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Frontiers in Pharmacology 2024Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent... (Review)
Review
Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent therapeutic interventions for cerebral I/R injury are still very limited. Melatonin, an endogenous hormone, was found to be valid in preventing I/R injury in a variety of organs. However, a systematic review covering all neuroprotective effects of melatonin in cerebral I/R injury has not been reported yet. Thus, we perform a comprehensive overview of the influence of melatonin on cerebral I/R injury by collecting all available literature exploring the latent effect of melatonin on cerebral I/R injury as well as ischemic stroke. In this systematic review, we outline the extensive scientific studies and summarize the beneficial functions of melatonin, including reducing infarct volume, decreasing brain edema, improving neurological functions and attenuating blood-brain barrier breakdown, as well as its key protective mechanisms on almost every aspect of cerebral I/R injury, including inhibiting oxidative stress, neuroinflammation, apoptosis, excessive autophagy, glutamate excitotoxicity and mitochondrial dysfunction. Subsequently, we also review the predictive and therapeutic implications of melatonin on ischemic stroke reported in clinical studies. We hope that our systematic review can provide the most comprehensive introduction of current advancements on melatonin in cerebral I/R injury and new insights into personalized diagnosis and treatment of ischemic stroke.
PubMed: 38375039
DOI: 10.3389/fphar.2024.1356112 -
Obstetrics & Gynecology Science Mar 2024This study aimed to review randomized controlled trials (RCTs) investigating the effects of dietary antioxidant supplements on the severity of endometriosis-related pain...
The effect of antioxidant supplementation on dysmenorrhea and endometriosis-associated painful symptoms: a systematic review and meta-analysis of randomized clinical trials.
This study aimed to review randomized controlled trials (RCTs) investigating the effects of dietary antioxidant supplements on the severity of endometriosis-related pain symptoms. The PubMed/Medline, Scopus, and Web of Science databases were searched until April 2022. Additionally, we manually searched the reference lists. Endpoints were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) in a random-effects model. The I2 statistic was used to assess heterogeneity. Ten RCTs were included in this meta-analysis. Overall, 10 studies were related to dysmenorrhea, four to dyspareunia, and four to pelvic pain. Antioxidants significantly reduced dysmenorrhea (SMD, -0.48; 95% CI, -0.82 to -0.13; I2=75.14%). In a subgroup analysis, a significant reduction of dysmenorrhea was observed only in a subset of trials that administered vitamin D (SMD, -0.59; 95% CI, -1.13 to -0.06; I2=69.59%) and melatonin (SMD, -1.40; 95% CI, -2.47 to -0.32; I2=79.15%). Meta-analysis results also suggested that antioxidant supplementation significantly improved pelvic pain (SMD, -1.51; 95% CI, -2.74 to -0.29; I2=93.96%), although they seem not to have a significant beneficial impact on the severity of dyspareunia. Dietary antioxidant supplementation seems to beneficially impact the severity of endometriosis-related dysmenorrhea (with an emphasis on vitamin D and melatonin) and pelvic pain. However, due to the relatively small sample size and high heterogeneity, the findings should be interpreted cautiously, and the importance of further well-designed clinical studies cannot be overstated.
PubMed: 38221738
DOI: 10.5468/ogs.23210 -
Cureus Nov 2023The gut microbiota is a community situated in the gastrointestinal tract that consists of bacteria thriving and contributing to the functions of our body. It is heavily... (Review)
Review
The gut microbiota is a community situated in the gastrointestinal tract that consists of bacteria thriving and contributing to the functions of our body. It is heavily influenced by what individuals eat, as the quality, amount, and frequency of food consumed can favor and inhibit specific bacteria. Type-2 diabetes mellitus (T2DM) is a common but detrimental condition that arises from excessive hyperglycemia, leading to either insulin resistance or damage to the B-cells that produce insulin in the pancreas. A poor diet high in sugar and fats leads to hyperglycemia, and as this persists, it can lead to the development of T2DM. Both insulin resistance and damage to B-cells are greatly affected by the diet an individual consumes, but is there a more involved relationship between the gut microbiota and T2DM? This paper aimed to evaluate the changes in the gut microbiota in patients with T2DM and the impacts of the changes in gut microbiota. and prevailed in patients with T2DM and healthy control, but their abundance varied greatly. There was also a significant decrease in bacteria like spp.and associated with insulin resistance. High levels of BMI in patients with T2DM have also been associated with increased levels of which has been associated with decreased fat metabolism and increased BMI. Metabolites such as butyrates and melatonin have also been identified as influencing the development and progression of T2DM. Testosterone levels have also been greatly influenced by the gut microbiota changes in T2DM, such that males with lower testosterone have a greater abundance of bacteria like and Identifying these changes and how they impact the body may lead to a treatment addressing insulin dysfunction and the changes that the altered gut microbiota leads to. Future research should address how treatment methods such as healthy diets, exercise, and anti-diabetics affect the gut microbiota and see if they influence sustained changes and reduced hyperglycemia.
