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1.
Therapeutic potential of melatonin in colorectal cancer: Focus on lipid metabolism and gut microbiota.
Pan, S, Guo, Y, Hong, F, Xu, P, Zhai, Y
Biochimica et biophysica acta. Molecular basis of disease. 2022;(1):166281
Abstract
Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. The occurrence and development of CRC are complicated processes. Obesity and dysbacteriosis have been increasingly regarded as the main risk factors for CRC. Understanding the etiology of CRC from multiple perspectives is conducive to screening for some potential drugs or new treatment strategies to limit the serious side effects of conventional treatment and prolong the survival of CRC patients. Melatonin, a natural indoleamine, is mainly produced by the pineal gland, but it is also abundant in other tissues, including the gastrointestinal tract, retina, testes, lymphocytes, and Harder's glands. Melatonin could participate in lipid metabolism by regulating adipogenesis and lipolysis. Additionally, many studies have focused on the potential beneficial effects of melatonin in CRC, such as promotion of apoptosis; inhibition of cell proliferation, migration, and invasion; antioxidant activity; and immune regulation. Meaningfully, gut microbiota is the main determinant of all aspects of health and disease (including obesity and tumorigenesis). The gut microbiota is of great significance for understanding the relationship between obesity and increased risk of CRC. Although the current understanding of how the melatonin-mediated gut microbiota coordinates a variety of physiological and pathological activities is fairly comprehensive, there are still many unknown topics to be explored in the face of a complex nutritional status and a changeable microbiota. This review summarizes the potential links among melatonin, lipid metabolism, gut microbiota, and CRC to promote the development of melatonin as a preventive and therapeutic agent for CRC.
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2.
Protective Effects of Melatonin against Obesity-Induced by Leptin Resistance.
Suriagandhi, V, Nachiappan, V
Behavioural brain research. 2022;:113598
Abstract
Consumption of an exceedingly high-fat diet with irregular eating and sleeping habits is typical in the current sedentary lifestyle, leading to chronic diseases like obesity and diabetes mellitus. Leptin is a primary appetite-regulating hormone that binds to its receptors in the hypothalamic cell membrane and regulates downstream appetite-regulating neurons NPY/AgRp and POMC in the hypothalamus. Based on the fat content of the adipose tissue, leptin is secreted, and excess accumulation of fat in adipose tissue stimulates the abnormal secretion of leptin. The secreted leptin circulating in the bloodstream uses its transporters to cross the blood-brain barrier (BBB) and reach the CSF. There is a saturation limit for leptin bound to its transporters to cross the BBB, and increased leptin secretion in adipose tissue has a defect in its transport across the BBB. Leptin resistance is due to excess leptin, a saturation of its transporters, and deficiency in either the receptor level or signalling in the hypothalamus. Leptin resistance leads to obesity due to excess food intake and less energy expenditure. Normal leptin secretion follows a rhythm, and alteration in the lifestyle leads to hormonal imbalances and increases ROS generation leading to oxidative stress. The sleep disturbance causes obesity with increased lipid accumulation in adipose tissue. Melatonin is the master regulator of the sleep-wake cycle secreted by the pineal gland during the night. It is a potent antioxidant with anti-inflammatory properties. Melatonin is secreted in a pattern called the circadian rhythm in humans as well. Research indicates that melatonin plays a vital role in hormonal regulation and energy metabolism, including leptin signalling and secretion. Studying the role of melatonin in leptin regulation will help us combat the pathologies of obesity caused by leptin resistance.
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3.
Melatonin Levels in Children with Obesity Are Associated with Metabolic Risk and Inflammatory Parameters.
Gombert, M, Martin-Carbonell, V, Pin-Arboledas, G, Carrasco-Luna, J, Carrasco-García, Á, Codoñer-Franch, P
Nutrients. 2021;(10)
Abstract
Melatonin, the hormone of circadian rhythm regulation, is involved in the modulation of mitochondrial activity through its antioxidant and anti-inflammatory properties. Alteration of circadian rhythms such as sleep is related to obesity and metabolic pathogenesis in adulthood, but studies during childhood are scarce. The present study investigated the association of melatonin with metabolic and inflammatory markers in children with (n = 113) and without obesity (n = 117). Melatonin was measured in saliva four and two hours before bedtime, and after one hour of sleep. Cardiometabolic factors, high sensitivity C-reactive protein, immune markers (monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, tumor necrosis α and interferon-γ), leptin and ghrelin were determined. Sleep duration was recorded by a questionnaire. The melatonin level at 1 h after sleep was found to be increased more than twofold in children with obesity (90.16 (57.16-129.16) pg/mL) compared to controls (29.82 (19.05-61.54) pg/mL, p < 0.001) and was related to fat mass (rho = 0.294, p < 0.001); melatonin levels at 1 h after sleep were inversely correlated with high-density lipoprotein cholesterol. Positive correlation was found with apolipoprotein B, adipokines, high sensitivity C-reactive protein, plasminogen activator inhibitor-1 and tumor necrosis factor-α. Shorter sleep duration and earlier waking times were recorded in children with obesity. In conclusion, melatonin in children with obesity appears to be involved in the global metabolic and inflammatory alteration of this condition.
