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1.
Braz. j. biol ; 84: e253061, 2024. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1364520

RESUMO

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.


A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados ​​como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.


Assuntos
Ratos , Células-Tronco , Fibrose , Fígado , Hepatopatias , Melatonina
2.
Behav Brain Res ; 436: 114083, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36049659

RESUMO

PURPOSE: The aim of this comprehensive systematic review and meta-analysis was to evaluate the beneficial effects of melatonin supplementation on brain-derived neurotrophic factor (BDNF) concentration and clinical depressive disorder. METHODS: A comprehensive electronic search was conducted of Medlin, Web of Science, Science Direct, and Google scholar, from database inception to January 20, 2021. Studies were eligible if they: (1) were a clinical trial; (2) enrolled adults; (3) assessed the effect of melatonin supplementation on serum concentration of BDNF or depression score. Overall effects, as weighted mean difference (WMD), were calculated for concentration of BDNF and depression score. RESULTS: Melatonin supplementation yielded no significant effect on BDNF concentration (WMD: -5.61; 95% CI: -14.10, 2.88; I-square: 85.6%), but improved depression by decreasing the score (WMD: -0.76; 95% CI: -1.12, -0.4; I-square: 88.0%). Due to high heterogeneity between studies, subgroup analysis for gender, duration and dose in BDNF studies and duration, age, dose, continent and Questionnaire type in depression studies, was utilised. The subgroup analysis showed that melatonin supplementation had a significant decreasing effect on BDNF levels in doses ≤ 10 mg/day, with more than 4 weeks of duration, and in men. CONCLUSION: The present study revealed that melatonin supplementation has a decreasing effect on depression in all duration of studies and doses subgroup and in age more than 65 years in depression studies but heterogenicity of the included studies, did not allow a definitive conclusion. There is limited evidence for effects of melatonin on serum BDNF. IMPLICATIONS FOR PRACTICE: Melatonin is a safe and effective supplement for depressive patients.


Assuntos
Melatonina , Adulto , Idoso , Fator Neurotrófico Derivado do Encéfalo , Depressão/tratamento farmacológico , Suplementos Nutricionais/análise , Humanos , Masculino , Melatonina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
J Hazard Mater ; 443(Pt A): 130212, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36308936

RESUMO

Pesticide overuse has led to serious global concerns regarding food safety and environmental pollution. Although the reduction of pesticide residue is critical, our knowledge about induced pesticide metabolism in plants remains fragmentary. Melatonin (N-acetyl-5-methoxytryptamine) is an effective stress-relieving agent in both animals and plants, but little is known about the melatonin signaling mechanism and its effect on pesticide metabolism in plants. Here, we found that exogenous melatonin treatment significantly reduced chlorothalonil residue by 41 % but suppression of endogenous melatonin accumulation increased chlorothalonil residue in tomato leaves. Moreover, melatonin increased photosynthesis, Fv/Fm, Calvin cycle enzyme activity, antioxidant enzyme activity, glutathione pool, and RESPIRATORY BURST HOMOLOG1 (RBOH1) expression in tomato leaves. However, the upregulation of RBOH1, CYP724B2, GST1, GST2, GSH and ABC, the increased glutathione concentrations and the activity of detoxification enzymes due to melatonin treatment were all significantly attenuated by the treatment with an NADPH oxidase inhibitor and a ROS scavenger, indicating a clear relationship between the reduction of pesticide residue and induction in detoxifying enzymes and genes upon melatonin treatment in an apoplastic H2O2-dependent manner. These results reveal that melatonin-induced reduction in chlorothalonil residue is mediated by H2O2 signaling in tomato leaves.


Assuntos
Lycopersicon esculentum , Melatonina , Resíduos de Praguicidas , Praguicidas , Lycopersicon esculentum/metabolismo , Melatonina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Resíduos de Praguicidas/metabolismo , Folhas de Planta/metabolismo , Antioxidantes/metabolismo , Glutationa/metabolismo , Praguicidas/metabolismo
4.
Appl Ergon ; 106: 103882, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36081186

