Seed priming with melatonin improves the seed germination of waxy maize under chilling stress.

PMID: 

Sci Rep. 2019 Oct 21 ;9(1):15044. Epub 2019 Oct 21. PMID: 31636312

Abstract Title: 

Seed Priming with Melatonin Improves the Seed Germination of Waxy Maize under Chilling Stress via Promoting the Antioxidant System and Starch Metabolism.

Abstract: 

Chilling stress is one of the major abiotic stresses affecting waxy maize plant growth. Melatonin (MT) is able to improve tolerance to abiotic stress in plants. To investigate the effects of seed priming with MT on tolerance to chilling stress in waxy maize, the seed germination characteristics and physiological parameters were tested with varied MT concentrations (0, 50, 100 µM) and treatment times (12, 24 h) at ambient (25 °C) and chilling (13 °C) temperature. MT primed seeds significantly enhanced the germination potential (by 20.29% and 50.71%, respectively), germination rate (by 20.88% and 33.72%), and increased the radicle length (by 90.73% and 217.14%), hypocotyl length (by 60.28% and 136.14%), root length (by 74.59% and 108.70%), and seed vigor index (46.13%, 63.81%), compared with the non-priming seeds under chilling stress. No significant difference was found in priming time between primed and non-primed seeds. In addition, lower HOand malondialdehyde concentrations, increased antioxidant enzyme activities (superoxide dismutase, peroxidase, catalase and ascorbateperoxidase), and promoted starch metabolism were found in primed seeds compared to non-primed ones. It was suggested that seed priming with MT improved waxy maize seed germination under chilling stress through improving antioxidant system and starch metabolism, which protected from oxidative damage.

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This review highlights that melatonin can be an adjuvant therapy and be beneficial in treating patients suffering from colorectal cancer.

PMID: 

Biomed Res Int. 2019 ;2019:9740568. Epub 2019 Sep 17. PMID: 31637261

Abstract Title: 

Therapeutic Opportunities in Colorectal Cancer: Focus on Melatonin Antioncogenic Action.

Abstract: 

Colorectal cancer (CRC) influences individual health worldwide with high morbidity and mortality. Melatonin, which shows multiple physiological functions (e.g., circadian rhythm, immune modulation, and antioncogenic action), can be present in almost all organisms and found in various tissues including gastrointestinal tract. Notably, melatonin disruption is closely associated with the elevation of CRC incidence, indicating that melatonin is effective in suppressing CRC development and progression. Mechanistically, melatonin favors in activating apoptosis and colon cancer immunity, while reducing proliferation, autophagy, metastasis, and angiogenesis, thereby exerting its anticarcinogenic effects. This review highlights that melatonin can be an adjuvant therapy and be beneficial in treating patients suffering from CRC.

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Molecular and cellular mechanisms of melatonin in osteosarcoma.

PMID: 

Cells. 2019 Dec 12 ;8(12). Epub 2019 Dec 12. PMID: 31842295

Abstract Title: 

Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma.

Abstract: 

Osteosarcoma, the most common primary bone malignancy, occurs most frequently in adolescents with a peak of incidence at 11-15 years. Melatonin, an indole amine hormone, shows a wide range of anticancer activities. The decrease in melatonin levels simultaneously concurs with the increase in bone growth and the peak age distribution of osteosarcoma during puberty, so melatonin has been utilized as an adjunct to chemotherapy to improve the quality of life and clinical outcomes. While a large amount of research has been conducted to understand the complex pleiotropic functions and the molecular and cellular actions elicited by melatonin in various types of cancers, a few review reports have focused on osteosarcoma. Herein, we summarized the anti-osteosarcoma effects of melatonin and its underlying molecular mechanisms to illustrate the known significance of melatonin in osteosarcoma and to address cellular signaling pathways of melatonin in vitro and in animal models. Even in the same kind of osteosarcoma, melatonin has been sparingly investigated to counteract tumor growth, apoptosis, and metastasis through different mechanisms, depending on different cell lines. We highlighted the underlying mechanism of anti-osteosarcoma properties evoked by melatonin, including antioxidant activity, anti-proliferation, induction of apoptosis, and the inhibition of invasion and metastasis. Moreover, we discussed the drug synergy effects of the role of melatonin involved and the method to fortify the anti-cancer effects on osteosarcoma. As a potential therapeutic agent, melatonin is safe for children and adolescents and is a promising candidate for an adjuvant by reinforcing the therapeutic effects and abolishing the unwanted consequences of chemotherapies.

