatonin”, “dog”, “cat”, “circadian”, “rhythm”, “mammals”, desde que investigassem o envolvimento da indolamina na fisiopatologia de animais de companhia, ou que utilizassem a melatonina como método terapêutico no campo da Medicina Veterinária. Os artigos escolhidos dataram de 1958 até 2020. Os resultados demonstraram efeitos diversos, em várias áreas de especializações da veterinária, entre essas, oncologia, oftalmologia, anestesiologia, reprodução, endocrinologia, neurologia, dermatologia e gastroenterologia. Apesar dos resultados obtidos, a melatonina ainda é pouco estudada em trabalhos clínicos e científicos veterinários e, por isso, necessita de mais investigação, uma vez que possui potencial terapêutico em muitas das enfermidades que acometem animais de companhia. Palavras-chave: Glândula Pineal. Medicina Veterinária. Cães. Gatos. Abstract Melatonin, N-acetyl-5-methoxy-tryptamine, is an indolamine that has various effects in the organism, from regulation of circadian rhythms to immune system modulation, sleep induction in some species and to scavenger of free radicals. This review aimed to described the history, action mechanisms and melatonin effects, in addition to, also describe studies focusing in therapeutic use of melatonin in pathologies associated with companion animals, specially dogs and cats. This review can be classified as integrative, with a methodology consisting of selected articles from online platforms, PubMed and Google Scholar, using the combination of keywords such as “melatonin”, “dog”, “cat”, “circadian”, “rhythm”, “mammals”, since they investigate the indolamine involvement in the companion animals pathophysiology, or that use melatonin as a therapeutic method in the Veterinary Medicine field. The selected articles were from 1958 to 2020. The results demonstrated different effects in some veterinary specialization areas, including oncology, ophthalmology, anesthesiology, reproduction, endocrinology, neurology, dermatology and gastroenterology. Despite the results obtained, melatonin is still poorly studied in clinical and scientific veterinary and, therefore, needs further investigation, since it has therapeutic potential in many diseases that affect companion animals. Keywords: Pineal Gland. Veterinary Medicine. Dogs. Cats.
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Mondes, Pedro Henrique de Lima, i Eduardo Koji Tamura. "Melatonina em Animais de Companhia: uma Revisão de Literatura". Ensaios e Ciência C Biológicas Agrárias e da Saúde 25, nr 5-esp. (14.03.2022): 671–81. http://dx.doi.org/10.17921/1415-6938.2021v25n5-esp.p671-681.
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A melatonina, N-acetil-5-metoxi-triptamina, é uma indolamina que possui diversas ações no organismo, desde regulação de ritmos circadianos, modulação do sistema imune, indutor do sono em determinas espécies e até eliminação de radicais livres. O objetivo desta revisão foi descrever o histórico, a síntese, os mecanismos de ação e os efeitos da melatonina, além de descrever trabalhos que utilizaram a melatonina em patologias associadas aos animais domésticos, em especial, nos cães e nos gatos. Esta revisão pode ser classificada como integrativa, com metodologia que consistiu em selecionar artigos das plataformas online como PubMed e Google Acadêmico, com a combinação de palavras-chave como “melatonin”, “dog”, “cat”, “circadian”, “rhythm”, “mammals”, desde que investigassem o envolvimento da indolamina na fisiopatologia de animais de companhia, ou que utilizassem a melatonina como método terapêutico no campo da Medicina Veterinária. Os artigos escolhidos dataram de 1958 até 2020. Os resultados demonstraram efeitos diversos, em várias áreas de especializações da veterinária, entre essas, oncologia, oftalmologia, anestesiologia, reprodução, endocrinologia, neurologia, dermatologia e gastroenterologia. Apesar dos resultados obtidos, a melatonina ainda é pouco estudada em trabalhos clínicos e científicos veterinários e, por isso, necessita de mais investigação, uma vez que possui potencial terapêutico em muitas das enfermidades que acometem animais de companhia. Palavras-chave: Glândula Pineal. Medicina Veterinária. Cães. Gatos. Abstract Melatonin, N-acetyl-5-methoxy-tryptamine, is an indolamine that has various effects in the organism, from regulation of circadian rhythms to immune system modulation, sleep induction in some species and to scavenger of free radicals. This review aimed to described the history, action mechanisms and melatonin effects, in addition to, also describe studies focusing in therapeutic use of melatonin in pathologies associated with companion animals, specially dogs and cats. This review can be classified as integrative, with a methodology consisting of selected articles from online platforms, PubMed and Google Scholar, using the combination of keywords such as “melatonin”, “dog”, “cat”, “circadian”, “rhythm”, “mammals”, since they investigate the indolamine involvement in the companion animals pathophysiology, or that use melatonin as a therapeutic method in the Veterinary Medicine field. The selected articles were from 1958 to 2020. The results demonstrated different effects in some veterinary specialization areas, including oncology, ophthalmology, anesthesiology, reproduction, endocrinology, neurology, dermatology and gastroenterology. Despite the results obtained, melatonin is still poorly studied in clinical and scientific veterinary and, therefore, needs further investigation, since it has therapeutic potential in many diseases that affect companion animals. Keywords: Pineal Gland. Veterinary Medicine. Dogs. Cats.
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Tan, Dun-Xian, i Russel J. Reiter. "An evolutionary view of melatonin synthesis and metabolism related to its biological functions in plants". Journal of Experimental Botany 71, nr 16 (15.05.2020): 4677–89. http://dx.doi.org/10.1093/jxb/eraa235.
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Abstract Plant melatonin research is a rapidly developing field. A variety of isoforms of melatonin’s biosynthetic enzymes are present in different plants. Due to the different origins, they exhibit independent responses to the variable environmental stimuli. The locations for melatonin biosynthesis in plants are chloroplasts and mitochondria. These organelles have inherited their melatonin biosynthetic capacities from their bacterial ancestors. Under ideal conditions, chloroplasts are the main sites of melatonin biosynthesis. If the chloroplast pathway is blocked for any reason, the mitochondrial pathway will be activated for melatonin biosynthesis to maintain its production. Melatonin metabolism in plants is a less studied field; its metabolism is quite different from that of animals even though they share similar metabolites. Several new enzymes for melatonin metabolism in plants have been cloned and these enzymes are absent in animals. It seems that the 2-hydroxymelatonin is a major metabolite of melatonin in plants and its level is ~400-fold higher than that of melatonin. In the current article, from an evolutionary point of view, we update the information on plant melatonin biosynthesis and metabolism. This review will help the reader to understand the complexity of these processes and promote research enthusiasm in these fields.
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A, Tavartkiladze. "The Role of Melatonin and Matrix Metalloproteinases in Breast Cancer Pathogenesis: A Comprehensive Review". Advances in Pharmacology & Clinical Trials 9, nr 3 (4.07.2024): 1–11. http://dx.doi.org/10.23880/apct-16000240.