RESUMO

Long-haul cabin crew regularly report misalignment between their circadian phase and the external world (i.e. jet lag). The extent to which changes in circadian phase relate to reported levels of jet lag remains unclear. The main aim of the present study was first to evaluate the relationship between objective (circadian phase) and subjective jet lag and second to explore the relative role of both subjective and objective psycho-behavioural factors in predicting the subjective experience of jet lag. Twenty-eight long-haul cabin crew completed questionnaires measuring diurnal preference, trip characteristics and subjective jet lag as a single and as a multidimensional measure. Sleep was monitored using actigraphy and urinary melatonin peak time was measured, at baseline (T1), e.g. before a long-haul trip and post-trip on the crew's first recovery day (T2). Subjective jet lag was also measured at both time points. At T1, later circadian phase related to increased unidimensional jet lag, however, a post-trip discrepancy was found between objective and subjective uni- and multidimensional jet lag measured at T2 and change from T1 to T2. After controlling for direction and size of circadian phase, increased uni- and multidimensional subjective jet lag was predicted by depressed mood states. The regression models including phase, diurnal preference, departure time on the outbound sector and arousal levels accounted for 28% of the variance in unidimensional jet lag and 53% of the variance in multidimensional jet lag. It was concluded that there is a discordance between objective and subjective jet lag post-trip. Further, subjective jet lag in long-haul cabin crew is better explained by mood impairment than circadian phase. The results are discussed with reference to the gap between subjective and objective jet lag and the role of psychology rather than just biology in the jet lag experience. The implications for improving health and safety in the workplace, through a better understanding of the role of human factors in the management of jet lag, are discussed.


Assuntos
Síndrome do Jet Lag , Melatonina , Humanos , Síndrome do Jet Lag/psicologia , Sono , Actigrafia , Ritmo Circadiano
5.
Biol Res ; 55(1): 33, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333811

RESUMO

BACKGROUND: Ionizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis. METHODS: Rats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation. RESULTS: Serum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2'-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology. CONCLUSIONS: These results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.


Assuntos
Melatonina , Masculino , Ratos , Animais , Melatonina/farmacologia , Testículo/metabolismo , Sêmen/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Radiação Ionizante , Estresse Oxidativo , Anti-Inflamatórios/farmacologia
6.
Nutrients ; 14(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36364847

RESUMO

BACKGROUND: Lifestyle and environmental factors can negatively impact fertility by means of oxidative stress. In this context, antioxidant supplementation therapy has gained much interest in recent years, and different molecules, alone or in combination, have been studied. OBJECTIVE: The purpose of the present review is to investigate the evidence regarding the efficacy of coenzyme Q10 (CoQ10) and melatonin on male infertility. METHODS: A literature search using PUBMED database from 2000 to October 2022 was performed to explore the role of CoQ10 and melatonin on male reproductive function. CONCLUSIONS: The analysis involved a narrative synthesis. CoQ10, alone or in combination, appears to reduce testicular oxidative stress and sperm DNA fragmentation and to improve sperm parameters; particularly sperm motility. Moreover, CoQ10 treatment is associated with higher pregnancy rates, both naturally and through assisted reproductive technology (ART). Larger studies are needed to precisely determine its clinical efficacy. Melatonin is a known antioxidant and preclinical studies have shown its ability to modulate reproductive function through hormonal and immune system regulation and sperm cell proliferation. Regardless, clinical studies are necessary to assess its potential in male infertility.


Assuntos
Infertilidade Masculina , Melatonina , Gravidez , Feminino , Masculino , Humanos , Motilidade Espermática , Melatonina/uso terapêutico , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Sêmen , Ubiquinona/uso terapêutico , Infertilidade Masculina/tratamento farmacológico , Estresse Oxidativo
7.
J Plant Physiol ; 279: 153855, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36335894

RESUMO

The involvement of nitric oxide (NO) in exogenous melatonin (MT)-induced isoflavone accumulation and growth improvement in NaCl-stressed soybeans was investigated in this study. The results demonstrated that MT increased the activity of nitrate reductase (NR) and upregulated the relative expression of NR1, NR2, and nitric oxide synthase1, which subsequently led to an increase in NO content. MT and sodium nitroprusside (SNP, as an NO donor) markedly increased isoflavone content by enhancing the activities of cinnamic acid 4-hydroxylase (C4H) and phenylalanine ammonia lyase (PAL), and by upregulating gene expression of C4H, Isoflavone synthase, PAL, and Chalcone isomerase 1A, which are involved in isoflavone biosynthesis. Moreover, MT, as well as SNP, improved the growth and biomass of NaCl-treated soybeans by increasing the activities of superoxide dismutase, catalase, and peroxidase, and reducing the accumulation of H2O2 and O2•- in soybeans under NaCl stress. These MT-induced responses were entirely reversed by the supply of 4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO, a specific scavenger of NO), which in turn considerably decreased endogenous NO content. These results suggest that NO acts as an important downstream signal molecule, mediating MT-induced isoflavone accumulation and growth improvement in NaCl-stressed soybeans.


