Asunto(s)

Dermatitis Atópica , Melatonina , Índice de Severidad de la Enfermedad , Calidad del Sueño , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Melatonina/administración & dosificación , Melatonina/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

OBJECTIVE: This study investigates the therapeutic effects of colchicine and melatonin on endometriotic implants in an experimentally created endometriosis model in rats. STUDY DESIGN: Forty-four adult female Wistar albino rats weighing between 260 and 300 g, 8 weeks old, were selected for the study. The unilateral uterine horn of rats with a bicornuate uterus was excised for 1 cm, washed with sterile saline, incised longitudinally, and the endometrium was exposed. A 0.5*0.5 cm endometrial tissue sample taken with a scalpel was implanted with suturing (4/0 Vicryl) to the abdominal wall. Forty-four rats were divided into four groups. Group 1 was randomized as the endometriosis group (control), Group 2 as endometriosis + colchicine treatment, Group 3 as endometriosis + melatonin treatment, and Group 4 as the endometriosis + melatonin + colchicine treatment group. The colchicine (Sigma Chemical Co., St Louis, Missouri) group was administered orally at a dose of 0.1 mg/kg, and the Melatonin group orally at a dose of melatonin (20 mg/kg per day). Treatment continued daily for 30 days. RESULTS: In the post-treatment focal diameter measurements, the endometrial focal diameter in the colchicine and colchicine + melatonin group was significantly lower than the control group (p=0.026). Bcl-2 levels of the colchicine group were lower than the control group and the melatonin group (p=0.021). CONCLUSION: Colchicine and melatonin reduce adhesion to the peritoneal surface in ectopic endometrial cells. It also acts by increasing apoptosis and decreasing cell survival.

Asunto(s)

Colchicina , Modelos Animales de Enfermedad , Endometriosis , Endometrio , Melatonina , Ratas Wistar , Femenino , Animales , Colchicina/farmacología , Colchicina/administración & dosificación , Endometriosis/tratamiento farmacológico , Endometriosis/patología , Melatonina/farmacología , Melatonina/administración & dosificación , Melatonina/uso terapéutico , Ratas , Endometrio/efectos de los fármacos , Endometrio/patología , Humanos

RESUMEN

Addressing insulin resistance or hyperinsulinemia might offer a viable treatment approach to stop the onset of diabetic cardiomyopathy, as these conditions independently predispose to the development of the disease, which is initially characterized by diastolic abnormalities. The development of diabetic cardiomyopathy appears to be driven mainly by insulin resistance or impaired insulin signalling and/or hyperinsulinemia. Oxidative stress, hypertrophy, fibrosis, cardiac diastolic dysfunction, and, ultimately, systolic heart failure are the outcomes of these pathophysiological alterations. Melatonin is a ubiquitous indoleamine, a widely distributed compound secreted mainly by the pineal gland, and serves a variety of purposes in almost every living creature. Melatonin is found to play a leading role by improving myocardial cell metabolism, decreasing vascular endothelial cell death, reversing micro-circulation disorders, reducing myocardial fibrosis, decreasing oxidative and endoplasmic reticulum stress, regulating cell autophagy and apoptosis, and enhancing mitochondrial function. This review highlights a relationship between insulin resistance and associated cardiomyopathy. It explores the potential therapeutic strategies offered by the neurohormone melatonin, an important antioxidant that plays a leading role in maintaining glucose homeostasis by influencing the glucose transporters independently and through its receptors. The vast distribution of melatonin receptors in the body, including beta cells of pancreatic islets, asserts the role of this indole molecule in maintaining glucose homeostasis. Melatonin controls the production of GLUT4 and/or the phosphorylation process of the receptor for insulin and its intracellular substrates, activating the insulin-signalling pathway through its G-protein-coupled membrane receptors.

Asunto(s)

Cardiomiopatías Diabéticas , Resistencia a la Insulina , Melatonina , Melatonina/metabolismo , Melatonina/uso terapéutico , Melatonina/farmacología , Resistencia a la Insulina/fisiología , Humanos , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/patología , Animales , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Transducción de Señal/efectos de los fármacos

