Melatonin and Vitamin D in Diseases and Health

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 92418

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Special Issue Information

Dear Colleagues,

The recent years have provided new insights into the identification and characterization of new properties of melatonin, vitamin D, and their metabolites. Numerous studies have revealed new biological capacities and health-related or clinical applications for these substances including neurodegeneration, cancer, cardiovascular diseases, and many others. Recent advances have revised or identified new mechanisms of their action that involve defining specific receptors or regulatory proteins or organelles such as mitochondria mediating their phenotypic activity, and have established precise mechanisms of the metabolic activation and/or inactivation of these compounds. These advances define novel pharmaceutical, nutraceutical, and cosmeceutical targets for improving health in the chemoprevention or treatment of different diseases.

The goal of this Special Issue titled “Melatonin and Vitamin D in Diseases and Health” is to collect the latest research findings on a broad range of research topics concerning the effects of dietary factors on a variety of health aspects. We welcome original experimental research, review articles, and commentary articles leading to a better understanding of the biological actions of nutritional factors, their role in disease pathogenesis, and their potential roles in preventive healthcare and treatment.

Dr. Konrad Kleszczyński
Prof. Dr. Andrzej Slominski
Guest Editors

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Keywords

  • melatonin
  • metabolites of melatonin
  • vitamin D
  • melanoma
  • skin diseases
  • treatment
  • mitochondria
  • oxidative stress
  • vitamin C
  • vitamin E
  • vitamin A

Published Papers (13 papers)

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Research

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13 pages, 302 KiB  
Article
COVID-19: Focusing on the Link between Inflammation, Vitamin D, MAPK Pathway and Oxidative Stress Genetics
by Jessica Cusato, Alessandra Manca, Alice Palermiti, Jacopo Mula, Martina Costanzo, Miriam Antonucci, Francesco Chiara, Elisa Delia De Vivo, Domenico Maiese, Micol Ferrara, Stefano Bonora, Giovanni Di Perri, Antonio D’Avolio and Andrea Calcagno
Antioxidants 2023, 12(5), 1133; https://doi.org/10.3390/antiox12051133 - 20 May 2023
Viewed by 1911
Abstract
An uncontrolled inflammatory response during SARS-CoV-2 infection has been highlighted in several studies. This seems to be due to pro-inflammatory cytokines whose production could be regulated by vitamin D, ROS production or mitogen-activated protein kinase (MAPK). Several genetic studies are present in the [...] Read more.
An uncontrolled inflammatory response during SARS-CoV-2 infection has been highlighted in several studies. This seems to be due to pro-inflammatory cytokines whose production could be regulated by vitamin D, ROS production or mitogen-activated protein kinase (MAPK). Several genetic studies are present in the literature concerning genetic influences on COVID-19 characteristics, but there are few data on oxidative stress, vitamin D, MAPK and inflammation-related factors, considering gender and age. Therefore, the aim of this study was to evaluate the role of single nucleotide polymorphisms in these pathways, clarifying their impact in affecting COVID-19-related clinical features. Genetic polymorphisms were evaluated through real-time PCR. We prospectively enrolled 160 individuals: 139 patients were positive for SARS-CoV-2 detection. We detected different genetic variants able to affect the symptoms and oxygenation. Furthermore, two sub-analyses were performed considering gender and age, showing a different impact of polymorphisms according to these characteristics. This is the first study highlighting a possible contribution of genetic variants of these pathways in affecting COVID-19 clinical features. This may be relevant in order to clarify the COVID-19 etiopathogenesis and to understand the possible genetic contribution for further SARS infections. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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16 pages, 1244 KiB  
Article
Non-Melanoma Skin Cancer and Vitamin D: The “Lost Sunlight” Paradox and the Oxidative Stress Explanation
by Emmanouil Karampinis, Athina-Maria Aloizou, Efterpi Zafiriou, Alexandra Bargiota, Zoi Skaperda, Demetrios Kouretas and Angeliki-Viktoria Roussaki-Schulze
Antioxidants 2023, 12(5), 1107; https://doi.org/10.3390/antiox12051107 - 17 May 2023
Cited by 13 | Viewed by 2267
Abstract
UV radiation (UVR) is responsible for inducing both harmful and beneficial effects on skin health. Specifically, it has been reported to disrupt oxidant and antioxidant levels, leading to oxidative stress conditions in skin tissue. This phenomenon might trigger photo-carcinogenesis, resulting in melanoma, NMSC [...] Read more.