PubMed: 38161953
DOI: 10.7759/cureus.49740 -
Neuroscience and Biobehavioral Reviews Feb 2024Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural... (Review)
Review
BACKGROUND
Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural interventions (plant/endogenously-derived) to reduce treatment-related cognitive impairments.
METHODS
PubMed, EMBASE, PsycINFO, Web of Science, and Scopus were searched and SYRCLE's tool was used for risk of bias assessment of the 134 included articles.
RESULTS
High variability was observed and risk of bias analysis showed overall poor quality of reporting. Results generally showed positive effects in the intervention group versus cancer-therapy only group (67% of 156 cognitive measures), with only 15 (7%) measures reporting cognitive impairment despite intervention. Both artificial (61%) and natural (75%) interventions prevented cognitive impairment. Artificial interventions involving GSK3B inhibitors, PLX5622, and NMDA receptor antagonists, and natural interventions utilizing melatonin, curcumin, and N-acetylcysteine, showed most consistent outcomes.
CONCLUSIONS
Both artificial and natural interventions may prevent cognitive impairment in rodents, which merit consideration in future clinical trials. Greater consistency in design is needed to enhance the generalizability across studies, including timing of cognitive tests and description of treatments and interventions.
Topics: Humans; Animals; Cognitive Dysfunction; Cancer Survivors
PubMed: 38135266
DOI: 10.1016/j.neubiorev.2023.105514 -
Frontiers in Cardiovascular Medicine 2023Oxidative stress induced by the excessive production of reactive oxygen species is one of the primary mechanisms implicated in anthracycline (ANT)-induced... (Review)
Review
BACKGROUND
Oxidative stress induced by the excessive production of reactive oxygen species is one of the primary mechanisms implicated in anthracycline (ANT)-induced cardiotoxicity. There is a strong clinical need for a molecule capable of effectively preventing and reducing the oxidative damage caused by ANT. In vitro and studies conducted in mice have shown that melatonin stimulates the expression of antioxidative agents and reduces lipid peroxidation induced by ANT.
METHODS
We investigated this issue through a meta-analysis of murine model studies. The outcome of the meta-analysis was to compare oxidative damage, estimated by products of lipid peroxidation (MDA = Malondialdehyde) and markers of oxidative stress (SOD = Superoxide Dismutase, GSH = Glutathione), along with a marker of cardiac damage (CK-MB = creatine kinase-myocardial band), assessed by measurements in heart and/or blood samples in mice undergoing ANT chemotherapy and assuming melatonin vs. controls. The PubMed, OVID-MEDLINE and Cochrane library databases were analysed to search English-language review papers published from the inception up to August 1st, 2023. Studies were identified by using Me-SH terms and crossing the following terms: "melatonin", "oxidative stress", "lipid peroxidation", "anthracycline", "cardiotoxicity".
RESULTS
The metanalysis included 153 mice administered melatonin before, during or immediately after ANT and 153 controls from 13 studies. Compared with controls, the levels of all oxidative stress markers were significantly better in the pooled melatonin group, with standardized mean differences (SMD) for MDA, GSH and SOD being -8.03 ± 1.2 (CI: -10.43/-5.64, < 0.001), 7.95 ± 1.8 (CI: 4.41/11.5, < 0.001) and 3.94 ± 1.6 (CI: 0.77/7.12, = 0.015) respectively. Similarly, compared with controls, CK-MB levels reflecting myocardial damage were significantly lower in the pooled melatonin group, with an SMD of -4.90 ± 0.5 (CI: -5.82/-3.98, < 0.001).