RESUMEN

To explore the effects of Du Meridian moxibustion combined with ear acupuncture on clinical symptoms and serum neurotransmitters in patients with coronary heart disease and insomnia. This study is a retrospective study. From June 2021 to May 2023, 116 patients with coronary heart disease and insomnia treated at our hospital were selected as subjects. They were divided into 2 groups according to the treatment. The control group received treatment with alprazolam, while the experimental group received Du Meridian moxibustion combined with ear acupuncture in addition to alprazolam treatment. The efficacy of the 2 groups was compared, and the levels of cardiac function indicators, serum melatonin, leptin, and neurotransmitters were measured. The total effectiveness rate in the experimental group was 93.10% (with a cure rate of 36.21%, a significant improvement rate of 41.38%, and an effective rate of 15.52%), which was significantly higher than the 79.31% in the control group (with a cure rate of 24.14%, a significant improvement rate of 32.76%, and an effective rate of 22.41%) (P < .05). Both groups exhibited an increase in left ventricular ejection fraction, stroke volume, and cardiac output after treatment compared to before treatment. Additionally, left ventricular end-systolic diameter decreased after treatment compared to before treatment, but the cardiac function was compared between the 2 groups after treatment (P > .05). In both groups, serum melatonin and serotonin (5-HT) levels increased after treatment compared to before treatment, while serum leptin, dopamine, and glutamate levels decreased after treatment compared to before treatment. Furthermore, the experimental group had higher serum melatonin, 5-HT, and gamma-aminobutyric acid levels compared to the control group, and lower serum leptin, dopamine, and glutamate levels compared to the control group (P < .05). The serum traditional Chinese medicine syndrome score and Pittsburgh sleep quality index score of the 2 groups decreased after treatment, and the experimental group was lower than the conventional group (P < .05). The combination of Du Meridian acupuncture with ear acupuncture in the treatment of insomnia in coronary heart disease can regulate the expression of serum melatonin, leptin, and neurotransmitters, alleviate symptoms, and improve therapeutic efficacy.

Asunto(s)

Terapia por Acupuntura , Alprazolam , Enfermedad Coronaria , Leptina , Melatonina , Moxibustión , Neurotransmisores , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Masculino , Femenino , Persona de Mediana Edad , Terapia por Acupuntura/métodos , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Trastornos del Inicio y del Mantenimiento del Sueño/sangre , Melatonina/sangre , Melatonina/uso terapéutico , Estudios Retrospectivos , Moxibustión/métodos , Enfermedad Coronaria/terapia , Enfermedad Coronaria/sangre , Alprazolam/uso terapéutico , Leptina/sangre , Neurotransmisores/sangre , Anciano , Terapia Combinada , Meridianos , Serotonina/sangre , Resultado del Tratamiento

RESUMEN

Evidence concerning the osteotoxic effects of chemotherapy (doxorubicin) has been previously described. Periodontitis also progressively increases in patients receiving chemotherapy; however, the beneficial effects of melatonin and metformin on the alleviation of doxorubicin-induced osteotoxicity have never been investigated. Therefore, we investigated the negative impact of doxorubicin on alveolar bone homeostasis and the benefits of melatonin and metformin on the attenuation of doxorubicin-induced alveolar bone toxicity. Male Wistar rats were divided into 4 groups to receive either 1 mL of normal saline solution as a control group, 3 mg/kg of doxorubicin, 3 mg/kg of doxorubicin plus 10 mg/kg of melatonin, or 3 mg/kg of doxorubicin plus 250 mg/kg of metformin. Doxorubicin treatment was given on days 0, 4, 8, 15, 22, and 29, while interventions were given daily on days 0 to 29. Following euthanasia, blood and alveolar bones were collected for evaluation of oxidative stress, bone remodeling, inflammation, microarchitecture, and periodontal condition. We found that doxorubicin increased systemic oxidative stress, decreased antioxidative capacity, increased inflammation, decreased bone formation, increased bone reabsorption, impaired microarchitecture, and impaired periodontal condition of the alveolar bone. Although cotreatment with melatonin or metformin resulted in some improvement in these parameters, cotreatment with melatonin was more effective than cotreatment with metformin in terms of decreasing oxidative stress, reducing bone resorption, and improving microarchitecture and periodontal condition. All of these findings highlight the potential for antioxidants, especially melatonin, to ameliorate doxorubicin-induced alveolar bone toxicity.

