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Current Medicinal Chemistry 2024During the COVID-19 pandemic, people suffered from major mental health problems. These include stress, anxiety, and confusion about the existing situation of home... (Review)
Review
BACKGROUND
During the COVID-19 pandemic, people suffered from major mental health problems. These include stress, anxiety, and confusion about the existing situation of home confinement. Melatonin is a popular anti-inflammatory and antioxidant molecule sold as an over-the-counter dietary supplement.
OBJECTIVE
This review discusses the indications for using melatonin in the context of the COVID-19 pandemic, including treatment.
METHODS
A comprehensive search of publications was conducted in electronic databases focusing on the administration of melatonin in COVID-19.
RESULTS
Stress has a huge negative impact on sleep routines and the quality of life of individuals. Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The administration of melatonin protects against viral and other pathogens and speeds clinical recovery.
CONCLUSION
In patients admitted to intensive care units, melatonin decreases the risks of severe complications, such as thrombosis and sepsis, and mortality rates. In addition, it is efficacious in lowering vessel permeability, depression, and sedation, and improving the quality of sleep, which could also help COVID-19 patients achieve better clinical outcomes.
Topics: Humans; COVID-19; Melatonin; Pandemics; Quality of Life; Sleep; Dietary Supplements
PubMed: 36825700
DOI: 10.2174/0929867330666230224093849 -
Neurourology and Urodynamics Apr 2024Causes of nocturia may extend beyond primary bladder pathology and it has been commonly associated as a side effect of sleep disorders. This has led to the study of... (Review)
Review
AIM
Causes of nocturia may extend beyond primary bladder pathology and it has been commonly associated as a side effect of sleep disorders. This has led to the study of melatonin and melatonin receptor agonists as a primary treatment for nocturia hypothesized to be secondary to sleep disorders. We aim to systematically review the efficacy and reported safety of melatonin and melatonin receptor agonists in the treatment of nocturia.
METHODS
A search strategy of EMBASE and Pubmed/Medline databases was utilized to identify eligible studies. Two thousand and twenty-eight unique references were identified in concordance with the Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines for systematic reviews, of which nine papers met the inclusion criteria. The Cochrane Collaboration risk of bias criteria in the open label and nonplacebo studies was used to assess bias.
RESULTS
The nine studies identified included 3 randomized double-blinded placebo-controlled trials, 2 randomized non-placebo trial, and 4 prospective open-label trials. Three utilized the melatonin-receptor agonist ramelteon (8 mg) and six utilized melatonin (four 2 mg extended release, two 2 mg normal release). Nocturia improved in 8 studies varying from moderate to low efficacy related to reduction in nocturia episodes. Five studies evaluated sleep parameters finding improvement in both nocturia and sleep quality. Male subjects represented 76.8% of 371 total subjects in prospective and randomized trials. Ramelteon and melatonin were both reported as well tolerated during nocturia treatment. A meta-analysis was not able to be performed due to the heterogeneity of bladder diagnoses.
CONCLUSIONS
At this time, there is insufficient evidence to routinely recommend melatonin as an effective treatment for nocturia given the limitations of current clinical studies. Randomized placebo-controlled trials and prospective open label studies in non-neurogenic populations report a trend towards nocturia improvement with good tolerability and rare side effects. Therefore, further larger scale randomized trials with focused urologic diagnoses in well-characterized patient populations are warranted.
Topics: Humans; Male; Nocturia; Melatonin; Prospective Studies; Receptors, Melatonin; Systematic Reviews as Topic; Sleep Wake Disorders; Indenes
PubMed: 38456646
DOI: 10.1002/nau.25443 -
Biochimica Et Biophysica Acta.... Oct 2023Obesity is well-established as a common comorbidity in ischemic stroke. The increasing evidence has revealed that it also associates with the exacerbation of brain...
