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Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19

2020-09 El-Missiry MA, El-Missiry ZMA, Othman AI

Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages.

Structural and physico-chemical evaluation of melatonin and its solution-state excited properties, with emphasis on its binding with novel coronavirus proteins

2020-08 Al-Zaqri N, Pooventhiran T, Alsalme A, Warad I, John AM, Thomas R

Melatonin is a natural hormone from the pineal gland that regulates the sleep-wake cycle. We examined the structure and physico-chemical properties of melatonin using electronic structure methods and molecular-mechanics tools. Density functional theory (DFT) was used to optimise the ground-state geometry of the molecule from frontier molecular orbitals, which were analysed using the B3LYP functional.

Predictions of melatonin suppression during the early biological night and their implications for residential light exposures prior to sleeping

2020-08 Rea MS, Nagare R, Figueiro MG

The magnitude of nocturnal melatonin suppression depends upon the spectrum, amount, and duration of light exposure. The functional relationship between melatonin suppression and the light spectrum and amount have been previously described. Only one duration-dependent parameter was needed to extend this functional relationship to predict nocturnal melatonin suppression during the early biological night from a variety of published studies.

Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment

2020-08 Martín Giménez VM, Inserra F, Tajer CD, Mariani J, Ferder L, Reiter RJ, Manucha W

COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level.

Melatonin Suppresses Renal Cortical Fibrosis by Inhibiting Cytoskeleton Reorganization and Mitochondrial Dysfunction through Regulation of miR-4516

2020-07 Yoon YM, Go G, Yun CW, Lim JH, Lee JH, Lee SH

Renal fibrosis, a major risk factor for kidney failure, can lead to chronic kidney disease (CKD) and is caused by cytoskeleton reorganization and mitochondrial dysfunction. In this study, we investigated the potential of melatonin treatment to reduce renal fibrosis by recovering the cytoskeleton reorganization and mitochondrial dysfunction.

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis

2020-07 Hazra S, Chaudhuri AG, Tiwary BK, Chakrabartia N

The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19.

Plasticity of glucose metabolism in activated immune cells: advantages for melatonin inhibition of COVID-19 disease

2020-06 Reiter RJ, Sharma R, Ma Q, Liu C, Manucha W, Abreu-Gonzalez P, Dominguez-Rodriguez A

COVID-19 has infected hundreds of thousands and killed tens of thousands of people worldwide and it continues to ravage societies as well as fiscal and economic stability of several countries.  Currently, several drugs that were designed for other conditions have been repurposed to counter the COVID-19 pandemic.  Some have modest efficacy in resisting this disease, but all of them have significant toxicity.  Several pharmaceutical companies are rushing to develop vaccines, but their availability is 8 to 12 months in the future.  In the meantime, readily available and affordable molecules that will have utility as COVID-19 antidotes are being sought.

Melatonin, cardiovascular disease and COVID-19: A potential therapeutic strategy?

2020-06 Dominguez-Rodriguez A, Abreu-Gonzalez P, Marik PE, Reiter RJ 

The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. SARS-CoV-2 induced endothelial dysfunction and cardiovascular injury are probably initiated by increases in the phosphorylation levels of JAK2 and STAT3 and resultant reactive oxygen species (ROS) formation. These pathological alterations are speculated to be strikingly reversed by melatonin.

Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series

2020-06 Castillo RR, Quizon GRA, Juco MJM, Roman ADE, de Leon DG, Punzalan FER, Guingon RBL, Morales DD, Tan DX, Reiter RJ

Treatment for coronavirus disease 2019 (COVID19) pneumonia remains empirical and the search for therapies that can improve outcomes continues. Melatonin has been shown to have anti-inflammatory, antioxidant, and immune-modulating effects that may address key pathophysiologic mechanisms in the development and progression of acute respiratory distress syndrome (ARDS), which has been implicated as the likely cause of death in COVID19.

Dietary Melatonin Therapy Alleviates the Lamina Cribrosa Damages in Patients With Mild Cognitive Impairments: A Double-Blinded, Randomized Controlled Study.

2020-05 Xu L, Yu H, Sun H, Hu B, Geng Y

Alzheimer's disease (AD) is a degenerative disease that is characterized by massive neuron devastations in the hippocampus and cortex. Mild cognitive impairment (MCI) is the transitory stage between normality and AD dementia. This study aimed to investigate the melatonin induced effects on the lamina cribrosa thickness (LCT) of patients with MCI.

The Effects of Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

2020-05 Ostadmohammadi V, Soleimani A, Bahmani F, Aghadavod E, Ramezani R, Reiter RJ, Mansournia MA, Banikazemi Z, Soleimani M, Zaroudi M, Asemi Z

This study evaluated the effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis (HD) patients.