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The results of this systematic review indicated that co-administration of melatonin ameliorates the doxorubicin-induced cardiotoxicity.

PMID: 

Life Sci. 2019 Dec 13:117173. Epub 2019 Dec 13. PMID: 31843530

Abstract Title: 

The role of melatonin on doxorubicin-induced cardiotoxicity: A systematic review.

Abstract: 

PURPOSE: Doxorubicin, as an effective chemotherapeutic drug, is commonly used for combating various solid and hematological tumors. However, doxorubicin-induced cardiotoxicity is considered as a serious adverse effect, and it limits the clinical use of this chemotherapeutic drug. The use of melatonin can lead to a decrease in the cardiotoxic effect induced by doxorubicin. The aim of this review was to evaluate the potential role of melatonin in the prevention of doxorubicin-induced cardiotoxicity.METHODS: This review was conducted by a full systematic search strategy based on PRISMA guidelines for the identification of relevant literature in the electronic databases of PubMed, Web of Science, Embase, and Scopus up to January 2019 using search terms in the titles and abstracts. 286 articles were screened in accordance with our inclusion and exclusion criteria. Finally, 28 articles were selected in this systematic review.RESULTS: The findings demonstrated that doxorubicin-treated groups had increased mortality, decreased body weight and heart weight, and increased ascites compared to the control groups; the co-administration of melatonin revealed an opposite pattern compared to the doxorubicin-treated groups. Also, this chemotherapeutic agent can lead to biochemical and histopathological changes; as for most of the cases, these alterations were reversed near to normal levels (control groups) by melatonin co-administration. Melatonin exerts these protection effects through mechanisms of anti-oxidant, anti-apoptosis, anti-inflammatory, and mitochondrial function.CONCLUSION: The results of this systematic review indicated that co-administration of melatonin ameliorates the doxorubicin-induced cardiotoxicity.

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melatonin potentially plays a role in suppression of uterine leiomyoma growth.

PMID: 

J Pineal Res. 2020 Jan ;68(1):e12620. Epub 2019 Nov 28. PMID: 31710386

Abstract Title: 

Melatonin activates cell death programs for the suppression of uterine leiomyoma cell proliferation.

Abstract: 

The circadian nature of melatonin has a protective effect on the progression of female reproductive cancers, including breast and ovarian cancers. However, the effect of melatonin on the growth of uterine leiomyoma is still unclear. In this study, we found that the growth of uterine leiomyoma ELT3 cells was reduced by treatment with melatonin. Treatment with melatonin increased the distribution of sub-G1 phase and increased DNA condensation in ELT3 cells. Melatonin-induced apoptosis and autophagy cell death progression were observed in ELT3 cells. Melatonin exerts a highly selective effect on primary normal human uterine smooth muscle (UtSMC) cells. The UtSMC cell cycle was arrested by melatonin treatment through up-regulation of p21, p27, and PTEN protein expression, but melatonin did not further promote apoptosis program activation. Melatonin reduced cell proliferation in ELT3 cells underlying the activation of melatonin MT1 and MT2 receptors, which in turn down-regulated the Akt-ERK1/2-NFκB signaling pathway. Melatonin reduced ELT3 tumor growth in both xenograft and orthotopic uterine tumor mice models. The extracellular matrix of the tumor was also reduced by melatonin treatment. Taken together, these results suggest that melatonin potentially plays a role in suppression of uterine leiomyoma growth.

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Melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells.

PMID: 

Free Radic Biol Med. 2019 Oct 24. Epub 2019 Oct 24. PMID: 31669348

Abstract Title: 

Melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells by preserving SIRT1-mediated intracellular antioxidant properties.

Abstract: 

