Melatonin Exposure Research Articles

Investigation of the structural changes in the hippocampus and prefrontal cortex using FTIR spectroscopy in sleep deprived mice

Sleep is a basic, physiological requirement for living things to survive and is a process that covers one third of our lives. Melatonin is a hormone that plays an important role in the regulation of sleep. Sleep deprivation affect brain structures and functions. Sleep deprivation causes a decrease in brain activity, with particularly negative effects on the hippocampus and prefrontal cortex. Despite the essential role of protein and lipids vibrations, polysaccharides, fatty acid side chains functional groups, and ratios between amides in brain structures and functions, the brain chemical profile exposed to gentle handling sleep deprivation model versus Melatonin exposure remains unexplored. Therefore, the present study, aims to investigate a molecular profile of these regions using FTIR spectroscopy measurement’s analysis based on lipidomic approach with chemometrics and multivariate analysis to evaluate changes in lipid composition in the hippocampus, prefrontal regions of the brain. In this study, C57BL/6J mice were randomly assigned to either the control or sleep deprivation group, resulting in four experimental groups: Control (C) (n = 6), Control + Melatonin (C + M) (n = 6), Sleep Deprivation (S) (n = 6), and Sleep Deprivation + Melatonin (S + M) (n = 6). Interventions were administered each morning via intraperitoneal injections of melatonin (10 mg/kg) or vehicle solution (%1 ethanol + saline), while the S and S + M groups underwent 6 h of daily sleep deprivation from using the Gentle Handling method. All mice were individually housed in cages with ad libitum access to food and water within a 12-hour light–dark cycle. Results presented that the brain regions affected by insomnia. The structure of phospholipids, changed. Yet, not only changes in lipids but also in amides were noticed in hippocampus and prefrontal cortex tissues. Additionally, FTIR results showed that melatonin affected the lipids as well as the amides fraction in cortex and hippocampus collected from both control and sleep deprivation groups.

The dark side of apnea: altered 24-hour melatonin secretion in obstructive sleep apnea (OSAS) is disease severity dependent

PurposeMelatonin aids in the synchronization of the circadian rhythm to the external environment. Few studies have tried to elucidate the relationship between melatonin and obstructive sleep apnea syndrome (OSAS). These often include few patients, do not differentiate between OSAS severity and/or do not analyse a 24-h melatonin profile. This study set out to investigate disease severity dependent differences in 24-h salivary melatonin secretion of OSAS patients compared to a reference population in a retrospective design.Methods24-h salivary melatonin profiles of 169 OSAS patients were analysed (55 light, 66 moderate, 48 severe) as well as 91 reference patients. Several aspects of the melatonin curve were analysed and stratified according to OSAS severity. Parameters included: dim light melatonin onset (DLMO), time of returning below DLMO (DLMOoff), peak melatonin concentration and time, and total melatonin exposure.ResultsSignificant effects were corrected for confounding by age and sex using linear regression. Our analysis shows that, compared to reference and in a disease dependent manner, OSAS patients have a significantly lower 24-h melatonin curve, lower melatonin peak concentration, lower total melatonin exposure and a smaller proportion of patients reach DLMO. The differences in peak melatonin production and total melatonin exposure were resistant to confounding by age and/or sex.ConclusionThis study describes clear OSAS severity dependent abnormalities in melatonin production in OSAS patients, independent of sex and/or age. Future research should indicate whether oral melatonin supplementation has beneficial effects in OSAS patients with attenuated endogenous melatonin production.

