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1.
The effects of melatonin on neurohormonal regulation in cardiac cachexia: A mechanistic review.
Jafari-Vayghan, H, Saleh-Ghadimi, S, Maleki, V, Moludi, J, Alizadeh, M
Journal of cellular biochemistry. 2019;(10):16340-16351
Abstract
Heart failure (HF) is one of the prominent health concerns and its morbidity is comparable to many malignancies. Cardiac cachexia (CC), characterized by significant weight loss and muscle wasting, frequently occurs in progressive stage of HF. The pathophysiology of CC is multifactorial including nutritional and gastrointestinal alterations, immunological and neurohormonal activation, and anabolic/catabolic imbalance. Neurohormones are critically involved in the development of both HF and CC. Melatonin is known as an anti-inflammatory and antioxidant hormone. It seems that melatonin possibly regulates the neurohormonal signaling pathway related to muscle wasting in CC, but limited comprehensive data is available on the mechanistic aspects of its activity. In this, we reviewed the reports regarding the role of neurohormones in CC occurrence and possible activity of melatonin in modulation of HF and subsequently CC via neurohormonal regulation. In addition, we have discussed proposed mechanisms of action for melatonin considering its possible interactions with neurohormones. In conclusion, melatonin likely regulates the signaling pathways related to muscle wasting in CC by reducing tumor necrosis factor α levels and activating the gene expression of insulin-like growth factor-1. Also, this hormone inhibits the proteolytic pathway by inhibiting nuclear factor-κB (NF-κB), renin-angiotensin system and forkhead box protein O1 pathways and could increase protein synthesis by activating Akt and mammalian target of rapamycin. To elucidate the positive role of melatonin in CC and exact mechanisms related to muscle wasting more cellular and clinical trial studies are needed.
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2.
Potential use of melatonin in skin cancer treatment: A review of current biological evidence.
Pourhanifeh, MH, Mahdavinia, M, Reiter, RJ, Asemi, Z
Journal of cellular physiology. 2019;(8):12142-12148
Abstract
Skin cancer, particularly melanoma, is a leading cause of death worldwide. The therapeutic methods for this malignancy are not effective, and due to the side effects of these treatments, applying an appropriate alternative or complementary treatment is important. According to available data, melatonin as the main product of the pineal gland has oncostatic and antitumoral properties. Also, melatonin acts as an anti-inflammatory and reactive oxygen species inducer agent which suppresses the growth of tumors. It also has apoptosis induction characteristics through regulating signaling pathways, including heat shock protein 70, nuclear factor-erythroid 2 p45-related factor 2 and others. Thus, adding melatonin to chemo- and radiotherapy may have synergistic therapeutic effects and increase the survival time in patients with skin cancer. Few clinical studies have evaluated the efficacy of melatonin in skin cancer. Based on the related mechanisms, this review discusses about how melatonin may improve outcomes in skin cancer patients.
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3.
Melatonin As a Modulator of Degenerative and Regenerative Signaling Pathways in Injured Retinal Ganglion Cells.
Juybari, KB, Hosseinzadeh, A, Ghaznavi, H, Kamali, M, Sedaghat, A, Mehrzadi, S, Naseripour, M
Current pharmaceutical design. 2019;(28):3057-3073
Abstract
Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.
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4.
Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms.
Chuffa, LGA, Lupi, LA, Cucielo, MS, Silveira, HS, Reiter, RJ, Seiva, FRF
International journal of molecular sciences. 2019;(1)
Abstract
The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the "receptivity window". Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine-placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.
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5.
Melatonin: A New Plant Hormone and/or a Plant Master Regulator?
Arnao, MB, Hernández-Ruiz, J
Trends in plant science. 2019;(1):38-48
Abstract
Melatonin is a pleiotropic molecule with many diverse actions in plants. It is considered primarily an antioxidant with important actions in the control of reactive oxygen and nitrogen species (ROS and RNS), among other free radicals, and harmful oxidative molecules present in plant cells. In addition, plant melatonin is involved in multiple physiological actions, such as growth, rooting, seed germination, photosynthesis, and protection against abiotic and/or biotic stressors. The recent identification of the first plant melatonin receptor opened the door to this regulatory molecule being considered a new plant hormone. However, due to the diversity of its actions, melatonin has also been proposed as a plant master regulator. Here, we discuss the most recent data in respect to both perspectives.
