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International Journal of Molecular... Jun 2024Endometriosis in half of affected women is closely related to problems with fertility. Endometriosis-associated infertility is caused by a wide range of abnormalities... (Review)
Review
Endometriosis in half of affected women is closely related to problems with fertility. Endometriosis-associated infertility is caused by a wide range of abnormalities affecting the female reproductive tract, from oocyte quality impairment to disturbances in the eutopic endometrium or mechanical abnormalities resulting from disease progression. Since supportive antioxidant therapies, in addition to surgical treatment or assisted reproductive techniques (ARTs), have overall been proven to be effective tools in endometriosis management, the objective of our review was to analyze the role of antioxidant substances, including vitamins, micronutrients, N-acetylcysteine (NAC), curcumin, melatonin, and resveratrol, in endometriosis-related infertility. Most of these substances have been proven to alleviate the systemic oxidant predominance, which has been expressed through decreased oxidative stress (OS) markers and enhanced antioxidative defense. In addition, we demonstrated that the predominant effect of the aforementioned substances is the inhibition of the development of endometriotic lesions as well as the suppression of pro-inflammatory molecules. Although we can undoubtedly conclude that antioxidants are beneficial in fertility support, further studies explaining the detailed pathways of their action are needed.
Topics: Endometriosis; Humans; Female; Antioxidants; Oxidative Stress; Infertility, Female; Acetylcysteine
PubMed: 38928002
DOI: 10.3390/ijms25126298 -
Cancers Jun 2024Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian... (Review)
Review
Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian reserve suppression and estrogen deficiency result in reduced quality of life for cancer patients and are frequently the cause of infertility and early menopause. Classic alkylating cytostatics are among the most toxic chemotherapeutics in this regard. They cause DNA damage in ovarian follicles and the cells they contain, and they can also induce oxidative stress or affect numerous signaling pathways. In vitro tests, animal models, and a few studies among women have investigated the effects of various agents on the protection of the ovarian reserve during classic chemotherapy. In this review article, we focused on the possible beneficial effects of selected hormones (anti-Müllerian hormone, ghrelin, luteinizing hormone, melatonin), agents affecting the activity of apoptotic pathways and modulating gene expression (C1P, S1P, microRNA), and several natural (quercetin, rapamycin, resveratrol) and synthetic compounds (bortezomib, dexrazoxane, goserelin, gonadoliberin analogs, imatinib, metformin, tamoxifen) in preventing gynotoxic effects induced by commonly used cytostatics. The presented line of research appears to provide a promising strategy for protecting and/or improving the ovarian reserve in the studied group of cancer patients. However, well-designed clinical trials are needed to unequivocally assess the effects of these agents on improving hormonal function and fertility in women treated with ovotoxic anticancer drugs.
PubMed: 38927992
DOI: 10.3390/cancers16122288 -
Biomedicines May 2024Oxidative stress, arising from an imbalance between reactive oxygen species (ROS) and antioxidants, contributes significantly to oral cancer such as oral squamous cell... (Review)
Review
Oxidative stress, arising from an imbalance between reactive oxygen species (ROS) and antioxidants, contributes significantly to oral cancer such as oral squamous cell carcinoma (OSCC) initiation, promotion, and progression. ROS, generated both internally and externally, induce cellular damage including DNA mutations and lipid peroxidation, fostering oncogene activation and carcinogenesis. The objective of this review was to cover and analyze the interplay between ROS and antioxidants, influencing the key processes such as cell proliferation, apoptosis, and angiogenesis, shaping the trajectory of OSCC development. Despite the promise of antioxidants to halt cancer progression and mitigate oxidative damage, their therapeutic efficacy remains debated. The conducted literature search highlighted potential biomarkers that indicate levels of oxidative stress, showing promise for the early detection and monitoring of OSCC. Furthermore, melatonin has emerged as a promising adjunct therapy for OSCC, exerting antioxidant and oncostatic effects by modulating tumor-associated neutrophils and inhibiting cancer cell survival and migration. In addition, this review aims to shed light on developing personalized therapeutic strategies for patients with OSCC such as melatonin therapy, which will be discussed. Research is needed to elucidate the underlying mechanisms and clinical implications of oxidative stress modulation in the context of oral cancer.