Melatonin as a chronobiotic/cytoprotective agent in bone. Doses involved

AbstractBecause the chronobiotic and cytoprotective molecule melatonin diminishes with age, its involvement in postmenopausal and senescence pathology has been considered since long. One relevant melatonin target site in aging individuals is bone where melatonin chronobiotic effects mediated by MT1 and MT2 receptors are demonstrable. Precursors of bone cells located in bone marrow are exposed to high quantities of melatonin and the possibility arises that melatonin acts a cytoprotective compound via an autacoid effect. Proteins that are incorporated into the bone matrix, like procollagen type I c‐peptide, augment after melatonin exposure. Melatonin augments osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts. Osteoclasts are target cells for melatonin as they degrade bone partly by generating free radicals. Osteoclast activity and bone resorption are impaired via the free radical scavenger properties of melatonin. The administration of melatonin in chronobiotic doses (less than 10 mg daily) is commonly used in clinical studies on melatonin effect on bone. However, human equivalent doses allometrically derived from animal studies are in the 1–1.5 mg/kg/day range for a 75 kg human adult, a dose rarely used clinically. In view of the absence of toxicity of melatonin in phase 1 pharmacological studies with doses up to 100 mg in normal volunteers, further investigation is needed to determine whether high melatonin doses have higher therapeutic efficacy in preventing bone loss.

Melatonin as an Antimicrobial Adjuvant and Anti-Inflammatory for the Management of Recurrent Clostridioides difficile Infection.

Background:Clostridioides difficile (C. difficile) infection (CDI) is strongly associated with inflammation and has the potential to cause recurrent infections. Pre-clinical data suggest that melatonin has beneficial effects in the gastrointestinal tract due to its anti-inflammatory and antibacterial properties. This analysis examines the association between melatonin and the risk of recurrent CDI. Methods: A retrospective cohort study was conducted among patients with an inpatient diagnosis of CDI along with a positive C. difficile polymerase chain reaction (PCR) or enzyme immunoassay (EIA) test result. Patients were followed until the first study end point (death) or the first instance of recurrent infection. Propensity-score weighting was utilized accounting for confounding factors and weighted Cox models were estimated. Results: A total of 24,782 patients met the inclusion criteria, consisting of 3457 patients exposed to melatonin and 21,325 patients with no melatonin exposure. The results demonstrate that those exposed to melatonin were associated with a 21.6% lower risk of recurrent CDI compared to patients without melatonin exposure (HR = 0.784; 95% CI = 0.674-0.912). Conclusion: Our results demonstrate a decreased rate of recurrent CDI in patients exposed to melatonin. Further research on melatonin as an antimicrobial adjuvant and anti-inflammatory is warranted for the management of recurrent CDI.

The effect of the photoperiod on the serotonergic system of the thymus and its role in the ­implementation of the effects of exogenous melatonin

Background. It was believed that the functioning of the immune organs is photoindependent, but there are a number of works that testify to the effect of the photoperiod shift on the functioning of the immune organs. We hypothesized that the absence of a photoperiod under constant light or constant dark would affect the serotonergic system of the thymus gland, as well as the direction and intensity of melatonin exposure.
 Aim. Study of serotonin-containing thymus cells under conditions of experimental desynchronosis and the role of the photoperiod in the realization of the effects of exogenous melatonin.
 Material and methods. A comparative study of serotonin-containing thymus cells of 8-week-old Wistar rats, which were divided into 6 groups, was carried out. The first and second groups were kept under conditions of natural photoperiod, the third and fourth in conditions of constant darkening, the fifth and sixth groups in conditions of constant illumination within 4 weeks. Melatonin ad libitum at a concentration of 4 mg/l with water was received by animals of the second, fourth and sixth groups for 4 weeks. To determine the level of serotonin in cells, monoclonal antibodies to 5-HT were used. Conclusions about the serotonin content in the cells were made by measuring the optical density of the substance in 100 cells for each animal using the SigmaScan Pro5 program. Descriptive statistical processing was performed using the Statistica 17 program. The data obtained for each group of animals were averaged, the standard error and standard deviation were calculated.
 Results. Artificial darkening reduced the serotonin content in 5-HT-immunoreactive cells of the cortical substance by 2.4 times (p=0.001), and constant illumination increased this indicator by 1.9 times (p=0.001). When melatonin was administered to animals kept in dark conditions for 4 weeks, the optical density of serotonin increased by 3.6 times (p 0.0001). Administration of melatonin to animals under constant illumination led to an increase in the optical density of serotonin in the cells of the diffuse endocrine system at the border of the cortex and medulla of the lobules by 1.5 times (p=0.002).
 Conclusion. The cells of the diffuse endocrine system of the thymus are sensitive to changes in the photoperiod, and the introduction of melatonin has a multidirectional effect on the amount and optical density of serotonin under different light conditions.