Asunto(s)

Pérdida de Hueso Alveolar , Proceso Alveolar , Antioxidantes , Doxorrubicina , Melatonina , Metformina , Estrés Oxidativo , Ratas Wistar , Melatonina/farmacología , Melatonina/uso terapéutico , Animales , Metformina/farmacología , Metformina/uso terapéutico , Doxorrubicina/toxicidad , Masculino , Ratas , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Pérdida de Hueso Alveolar/prevención & control , Proceso Alveolar/efectos de los fármacos , Antibióticos Antineoplásicos/toxicidad , Remodelación Ósea/efectos de los fármacos , Microtomografía por Rayos X

RESUMEN

Melatonin (MEL) has shown positive effects in anti-inflammatory and anti-oxidative stress research. This study investigates whether MEL can positively impact bone loss induced by valproic acid (VPA) in rats. The study examines changes in MC3T3-E1 cell viability and osteogenic potential, along with osteoclast differentiation in RAW264.7 cells in the presence of VPA using CCK-8, ALP staining, AR staining, and TRAP staining. In vitro experiments reveal that VPA-induced inhibition of osteogenic differentiation and promotion of osteoclastic differentiation are linked to increased inflammation and oxidative stress. Furthermore, MEL has demonstrated the ability to reduce oxidative stress and inflammation, boost osteogenic differentiation, and inhibit osteoclast differentiation. Animal experiments confirm that MEL significantly increases SOD2 expression and decreases TNF-α expression, leading to the restoration of impaired bone metabolism, enhanced bone strength, and higher bone mineral density. The combined experimental results strongly suggest that MEL can enhance osteogenic activity in the presence of VPA by reducing inflammation and oxidative stress, impeding osteoclast differentiation, and alleviating bone loss in VPA-treated rat models.

Asunto(s)

Antiinflamatorios , Diferenciación Celular , Melatonina , Osteoclastos , Osteogénesis , Osteoporosis , Estrés Oxidativo , Ratas Sprague-Dawley , Ácido Valproico , Animales , Ácido Valproico/uso terapéutico , Ácido Valproico/farmacología , Estrés Oxidativo/efectos de los fármacos , Melatonina/farmacología , Melatonina/uso terapéutico , Osteoporosis/tratamiento farmacológico , Ratones , Células RAW 264.7 , Osteogénesis/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Ratas , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Femenino , Diferenciación Celular/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo

RESUMEN

Traumatic brain injuries (TBIs) constitute a significant public health issue and a major source of disability and death in the United States and worldwide. TBIs are strongly associated with high morbidity and mortality rates, resulting in a host of negative health outcomes and long-term complications and placing a heavy financial burden on healthcare systems. One promising avenue for the prevention and treatment of brain injuries is the design of TBI-specific supplementation and dietary protocols centred around nutraceuticals and biochemical compounds whose mechanisms of action have been shown to interfere with, and potentially alleviate, some of the neurophysiological processes triggered by TBI. For example, evidence suggests that creatine monohydrate and omega-3 fatty acids (DHA and EPA) help decrease inflammation, reduce neural damage and maintain adequate energy supply to the brain following injury. Similarly, melatonin supplementation may improve some of the sleep disturbances often experienced post-TBI. The scope of this narrative review is to summarise the available literature on the neuroprotective effects of selected nutrients in the context of TBI-related outcomes and provide an evidence-based overview of supplementation and dietary protocols that may be considered in individuals affected by-or at high risk for-concussion and more severe head traumas. Prophylactic and/or therapeutic compounds under investigation include creatine monohydrate, omega-3 fatty acids, BCAAs, riboflavin, choline, magnesium, berry anthocyanins, Boswellia serrata, enzogenol, N-Acetylcysteine and melatonin. Results from this analysis are also placed in the context of assessing and addressing important health-related and physiological parameters in the peri-impact period such as premorbid nutrient and metabolic health status, blood glucose regulation and thermoregulation following injury, caffeine consumption and sleep behaviours. As clinical evidence in this research field is rapidly emerging, a comprehensive approach including appropriate nutritional interventions has the potential to mitigate some of the physical, neurological, and emotional damage inflicted by TBIs, promote timely and effective recovery, and inform policymakers in the development of prevention strategies.

Asunto(s)

Lesiones Traumáticas del Encéfalo , Suplementos Dietéticos , Humanos , Lesiones Traumáticas del Encéfalo/dietoterapia , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Ácidos Grasos Omega-3/administración & dosificación , Fármacos Neuroprotectores/uso terapéutico , Melatonina/uso terapéutico , Melatonina/administración & dosificación , Creatina , Dieta/métodos