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Background: Breast cancer is a heterogeneous disease with molecular subtypes including Triple Negative Breast Cancer (TNBC), HER2/neu-positive, Luminal Type A, and Luminal Type B, each with unique clinical behaviors and therapeutic responses. This study investigates the role of melatonin, matrix metalloproteinases (MMPs), pro-inflammatory cytokines (IL6 and TNF-alpha), and lactate dehydrogenase (LDH) isoenzymes in breast cancer pathogenesis. Methods: Over three years, 171 breast cancer patients were studied. Blood and urine samples were collected to measure melatonin, MMPs, IL-6, TNF-alpha, LDH-1, and LDH-5 levels. Circulating tumor cells (CTCs) were isolated using density gradient centrifugation and immunomagnetic separation. Melatonin receptor expression on CTCs was analyzed by flow cytometry and immunocytochemistry. Plasma concentrations of melatonin were measured using high-performance liquid chromatography (HPLC), and MMPs, IL-6, TNF-alpha, LDH isoenzymes were quantified using enzyme-linked immunosorbent assays (ELISAs) and electrophoretic methods. Results: The expression of melatonin receptors was lowest in TNBC patients, higher in HER2/neu-positive and ER/PRnegative patients, and highest in Luminal Type A and B patients. TNBC patients exhibited elevated LDH-1 and inflammatory cytokines (IL-6, TNF-alpha), with significantly decreased melatonin levels. HER2/neu-positive patients showed elevated LDH5 and moderate decreases in melatonin. Luminal Type B and A patients had varying degrees of biomarker elevation and melatonin receptor expression. Discussion: The findings suggest a correlation between reduced melatonin signaling and aggressive breast cancer phenotypes, particularly TNBC. Elevated MMPs and pro-inflammatory cytokines underscore the role of inflammation and ECM degradation in cancer progression. Melatonin’s potential inhibitory effects on these pathways highlight its therapeutic promise. The combined assessment of melatonin, MMPs, cytokines, and LDH could guide personalized treatment strategies. Conclusion: This study underscores melatonin’s multifaceted role in breast cancer pathogenesis. Melatonin receptor expression, along with MMP, IL-6, TNF-alpha, and LDH levels, provides a detailed molecular landscape of breast cancer subtypes. Integrating melatonin supplementation into therapeutic regimens holds promise for improving outcomes, particularly inaggressive subtypes like TNBC. Further research and clinical trials are essential to validate these findings and develop effective melatonin-based therapies.
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Reiter, Russel J., Dun Xian Tan i Annia Galano. "Melatonin: Exceeding Expectations". Physiology 29, nr 5 (wrzesień 2014): 325–33. http://dx.doi.org/10.1152/physiol.00011.2014.
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Melatonin is a small, highly conserved indole with numerous receptor-mediated and receptor-independent actions. Receptor-dependent functions include circadian rhythm regulation, sleep, and cancer inhibition. The receptor-independent actions relate to melatonin's ability to function in the detoxification of free radicals, thereby protecting critical molecules from the destructive effects of oxidative stress under conditions of ischemia/reperfusion injury (stroke, heart attack), ionizing radiation, and drug toxicity, among others. Melatonin has numerous applications in physiology and medicine.
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Maharaj, Deepa S., Beverley D. Glass i Santy Daya. "Melatonin: New Places in Therapy". Bioscience Reports 27, nr 6 (20.11.2007): 299–320. http://dx.doi.org/10.1007/s10540-007-9052-1.
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The fact that the full extent of the function of the pineal gland has not yet been elucidated, has stimulated melatonin research worldwide. This review introduces melatonin's mechanism of action, direct and indirect antioxidant actions as well as the antioxidant properties of its metabolites, 6-hydroxymelatonin (6-OHM) and N-acetyl-N-formyl-5-methoxykynurenamine (AFMK). At present the mechanism of action is proposed to be receptor-, protein- and nonprotein-mediated. From its popular role in the treatment of jetlag, melatonin is now implicated in the reduction of oxidative stess, both as a free radical scavenger and antioxidant. Melatonin's direct scavenging action in respect of the following will be discussed: superoxide anions, hydrogen peroxide, hydroxyl radicals, singlet oxygen, peroxy radicals and nitric oxide/peroxy nitrite anions. In addition melatonin also possesses indirect antioxidant activity and the role of its metabolites, AFMK and 6-OHM will be presented. It is these free radical scavenging and antioxidant properties of melatonin that has shifted the focus from that of merely strengthening circadian rhythms to that of neuroprotectant: a new place in therapy.
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Talib, Dunya, i Rana. "Multifaceted Roles of Melatonin in Sleep Disorders". Wasit Journal for Pure sciences 3, nr 2 (30.06.2024): 207–20. http://dx.doi.org/10.31185/wjps.366.
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Hormone protein melatonin helps regulate the sleep–wake cycle or circadian rhythm, making it a critical substance in sleep regulation. Melatonin synthesis mainly occurs in the epiphysis of the pineal gland, although extra-pineal melatonin has been observed in other sites of the body, such as salivary glands, the gastrointestinal tract, the placenta and breast milk. Over the years, research into melatonin has shown that it has multiple roles in sleep disorders, revealing its mechanisms of action, clinical implications and therapeutic performance. In this paper, we review recent findings on the role of melatonin in sleep disorders which include insomnia, delayed sleep phase disorder (DSPD), jet lag, and shift work sleep disorder (SWSD). In addition, we report results where melatonin agonists and novel therapeutic targets have been designed and utilized to manipulate the melatonin receptors. This paper helps delineate melatonin’s role in sleep disorders from the literature, and clarify new perspectives for prevention and treatment of human health.
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WU, CHING‐SHYI, SEW‐FEN LEU, HSI‐YUAN YANG i BU‐MIIN HUANG. "Melatonin Inhibits the Expression of Steroidogenic Acute Regulatory Protein and Steroidogenesis in MA‐10 Cells". Journal of Andrology 22, nr 2 (4.03.2001): 245–54. http://dx.doi.org/10.1002/j.1939-4640.2001.tb02177.x.
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ABSTRACT: The effects of melatonin on steroidogenesis and steroidogenic acute regulatory (StAR) protein expression were investigated in MA‐10 mouse Leydig tumor cells. MA‐10 cells were treated with human chorionic gonadotropin/cyclic adenosine monophosphate (hCG/cAMP) analogue alone or with hCG/cAMP analogue plus melatonin in different dosages (0.1 nM to 10 μM). Steroid production and the expression of StAR protein were measured. Melatonin directly inhibited hCG‐ or dbcAMP‐stimulated progesterone production in MA‐10 cells within 3 hours. The inhibitory effects of melatonin on hCG‐ or dbcAMP‐stimulated stroid production in MA‐10 cells were abolished by a comparative melatonin receptor antagonist, luzindole. 22R‐hydroxycholesterol reversed melatonin's inhibitory effects, which illustrated that melatonin did not suppress P450scc enzyme activity. Moreover, StAR protein expression stimulated by hCG and dbcAMP was maximally reduced by 10 nM of melatonin treatment for 3 hours. The effects of prolonged exposure (12 h) to melatonin with dbcAMP stimulation in MA‐10 cells were also examined. The expression of StAR protein and steroid production were reduced by melatonin concentrations from 1 nM to 10 μM. However, melatonin at a dose of 1 nM had no effect in 3‐hour treatment. Our results indicate that melatonin suppressed MA‐10 mouse Leydig cell steroidogenesis through specific binding sites by blocking StAR protein expression without altering the activity of P450scc enzyme.