CONCLUSION
Melatonin mitigates the oxidative damage induced by ANT in mouse model. High-quality human clinical studies are needed to further evaluate the use of melatonin as a preventative/treatment strategy for ANT-induced cardiotoxicity.
PubMed: 38075951
DOI: 10.3389/fcvm.2023.1289384 -
BMC Anesthesiology Nov 2023Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia.
METHODS
PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA.
RESULTS
Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02).
CONCLUSIONS
Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients.
Topics: Child; Humans; Adolescent; Midazolam; Dexmedetomidine; Emergence Delirium; Melatonin; Sevoflurane; Methyl Ethers; Premedication
PubMed: 38037000
DOI: 10.1186/s12871-023-02356-x -
Physical Activity and Nutrition Sep 2023Humans show near-24-h physiological and behavioral rhythms, which encompass the daily cycle of sleep and wakefulness. Exercise stimulates circadian rhythms, including...
PURPOSE
Humans show near-24-h physiological and behavioral rhythms, which encompass the daily cycle of sleep and wakefulness. Exercise stimulates circadian rhythms, including those of cortisol, melatonin, and core body temperature, and affects sleep quality. We systematically reviewed studies that examined the effects of exercise intensity and timing on physiological circadian rhythms and sleep quality.
METHODS
In this systematic review, we used the online databases PubMed, Science Direct, Web of Science, and Embase. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two independent and experienced systematic reviewers performed the search and selected relevant studies. The participant, intervention, comparison, and outcome characteristics were: (1) adults; (2) exercise treatment; (3) no exercise treatment or different types of exercise (pre-exercise baseline); (4) cortisol, melatonin, or core body temperature measurement, and subjective or objective sleep quality assessments.
RESULTS
We identified 9 relevant articles involving 201 participants (77.1% of whom were male). Our review revealed that short-term evening exercise delayed melatonin rhythm and increased nocturnal core body temperature; however, no negative effects on non-rapid eye movement sleep and sleep efficiency were observed. Moreover, no differences in sleep quality were observed between acute high-intensity and moderate-intensity exercises. With long exercise durations, the core body temperature tended to increase and return to baseline levels at 30-120 min.
CONCLUSION
Our review showed that short-term evening exercise and high-intensity exercise did not have a significant negative effect on sleep quality but physiological circadian rhythm tended to alter. Longterm morning exercise tended to decrease cortisol concentrations after awakening and improve sleep quality. Future studies should examine the effects of long-term exercise timing and intensity on circadian rhythm and sleep.
PubMed: 37946447
DOI: 10.20463/pan.2023.0029 -
Life (Basel, Switzerland) Sep 2023Environmental light entrains many physiological and behavioural processes to the 24 h solar cycle. Such light-driven circadian rhythms are centrally controlled by the... (Review)
Review
Environmental light entrains many physiological and behavioural processes to the 24 h solar cycle. Such light-driven circadian rhythms are centrally controlled by the suprachiasmatic nucleus (SCN), which receives information from the short-wavelength-sensitive intrinsically photosensitive retinal ganglion cells. The SCN synchronizes local clocks throughout the body affecting sleep/wake routines and the secretion of neuroendocrine-linked hormones such as melatonin from the pineal gland and cortisol via the hypothalamic pituitary adrenal (HPA) axis. Although the effects of light parameters on melatonin have been recently reviewed, whether the experimental variation of the spectral power distribution and intensity of light can induce changes in cortisol rhythms remains unclear. Thus, this systematic review evaluated the effects of daytime exposure to lights of different spectral wavelength characteristics and luminance intensity on the cortisol levels in healthy individuals. A search of the PubMed, Web of Science, EMBASE, CINAHL, Medline, PsycINFO and Cochrane Library databases on 19 June 2023 identified 3418 articles, of which 12 studies (profiling 337 participants) met the inclusion and risk of bias criteria. An analysis of the literature indicated that exposure to bright lights of any colour during the late night or early morning can induce significant increases in cortisol secretion relative to time-matched dim light comparison conditions. Furthermore, exposure to bright lights with stronger short-wavelength (blue/green) components in the early morning typically induced greater increases in cortisol relative to lights with stronger long-wavelength (red) components. Thus, the circadian regulation of cortisol is sensitive to the wavelength composition of environmental lighting, in line with the more commonly studied melatonin. As such, wavelength characteristics should be optimized and reported in light intervention studies (particularly for the investigation of cortisol-associated disorders and HPA axis function), and exposure to short-wavelength light during sensitive periods should be carefully considered in constructed environments (e.g., bedroom and classroom lighting and device screens).