RESUMEN

BACKGROUND: Melatonin, one of the most versatile hormones in the body, is well appreciated in managing circadian rhythm and for antioxidant properties. Produced in the pineal gland and within mitochondria, melatonin influences many physiologic processes through receptor mediated and direct effects. OBJECTIVE: The present investigation explores the evolving pharmacologic properties of melatonin, as well as current therapeutic uses in areas where mitigating oxidative stress, inflammation, and cellular senescence. This review also delves into novel therapeutic potential of melatonin and how current research is revealing a wide array of therapeutic promise in pain medicine. STUDY DESIGN: A systematic review of randomized controlled trials (RCTs) and observational studies was performed using various search engines focused on melatonin and its role in pain medicine. METHODS: The available literature on melatonin and pain medicine was reviewed. A comprehensive literature search of multiple databases from 1966 to July 2024, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into qualitative and quantitative evidence synthesis. OUTCOME MEASURES: The primary outcome measure was the proportion of patients receiving melatonin with significant relief and functional improvement of greater than 50% of at least 3 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months). RESULTS: Melatonin can affect intervertebral disc (IVD) health through the enhancement of survival and function of nucleus pulposus cells, primarily through activation of the ERK1/2 signaling pathway. Melatonin also influences the biochemical environment of the IVD by modulating inflammation and oxidative stress, crucial factors in the pathogenesis of disc degeneration. Melatonin has been shown to reduce senescence and promote autophagy within disc cells, vital for clearing out damaged cellular components, preserving cellular function and preventing deterioration associated with aging and degenerative diseases. LIMITATIONS: Despite the availability of multiple studies, the paucity of clinical pain related literature is considered as the major drawback. CONCLUSION: Based on the present systematic review, melatonin plays a critical role in sleep, but evolving studies have demonstrated substantive roles in mitigating degenerative conditions in various tissues, including IVD degeneration. Ongoing studies will better clarify the role of melatonin as a potential therapeutic agent, including the targeted delivery to various body regions.

Asunto(s)

Degeneración del Disco Intervertebral , Melatonina , Melatonina/uso terapéutico , Humanos , Degeneración del Disco Intervertebral/tratamiento farmacológico , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Manejo del Dolor/métodos

RESUMEN

BACKGROUND: Melatonin is commonly used to treat sleep disturbance in children and adolescents, although uncertainties about its optimal use remain. OBJECTIVE: To determine to what extent prescribing of melatonin complies with evidence-based clinical practice standards. METHODS: As part of a quality improvement programme, the Prescribing Observatory for Mental Health conducted a retrospective clinical audit in UK services for children and adolescents. FINDINGS: Data were submitted for 4151 children and adolescents up to 18 years of age, treated with melatonin: 3053 (74%) had a diagnosis of neurodevelopmental disorder. In 2655 (73%) of the 3651 patients prescribed melatonin to be taken regularly, the main reason was to reduce sleep latency (time taken to fall asleep). In 409 patients recently starting melatonin, a non-pharmacological intervention had already been tried in 279 (68%). The therapeutic response of patients early in treatment (n=899) and on long-term treatment (n=2353) had been assessed and quantified in 36% and 31%, respectively, while for review of side effects, the respective proportions were 46% and 43%. Planned treatment breaks were documented in 317 (13%) of those on long-term treatment. CONCLUSIONS: Melatonin was predominantly prescribed for evidence-based clinical indications, but the clinical review and monitoring of this treatment fell short of best practice. CLINICAL IMPLICATIONS: With limited methodical review of melatonin use in their patients, clinicians will fail to garner reliable information on its risks and benefits for individual patients. The lack of such practice-based evidence may increase the risk of melatonin being inappropriately targeted or continued despite being ineffective or no longer indicated.

Asunto(s)

Auditoría Clínica , Melatonina , Humanos , Melatonina/uso terapéutico , Melatonina/administración & dosificación , Niño , Adolescente , Reino Unido , Femenino , Masculino , Estudios Retrospectivos , Preescolar , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Lactante , Depresores del Sistema Nervioso Central/uso terapéutico

RESUMEN

Diclofenac (DF), a non-steroidal anti-inflammatory drug, is commonly used to relieve pain and inflammation. High doses of DF might induce acute kidney injury (AKI), particularly in elderly, a known vulnerable population. AIM: We aimed to assess the protective role of melatonin (Mel) on DF-induced AKI in aged rats and to highlight the underpinning mechanisms include, oxidative stress and inflammation focusing on microRNA-34a (miR-34a), nuclear factor erythroid-2-related factor-2/hemeoxygenase-1 (Nrf2/HO-1) and NLR family-pyrin domain containing-3 (NLRP3) inflammasome pathways, and to elucidate the possibility of epithelial sodium channel (ENaC) involvement. MATERIALS AND METHODS: Thirty old male Wistar rats were allocated randomly into 3 groups: Control, DF and Mel-DF groups. KEY FINDINGS: Melatonin provided nephroprotective effects against DF-induced AKI via attenuating the expression of renal miR-34a and subsequently promoting the signaling of Nrf2/HO-1 with elevation of the antioxidant defense capacity and suppressing NLRP3 inflammasomes. Melatonin alleviated DF-induced hypernatremia via decreasing the ENaC expression. Renal histopathological examination revealed significant reduction in vascular congestion, mononuclear infiltration, glomerulo-tubular damage, fibrosis and TNF-α optical density. SIGNIFICANCE: It can be assumed that melatonin is a promising safe therapeutic agent in controlling DF-induced AKI in elderly.