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Liu, Lifeng, Ying Xu, Russel J. Reiter, Yutao Pan, Di Chen, Yangzhou Liu, Xingyu Pu, Liguo Jiang i Zengchun Li. "Inhibition of ERK1/2 Signaling Pathway is Involved in Melatonin's Antiproliferative Effect on Human MG-63 Osteosarcoma Cells". Cellular Physiology and Biochemistry 39, nr 6 (2016): 2297–307. http://dx.doi.org/10.1159/000447922.
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Background: In a previous study, we found that melatonin inhibits MG-63 osteosarcoma cell proliferation; however, the underlying mechanisms remain elusive. Mitogen-activated protein kinase (MAPK) and Akt signaling pathways play key roles in the anticancer effects of melatonin. Aims: The present study investigated whether MAPK and Akt signaling pathways are involved in melatonin's antiproliferative actions on the human MG-63 osteosarcoma cells. Methods/Results: Western blot analysis confirmed that melatonin significantly inhibited phosphorylation of ERK1/2 but not p38, JNK, or Akt. The expression of ERK1/2, p38, JNK, and Akt was not altered by melatonin. PD98059 and melatonin alone, and especially in combination, significantly inhibited cell proliferation. The changes included G1 and G2/M phase arrest of the cell cycle, and a downregulation of the expression at both the protein and mRNA levels of cyclin D1 and CDK4 (related to the G1 phase) and of cyclin B1 and CDK1 (related to the G2/M phase) as measured by flow cytometry after propidium iodide staining, and both western blot and real-time PCR, respectively. Furthermore, the combination of PD98059 and melatonin synergistically and markedly augmented the action of either agent alone. Co-immunoprecipitation further confirmed that there was an interaction between p-ERK1/2 and cyclin D1, CDK4, cyclin B1, or CDK1, which was blunted in the presence of melatonin or PD98059. Conclusion: These findings suggest that melatonin's antiproliferative action is mediated by inhibition of the ERK1/2 signaling pathway rather than the p38, JNK, or Akt pathways.
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Zhao, Shisu, Yanjun Dong, Yuanyuan Li, Zixu Wang, Yaoxing Chen i Yulan Dong. "Melatonin Alleviates Lipopolysaccharide-Induced Abnormal Pregnancy through MTNR1B Regulation of m6A". International Journal of Molecular Sciences 25, nr 2 (5.01.2024): 733. http://dx.doi.org/10.3390/ijms25020733.
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Pregnancy is a highly intricate and delicate process, where inflammation during early stages may lead to pregnancy loss or defective implantation. Melatonin, primarily produced by the pineal gland, exerts several pharmacological effects. N6-methyladenosine (m6A) is the most prevalent mRNA modification in eukaryotes. This study aimed to investigate the association between melatonin and m6A during pregnancy and elucidate the underlying protective mechanism of melatonin. Melatonin was found to alleviate lipopolysaccharide (LPS)-induced reductions in the number of implantation sites. Additionally, it mitigated the activation of inflammation, autophagy, and apoptosis pathways, thereby protecting the pregnancy process in mice. The study also revealed that melatonin regulates uterine m6A methylation levels and counteracts abnormal changes in m6A modification of various genes following LPS stimulation. Furthermore, melatonin was shown to regulate m6A methylation through melatonin receptor 1B (MTNR1B) and subsequently modulate inflammation, autophagy, and apoptosis through m6A. In conclusion, our study demonstrates that melatonin protects pregnancy by influencing inflammation, autophagy, and apoptosis pathways in an m6A-dependent manner via MTNR1B. These findings provide valuable insights into the mechanisms underlying melatonin’s protective effects during pregnancy and may have implications for potential therapeutic strategies in managing pregnancy-related complications.
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Di, Hongmei, Chenlu Zhang, Aolian Zhou, Huanhuan Huang, Yi Tang, Huanxiu Li, Zhi Huang, Fen Zhang i Bo Sun. "Transcriptome Analysis Reveals the Mechanism by Which Exogenous Melatonin Treatment Delays Leaf Senescence of Postharvest Chinese Kale (Brassica oleracea var. alboglabra)". International Journal of Molecular Sciences 25, nr 4 (13.02.2024): 2250. http://dx.doi.org/10.3390/ijms25042250.
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Melatonin, a pleiotropic small molecule, is employed in horticultural crops to delay senescence and preserve postharvest quality. In this study, 100 µM melatonin treatment delayed a decline in the color difference index h* and a*, maintaining the content of chlorophyll and carotenoids, thereby delaying the yellowing and senescence of Chinese kale. Transcriptome analysis unequivocally validates melatonin’s efficacy in delaying leaf senescence in postharvest Chinese kale stored at 20 °C. Following a three-day storage period, the melatonin treatment group exhibited 1637 differentially expressed genes (DEGs) compared to the control group. DEG analysis elucidated that melatonin-induced antisenescence primarily governs phenylpropanoid biosynthesis, lipid metabolism, plant signal transduction, and calcium signal transduction. Melatonin treatment up-regulated core enzyme genes associated with general phenylpropanoid biosynthesis, flavonoid biosynthesis, and the α-linolenic acid biosynthesis pathway. It influenced the redirection of lignin metabolic flux, suppressed jasmonic acid and abscisic acid signal transduction, and concurrently stimulated auxin signal transduction. Additionally, melatonin treatment down-regulated RBOH expression and up-regulated genes encoding CaM, thereby influencing calcium signal transduction. This study underscores melatonin as a promising approach for delaying leaf senescence and provides insights into the mechanism of melatonin-mediated antisenescence in postharvest Chinese kale.
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Lütfullah BAŞLAK, Özlem ÜZAL i Fikret YAŞAR. "Üşüme Stresi Altında Hıyar (Cucumis sativus L.) Fidelerinin Bazı Morfolojik Karakterleri Üzerine Melatonin Uygulamalarının Etkisi". ISPEC Journal of Agricultural Sciences 5, nr 2 (2.06.2021): 350–61. http://dx.doi.org/10.46291/ispecjasvol5iss2pp350-361.
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Beith F1 hıyar çeşidinin kullanıldığı araştırmada; üşümenin ve yapraktan uygulanan melatoninin fidelerin bazı morfolojik karakterleri üzerine etkileri araştırılmaya çalışılmıştır. 3-4 gerçek yapraklı iken üşüme uygulanan fidelere 0, 1, 10, 20, 30 ve 40 μM melatonin içeren saf (distile) su bitkilerin yapraklarına püskürtülmüştür. Melatonin uygulamasından 1 tam gün sonra bitkilerin yarısı iklim dolabında 15 gün süre ile üşüme stresine maruz bırakılmış, diğer yarısı ise iklim odasında normal koşullarda (25/20 °C aydınlık/karanlık) tutulmuştur. Üşüme stresine maruz kalan bitkiler 15 gün süreyle 5±1 °C karanlık (12 saat) / 10±1 °C aydınlık (12 saat)’da inkibatörde tutulduktan sonra örnekler alınmıştır. Bitkilerin, bazı büyüme parametreleri ve yaprak renk değerleri ölçülmüştür. Bitki gelişim parametreleri değerlendirildiğinde, üşüme stresi uygulanan bitkilerden 30 ve 40 µM melatonin uygulanan bitkilerin bitki büyümesini sınırlandırdığı belirlenmiştir. Ayrıca hiç melatonin uygulanmamış bitkiler en yüksek skala değerine sahip olurken, buna karşılık yapılan melatonin uygulamalarının görsel hasarın azaltılmasında etkili olduğu ve en az görsel hasarın 40 µM melatonin uygulamasında olduğu gözlemlenmiştir. Sonuç olarak, melatonin uygulamalarının üşüme stresinin yol açtığı zararlı etkilerin azaltılmasında olumlu etki yapabilecek fizyolojik etkili bir yardımcı uygulama olabileceği düşünülmüştür.
