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1.
Zhonghua Yan Ke Za Zhi ; 60(6): 547-558, 2024 Jun 11.
Article in Chinese | MEDLINE | ID: mdl-38825955

ABSTRACT

With the increasing prevalence of myopia among adolescents, the pathogenesis of this condition has garnered significant attention. Studies have discovered the expression of various hormone receptors in ocular tissues of both animals and humans. Additionally, changes in hormone levels accompany the development of myopia, although the exact relationships remain inconclusive. This article reviews the potential influences and mechanisms of action of endogenous hormones such as melatonin, serotonin, insulin, glucagon, sex hormones, vitamin D, and prostaglandins in ocular tissues including the retina, choroid, and sclera. It elaborates on the relationship between fluctuations in these hormone levels and the progression of myopia, aiming to provide guidance for exploring targets for myopia prevention and control.


Subject(s)
Melatonin , Myopia , Humans , Myopia/metabolism , Melatonin/metabolism , Vitamin D/metabolism , Serotonin/metabolism , Insulin/metabolism , Glucagon/metabolism , Animals , Gonadal Steroid Hormones/metabolism , Prostaglandins/metabolism , Hormones/metabolism , Retina/metabolism
2.
Sci Rep ; 14(1): 12718, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830921

ABSTRACT

This study evaluated retinal and choroidal microvascular changes in night shift medical workers and its correlation with melatonin level. Night shift medical workers (group A, 25 workers) and non-night shift workers (group B, 25 workers) were recruited. The images of macula and optic nerve head were obtained by swept-source OCT-angiography. Vessel density of retina, choriocapillaris (CC), choriocapillaris flow deficit (CC FD), choroidal thickness (CT) and choroidal vascularity index (CVI) were measured. 6-sulfatoxymelatonin concentration was analyzed from the morning urine. CC FD and CVI were significantly decreased and CT was significantly increased in group A (all P < 0.05). 6-sulfatoxymelatonin concentration was significantly lower in group A (P < 0.05), which was significantly positively correlated with CC FD size (r = 0.318, P = 0.024) and CVI of the most regions (maximum r-value was 0.482, P < 0.001), and was significantly negatively associated with CT of all regions (maximum r-value was - 0.477, P < 0.001). In night shift medical workers, the reduction of melatonin was significantly correlated with CT thickening, CVI reduction and CC FD reduction, which suggested that they might have a higher risk of eye diseases. CC FD could be a sensitive and accurate indicator to reflect CC perfusion.


Subject(s)
Choroid , Melatonin , Microvessels , Retinal Vessels , Tomography, Optical Coherence , Humans , Choroid/blood supply , Choroid/diagnostic imaging , Tomography, Optical Coherence/methods , Male , Adult , Female , Melatonin/urine , Melatonin/analogs & derivatives , Microvessels/diagnostic imaging , Retinal Vessels/diagnostic imaging , Middle Aged , Shift Work Schedule/adverse effects , Angiography/methods , Retina/diagnostic imaging
3.
BMC Genom Data ; 25(1): 41, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711007

ABSTRACT

BACKGROUND: Class III peroxidase (POD) enzymes play vital roles in plant development, hormone signaling, and stress responses. Despite extensive research on POD families in various plant species, the knowledge regarding the POD family in Chinese pear (Pyrus bretschenedri) is notably limited. RESULTS: We systematically characterized 113 POD family genes, designated as PbPOD1 to PbPOD113 based on their chromosomal locations. Phylogenetic analysis categorized these genes into seven distinct subfamilies (I to VII). The segmental duplication events were identified as a prevalent mechanism driving the expansion of the POD gene family. Microsynteny analysis, involving comparisons with Pyrus bretschenedri, Fragaria vesca, Prunus avium, Prunus mume and Prunus persica, highlighted the conservation of duplicated POD regions and their persistence through purifying selection during the evolutionary process. The expression patterns of PbPOD genes were performed across various plant organs and diverse fruit development stages using transcriptomic data. Furthermore, we identified stress-related cis-acting elements within the promoters of PbPOD genes, underscoring their involvement in hormonal and environmental stress responses. Notably, qRT-PCR analyses revealed distinctive expression patterns of PbPOD genes in response to melatonin (MEL), salicylic acid (SA), abscisic acid (ABA), and methyl jasmonate (MeJA), reflecting their responsiveness to abiotic stress and their role in fruit growth and development. CONCLUSIONS: In this study, we investigated the potential functions and evolutionary dynamics of PbPOD genes in Pyrus bretschenedri, positioning them as promising candidates for further research and valuable indicators for enhancing fruit quality through molecular breeding strategies.