Postmenopausal osteoporosis (OP) is one of the most common bone diseases that affects millions of aging women. Reduced osteogenesis and increased oxidative stress have been implicated in bone marrow mesenchymal stem cells (BMMSCs) derived from OP patients. Melatonin has shown positive effects on osteoblast differentiation and bone formation; however, it was unknown whether melatonin could restore OP-impaired osteogenic potential of BMMSCs and what the underlying mechanisms entailed. The objective of this study is to investigate (1) whether melatonin can restore the impaired osteogenic potential of OP BMMSCs by preserving their antioxidant functions, and if so, (2) whether intravenous administration of melatonin can prevent OP-induced bone loss in ovariectomized (OVX) rats. Ovariectomies were performed in female rats and BMMSCs were isolated from the osteoporotic rats 3 months later. In vitro treatment with melatonin successfully improved the osteogenic differentiation of OP BMMSCs, as evidenced by increased levels of matrix mineralization and osteoblast-specific genes. In melatonin-treated OP BMMSCs, intracellular oxidative stress was significantly attenuated, while levels of intracellular antioxidant enzymes were noticeably up-regulated – particularly superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1). Silent information regulator type 1 (SIRT1) was involved in the melatonin-mediated recovery of osteogenesis and antioxidant functions. Meanwhile, in vivo injections of melatonin via the tail vein successfully ameliorated the bone micro-architecture in ovariectomized rat femurs. Further experiments confirmed that BMMSCs derived from melatonin-treated OVX rats exerted well-preserved antioxidant properties and osteogenic potential. Our findings demonstrate that the administration of melatonin is a promising strategy for treating patients with postmenopausal OP by preserving the antioxidant properties and osteogenic potential of their BMMSCs.

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Melatonin decreases in vitro viability and migration of spheres derived from CF41.Mg canine mammary carcinoma cells.

PMID: 

BMC Vet Res. 2019 Nov 4 ;15(1):390. Epub 2019 Nov 4. PMID: 31684950

Abstract Title: 

Melatonin decreases in vitro viability and migration of spheres derived from CF41.Mg canine mammary carcinoma cells.

Abstract: 

BACKGROUND: Mammary cancer is a common disease affecting female dogs, where approximately 50% of the cases are malignant. There is a subpopulation of cancer cells with stem cell-like features within the tumour microenvironment, which can form in vitro spheres, cell structures that grow in anchor-free conditions. This cell population shows resistance to conventional antitumor treatments explaining in part the recurrence of some type of cancers. It has been previously reported that spheres derived from CF41.Mg canine mammary carcinoma cells exhibit several stemness features. Melatonin has shown antitumor effects on cancer mammary cells; nevertheless, its effects have been poorly evaluated on canine mammary cancer stem-like cells. In this regard, it has described that melatonin decreases the expression of OCT-4 in CMT-U2229 mammary cancer cells, a transcription factor that participates in the modulation of self-renewal and drug resistance in cancer stem-like cells. The aim of this study was to compare the effects of melatonin on viability and migration of canine mammary carcinoma CF41.Mg-spheres, and CF41.Mg-parental cells. CF41.Mg cells were grown in DMEM high-glucose medium containing 10% bovine foetal serum. CF41.Mg-spheres were cultured in ultra-low attachment plates with serum-free DMEM/F12 containing several growth factors. Cell viability (MTS reduction) and migration (transwell) assays were conducted in presence of melatonin (0.01, 0.1 or 1 mM).RESULTS: Melatonin decreased cell viability at 1 mM (P 

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Melatonin ameliorates cerebral ischemia/reperfusion injury through SIRT3 activation.

PMID: 

Life Sci. 2019 Dec 15 ;239:117036. Epub 2019 Nov 4. PMID: 31697951

Abstract Title: 

Melatonin ameliorates cerebral ischemia/reperfusion injury through SIRT3 activation.

Abstract: 

AIMS: Previous literature has shown that melatonin plays a critical role in protecting against cerebral ischemia/reperfusion (I/R) injury. Sirtuin3(SIRT3), as one member of the sirtuin family, protects against oxidative stress-related diseases. However, the association between melatonin and SIRT3 in cerebral I/R injury is not well understood. Our experiment was planned to investigate whether melatonin protects against cerebral I/R injury through SIRT3 activation.MAIN METHODS: We selected transient middle cerebral artery occlusion (tMCAO) mice as the model of cerebral I/R injury. Male C57/BL6 mice were pre-treated with or without a selective SIRT3 inhibitor and then subjected to tMCAO surgery. Melatonin (20 mg/kg) was given to mice by intraperitoneal injection after ischemia and before reperfusion. Then, we observed the changes in the SIRT3 and downstream relative proteins, infarction volume, neurological score, Nissl, H&E and TUNEL staining, and the expression of apoptosis proteins after tMCAO.KEY FINDINGS: Melatonin upregulated the expression of SIRT3 after tMCAO, and alleviated the neurological dysfunction and cell apoptosis through SIRT3 activation.SIGNIFICANCE: Our research proved that melatonin promoted SIRT3 expression after tMCAO and alleviated cerebral I/R injury by activating the SIRT3 signaling pathway. This study provides novel therapeutic targets and mechanisms for the treatment of ischemic stroke in the clinic, especially during cerebrovascular reperfusion.

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