UV radiation (UVR) is responsible for inducing both harmful and beneficial effects on skin health. Specifically, it has been reported to disrupt oxidant and antioxidant levels, leading to oxidative stress conditions in skin tissue. This phenomenon might trigger photo-carcinogenesis, resulting in melanoma, NMSC (non-melanoma skin cancer), such as BCC (basal cell carcinoma) and SCC (squamous cell carcinoma), and actinic keratosis. On the other hand, UVR is essential for the production of adequate vitamin D levels, a hormone with important antioxidant, anticancer and immunomodulatory properties. The exact mechanisms implicated in this two-fold action are not well understood, as there still no clear relation established between skin cancer and vitamin D status. Oxidative stress seems to be a neglected aspect of this complex relation, despite its role in both skin cancer development and vitamin D deficiency. Therefore, the aim of the present study is to examine the correlation between vitamin D and oxidative stress in skin cancer patients. A total of 100 subjects (25 with SCC, 26 with BCC, 23 with actinic keratosis, and 27 controls) were assessed in terms of 25-hydroxyvitamin D (25(OH) D) and redox markers such as thiobarbituric acid reactive substances (TBARS), protein carbonyls, total antioxidant capacity (TAC) in plasma, glutathione (GSH) levels and catalase activity in erythrocytes. The majority of our patients revealed low vitamin D levels; 37% of the subjects showed deficiency (<20 ng/mL) and 35% insufficiency (21–29 ng/mL). The mean 25(OH) D level of the NMSC patients (20.87 ng/mL) was also found to be significantly lower (p = 0.004) than that of the non-cancer patients (28.14 ng/mL). Furthermore, higher vitamin D levels were also correlated with lower oxidative stress (positive correlation with GSH, catalase activity TAC index and negative correlation with TBARS and CARBS indices). NMSC patients diagnosed with SCC showed lower catalase activity values compared to non-cancer patients (p < 0.001), with the lowest values occurring in patients with a chronic cancer diagnosis (p < 0.001) and vitamin D deficiency (p < 0.001). Higher GSH levels (p = 0.001) and lower TBARS levels (p = 0.016) were found in the control group compared to the NMSC group, and to patients with actinic keratosis. Higher levels of CARBS were observed in patients with SCC (p < 0.001). Non-cancer patients with vitamin D sufficiency showed higher TAC values compared to non-cancer patients with vitamin D deficiency (p = 0.023) and to NMSC patients (p = 0.036). The above-mentioned results indicate that NMSC patients reveal increased levels of oxidative damage markers compared to control levels, while vitamin D status plays a critical role in the determination of individuals’ oxidative status. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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13 pages, 3898 KiB  
Article
Human Naa50 Shows Serotonin N-Acetyltransferase Activity, and Its Overexpression Enhances Melatonin Biosynthesis, Resulting in Osmotic Stress Tolerance in Rice
by Kyungjin Lee and Kyoungwhan Back
Antioxidants 2023, 12(2), 319; https://doi.org/10.3390/antiox12020319 - 30 Jan 2023
Cited by 2 | Viewed by 1510
Abstract
A new clade of serotonin N-acetyltransferase (SNAT), the penultimate enzyme in the melatonin biosynthetic pathway, has been reported in the archaeon Thermoplasma volcanium. The closest homolog of archaea SNAT in human was an N-alpha-acetyltransferase50 (Naa50). To determine whether human Naa50 [...] Read more.