PubMed: 37895351
DOI: 10.3390/life13101968 -
Nutrients Oct 2023Melatonin is a hormone that has shown anti-inflammatory actions, reduced oxidative stress, and has effects on physical performance, so the aim of this study was to... (Review)
Review
BACKGROUND
Melatonin is a hormone that has shown anti-inflammatory actions, reduced oxidative stress, and has effects on physical performance, so the aim of this study was to review the effects of melatonin supplementation on the performance of professional soccer players.
METHODS
Critical and systematic review. Data were obtained by performing searches in the following bibliographic databases: Web of Science, MEDLINE (via PubMed), Embase, Cochrane Library, and Scopus. The terms used were "Soccer Athlete", "Melatonin", and "Soccer Performance", using "Humans" as a filter. The search update was in May 2023.
RESULTS
Having applied the inclusion and exclusion criteria, eight articles were selected out of 59 retrieved references. The dose of melatonin administered in the studies ranged between 5 and 8 mg. The outcomes showed a decrease in oxidative stress, muscle damage, and inflammatory markers in the melatonin-treated group.
CONCLUSIONS
Exogenously administered melatonin seems to attenuate some of the effects derived from physical exercise, such as oxidative stress, inflammation, and muscle damage, in professional football players, and since it has no potential adverse effects, it could be interesting to apply it in this population. However, the direct effects of melatonin supplementation on physical performance have not been demonstrated, so more research is needed on the intervention period and effective dose and with larger participant populations.
Topics: Humans; Soccer; Melatonin; Oxidative Stress; Dietary Supplements
PubMed: 37892543
DOI: 10.3390/nu15204467 -
Frontiers in Neurology 2023Since its discovery as an antioxidant, melatonin has been increasingly recognized for its therapeutic potential beyond sleep disturbances in neurodegenerative disorders....
OBJECTIVE
Since its discovery as an antioxidant, melatonin has been increasingly recognized for its therapeutic potential beyond sleep disturbances in neurodegenerative disorders. This study aims to evaluate efficacy of various melatonin doses, treatment durations, and formulations, in alleviating motor symptoms and sleep disturbances in Parkinson's disease, the second most common neurodegenerative disorder worldwide.
METHODS
PubMed, Cochrane Library, ClinicalTrials.gov and other databases were systematically searched to retrieve randomized controlled trials (RCTs) administrating melatonin to Parkinson's disease patients until June 10th, 2023. Outcomes including Unified Parkinson Disease Rating Scale (UPDRS) scores and Pittsburgh Sleep Quality Index (PSQI) scores, were pooled and reported as mean differences (MD) with 95% confidence intervals (CIs). Meta-analysis was performed using an inverse variance random-effects model in Review Manager 5.4 software. Trial Sequential Analysis was performed to avoid false-positive results from random errors.
RESULTS
Five RCTs with a total of 155 patients were included. Statistically significant reductions in UPDRS total scores were observed in groups receiving Melatonin ≥10 mg/day (MD = -11.35, 95% CI: -22.35 to -0.35, I = 0%, = 0.04) and immediate release formulations (MD = -11.35, 95% CI: -22.35 to -0.35, I = 0%, = 0.04). No significant effects on individual UPDRS II, III, and IV scores were observed, regardless of melatonin dosage and treatment duration. Moreover, significant improvements in PSQI scores were observed with only immediate-release melatonin formulations (MD = -2.86, 95% CI: -4.74 to -0.97, I = 0%, = 0.003).
CONCLUSION
Melatonin ≥10 mg/day for a minimum duration of ≥12 weeks in immediate-release formulations consistently demonstrated significant therapeutic potential in improving motor symptom and sleep disturbances in Parkinson disease. However, further trials are warranted to investigate its impact when initiated early in the disease course to fully explore its true therapeutic potential.
SYSTEMATIC REVIEW REGISTRATION
Unique identifier: CRD42023427491 (PROSPERO).
PubMed: 37881313
DOI: 10.3389/fneur.2023.1265789