Obesity is well-established as a common comorbidity in ischemic stroke. The increasing evidence has revealed that it also associates with the exacerbation of brain pathologies, resulting in increasingly severe neurological outcomes following cerebral ischemia and reperfusion (I/R) damage. Mechanistically, pyroptosis and necroptosis are novel forms of regulated death that relate to the propagation of inflammatory signals in case of cerebral I/R. Previous studies noted that pyroptotic and necroptotic signaling were exacerbated in I/R brain of obese animals and led to the promotion of brain tissue injury. This study aimed to investigate the roles of melatonin on pyroptosis, necroptosis, and pro-inflammatory pathways occurring in the I/R brain of obese rats. Male Wistar rats were given a high-fat diet for 16 weeks to induce the obese condition, and then were divided into 4 groups: Sham-operated, I/R treated with vehicle, I/R treated with melatonin (10 mg/kg), and I/R treated with glycyrrhizic acid (10 mg/kg). All drugs were administered via intraperitoneal injection at the onset of reperfusion. The development of neurological deficits, cerebral infarction, histological changes, neuronal death, and glial cell hyperactivation were investigated. This study revealed that melatonin effectively improved these detrimental parameters. Furthermore, the processes of pyroptosis, necroptosis, and inflammation were all diminished by melatonin treatment. A summary of the findings is that melatonin effectively reduces ischemic brain pathology and thereby improves post-stroke outcomes in obese rats by modulating pyroptosis, necroptosis, and inflammation.
Topics: Rats; Male; Animals; Pyroptosis; Melatonin; Neuroinflammatory Diseases; Necroptosis; Rats, Wistar; Brain Ischemia; Reperfusion Injury; Inflammation; Obesity
PubMed: 37302429
DOI: 10.1016/j.bbadis.2023.166785 -
Journal of Sleep Research Dec 2023Melatonin has gained growing interest as a treatment of insomnia, despite contradictory findings, and a low level of evidence. A systematic review and meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
Melatonin has gained growing interest as a treatment of insomnia, despite contradictory findings, and a low level of evidence. A systematic review and meta-analysis was conducted following PRISMA criteria, to assess the efficacy of melatonin and ramelteon compared with placebo on sleep quantity and quality in insomnia disorder, while also considering factors that may impact their efficacy. This review included 22 studies, with 4875 participants, including 925 patients treated with melatonin, 1804 treated with ramelteon and 2297 receiving a placebo. Most studies evaluated the acute efficacy of prolonged release (PR) melatonin in insomnia disorder. Compared with placebo, PR melatonin appears efficacious with a small to medium effect size on subjective sleep onset latency (sSOL) (p = 0.031; weighted difference = -6.30 min), objective sleep onset latency (oSOL) (p < 0.001; weighted difference = -5.05 min), and objective sleep efficiency (oSE) (p = 0.043; weighted difference = 1.91%). For the subgroup mean age of patients ≥55, PR melatonin was efficacious on oSE with a large effect size (p < 0.001; weighted difference = 2.95%). Ramelteon was efficacious with a large effect size at 4 weeks on objective total sleep time (oTST) (p = 0.010; weighted difference = 17.9 min), subjective total sleep time (sTST) (p = 0.006; weighted difference = 11.7 min), sSOL (p = 0.009; weighted difference = -8.74 min), and oSOL (p = 0.017; weighted difference = -14 min). Regarding long-term effects, ramelteon has a large effect size on oTST (p < 0.001; weighted difference = 2.02 min) and sTST (p < 0.001; weighted difference = 14.5 min). PR melatonin and ramelteon appear efficacious compared with placebo for insomnia symptoms with PR melatonin showing mostly small to medium effect sizes. PR melatonin for individuals with a mean age ≥ 55 and ramelteon show larger effect sizes.
Topics: Humans; Adult; Sleep Initiation and Maintenance Disorders; Sleep; Melatonin; Indenes
PubMed: 37434463
DOI: 10.1111/jsr.13939 -
British Journal of Pharmacology Dec 2023Acute lung injury (ALI) is a serious, life-threatening inflammation of the lungs that still lacks effective treatment. We previously showed that serine protease...
BACKGROUND AND PURPOSE
Acute lung injury (ALI) is a serious, life-threatening inflammation of the lungs that still lacks effective treatment. We previously showed that serine protease inhibitor B1 (SerpinB1) protects against ALI induced by orthotopic autologous liver transplantation. However, the role of SerpinB1 in lipopolysaccharide (LPS)-induced ALI and its regulatory mechanisms are not known.