A new clade of serotonin N-acetyltransferase (SNAT), the penultimate enzyme in the melatonin biosynthetic pathway, has been reported in the archaeon Thermoplasma volcanium. The closest homolog of archaea SNAT in human was an N-alpha-acetyltransferase50 (Naa50). To determine whether human Naa50 (hNaa50) shows SNAT enzyme activity, we chemically synthesized and expressed the hNaa50 gene in Escherichia coli, followed by Ni2+ affinity purification. Purified recombinant hNaa50 showed SNAT activity (Km and Vmax values of 986 μM and 1800 pmol/min/mg protein, respectively). To assess its in vivo function, hNaa50 was overexpressed in rice (hNaa50-OE). The transgenic rice plants produced more melatonin than nontransgenic wild-type rice, indicating that hNaa50 is functionally coupled with melatonin biosynthesis. Due to its overproduction of melatonin, hNaa50-OE had a higher tolerance against osmotic stress than the wild type. Enhanced expression of the chaperone genes BIP1 and CNX in hNaa50-OE plants was responsible for the increased tolerance. It is concluded that hNaa50 harbors serotonin N-acetyltransferase enzyme activity in addition to its initial N-alpha-acetyltransferase, suggesting the bifunctionality of the hNaa50 enzyme toward serotonin and protein substrates. Consequently, ectopic overexpression of hNaa50 in rice enhanced melatonin synthesis, indicating that hNaa50 is in fact involved in melatonin biosynthesis. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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13 pages, 1729 KiB  
Article
Assessment of Melatonin-Cultured Collagen/Chitosan Scaffolds Cross-Linked by a Glyoxal Solution as Biomaterials for Wound Healing
by Beata Kaczmarek-Szczepańska, Judith M. Pin, Lidia Zasada, Mauritz M. Sonne, Russel J. Reiter, Andrzej T. Slominski, Kerstin Steinbrink and Konrad Kleszczyński
Antioxidants 2022, 11(3), 570; https://doi.org/10.3390/antiox11030570 - 17 Mar 2022
Cited by 8 | Viewed by 2924
Abstract
Chitosan (CTS) and collagen (Coll) are natural biomaterials that have been extensively used in tissue engineering or wound healing applications, either separately or as composite materials. Most methods to fabricate CTS/Coll matrices employ chemical crosslinking to obtain solid and stable scaffolds with the [...] Read more.
Chitosan (CTS) and collagen (Coll) are natural biomaterials that have been extensively used in tissue engineering or wound healing applications, either separately or as composite materials. Most methods to fabricate CTS/Coll matrices employ chemical crosslinking to obtain solid and stable scaffolds with the necessary porosity and mechanical properties to facilitate regeneration. In this study, we comparatively assessed the physicochemical properties of 3D scaffolds loaded with a cross-linker, glyoxal. Using a scanning electron microscope, we evaluated the microstructure of resultant matrices and their mechanistic testing by the determination of the compressive modulus (Emod), the maximum force (Fmax), thermogravimetric analysis (TG), Fourier Transform Infrared Spectroscopy–Attenuated Total Reflectance (FTIR-ATR), and proliferation rate in vitro using human epidermal keratinocytes and dermal fibroblasts cultured in presence of melatonin solution (10−5 M). We observed that enhanced content of collagen (50CTS/50Coll or 20CTS/80Coll compared to 80CTS/20Coll) significantly elevated the physicochemical capacities of resultant materials. Besides, presence of 5% glyoxal increased porosity, Emod and Fmax, compared to scaffolds without glyoxal. Finally, keratinocytes and dermal fibroblasts cultured on subjected matrices in presence of melatonin revealed a prominently enhanced growth rate. This indicates that the combination of glyoxal and melatonin make it imperative to consider these materials as a promising approach for targeting skin tissue engineering or regenerative dermatology. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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14 pages, 2487 KiB  
Article
Melatonin Prevents Chronic Kidney Disease-Induced Hypertension in Young Rat Treated with Adenine: Implications of Gut Microbiota-Derived Metabolites
by Chien-Ning Hsu, Hung-Wei Yang, Chih-Yao Hou, Guo-Ping Chang-Chien, Sufan Lin and You-Lin Tain
Antioxidants 2021, 10(8), 1211; https://doi.org/10.3390/antiox10081211 - 28 Jul 2021
Cited by 13 | Viewed by 2811
Abstract
Melatonin, a signaling hormone with pleiotropic biofunctions, has shown health benefits. Trimethylamine-N-oxide (TMAO) and asymmetric dimethylarginine (ADMA) are uremic toxins involved in the development of hypertension. TMAO originates from trimethylamine (TMA), a gut microbial product. ADMA is an endogenous nitric oxide (NO) synthase [...] Read more.
