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Medical Studies on Melatonin

Inflammation, immunity and potential target therapy of SARS-COV-2: A total scale analysis review

2021-04 Smail SW, Saeed M, Alkasalias T, Khudhur ZO, Younus DA, Rajab MF, Abdulahad WH, Hussain HI, Niaz K, Safdar M

Coronavirus disease-19 (COVID-19) is a complex disease that causes illness ranging from mild to severe respiratory problems. It is caused by a novel coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) that is an enveloped positive-sense single-stranded RNA (+ssRNA) virus belongs to coronavirus CoV family.

SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: beneficial effects of melatonin

2021-03 Mehrzadi S, Karimi MY, Fatemi A, Reiter RJ, Hosseinzadeh A

Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities.

Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder

2021-02 Lalanne S, Fougerou-Leurent C, Anderson GM, Schroder CM, Nir T, Chokron S, Delorme R, Claustrat B, Bellissant E, Kermarrec S, Franco P, Denis L, Tordjman S

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.

Role of Melatonin on Virus-Induced Neuropathogenesis-A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection.

2021-01 Wongchitrat P, Shukla M, Sharma R, Govitrapong P, Reiter RJ

Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and encephalitis are common.

Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers

2021-01 Fernandes PA, Kinker GS, Navarro BV, Jardim VC, Ribeiro-Paz ED, Córdoba-Moreno MO, Santos-Silva D, Muxel SM, Fujita A,  Moraes C, Nakaya HI, Buckeridge MS, Markus RP

The pandemic dissemination of the SARS-CoV-2 led, on the one hand, to a worldwide effort to develop mechanistic-based therapeutics and vaccines, and on the other hand, the searching for determining the spreaders and the mechanisms of transmission. Melatonin, a multitask molecule, orchestrates defense responses by allowing the proper mounting, duration, and magnitude of innate immune responses.

Evening home lighting adversely impacts the circadian system and sleep

2020-11 Cain SW, McGlashan EM, Vidafar P, Mustafovska J, Curran SPN, Wang X, Mohamed A, Kalavally V, Phillips AJK

The regular rise and fall of the sun resulted in the development of 24-h rhythms in virtually all organisms. In an evolutionary heartbeat, humans have taken control of their light environment with electric light. Humans are highly sensitive to light, yet most people now use light until bedtime. We evaluated the impact of modern home lighting environments in relation to sleep and individual-level light sensitivity using a new wearable spectrophotometer.

A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19

2020-10 Zhou Y, Hou Y, Shen J, Kallianpur A, Zein J, Culver DA, Farha S, Comhair S, Fiocchi C, Gack MU, Mehra R, Stappenbeck T, Chan T, Eng C, Jung JU, Jehi L, Erzurum S, Cheng F

The global Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, diseases manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations.

Melatonin is significantly associated with survival of intubated COVID-19 patients

2020-10 Ramlall V, Zucker J, Tatonetti N

Respiratory distress requiring intubation is the most serious complication associated with coronavirus disease 2019 (COVID-19). In this retrospective study, we used survival analysis to determine whether or not mortality following intubation was associated with hormone exposure in patients treated at New York Presbyterian/ Columbia University Irving Medical Center. Here, we report the overall hazards ratio for each hormone for exposure before and after intubation for intubated and mechanically ventilated patients.

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

2020-09 Tan DX, Hardeland R

Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen's spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution.

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.

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.

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.

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