EXPERIMENTAL APPROACH
Wild-type (WT) and SerpinB1 knockout (KO) mice were treated with intratracheal LPS stimulation to induce ALI. Some of the WT and KO mice were injected i.p. with melatonin, a rhythm-related protein Rev-erbα agonist. The circadian rhythm in WT mice was disrupted by exposing mice to 24 h of continuous dark or light conditions after intratracheal LPS. Neutrophils were isolated from alveolar lavage fluid of WT and KO mice, and from human peripheral blood. Neutrophils were treated with LPS and melatonin.
KEY RESULTS
Disruption of circadian rhythm by either 24-h dark or light conditions exacerbated LPS-induced ALI and decreased expression of Rev-erbα and SerpinB1 protein in lung, whereas melatonin treatment increased SerpinB1 expression and attenuated LPS-induced ALI in WT mice, but not in KO mice. In isolated neutrophils, Rev-erbα was co-localized with SerpinB1 and bound to its promoter to trigger SerpinB1 transcription. Furthermore, LPS stimulation increased formation of neutrophil extracellular traps, which was reversed by melatonin treatment in neutrophils from WT mice, but not from KO mice.
CONCLUSION AND IMPLICATIONS
In mice, SerpinB1 is rhythmically regulated by Rev-erbα, and its down-regulation exacerbates LPS-induced ALI by inducing formation of neutrophil extracellular traps.
Topics: Mice; Animals; Humans; Lipopolysaccharides; Serine Proteinase Inhibitors; Melatonin; Lung; Acute Lung Injury; Mice, Knockout; Mice, Inbred C57BL
PubMed: 37350044
DOI: 10.1111/bph.16175 -
European Journal of Epidemiology Oct 2023Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a...
Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions were analyzed via a two-step procedure based on logic regression. The Bayesian false-discovery probability (BFDP) was used for all analyses to account for multiple testing. Noteworthy associations (BFDP < 0.8) included 10 linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g. rs1386492: OR = 1.07, 95% CI 1.02-1.12), and a SNP in the mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR = 1.11, 95% CI 1.04-1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with TPH2- and MAPK-related SNPs (e.g. rs1386483 ∧ rs1473473 ∧ rs3729931: OR = 1.20, 95% CI 1.09-1.32). In line with the light-at-night hypothesis that links shift work with elevated breast-cancer risks our results point to SNPs in TPH2 and MAPK-genes that may impact the intricate network of circadian regulation.
Topics: Humans; Female; Breast Neoplasms; Melatonin; Bayes Theorem; Polymorphism, Single Nucleotide; Logistic Models; Case-Control Studies; Genetic Predisposition to Disease
PubMed: 37789226
DOI: 10.1007/s10654-023-01048-7 -
Journal of Healthcare Engineering 2023100 healthy perimenopausal women were recruited and randomly assigned to two groups, with 50 subjects in each group. In the control group, placebo was administrated... (Randomized Controlled Trial)
Randomized Controlled Trial
METHOD
100 healthy perimenopausal women were recruited and randomly assigned to two groups, with 50 subjects in each group. In the control group, placebo was administrated daily for 3 cycles (4 weeks of treatment for 1 cycle and drug withdrawals for 1 week). The study group received 3 mg oral melatonin treatment daily in the same period of time. All subjects completed the study. We compared the uterine volume, endometrial thickness, LH (luteinizing hormone), FSH (follicle generating hormone), E2 (estradiol), and melatonin levels during daytime between the two groups before and after the study. Moreover, perimenopause syndrome, sleep, mood, and QoL were analyzed at the baseline and 3 cycles by the questionnaires of the Kupperman index, the Pittsburgh sleep quality index (PSQI), the Hamilton anxiety scale (HAMA), and the Hamilton depression scale (HAMD), as well as menopausal QoL (MENQOL), respectively. Any adverse reactions experienced by the subjects were also compared in the study. Finally, 91 participants (92%) completed the whole study, 47 and 44 in the study and control groups, respectively, and their data were considered in subsequent analyses.