PubMed: 38927357
DOI: 10.3390/biomedicines12061150 -
Biomolecules May 2024Insomnia, also known as sleeplessness, is a sleep disorder due to which people have trouble sleeping, followed by daytime sleepiness, low energy, irritability, and a...
Insomnia, also known as sleeplessness, is a sleep disorder due to which people have trouble sleeping, followed by daytime sleepiness, low energy, irritability, and a depressed mood. It may result in an increased risk of accidents of all kinds as well as problems focusing and learning. Dietary supplements have become popular products for alleviating insomnia, while the lenient requirements for pre-market research result in unintelligible mechanisms of different combinations of dietary supplements. In this study, we aim to systematically identify the molecular mechanisms of a sleep cocktail's pharmacological effects based on findings from network pharmacology and molecular docking. A total of 249 targets of the sleep cocktail for the treatment of insomnia were identified and enrichment analysis revealed multiple pathways involved in the nervous system and inflammation. Protein-protein interaction (PPI) network analysis and molecular complex detection (MCODE) analysis yielded 10 hub genes, including AKT1, ADORA1, BCL2, CREB1, IL6, JUN, RELA, STAT3, TNF, and TP53. Results from weighted correlation network analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of insomnia-related transcriptome data from peripheral blood mononuclear cells (PBMCs) showed that a sleep cocktail may also ease insomnia via regulating the inflammatory response. Molecular docking results reveal good affinity of Sleep Cocktail to 9 selected key targets. It is noteworthy that the crucial target HSP90AA1 binds to melatonin most stably, which was further validated by MD simulation.
Topics: Humans; Molecular Docking Simulation; Network Pharmacology; Protein Interaction Maps; Sleep Initiation and Maintenance Disorders; Dietary Supplements; Sleep
PubMed: 38927034
DOI: 10.3390/biom14060630 -
Journal of Experimental & Clinical... Jun 2024
PubMed: 38926774
DOI: 10.1186/s13046-024-03104-w -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore its mechanisms via the...
OBJECTIVES
To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore its mechanisms via the PI3K/AKT signaling pathway, aiming to provide a basis for the clinical application of melatonin.
METHODS
Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group, an HIBD group, and a melatonin group (=9 each). The neonatal rat HIBD model was established using the classic Rice-Vannucci method. Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining. Autophagy-related protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunofluorescence staining and Western blot analysis. Phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein expression levels were measured by immunohistochemistry and Western blot. The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis.
RESULTS
Twenty-four hours post-modeling, neurons in the sham operation group displayed normal size and orderly arrangement. In contrast, neurons in the HIBD group showed swelling and disorderly arrangement, while those in the melatonin group had relatively normal morphology and more orderly arrangement. Nissl bodies were normal in the sham operation group but distorted in the HIBD group; however, they remained relatively intact in the melatonin group. The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group, but was reduced in the melatonin group compared to the HIBD group (<0.05). The number of p-PI3K and p-AKT cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group (<0.05). LC3 and Beclin-1 protein expression levels were higher, and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group (<0.05); however, in the melatonin group, LC3 and Beclin-1 levels decreased, and p-PI3K and p-AKT increased compared to the HIBD group (<0.05). The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K and p-AKT cells between the two groups (<0.05).
CONCLUSIONS
Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD, thereby alleviating HIBD. This mechanism is associated with the PI3K/AKT pathway.
Topics: Animals; Melatonin; Hypoxia-Ischemia, Brain; Rats, Sprague-Dawley; Rats; Proto-Oncogene Proteins c-akt; Animals, Newborn; Cerebral Cortex; Autophagy; Phosphatidylinositol 3-Kinases; Neurons; Signal Transduction; Male; Female
PubMed: 38926381
DOI: 10.7499/j.issn.1008-8830.2312053 -
Metabolites Jun 2024Bell peppers ( L.) are prone to chilling injury (CI) when stored at temperatures below 7 °C. Melatonin, a natural plant regulator, plays a critical role in defending...