Assuntos
Fabaceae , Isoflavonas , Melatonina , Soja , Isoflavonas/farmacologia , Cloreto de Sódio/farmacologia , Óxido Nítrico , Melatonina/farmacologia , Peróxido de Hidrogênio , Fenilalanina Amônia-Liase
9.
Medicine (Baltimore) ; 101(43): e31411, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36316858

RESUMO

BACKGROUND: Up to 80% of patients in the intensive care unit (ICU) suffer from delirium. Studies on the preventative use of melatonin in the ICU have produced mixed results. We performed a systematic review and meta-analysis to evaluate whether early administration of melatonin reduces the prevalence of delirium in critically ill patients. METHODS: We searched Medline, Embase, and the Cochrane Library for randomized controlled trials comparing melatonin or melatonin agonists to placebo in ICU setting. The population included adult patients in the ICU. The primary outcome was the prevalence of delirium. Secondary outcomes included duration of delirium, delirium-free day, serum melatonin concentration, need for sedation, duration of mechanical ventilation, hospital and ICU length of stay (LOS), all-cause mortality, sleep quality, and adverse events. Trial sequential analysis (TSA) was performed on the primary outcome to prevent the risk of random error and multiplicity phenomenon as a result of repeated significance testing across all the included trials. RESULTS: Twelve trials with a total of 2538 patients were analyzed. When all trials were pooled, the incidence of delirium in ICU patients who received melatonin was significantly lower than in those who received placebo (risk ratio, 0.77; 95% confidence interval: 0.61-0.96; I2 = 56%). There were no significant differences in secondary outcomes including duration of delirium, duration of mechanical ventilation, ICU LOS, hospital LOS, and mortality. TSA indicated that Z-curve crossed the traditional boundary, but did not cross the monitoring boundary for benefit, which indicated that it is still inconclusive that melatonin affects the incidence of delirium. CONCLUSIONS: This meta-analysis found that early administration of melatonin may result in a decreased delirium prevalence in critically ill patients. However, the sensitivity analysis of high-quality studies did not support this finding. In addition, TSA demonstrated that the result may have false-positive error. Therefore, this finding should be interpreted with caution. Further studies are needed to examine the effectiveness of prophylactic melatonin on the prevalence and duration of ICU delirium in the future.


Assuntos
Estado Terminal , Melatonina , Adulto , Humanos , Melatonina/uso terapêutico , Unidades de Terapia Intensiva , Cuidados Críticos , Tempo de Internação
10.
Cells ; 11(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36359862

RESUMO

Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin's functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin's cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.


Assuntos
Glioblastoma , Melatonina , Humanos , Camundongos , Animais , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Melatonina/farmacologia , Melatonina/uso terapêutico , Glicólise , Divisão Celular , Concentração de Íons de Hidrogênio
11.
J Environ Pathol Toxicol Oncol ; 41(4): 55-84, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36374962

RESUMO

Melatonin is primarily synthesized in the pineal gland under the influence of noradrenergic stimulation at night. It regulates the sleep-wake cycle, gonadal activity, redox homeostasis, immune functions, and anticarcinogenic effects at the normal physiological state. The activity of melatonin is mediated by membrane-bound G protein-coupled receptors MT1 and MT2. Circadian deregulation, exposure to light-at-night, shift work, and jet lag disrupt the melatonin rhythm. A low level of circulatory melatonin concentration influences the development of many cancers, including breast cancer. Melatonin acts as an anticancer agent in breast tissue. It suppresses metabolic activity, regulates cell-signaling pathways, and subsequently blocks cell proliferation. This indolamine induces apoptosis, inhibits chronic inflammation and metastasis. Melatonin restricts the functions of estrogen receptor α and also inhibits aromatase activity. Melatonin is a potent antioxidant that reduces the chemoresistance capacity of breast cancer cells. At therapeutic levels, it potentially increases the efficacy of chemotherapeutic agents and decreases their adverse effects during the treatment of breast cancer. The present review focuses on the antineoplastic activity of melatonin against breast cancer. Emphasis has been given to the possible use of melatonin in the treatment of breast cancer.