Melatonin, a signaling hormone with pleiotropic biofunctions, has shown health benefits. Trimethylamine-N-oxide (TMAO) and asymmetric dimethylarginine (ADMA) are uremic toxins involved in the development of hypertension. TMAO originates from trimethylamine (TMA), a gut microbial product. ADMA is an endogenous nitric oxide (NO) synthase inhibitor. We examined whether melatonin therapy could prevent hypertension and kidney disease by mediating gut microbiota-derived metabolites and the NO pathway using an adenine-induced chronic kidney disease (CKD) young rat model. Six-week-old young Sprague Dawley rats of both sexes were fed a regular diet (C group), a diet supplemented with 0.5% adenine (CKD group), or adenine plus 0.01% melatonin in their drinking water (CKD + M group) for three weeks (N = 8/group). Adenine-fed rats developed renal dysfunction, hypertension, renal hypertrophy and increased uremic toxin levels of TMAO and ADMA. Melatonin therapy prevented hypertension in both sexes and attenuated kidney injury in males. Melatonin reversed the changes to the plasma TMAO-to-TMA ratio induced by CKD in both sexes. Besides, the protective effects of melatonin were associated with restoration of gut microbiota alterations, including increased α-diversity, and enhancement of the abundance of the phylum Proteobacteria and the genus Roseburia in male rats. Melatonin therapy also partially prevented the increases in ADMA in male CKD rats. Melatonin sex-specifically protected young rats against hypertension and kidney injury induced by CKD. The results of this study contribute toward a greater understanding of the interaction between melatonin, gut microbiota-derived metabolites, and the NO pathway that is behind CKD, which will help to prevent CKD-related disorders in children. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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17 pages, 10297 KiB  
Article
Melatonin Successfully Rescues the Hippocampal Molecular Machinery and Enhances Anti-oxidative Activity Following Early-Life Sleep Deprivation Injury
by Hung-Ming Chang, Hsing-Chun Lin, Hsin-Lin Cheng, Chih-Kai Liao, To-Jung Tseng, Ting-Yi Renn, Chyn-Tair Lan and Li-You Chen
Antioxidants 2021, 10(5), 774; https://doi.org/10.3390/antiox10050774 - 13 May 2021
Cited by 6 | Viewed by 3281
Abstract
Early-life sleep deprivation (ESD) is a serious condition with severe cognitive sequelae. Considering hippocampus plays an essential role in cognitive regulation, the present study aims to determine whether melatonin, a neuroendocrine beard with significant anti-oxidative activity, would greatly depress the hippocampal oxidative stress, [...] Read more.
