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20 pages, 1135 KiB  
Review
Selenium as an Antioxidant: Roles and Clinical Applications in Critically Ill and Trauma Patients: A Narrative Review
by Jae-Gil Lee, Ji-Young Jang and Seung-Min Baik
Antioxidants 2025, 14(3), 294; https://doi.org/10.3390/antiox14030294 - 28 Feb 2025
Viewed by 208
Abstract
Selenium plays an indispensable role in antioxidant defense through its incorporation into selenoproteins, including glutathione peroxidase (GPx) and thioredoxin reductase. In the context of trauma and critical illness, systemic inflammation and oxidative stress frequently deplete selenium reserves, compromising the body’s antioxidant defenses. This [...] Read more.
Selenium plays an indispensable role in antioxidant defense through its incorporation into selenoproteins, including glutathione peroxidase (GPx) and thioredoxin reductase. In the context of trauma and critical illness, systemic inflammation and oxidative stress frequently deplete selenium reserves, compromising the body’s antioxidant defenses. This deficiency exacerbates immune dysfunction, elevates the risk of multi-organ dysfunction syndrome, and increases susceptibility to infections and mortality. Observational studies have consistently shown that lower selenium levels correlate with poorer clinical outcomes, such as extended stays in intensive care units and higher mortality rates. Supplementation of selenium has demonstrated promise in restoring GPx activity, reducing oxidative stress markers, and supporting recovery, particularly in patients with pre-existing selenium deficiency. While the impact on mortality remains variable across clinical trials, early and targeted supplementation appears to be beneficial, especially when combined with other micronutrients like vitamins C and E or zinc. These combinations enhance the antioxidant response and tackle the complex oxidative pathways in critically ill and trauma patients. Importantly, the clinical benefits of selenium supplementation appear to be influenced by baseline selenium status, with patients exhibiting severe deficiency deriving the most pronounced improvements in oxidative stress markers, immune function, and recovery. This review highlights the critical importance of addressing selenium deficiency, advocating for personalized therapeutic strategies. However, further large-scale studies are essential to optimize dosing regimens, refine combination therapies, and validate selenium’s therapeutic potential in trauma and critical care settings. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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Figure 1
<p>A simplified graph illustrating the systemic immune response following trauma, showing the progression of SIRS (systemic inflammatory response syndrome) and CARS (compensatory anti-inflammatory response syndrome) over time. The graph highlights how the body transitions from an initial inflammatory phase (SIRS) to an anti-inflammatory recovery phase (CARS), eventually returning to homeostasis if recovery is successful. SIRS typically emerges within the first few hours post-injury, driven by the release of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. CARS, characterized by anti-inflammatory mediators, follows within 24–48 h and can persist for several days to weeks, depending on the severity of trauma and host immune response. Recent evidence suggests that these two phases can overlap, with simultaneous pro- and anti-inflammatory signaling contributing to immune dysregulation in critically ill patients (Adapted from Cavaillon JM J, et al. J Endotoxin Res. 2001; 7 (2): 85–93. PMID: 11521088 [<a href="#B23-antioxidants-14-00294" class="html-bibr">23</a>]).</p>
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<p>Mechanism of glutathione peroxidase (GPx) redox pathway. Selenol (-SeH) in GPx is oxidized to selenic acid (-SeOH) by peroxide (ROOH), releasing H<sub>2</sub>O. Glutathione (GSH) reduces -SeOH to a selenenyl-sulfide intermediate (-Se-SG), which is further reduced to regenerate selenol (-SeH) while forming oxidized glutathione (GSSG). GSSG is reduced back to GSH by NADPH-dependent glutathione reductase (GR), with NADPH regenerated via glucose 6-phosphate dehydrogenase (G6PD) (Adapted from Pei J, et al. Front Pharmacol. 2023. DOI:10.3389/fphar.2023.1147414 [<a href="#B66-antioxidants-14-00294" class="html-bibr">66</a>]).</p>
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<p>Conceptual summary of clinical outcomes related to selenium deficiency and selenium supplementation in critically ill and trauma patients. This figure outlines the causes of selenium deficiency, including oxidative stress and inflammation, as well as the complications such as ARDS, AKI, and infections like VAP and BSI. It also illustrates the potential benefits of selenium supplementation, including reduced oxidative stress, improved oxygenation, and shorter ICU stays. This figure is a conceptual representation summarizing key findings from multiple studies rather than data from a single source. ARDS, acute respiratory distress syndrome; AKI, acute kidney injury; VAP, ventilator-associated pneumonia; BSI, bloodstream infection, ICU, intensive care unit; LOS, length of stay.</p>
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47 pages, 4501 KiB  
Review
Micronutrient Biofortification in Wheat: QTLs, Candidate Genes and Molecular Mechanism
by Adnan Nasim, Junwei Hao, Faiza Tawab, Ci Jin, Jiamin Zhu, Shuang Luo and Xiaojun Nie
Int. J. Mol. Sci. 2025, 26(5), 2178; https://doi.org/10.3390/ijms26052178 - 28 Feb 2025
Viewed by 198
Abstract
Micronutrient deficiency (hidden hunger) is one of the serious health problems globally, often due to diets dominated by staple foods. Genetic biofortification of a staple like wheat has surfaced as a promising, cost-efficient, and sustainable strategy. Significant genetic diversity exists in wheat and [...] Read more.
