PMID: 

Neurochem Int. 2020 Jan ;132:104601. Epub 2019 Nov 12. PMID: 31726088

Abstract Title: 

Melatonin attenuates streptozotocin-induced Alzheimer-like features in hyperglycemic rats.

Abstract: 

Diabetes mellitus (DM) is increasingly recognized as a risk for developing of Alzheimer's disease (AD). Accordingly, it has been reported that melatonin level is disturbed in both DM and AD which indicates its involvement in the pathophysiology of these diseases. In this study, the neuroprotective activities and relevant mechanisms of melatonin were evaluated in diabetic rat model. Rats were subcutaneously injected with melatonin (10 mg/kg) for 42 consecutive days. Single dose of streptozotocin (60 mg/kg STZ) was intraperitoneally injected. Morris water maze, Western blot and immunohistochemistry analysis of proteins in the hippocampus were measured. We found that melatonin was effective in protecting against memory impairment and decreased formation of Aβ42 peptide and phosphorylated tau in the hippocampus of STZ-treated rats. Melatonin significantly restored the reduction in phospho-insulin receptor β (p-IRβ) and ameliorated the increase of inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) in STZ-treated rats. Furthermore, it restored the phosphorylation of glycogen synthase kinase 3β (GSK3β), indicating a decreased activity of GSK3β. Melatonin prevented amyloidogenic processing of β-amyloid precursor protein (βAPP) by significantly inhibited β-site APP cleaving enzyme (BACE1), presenilin 1 (PS1), and β-cleaved C-terminal fragment (C99). In conclusion, melatonin ameliorates memory deficits in STZ-induced hyperglycemia rats by restoring insulin signaling pathway which is independent of its effects on blood glucose and insulin levels. Thus, melatonin might be a therapeutic optionfor helping patients suffering from diabetes and contributed to Alzheimer's disease.

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PMID: 

Nefrologia. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31735377

Abstract Title: 

Melatonin ameliorates the drug induced nephrotoxicity: Molecular insights.

Abstract: 

BACKGROUND: Drug-induced nephrotoxicity is a frequent adverse event that can lead to acute or chronic kidney disease and increase the healthcare expenditure. It has high morbidity and mortality incidence in 40-70% of renal injuries and accounts for 66% cases of renal failure in elderly population.OBJECTIVE: Amelioration of drug-induced nephrotoxicity has been long soughed to improve the effectiveness of therapeutic drugs. This study was conducted to review the melatonin potential to prevent the pathogenesis of nephrotoxicity induced by important nephrotoxic drugs.METHODS: We analyzed the relevant studies indexed in Pubmed, Medline, Scielo and Web of science to explain the molecular improvements following melatonin co-administration with special attention to oxidative stress, inflammation and apoptosis as key players of drug-induced nephrotoxicity.RESULTS: A robust consensus among researchers of these studies suggested that melatonin efficiently eradicate the chain reaction of free radical production and induced the endogenous antioxidant enzymes which attenuate the lipid peroxidation of cellular membranes and subcellular oxidative stress in drug-induced nephrotoxicity. This agreement was further supported by the melatonin role in disintegration of inflammatory process through inhibition of principle pro-inflammatory or apoptotic cytokines such as TNF-α and NF-κB. These studies highlighted that alleviation of drug-induced renal toxicity is a function of melatonin potential to down regulate the cellular inflammatory and oxidative injury process and to stimulate the cellular repair or defensive mechanisms.CONCLUSION: The comprehensive nephroprotection and safer profile suggests the melatonin to be a useful adjunct to improve the safety of nephrotoxic drugs.

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PMID: 

J Reprod Dev. 2019 Nov 15. Epub 2019 Nov 15. PMID: 31735743

Abstract Title: 

Melatonin protects against Epirubicin-induced ovarian damage.