Early-life sleep deprivation (ESD) is a serious condition with severe cognitive sequelae. Considering hippocampus plays an essential role in cognitive regulation, the present study aims to determine whether melatonin, a neuroendocrine beard with significant anti-oxidative activity, would greatly depress the hippocampal oxidative stress, improves the molecular machinery, and consequently exerts the neuro-protective effects following ESD. Male weanling Wistar rats (postnatal day 21) were subjected to ESD for three weeks. During this period, the animals were administered normal saline or melatonin (10 mg/kg) via intraperitoneal injection between 09:00 and 09:30 daily. After three cycles of ESD, the animals were kept under normal sleep/wake cycle until they reached adulthood and were sacrificed. The results indicated that ESD causes long-term effects, such as impairment of ionic distribution, interruption of the expressions of neurotransmitters and receptors, decreases in the levels of several antioxidant enzymes, and impairment of several signaling pathways, which contribute to neuronal death in hippocampal regions. Melatonin administration during ESD prevented these effects. Quantitative evaluation of cells also revealed a higher number of neurons in the melatonin-treated animals when compared with the saline-treated animals. As the hippocampus is critical to cognitive activity, preserving or even improving the hippocampal molecular machinery by melatonin during ESD not only helps us to better understand the underlying mechanisms of ESD-induced neuronal dysfunction, but also the therapeutic use of melatonin to counteract ESD-induced neuronal deficiency. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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20 pages, 3361 KiB  
Article
Differential and Overlapping Effects of Melatonin and Its Metabolites on Keratinocyte Function: Bioinformatics and Metabolic Analyses
by Joanna Stefan, Tae-Kang Kim, Fiona Schedel, Zorica Janjetovic, David K. Crossman, Kerstin Steinbrink, Radomir M. Slominski, Jaroslaw Zmijewski, Meri K. Tulic, Russel J. Reiter, Konrad Kleszczyński and Andrzej T. Slominski
Antioxidants 2021, 10(4), 618; https://doi.org/10.3390/antiox10040618 - 17 Apr 2021
Cited by 7 | Viewed by 3130
Abstract
We investigated the effects of melatonin and its selected metabolites, i.e., N1-Acetyl-N2-formyl-5-methoxykynurenamine (AFMK) and 6-hydroxymelatonin (6(OH)Mel), on cultured human epidermal keratinocytes (HEKs) to assess their homeostatic activities with potential therapeutic implications. RNAseq analysis revealed a significant number [...] Read more.
We investigated the effects of melatonin and its selected metabolites, i.e., N1-Acetyl-N2-formyl-5-methoxykynurenamine (AFMK) and 6-hydroxymelatonin (6(OH)Mel), on cultured human epidermal keratinocytes (HEKs) to assess their homeostatic activities with potential therapeutic implications. RNAseq analysis revealed a significant number of genes with distinct and overlapping patterns, resulting in common regulation of top diseases and disorders. Gene Set Enrichment Analysis (GSEA), Reactome FIViZ, and Ingenuity Pathway Analysis (IPA) showed overrepresentation of the p53-dependent G1 DNA damage response gene set, activation of p53 signaling, and NRF2-mediated antioxidative pathways. Additionally, GSEA exhibited an overrepresentation of circadian clock and antiaging signaling gene sets by melatonin derivatives and upregulation of extension of telomere signaling in HEKs, which was subsequently confirmed by increased telomerase activity in keratinocytes, indicating possible antiaging properties of metabolites of melatonin. Furthermore, Gene Ontology (GO) showed the activation of a keratinocyte differentiation program by melatonin, and GSEA indicated antitumor and antilipidemic potential of melatonin and its metabolites. IPA also indicated the role of Protein Kinase R (PKR) in interferon induction and antiviral response. In addition, the test compounds decreased lactate dehydrogenase A (LDHA) and lactate dehydrogenase C (LDHC) gene expression. These results were validated by qPCR and by Seahorse metabolic assay with significantly decreased glycolysis and lactate production under influence of AFMK or 6(OH)Mel in cells with a low oxygen consumption rate. In summary, melatonin and its metabolites affect keratinocytes’ functions via signaling pathways that overlap for each tested molecule with some distinctions. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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Review

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20 pages, 1999 KiB  
Review
Melatonin: A Potential Regulator of DNA Methylation
by Kinga Linowiecka, Andrzej T. Slominski, Russel J. Reiter, Markus Böhm, Kerstin Steinbrink, Ralf Paus and Konrad Kleszczyński
Antioxidants 2023, 12(6), 1155; https://doi.org/10.3390/antiox12061155 - 25 May 2023
Cited by 9 | Viewed by 3904
Abstract
The pineal gland-derived indoleamine hormone, melatonin, regulates multiple cellular processes, ranging from chronobiology, proliferation, apoptosis, and oxidative damage to pigmentation, immune regulation, and mitochondrial metabolism. While melatonin is best known as a master regulator of the circadian rhythm, previous studies also have revealed [...] Read more.