Micronutrient deficiency (hidden hunger) is one of the serious health problems globally, often due to diets dominated by staple foods. Genetic biofortification of a staple like wheat has surfaced as a promising, cost-efficient, and sustainable strategy. Significant genetic diversity exists in wheat and its wild relatives, but the nutritional profile in commercial wheat varieties has inadvertently declined over time, striving for better yield and disease resistance. Substantial efforts have been made to biofortify wheat using conventional and molecular breeding. QTL and genome-wide association studies were conducted, and some of the identified QTLs/marker-trait association (MTAs) for grain micronutrients like Fe have been exploited by MAS. The genetic mechanisms of micronutrient uptake, transport, and storage have also been investigated. Although wheat biofortified varieties are now commercially cultivated in selected regions worldwide, further improvements are needed. This review provides an overview of wheat biofortification, covering breeding efforts, nutritional evaluation methods, nutrient assimilation and bioavailability, and microbial involvement in wheat grain enrichment. Emerging technologies such as non-destructive hyperspectral imaging (HSI)/red, green, and blue (RGB) phenotyping; multi-omics integration; CRISPR-Cas9 alongside genomic selection; and microbial genetics hold promise for advancing biofortification. Full article
(This article belongs to the Special Issue Wheat Genetics and Genomics: 3rd Edition)
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<p>Proposed simplified illustration of Fe, Zn, and Se uptake, transport, and sequestration in wheat based on evidence from model species or wheat; question marks show unidentified transporters. PS; phytosiderophore, PSVs; protein storage vacuole; SP = small proteins, Chelators = nicotian.</p>
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<p>An infographic illustration of the omics integration with speed breeding and genome editing can help attain wheat biofortification.</p>
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22 pages, 2310 KiB  
Article
Enhancing Organic Selenium Forms in Alfalfa Forage Through Inorganic Selenium Foliar Application: Insights from Laboratory and Field Studies Using X-Ray Spectroscopy
by María-Jesús Sánchez-Martín, Mónica Gaggiotti, Laura Simonelli, Carlo Marini, Federico Marini, Roberto Boada, Mercè Llugany, Manuel Valiente, Gabriel Céccoli, María Micaela Stoffel, Marcia Viltres-Portales, Juan Manuel Picco, María Gabriela Guevara and Fernando Felipe Muñoz
Agronomy 2025, 15(3), 580; https://doi.org/10.3390/agronomy15030580 - 26 Feb 2025
Viewed by 265
Abstract
Selenium (Se) is an essential micronutrient, yet its deficiency remains a global concern. This study investigates the biofortification of alfalfa (Medicago sativa cv. ProINTA Super Monarca GR9) via foliar Se application to enhance Se accumulation and transformation into bioavailable organic forms. A [...] Read more.