Effect of Nocturnal Melatonin Intake on Cellular Damage and Recovery From Repeated Sprint Performance During an Intensive Training Schedule.

2020-05 Farjallah MA, Ghattassi K, Ben Mahmoud L, Graja A, Boudaya M, Elleuch H, Jammoussi K, Sahnoun Z, Souissi N, Chtourou H, Hammouda O

An optimal recovery between training sessions is of similar if not greater importance as the training content and program of the training, itself. One of the most used strategies for improving recovery is the ingestion of supplements.

Can melatonin reduce the severity of COVID-19 pandemic?

2020-04 Shneider A, Kudriavtsev A, Vakhrusheva A

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks.

Clinical Impact of Melatonin on Breast Cancer Patients Undergoing Chemotherapy; Effects on Cognition, Sleep and Depressive Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial.

2020-04 Palmer ACS, Zortea M, Souza A, Santos V, Biazús JV, Torres ILS, Fregni F, Caumo W

This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment.

Melatonin alleviates cardiac fibrosis via inhibiting lncRNA MALAT1/miR-141-mediated NLRP3 inflammasome and TGF-β1/Smads signaling in diabetic cardiomyopathy.

2020-04 Che H, Wang Y, Li H, Li Y, Sahil A, Lv J, Liu Y, Yang Z, Dong R, Xue H, Wang L

Melatonin is a hormone produced by the pineal gland, and it has extensive beneficial effects on various tissue and organs; however, whether melatonin has any effect on cardiac fibrosis in the pathogenesis of diabetic cardiomyopathy (DCM) is still unknown.

Antioxidant and Anti-Inflammatory Properties of Melatonin in Patients With Type 2 Diabetes Mellitus With Periodontal Disease Under Non-Surgical Periodontal Therapy: A Double-Blind, Placebo-Controlled Trial.

2020-03 Zare Javid A, Hosseini SA, Gholinezhad H, Moradi L, Haghighi-Zadeh MH, Bazyar H

The imbalance between pro-oxidant and antioxidant systems often leads to further oxidative damage in the pathogenesis of both diabetes and periodontal disease. This study aimed to investigate the antioxidant and anti-inflammatory properties of melatonin in type 2 diabetes mellitus (T2DM) patients with periodontal disease (PD) under non-surgical periodontal therapy (NSPT).

Melatonin a Promising Candidate for DNA Double-Stranded Breaks Reduction in Patients Undergoing Abdomen-Pelvis Computed Tomography Examinations.

2020-03 Eskandari A, Mahmoudzadeh A, Shirazi A, Esmaely F, Carnovale C, Cheki M

Cancer incidence is 24% greater in children and young adults exposed to Computed Tomography (CT) scans than those unexposed. Non-repair of ionizing radiation-induced DNA double-Strand Breaks (DSBs) can initiate carcinogenesis. In the present study, we aimed to investigate the radioprotective potential of melatonin against DSBs in peripheral blood lymphocytes of patients undergoing the abdomen-pelvis CT examinations.

Effectiveness of Complementary and Alternative Medicine Interventions for Sleep Quality in Adult Intensive Care Patients: A Systematic Review.

2020-03 Cooke M, Ritmala-Castrén M, Dwan T, Mitchell M

Pharmacological interventions for sleep (analgesic, sedative and hypnotic agents) can both disrupt and induce sleep and have many negative side effects within the intensive care population. The use of complementary and alternative medicine therapies to assist with sleep has been studied but given the variety of modalities and methodological limitations no reliable conclusions have been drawn.

Short Sleep Is Associated With Low Bone Mineral Density and Osteoporosis in the Women’s Health Initiative.

2020-02 Ochs-Balcom HM, Hovey KM, Andrews C, Cauley JA, Hale L, Li W, Bea JW, Sarto GE, Stefanick ML, Stone KL, Watts NB, Zaslavsky O, Wactawski-Wende J

Short sleep duration, recognized as a public health epidemic, is associated with adverse health conditions, yet little is known about the association between sleep and bone health. We tested the associations of usual sleep behavior and bone mineral density (BMD) and osteoporosis.

Circadian rhythm and its association with birth and infant outcomes: research protocol of a prospective cohort study.

2020-02 Kaur S, Teoh AN, Shukri NHM, Shafie SR, Bustami NA, Takahashi M, Lim PJ, Shibata S

Circadian rhythm plays an important role as our internal body's clock that synchronizes behavior and physiology according to the external 24-h light-dark cycle. Past studies have associated disrupted circadian rhythm with higher risk of miscarriages, preterm birth and low birth weights. This paper described the protocol of a prospective cohort study which aims to determine the circadian rhythm in pregnant women, identify its association with maternal factors during pregnancy, gestational weight gain, birth and infant outcomes.