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6.
Recent advancements in the mechanism of nitric oxide signaling associated with hydrogen sulfide and melatonin crosstalk during ethylene-induced fruit ripening in plants.
Mukherjee, S
Nitric oxide : biology and chemistry. 2019;:25-34
Abstract
The current review focuses on the significant role of nitric oxide (NO) in modulating ethylene-induced fruit ripening responses in plants. In this context, hydrogen sulfide (H2S) and melatonin mediated crosstalk mechanisms have been discussed with recent updates. Physiological and biochemical events associated with climacteric fruit ripening involves a plethora of effects mediated by these biomolecules. In the last few years of progress in fruit ripening physiology, the involvement of hydrogen sulfide in relation to NO remains as a nascent field of research. The importance of nitric oxide as a freely diffusible and membrane permeable biomolecule leads to its applications in post-harvest fruit storage. The process of field to market transition of edible fruits involves various intermediate stages of post-harvest storage and transport. Fruits harvested in the pre-climacteric stage are intended to be stored and transported for longer durations. However, this does not confer proper development of aroma and flavor in the post-harvest stages. Nitric oxide and ethylene crosstalk is mediated by hydrogen sulfide and melatonin activity which regulate various metabolic pathways associated with fruit ripening. A surge in the reactive nitrogen species (RNS), sugar metabolism, and plastid biogenesis are the plausible effects of NO-ethylene crosstalk. NO-mediated regulations of carbon metabolism and phytohormone levels are essential components of fruit ripening process. Melatonin by the virtue of its functional group possesses strong anti-oxidative properties. Recent updates suggest crosstalk mechanisms associated with melatonin-ethylene and nitric oxide in plants. The present review briefly summarizes the current understandings of fruit ripening physiology manifested by the effects of NO, H2S and melatonin signaling. The agri-horticultural applications of exogenous NO/H2S donors and melatonin treatment impose major benefits for delaying postharvest fruit senescence.
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7.
The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and meta-analysis of randomized controlled trials.
Akbari, M, Ostadmohammadi, V, Tabrizi, R, Lankarani, KB, Heydari, ST, Amirani, E, Reiter, RJ, Asemi, Z
Inflammopharmacology. 2018;(4):899-907
Abstract
OBJECTIVE This systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to determine the effect of melatonin supplementation on the inflammatory markers among individuals with metabolic syndrome (MetS) and related disorders. METHODS We searched the following databases up to March 2018: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran's Q test and I-square (I2) statistic. Data were pooled using the random effect model and standardized mean difference (SMD) was considered as the summary effect size. RESULTS Six trials of 317 potential reports were identified to be suitable for our meta-analysis. The pooled results using random effects model indicated that melatonin supplementation significantly reduced C-reactive protein (CRP) (SMD = - 1.80; 95% CI - 3.27, - 0.32; P = 0.01; I2: 95.2) and interleukin 6 (IL-6) concentrations (SMD = - 2.02; 95% CI - 3.57, - 0.47; P = 0.01; I2: 91.2) among patients with MetS and related disorders; however, it did not affect tumor necrosis factor-α (TNF-α) concentrations (SMD = - 1.87; 95% CI - 3.81, 0.07; P = 0.05; I2: 94.4). CONCLUSIONS In summary, the current meta-analysis showed the promising effect of melatonin administration on reducing CRP and IL-6, but not TNF-α levels among patients with MetS and related disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.
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8.
Docking studies for melatonin receptors.
