Melatonin: Translation of Ongoing Studies Into Possible Therapeutic Applications Outside Sleep Disorders.

PURPOSE: Melatonin, a natural hormone mainly synthesized by the pineal gland, is regulated by circadian rhythm. Synthetic melatonin is not approved by the US Food and Drug Administration for any indication. However, melatonin receptor agonists such as ramelteon and tasimelteon are US Food and Drug Administration approved and are considered by the American Academy of Family Physicians for the treatment of insomnia. Due to the availability of over-the-counter products in some countries and the increasing use of melatonin, it is interesting to highlight knowledge regarding the potential benefits of melatonin outside sleep disorders. METHODS: This narrative review included published reports in EMBASE and MEDLINE databases between 1975 and 2021 relating to the therapeutic applications of melatonin. FINDINGS: Based on the quality of the evidence published to date, the most promising non-insomnia indications are for treating ischemia/reperfusion injury, primary headache disorders, fibromyalgia, glucose control, and blood pressure control. IMPLICATIONS: Most of the studies were preclinical and in in vivo and in vitro phases. More clinical trials are needed before recommending melatonin as a treatment in clinical practice.

Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy.

OBJECTIVE: To discuss the use of melatonin as an early treatment option on the first day of diagnosis for COVID-19. METHODS: Medical Subject Headings terms "COVID-19" and "viral diseases" were manually searched on PubMed, and relevant articles were included. RESULTS: The results showed that melatonin acts to reduce reactive oxygen species-mediated damage, cytokine-induced inflammation, and lymphopenia in viral diseases similar to COVID-19. CONCLUSION: These conclusions provide evidence for potential benefits in melatonin use for COVID-19 treatment as early as the day of diagnosis.

Correction: Protein fractional synthesis rates within tissues of high- and low-active mice.

[This corrects the article DOI: 10.1371/journal.pone.0242926.].

Protein fractional synthesis rates within tissues of high- and low-active mice.

With the rise in physical inactivity and its related diseases, it is necessary to understand the mechanisms involved in physical activity regulation. Biological factors regulating physical activity are studied to establish a possible target for improving the physical activity level. However, little is known about the role metabolism plays in physical activity regulation. Therefore, we studied protein fractional synthesis rate (FSR) of multiple organ tissues of 12-week-old male mice that were previously established as inherently low-active (n = 15, C3H/HeJ strain) and high-active (n = 15, C57L/J strain). Total body water of each mouse was enriched to 5% deuterium oxide (D2O) via intraperitoneal injection and maintained with D2O enriched drinking water for about 24 h. Blood samples from the jugular vein and tissues (kidney, heart, lung, muscle, fat, jejunum, ileum, liver, brain, skin, and bone) were collected for enrichment analysis of alanine by LC-MS/MS. Protein FSR was calculated as -ln(1-enrichment). Data are mean±SE as fraction/day (unpaired t-test). Kidney protein FSR in the low-active mice was 7.82% higher than in high-active mice (low-active: 0.1863±0.0018, high-active: 0.1754±0.0028, p = 0.0030). No differences were found in any of the other measured organ tissues. However, all tissues resulted in a generally higher protein FSR in the low-activity mice compared to the high-activity mice (e.g. lung LA: 0.0711±0.0015, HA: 0.0643±0.0020, heart LA: 0.0649± 0.0013 HA: 0.0712±0.0073). Our observations suggest that high-active mice in most organ tissues are no more inherently equipped for metabolic adaptation than low-active mice, but there may be a connection between protein metabolism of kidney tissue and physical activity level. In addition, low-active mice have higher organ-specific baseline protein FSR possibly contributing to the inability to achieve higher physical activity levels.