Effect of Melatonin Supplementation in Combination With Neoadjuvant Chemotherapy to miR-210 and CD44 Expression and Clinical Response Improvement in Locally Advanced Oral Squamous Cell Carcinoma: A Randomized Controlled Trial.

2020-02 Kartini D, Taher A, Panigoro SS, Setiabudy R, Jusman SW, Haryana SM, Abdullah M, Rustamadji P, Purwanto DJ, Sutandyo N, Suroyo I, Siregar BH, Maruli H, Sungkar S

Squamous cell carcinoma of the oral cavity (OSCC) is the sixth most common malignancy. Surgery is mainstay treatment for oral cancers. Surgery in locally advanced OSCC presents many challenges primarily because the head and neck have critical structures that can be damaged by tumor or treatment.

Influence of Dietary Sources of Melatonin on Sleep Quality: A Review.

2020-01 Pereira N, Naufel MF, Ribeiro EB, Tufik S, Hachul H

Sleep is an essential biological phenomenon, being a physiological and behavioral process necessary for quality of life. Melatonin is a circadian hormone produced at night by the pineal gland, regulated by the light/dark cycle, under the control of the suprachiasmatic nucleus. Melatonin is an indoleamine, synthesized from the essential amino acid tryptophan via serotonin. Melatonin is also found in plants, where it helps fight oxidative stress. To present a systematic review on the ability of food sources of melatonin to promote healthy sleep.

The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial.

2019-12 Madsen MT, Zahid JA, Hansen CH, Grummedal O, Hansen JR, Isbrand A, Andersen UO, Andersen LJ, Taskiran M, Simonsen E, Gögenur I

Depression following acute coronary syndrome is prevalent and associated with increased mortality and morbidity. Melatonin may function as a primary prophylactic antidepressant substance and alleviate depressive symptoms. The study was undertaken to determine if melatonin administered following an acute coronary syndrome (ACS) could prevent development of depression.

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms.

2019-12 Chuffa LGA, Lupi LA, Cucielo MS, Silveira HS, Reiter RJ, Seiva FRF

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 Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial.

2019-11 Palmer ACS, Souza A, Dos Santos VS, Cavalheiro JAC, Schuh F, Zucatto AE, Biazus JV, Torres ILDS, Fregni F, Caumo W

Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS).

Reduced melatonin synthesis in pregnant night workers: Metabolic implications for offspring.

2019-11 Nehme PA, Amaral F, Lowden A, Skene DJ, Cipolla-Neto J, Moreno CRC

Several novel animal studies have shown that intrauterine metabolic programming can be modified in the event of reduced melatonin synthesis during pregnancy, leading to glucose intolerance and insulin resistance in the offspring. It is therefore postulated that female night workers when pregnant may expose the offspring to unwanted health threats.

Melatonin has profound effects on mitochondrial dynamics in myocardial ischaemia/reperfusion.

2019-11 Dube K, Dhanabalan K, Salie R, Blignaut M, Huisamen B, Lochner A

Research focus recently shifted to mitochondrial dynamics and the role of fusion and fission in cardioprotection. The aim of this study was to evaluate (i) the function and dynamics of mitochondria isolated from hearts exposed to ischaemia/reperfusion (I/R) (ii) the effects of melatonin, a powerful cardioprotectant, on mitochondrial dynamics in I/R.

Infusion of Melatonin Into the Paraventricular Nucleus Ameliorates Myocardial Ischemia-Reperfusion Injury by Regulating Oxidative Stress and Inflammatory Cytokines.

2019-10 Yang JB, Kang YM, Zhang C, Yu XJ, Chen WS

Melatonin, the receptors for which are abundant in the hypothalamic paraventricular nucleus (PVN), can protect the heart from myocardial ischemia-reperfusion (MI/R) injury. The aim of this study was to determine whether the infusion of melatonin into the PVN protects the heart from MI/R injury by suppressing oxidative stress or regulating the balance between proinflammatory cytokines and anti-inflammatory cytokines in MI/R rats.

Melatonin for prevention of placental malperfusion and fetal compromise associated with intrauterine inflammation-induced oxidative stress in a mouse model.

2019-10 Lee JY, Li S, Shin NE, Na Q, Dong J, Jia B, Jones-Beatty K, McLane MW, Ozen M, Lei J, Burd I

Melatonin has been shown to reduce oxidative stress and mitigate hypercoagulability. We hypothesized that maternally administered melatonin may reduce placental oxidative stress and hypercoagulability associated with exposure to intrauterine inflammation (IUI) and consequently improve fetoplacental blood flow and fetal sequelae.

An integrated approach to diagnosing and managing sleep disorders in menopausal women.