Melatonin protects against maternal diabetes-associated meiotic defects by maintaining mitochondrial function

Maternal diabetes has been widely reported to adversely affect oocyte quality. Although various molecules and pathways may be involved in this process, strategies to prevent maternal diabetes-induced deterioration of oocyte quality remain unexplored. Melatonin is synthesized by the pineal gland and has been shown to have beneficial effects on oocyte quality owing to its antioxidative function. In the present study, we found that the exposure of oocytes of diabetic mice to melatonin, in vitro, alleviated aberrant oocyte maturation competence. Notably, melatonin supplementation attenuated defects in spindle organization and chromosome alignment by mediating the expression of TPX2 and pericentrin localization. Importantly, melatonin eliminated the accumulation of reactive oxygen species and increased the cytosolic Ca2+ levels in diabetic oocytes by maintaining mitochondrial function. Moreover, the occurrence of autophagy and apoptosis was reversed in diabetic oocytes after melatonin exposure via decreased LC3β expression. Collectively, our findings provide evidence that melatonin supplementation can protect oocytes from maternal diabetes-related meiotic defects and poor egg quality, providing a potential strategy for improving oocyte quality in assisted reproductive technologies.

Pediatric Melatonin Ingestions - United States, 2012-2021.

Melatonin is an endogenous neurohormone that regulates the sleep-wake cycle (1). It is used therapeutically for insomnia in adults and for primary sleep disorders in children (2). Melatonin is regulated by the Food and Drug Administration (FDA) as a dietary supplement. Various synthetic melatonin preparations are widely available over the counter (OTC) in the United States with sales increasing from $285 million in 2016 to $821 million in 2020 (3). Children are at increased risk for melatonin exposure because of the supplement's widespread use and growing popularity as a sleep aid. In 2020, melatonin became the most frequently ingested substance among children reported to national poison control centers (4); however, more research is needed to describe the toxicity and outcomes associated with melatonin ingestions in children. This study assessed isolated melatonin ingestions among the pediatric population (defined here as children, adolescents, and young adults aged ≤19 years) during January 1, 2012-December 31, 2021, using the American Association of Poison Control Centers' National Poison Data System (NPDS). During the 10-year study period, 260,435 pediatric melatonin ingestions were reported to NPDS, and the annual number of ingestions increased 530%. In addition, pediatric melatonin ingestions accounted for 4.9% of all pediatric ingestions reported to poison control centers in 2021 compared with 0.6% in 2012. Pediatric hospitalizations and more serious outcomes due to melatonin ingestions increased during the study period, primarily related to an increase in unintentional ingestions among children aged ≤5 years. Five children required mechanical ventilation, and two died. Consumers and health care professionals should be encouraged to report any melatonin product-related adverse events to MedWatch, the FDA's medical product safety reporting program. Public health initiatives should focus on raising awareness of increasing numbers of melatonin ingestions among children and on the development of preventive measures to eliminate this risk.

Transcriptional effects of melatonin on the gut commensal bacterium Klebsiella aerogenes.

Klebsiella (nee Enterobacter) aerogenes is the first human gut commensal bacterium with a documented sensitivity to the pineal/gastrointestinal hormone melatonin. Exogenous melatonin specifically increases the size of macrocolonies on semisolid agar and synchronizes the circadian clock of K. aerogenes in a concentration dependent manner. However, the mechanisms driving these phenomena are unknown. In this study, we applied RNA sequencing to identify melatonin sensitive transcripts during culture maturation. This work demonstrates that the majority of melatonin sensitive genes are growth stage specific. Melatonin exposure induced differential gene expression of 81 transcripts during exponential growth and 30 during early stationary phase. This indole molecule affects genes related to biofilm formation, fimbria biogenesis, transcriptional regulators, carbohydrate transport and metabolism, phosphotransferase systems (PTS), stress response, metal ion binding and transport. Differential expression of biofilm and fimbria-related genes may be responsible for the observed differences in macrocolony area. These data suggest that melatonin enhances Klebsiella aerogenes host colonization.