Bell peppers ( L.) are prone to chilling injury (CI) when stored at temperatures below 7 °C. Melatonin, a natural plant regulator, plays a critical role in defending against different pre- and post-harvest abiotic stresses, including those associated with cold storage. This study aimed to assess the effects of applying exogenous melatonin alone and in combination with a commercial wax on the CI tolerance, postharvest life, and potential biomarker search of red bell peppers. In the initial experiment, the effective melatonin concentration to reduce CI effects was determined. Peppers were sprayed with either distilled water (control) or a melatonin aqueous solution (M100 = 100 μM or M500 = 500 μM) and then stored for 33 d at 4 °C, followed by 2 d at 20 °C. The M500 treatment proved to be more effective in reducing fruit CI incidence (superficial scalds) and metabolic rate, while weight loss, softening, and color were comparable to the control. A second experiment assessed the potential synergistic effects of a combined melatonin and commercial wax treatment on pepper CI and quality. Fruits were sprayed with distilled water (control), melatonin (M500), commercial wax (Wax), or the combined treatment (Wax + M500) and stored for 28 d at 4 °C, followed by 2 d at 20 °C. The Wax + M500 was the most effective in significantly reducing the incidence of fruit CI symptoms and calyx fungal infection. Furthermore, this combined treatment enhanced fruit weight loss prevention compared with individual melatonin or wax treatment. Also, Wax + M500-treated peppers exhibited notable proline accumulation, indicative of a metabolic response counteracting the cold effects, resulting in better fruit stress acclimation. This treatment also preserved the peppers' color and antioxidant capacity. In summary, these findings highlight the suitability of applying a combined Wax + M500 treatment as a highly effective strategy to enhance the CI tolerance of peppers and extend their postharvest life.
PubMed: 38921464
DOI: 10.3390/metabo14060330 -
Cells Jun 2024Envenomation by the in the Western Ghats of India (particularly in the Malabar region of Kerala) and the subcontinent island nation of Sri Lanka is known to inflict...
Envenomation by the in the Western Ghats of India (particularly in the Malabar region of Kerala) and the subcontinent island nation of Sri Lanka is known to inflict devastating mortality and morbidity. Currently, bites in India are devoid of anti-venom regimens. A detailed characterization of the venom is essential to stress the need for therapeutic anti-venom. Notably, the deleterious effects of this venom on human blood cells have largely remained less explored. Therefore, in continuation of our previous study, in the present study, we envisioned investigating the effect of venom on the morphological and physiological properties of red blood cells (RBCs). The venom readily induced deleterious morphological changes and, finally, the aggregation of washed RBCs. The aggregation process was independent of the ROS and the intracellular Ca ion concentration. Confocal and scanning electron microscopy (SEM) images revealed the loss of biconcave morphology and massive cytoskeletal disarray. Crenation or serrated plasma membrane projections were evenly distributed on the surface of the RBCs. The venom did not cause the formation of methemoglobin in washed RBCs but was significantly induced in whole blood. Venom did not affect glucose uptake and Na/K -ATPase activity but inhibited glucose 6 phosphate dehydrogenase activity and decreased the fluidity of the plasma membrane. Venom-induced RBC aggregates exhibited pro-coagulant activity but without affecting platelet aggregation. In pre-incubation or co-treatment studies, none of the bioactive compounds, such as melatonin, curcumin, fisetin, berberine, and quercetin, sugars such as mannose and galactose, and therapeutic polyvalent anti-venoms (Bharat and VINS) were inhibited, whereas only N-acetylcysteine and monovalent anti-venom could inhibit venom-induced deleterious morphological changes and aggregation of RBCs. In post-treatment studies, paradoxically, none of the bioactives and anti-venoms, including N-acetylcysteine and monovalent anti-venom, reversed the venom-induced RBC aggregates.
Topics: Animals; Humans; Erythrocytes; Acetylcysteine; Crotalid Venoms; Erythrocyte Aggregation; Antivenins; Calcium; Crotalinae; Reactive Oxygen Species
PubMed: 38920625
DOI: 10.3390/cells13120994 -
Indian Journal of Psychiatry May 2024Postoperative delirium is a common complication in patients undergoing elective surgery under general anesthesia. We aimed to minimize the incidence with an oral dose of...