RESULTS
After therapy, the two groups were similar in the uterine volume and endometrial thickness. In contrast to the control group, the study group showed notably decreased LH and FSH levels. No notable difference was discovered in E2 and melatonin levels between the two groups in the study. Moreover, the study group exhibited a significantly lower score in the Kupperman index, PSQI, HAMA, HAMD, and MENQOL scale than the control group. Moreover, the two groups had no notable difference in adverse reactions.
CONCLUSION
Melatonin was a useful treatment to relieve climacteric symptoms and improve sleep, mood, and life quality in perimenopausal women without obvious adverse reactions.
Topics: Female; Humans; Perimenopause; Melatonin; Quality of Life; Sleep; Affect; Follicle Stimulating Hormone
PubMed: 37854169
DOI: 10.1155/2023/2198804 -
Journal of Pineal Research Sep 2023Melatonina natural harmless molecule-displays versatile roles in human health and crop disease control such as for rice blast. Rice blast, caused by the filamentous...
Melatonina natural harmless molecule-displays versatile roles in human health and crop disease control such as for rice blast. Rice blast, caused by the filamentous fungus Magnaporthe oryzae, is one devastating disease of rice. Application of fungicides is one of the major measures in the control of various crop diseases. However, fungicide resistance in the pathogen and relevant environmental pollution are becoming serious problems. By screening for possible synergistic combinations, here, we discovered an eco-friendly combination for rice blast control, melatonin, and the fungicide isoprothiolane. These compounds together exhibited significant synergistic inhibitory effects on vegetative growth, conidial germination, appressorium formation, penetration, and plant infection by M. oryzae. The combination of melatonin and isoprothiolane reduced the effective concentration of isoprothiolane by over 10-fold as well as residual levels of isoprothiolane. Transcriptomics and lipidomics revealed that melatonin and isoprothiolane synergistically interfered with lipid metabolism by regulating many common targets, including the predicted isocitrate lyase-encoding gene MoICL1. Furthermore, using different techniques, we show that melatonin and isoprothiolane interact with MoIcl1. This study demonstrates that melatonin and isoprothiolane function synergistically and can be used to reduce the dosage and residual level of isoprothiolane, potentially contributing to the environment-friendly and sustainable control of crop diseases.
Topics: Humans; Fungicides, Industrial; Magnaporthe; Melatonin; Oryza; Plant Diseases
PubMed: 37458404
DOI: 10.1111/jpi.12896 -
Revista Da Associacao Medica Brasileira... 2023
Topics: Humans; Female; Melatonin; Breast Neoplasms
PubMed: 37812812
DOI: 10.1590/1806-9282.697EDIT -
Journal of Pineal Research Dec 2023Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating...
Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating melatonin levels. Melatonin is a potent antioxidant and exogenous melatonin treatment is neuroprotective in experimental HD models. In neurons, melatonin is exclusively synthesized in the mitochondrial matrix. Thus, we investigated the integrity of melatonin biosynthesis pathways in pineal and extrapineal brain areas in human HD brain samples, in the R6/2 mouse model of HD and in full-length mutant huntingtin knock-in cells. Aralkylamine N-acetyltransferase (AANAT) is the rate-limiting step enzyme in the melatonin biosynthetic pathway. We found that AANAT expression is significantly decreased in the pineal gland and the striatum of HD patients compared to normal controls. In the R6/2 mouse forebrain, AANAT protein expression was decreased in synaptosomal, but not nonsynaptosomal, mitochondria and was associated with decreased synaptosomal melatonin levels compared to wild type mice. We also demonstrate sequestration of AANAT in mutant-huntingtin protein aggregates likely resulting in decreased AANAT bioavailability. Paradoxically, AANAT mRNA expression is increased in tissues where AANAT protein expression is decreased, suggesting a potential feedback loop that is, ultimately unsuccessful. In conclusion, we demonstrate that pineal, extrapineal, and synaptosomal melatonin levels are compromised in the brains of HD patients and R6/2 mice due, at least in part, to protein aggregation.
Topics: Humans; Mice; Animals; Melatonin; Huntington Disease; Pineal Gland
PubMed: 37721126
DOI: 10.1111/jpi.12909