Asunto(s)

Lesión Renal Aguda , Antiinflamatorios no Esteroideos , Diclofenaco , Melatonina , Estrés Oxidativo , Ratas Wistar , Animales , Melatonina/farmacología , Melatonina/uso terapéutico , Masculino , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Ratas , Antiinflamatorios no Esteroideos/farmacología , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Sustancias Protectoras/farmacología , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo

RESUMEN

BACKGROUND: Patients with lung cancer exhibit the poorest outcomes when infected with coronavirus disease 2019 (COVID-19). However, the potential impact of COVID-19 on the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) remains unknown. METHODS: Expression data and clinical information were sourced from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognostic, differentially expressed circadian-related genes (CRGs) were identified using multivariate Cox regression and LASSO regression analyses to establish an immune-related gene signature. The clinical value, immune landscape, somatic mutations, and drug sensitivity of high- and low-risk groups were assessed using Kaplan-Meier curves and immunotherapy cohorts. Finally, in vitro and in vivo experiments were conducted to elucidate the molecular function of melatonin in regulating the immune microenvironment and therapeutic resistance. RESULTS: Three circadian-related patterns and distinct CRGs clusters were identified based on the abnormal expression of 13 CRGs. Circadian genomic phenotypes were identified based on 13 circadian phenotype-related differentially expressed genes (DEGs). A CRGs risk signature was constructed; the high CRGs risk group displayed an immunosuppressive TME, poor survival, and therapy resistance. Melatonin reversed EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance by regulating immune cell infiltration into the TME, both in vitro and in vivo. CONCLUSIONS: The investigation revealed crosstalk between CRGs signatures and immune infiltration patterns in LUAD and COVID-19. Melatonin acted as a promising agent to suppress the malignant features of lung cancer and enhance treatment sensitivity by modulating the TME.

Asunto(s)

Adenocarcinoma del Pulmón , COVID-19 , Resistencia a Antineoplásicos , Neoplasias Pulmonares , Melatonina , Inhibidores de Proteínas Quinasas , SARS-CoV-2 , Microambiente Tumoral , COVID-19/inmunología , COVID-19/genética , Humanos , Melatonina/uso terapéutico , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , SARS-CoV-2/inmunología , Resistencia a Antineoplásicos/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Receptores ErbB/genética , Animales , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Transcriptoma , Femenino , Masculino , Ritmo Circadiano/genética

RESUMEN

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of unknown etiology characterized by infiltration of encephalitogenic cells in the central nervous system (CNS) resulting in the presence of multifocal areas of demyelination leading to neurodegeneration. The infiltrated immune cells population is composed mainly of effector CD4+ and CD8+ T lymphocytes, B cells, macrophages, and dendritic cells that secrete pro-inflammatory factors that eventually damage myelin leading to axonal damage. The most common clinical form of MS is relapsing-remitting (RR), characterized by neuroinflammatory episodes followed by partial or total recovery of neurological deficits. The first-line treatment for RRMS relapses is a high dose of glucocorticoids, especially methylprednisolone, for three to five consecutive days. Several studies have reported the beneficial effects of melatonin in the context of neuroinflammation associated with MS or experimental autoimmune encephalomyelitis (EAE), the preclinical model for MS. Therefore, the objective of this study was to evaluate the effect of the combined treatment of melatonin and methylprednisolone on the neuroinflammatory response associated with the EAE development. This study shows for the first time the protective synergistic effect of co-treatment with melatonin and methylprednisolone on reducing the severity of EAE by decreasing CD4 lymphocytes, B cells, macrophages and dendritic cells in the CNS, as well as modulating the population of infiltrated T and B cells toward regulatory phenotypes to the detriment of pro-inflammatory effector functions. In addition to the potentiation of the protective role of methylprednisolone, treatment with melatonin from the clinical onset of EAE improves the natural course of the EAE and the response to a subsequent treatment with methylprednisolone in a later relapse of the disease, pointing melatonin as potential therapeutic tool in combination with methylprednisolone for the treatment of relapses in MS.