Subject(s)
Gene Expression Regulation, Plant , Phylogeny , Plant Growth Regulators , Pyrus , Pyrus/genetics , Gene Expression Regulation, Plant/drug effects , Plant Growth Regulators/pharmacology , Plant Growth Regulators/metabolism , Melatonin/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Oxylipins/pharmacology , Cyclopentanes/pharmacology , Peroxidase/genetics , Peroxidase/metabolism , Acetates/pharmacology , Acetates/metabolism , Fruit/genetics , Fruit/growth & development
4.
PLoS One ; 19(5): e0303040, 2024.
Article in English | MEDLINE | ID: mdl-38713652

ABSTRACT

In the present study, we attempted to use melatonin combined with germination treatment to remove pesticide residues from contaminated grains. High levels of pesticide residues were detected in soybean seeds after soaking with chlorothalonil (10 mM) and malathion (1 mM) for 2 hours. Treatment with 50 µM melatonin for 5 days completely removed the pesticide residues, while in the control group, only 61-71% of pesticide residues were removed from soybean sprouts. Compared with the control, melatonin treatment for 7 days further increased the content of ascorbic acid (by 48-66%), total phenolics (by 52-68%), isoflavones (by 22-34%), the total antioxidant capacity (by 37-40%), and the accumulated levels of unsaturated fatty acids (C18:1, C18:2, and C18:3) (by 17-30%) in soybean sprouts. Moreover, melatonin treatment further increased the accumulation of ten components of phenols and isoflavones in soybean sprouts relative to those in the control. The ability of melatonin to accelerate the degradation of pesticide residues and promote the accumulation of antioxidant metabolites might be related to its ability to trigger the glutathione detoxification system in soybean sprouts. Melatonin promoted glutathione synthesis (by 49-139%) and elevated the activities of glutathione-S-transferase (by 24-78%) and glutathione reductase (by 38-61%). In summary, we report a new method in which combined treatment by melatonin and germination rapidly degrades pesticide residues in contaminated grains and improves the nutritional quality of food.


Subject(s)
Antioxidants , Germination , Glycine max , Melatonin , Nutritive Value , Pesticide Residues , Seeds , Melatonin/pharmacology , Germination/drug effects , Pesticide Residues/analysis , Seeds/drug effects , Seeds/chemistry , Seeds/metabolism , Seeds/growth & development , Glycine max/drug effects , Glycine max/growth & development , Glycine max/metabolism , Glycine max/chemistry , Antioxidants/metabolism , Edible Grain/drug effects , Edible Grain/metabolism , Phenols/analysis , Food Contamination/analysis , Glutathione/metabolism
5.
BMC Plant Biol ; 24(1): 380, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720246

ABSTRACT

BACKGROUND: Soybean (Glycine max), a vital grain and oilseed crop, serves as a primary source of plant protein and oil. Soil salinization poses a significant threat to soybean planting, highlighting the urgency to improve soybean resilience and adaptability to saline stress. Melatonin, recently identified as a key plant growth regulator, plays crucial roles in plant growth, development, and responses to environmental stress. However, the potential of melatonin to mitigate alkali stress in soybeans and the underlying mechanisms remain unclear. RESULTS: This study investigated the effects of exogenous melatonin on the soybean cultivar Zhonghuang 13 under alkaline stress. We employed physiological, biochemical, transcriptomic, and metabolomic analyses throughout both vegetative and pod-filling growth stages. Our findings demonstrate that melatonin significantly counteracts the detrimental effects of alkaline stress on soybean plants, promoting plant growth, photosynthesis, and antioxidant capacity. Transcriptomic analysis during both growth stages under alkaline stress, with and without melatonin treatment, identified 2,834 and 549 differentially expressed genes, respectively. These genes may play a vital role in regulating plant adaptation to abiotic stress. Notably, analysis of phytohormone biosynthesis pathways revealed altered expression of key genes, particularly in the ARF (auxin response factor), AUX/IAA (auxin/indole-3-acetic acid), and GH3 (Gretchen Hagen 3) families, during the early stress response. Metabolomic analysis during the pod-filling stage identified highly expressed metabolites responding to melatonin application, such as uteolin-7-O-(2''-O-rhamnosyl)rutinoside and Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside, which helped alleviate the damage caused by alkali stress. Furthermore, we identified 183 differentially expressed transcription factors, potentially playing a critical role in regulating plant adaptation to abiotic stress. Among these, the gene SoyZH13_04G073701 is particularly noteworthy as it regulates the key differentially expressed metabolite, the terpene metabolite Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. WGCNA analysis identified this gene (SoyZH13_04G073701) as a hub gene, positively regulating the crucial differentially expressed metabolite of terpenoids, Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. Our findings provide novel insights into how exogenous melatonin alleviates alkali stress in soybeans at different reproductive stages. CONCLUSIONS: Integrating transcriptomic and metabolomic approaches, our study elucidates the mechanisms by which exogenous melatonin ameliorates the inhibitory effects of alkaline stress on soybean growth and development. This occurs through modulation of biosynthesis pathways for key compounds, including terpenes, flavonoids, and phenolics. Our findings provide initial mechanistic insights into how melatonin mitigates alkaline stress in soybeans, offering a foundation for molecular breeding strategies to enhance salt-alkali tolerance in this crop.