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Williams, Wynford R. "Dampening of neurotransmitter action: molecular similarity within the melatonin structure". Endocrine Regulations 52, nr 4 (1.10.2018): 199–207. http://dx.doi.org/10.2478/enr-2018-0025.
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AbstractObjectives. Melatonin initiates physiologic and therapeutic responses in various tissues through binding to poorly defined MT receptors regulated by G-proteins and purine nucleotides. Melatonin’s interaction with other G-protein regulated receptors, including those of serotonin, is unclear. This study explores the potential for the interaction of melatonin with nucleotide and receptor ligand structures. Methods. The study uses a computational program to investigate relative molecular similarity by the comparative superimposition and quantitative fitting of molecular structures to adenine and guanine nucleotide templates. Results. A minimum energy melatonin conformer replicates the nucleotide fits of ligand structures that regulate Gαi and Gαq proteins via serotonin, dopamine, opioid, α-adrenoceptor, and muscarinic receptor classes. The same conformer also replicates the nucleotide fits of ligand structures regulating K+ and Ca2+ ion channels. The acyl-methoxy distance within the melatonin conformer matches a carbonyl-hydroxyl distance in guanine nucleotide. Conclusion. Molecular similarity within the melatonin and ligand structures relates to the established effects of melatonin on cell receptors regulated by purine nucleotides in cell signal transduction processes. Pharmacologic receptor promiscuity may contribute to the widespread effects of melatonin.
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Cook, Jonathan S., i Chester A. Ray. "Melatonin attenuates the vestibulosympathetic but not vestibulocollic reflexes in humans: selective impairment of the utricles". Journal of Applied Physiology 109, nr 6 (grudzień 2010): 1697–701. http://dx.doi.org/10.1152/japplphysiol.00698.2010.
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Melatonin has been reported to decrease nerve activity of medial vestibular nuclei in the rat and is associated with attenuated muscle sympathetic nerve activity (MSNA) responses to baroreceptor unloading in humans. The purpose of this study was to determine if melatonin alters the vestibulosympathetic reflex (VSR) and vestibulocollic reflex (VCR) in humans. In study 1, MSNA, arterial blood pressure, and heart rate were measured in 12 healthy subjects (28 ± 1 yr; 6 men, 6 women) during head-down rotation (HDR) before and 45 min after ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the opposite treatment (melatonin or placebo). Melatonin significantly attenuated MSNA responses during HDR compared with placebo (burst frequency Δ 4 ± 1 vs. Δ 7 ± 1 bursts/min, and total MSNA Δ 51 ± 20 and Δ 96 ± 15%, respectively; P < 0.02). In study 2, vestibular evoked myogenic potentials (VEMP) were measured in 10 healthy subjects (26 ± 1 yr; 4 men and 6 women) before and after ingestion of 3 mg melatonin. Melatonin did not alter the timing of the p13 and n23 peaks (pre-melatonin 13.2 ± 0.4 and 21.3 ± 0.6 ms vs. post-melatonin 13.5 ± 0.4 and 21.4 ± 0.7 ms, respectively) or the p13-n23 interpeak amplitudes [pre-melatonin 22.5 ± 4.6 arbitrary units (au) and post-melatonin 22.7 ± 4.6 au]. In summary, melatonin attenuates the VSR and supports the concept that melatonin negatively affects orthostatic tolerance. However, melatonin does not alter the VCR in humans suggesting melatonin's effect on the VSR appears to be mediated by the utricles.
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Alonso-Vale, Maria Isabel Cardoso, Sandra Andreotti, Sidney Barnabé Peres, Gabriel Forato Anhê, Cristina das Neves Borges-Silva, José Cipolla Neto i Fabio Bessa Lima. "Melatonin enhances leptin expression by rat adipocytes in the presence of insulin". American Journal of Physiology-Endocrinology and Metabolism 288, nr 4 (kwiecień 2005): E805—E812. http://dx.doi.org/10.1152/ajpendo.00478.2004.
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Leptin and melatonin play an important role in the regulation of body mass and energy balance. Both hormones show a circadian rhythm, with increasing values at night. In addition, melatonin receptors were recently described in adipocytes, where leptin is synthesized. Here, we investigated the influence of melatonin and its interaction with insulin and dexamethasone on leptin expression. Isolated rat adipocytes were incubated with melatonin (1 nM) alone or in combination with insulin (5 nM) and/or dexamethasone (7 nM) for 6 h. Melatonin or insulin alone did not affect leptin expression, but together they increased it by 120%. Dexamethasone increased leptin mRNA content (105%), and this effect was not enhanced by melatonin. Simultaneous treatment with the three hormones provoked a further increase in leptin release (250%) and leptin mRNA (100%). Melatonin prevented the forskolin-induced inhibition (95%) of leptin expression. In addition, melatonin's ability to stimulate leptin release (in the presence of insulin) was completely blocked by pertussis toxin and luzindole. To gain further insight into the molecular basis of melatonin and insulin synergism, the insulin-signaling pathway was investigated. Melatonin increased the insulin-induced insulin receptor-β tyrosine phosphorylation, which led to an increased serine phosphorylation of the downstream convergent protein Akt. We concluded that melatonin interacts with insulin and upregulates insulin-stimulated leptin expression. These effects are caused by melatonin binding to the pertussis toxin-sensitive Gi protein-coupled membrane receptor (MT1 subtype) and the cross talk with insulin, since insulin receptor and its convergent target Akt are coactivated by melatonin.
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Tang, Kuo-Shu, Chun-Yi Ho, Chien-Ning Hsu i You-Lin Tain. "Melatonin and Kidney Health: From Fetal Stage to Later Life". International Journal of Molecular Sciences 24, nr 9 (30.04.2023): 8105. http://dx.doi.org/10.3390/ijms24098105.
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Melatonin, an endogenous hormone mainly released at night by the pineal gland, has multifaceted biofunctions. Emerging evidence points to melatonin having a crucial role in kidney health and disease. As the prevalence of chronic kidney disease (CKD) is still rising, a superior strategy to advance global kidney health is needed to not just treat CKD, but prevent it early on. Adult kidney disease can have its origins in early life. This review aims to evaluate the recent literature regarding melatonin’s effect on kidney development, its clinical uses in the early stage of life, animal models documenting preventive applications of melatonin on offspring’s kidney-related disease, and a thorough summary of therapeutic considerations concerning melatonin supplementation.