Alkozi, HA, Sánchez Montero, JM, Doadrio, AL, Pintor, J
Expert opinion on drug discovery. 2018;(3):241-248
Abstract
Melatonin is a neurohormone that controls many relevant physiological processes beyond the control of circadian rhythms. Melatonin's actions are carried out by two main types of melatonin receptors; MT1 and MT2. These receptors are important, and not just because of the biological actions of its natural agonist; but also, because melatonin analogues can improve or antagonize their biological effect. Area covered: The following article describes the importance of melatonin as a biologically relevant molecule. It also defines the receptors for this substance, as well as the second messengers coupled to these receptors. Lastly, the article describes the amino acid residues involved in the docking process in both MT1 and MT2 melatonin receptors. Expert opinion: The biological actions of melatonin and their interpretations are becoming more relevant and therefore require the development of new pharmacological tools. Understanding the second messenger mechanisms involved in melatonin actions, as well as the characteristics of the docking of this molecule to MT1 and MT2 melatonin receptors, will permit the development of more selective agonists and antagonists which will help us to better understand this molecule as well to develop new therapeutic compounds.
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9.
Phytomelatonin: a universal abiotic stress regulator.
Wang, Y, Reiter, RJ, Chan, Z
Journal of experimental botany. 2018;(5):963-974
Abstract
Melatonin, a derivative of tryptophan, was first detected in plant species in 1995 and it has been shown to be a diverse regulator during plant growth and development, and in stress responses. Recently, great progress has been made towards determining the detailed functions of melatonin in plant responses to abiotic stress. Melatonin priming improves plant tolerance to cold, heat, salt, and drought stresses through regulation of genes involved in the DREB/CBF, HSF, SOS, and ABA pathways, respectively. As a scavenger of free radicals, melatonin also directly detoxifies reactive oxygen species, thus alleviating membrane oxidation. Abiotic stress-inhibited photosynthesis is partially recovered and metabolites accumulate in the presence of melatonin, leading to improved plant growth, delayed leaf senescence, and increased stress tolerance. In this review, we summarize the interactions of melatonin with phytohormones to regulate downstream gene expression, protein stabilization, and epigenetic modification in plants. Finally, we consider the need for, and approaches to, the identification of melatonin receptors and components during signaling transduction pathways.
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10.
Chronomedicine and type 2 diabetes: shining some light on melatonin.
Forrestel, AC, Miedlich, SU, Yurcheshen, M, Wittlin, SD, Sellix, MT
Diabetologia. 2017;(5):808-822
Abstract
In mammals, the circadian timing system drives rhythms of physiology and behaviour, including the daily rhythms of feeding and activity. The timing system coordinates temporal variation in the biochemical landscape with changes in nutrient intake in order to optimise energy balance and maintain metabolic homeostasis. Circadian disruption (e.g. as a result of shift work or jet lag) can disturb this continuity and increase the risk of cardiometabolic disease. Obesity and metabolic disease can also disturb the timing and amplitude of the clock in multiple organ systems, further exacerbating disease progression. As our understanding of the synergy between the timing system and metabolism has grown, an interest has emerged in the development of novel clock-targeting pharmaceuticals or nutraceuticals for the treatment of metabolic dysfunction. Recently, the pineal hormone melatonin has received some attention as a potential chronotherapeutic drug for metabolic disease. Melatonin is well known for its sleep-promoting effects and putative activity as a chronobiotic drug, stimulating coordination of biochemical oscillations through targeting the internal timing system. Melatonin affects the insulin secretory activity of the pancreatic beta cell, hepatic glucose metabolism and insulin sensitivity. Individuals with type 2 diabetes mellitus have lower night-time serum melatonin levels and increased risk of comorbid sleep disturbances compared with healthy individuals. Further, reduced melatonin levels, and mutations and/or genetic polymorphisms of the melatonin receptors are associated with an increased risk of developing type 2 diabetes. Herein we review our understanding of molecular clock control of glucose homeostasis, detail the influence of circadian disruption on glucose metabolism in critical peripheral tissues, explore the contribution of melatonin signalling to the aetiology of type 2 diabetes, and discuss the pros and cons of melatonin chronopharmacotherapy in disease management.