Subject(s)
Glycine max , Melatonin , Stress, Physiological , Transcriptome , Melatonin/pharmacology , Glycine max/genetics , Glycine max/drug effects , Glycine max/growth & development , Glycine max/metabolism , Stress, Physiological/drug effects , Stress, Physiological/genetics , Transcriptome/drug effects , Gene Expression Regulation, Plant/drug effects , Metabolomics , Gene Expression Profiling , Alkalies , Plant Growth Regulators/metabolism , Plant Growth Regulators/pharmacology , Metabolome/drug effects
6.
Nutrients ; 16(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38794660

ABSTRACT

Breastfeeding is the most appropriate source of a newborn's nutrition; among the plethora of its benefits, its modulation of circadian rhythmicity with melatonin as a potential neuroendocrine transducer has gained increasing interest. Transplacental transfer assures melatonin provision for the fetus, who is devoid of melatonin secretion. Even after birth, the neonatal pineal gland is not able to produce melatonin rhythmically for several months (with an even more prolonged deficiency following preterm birth). In this context, human breast milk constitutes the main natural source of melatonin: diurnal dynamic changes, an acrophase early after midnight, and changes in melatonin concentrations according to gestational age and during the different stages of lactation have been reported. Understudied thus far are the factors impacting on (changes in) melatonin content in human breast milk and their clinical significance in chronobiological adherence in the neonate: maternal as well as environmental aspects have to be investigated in more detail to guide nursing mothers in optimal feeding schedules which probably means a synchronized instead of mistimed feeding practice. This review aims to be thought-provoking regarding the critical role of melatonin in chrononutrition during breastfeeding, highlighting its potential in circadian entrainment and therefore optimizing (neuro)developmental outcomes in the neonatal setting.


Subject(s)
Breast Feeding , Circadian Rhythm , Lactation , Melatonin , Milk, Human , Humans , Melatonin/metabolism , Melatonin/administration & dosage , Milk, Human/chemistry , Milk, Human/metabolism , Circadian Rhythm/physiology , Female , Infant, Newborn , Lactation/physiology , Infant Nutritional Physiological Phenomena/physiology
7.
Brain Behav ; 14(5): e3515, 2024 May.
Article in English | MEDLINE | ID: mdl-38702895

ABSTRACT

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.


Subject(s)
Hippocampus , Melatonin , Memory Disorders , Neuronal Plasticity , Sleep Deprivation , Animals , Melatonin/pharmacology , Melatonin/administration & dosage , Sleep Deprivation/complications , Sleep Deprivation/drug therapy , Sleep Deprivation/physiopathology , Mice , Male , Hippocampus/metabolism , Hippocampus/drug effects , Female , Memory Disorders/drug therapy , Memory Disorders/etiology , Memory Disorders/physiopathology , Neuronal Plasticity/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Pregnancy , Maternal Deprivation , Cognitive Dysfunction/etiology , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/physiopathology , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Brain-Derived Neurotrophic Factor/metabolism , Neuroinflammatory Diseases/drug therapy
8.
Reprod Fertil Dev ; 362024 May.
Article in English | MEDLINE | ID: mdl-38753959