Assuntos
Antineoplásicos , Melatonina , Neoplasias , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Transdução de Sinais
12.
Int J Mol Sci ; 23(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36361683

RESUMO

More research is required to understand how melatonin protects neurons. The study aimed to find out if and how long non-coding RNA (lncRNA) contributes to melatonin's ability to defend the hippocampus from H2O2-induced oxidative injury. LncRNAs related to oxidative injury were predicted by bioinformatics methods. Mouse hippocampus-derived neuronal HT22 cells were treated with H2O2 with or without melatonin. Viability and apoptosis were detected by Cell Counting Kit-8 and Hoechst33258. RNA and protein levels were measured by quantitative real-time PCR, Western blot, and immunofluorescence. Bioinformatics predicted that 38 lncRNAs were associated with oxidative injury in mouse neurons. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was related to H2O2-induced oxidative injury and up-regulated by melatonin in HT22 cells. The knockdown of NEAT1 exacerbated H2O2-induced oxidative injury, weakened the moderating effect of melatonin, and abolished the increasing effect of melatonin on the mRNA and protein level of Slc38a2. Taken together, melatonin attenuates H2O2-induced oxidative injury by upregulating lncRNA NEAT1, which is essential for melatonin stabilizing the mRNA and protein level of Slc38a2 for the survival of HT22 cells. The research may assist in the treatment of oxidative injury-induced hippocampal degeneration associated with aging using melatonin and its target lncRNA NEAT1.


Assuntos
Melatonina , MicroRNAs , RNA Longo não Codificante , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Melatonina/farmacologia , Peróxido de Hidrogênio/toxicidade , Hipocampo/metabolismo , Apoptose/genética , Estresse Oxidativo , RNA Mensageiro/metabolismo , MicroRNAs/genética
13.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36361700

RESUMO

Abiotic stresses, such as drought, salinity, heat, cold, and heavy metals, are associated with global climate change and hamper plant growth and development, affecting crop yields and quality. However, the negative effects of abiotic stresses can be mitigated through exogenous treatments using small biomolecules. For example, the foliar application of melatonin provides the following: it protects the photosynthetic apparatus; it increases the antioxidant defenses, osmoprotectant, and soluble sugar levels; it prevents tissue damage and reduces electrolyte leakage; it improves reactive oxygen species (ROS) scavenging; and it increases biomass, maintains the redox and ion homeostasis, and improves gaseous exchange. Glutathione spray upregulates the glyoxalase system, reduces methylglyoxal (MG) toxicity and oxidative stress, decreases hydrogen peroxide and malondialdehyde accumulation, improves the defense mechanisms, tissue repairs, and nitrogen fixation, and upregulates the phytochelatins. The exogenous application of proline enhances growth and other physiological characteristics, upregulates osmoprotection, protects the integrity of the plasma lemma, reduces lipid peroxidation, increases photosynthetic pigments, phenolic acids, flavonoids, and amino acids, and enhances stress tolerance, carbon fixation, and leaf nitrogen content. The foliar application of glycine betaine improves growth, upregulates osmoprotection and osmoregulation, increases relative water content, net photosynthetic rate, and catalase activity, decreases photorespiration, ion leakage, and lipid peroxidation, protects the oxygen-evolving complex, and prevents chlorosis. Chemical priming has various important advantages over transgenic technology as it is typically more affordable for farmers and safe for plants, people, and animals, while being considered environmentally acceptable. Chemical priming helps to improve the quality and quantity of the yield. This review summarizes and discusses how exogenous melatonin, glutathione, proline, and glycine betaine can help crops combat abiotic stresses.


Assuntos
Melatonina , Melatonina/metabolismo , Betaína/farmacologia , Betaína/metabolismo , Prolina/farmacologia , Prolina/metabolismo , Glutationa/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Fisiológico/fisiologia
14.
Int J Mol Sci ; 23(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36362201