Abstract: 

One major side effect of chemotherapy that young women with cancer suffer from is ovarian damage. Therefore, it is necessary to study the pathogenesis of chemotherapeutic drugs in order to develop pharmaceutical agents to preserve fertility. Epirubicin is one of the commonly used chemotherapy drugs for breast cancer patients. This research explored the side effects of epirubicin in mice. We found that epirubicin significantly reduced the body weight, the weight of the ovaries and uteri, and the pups' number, while melatonin, which is extremely resistant to oxidation, significantly reduced these damages. Moreover, co-treatment with melatonin prevented epirubicin-induced decrease in Eand progesterone, and the loss of follicles. Mechanism study showed that melatonin significantly reduced the levels of proapoptotic genes p53, Caspase3, and Caspase9 while it upregulated antiapoptotic factors Bcl-2 and Bcl2l1, and antioxidant genes superoxide dismutase 1 and catalase compared with the epirubicin group. In addition, melatonin markedly reduced reactive oxygen species (ROS) and the transcription of Caspase12 and Chop, which is vital in endoplasmic reticulum stress (ERS)-mediated apoptosis. These results indicate melatonin protects against epirubicin-induced ovarian damage by reducing ROS-induced ERS. Therefore, melatonin has a therapeutic potential for the protection of ovarian function and preservation of fertility during chemotherapy.

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PMID: 

Front Endocrinol (Lausanne). 2019 ;10:750. Epub 2019 Nov 5. PMID: 31749764

Abstract Title: 

Melatonin Supplementation Decreases Hypertrophic Obesity and Inflammation Induced by High-Fat Diet in Mice.

Abstract: 

Obesity results from critical periods of positive energy balance characterized by caloric intake greater than energy expenditure. This disbalance promotes adipose tissue dysfunction which is related to other comorbidities. Melatonin is a low-cost therapeutic agent and studies indicate that its use may improve obesity-related disorders. To evaluate if the melatonin is efficient in delaying or even blocking the damages caused by excessive ingestion of a high-fat diet (HFD) in mice, as well as improving the inflammatory profile triggered by obesity herein, male C57BL/6 mice of 8 weeks were induced to obesity by a HFD and treated for 10 weeks with melatonin. The results demonstrate that melatonin supplementation attenuated serum triglyceride levels and total and LDL cholesterol and prevented body mass gain through a decreased lipogenesis rate and increased lipolytic capacity in white adipocytes, with a concomitant increment in oxygen consumption andandexpression. Altogether, these effects prevented adipocyte hypertrophy caused by HFD and reflected in decreased adiposity. Finally, melatonin supplementation reduced the crown-like-structure (CLS) formation, characteristic of the inflammatory process by macrophage infiltration into white adipose tissue of obese subjects, as well as decreased the gene expression of inflammation-related factors, such as leptin and MCP1. Thus, the melatonin can be considered a potential therapeutic agent to attenuate the metabolic and inflammatory disorders triggered by obesity.

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PMID: 

J Pineal Res. 2019 Nov 27:e12627. Epub 2019 Nov 27. PMID: 31773776

Abstract Title: 

Melatonin enhances mitochondrial biogenesis and protects against rotenone-induced mitochondrial deficiency in early porcine embryos.

Abstract: 

Melatonin, a major hormone of the pineal gland, exerts many beneficial effects on mitochondria. Several studies have shown that melatonin can protect against toxin-induced oocyte quality impairment during maturation. However, there is little information regarding the beneficial effects of melatonin on toxin-exposed early embryos, and the mechanisms underlying such effects have not been determined. Rotenone, a chemical widely used in agriculture, induces mitochondrial toxicity, therefore, damaging the reproductive system, impairing oocyte maturation, ovulation, and fertilization. We investigated whether melatonin attenuated rotenone exposure-induced impairment of embryo development by its mitochondrial protection effect. Activated oocytes were randomly assigned to four groups, the control, melatonin treatment, rotenone-exposed, and"rotenone + melatonin"groups. Treatment with melatonin abrogated rotenone-induced impairment of embryo development, mitochondrial dysfunction, and ATP deficiency, and significantly decreased oxidative stress and apoptosis. Melatonin also increased SIRT1 and PGC-1α expression, which promoted mitochondrial biogenesis. SIRT1 knockdown or pharmacological inhibition abolished melatonin's ability to revert rotenone-induced impairment. Thus, melatonin rescued rotenone-induced impairment of embryo development by reducing ROS production and promoting mitochondrialbiogenesis. This study shows that melatonin rescues toxin-induced impairment of early porcine embryo development by promoting mitochondrial biogenesis.

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PMID: 

Bull Exp Biol Med. 2019 Dec ;168(2):242-246. Epub 2019 Nov 27. PMID: 31776954

Abstract Title: 

Melatonin Stimulates Epithelium Migration in Wound Models In Vitro and In Vivo.