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4.
Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc.
Corrao, S, Mallaci Bocchio, R, Lo Monaco, M, Natoli, G, Cavezzi, A, Troiani, E, Argano, C
Nutrients. 2021;(4)
Abstract
More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.
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5.
Melatonin Confers Plant Cadmium Tolerance: An Update.
Gu, Q, Wang, C, Xiao, Q, Chen, Z, Han, Y
International journal of molecular sciences. 2021;(21)
Abstract
Cadmium (Cd) is one of the most injurious heavy metals, affecting plant growth and development. Melatonin (N-acetyl-5-methoxytryptamine) was discovered in plants in 1995, and it is since known to act as a multifunctional molecule to alleviate abiotic and biotic stresses, especially Cd stress. Endogenously triggered or exogenously applied melatonin re-establishes the redox homeostasis by the improvement of the antioxidant defense system. It can also affect the Cd transportation and sequestration by regulating the transcripts of genes related to the major metal transport system, as well as the increase in glutathione (GSH) and phytochelatins (PCs). Melatonin activates several downstream signals, such as nitric oxide (NO), hydrogen peroxide (H2O2), and salicylic acid (SA), which are required for plant Cd tolerance. Similar to the physiological functions of NO, hydrogen sulfide (H2S) is also involved in the abiotic stress-related processes in plants. Moreover, exogenous melatonin induces H2S generation in plants under salinity or heat stress. However, the involvement of H2S action in melatonin-induced Cd tolerance is still largely unknown. In this review, we summarize the progresses in various physiological and molecular mechanisms regulated by melatonin in plants under Cd stress. The complex interactions between melatonin and H2S in acquisition of Cd stress tolerance are also discussed.
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6.
Melatonin interferes with COVID-19 at several distinct ROS-related steps.
Camp, OG, Bai, D, Gonullu, DC, Nayak, N, Abu-Soud, HM
Journal of inorganic biochemistry. 2021;:111546
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Abstract
Recent studies have shown a correlation between COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the distinct, exaggerated immune response titled "cytokine storm". This immune response leads to excessive production and accumulation of reactive oxygen species (ROS) that cause clinical signs characteristic of COVID-19 such as decreased oxygen saturation, alteration of hemoglobin properties, decreased nitric oxide (NO) bioavailability, vasoconstriction, elevated cytokines, cardiac and/or renal injury, enhanced D-dimer, leukocytosis, and an increased neutrophil to lymphocyte ratio. Particularly, neutrophil myeloperoxidase (MPO) is thought to be especially abundant and, as a result, contributes substantially to oxidative stress and the pathophysiology of COVID-19. Conversely, melatonin, a potent MPO inhibitor, has been noted for its anti-inflammatory, anti-oxidative, anti-apoptotic, and neuroprotective actions. Melatonin has been proposed as a safe therapeutic agent for COVID-19 recently, having been given with a US Food and Drug Administration emergency authorized cocktail, REGEN-COV2, for management of COVID-19 progression. This review distinctly highlights both how the destructive interactions of HOCl with tetrapyrrole rings may contribute to oxygen deficiency and hypoxia, vitamin B12 deficiency, NO deficiency, increased oxidative stress, and sleep disturbance, as well as how melatonin acts to prevent these events, thereby improving COVID-19 prognosis.
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7.
Role of Melatonin in Angiotensin and Aging.
Sehirli, AO, Sayıner, S, Chukwunyere, U, Serakinci, N
Molecules (Basel, Switzerland). 2021;(15)
Abstract
The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase pathway, which in turn results in the production of reactive oxygen species. This radical oxygen-containing molecule has been linked to aging and several age-related disorders, including renal damage. Considering the role of angiotensin in aging, melatonin might relieve angiotensin-II-induced stress by enhancing the mitochondrial calcium uptake 1 pathway, which is crucial in preventing the mitochondrial calcium overload that may trigger increased production of reactive oxygen species and oxidative stress. This review highlights the role and importance of melatonin together with angiotensin in aging and age-related diseases.
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Comparison of IVF and IVM outcomes in the same patient treated with a modified IVM protocol along with an oocytes-maturing system containing melatonin: A pilot study.