RESUMO

The concentration of melatonin is elevated during the night when patients mainly wear removable orthodontic appliances. Next to periodontal ligament fibroblasts and osteoblasts, macrophages react to mechanical strain with an increased expression of inflammatory mediators. Here, we investigated the impact of melatonin on RAW264.7 macrophages exposed to tensile or compressive strain occurring during orthodontic tooth movement in the periodontal ligament. Before exposure to mechanical strain for 4 h, macrophages were pre-incubated with different melatonin concentrations for 24 h, to determine the dependence of melatonin concentration. Afterwards, we performed experiments with and without mechanical strain, the most effective melatonin concentration (25 µM), and the melatonin receptor 2 (MT2) specific antagonist 4P-PDOT. The expression of inflammatory genes and proteins was investigated by RT-qPCR, ELISAs, and immunoblot. Both tensile and compressive strain increased the expression of the investigated inflammatory factors interleukin-1-beta, interleukin-6, tumor necrosis factor alpha, and prostaglandin endoperoxide synthase-2. This effect was inhibited by the addition of melatonin. Incubation with 4P-PDOT blocked this anti-inflammatory effect of melatonin. Melatonin had an anti-inflammatory effect on macrophages exposed to mechanical strain, independent of the type of mechanical strain. As inhibition was possible with 4P-PDOT, the MT2 receptor might be involved in the regulation of the observed effects.


Assuntos
Melatonina , Humanos , Melatonina/farmacologia , Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo , Macrófagos/metabolismo , Anti-Inflamatórios
15.
BMC Neurosci ; 23(1): 65, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384473

RESUMO

BACKGROUND: One of the most serious nervous system diseases is spinal cord injury(SCI), which is increasing for various reasons. Although no definitive treatment has yet been identified for SCI, one possible treatment is adipose-derived stem cells(ADSCs). However, a key issue in transplantation is improving cells' survival and function in the target tissue. Melatonin(MT) hormone with antioxidant properties can prolong cell survival and improve cell function. This study investigates the pre-conditioning of ADSCs with melatonin for enhancing the engraftment and neurological function of rats undergoing SCI. METHODS: 42 male Sprague-Dawley rats were divided into six groups, including Control, Sham, Model, Vehicle, and Lesion treatments A and B. After acquiring white adipose tissue, stem cells were evaluated by flow cytometry. SCI was then applied in Model, Vehicle, A, and B groups. Group A and B received ADSCs and ADSCs + melatonin, respectively, 1 week after SCI, but the vehicle received only an intravenous injection for simulation; The other groups were recruited for the behavioral test. Immunohistochemistry(IHC) was used to assess the engraftment and differentiation of ADSCs in the SCI site. Basso, Beattie, and Bresnahan's score was used to evaluate motor function between the six groups. RESULTS: Histological studies and cell count confirmed ADSCs implantation at the injury site, which was higher in the MT-ADSCs (P < 0.001). IHC revealed the differentiation of ADSCs and MT-ADSCs into neurons, astrocytes, and oligodendrocyte lineage cells, which were higher in MT-ADSCs. Functional improvement was observed in SCI + ADSCs and SCI + MT-ADSCs groups. CONCLUSION: The pre-conditioning of ADSCs with melatonin positively affects engraftment and neuronal differentiation in SCI but does not impact performance improvement compared to the ADSCs.


Assuntos
Melatonina , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Masculino , Ratos , Animais , Melatonina/farmacologia , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Modelos Animais de Doenças
16.
Ying Yong Sheng Tai Xue Bao ; 33(10): 2725-2735, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36384608

RESUMO

To explore whether there is an interaction between melatonin (MT) and calcium (Ca2+) in regulating heat tolerance of plants, we analyzed the response of endogenous MT and Ca2+ to heat stress, and examined the effect of MT and Ca2+ on the reactive oxygen (ROS) accumulation, antioxidant system, and transcripts of heat shock factor (HSF) and heat shock proteins (HSPs) of cucumber seedlings under high temperature stress. Seedlings were foliar sprayed with 100 µmol·L-1 MT, 10 mmol·L-1 CaCl2, 3 mmol·L-1 ethylene glycol tetraacetic acid (EGTA, Ca2+ chelating agent) +100 µmol·L-1 MT, 0.05 mmol·L-1 chlorpromazine (calmodulin antagonist, CPZ) +100 µmol·L-1 MT, 100 µmol·L-1 p-chlorophenylalanine (p-CPA, inhibitor of MT) +10 mmol·L-1 CaCl2 or deionized water (H2O), respectively. The results showed that both endogenous MT and Ca2+ in cucumber seedlings were induced by high temperature stress. The seedlings treated with exogenous MT showed significant increases in the mRNA expression of calmodulin (CaM), calcium-dependent protein kinase (CDPK5), calcineurin B-like protein (CBL3) and CBL interacting protein kinase (CIPK2) compared with the control at normal temperature. The mRNA levels of tryptophane decarboxylase (TDC), 5-hydroxytryptamine-N-acetyltransferase (SNAT) and N-acetyl-5-hydroxytryptamine methyltransferase (ASMT), key genes of MT biosynthesis and endogenous MT content were also induced by Ca2+ in cucumber seedlings. Exogenous MT and CaCl2 alleviated the heat-induced oxidative damage through increasing antioxidant ability, reducing the accumulation of reactive oxygen species (ROS), and upregulating the mRNA abundances of HSF7, HSP70.1 and HSP70.11, as evidenced by mild thermal damage symptoms, lower heat injury index and electrolyte leakage under heat stress. The positive effect of MT-induced antioxidant capacity and mRNA expression of HSPs was removed by adding EGTA and CPZ in stressed seedlings. Similarly, the mitigating role of Ca2+ in the peroxidation damage to high temperature stress was reversed by p-CPA. These results suggested that both MT and Ca2+ could induce heat tolerance of cucumber seedlings, which had crosstalk in the process of heat stress signal transduction.