ABSTRACT

Context Melatonin may have a heat-stress-alleviating role during pregnancy. Aims To investigate the effects of melatonin administration during the first half of pregnancy on heat-tolerance capacity and pregnancy outputs of naturally heat-stressed rabbits. Methods Forty female rabbits were stratified equally into two experimental groups and daily received 1mg melatonin/kg body weight or not (control) for 15 consecutive days post-insemination. Heat tolerance indices, hormone profile, ovarian structures, and fetal loss were determined. Key results Treatment with melatonin significantly decreased respiration rate and rectal temperature, improved concentrations of nitric oxide, and tended to decrease malondialdehyde concentrations (P =0.064) compared to control. Melatonin treatment significantly increased concentrations of high-density lipoprotein, oestradiol, and progesterone compared to control. No significant differences in the numbers of visible ovarian follicles, corpora lutea, and total implantation sites on day 18 of pregnancy were observed between experimental groups. However, melatonin treatment significantly reduced the number of absorbed implantation sites and significantly improved amniotic fluid volume and conception rate compared to control. Conclusions Melatonin administration during the first half of pregnancy can improve reproductive performance of heat-stressed female rabbits. Implications Melatonin can improve fetal survivability via improving heat-tolerance capacity of does and steroidogenesis.


Subject(s)
Heat-Shock Response , Melatonin , Reproduction , Animals , Female , Melatonin/pharmacology , Melatonin/administration & dosage , Rabbits , Pregnancy , Heat-Shock Response/drug effects , Heat-Shock Response/physiology , Reproduction/drug effects , Reproduction/physiology , Progesterone/pharmacology , Heat Stress Disorders/veterinary , Heat Stress Disorders/drug therapy , Heat Stress Disorders/metabolism , Ovary/drug effects , Estradiol/pharmacology , Estradiol/administration & dosage , Thermotolerance/drug effects
9.
J Pineal Res ; 76(4): e12960, 2024 May.
Article in English | MEDLINE | ID: mdl-38747028

ABSTRACT

Natural products, known for their environmental safety, are regarded as a significant basis for the modification and advancement of fungicides. Melatonin, as a low-cost natural indole, exhibits diverse biological functions, including antifungal activity. However, its potential as an antifungal agent has not been fully explored. In this study, a series of melatonin derivatives targeting the mitogen-activated protein kinase (Mps1) protein of fungal pathogens were synthesized based on properties of melatonin, among which the trifluoromethyl-substituted derivative Mt-23 exhibited antifungal activity against seven plant pathogenic fungi, and effectively reduced the severity of crop diseases, including rice blast, Fusarium head blight of wheat and gray mold of tomato. In particular, its EC50 (5.4 µM) against the rice blast fungus Magnaporthe oryzae is only one-fourth that of isoprothiolane (22 µM), a commercial fungicide. Comparative analyzes revealed that Mt-23 simultaneously targets the conserved protein kinase Mps1 and lipid protein Cap20. Surface plasmon resonance assays showed that Mt-23 directly binds to Mps1 and Cap20. In this study, we provide a strategy for developing antifungal agents by modifying melatonin, and the resultant melatonin derivative Mt-23 is a commercially valuable, eco-friendly and broad-spectrum antifungal agent to combat crop disease.


Subject(s)
Antifungal Agents , Melatonin , Melatonin/pharmacology , Melatonin/chemistry , Melatonin/analogs & derivatives , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Plant Diseases/microbiology , Fungal Proteins/metabolism , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Fungicides, Industrial/chemical synthesis
10.
J Int Med Res ; 52(5): 3000605241239854, 2024 May.
Article in English | MEDLINE | ID: mdl-38735057

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). METHODS: We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. RESULTS: In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). CONCLUSION: Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.


Subject(s)
Delirium , Melatonin , Postoperative Complications , Melatonin/therapeutic use , Melatonin/administration & dosage , Melatonin/adverse effects , Humans , Postoperative Complications/prevention & control , Postoperative Complications/drug therapy , Delirium/prevention & control , Delirium/drug therapy , Perioperative Care/methods , Indenes/therapeutic use , Indenes/adverse effects , Indenes/administration & dosage , Randomized Controlled Trials as Topic , Length of Stay , Treatment Outcome , Hospital Mortality
11.
J Pineal Res ; 76(4): e12963, 2024 May.
Article in English | MEDLINE | ID: mdl-38779971