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Reiter, Russel J., Dun-Xian Tan, Juan C. Mayo, Rosa M. Sainz, Josefa Leon i Zbigniew Czarnocki. "Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans." Acta Biochimica Polonica 50, nr 4 (31.12.2003): 1129–46. http://dx.doi.org/10.18388/abp.2003_3637.
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This brief resume enumerates the multiple actions of melatonin as an antioxidant. This indoleamine is produced in the vertebrate pineal gland, the retina and possibly some other organs. Additionally, however, it is found in invertebrates, bacteria, unicellular organisms as well as in plants, all of which do not have a pineal gland. Melatonin's functions as an antioxidant include: a), direct free radical scavenging, b), stimulation of antioxidative enzymes, c), increasing the efficiency of mitochondrial oxidative phosphorylation and reducing electron leakage (thereby lowering free radical generation), and 3), augmenting the efficiency of other antioxidants. There may be other functions of melatonin, yet undiscovered, which enhance its ability to protect against molecular damage by oxygen and nitrogen-based toxic reactants. Numerous in vitro and in vivo studies have documented the ability of both physiological and pharmacological concentrations to melatonin to protect against free radical destruction. Furthermore, clinical tests utilizing melatonin have proven highly successful; because of the positive outcomes of these studies, melatonin's use in disease states and processes where free radical damage is involved should be increased.
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Yan, Manwen, Mingyan Li, Zhuoying Ding, Fei Qiao i Xuefei Jiang. "Plant Hormone Signals Mediate Melatonin Synthesis to Enhance Osmotic Stress Tolerance in Watermelon Cells". Horticulturae 9, nr 8 (14.08.2023): 927. http://dx.doi.org/10.3390/horticulturae9080927.
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Melatonin, a multifunctional signaling molecule, has been shown to play a significant role in response to abiotic stress. Several species have been reported to unveil melatonin’s effect on osmotic stress; however, the signal transduction mechanism of phytohormone-mediated melatonin biosynthesis in plant species remains unclear. In this study, although plants can biosynthesize melatonin, the exogenous application of melatonin to watermelon cells can improve cell growth in response to osmotic stress by regulating the antioxidant machinery of cells. Regarding the melatonin synthesis pathway, ClOMT (ClASMT and ClCOMT) is a multi-gene family, and ClSNAT has two members. Both ClOMTs and ClSNATs harbor the cis-elements in their promoter regions responding to various hormones. Among abscisic acid (ABA), methyl jasmonate (MeJA), and salicylic acid (SA), ABA treatment observably upregulated the expression of ClOMTs and ClSNATs, and the accumulation of melatonin with ABA treatment reached a level comparable to that with osmotic stress by mannitol treatment. Furthermore, when hormone biosynthesis inhibitors were added to cells before osmotic stress, the expression of ClOMTs and ClSNATs, as well as melatonin accumulation, were significantly suppressed with the ABA biosynthesis inhibitor. This study demonstrated the crucial role of melatonin biosynthesis in response to osmotic stress via plant hormone signal transduction. It showed that ABA signaling plays a dominant role in melatonin synthesis under osmotic stress.
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Ran, Yuanyuan, Lin Ye, Zitong Ding, Fuhai Gao, Shuiqing Yang, Boyan Fang, Zongjian Liu i Jianing Xi. "Melatonin Protects Against Ischemic Brain Injury by Modulating PI3K/AKT Signaling Pathway via Suppression of PTEN Activity". ASN Neuro 13 (styczeń 2021): 175909142110228. http://dx.doi.org/10.1177/17590914211022888.
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Stroke is one of the leading causes of death and disability worldwide with limited therapeutic options. Melatonin can attenuate ischemic brain damage with improved functional outcomes. However, the cellular mechanisms of melatonin-driven neuroprotection against post-stroke neuronal death remain unknown. Here, distal middle cerebral artery occlusion (dMCAO) was performed in C57BL/6j mice to develop an ischemic stroke in vivo model. Melatonin was injected intraperitoneally immediately after ischemia, and 24 and 48 hours later. Melatonin treatment, with 5 to 20 mg/kg, elicited a dose-dependent decrease in infarct volume and concomitant increase in sensorimotor function. At the molecular level, phosphorylation of PTEN and Akt were increased, whereas PTEN activity was decreased in melatonin treated animals 72 hours after dMCAO. At the cellular level, oxygenglucose deprivation (OGD) challenge of neuronal cell line Neuro-2a (N2a) and primary neurons supported melatonin’s direct protection against neuronal cell death. Melatonin treatment reduced LDH release and neuronal apoptosis at various time points, markedly increased Akt phosphorylation in neuronal membrane, but significantly suppressed it in the cytoplasm of post-OGD neurons. Mechanistically, melatonin-induced Akt phosphorylation and neuronal survival was blocked by Wortmannin, a potent PIP3 inhibitor, exposing increased PI3K/Akt activation as a central player in melatonin-driven neuroprotection. Finally, PTEN knock-down through siRNA significantly inhibited PI3K/Akt activation and cell survival following melatonin treatment, suggesting that melatonin protection against ischemic brain damage, is at least partially, dependent on modulation of the PTEN/PI3K/Akt signaling axis.
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Reiter, Russel J., Sergio Rosales-Corral i Ramaswamy Sharma. "Melatonin: Protection of the Intervertebral Disc". Melatonin Research 2, nr 3 (31.08.2019): 1–9. http://dx.doi.org/10.32794/mr11250028.
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Low back pain (lumbar pain) due to injury of or damage to intervertebral discs is common in all societies. The loss of work time as a result of this problem is massive. Recent research suggests that melatonin may prevent or counteract intervertebral disc damage. This may be especially relevant in aging populations given that endogenous melatonin, in most individuals, dwindles with increasing age. The publications related to melatonin and its protection of the intervertebral disc are reviewed herein, including definition of some molecular mechanisms that account for melatonin’s protective actions.
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Hardeland, Ruediger. "Melatonin and retinoid orphan receptors: Demand for new interpretations after their exclusion as nuclear melatonin receptors". Melatonin Research 1, nr 1 (3.12.2018): 78–93. http://dx.doi.org/10.32794/mr11250005.
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The demonstrated incapability of the retinoic acid receptor-related orphan receptor-α (RORα) to bind melatonin inevitably requires consequences for interpreting numerous reports on actions of this protein as far as it was believed to be a nuclear melatonin receptor. While the synthetic compound CGP 52608 is, in fact, a ligand of RORα, effects obtained with this molecule can no longer be attributed to melatonin. Moreover, the sometimes assumed interplay between melatonin membrane receptors and RORα as nuclear receptors has to be dropped. Conclusions on melatonin’s actions via RORα that were based on a lack of demonstrable involvement of membrane receptors appear to have been precocious. Nevertheless, findings on melatonin uptake into the nucleus may still be taken as a hint for nuclear melatonin receptors, but this would require thorough characterization. Although RORα does not bind melatonin, it is interrelated to the latter in regulatory terms by involvement of cellular circadian oscillators. A mode of action seems to be the upregulation of sirtuin-1 by melatonin, deacetylation of poly ADP ribose polymerase-γ coactivator-1α (PGC-1α) by sirtuin-1, and facilitation of RORα binding to its response element by deacetylated PGC-1α, a route that had been shown to exist in circadian oscillators, thereby enhancing their amplitude.