Li, X, Mu, Y, Elshewy, N, Ding, D, Zou, H, Chen, B, Chen, C, Wei, Z, Cao, Y, Zhou, P, et al
Life sciences. 2021;:118706
Abstract
AIM: To compare embryonic developmental competence and clinical outcomes of oocytes matured in vivo (IVF oocytes) and those matured in vitro (IVM oocytes) from the same IVM/IVF cycles, and to analyze the clinical efficiency of a melatonin-supplemented in vitro maturation system combined with a modified IVM/IVF protocol. MAIN METHODS We randomly recruited 22 patients undergoing IVM/IVF treatment protocol in our medical centre. The fertilization, cleavage and blastocyst formation rates, as well as clinical pregnancy, implantation and live birth/ongoing pregnancy rates were analysed and compared between IVF and IVM oocytes. We evaluated mitochondrial function indicators by fluorescence staining and confocal microscopy, including mitochondrial membrane potential, reactive oxygen species and calcium (Ca2+) levels in 15 IVF and 15 IVM oocytes. KEY FINDINGS There were no significant differences in fertilization or blastocyst formation rates between the IVF and IVM groups, whereas the cleavage rate was significantly higher in the IVF versus IVM group (100% vs 93.4 ± 10.9%, p = 0.03). There were no significant differences in the clinical pregnancy, implantation or live birth/ongoing pregnancy rates between the two groups. The cumulative clinical pregnancy and ongoing pregnancy/live birth rate per pick-up oocyte in the IVM/IVF treatment cycles were 68.2% (15/22) and 54.5% (12/22), respectively. The reactive oxygen species and Ca2+ levels were significantly increased, and mitochondrial membrane potential was significantly decreased, in IVM compared with IVF oocytes. SIGNIFICANCE The modified IVM/IVF protocol can be effectively applied to the treatment of some indicated patients and achieve ideal clinical outcomes, even though the developmental potential of IVM oocytes may not be as high as IVF oocytes.
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Blood-brain barrier dysfunction in hemorrhagic transformation: a therapeutic opportunity for nanoparticles and melatonin.
Figueroa, EG, González-Candia, A, Caballero-Román, A, Fornaguera, C, Escribano-Ferrer, E, García-Celma, MJ, Herrera, EA
Journal of neurophysiology. 2021;(6):2025-2033
Abstract
Stroke is the second leading cause of death worldwide, estimated that one-sixth of the world population will suffer it once in their life. The most common type of this medical condition is the ischemic stroke (IS), produced by a thrombotic or embolic occlusion of a major cerebral artery or its branches, leading to the formation of a complex infarct region caused by oxidative stress, excitotoxicity, and endothelial dysfunction. Nowadays, the immediate treatment for IS involves thrombolytic agents or mechanical thrombectomy, depending on the integrity of the blood-brain barrier (BBB). A common stroke complication is the hemorrhagic transformation (HT), which consists of bleeding into the ischemic brain area. Currently, better treatments for IS are urgently needed. As such, the neurohormone melatonin has been proposed as a good candidate due to its antioxidant, anti-inflammatory, and neuroprotective effects, particularly against lipid peroxidation and oxidative stress during brain ischemia. Here, we proposed to develop intravenous or intranasal melatonin nanoformulation to specifically target the brain in patients with stroke. Nowadays, the challenge is to find a formulation able to cross the barriers and reach the target organ in an effective dose to generate the pharmacological effect. In this review, we discuss the current literature about stroke pathophysiology, melatonin properties, and its potential use in nanoformulations as a novel therapeutic approach for ischemic stroke.
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10.
Metal ion homeostasis with emphasis on zinc and copper: Potential crucial link to explain the non-classical antioxidative properties of vitamin D and melatonin.
Martín Giménez, VM, Bergam, I, Reiter, RJ, Manucha, W
Life sciences. 2021;:119770
Abstract
Metal ion homeostasis is an essential physiological mechanism necessary for achieving an adequate balance of these ions' concentrations in the different cellular compartments. This fact is of great importance because both an excess and a deficiency of cellular metal ion levels are usually equally harmful due to the exacerbated increase in oxidative stress that may occur in both cases. Metal ion homeostasis ensures an equilibrium among multiple functions associated with the body's antioxidative defense network controlled by metallic micronutrients such as zinc and copper, some of the central regulators of redox processes. These micronutrients significantly modulate the activity of some isoforms of superoxide dismutase (SOD) and other enzymes such as metallothioneins (MTs) and ceruloplasmin (CP), which are directly or indirectly involved in the regulation of redox homeostasis. Although it is well known that both melatonin (MEL) and vitamin D have important roles as natural antioxidants, often some of these effects are related to their actions on antioxidative processes dependent on metal ions. Thus, in addition to their classical antioxidative properties usually associated with mitochondrial effects, it is known that MEL and vitamin D modulate the expression and activity of Cu/Zn-dependent SOD isoforms, MTs and CP; function as copper chelators and regulate genomic and non-genomic mechanisms related to the zinc transport. This review summarizes the main findings related to the crucial participation of zinc and copper in physiological antioxidative status and their relationship with the non-classical antioxidant effects of MEL and vitamin D, suggesting a potential synergism among these four micronutrients.