BACKGROUND
Postoperative delirium is a common complication in patients undergoing elective surgery under general anesthesia. We aimed to minimize the incidence with an oral dose of 3 mg of melatonin administered the night before surgery.
METHODS
Hundred and sixty-two patients aged 40-80 years posted for various urological and gastrointestinal surgeries under general anesthesia with no preoperative cognitive deficits were randomly distributed equally to melatonin or control groups. In the control group, routine premedication was done with tablet alprazolam (0.25 mg) and ranitidine (150 mg), but in the melatonin group, the patients were given 3 mg melatonin orally the night before surgery along with routine premedication. The CAM scale was used for diagnosis of postoperative delirium.
RESULTS
Incidence of delirium was significantly lower in the melatonin group, 23.5%, 8.6%, and 2.5% at 6, 24, and 48 hours, respectively, and the corresponding mean (SD) values of CAM scores were 1.37 (1.30), 1.07 (1.03), and 0.69 (0.80). In contrast, the incidence of delirium was 46.9%, 30.9%, and 16% at 6, 24, and 48 hours, respectively, in the control group. There was a significant reduction in anxiety, a lower incidence of cognitive dysfunction (i.e., MoCA score <26), and improvement in sleep quality in the melatonin group at 6, 24, 48, and 72 hours after the surgical intervention. The generalized estimating equations model (GEE) model was used to study change in MoCA and CAM scores over time between the two groups, and it showed a significant interaction between time and treatment groups ( < 0.001).
CONCLUSIONS
Melatonin premedication reduced incidence of postoperative delirium and cognitive dysfunction and was associated with better sleep quality and anxiolysis.
PubMed: 38919573
DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_965_23 -
BMC Plant Biology Jun 2024Cowpea wilt is a harmful disease caused by Fusarium oxysporum, leading to substantial losses in cowpea production. Melatonin reportedly regulates plant immunity to...
BACKGROUND
Cowpea wilt is a harmful disease caused by Fusarium oxysporum, leading to substantial losses in cowpea production. Melatonin reportedly regulates plant immunity to pathogens; however the specific regulatory mechanism underlying the protective effect of melatonin pretreated of cowpea against Fusarium oxysporum remains known. Accordingly, the study sought to evaluate changes in the physiological and biochemical indices of cowpea following melatonin treated to facilitate Fusarium oxysporum resistance and elucidate the associated molecular mechanism using a weighted gene coexpression network.
RESULTS
Treatment with 100 µM melatonin was effective in increasing cowpea resistance to Fusarium oxysporum. Glutathione peroxidase (GSH-PX), catalase (CAT), and salicylic acid (SA) levels were significantly upregulated, and hydrogen peroxide (HO) levels were significantly downregulated in melatonin treated samples in roots. Weighted gene coexpression network analysis of melatonin- and Fusarium oxysporum-treated samples identified six expression modules comprising 2266 genes; the number of genes per module ranged from 9 to 895. In particular, 17 redox genes and 32 transcription factors within the blue module formed a complex interconnected expression network. KEGG analysis revealed that the associated pathways were enriched in secondary metabolism, peroxisomes, phenylalanine metabolism, flavonoids, and flavonol biosynthesis. More specifically, genes involved in lignin synthesis, catalase, superoxide dismutase, and peroxidase were upregulated. Additionally, exogenous melatonin induced activation of transcription factors, such as WRKY and MYB.
CONCLUSIONS
The study elucidated changes in the expression of genes associated with the response of cowpea to Fusarium oxysporum under melatonin treated. Specifically, multiple defence mechanisms were initiated to improve cowpea resistance to Fusarium oxysporum.
Topics: Plant Diseases; Melatonin; Disease Resistance; Fusarium; Vigna; Gene Regulatory Networks; Gene Expression Regulation, Plant; Salicylic Acid
PubMed: 38918732
DOI: 10.1186/s12870-024-05289-w