Selenium (Se) is an essential micronutrient, yet its deficiency remains a global concern. This study investigates the biofortification of alfalfa (Medicago sativa cv. ProINTA Super Monarca GR9) via foliar Se application to enhance Se accumulation and transformation into bioavailable organic forms. A controlled environment experiment in a plant growth chamber and a one-season open-field trial (January 2023, Argentina) were conducted. Treatments included sodium selenate (Se(VI)), sodium selenite (Se(IV)), and a 1:1 mixture, applied at 45 and 90 g Se ha−1, with and without the biostimulant BIOFORGE®. Treated plants exhibited increased Se content, correlating with the applied doses. X-ray absorption spectroscopy (XAS) confirmed that most inorganic Se was transformed into organic Se forms, with Se(IV) treatments yielding the highest concentrations of organic Se species such as selenocysteine (SeCys) and selenomethionine (SeMet). Open-field trials showed a complete conversion of Se, though total Se accumulation was lower than in controlled conditions. Se treatments did not affect forage quality or biomass production. The biostimulant slightly reduced Se uptake but did not compromise biofortification. These results highlight Se(IV) as the optimal treatment for alfalfa biofortification, presenting a sustainable strategy to enhance dietary Se intake through functional foods. Full article
(This article belongs to the Special Issue Conventional and Alternative Fertilization of Crops)
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<p>Effect of foliar selenium application on the leaf net photosynthetic rate (Pn) in alfalfa plants grown under different Se treatments in controlled conditions. -BIO: without biostimulant, +BIO: with biostimulant (BIOFORGE<sup>®</sup> 600 mL ha<sup>−1</sup>), Se(Mix):Se(VI)/Se(IV) (1:1). Results are expressed as mean (n = 5) ± SE. Means not sharing any letter are significantly different by LSD test at <span class="html-italic">p</span> &lt; 0.05 level of significance.</p>
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<p>Total selenium concentration in the aerial part of alfalfa plants grown under different Se treatments in controlled conditions. -BIO: without biostimulant, +BIO: with biostimulant (BIOFORGE<sup>®</sup> 600 mL ha<sup>−1</sup>), Se(Mix): Se(VI)/Se(IV) (1:1). Results are expressed as mean (n = 3) ± SE. Means not sharing any letter are significantly different by the LSD test at <span class="html-italic">p</span> &lt; 0.05 level of significance.</p>
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<p>(<b>A</b>) Se K-edge XANES spectra collected over the aerial part of alfalfa plants grown under different selenium treatments in controlled conditions and compared with references (top row) and (<b>B</b>) with the obtained MCR components. Different selenium treatments are represented with different colors, where blue, red and violet corresponds to Se(VI), Se(IV) and Se(Mix); dark and light colors to 90 and 45 g ha<sup>−1</sup> of dose; and continuous and dashed lines to with and without biostimulant, respectively.</p>
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<p>MCR component relative concentrations for the laboratory culture. Components 1, 2, 3, and 5 correspond to Se(VI), Se(IV), SeCys, and SeMet/SeMetCys, respectively. Component 4 represents unknown Se species.</p>
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<p>MCR concentrations as a function of selenium content, distinguishing between Se(IV) (left), Se(Mix) (middle), and Se(VI) (right) applications.</p>
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<p>Correlation map between Se species concentrations and agronomic parameters.</p>
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<p>Total selenium concentration in the aerial parts of alfalfa plants grown under different Se treatments in open-field conditions. -BIO: without biostimulant; +BIO: with biostimulant (BIOFORGE<sup>®</sup> 600 mL ha<sup>−1</sup>). Results are expressed as the mean (n = 3) ± SE. Means not sharing any letter are significantly different according to the LSD test at <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>(<b>A</b>) Se K-edge XANES spectra collected from alfalfa plants grown under different selenium treatments in open-field conditions, compared with references and (<b>B</b>) the MCR components obtained. The different treatments are represented with distinct colors: dark and light shades correspond to doses of 90 and 45 g ha<sup>−1</sup>, respectively; continuous and dashed lines indicate treatments with and without the biostimulant, respectively.</p>
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<p>MCR component relative concentrations for open-field cultures. Components 1, 2, 3, and 5 correspond to Se(VI), Se(IV), SeCys, and SeMet/SeMeCys, respectively. Component 4 represents unknown Se species.</p>
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<p>Correlation map between the Se species concentrations and the agronomic parameters for open-field cultivations.</p>
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31 pages, 1832 KiB  
Review
Unveiling the Role of Selenium in Child Development: Impacts on Growth, Neurodevelopment and Immunity
by Gulnara Batyrova, Gulaim Taskozhina, Gulmira Umarova, Yeskendir Umarov, Marina Morenko, Bakhtiyar Iriskulov, Khatimya Kudabayeva and Yerlan Bazargaliyev
J. Clin. Med. 2025, 14(4), 1274; https://doi.org/10.3390/jcm14041274 - 14 Feb 2025
Viewed by 380
Abstract
Selenium (Se) is a vital trace element for children, playing a crucial role in numerous physiological processes, including antioxidant defense, immune regulation, thyroid function, and bone metabolism. Emerging evidence highlights its potential impact on child development and growth while also underscoring the complexity [...] Read more.