Assuntos
Cucumis sativus , Melatonina , Cucumis sativus/genética , Melatonina/farmacologia , Cálcio , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Calmodulina/genética , Calmodulina/metabolismo , Calmodulina/farmacologia , Ácido Egtázico/farmacologia , Cloreto de Cálcio/metabolismo , Cloreto de Cálcio/farmacologia , Temperatura , Estresse Fisiológico , Plântula/fisiologia , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia
17.
BMC Vet Res ; 18(1): 403, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376876

RESUMO

This study aimed to determine the effects of melatonin administration on testicular vascular perfusion in relation to steroid hormones and semen characteristics in dogs. The study included 12 normospermic German shepherd dogs (weighed 35 ± 0.5 kg and aged 4 ± 0.5 years). Males received a single melatonin administration (melatonin dimethyl sulfoxide + corn oil via subcutaneous route; MEL; n = 6), while the rest of the animals served as controls (dimethyl sulfoxide + corn oil; Control; n = 6). Males were subjected to routine examination on days -15, 0, 15, 30, 45, and 60. All examined dogs were subjected to Doppler screening, semen collection, and blood sampling. The MEL group showed a significant (P < 0.05) elevation in semen volume, concentration, percentage of sperm motility, and total sperm × 106 / ejaculate compared to other control males. Doppler indices as resistance (RI) and pulsatility (PI) indices declined (P < 0.05) from D 30 (1.02 ± 0.01) until day 60 (0.87 ± 0.02) of treatment. In MEL males, the peak systolic point of velocity (PSV; cm/sec) of the testicular artery elevated (P < 0.05) on day 60 (20.15 ± 0.99) compared to its value on day 0 (17.39 ± 1.84). On D 60, the levels of testosterone (T), estradiol 17-ß (E2), and nitric oxide (NO) elevated (P < 0.05). A negative correlation was detected between testicular volume, scrotal circumference (SC), T levels, Doppler indices, and velocities. In conclusion, single melatonin administration could improve testicular vascularization via increasing Doppler velocities and intratesticular colored areas. In addition, it could improve semen picture and steroids (T and E2) and nitric oxide.


Assuntos
Melatonina , Sêmen , Cães , Masculino , Animais , Motilidade Espermática , Melatonina/farmacologia , Dimetil Sulfóxido , Óleo de Milho , Óxido Nítrico , Análise do Sêmen/veterinária , Testículo/diagnóstico por imagem , Esteroides , Hemodinâmica , Artérias
18.
Microbiome ; 10(1): 194, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36376894

RESUMO

BACKGROUND: Seasonal breeding in mammals has been widely recognized to be regulated by photoperiod, but the association of gut microbiota with photoperiodic regulation of seasonal breeding has never been investigated. RESULTS: In this study, we investigated the association of gut microbiota with photoperiod-induced reproduction in male Brandt's voles (Lasiopodomys brandtii) through a long-day and short-day photoperiod manipulation experiment and fecal microbiota transplantation (FMT) experiment. We found photoperiod significantly altered reproductive hormone and gene expression levels, and gut microbiota of voles. Specific gut microbes were significantly associated with the reproductive hormones and genes of voles during photoperiod acclimation. Transplantation of gut microbes into recipient voles induced similar changes in three hormones (melatonin, follicle-stimulating hormone, and luteinizing hormone) and three genes (hypothalamic Kiss-1, testicular Dio3, and Dio2/Dio3 ratio) to those in long-day and short-day photoperiod donor voles and altered circadian rhythm peaks of recipient voles. CONCLUSIONS: Our study firstly revealed the association of gut microbiota with photoperiodic regulation of seasonal breeding through the HPG axis, melatonin, and Kisspeptin/GPR54 system. Our results may have significant implications for pest control, livestock animal breeding, and human health management. Video Abstract.