Asunto(s)

Modelos Animales de Enfermedad , Sinergismo Farmacológico , Encefalomielitis Autoinmune Experimental , Melatonina , Metilprednisolona , Esclerosis Múltiple , Melatonina/farmacología , Melatonina/uso terapéutico , Melatonina/administración & dosificación , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Animales , Metilprednisolona/farmacología , Metilprednisolona/uso terapéutico , Ratones , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Femenino , Enfermedades Neuroinflamatorias/etiología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/inmunología , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo

RESUMEN

BACKGROUND: To investigate whether melatonin supplementation can enhance cardiometabolic risk factors, reduce oxidative stress, and improve hormonal and pregnancy-related factors in patients with PCOS. METHODS: We conducted a systematic search of PubMed/Medline, Scopus, and the Cochrane Library for articles published in English from inception to March 2023. We included randomized controlled trials (RCTs) on the use of melatonin for patients with polycystic ovary syndrome (PCOS). We performed a meta-analysis using a random-effects model and calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs). RESULTS: Six studies met the inclusion criteria. The result of meta-analysis indicated that melatonin intake significantly increase TAC levels (SMD: 0.87, 95% CI: 0.46, 1.28, I2 = 00.00%) and has no effect on FBS, insulin, HOMA-IR, TC, TG, HDL, LDL, MDA, hs-CRP, mFG, SHBG, total testosterone, and pregnancy rate in patients with PCOS compare to controls. The included trials did not report any adverse events. CONCLUSION: Melatonin is a potential antioxidant that may prevent damage from oxidative stress in patients with PCOS. However, the clear effect of melatonin supplementation on cardiometabolic risk factors, hormonal outcomes, and pregnancy-related outcomes needs to be evaluated further in large populations and long-term RCTs.

Asunto(s)

Factores de Riesgo Cardiometabólico , Suplementos Dietéticos , Melatonina , Estrés Oxidativo , Síndrome del Ovario Poliquístico , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Melatonina/farmacología , Melatonina/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/sangre , Femenino , Estrés Oxidativo/efectos de los fármacos , Embarazo , Hormonas/sangre , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/administración & dosificación

RESUMEN

According to our preliminary study, melatonin and its N-amide derivatives (N-(2-(1-4-bromobenzoyl-5-methoxy-1H-indol-3-yl)ethyl)acetamide (BBM) and 4-bromo-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)benzamide (EBM)) inhibited the marker of acute inflammation in tests in vitro and in vivo. The anti-inflammatory agent is intended for the prevention and treatment of chemotherapy-induced toxicity. In this study aimed to evaluate the effect of melatonin and its derivatives on mechanisms related to chemotherapy-induced oral mucositis by in vitro ROS and 5-FU-induced human keratinocyte cells as well as in vivo oral mucositis model. In in vitro H2O2-induced HaCaT cells, BBM had the highest level of protection (34.57%) at a concentration 50 µM, followed by EBM (26.41%), and melatonin (7.9%). BBM also protected cells against 5-FU-induced to 37.69-27.25% at 12.5-100 µM while EBM was 36.93-29.33% and melatonin was 22.5-11.39%. In in vivo 5-FU-induced oral mucositis in mice, melatonin, BBM, and EBM gel formulations protected tissue damage from 5-FU similar to the standard compound, benzydamine. Moreover, the weight of mice and food consumption recovered more quickly in the BBM group. These findings suggested that it was possible to develop BBM and EBM as new therapeutic agents for the treatment of oral mucositis.

Asunto(s)

Melatonina , Estomatitis , Melatonina/farmacología , Melatonina/uso terapéutico , Estomatitis/inducido químicamente , Estomatitis/tratamiento farmacológico , Estomatitis/prevención & control , Estomatitis/patología , Animales , Humanos , Ratones , Queratinocitos/efectos de los fármacos , Fluorouracilo/efectos adversos , Fluorouracilo/toxicidad , Masculino , Especies Reactivas de Oxígeno/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis and high mortality rates. Therefore, it is necessary to identify new targets and therapeutic strategies to improve the prognosis of patients with PDAC. Integrative therapies are increasingly being used to boost the efficacy of the known anticancer therapeutic approaches. Hence, this study aimed to evaluate the effects of a novel combination of different potential anticancer molecules, melatonin (MLT), cannabidiol (CBD), and oxygen-ozone (O2/O3) to treat PDAC using in vitro and in vivo models of human PDAC. The effect of this combination was investigated in combination with gemcitabine (GEM), the most common chemotherapeutic drug used for PDAC treatment. The combination of MLT + CBD + O2/O3 was more effective than the individual treatments in inhibiting PDAC cell viability and proliferation, inducing cell death, and modulating the RAS pathway protein levels. Moreover, different combinations of treatments reduced tumor mass in the PDAC mouse model, thus promoting the effect of GEM. In conclusion, a mixture of MLT + CBD + O2/O3 could serve as a potential adjuvant therapeutic strategy for PDAC.