The pineal gland-derived indoleamine hormone, melatonin, regulates multiple cellular processes, ranging from chronobiology, proliferation, apoptosis, and oxidative damage to pigmentation, immune regulation, and mitochondrial metabolism. While melatonin is best known as a master regulator of the circadian rhythm, previous studies also have revealed connections between circadian cycle disruption and genomic instability, including epigenetic changes in the pattern of DNA methylation. For example, melatonin secretion is associated with differential circadian gene methylation in night shift workers and the regulation of genomic methylation during embryonic development, and there is accumulating evidence that melatonin can modify DNA methylation. Since the latter one impacts cancer initiation, and also, non-malignant diseases development, and that targeting DNA methylation has become a novel intervention target in clinical therapy, this review discusses the potential role of melatonin as an under-investigated candidate epigenetic regulator, namely by modulating DNA methylation via changes in mRNA and the protein expression of DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins. Furthermore, since melatonin may impact changes in the DNA methylation pattern, the authors of the review suggest its possible use in combination therapy with epigenetic drugs as a new anticancer strategy. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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23 pages, 2144 KiB  
Review
Vitamin D Determinants, Status, and Antioxidant/Anti-inflammatory-Related Effects in Cardiovascular Risk and Disease: Not the Last Word in the Controversy
by Giulia Della Nera, Laura Sabatino, Melania Gaggini, Francesca Gorini and Cristina Vassalle
Antioxidants 2023, 12(4), 948; https://doi.org/10.3390/antiox12040948 - 18 Apr 2023
Cited by 13 | Viewed by 3684
Abstract
Beyond its key role in calcium homeostasis, vitamin D has been found to significantly affect the cardiovascular (CV) system. In fact, low vitamin D levels have been associated with increased CV risk, as well as increased CV morbidity and mortality. The majority of [...] Read more.
Beyond its key role in calcium homeostasis, vitamin D has been found to significantly affect the cardiovascular (CV) system. In fact, low vitamin D levels have been associated with increased CV risk, as well as increased CV morbidity and mortality. The majority of effects of this molecule are related directly or indirectly to its antioxidative and anti-inflammatory properties. Generally, vitamin D insufficiency is considered for 25-hydroxyvitamin D (25(OH)D) levels between 21–29 ng/mL (corresponding to 52.5–72.5 nmol/L), deficiency as 25(OH)D levels less than 20 ng/mL (<50 nmol/L), and extreme deficiency as 25(OH)D less than 10 ng/mL (<25 nmol/L). However, the definition of an optimal vitamin D status, as defined by 25(OH)D, remains controversial for many extra-bone conditions, including CV disease. In this review, confounding factors affecting the 25(OH)D measurement and status will be discussed. In particular, available evidence on the mechanism and role of vitamin D in relation to CV risk and disease through its antioxidant effect will be reported, also facing the aspect regarding the debate on the minimum blood 25(OH)D level required to ensure optimal CV health. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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16 pages, 1066 KiB  
Review
Developmental and Early Life Origins of Hypertension: Preventive Aspects of Melatonin
by You-Lin Tain and Chien-Ning Hsu
Antioxidants 2022, 11(5), 924; https://doi.org/10.3390/antiox11050924 - 8 May 2022
Cited by 3 | Viewed by 2420
Abstract
Hypertension represents a major disease burden worldwide. Abundant evidence suggests that hypertension can originate in early life. Adverse programming processes can be prevented by early life intervention—namely, reprogramming—to avoid developing chronic diseases later in life. Melatonin is an endogenously produced hormone with a [...] Read more.