Assuntos
Microbioma Gastrointestinal , Melatonina , Animais , Humanos , Masculino , Fotoperíodo , Microbioma Gastrointestinal/genética , Melatonina/metabolismo , Estações do Ano , Arvicolinae/fisiologia
19.
Biomolecules ; 12(11)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36358996

RESUMO

Clinical sequelae and symptoms for a considerable number of COVID-19 patients can linger for months beyond the acute stage of SARS-CoV-2 infection, "long COVID". Among the long-term consequences of SARS-CoV-2 infection, cognitive issues (especially memory loss or "brain fog"), chronic fatigue, myalgia, and muscular weakness resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are of importance. Melatonin may be particularly effective at reducing the signs and symptoms of SARS-CoV-2 infection due to its functions as an antioxidant, anti-inflammatory, and immuno-modulatory agent. Melatonin is also a chronobiotic medication effective in treating delirium and restoring the circadian imbalance seen in COVID patients in the intensive care unit. Additionally, as a cytoprotector, melatonin aids in the prevention of several COVID-19 comorbidities, including diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases. This narrative review discusses the application of melatonin as a neuroprotective agent to control cognitive deterioration ("brain fog") and pain in the ME/CFS syndrome-like documented in long COVID. Further studies on the therapeutic use of melatonin in the neurological sequelae of SARS-CoV-2 infection are warranted.


Assuntos
COVID-19 , Síndrome de Fadiga Crônica , Melatonina , Humanos , COVID-19/tratamento farmacológico , Melatonina/uso terapêutico , SARS-CoV-2 , Síndrome de Fadiga Crônica/tratamento farmacológico , Síndrome de Fadiga Crônica/diagnóstico
20.
J Adv Res ; 41: 1-12, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36328739

RESUMO

INTRODUCTION: The human genome encodes two melatonin receptors (MT1 and MT2) that relay melatonin signals to cellular interior. Accumulating evidence has linked melatonin to multiple health benefits, among which its anticancer effects have become well-established. However, the implications of its receptors in lung adenocarcinoma have so far remained incompletely understood. OBJECTIVES: This study aims to investigate the response of the MT1 receptor to melatonin treatment and its dynamic regulation by ubiquitin-specific protease 8 (USP8) in lung adenocarcinoma. METHODS: The mRNA levels of MT1 and MT2 receptors were analyzed with sequencing data. The expression and localization of the MT1 receptor with melatonin treatment were investigated by immunoblotting, immunofluorescence and confocal microscopy assays. Endocytic deubiquitylases were screened to identify MT1 association. The effects of USP8 were assessed with shRNA-mediated knockdown and small molecule inhibitor. The combined efficacy of melatonin and USP8 suppression was also evaluated using xenograft animal models. RESULTS: Bioinformatic analysis revealed increased expression of the MT1 receptor in lung adenocarcinoma tissues. Melatonin treatment leads to the downregulation of the MT1 receptor in lung adenocarcinoma cells, which is attributed to receptor endocytosis and lysosomal degradation via the canonical endo-lysosomal route. USP8 negatively regulates the endocytic degradation of the MT1 receptor incurred by melatonin exposure and thus protects lung adenocarcinoma cell growth. USP8 suppression by knockdown or pharmacological inhibition effectively deters cancer cell proliferation and sensitizes lung adenocarcinoma cells to melatonin in vitro. Furthermore, USP8 silencing significantly potentiates the anticancer effects of melatonin in xenograft tumor models. CONCLUSION: The MT1 receptor responds to melatonin treatment and is endocytosed for lysosomal degradation that is counteracted by USP8. The inhibition of USP8 demonstrates tumor-suppressive effects and thus can be exploited as potential therapeutic strategy either as monotherapy or combined therapy with melatonin.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Melatonina , Animais , Humanos , Receptor MT1 de Melatonina/genética , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo , Melatonina/farmacologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Proteases Específicas de Ubiquitina
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