The ubiquitin-specific protease 8 antagonizes melatonin-induced endocytic degradation of MT1 receptor to promote lung adenocarcinoma growth

IntroductionThe 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. ObjectivesThis 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. MethodsThe 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. ResultsBioinformatic 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. ConclusionThe 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.

Metabolite and Transcriptome Profiling Analysis Revealed That Melatonin Positively Regulates Floral Scent Production in Hedychium coronarium.

Melatonin is a pleiotropic molecule that regulates a variety of developmental processes. Floral volatiles are important features of flowers that facilitate flower–visitor interactions by attracting pollinators, structure flower–visitor communities, and play defensive roles against plant and flower antagonists. Aside from their role in plants, floral volatiles are an essential ingredient in cosmetics, perfumes, pharmaceuticals, and flavorings. Herein, integrated metabolomic and transcriptomic approaches were carried out to analyze the changes triggered by melatonin exposure during the Hedychium coronarium flower development stages. Quantitative analysis of the volatiles of H. coronarium flowers revealed that volatile organic compound emission was significantly enhanced after melatonin exposure during the half bloom (HS), full bloom (FB) and fade stage (FS). Under the melatonin treatment, the emission of volatile contents was highest during the full bloom stage of the flower. Variable importance in projection (VIP) analysis and partial least-squares discriminant analysis (PLS-DA) identified 15 volatile compounds with VIP > 1 that were prominently altered by the melatonin treatments. According to the transcriptome sequencing data of the HS, FB, and FS of the flowers, 1,372, 1,510, and 1,488 differentially expressed genes were identified between CK-HS and 100MT-HS, CK-FB and 100MT-FB, and CK-FS and 100MT-FS, respectively. Among the significant differentially expressed genes (DEGs), 76 were significantly upregulated and directly involved in the floral scent biosynthesis process. In addition, certain volatile organic compounds were substantially linked with various DEGs after combining the metabolome and transcriptome datasets. Moreover, some transcription factors, such as MYB and bHLH, were also significantly upregulated in the comparison, which might be related to the floral aroma mechanism. Our results suggested that melatonin increased floral aroma production in H. coronarium flowers by modifying the expression level of genes involved in the floral scent biosynthesis pathway. These findings serve as a foundation for future research into the molecular mechanisms underlying the dynamic changes in volatile contents induced by melatonin treatment in H. coronarium.

Anticonvulsant activity of melatonin and its success in ameliorating epileptic comorbidity-like symptoms in zebrafish

Epilepsy is one of common neurological disorders, greatly distresses the well-being of the sufferers. Melatonin has been used in clinical anti-epileptic studies, but its effect on epileptic comorbidities is unknown, and the underlying mechanism needs further investigation. Herein, by generating PTZ-induced zebrafish seizure model, we carried out interdisciplinary research using neurobehavioral assays, bioelectrical detection, molecular biology, and network pharmacology to investigate the activity of melatonin as well as its pharmacological mechanisms. We found melatonin suppressed seizure-like behavior by using zebrafish regular locomotor assays. Zebrafish freezing and bursting activity assays revealed the ameliorative effect of melatonin on comorbidity-like symptoms. The preliminary screening results of neurobehavioral assays were further verified by the expression of key genes involved in neuronal activity, neurodevelopment, depression and anxiety, as well as electrical signal recording from the midbrain of zebrafish. Subsequently, network pharmacology was introduced to identify potential targets of melatonin and its pathways. Real-time qPCR and protein-protein interaction (PPI) were conducted to confirm the underlying mechanisms associated with glutathione metabolism. We also found that melatonin receptors were involved in this process, which were regulated in response to melatonin exposure before PTZ treatment. The antagonists of melatonin receptors affected anticonvulsant activity of melatonin. Overall, current study revealed the considerable ameliorative effects of melatonin on seizure and epileptic comorbidity-like symptoms and unveiled the underlying mechanism. This study provides an animal model for the clinical application of melatonin in the treatment of epilepsy and its comorbidities.