Hypertension represents a major disease burden worldwide. Abundant evidence suggests that hypertension can originate in early life. Adverse programming processes can be prevented by early life intervention—namely, reprogramming—to avoid developing chronic diseases later in life. Melatonin is an endogenously produced hormone with a multifaceted biological function. Although melatonin supplementation has shown benefits for human health, less attention has been paid to exploring its reprogramming effects on the early life origins of hypertension. In this review, first, we discuss the physiological roles of melatonin in pregnancy, fetal development, and the regulation of blood pressure. Then, we summarize the epidemiological and experimental evidence for the early life origins of hypertension. This is followed by a description of the animal models used to examine early melatonin therapy as a reprogramming strategy to protect against the early life origins of hypertension. A deeper understanding of the developmental programming of hypertension and recent advances in early melatonin intervention might provide a path forward in reducing the global burden of hypertension. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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79 pages, 2046 KiB  
Review
Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders
by Doris Loh and Russel J. Reiter
Antioxidants 2021, 10(9), 1483; https://doi.org/10.3390/antiox10091483 - 17 Sep 2021
Cited by 21 | Viewed by 52581
Abstract
Biomolecular condensates are membraneless organelles (MLOs) that form dynamic, chemically distinct subcellular compartments organizing macromolecules such as proteins, RNA, and DNA in unicellular prokaryotic bacteria and complex eukaryotic cells. Separated from surrounding environments, MLOs in the nucleoplasm, cytoplasm, and mitochondria assemble by liquid–liquid [...] Read more.
Biomolecular condensates are membraneless organelles (MLOs) that form dynamic, chemically distinct subcellular compartments organizing macromolecules such as proteins, RNA, and DNA in unicellular prokaryotic bacteria and complex eukaryotic cells. Separated from surrounding environments, MLOs in the nucleoplasm, cytoplasm, and mitochondria assemble by liquid–liquid phase separation (LLPS) into transient, non-static, liquid-like droplets that regulate essential molecular functions. LLPS is primarily controlled by post-translational modifications (PTMs) that fine-tune the balance between attractive and repulsive charge states and/or binding motifs of proteins. Aberrant phase separation due to dysregulated membrane lipid rafts and/or PTMs, as well as the absence of adequate hydrotropic small molecules such as ATP, or the presence of specific RNA proteins can cause pathological protein aggregation in neurodegenerative disorders. Melatonin may exert a dominant influence over phase separation in biomolecular condensates by optimizing membrane and MLO interdependent reactions through stabilizing lipid raft domains, reducing line tension, and maintaining negative membrane curvature and fluidity. As a potent antioxidant, melatonin protects cardiolipin and other membrane lipids from peroxidation cascades, supporting protein trafficking, signaling, ion channel activities, and ATPase functionality during condensate coacervation or dissolution. Melatonin may even control condensate LLPS through PTM and balance mRNA- and RNA-binding protein composition by regulating N6-methyladenosine (m6A) modifications. There is currently a lack of pharmaceuticals targeting neurodegenerative disorders via the regulation of phase separation. The potential of melatonin in the modulation of biomolecular condensate in the attenuation of aberrant condensate aggregation in neurodegenerative disorders is discussed in this review. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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Other

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24 pages, 621 KiB  
Systematic Review
Vitamin D from UV-Irradiated Mushrooms as a Way for Vitamin D Supplementation: A Systematic Review on Classic and Nonclassic Effects in Human and Animal Models
by Mariangela Rondanelli, Alessia Moroni, Marco Zese, Clara Gasparri, Antonella Riva, Giovanna Petrangolini, Simone Perna and Giuseppe Mazzola
Antioxidants 2023, 12(3), 736; https://doi.org/10.3390/antiox12030736 - 16 Mar 2023
Cited by 4 | Viewed by 2861
Abstract
Recent literature has shown that vitamin D, in addition to its well-known activity on the skeleton, has many positive effects on health. Unfortunately, it is not easy to meet intake needs solely with food. Mushrooms could provide a valid way to achieve this [...] Read more.