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Bier, Ariel, Rawan Khashab, Yehonatan Sharabi, Ehud Grossman i Avshalom Leibowitz. "Melatonin Prevents T Lymphocyte Infiltration to the Kidneys of Hypertensive Rats, Induced by a High-Salt Diet, by Preventing the Expression of CXCR3 Ligand Chemokines". Nutrients 13, nr 10 (13.10.2021): 3577. http://dx.doi.org/10.3390/nu13103577.
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In a previous study, we demonstrated that melatonin prevents kidney damage in a salt-induced hypertension model by decreasing oxidative stress. We hypothesized that this effect involves melatonin’s immunomodulatory properties. In vivo Study-Dahl salt-sensitive (DSS) rats were fed normal chow, a high-salt diet (HSD), or a HSD and melatonin (30 mg/kg/day) in their water for eight weeks. Kidneys were harvested for immediate lymphocyte isolation and characterization by Flow cytometry (CD3+CD4+ and CD3+CD8+) and for lymphocyte chemoattractant (mainly CXCL chemokines) gene expression studies. In vitro study-rat mesangial cells (RMC) were cultured in a high-salt medium without and with melatonin. A HSD was associated with significant renal infiltration of CD4+ and CD8+ T lymphocytes compared to control. Melatonin significantly reduced renal lymphocyte infiltration. A HSD significantly increased mRNA expression of CXCL chemokines. Adding melatonin to the HSD abolished this effect. Treating RMC cells with salt increased the expression of CXCL10 and CXCL11 but not CXCL9. Adding melatonin to the culture media prevented this increase. Treating HSD-fed rats with melatonin decreased renal lymphocyte chemoattractant mRNA expression and is associated with significantly reducing renal T lymphocyte infiltration. Salt may have a direct effect on chemokine-producing renal cells, which is blunted by melatonin treatment.
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Bier, Ariel, Rawan Khashab, Yehonatan Sharabi, Ehud Grossman i Avshalom Leibowitz. "Melatonin Prevents T Lymphocyte Infiltration to the Kidneys of Hypertensive Rats, Induced by a High-Salt Diet, by Preventing the Expression of CXCR3 Ligand Chemokines". Nutrients 13, nr 10 (13.10.2021): 3577. http://dx.doi.org/10.3390/nu13103577.
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In a previous study, we demonstrated that melatonin prevents kidney damage in a salt-induced hypertension model by decreasing oxidative stress. We hypothesized that this effect involves melatonin’s immunomodulatory properties. In vivo Study-Dahl salt-sensitive (DSS) rats were fed normal chow, a high-salt diet (HSD), or a HSD and melatonin (30 mg/kg/day) in their water for eight weeks. Kidneys were harvested for immediate lymphocyte isolation and characterization by Flow cytometry (CD3+CD4+ and CD3+CD8+) and for lymphocyte chemoattractant (mainly CXCL chemokines) gene expression studies. In vitro study-rat mesangial cells (RMC) were cultured in a high-salt medium without and with melatonin. A HSD was associated with significant renal infiltration of CD4+ and CD8+ T lymphocytes compared to control. Melatonin significantly reduced renal lymphocyte infiltration. A HSD significantly increased mRNA expression of CXCL chemokines. Adding melatonin to the HSD abolished this effect. Treating RMC cells with salt increased the expression of CXCL10 and CXCL11 but not CXCL9. Adding melatonin to the culture media prevented this increase. Treating HSD-fed rats with melatonin decreased renal lymphocyte chemoattractant mRNA expression and is associated with significantly reducing renal T lymphocyte infiltration. Salt may have a direct effect on chemokine-producing renal cells, which is blunted by melatonin treatment.
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Anderson, George, Cathy Vaillancourt, Michael Maes i Russel J. Reiter. "Breast Feeding and Melatonin: Implications for Improving Perinatal Health". Journal of Breastfeeding Biology 1, nr 1 (22.07.2016): 8–20. http://dx.doi.org/10.14302/issn.2644-0105.jbfb-16-1121.
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The biological underpinnings that drive the plethora of breastfeeding benefits over formula-feeding is an area of intense research, given the cognitive and emotional benefits as well as the offsetting of many childhood- and adult-onset medical conditions that breast-feeding provides. In this article, we review the research on the role of melatonin in driving some of these breastfeeding benefits. Melatonin is a powerful antioxidant, anti-inflammatory and antinociceptive as well as optimizing mitochondrial function. Melatonin is produced by the placenta and, upon parturition, maternal melatonin is passed to the infant upon breastfeeding with higher levels in night-time breast milk. As such, some of the benefits of breastfeeding may be mediated by the higher levels of maternal circulating night-time melatonin, allowing for circadian and antioxidant effects, as well as promoting the immune and mitochondrial regulatory aspects of melatonin; these actions may positively modulate infant development. Herein, it is proposed that some of the benefits of breastfeeding may be mediated by melatonin's regulation of the infant's gut microbiota and immune responses. As such, melatonin is likely to contribute to the early developmental processes that affect the susceptibility to a range of adult onset conditions. Early research on animal models has shown promising results for the regulatory role of melatonin.
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Gao, Qiang, Chi Zhang, Jiaxin Li, Han Xu, Xiaocheng Guo, Qi Guo, Chen Zhao, Haixu Yao, Yuhan Jia i Hui Zhu. "Melatonin Attenuates H2O2-Induced Oxidative Injury by Upregulating LncRNA NEAT1 in HT22 Hippocampal Cells". International Journal of Molecular Sciences 23, nr 21 (25.10.2022): 12891. http://dx.doi.org/10.3390/ijms232112891.
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More research is required to understand how melatonin protects neurons. The study aimed to find out if and how long non-coding RNA (lncRNA) contributes to melatonin’s ability to defend the hippocampus from H2O2-induced oxidative injury. LncRNAs related to oxidative injury were predicted by bioinformatics methods. Mouse hippocampus-derived neuronal HT22 cells were treated with H2O2 with or without melatonin. Viability and apoptosis were detected by Cell Counting Kit-8 and Hoechst33258. RNA and protein levels were measured by quantitative real-time PCR, Western blot, and immunofluorescence. Bioinformatics predicted that 38 lncRNAs were associated with oxidative injury in mouse neurons. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was related to H2O2-induced oxidative injury and up-regulated by melatonin in HT22 cells. The knockdown of NEAT1 exacerbated H2O2-induced oxidative injury, weakened the moderating effect of melatonin, and abolished the increasing effect of melatonin on the mRNA and protein level of Slc38a2. Taken together, melatonin attenuates H2O2-induced oxidative injury by upregulating lncRNA NEAT1, which is essential for melatonin stabilizing the mRNA and protein level of Slc38a2 for the survival of HT22 cells. The research may assist in the treatment of oxidative injury-induced hippocampal degeneration associated with aging using melatonin and its target lncRNA NEAT1.
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Contreras-Correa, Zully E., Riley D. Messman, Rebecca M. Swanson i Caleb O. Lemley. "Melatonin in Health and Disease: A Perspective for Livestock Production". Biomolecules 13, nr 3 (7.03.2023): 490. http://dx.doi.org/10.3390/biom13030490.