Roles of Melatonin in Goat Hair Follicle Stem Cell Proliferation and Pluripotency Through Regulating the Wnt Signaling Pathway.

Emerging studies show that melatonin promotes cashmere development through hypodermic implantation. However, the impact and underlying mechanisms are currently unknown. In vitro study has previously demonstrated that melatonin induces cashmere growth by regulating the proliferation of goat secondary hair follicle stem cells (gsHFSCs), but there is limited information concerning the effects of melatonin on cell pluripotency. It is also known that Wnt signaling may actively participate in regulating cell proliferation and stem cell pluripotency. Therefore, in the current investigation, goat hair follicle stem cells were exposed to multiple concentrations of melatonin and different culture times to reveal the relationship between melatonin and the activation of Wnt signaling. A proportionally high Catenin beta-1 (CTNNB1) response was induced by 500 ng/L of melatonin, but it was then suppressed with the dosages over 1,000 ng/L. Greater amounts of CTNNB1 entered the cell nuclei by extending the exposure time to 72 h, which activated transcription factor 4/lymphoid enhancer-binding factor 1 and promoted the expression of the proliferation-related genes C-MYC, C-JUN, and CYCLIND1. Moreover, nuclear receptor ROR-alpha (RORα) and bone morphogenetic protein 4 (BMP4) were employed to analyze the underlying mechanism. RORα presented a sluggish concentration/time-dependent rise, but BMP4 was increased dramatically by melatonin exposure, which revealed that melatonin might participate in regulating the pluripotency of hair follicle stem cells. Interestingly, NOGGIN, which is a BMP antagonist and highly relevant to cell stemness, was also stimulated by melatonin. These findings demonstrated that melatonin exposure and/or NOGGIN overexpression in hair follicle stem cells might promote the expression of pluripotency markers Homeobox protein NANOG, Organic cation/carnitine transporter 4, and Hematopoietic progenitor cell antigen CD34. Our findings here provided a comprehensive view of Wnt signaling in melatonin stimulated cells and melatonin mediated stemness of gsHFSCs by regulating NOGGIN, which demonstrates a regulatory mechanism of melatonin enhancement on the growth of cashmere.

Evaluation of Melatonin Practices for Delirium in Pediatric Critically Ill Patients.

To determine the use of melatonin and its role in therapy for pediatric delirium (as either prophylaxis or treatment for delirium) in an academic medical center's PICU. This retrospective, single-center study reviewed patients between 1 and 18 years of age admitted to the PICU between April 1, 2014, and February 29, 2019. Patients were included if they were admitted for greater than 48 hours and received melatonin for the indication of "delirium." Patients were excluded if melatonin was a home medication. Data collected included baseline characteristics, sedation and antipsychotic usage, assessment scores, and admission overview data. Descriptive statistics were used to report categorical data as percentages. A total of 63 patients were included. Thirty-nine patients (62%) required antipsychotics post-melatonin exposure, with risperidone being the most frequently used agent. The average cumulative antipsychotic exposure pre- and post-melatonin initiation was 2 versus 13 days. The average cumulative exposure to sedating agents, including opioids, benzodiazepines, ketamine, dexmedetomidine, and propofol, pre- and post-melatonin initiation was 13 versus 10 days. The average hospital and PICU lengths of stay were 54 and 39 days, respectively. The initiation of melatonin was also associated with lighter levels of sedation and decreased pain scores. Although the initiation of melatonin does not appear to decrease antipsychotic use, the results of this study may suggest a potential prophylactic effect in reducing the days of sedation the patient receives while inpatient.