Abstract: 

We studied the effect of bovine brain gangliosides, individual ganglioside GM1, and melatonin on the rate of wound closure under in vitro conditions and the effect of melatonin on the rate of wound healing under in vivo conditions. It was shown that bovine brain gangliosides and melatonin reliably increased cell migration in the experimental wound model. This effect was detected when the cell cultures were treated with the test preparations after wound infliction and when the cultures of human keratinocytes were pretreated before wounding. Analysis of the effect of melatonin on the rate of wound healing in vivo showed that melatonin accelerated this process, especially at the middle stages corresponding to the proliferation phase (days 3-6 after surgery). Histological analysis revealed intensification of epidermal cell proliferation at the edges of the wound starting from day 4 after surgery.

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PMID: 

Cardiovasc Res. 2019 Nov 27. Epub 2019 Nov 27. PMID: 31774487

Abstract Title: 

Melatonin inhibits inflammasome-associated activation of endothelium and macrophages attenuating pulmonary arterial hypertension.

Abstract: 

AIM: Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome associated with pulmonary/systemic inflammation. Melatonin relieves PAH, but the molecular mode of action remains unclear. Here, we investigated the role of melatonin in normalizing vascular homeostasis.METHODS AND RESULTS: Light-time mean serum melatonin concentration was lower in patients with PAH than in normal controls (11.06± 3.44 (7.13-15.6) vs. 14.55 ± 1.28 (8.0-19.4) pg/ml), which was negatively correlated with increased serum levels of interleukin-1β (IL-1β) in patients with PAH. We showed that inflammasomes were activated in the PAH mice model and that melatonin attenuated IL-1β secretion. On one hand, melatonin reduced the number of macrophages in lung by inhibiting the endothelial chemokines and adhesion factors. Moreover, use of Il1r-/- mice, Caspase1/11-/- mice and melatonin-treated mice revealed that melatonin reduced hypoxia-induced vascular endothelial leakage in the lung. On the other hand, we verified that melatonin reduced the formation of inflammasome multiprotein complexes by modulating calcium ions in macrophages using a live cell station, and melatonin decreased inositol triphosphate and increased cAMP. Furthermore, knockdown of melatonin membrane receptors blocked melatonin function, and a melatonin membrane receptors agonist inactivated inflammasomes in macrophages.CONCLUSIONS: Melatonin attenuated inflammasome-associated vascular disorders by directly improving endothelial leakage and decreasing the formation of inflammasome multiprotein complexes in macrophages. Taken together, our data provide a theoretical basis for applying melatonin clinically, and inflammasomes may be a possible target of PAH treatment.TRANSLATIONAL PERSPECTIVE: PAH is a pathophysiological syndrome associated with inflammation. Our study is the first to report a decrease in melatonin levels in patients with PAH, which provides insight to investigate melatonin or other circadian rhythm-related factors in the etiology of PAH. We demonstrate that melatonin improved PAH by inactivating inflammasome in the lungs of several mice models. The fact that melatonin is an endogenous hormone, may present an advantage for PAH therapy. Our data provide a theoretical basis for applying melatonin clinically, and inflammasomes may be a possible target of PAH treatment.

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PMID: 

Sci Rep. 2019 Oct 8 ;9(1):14425. Epub 2019 Oct 8. PMID: 31595026

Abstract Title: 

Global gene expression analysis of Escherichia coli K-12 DH5α after exposure to 2.4 GHz wireless fidelity radiation.

Abstract: 

This study investigated the non-thermal effects of Wi-Fi radiofrequency radiation of 2.4 GHz on global gene expression in Escherichia coli K-12 DH5α. High-throughput RNA-sequencing of 2.4 GHz exposed and non-exposed bacteria revealed that 101 genes were differentially expressed (DEGs) at P ≤ 0.05. The up-regulated genes were 52 while the down-regulated ones were 49. QRT-PCRanalysis of pgaD, fliC, cheY, malP, malZ, motB, alsC, alsK, appB and appX confirmed the RNA-seq results. About 7% of DEGs are involved in cellular component organization, 6% in response to stress stimulus, 6% in biological regulation, 6% in localization, 5% in locomotion and 3% in cell adhesion. Database for annotation, visualization and integrated discovery (DAVID) functional clustering revealed that DEGs with high enrichment score included genes for localization of cell, locomotion, chemotaxis, response to external stimulus and cell adhesion. Kyoto encyclopedia of genes and genomes (KEGG) pathways analysis showed that the pathways for flagellar assembly, chemotaxis and two-component system were affected. Go enrichment analysis indicated that the up-regulated DEGs are involved in metabolic pathways, transposition, response to stimuli, motility, chemotaxis and cell adhesion. The down-regulated DEGs are associated with metabolic pathways and localization of ions and organic molecules. Therefore, the exposure of E. coli DH5α to Wi-Fi radiofrequency radiation for 5 hours influenced several bacterial cellular and metabolic processes.