Asunto(s)

Carcinoma Ductal Pancreático , Melatonina , Neoplasias Pancreáticas , Melatonina/farmacología , Melatonina/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Humanos , Animales , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Ratones , Línea Celular Tumoral , Gemcitabina , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Supervivencia Celular/efectos de los fármacos

RESUMEN

BACKGROUND: Oxidative stress is a well-known pathological factor driving neuronal loss and age-related neurodegenerative diseases. Melatonin, coenzyme Q10 and lecithin are three common nutrients with an antioxidative capacity. Here, we examined the effectiveness of them administrated individually and in combination in protecting against oxidative stress-induced neuronal death in vitro, and neurodegenerative conditions such as Alzheimer's disease and associated deficits in vivo. METHODS: Mouse neuroblastoma Neuro-2a (N2a) cells were exposed with H2O2 for 6 h, and subsequently treated with melatonin, coenzyme Q10, and lecithin alone or in combination for further 24 h. Cell viability was assessed using the CCK-8 assay. Eight-week-old male mice were intraperitoneally injected with D-(+)-galactose for 10 weeks and administrated with melatonin, coenzyme Q10, lecithin, or in combination for 5 weeks starting from the sixth week, followed by behavioral tests to assess the effectiveness in mitigating neurological deficits, and biochemical assays to explore the underlying mechanisms. RESULTS: Exposure to H2O2 significantly reduced the viability of N2a cells and increased oxidative stress and tau phosphorylation, all of which were alleviated by treatment with melatonin, coenzyme Q10, lecithin alone, and, most noticeably, by combined treatment. Administration of mice with D-(+)-galactose-induced oxidative stress and tau phosphorylation, brain aging, impairments in learning and memory, anxiety- and depression-like behaviors, and such detrimental effects were mitigated by melatonin, coenzyme Q10, lecithin alone, and, most consistently, by combined treatment. CONCLUSIONS: These results suggest that targeting oxidative stress via supplementation of antioxidant nutrients, particularly in combination, is a better strategy to alleviate oxidative stress-mediated neuronal loss and brain dysfunction due to age-related neurodegenerative conditions.

Asunto(s)

Antioxidantes , Peróxido de Hidrógeno , Neuronas , Estrés Oxidativo , Ubiquinona , Animales , Estrés Oxidativo/efectos de los fármacos , Ratones , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Ubiquinona/administración & dosificación , Masculino , Antioxidantes/farmacología , Peróxido de Hidrógeno/toxicidad , Neuronas/efectos de los fármacos , Neuronas/patología , Línea Celular Tumoral , Melatonina/farmacología , Melatonina/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Proteínas tau/metabolismo , Fármacos Neuroprotectores/farmacología , Galactosa/toxicidad , Quimioterapia Combinada

RESUMEN

BACKGROUND: The prevalence of dementia around the world is increasing, and these patients are more likely to have cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorders over their lifetime. Previous studies have proven that melatonin could improve memory loss, but its specific mechanism is still confused. METHODS: In this study, we used in vivo and in vitro models to examine the neuroprotective effect of melatonin on scopolamine (SCOP)-induced cognitive dysfunction. The behavioral tests were performed. 18F-FDG PET imaging was used to assess the metabolism of the brain. Protein expressions were determined through kit detection, Western blot, and immunofluorescence. Nissl staining was conducted to reflect neurodegeneration. MTT assay and RNAi transfection were applied to perform the in vitro experiments. RESULTS: We found that melatonin could ameliorate SCOP-induced cognitive dysfunction and relieve anxious-like behaviors or HT22 cell damage. 18F-FDG PET-CT results showed that melatonin could improve cerebral glucose uptake in SCOP-treated mice. Melatonin restored the cholinergic function, increased the expressions of neurotrophic factors, and ameliorated oxidative stress in the brain of SCOP-treated mice. In addition, melatonin upregulated the expression of silent information regulator 1 (SIRT1), which further relieved endoplasmic reticulum (ER) stress by decreasing the expression of phosphorylate inositol-requiring enzyme (p-IRE1α) and its downstream, X-box binding protein 1 (XBP1). CONCLUSIONS: These results indicated that melatonin could ameliorate SCOP-induced cognitive dysfunction through the SIRT1/IRE1α/XBP1 pathway. SIRT1 might be the critical target of melatonin in the treatment of dementia.