Endogenous melatonin generation plays a positive role in chilling tolerance in relation to redox homeostasis in litchi fruit during refrigeration

The potent role of endogenous melatonin (MEL) in affecting chilling injury (CI) and related chilling tolerance regulatory mechanisms in harvested litchi fruit during refrigeration at 4 °C were investigated in this study. In the first experiment, exogenous MEL exposure exerted an inhibitory impact on the development of CI severity in refrigerated litchi fruit, as indicated by the lower CI index and delayed red color loss of pericarp, whereas treatment with p-chlorophenylalanine (p-CPA), an inhibitor of MEL biosynthesis, aggravated the degree of CI. The suppression of CI afforded by exogenous MEL was abated under the combined application of exogenous MEL and p-CPA. In the second experiment, the effects of p-CPA alone treatment on changes in biochemical parameters during refrigeration were analyzed. The results showed that p-CPA down-regulated the expressions of MEL biosynthesis genes, including LcTDC, LcT5H and LcSNAT, contributing to reduced generation of endogenous serotonin and MEL. p-CPA treatment accelerated oxidative stress-triggered membrane deterioration, as reflected by increases in relative leakage rate (RLR), reactive oxygen species (ROS) production, lipoxygenase (LOX) activity and malondialdehyde (MDA) accumulation. The membrane damage caused by p-CPA further resulted in loss of subcellular compartmentalization and enzymatic oxidation, as demonstrated by increased activities of polyphenol oxidase (PPO) and peroxidase (POD) in parallel with reduced contents of total phenolics and anthocyanin. Compared with control fruit, lower activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR), were observed in fruit receiving p-CPA. Additionally, p-CPA suppressed the expression levels of genes encoding oxidized protein repair-related enzymes, including LcMsrA1, LcMsrA2, LcMsrB1 and LcMsB2. These results suggest that endogenous MEL might confer a protective role against chilling stress by modulating cellular redox status in harvested litchi fruit during refrigeration.

Morphological differences in the pancreas of normo- and hypertensive rats after joint exposure of intermittent hypoxia and melatonin

The morphological changes in the pancreas of normo- and hypertensive rats after combined exposure to intermittent normobaric hypoxia and melatonin were studied. The study was conducted in the autumn on 24 normotensive (Wistar line) and 24 spontaneously hypertensive (SHR line) male rats. Experimental rats were daily exposed to hypoxic gas mixture in special sealed chamber. Hypoxic gas mixture (12 % oxygen in nitrogen) was supplied into this chamber from the membrane gas separator element in the intermittent mode: 15 min deoxygenation/ 15 min reoxygenation for 2 h. Exogenous melatonin was orally administered to experimental animals at 10 h in the morning at a dose of 5 mg / kg once a day. The total duration of the experiment was 28 d. Histological preparations of pancreatic tissue were prepared according to the standard methods. The morphometry of the preparations digital images was performed using the computer program ImageJ. The nature and severity of morphological changes in the pancreas of the experimental spontaneously hypertensive rats (hyperplasia of the nucleolus in the nucleus of exocrinocytes, a decrease in the amount of connective tissue) suggests that the combined effect of intermittent normobaric hypoxia and melatonin increases the activity of the exocrine part of the pancreas. At the same time, the activity of the endocrine part of the pancreas decreases, as evidenced by a decrease in the linear dimensions and area of the Langerhans islets, as well as the number of endocrinocytes contained in them. In Wistar rats, the combined effect of intermittent hypoxia and melatonin leads to the appearance of morphological signs of increased activity of both exocrine and endocrine pancreas functions. Thus, after prolonged combined exposure to intermittent normobaric hypoxia and melatonin, morphological signs of increased exocrine pancreas activity appear in both normotensive and hypertensive rats. At the same time, the activity of the endocrine function of the pancreas in experimental Wistar rats increases, while in SHR rats, on the contrary, decreases.