ABSTRACT

Artificial light at night (ALAN) is an emerging environmental pollutant that threatens public health. Recently, ALAN has been identified as a risk factor for obesity; however, the role of ALAN and its light wavelength in hepatic lipid metabolic homeostasis remains undetermined. We showed that chronic dim (~5 lx) ALAN (dLAN) exposure significantly promoted hepatic lipid accumulation in obese or diabetic mice, with the most severe effect of blue light and little effect of green or red light. These metabolic phenotypes were attributed to blue rather than green or red dLAN interfering with hepatic lipid metabolism, especially lipogenesis and lipolysis. Further studies found that blue dLAN disrupted hepatic lipogenesis and lipolysis processes by inhibiting hepatic REV-ERBs. Mechanistically, feeding behavior mediated the regulation of dLAN on hepatic REV-ERBs. In addition, different effects of light wavelengths at night on liver REV-ERBs depended on the activation of the corticosterone (CORT)/glucocorticoid receptor (GR) axis. Blue dLAN could activate the CORT/GR axis significantly while other wavelengths could not. Notably, we demonstrated that exogenous melatonin could effectively inhibit hepatic lipid accumulation and restore the hepatic GR/REV-ERBs axis disrupted by blue dLAN. These findings demonstrate that dLAN promotes hepatic lipid accumulation in mice via a short-wavelength-dependent manner, and exogenous melatonin is a potential therapeutic approach. This study strengthens the relationship between ALAN and hepatic lipid metabolism and provides insights into directing ambient light.


Subject(s)
Diet, High-Fat , Homeostasis , Light , Lipid Metabolism , Liver , Melatonin , Animals , Melatonin/pharmacology , Mice , Liver/metabolism , Liver/drug effects , Lipid Metabolism/drug effects , Lipid Metabolism/radiation effects , Diet, High-Fat/adverse effects , Homeostasis/drug effects , Male , Mice, Inbred C57BL , Blue Light
12.
FASEB J ; 38(10): e23678, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38780199

ABSTRACT

Melatonin (MLT), a conserved small indole compound, exhibits anti-inflammatory and antioxidant properties, contributing to its cardioprotective effects. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with atherosclerosis disease risk, and is known as an atherosclerosis risk biomarker. This study aimed to investigate the impact of MLT on Lp-PLA2 expression in the atherosclerotic process and explore the underlying mechanisms involved. In vivo, ApoE-/- mice were fed a high-fat diet, with or without MLT administration, after which the plaque area and collagen content were assessed. Macrophages were pretreated with MLT combined with ox-LDL, and the levels of ferroptosis-related proteins, NRF2 activation, mitochondrial function, and oxidative stress were measured. MLT administration significantly attenuated atherosclerotic plaque progression, as evidenced by decreased plaque area and increased collagen. Compared with those in the high-fat diet (HD) group, the levels of glutathione peroxidase 4 (GPX4) and SLC7A11 (xCT, a cystine/glutamate transporter) in atherosclerotic root macrophages were significantly increased in the MLT group. In vitro, MLT activated the nuclear factor-E2-related Factor 2 (NRF2)/SLC7A11/GPX4 signaling pathway, enhancing antioxidant capacity while reducing lipid peroxidation and suppressing Lp-PLA2 expression in macrophages. Moreover, MLT reversed ox-LDL-induced ferroptosis, through the use of ferrostatin-1 (a ferroptosis inhibitor) and/or erastin (a ferroptosis activator). Furthermore, the protective effects of MLT on Lp-PLA2 expression, antioxidant capacity, lipid peroxidation, and ferroptosis were decreased in ML385 (a specific NRF2 inhibitor)-treated macrophages and in AAV-sh-NRF2 treated ApoE-/- mice. MLT suppresses Lp-PLA2 expression and atherosclerosis processes by inhibiting macrophage ferroptosis and partially activating the NRF2 pathway.


Subject(s)
Atherosclerosis , Ferroptosis , Melatonin , NF-E2-Related Factor 2 , Animals , Ferroptosis/drug effects , NF-E2-Related Factor 2/metabolism , Melatonin/pharmacology , Mice , Atherosclerosis/metabolism , Atherosclerosis/drug therapy , Atherosclerosis/prevention & control , Atherosclerosis/pathology , Male , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Diet, High-Fat/adverse effects , Macrophages/metabolism , Macrophages/drug effects , Mice, Inbred C57BL , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Oxidative Stress/drug effects , Signal Transduction/drug effects , 1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism , 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics , Lipoproteins, LDL/metabolism , Antioxidants/pharmacology
13.
J Pineal Res ; 76(4): e12962, 2024 May.
Article in English | MEDLINE | ID: mdl-38775315