Selenium (Se) is a vital trace element for children, playing a crucial role in numerous physiological processes, including antioxidant defense, immune regulation, thyroid function, and bone metabolism. Emerging evidence highlights its potential impact on child development and growth while also underscoring the complexity of its mechanisms and the global variations in Se intake. The aim of this review is to comprehensively elucidate the significance of Se in various biological processes within the human body, with a focus on its role in child development and growth; its biochemical effects on the nervous system, thyroid function, immune system, and bone tissue; and the implications of Se deficiency and toxicity. This review integrates findings from experimental models, epidemiological studies, and clinical trials to explore Se’s role in neurodevelopment, growth regulation, and immune competence in children. Selenoproteins, which regulate oxidative stress and thyroid hormone and bone metabolism, are essential for normal growth and cognitive development in children. Se deficiency and toxicity has been linked to impaired immune function, growth retardation, and decreased immune function. The findings underscore Se’s influence on various biological pathways that are critical for healthy child development and its broader importance for child health. Public health strategies aimed at optimizing selenium intake may play a pivotal role in improving pediatric health outcomes worldwide. Full article
(This article belongs to the Special Issue Endocrine Disorders in Children)
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Graphical abstract

Graphical abstract
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<p>Selenium (Se) metabolism in the human body [<a href="#B61-jcm-14-01274" class="html-bibr">61</a>]. The metabolism of dietary Se, including its absorption, transport, and distribution. Se from food (e.g., selenomethionine and selenocysteine) is absorbed in the intestine, converted to hydrogen selenide (H<sub>2</sub>Se), and transported to the liver, where it is used for selenoprotein synthesis, including selenoprotein P. Selenoprotein P facilitates Se transport to target tissues such as the brain, kidneys, and bones, supporting essential biological functions.</p>
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<p>The role of selenium (Se) in child development and growth [<a href="#B74-jcm-14-01274" class="html-bibr">74</a>]. Se is involved in the regulation of neurotransmitter systems, which are critical for cognitive and neural development. Se protects the thyroid gland by contributing to the synthesis and regulation of thyroid hormones (T3 and T4), reducing the risk of thyroid disorders. Se supports healthy puberty and the development of the reproductive system. This is symbolized by a transition from childhood to adolescence, with representations of reproductive organs and hormonal signaling. Se plays a critical role in antioxidant defense by neutralizing ROS. Cells are depicted as shielded from oxidative damage, highlighting selenium’s contribution to cellular health. Selenium enhances immune responses, protecting against infections and modulating immune cell activity.</p>
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<p>Selenium-associated pathways contributing to neural damage [<a href="#B104-jcm-14-01274" class="html-bibr">104</a>]. Selenium is transported to neurons via its incorporation into selenoprotein P (SELENOP), which interacts with its receptor, low-density lipoprotein receptor-related protein 8 (LRP8), also referred to as apolipoprotein receptor E2 (ApoER2). This mechanism plays a crucial role in maintaining antioxidant defenses by enabling selenoproteins to mitigate the harmful effects of reactive oxygen species (ROS). Dysfunction in selenium transport pathways can lead to the suppression of protective mechanisms, upregulation of harmful gene expression, and the onset of mitochondrial dysfunction resulting from DNA damage. Such impairments are closely linked to the development of neurological disorders, including cognitive impairment.</p>
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<p>The role of selenium (Se) in metabolic pathways of inflammation [<a href="#B166-jcm-14-01274" class="html-bibr">166</a>]. The figure illustrates the role of selenium in mitigating oxidative stress at the cellular level through its incorporation into selenoproteins. Se modulates the NFkB signaling pathway, a key regulator of pro-inflammatory cytokine genes. This activation of leukocytes leads to increased cytokine expression.</p>
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20 pages, 315 KiB  
Article
Diet Quality and Nutritional Assessment of Menus Served in Spanish Defense Ministry Preschool Canteens
by Diego Lozano, María Abenoza, Susana Bayarri and Regina Lázaro
Nutrients 2025, 17(4), 661; https://doi.org/10.3390/nu17040661 - 12 Feb 2025
Viewed by 588
Abstract
Background/Objectives: A healthy diet in early childhood has been shown to be one of the essential mainstays for the development of children. Few studies have been conducted on preschool canteens, despite the fact that they play a crucial role. Our study aimed [...] Read more.