Recent literature has shown that vitamin D, in addition to its well-known activity on the skeleton, has many positive effects on health. Unfortunately, it is not easy to meet intake needs solely with food. Mushrooms could provide a valid way to achieve this goal, because they are one of the few sources of vitamin D. The aim of this systematic review was to summarize what has been reported in the literature on the treatment of animal and human models with irradiated commercial mushrooms, with particular attention paid to the effects on clinical outcomes associated with the classical and nonclassical vitamin D functions. A total of 18 articles were selected. Six studies were conducted on human samples, while twelve were focused on animal models. The six studies conducted in humans involved a large number of subjects (663), but the treatment period was relatively short (1–6 months). Furthermore, the treatment dosage was different in the various groups (600–3800 IU/day). Probably for this reason, the studies did not demonstrate clinical efficacy on the parameters evaluated (cognitive functions, muscle system/function, metabolic syndrome). Indeed, those studies demonstrated an efficacy in increasing the blood levels of 25(OH)D2, but not in increasing the levels of 25(OH)D total. In 9 of 12 studies conducted on the animal model, however, a clinical efficacy on bone metabolism, inflammation, and cognitive performance was demonstrated. The results of this systematic review indicate that the intake of vitamin D from irradiated mushrooms could possibly help to meet vitamin D needs, but the dosage and the time of treatment tested need to be evaluated. Therefore, studies conducted in humans for longer periods than the studies carried out up to now are necessary, with defined dosages, in order to also evaluate the clinical efficacy demonstrated in animal models both for the classical (bone metabolism) and nonclassical (muscle function, cognitive performance, anti-inflammatory, and antioxidant activities) effects of vitamin D. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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19 pages, 1111 KiB  
Systematic Review
Vitamin D3 and COVID-19 Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses
by Fausto Petrelli, Simone Oldani, Karen Borgonovo, Mary Cabiddu, Giuseppina Dognini, Mara Ghilardi, Maria Chiara Parati, Daniela Petro’, Lorenzo Dottorini, Carmen Rea, Veronica Lonati, Andrea Luciani and Antonio Ghidini
Antioxidants 2023, 12(2), 247; https://doi.org/10.3390/antiox12020247 - 22 Jan 2023
Cited by 7 | Viewed by 6517
Abstract
Background: The immune system (innate and adaptive) is influenced by vitamin D3, which affects gene expression and inflammatory pathways. An umbrella review was conducted to evaluate the power and accuracy of data connecting vitamin D3 to the outcomes of COVID-19 infection and to [...] Read more.
Background: The immune system (innate and adaptive) is influenced by vitamin D3, which affects gene expression and inflammatory pathways. An umbrella review was conducted to evaluate the power and accuracy of data connecting vitamin D3 to the outcomes of COVID-19 infection and to appraise the proof provided by published meta-analyses. Methods: MEDLINE, Embase, and the Cochrane Library were searched from database inception to 31 May 2022. Meta-analyses of prospective or retrospective observational studies and randomized trials were included. Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. Results: From 74 publications, 27 meta-analyses described five associations between vitamin D3 levels and supplementation and COVID-19 outcomes. Low levels of vitamin D3 were significantly associated with severity (highly suggestive evidence; OR = 1.97 [95% CI, 1.55–2.51], p < 0.01; I2 = 77%, p < 0.01) and mortality risk due to COVID-19 disease (OR = 1.83 [95% CI, 1.55–2.16], p < 0.01; I2 = 50%, p < 0.01). Vitamin D3 supplementation, after a diagnosis of COVID-19 infection, was associated with significantly reduced infection severity (e.g., ICU admission) and mortality. Conclusions: This umbrella review of the available evidence suggests that insufficient vitamin D3 may increase COVID-19 infection risk, severity, and mortality, in addition to showing a highly suggestive association between vitamin D3 supplementation and reduced severity and mortality among infected patients. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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