Asunto(s)

Disfunción Cognitiva , Melatonina , Escopolamina , Transducción de Señal , Sirtuina 1 , Proteína 1 de Unión a la X-Box , Melatonina/farmacología , Melatonina/uso terapéutico , Animales , Sirtuina 1/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Proteína 1 de Unión a la X-Box/metabolismo , Ratones , Masculino , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Aprendizaje por Laberinto/efectos de los fármacos

RESUMEN

BACKGROUND: Melatonin is a hormone produced by the pineal gland and it has antioxidant properties. AIM: This study aimed to evaluate the effects of melatonin on assisted reproductive technologies through a systematic review and a meta-analysis. MATERIALS AND METHODS: Search strategies were used in PubMed and in other databases covering the last 15 years. After screening for eligibility, 17 articles were selected for the systematic review. For the meta-analysis statistics, two groups were formed, the treatment group (with melatonin) and the control group (without melatonin) for various assisted reproduction outcomes. RESULTS: The main results were that no statistical differences were found concerning the clinical pregnancy outcome (p = 0.64), but there was a statistical difference with respect to Mature Oocytes (MII) (p = 0.001), antral follicle count (p = 0.0002), and the fertilization rate (p ≤ 0.0001). CONCLUSIONS: Melatonin had beneficial effects such as the improvement in the fertilization rate, although the authors did not obtain significance in the clinical pregnancy rate.

Asunto(s)

Melatonina , Índice de Embarazo , Melatonina/uso terapéutico , Melatonina/farmacología , Humanos , Femenino , Embarazo , Técnicas Reproductivas Asistidas , Antioxidantes/farmacología , Fertilización In Vitro/métodos , Fertilización In Vitro/efectos de los fármacos , Resultado del Embarazo , Fertilización/efectos de los fármacos , Fertilización/fisiología

RESUMEN

INTRODUCTION: Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia. METHODS AND ANALYSIS: This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels). ETHICS AND DISSEMINATION: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen's University Health Sciences Research Ethics Board (Queen's HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings. TRIAL REGISTRATION NUMBER: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.

Asunto(s)

Estudios Cruzados , Quimioterapia Combinada , Fibromialgia , Melatonina , Pregabalina , Humanos , Fibromialgia/tratamiento farmacológico , Melatonina/uso terapéutico , Melatonina/administración & dosificación , Pregabalina/uso terapéutico , Pregabalina/administración & dosificación , Método Doble Ciego , Adulto , Analgésicos/uso terapéutico , Analgésicos/administración & dosificación , Femenino , Persona de Mediana Edad , Manejo del Dolor/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Dimensión del Dolor , Dolor Crónico/tratamiento farmacológico , Resultado del Tratamiento

RESUMEN

Melatonin is a pineal hormone that regulates testicular activity (i.e., steroidogenesis and spermatogenesis) through two complementary mechanisms, indirect effects exerted via the hypothalamic-adenohypophyseal axis and direct actions that take place on the different cell populations of the male gonad. The effects of increased age on the testis and the general mechanisms involved in testicular pathology leading to infertility are still only poorly understood. However, there is growing evidence that link testicular aging and idiopathic male infertility to local inflammatory and oxidative stress events. Because literature data strongly indicate that melatonin exhibits anti-inflammatory and anti-oxidant properties, this review focuses on the potential benefits exerted by this indoleamine at testicular level in male reproductive fertility and aging. Taking into account that the effects of melatonin supplementation on testicular function are currently being investigated, the overview covers not only promising prospects but also many questions concerning the future therapeutic value of this indoleamine as an anti-aging drug as well as in the management of cases of male infertility for which there are no medical treatments currently available.

Asunto(s)

Envejecimiento , Antiinflamatorios , Antioxidantes , Infertilidad Masculina , Melatonina , Testículo , Masculino , Melatonina/uso terapéutico , Melatonina/farmacología , Humanos , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Testículo/efectos de los fármacos , Testículo/metabolismo , Infertilidad Masculina/tratamiento farmacológico , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Animales , Estrés Oxidativo/efectos de los fármacos