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Mounting evidence in the literature indicates an important role of endogenous and exogenous melatonin in driving physiological and molecular adaptations in livestock. Melatonin has been extensively studied in seasonally polyestrous animals whereby supplementation studies have been used to adjust circannual rhythms in herds of animals under abnormal photoperiodic conditions. Livestock undergo multiple metabolic and physiological adaptation processes throughout their production cycle which can result in decreased immune response leading to chronic illness, weight loss, or decreased production efficiency; however, melatonin’s antioxidant capacity and immunostimulatory properties could alleviate these effects. The cardiovascular system responds to melatonin and depending on receptor type and localization, melatonin can vasodilate or vasoconstrict several systemic arteries, thereby controlling whole animal nutrient partitioning via vascular resistance. Increased incidences of non-communicable diseases in populations exposed to circadian disruption have uncovered novel pathways of neurohormones, such as melatonin, influence health, and disease. Perturbations in immune function can negatively impact the growth and development of livestock which has been examined following melatonin supplementation. Specifically, melatonin can influence nutrient uptake, circulating nutrient profiles, and endocrine profiles controlling economically important livestock growth and development. This review focuses on the physiological, cellular, and molecular implications of melatonin on the health and disease of domesticated food animals.
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Mubarok, Syariful, Erni Suminar, Adzkia Husnul Abidat, Citra Ayu Setyawati, Erik Setiawan i Adine Syabina Buswar. "Overview of Melatonin’s Impact on Postharvest Physiology and Quality of Fruits". Horticulturae 9, nr 5 (15.05.2023): 586. http://dx.doi.org/10.3390/horticulturae9050586.
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Fruits are important horticultural commodities because they provide nutrients that help human health. Fruits are mostly consumed as fresh products; however, there are challenges in retaining the freshness, such as the rapid ripening process that triggers fruit deterioration and reduces fruit quality and nutrient content. The postharvest quality of horticultural crops is affected by pre-and postharvest treatment. Most farmers use chemical compounds and fungicides to prevent postharvest damage; however, this results in health hazards and environmental pollution. Melatonin can be used for maintaining and improving postharvest horticultural crops such as fruits. Melatonin is a new bioactive compound that is a potent free radical scavenger and antioxidant. It has been studied as an alternative to harmful chemicals used commercially in the postharvest management of fresh products. For human health, melatonin plays a regulatory role in circadian and seasonal rhythms, sleep, retinal functions, and the immune system. In plants, melatonin regulates many biological processes, particularly when plants have experienced abiotic stress, germination, aging, and growth. The effect of exogenous melatonin on fruit ripening has focused primarily on the relationship between melatonin and ethylene plant hormones. Many studies in recent years have discussed melatonin’s role in plants, particularly in delaying plant aging as an alternative way of increasing fruit shelf life. This review provides a comprehensive overview of melatonin biosynthesis in plants, factors that affect the content of melatonin in fruit, melatonin mechanisms in fruit ripening, the impact of melatonin on postharvest fruit quality, the effect of melatonin on postharvest quality, and the change in metabolite content of horticultural products, particularly fruits.
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Dhali, Tapan, Mona Sharma i Priyanka Hemrajani. "Melatonin - A Cutaneous Perspective". Nepal Journal of Dermatology, Venereology & Leprology 19, nr 2 (4.10.2021): 3–12. http://dx.doi.org/10.3126/njdvl.v19i2.39452.
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Melatonin (MLT) is an endogenous hormone secreted from the pineal gland, located deep in the brain in the epithalamus associated with numerous biological activities. The primary function of melatonin is to regulate sleep-wake cycles. However, research over the last few years has enlightened a range of functions associated with this molecule, including anti-inflammatory, direct and indirect antioxidant activity, regenerative tissue benefits, and preservation of mitochondrial function. Melatonin’s anti-inflammatory and antioxidant support, coupled with its mitochondrial modulation, makes it a vital molecule to use for skin health homeostasis. The cutaneous melatoninergic system’s widespread expression and pleiotropic activity provides for a high level of cell-specific selectivity. Several skin cells, including normal and malignant keratinocytes, melanocytes, fibroblasts and hair follicles, express melatonin receptors. Melatonin also has receptor-independent effects that protect against oxidative stress and can reduce ultraviolet radiation-induced damage. Several functions of melatonin in the skin have been experimentally implicated such as hair growth cycling, fur pigmentation, melanoma control, suppression of ultraviolet-induced damage to the skin cell. Melatonin may play a role in treating several dermatoses e.g., atopic eczema, psoriasis, melasma, ulcer healing, and malignant melanoma. There is a plethora of functional melatonin properties, which still await to be fully appreciated by dermatologists. The current review emphasizes few of the established uses and few emerging potentialities that render melatonin a promising candidate for managing several diseases.
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Reiter, Russel J., Dun-xian Tan, M. Pilar Terron, Luis J. Flores i Zbigniew Czarnocki. "Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions." Acta Biochimica Polonica 54, nr 1 (9.03.2007): 1–9. http://dx.doi.org/10.18388/abp.2007_3264.
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This review summarizes some of the recent findings concerning the long-held tenet that the enzyme, N-acetyltransferase, which is involved in the production of N-acetylserotonin, the immediate precursor of melatonin, may in fact not always control the quantity of melatonin generated. New evidence from several different laboratories indicates that hydroxyindole-O-methyltransferase, which O-methylates N-acetylserotonin to melatonin may be rate-limiting in some cases. Also, the review makes the point that melatonin's actions are uncommonly widespread in organs due to the fact that it works via membrane receptors, nuclear receptors/binding sites and receptor-independent mechanisms, i.e., the direct scavenging of free radicals. Finally, the review briefly summarizes the actions of melatonin and its metabolites in the detoxification of oxygen and nitrogen-based free radicals and related non-radical products. Via these multiple processes, melatonin is capable of influencing the metabolism of every cell in the organism.
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Hu, Xinyu, Jingwen Li, Xinyi Wang, Hanshu Liu, Tao Wang, Zhicheng Lin i Nian Xiong. "Neuroprotective Effect of Melatonin on Sleep Disorders Associated with Parkinson’s Disease". Antioxidants 12, nr 2 (6.02.2023): 396. http://dx.doi.org/10.3390/antiox12020396.
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Parkinson’s disease (PD) is a complex, multisystem disorder with both neurologic and systemic manifestations, which is usually associated with non-motor symptoms, including sleep disorders. Such associated sleep disorders are commonly observed as REM sleep behavior disorder, insomnia, sleep-related breathing disorders, excessive daytime sleepiness, restless legs syndrome and periodic limb movements. Melatonin has a wide range of regulatory effects, such as synchronizing circadian rhythm, and is expected to be a potential new circadian treatment of sleep disorders in PD patients. In fact, ongoing clinical trials with melatonin in PD highlight melatonin’s therapeutic effects in this disease. Mechanistically, melatonin plays its antioxidant, anti-inflammatory, anti-excitotoxity, anti-synaptic dysfunction and anti-apoptotic activities. In addition, melatonin attenuates the effects of genetic variation in the clock genes of Baml1 and Per1 to restore the circadian rhythm. Together, melatonin exerts various therapeutic effects in PD but their specific mechanisms require further investigations.