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PMID: 

J Biomed Phys Eng. 2019 Oct ;9(5):579-586. Epub 2019 Oct 1. PMID: 31750272

Abstract Title: 

Evaluation of Wi-Fi Radiation Effects on Antibiotic Susceptibility, Metabolic Activity and Biofilm Formation by Escherichia0157H7,and.

Abstract: 

Background: The radiation emitted from electromagnetic fields (EMF) can cause biological effects on prokaryotic and eukaryotic cells, including non-thermal effects.Objective: The present study evaluated the non-thermal effects of wireless fidelity (Wi-Fi) operating at 2.4 GHz part of non-ionizing EMF on different pathogenic bacterial strains (0157H7,). Antibiotic resistance, motility, metabolic activity and biofilm formation were examined.Material and Methods: In this case-control, a Wi-Fi router was used as a source of microwaves and also bacterial cells were exposed to Wi-Fi radiation continuously for 24 and 48 hours. The antibiotic susceptibility was carried out using a disc diffusion method on Müller Hinton agar plates. Motility of0157H7 was conducted on motility agar plates. Cell metabolic activity and biofilm formation were performed using 3-(4, 5-Dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and crystal violet quantification, respectively.Results: The exposure to Wi-Fi radiation altered motility and antibiotic susceptibility of0157H7. However, there was no effect Wi-Fi radiation on antibiotic susceptibility of. On the other hand, the exposed cells, as compared to the unexposed control, showed an increased metabolic activity and biofilm formation ability in0157H7,.Conclusion: These results proposed that Wi-Fi exposure acted on bacteria in stressful manner by increasing antibiotic resistance and motility of0157H7, as well as enhancing biofilm formation by0157H7,. The findings may have implications for the management of serious diseases caused by these infectious bacteria.

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PMID: 

Pathophysiology. 2019 Nov 21. Epub 2019 Nov 21. PMID: 31785933

Abstract Title: 

Wi-Fi decreases melatonin protective effect and increases hippocampal neuronal damage in pentylenetetrazole induced model seizures in rats.

Abstract: 

AIM: Epilepsy is a common brain disorder in which the seizures could cause a neuronal loss in the hippocampus. Oxidative stress has an important role in the pathology of epilepsy. Some studies indicate that Wi-Fi increases oxidative stress and suppresses antioxidant systems. The aim of this study is to investigate the effect of Wi-Fi on melatonin anticonvulsive effect and oxidative damage in pentylenetetrazole-induced epileptic seizures in rats.METHODS: In our study, we used 30 male Wistar Albino rats, 230-250 grams of the body weight. The animals were divided into five groups as control, saline (1 ml/kg/day olive oil for 30 days), Wi-Fi (12 h/day for 30 days), melatonin (10 mg/kg/day for 30 days) and melatonin + Wi-Fi (10 mg/kg/day +12 h/day for 30 days). In the thirtieth day, thirty minutes after the last drugs administration at the indicated doses, PTZ in 45 mg/kg was administered to induce epileptic seizure. The animals were observed for 30 min during the seizure stages (according to the Racine Scale) and first myoclonic jerk times (FMJ). Twenty-four hours after PTZ injection, brain tissues were removed for biochemical and histopathological evaluation. The hippocampal Cornu Ammonis (CA) 1, CA3 and DG (dentate gyrus) regions were histopathologically evaluated in terms of a neuronal damage in addition that oxidative stress markers (total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) were measured in brain tissues.RESULTS: Wi-Fi was not found to affect behavioral changes associated with epilepsy (p > 0.05). However, Wi-Fi reduced anticonvulsive and antioxidant effect of melatonin (p 

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