2019-10 Caretto M, Giannini A, Simoncini T

Sleep disorders increase in prevalence during the menopausal transition and they constitute a complex phenomenon. Insomnia, the main sleep disorder, can be a primary disorder or it can be secondary to hot flushes (HF), mood disorders, psychosocial factors, medical conditions, and other sleep disturbances, such as obstructive sleep apnoea (OSA) or restless legs syndrome (RLS).

The Circadian Syndrome: is the Metabolic Syndrome and much more!

2019-08 Zimmet P, Alberti KGMM, Stern N, Bilu C, El-Osta A, Einat H, Kronfeld-Schor N

The Metabolic Syndrome is a cluster of cardio-metabolic risk factors and comorbidities conveying high risk of both cardiovascular disease and type 2 diabetes. It is responsible for huge socio-economic costs with its resulting morbidity and mortality in most countries. The underlying aetiology of this clustering has been the subject of much debate.

Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment.

2019-08 Espino J, Macedo M, Lozano G, Ortiz Á, Rodríguez C, Rodríguez AB, Bejarano I

Unexplained infertility occurs when common causes for a couple's inability to conceive have been excluded. Although origins of idiopathic infertility are still unclear, factors, such as an altered oxidative balance, are believed to be involved. Melatonin is an outstanding antioxidant reportedly present in the follicular fluid (FF), which has been suggested as a useful tool in the management of human fertility.

Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain-injured patients.

2019-08 Blume C, Angerer M, Raml M, Del Giudice R, Santhi N, Pichler G, Kunz AB, Scarpatetti M, Trinka E, Schabus M

Healthy circadian rhythmicity has been suggested to relate to a better state of brain-injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC).

Co-administering Melatonin With an Estradiol-Progesterone Menopausal Hormone Therapy Represses Mammary Cancer Development in a Mouse Model of HER2-Positive Breast Cancer.

2019-07 Dodda BR, Bondi CD, Hasan M, Clafshenkel WP, Gallagher KM, Kotlarczyk MP, Sethi S, Buszko E, Latimer JJ, Cline JM, Witt-Enderby PA, Davis VL

Melatonin has numerous anti-cancer properties reported to influence cancer initiation, promotion, and metastasis. With the need for effective hormone therapies (HT) to treat menopausal symptoms without increasing breast cancer risk, co-administration of nocturnal melatonin with a natural, low-dose HT was evaluated in mice that develop primary and metastatic mammary cancer.

Pregnancy Induces an Earlier Chronotype in Both Mice and Women.

2019-06 Martin-Fairey CA, Zhao P, Wan L, Roenneberg T, Fay J, Ma X, McCarthy R, Jungheim ES, England SK, Herzog ED

Daily rhythms generated by endogenous circadian mechanisms and synchronized to the light-dark cycle have been implicated in the timing of birth in a wide variety of species. Although chronodisruption (e.g., shift work or clock gene mutations) is associated with poor reproductive outcomes, little is known about circadian timing during pregnancy.

Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives.

2019-06 Comai S, Lopez-Canul M, De Gregorio D, Posner A, Ettaoussi M, Guarnieri FC, Gobbi G

Melatonin (MLT), a neuromodulator mainly acting through two G-protein coupled receptors MT1 and MT2, regulates many brain functions, including circadian rhythms, mood, pain and sleep. MLT and non-selective MT1/MT2 receptor agonists are clinically used in neuropsychiatric and/or sleep disorders.

Effects of red light on sleep inertia.

2019-05 Figueiro MG, Sahin L, Roohan C, Kalsher M, Plitnick B, Rea MS

Sleep inertia, broadly defined as decrements in performance and lowering of alertness following waking, lasts for durations ranging between 1 min and 3 hrs. This study investigated whether, compared to a dim light condition (the control), exposure to long-wavelength (red) light delivered to closed eyelids during sleep (red light mask) and to eyes open upon waking (red light goggles) reduced sleep inertia.

Melatonin profiles during the third trimester of pregnancy and health status in the offspring among day and night workers: A case series.

2019-04 Nehme PA, Amaral FG, Middleton B, Lowden A, Marqueze E, França-Junior I, Antunes JLF, Cipolla-Neto J, Skene DJ, Moreno CRC

Successful pregnancy requires adaptation in maternal physiology. During intrauterine life the mother's circadian timing system supports successful birth and postnatal development. Maternal melatonin is important to transmit circadian timing and day length to the fetus.

Night workers have lower levels of antioxidant defenses and higher levels of oxidative stress damage when compared to day workers.

2019-03 Teixeira KRC, Dos Santos CP, de Medeiros LA, Mendes JA, Cunha TM, De Angelis K, Penha-Silva N,  de Oliveira EP, Crispim CA

The effects of circadian misalignment and work shift on oxidative stress profile of shift workers have not been explored in the literature. The present study aimed to evaluate the role of shift work (day and night) and social jetlag - a measure of circadian misalignment - with oxidative stress markers.

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