ABSTRACT

There is a need to develop therapies for neonatal encephalopathy (NE) in low- and middle-income countries (LMICs) where the burden of disease is greatest and therapeutic hypothermia (HT) is not effective. We aimed to assess the efficacy of melatonin following inflammation-amplified hypoxia-ischaemia (IA-HI) in the newborn piglet. The IA-HI model accounts for the contribution of infection/inflammation in this setting and HT is not cytoprotective. We hypothesised that intravenous melatonin (5% ethanol, at 20 mg/kg over 2 h at 1 h after HI + 10 mg/kg/12 h between 24 and 60 h) is safe and associated with: (i) reduction in magnetic resonance spectroscopy lactate/N-acetylaspartate (MRS Lac/sNAA); (ii) preservation of phosphorus MRS phosphocreatine/phosphate exchange pool (PCr/Epp); (iii) improved aEEG/EEG recovery and (iv) cytoprotection on immunohistochemistry. Male and female piglets underwent IA-HI by carotid artery occlusion and reduction in FiO2 to 6% at 4 h into Escherichia coli lipopolysaccharide sensitisation (2 µg/kg bolus + 1 µg/kg/h over 12 h). At 1 h after IA-HI, piglets were randomised to HI-saline (n = 12) or melatonin (n = 11). There were no differences in insult severity between groups. Target melatonin levels (15-30 mg/L) were achieved within 3 h and blood ethanol levels were <0.25 g/L. At 60 h, compared to HI-saline, melatonin was associated with a reduction of 0.197 log10 units (95% CrI [-0.366, -0.028], Pr(sup) 98.8%) in basal-ganglia and thalamic Lac/NAA, and 0.257 (95% CrI [-0.676, 0.164], Pr(sup) 89.3%) in white matter Lac/NAA. PCr/Epp was higher in melatonin versus HI-saline (Pr(sup) 97.6%). Melatonin was associated with earlier aEEG/EEG recovery from 19 to 24 h (Pr(sup) 95.4%). Compared to HI-saline, melatonin was associated with increased NeuN+ cell density (Pr(sup) 99.3%) across five of eight regions and reduction in TUNEL-positive cell death (Pr(sup) 89.7%). This study supports the translation of melatonin to early-phase clinical trials. Melatonin is protective following IA-HI where HT is not effective. These data guide the design of future dose-escalation studies in the next phase of the translational pipeline.


Subject(s)
Animals, Newborn , Hypoxia-Ischemia, Brain , Melatonin , Animals , Melatonin/pharmacology , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/drug therapy , Swine , Female , Male , Inflammation/metabolism , Inflammation/drug therapy , Disease Models, Animal
14.
J Pineal Res ; 76(4): e12961, 2024 May.
Article in English | MEDLINE | ID: mdl-38751172

ABSTRACT

Melatonin is a neurohormone synthesized from dietary tryptophan in various organs, including the pineal gland and the retina. In the pineal gland, melatonin is produced at night under the control of the master clock located in the suprachiasmatic nuclei of the hypothalamus. Under physiological conditions, the pineal gland seems to constitute the unique source of circulating melatonin. Melatonin is involved in cellular metabolism in different ways. First, the circadian rhythm of melatonin helps the maintenance of proper internal timing, the disruption of which has deleterious effects on metabolic health. Second, melatonin modulates lipid metabolism, notably through diminished lipogenesis, and it has an antidiabetic effect, at least in several animal models. Third, pharmacological doses of melatonin have antioxidative, free radical-scavenging, and anti-inflammatory properties in various in vitro cellular models. As a result, melatonin can be considered both a circadian time-giver and a homeostatic monitor of cellular metabolism, via multiple mechanisms of action that are not all fully characterized. Aging, circadian disruption, and artificial light at night are conditions combining increased metabolic risks with diminished circulating levels of melatonin. Accordingly, melatonin supplementation could be of potential therapeutic value in the treatment or prevention of metabolic disorders. More clinical trials in controlled conditions are needed, notably taking greater account of circadian rhythmicity.


Subject(s)
Circadian Rhythm , Homeostasis , Melatonin , Melatonin/metabolism , Animals , Humans , Circadian Rhythm/physiology , Homeostasis/physiology , Energy Metabolism/drug effects , Energy Metabolism/physiology , Pineal Gland/metabolism
15.
Cell Biochem Funct ; 42(4): e3995, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38751103

ABSTRACT

In recent years, seminal studies have been devoted to unraveling the puzzling mysteries associated with the cancer preventive/inhibitory role of melatonin. Our current knowledge of the translational mechanisms and the detailed structural insights have highlighted the characteristically exclusive role of melatonin in the inhibition of carcinogenesis and metastatic dissemination. This mini-review outlines recent discoveries related to mechanistic role of melatonin in prevention of carcinogenesis and metastasis. Moreover, another exciting facet of this mini-review is related to phenomenal breakthroughs linked with regulation of noncoding RNAs by melatonin in wide variety of cancers.