2600 MHz Radiofrequency Radiation Exposure and Protective Role of Melatonin: Effects on Epididymis

Objective: In this study, our aim is to investigate the possible protective effects of melatonin on potential damage caused by 2600 MHz radiofrequency (RF) radiation exposure on epididymis. Materials and Methods: 36 Wistar Albino male rats were divided into six groups. Group 1: Control, Group 2: Sham Control (mirror of RF exposure), Group 3: Sham Melatonin (mirror of RF exposure and melatonin injection), Group 4: Melatonin (melatonin injection), Group 5: RF (2600 MHz RF exposure), Group 6: RF and Melatonin (2600 MHz RF exposure and melatonin injection). During the experiment, body weights were measured and at the end of the 30-day experimental period, epididymis tissues were collected and examined with Hematoxylin-Eosin. Results: Epididymis was distinguished in normal histological appearance in the Control, Sham Control, Sham Melatonin and Melatonin groups. In the RF group, some structural degenerations were observed such as irregular tubule profile, deterioration and vacuolization in epithelium, loss of stereocilia, seperation in lateral and basal junctions of epithelium and immature sperm formation. In the RF and Melatonin group, the general histological appearance was found to be similar to the control groups except for some continuing degenerations. Conclusion: Taken together, 2600 MHz RF radiation exposure caused some structural degenerations on epididymis and melatonin administration provided therapeutic effects on these degenerations.

Melatonin enhances in vitro developmental competence of cumulus-oocyte complexes collected by ovum pick-up in prepubertal and adult dairy cattle

Bovine oocytes from prepubertal donors have been used for in vitro embryo production to decrease the generation interval. However, reduced cumulus-oocyte competence, mainly attributed to increased apoptosis, has been observed in oocytes/embryos collected from prepubertal donors. Here, we investigated the effects of the potent antioxidative molecule melatonin on cumulus-oocyte competence and embryo development in prepubertal and adult dairy cattle in vitro. A total of fifteen Holstein Friesian calves, six to ten months old (7.6 ± 1.34 months of age). And fifteen adult cows with one to four calvings (2.3 ± 0.96 calvings) were enrolled as ovum pick up (OPU) donors in this study. Cumulus-oocyte complexes (COCs) were cultured either in the presence or absence of melatonin (0.01 nM). The proportion of cleavage stages, blastocysts, and advanced blastocysts was determined. Embryo quality was assessed via differential staining to determine the total embryonic cells and allocation to the inner cell mass (ICM) and trophectoderm (TE) cells. Melatonin treatment yielded a greater percentage of blastocysts compared to the control group, i.e. oocytes from both adult cows (P = 0.0485; 24.8 ± 3.5% vs. 16.0 ± 3.4%, respectively), and from prepubertal donors (P = 0.0007; Melatonin 23.1 ± 5.1% vs. Control: 11.1 ± 3.5%). Adult cows had significantly (P = 0.0370) greater advanced blastocyst rates than those found in the prepubertal group (13.9%± vs. 7.0±%, respectively). Additionally, the number of ICM, total cells, and the ratios ICM: Total, ICM: TE, respectively, were greater (P < 0.05) after melatonin treatment compared with the control group (39.1 ± 2.8, 98.6 ± 5.7, 0.4 ± 0.01, and 0.7 ± 0.04 vs. 27.3 ± 2.9, 81.2 ± 5.8, 0.34 ± 0.01, and 0.52 ± 0.04, respectively). Blastocysts derived from adult cows had a greater number of TE (P = 0.01) and total embryonic cells (P = 0.0095) compared to the prepubertal donor group (63.5 ± 3.2 and 101.05 ± 4.8 vs. 48.9 ± 4.3 and 78.8 ± 6.5, respectively). Nevertheless, embryonic cell counting in embryos derived from prepubertal COCs equated to that observed from adult donors after melatonin exposure. In conclusion, these results indicate that the presence of melatonin during in vitro maturation improves cumulus-oocyte competence, embryo development, and quality by increasing the allocation of embryonic cells to the ICM compartment and the total number of embryonic cells in both adult and prepubertal bovine donors.

