Abstract Melatonin is a neuro-hormone with conserved roles in evolution. Initially synthetized as an antioxidant molecule, it has gained prominence as a key molecule in the regulation of the circadian rhythm. Melatonin exerts its effect by binding to cytoplasmic and intra-nuclear receptors, and is able to regulate the expression of key mediators of different signaling pathways. This ability has led scholars to investigate the role of melatonin in reversing the process of carcinogenesis, a process in which many signaling pathways are involved, and regulating these pathways may be of clinical significance. In this review, the role of melatonin in regulating multiple signaling pathways with important roles in cancer progression is discussed, and evidence regarding the beneficence of targeting malignancies with this approach is presented.
Abstract Accumulation of random molecular damage such as oxidative DNA damage and inflammation is extremely found to be involved in the aging process. Due to extreme energy requirements and high lipid levels, the brain is more susceptible to oxidative damage during aging especially under exposure to toxic elements such as arsenic. Therefore, this study was aimed to evaluate the ameliorative effects of melatonin, as a neurohormone, on the arsenic‐induced behavioral abnormalities, and the underlying mechanisms. Forty‐eight rats, as young and old aged groups were exposed to 5.55 g/kg body weight arsenic for 4 weeks and then 10 mg/kg melatonin for 2 weeks. Our results showed that arsenic led to anxiety‐like behavioral abnormalities in rats. Increased oxidative stress‐induced damage to DNA, lipids and proteins, decreased potential of antioxidant defense system, induced apoptosis, elevated inflammation, and alteration in the histology of cortical region of brains are observed in the rats exposed to arsenic. These effects were more prominent in aged rats in comparison to young rats. Melatonin successfully attenuates arsenic induced adverse effects on the brain in both age groups. In conclusion, our study shows that melatonin has significant ameliorative impact on age‐dependent cytotoxicity of arsenic in rats' brains.
N-[2-(5-methoxy-1H-indol-3-yl) ethyl] or simply melatonin is a biogenic amine produced by pineal gland and recently recognized various other organs. Because of a broad range of biological function melatonin is considered as a therapeutic agent with high efficacy in the treatment of multiple disorders, such as cancer, degenerative disorders and immune disease. However, since melatonin can affect receptors on the cellular membrane, in the nucleus and can act as an anti-oxidant molecule, some unwanted effects may be observed after administration. Therefore, the entrapment of melatonin in biocompatible, biodegradable and safe nano-delivery systems can prevent its degradation in circulation; decrease its toxicity with increased half-life, enhanced pharmacokinetic profile leading to improved patient compliance. Because of this, nanoparticles have been used to deliver melatonin in multiple studies, and the present article aims to cumulatively illustrate their findings.
Atherosclerosis is identified as the formation of atherosclerotic plaques, which could initiate the formation of a blood clot in which its growth to coronary artery can lead to a heart attack. N‐methyltransferase (NNMT) is an enzyme that converts the NAM (nicotinamide) to its methylated form, N1‐methylnicotinamide (MNAM). Higher levels of MNAM have been reported in cases with coronary artery disease (CAD). Further, MNAM increases endothelial prostacyclin (PGI2) and nitric oxide (NO) and thereby causes vasorelaxation. The vasoprotective, anti‐inflammatory and anti‐thrombotic roles of MNAM have been well documented; however, the exact underlying mechanisms remain to be clarified. Due to potential role of MNAM in the formation of lipid droplets (LDs), it might exert its function in coordination with lipids, and their targets. In this study, we summarized the roles of MNAM in cardiovascular system and highlighted its possible mode of actions.
Abstract Different strategies are applied for cellular cross‐talk and organization in multicellular organisms. Exosomes are a homogenous population of biological nanoparticles (30–100 nm), originated from multivesicular bodies. The exosomes (Exos) could regulate and affect both cellular physiology and pathophysiology in various organs, such as the female reproductive tract, by altering gene pathways and/or epigenetic programming. Besides, engineered Exos have the potential to be used as a novel drug and gene delivery tools. Here in this review, we discussed various aspects of exosome‐based intercellular communication in female reproductive microenvironments. Furthermore, we addressed the findings and issues related to Exos in reproductive biology to give a better view of the involved molecular mechanisms. Moreover, clinical applications of the Exos and their isolation source/methods have been considered to throw some light on the progression of new biological, diagnostic, and therapeutic approaches in clinical embryology.
Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian function, especially angiogenesis and follicular development. The actions of VEGF can be antagonized by its soluble receptors, soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble VEGF receptor 2 (sVEGFR-2), as they decrease its free form. In the present study, we evaluated the relationship between follicular fluid (FF) levels of AMD2, VEGF and its soluble receptors, and ICSI outcomes. Materials and Methods ICSI cycle outcomes were evaluated and FF levels of VEGF, sFlt-1, sVEGFR-2 and ADM2 were determined using ELISA kits. Results FF levels of ADM2, VEGF, and sVEGFR-2 were significantly higher in non-responders compared to other ovarian response groups (p < 0.05). There were significant correlations between ADM2, VEGF and sVEGFR-2 levels as well as VEGF/sFlt-1 and VEGF/sVEGFR-2 ratios (r = 0.586, 0.482, 0.260, and - 0.366, respectively). Based on the ROC curve, the cutoff value for ADM2 as a non-responder predictor was 348.55 (pg/ml) with a sensitivity of 67.7% and a specificity of 94.6%. Conclusions For the first time we measured FF ADM2 levels to determine the relationship to VEGF and its soluble receptors. We suggest that ADM2 could be a potential predictive marker for non-responders. Although the exact function of ADM2 in ovarian angiogenesis is not yet understood, our study may shed light on the possible role of ADM2 in folliculogenesis and ovulation.Einleitung Adrenomedullin 2 (ADM2) und der vaskuläre endotheliale Wachstumsfaktor (VEGF) wirken sich auf die ovarielle Funktion aus, insbesondere auf Angiogenese und Follikelentwicklung. Die Wirkung von VEGF kann durch seine löslichen Rezeptoren (den löslichen Fms-ähnlichen Tyrosinkinase-1 [sFlt-1] und den löslichen VEGF-Rezeptor 2 [sVEGFR-2]) antagonisiert werden, da diese Rezeptoren die freie Form von VEGF reduzieren. In dieser Studie haben wir den Zusammenhang zwischen den Follikelflüssigkeitsspiegeln von AMD2, VEGF und dessen löslichen Rezeptoren und dem Outcome nach ICSI untersucht. Material und Methoden Das Outcome nach ICSI-Zyklen wurde evaluiert und die Follikelflüssigkeitsspiegel von VEGF, sFlt-1, sVEGFR-2 und ADM2 wurden mithilfe von ELISA Kits bestimmt. Ergebnisse Die ADM2-, VEGF- und sVEGFR-2-Spiegel in der FF waren signifikant höher in der Gruppe von Frauen ohne ovarielle Reaktion verglichen mit anderen Gruppen mit ovarieller Reaktion (p < 0,05). Signifikante Korrelationen wurden zwischen den ADM2-, VEGF- und sVEGFR-2-Spiegeln sowie den VEGF/sFlt-1- und VEGF/sVEGFR-2-Quotienten festgestellt (r = 0,586, 0,482, 0,260 bzw. − 0,366). Gemäß der ROC-Kurve betrug der Cut-off-Wert für ADM2 als Prädiktor für keine ovarielle Reaktion 348,55 (pg/ml) mit einer Sensitivität von 67,7% und einer Spezifität von 94,6%. Schlussfolgerungen Wir haben zum ersten Mal die Follikelflüssigkeitsspiegel von ADM2 gemessen und diese Werte mit den Werten von VEGF sowie dessen lösliche Rezeptoren in Beziehung gesetzt. Wir weisen darauf hin, dass ADM2 potenziell ein prädiktiver Marker für das Fehlen einer ovariellen Reaktion sein könnte. Obwohl die genaue Funktion von ADM2 bei der ovariellen Angiogenese noch nicht vollständig geklärt ist, konnte unsere Studie etwas Licht auf auf die möglichen Rollen von ADM2 bei der Follikulogenese und der Ovulation werfen.
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