Subject(s)
Carcinogenesis , Melatonin , Neoplasm Metastasis , Neoplasms , RNA, Untranslated , Melatonin/metabolism , Humans , Carcinogenesis/metabolism , RNA, Untranslated/metabolism , Neoplasms/pathology , Neoplasms/metabolism , Animals
16.
JAMA Netw Open ; 7(5): e2412502, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38776087

ABSTRACT

This cohort study examines patterns of melatonin use among participants in the Adolescent Brain Cognitive Development (ABCD) Study and characterizes factors associated with use.


Subject(s)
Melatonin , Humans , Melatonin/therapeutic use , Child , Female , Male , Child, Preschool , Adolescent , United States , Cross-Sectional Studies , Infant
17.
Cells ; 13(10)2024 May 18.
Article in English | MEDLINE | ID: mdl-38786094

ABSTRACT

Post-stroke cognitive impairment (PSCI) remains the most common consequence of ischemic stroke. In this study, we aimed to investigate the role and mechanisms of melatonin (MT) in improving cognitive dysfunction in stroke mice. We used CoCl2-induced hypoxia-injured SH-SY5Y cells as a cellular model of stroke and photothrombotic-induced ischemic stroke mice as an animal model. We found that the stroke-induced upregulation of mitophagy, apoptosis, and neuronal synaptic plasticity was impaired both in vivo and in vitro. The results of the novel object recognition test and Y-maze showed significant cognitive deficits in the stroke mice, and Nissl staining showed a loss of neurons in the stroke mice. In contrast, MT inhibited excessive mitophagy both in vivo and in vitro and decreased the levels of mitophagy proteins PINK1 and Parkin, and immunofluorescence staining showed reduced co-localization of Tom20 and LC3. A significant inhibition of mitophagy levels could be directly observed under transmission electron microscopy. Furthermore, behavioral experiments and Nissl staining showed that MT ameliorated cognitive deficits and reduced neuronal loss in mice following a stroke. Our results demonstrated that MT inhibits excessive mitophagy and improves PSCI. These findings highlight the potential of MT as a preventive drug for PSCI, offering promising therapeutic implications.


Subject(s)
Cognitive Dysfunction , Melatonin , Mitophagy , Stroke , Animals , Melatonin/pharmacology , Melatonin/therapeutic use , Mitophagy/drug effects , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/pathology , Cognitive Dysfunction/etiology , Mice , Stroke/complications , Stroke/drug therapy , Stroke/pathology , Male , Humans , Disease Models, Animal , Mice, Inbred C57BL , Apoptosis/drug effects , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Neuronal Plasticity/drug effects , Cell Line, Tumor , Protein Kinases , Ubiquitin-Protein Ligases
18.
Plant Physiol Biochem ; 211: 108664, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703498

ABSTRACT

Water stress is a major cause of yield loss in peanut cultivation. Melatonin seed priming has been used to enhance stress tolerance in several crops, but not in peanut. We investigated the impact of seed priming with melatonin on the growth, development, and drought tolerance of two peanut cultivars, TUFRunner™ '511', a drought tolerant cultivar, and New Mexico Valencia A, a drought sensitive cultivar. Peanut seed priming tests using variable rates of melatonin (0-200 µM), indicated that 50 µM of melatonin resulted in more uniform seed germination and improved seedling growth in both cultivars under non stress conditions. Seed priming with melatonin also promoted vegetative growth, as evidenced by higher whole-plant transpiration, net CO2 assimilation, and root water uptake under both well-watered and water stress conditions in both cultivars. Higher antioxidant activity and protective osmolyte accumulation, lower reactive oxygen species accumulation and membrane damage were observed in primed compared with non-primed plants. Seed priming with melatonin induced a growth promoting effect that was more evident under well-watered conditions for TUFRunnner™ '511', whereas for New Mexico Valencia A, major differences in physiological responses were observed under water stress conditions. New Mexico Valencia A primed plants exhibited a more sensitized stress response, with faster down-regulation of photosynthesis and transpiration compared with non-primed plants. The results demonstrate that melatonin seed priming has significant potential to improve early establishment and promote growth of peanut under optimal conditions, while also improve stress tolerance during water stress.