The protective role of melatonin against the effects of different doses of caffeine on the fetus

Skeletal system and some organs development changes in rat fetuses with 30 and 60 mg/kg caffeine and melatonin's (10 mg/kg) protective role against rat fetuses were investigated. Groups (n = 4) were formed as Control, LDC, HDC, LDC+melatonin, HDC+melatonin and melatonin. Fetuses were taken by cesarean section and stained using dual skeletal staining method and FESEM. TRAP and AP immune-reactivity concentrations were calculated. Oxidative stress and inflammatory markers were also measured by liver, bone and placenta samples. TNF-α, IL-1ß, IL-6, VEGF-A, SOST and Fetuin-A levels were measured in tissue by using ELISA. TBARS, SOD, GSH, GSSG, TOS, TAS, measured by spectrophotometric assay method. The mRNA levels of Agtr2 gene expressed in placental tissues of control rats and in placental tissues of rats exposed to HDC, LDC, MEL, HDC+MEL, LDC+MEL were analyzed by Real-time PCR. The gene expressions of Agtr2 were significantly upregulated in the placentas exposed to HDC, MEL, HDC+MEL and LDC+MEL (P&lt;0,001). No significant difference in samples of the LDC group (P&gt;0,05). According to these data, caffeine used during pregnancy delayed ossification; melatonin, a powerful antioxidant, was found to eliminate this effect. Besides, changes in angiotensin receptor expression observed in response to a caffeine and melatonin exposure result from high dose and join effect.

Special Issue No. – 10, June, 2020 Journal &gt; Special Issue &gt; Special Issue No. – 10, June, 2020 &gt; Page 5 “Quantative Methods in Modern Science” organized by Academic Paper Ltd, Russia MORPHOLOGICAL AND ANATOMICAL FEATURES OF THE GENUS GAGEA SALISB., GROWING IN THE EAST KAZAKHSTAN REGION Authors: Zhamal T. Igissinova,Almash A. Kitapbayeva,Anargul S. Sharipkhanova,Alexander L. Vorobyev,Svetlana F. Kolosova,Zhanat

Special Issue No. – 10, June, 2020 Journal &gt; Special Issue &gt; Special Issue No. – 10, June, 2020 &gt; Page 5 “Quantative Methods in Modern Science” organized by Academic Paper Ltd, Russia MORPHOLOGICAL AND ANATOMICAL FEATURES OF THE GENUS GAGEA SALISB., GROWING IN THE EAST KAZAKHSTAN REGION Authors: Zhamal T. Igissinova,Almash A. Kitapbayeva,Anargul S. Sharipkhanova,Alexander L. Vorobyev,Svetlana F. Kolosova,Zhanat

SPRY4 is responsible for pathogenesis of adolescent idiopathic scoliosis by contributing to osteogenic differentiation and melatonin response of bone marrow-derived mesenchymal stem cells

Adolescent idiopathic scoliosis (AIS) is a complex, three-dimensional deformity of the spine that commonly occurs in pubescent girls. Decreased osteogenic differentiation and aberrant melatonin signalling have been demonstrated in mesenchymal stem cells (MSCs) from AIS patients and are implicated in the pathogenesis of AIS. However, the molecular mechanisms underlying these abnormal cellular features remain largely unknown. Our previous work comparing gene expression profiles between MSCs from AIS patients and healthy controls identified 1027 differentially expressed genes. In the present study, we focused on one of the most downregulated genes, SPRY4, in the MAPK signalling pathway and examined its role in osteogenic differentiation. We found that SPRY4 is markedly downregulated in AIS MSCs. Knockdown of SPRY4 impaired differentiation of healthy MSCs to osteoblasts, while SPRY4 overexpression in AIS MSCs enhanced osteogenic differentiation. Furthermore, melatonin treatment boosted osteogenic differentiation, whereas SPRY4 ablation ablated the promotional effects of melatonin. Moreover, SPRY4 was upregulated by melatonin exposure and contributed to osteogenic differentiation and melatonin response in a MEK-ERK1/2 dependent manner. Thus, loss of SPRY4 in bone marrow derived-MSCs results in reduced osteogenic differentiation, and these defects are further aggravated under the influence of melatonin. Our findings provide new insights for understanding the role of melatonin in AIS aetiology and highlight the importance of MSCs in AIS pathogenesis.