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Gao, Shiwei, Dezheng Wei, Dandan Pan, Fei Wang, Hui Kang i Yuxin Yao. "Melatonin Promotes Accumulation of Resveratrol and Its Derivatives through Upregulation of PAL, 4CL, C4H, and STS in Grape Seeds". Horticulturae 10, nr 1 (9.01.2024): 65. http://dx.doi.org/10.3390/horticulturae10010065.
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Melatonin’s role in regulating the biosynthesis of phenolic compounds, particularly stilbenes, remains unknown in grape seeds. In this study, widely targeted metabolomics analysis revealed that 82 phenolic compounds were differentially accumulated in grape seeds from the berries treated with melatonin. The accumulation of resveratrol and its 11 derivatives was largely increased in melatonin-treated berry seeds. Additionally, melatonin treatment of preveraison grape berries increased the resveratrol content in seeds during berry ripening. The results of RNA-Seq showed that a total of 399 genes were differentially expressed, which were mainly involved in the plant hormone signal transduction, metabolic, and biosynthesis of secondary metabolites pathways, in melatonin-treated berry seeds compared to control seeds. Additionally, five PALs, four 4CLs, one C4H, and four STSs were elucidated to be induced by melatonin in seeds at different time points after treatment. Therefore, melatonin promotes resveratrol accumulation and its derivatives, probably by upregulating the genes in the phenylpropanoid pathway, which provides precursors for resveratrol biosynthesis, and the STS genes in grape seeds.
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Shenoy, Pranita, Adriana Etcheverry, Jalyn Ia, Manisha Witmans i Mary Anne Tablizo. "Melatonin Use in Pediatrics: A Clinical Review on Indications, Multisystem Effects, and Toxicity". Children 11, nr 3 (9.03.2024): 323. http://dx.doi.org/10.3390/children11030323.
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Exogenous melatonin is typically used for sleep regulation in the context of insomnia either in healthy children or those with neurodevelopmental disabilities. It is also used for the management of circadian rhythm sleep disorders in pediatric and adolescent patients. There are also many other possible indications that we will discuss in this paper beyond the role of melatonin for sleep regulation, including its potential use for various areas of medicine such as inflammatory conditions. Since melatonin is unregulated in the United States, distributed over the counter and perceived to be natural and safe, it has become available in many forms in the last two decades. With increasing sleep disturbances and mental health problems after the COVID-19 pandemic, melatonin has become even more popular and studies have shown a dramatic increase in use as well as resulting side effects, including melatonin overdose. As melatonin is generally viewed by physicians as a benign medication, we hope to increase awareness of melatonin’s properties as well as negative side effects to optimize its use in the pediatric population.
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Pohanka, Miroslav. "Impact of melatonin on immunity: a review". Open Medicine 8, nr 4 (1.08.2013): 369–76. http://dx.doi.org/10.2478/s11536-013-0177-2.
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AbstractMelatonin is a hormone produced by the pineal gland. In addition to its hormonal effect, it has strong antioxidant properties. Melatonin is probably best known for its ability to control circadian rhythm; it is sold in many countries as a supplement or drug for improving of sleep quality. However, melatonin’s effect is not limited to control of circadian rhythm:. it is involved in other effects, including cell cycle control and regulation of several important enzymes, including inhibition of inducible nitric oxide synthase. Melatonin affects immunity as well. It can modulate the immune response on disparate levels with a significant effect on inflammation. The role of melatonin in body regulatory process is not well understood; only limited conclusions can be drawn from known data. The current review attempts to summarize both basic facts about melatonin’s effects and propose research on the lesser known issues in the future.
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Mańka, Sylwia, Zbigniew Baj i Ewa Majewska. "The influence of melatonin on apoptosis of human neutrophils". Postępy Higieny i Medycyny Doświadczalnej 73 (22.02.2019): 81–91. http://dx.doi.org/10.5604/01.3001.0013.0512.
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Aim: Melatonin (Mel) besides its main role in circadian and seasonal rhythm coordination, plays a role in immunoregulation and inflammatory responses. The melatonin’s ability to modulate apoptosis is one of its important roles related to its effect on immune system but the exact effect of its action and the mechanisms of apoptosis control by melatonin remain still unclear. The goal of our study was to examine the involvement of melatonin in the apoptosis of human neutrophils in vitro and possible mechanisms of this action. Material/Methods: We measured the effect of melatonin on the spontaneous and TNF-α-induced apoptosis of human neutrophils using propidium iodide and Annexin-V and on caspase-3 activation, apoptosis-related surface antigen expressions, intracellular reactive oxygen species (ROS) generation and cytochrome c release using flow cytometry and commercial reagents. Results: Melatonin does not affect spontaneous apoptosis of human neutrophils and mitochondrial cytochrome c release but protects the cells from the significant rise of TNF-α-induced apoptosis and cytochrome c release. Intracellular ROS generation in PMA-stimulated neutrophils did not change after the influence of melatonin but the significant drop of ROS generation in neutrophils stimulated with TNF- α was upregulated to the control level after preincubation of the neutrophils with melatonin. Melatonin did not change significantly Fas, Fas-L and active caspase-3 expressions in neutrophils. Conclusions: Melatonin does not affect the spontaneous apoptosis, however, inhibits TNF-α-induced apoptosis of human neutrophils. Our findings suggest that the intrinsic pathway of the process is a result of the melatonin induced mitochondrial alterations.
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Keskin, Goksal, Dilek Keskin, Ali Inal i Rahsan Ilikci. "Serum Melatonin levels in Sjögren patients (HUM7P.310)". Journal of Immunology 192, nr 1_Supplement (1.05.2014): 184.19. http://dx.doi.org/10.4049/jimmunol.192.supp.184.19.
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Abstract OBJECTIVES: Primary sjögren syndrome is a systemic autoimmune disease characterized by immune system abnormalities. It’s unclear how melatonin influences the immune responses. In this study we investigated the levels of serum melatonin in sjögren patients and melatonin’s diurnal rhythm. METHOD: In this study, 47 sjögren patients (35 female, 12 male, mean age 39,7 ± 11,5 years, mean disease duration 8,2 ± 2,7 years) and 28 healthy controls ( 21 female, 7 male, mean age 41,3± 7,7 years) were included. Serum melatonin levels were measured by ELISA, in the morning and night. RESULTS: In the sjögren patients group; the mean serum melatonin levels were 49, 2 ± 12,3 at night and 52,6 ± 5,1 in the morning. In the healthy control group; the mean serum melatonin levels were 77,1 ± 12,9 at night and 27,2 ± 6,1 in the morning. There was significant change in the diurnal rhythm of the melatonin in the sjögren patient group. Melatonin secretion at night was found to be lower, in the SSc patient group than the healthy control group, but in the morning was found to be higher. Those were statically significant (p<0.001, p<0.001 respectively). In the patient group, there was no statically significant difference between the serum levels in the morning and night. CONCLUSION: In this study, we found that diurnal rhythm of the melatonin changed in sjögren patients. These findings can be due to the effects of melatonin on the inflammatory responses.