Subject(s)
Arachis , Dehydration , Melatonin , Seeds , Melatonin/pharmacology , Melatonin/metabolism , Arachis/drug effects , Arachis/growth & development , Arachis/metabolism , Arachis/physiology , Seeds/drug effects , Seeds/growth & development , Water/metabolism , Germination/drug effects , Antioxidants/metabolism , Droughts , Photosynthesis/drug effects , Stress, Physiological/drug effects , Seedlings/drug effects , Seedlings/growth & development
19.
Expert Rev Neurother ; 24(6): 585-596, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38738544

ABSTRACT

INTRODUCTION: Sleep disorders represent an important comorbidity in individuals with ADHD. While the links between ADHD and sleep disturbances have been extensively investigated, research on the management of sleep disorders in individuals with ADHD is relatively limited, albeit expanding. AREAS COVERED: The authors searched PubMed, Medline, PsycInfo, Embase+Embase Classic, Web of Sciences databases, and clinicaltrials.gov up to 4 January 2024, for randomized controlled trials (RCTs) of any intervention for sleep disorders associated with ADHD. They retained 16 RCTs (eight on pharmacological and eight on non-pharmacological interventions), supporting behavioral intervention and melatonin, and nine ongoing RCTs registered on clinicaltrials.gov. EXPERT OPINION: The pool of RCTs testing interventions for sleep disorders in individuals with ADHD is expanding. However, to inform clinical guidelines, there is a need for additional research in several areas, including 1) RCTs based on a precise phenotyping of sleep disorders; 2) pragmatic RCTs recruiting neurodevelopmental populations representative of those seen in clinical services; 3) trials testing alternative interventions (e.g. suvorexant or light therapy) or ways to deliver them (e.g. online); 4) sequential and longer-term RCTs; 5) studies testing the impact of sleep interventions on outcomes other than sleep; 6) and implementation of advanced evidence synthesis and precision medicine approaches.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Sleep Wake Disorders , Humans , Attention Deficit Disorder with Hyperactivity/therapy , Attention Deficit Disorder with Hyperactivity/complications , Child , Sleep Wake Disorders/therapy , Randomized Controlled Trials as Topic , Melatonin/therapeutic use , Behavior Therapy
20.
Sci Rep ; 14(1): 11508, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38769439

ABSTRACT

There is a growing trend towards enhancing the post-harvest shelf life and maintaining the nutritional quality of horticultural products using eco-friendly methods. Raspberries are valued for their diverse array of phenolic compounds, which are key contributors to their health-promoting properties. However, raspberries are prone to a relatively short post-harvest lifespan. The present study aimed to investigate the effect of exogenous melatonin (MEL; 0, 0.001, 0.01, and 0.1 mM) on decay control and shelf-life extension. The results demonstrated that MEL treatment significantly reduced the fruit decay rate (P ≤ 0.01). Based on the findings, MEL treatment significantly increased titratable acidity (TA), total phenolics content (TPC), total flavonoid content (TFC), and total anthocyanin content (TAC). Furthermore, the MEL-treated samples showed increased levels of rutin and quercetin content, as well as antioxidant activity as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reduction activity potential (FRAP). Additionally, the samples exhibited higher levels of phenylalanine ammonia-lyase (PAL) and catalase (CAT) enzymes compared to the control samples. Moreover, the levels of pH, total soluble solids (TSS), and IC50 were decreased in the MEL-treated samples (P ≤ 0.01). The highest amount of TA (0.619 g/100 ml juice), rutin (16.722 µg/ml juice) and quercetin (1.467 µg/ml juice), and PAL activity (225.696 nm/g FW/min) was observed at 0.001 mM treatment, while, the highest amount of TAC (227.235 mg Cy-g/100 ml juice) at a concentration of 0.01 mM and CAT (0.696 u/g FW) and TAL activities (9.553 nm/100 g FW) at a concentration of 0.1 mM were obtained. Considering the lack of significant differences in the effects of melatonin concentrations and the low dose of 0.001 mM, this concentration is recommended for further research. The hierarchical cluster analysis (HCA) and principal component analysis (PCA) divided the treatments into three groups based on their characteristics. Based on the Pearson correlation between TPC, TFC, TAC, and TAA, a positive correlation was observed with antioxidant (DPPH and FRAP) and enzyme (PAL and CAT) activities. The results of this study have identified melatonin as an eco-friendly compound that enhances the shelf life of raspberry fruits by improving phenolic compounds, as well as antioxidant and enzyme activities.


Subject(s)
Antioxidants , Fruit , Melatonin , Phytochemicals , Rubus , Antioxidants/metabolism , Antioxidants/analysis , Melatonin/pharmacology , Rubus/chemistry , Phytochemicals/analysis , Phytochemicals/chemistry , Fruit/chemistry , Fruit/drug effects , Phenols/analysis , Flavonoids/analysis , Catalase/metabolism , Phenylalanine Ammonia-Lyase/metabolism , Anthocyanins/analysis
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