Background/Objectives: A healthy diet in early childhood has been shown to be one of the essential mainstays for the development of children. Few studies have been conducted on preschool canteens, despite the fact that they play a crucial role. Our study aimed to assess the dietary and nutritional quality of the menus served in Spanish Defense Ministry preschool education centers (1–3 years old) and to ascertain their compliance with dietary and nutritional recommendations. We also evaluated the influence of the canteen management model. Methods: Our cross-sectional observational study was carried out on the 448 menus offered in the 25 centers (operating under two management models: direct and contracted) of the Spanish Ministry of Defense during a school year all across the Spanish territory. Results: Under the contracted management model, the frequency of rice was low, as well as that of salads, eggs, fish, and fruit. The rotation within the fish group did not comply with recommendations, showing a shortage of oily fish. The menus’ energy values were correct, but the energy profile in the contracted management menus was higher than recommended in protein and fat while being lower in carbohydrates. The lipid profile was adequate. Values were high in cholesterol, simple sugars, fiber, vitamin K, selenium, potassium, and sodium; they were deficient in omega-3 fatty acids, vitamin D, iodine, and zinc. Conclusions: These results could help to establish special references or limits for the Spanish preschool population. Full article
(This article belongs to the Special Issue Healthy Nutrition and Lifestyle: The Role of the School)
18 pages, 8822 KiB  
Article
Microbial Selenium-Enriched Bacterial Fertilizer: Biofortification Technology to Boost Pea Sprout Quality and Selenium Content
by Yaqi Wang, Ying Li, Yu Wu, Yang Liu, Yadong Chen, Yanlong Zhang and Xiangqian Jia
Agronomy 2025, 15(2), 430; https://doi.org/10.3390/agronomy15020430 - 9 Feb 2025
Viewed by 600
Abstract
Selenium-enriched vegetables are a safe way to combat selenium deficiency in humans. Here, a new microbial selenium-enriched bacterial fertilizer (named “HJ”) was prepared and studied by dipping, and then its application strategy was optimized and compared with other commercially available selenium fertilizers. The [...] Read more.
Selenium-enriched vegetables are a safe way to combat selenium deficiency in humans. Here, a new microbial selenium-enriched bacterial fertilizer (named “HJ”) was prepared and studied by dipping, and then its application strategy was optimized and compared with other commercially available selenium fertilizers. The results showed that the application of HJ selenium fertilizer to peas by soaking (Se concentration 10 μg/mL) and foliar application (Se concentration 8 μg/mL) could effectively enhance their growth, selenium enrichment ability, stress tolerance and nutritional quality. In particular, the selenium content of peas in the HJ-treated group exhibited a significant increase of 69.86% in comparison with the control group. Moreover, HJ treated pea sprouts demonstrated enhanced antioxidant activity, as well as elevated levels of vitamin C and protein, amongst other observations. The findings of this study offer novel insights into the development of eco-friendly selenium fertilizers and provide guidance for optimal fertilizer application techniques. Full article
(This article belongs to the Section Soil and Plant Nutrition)
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<p>Schematic diagram of the experimental procedure. (<b>A</b>) Preparation of selenium-enriched bacterial fertilizer HJ. (<b>B</b>) Optimization of HJ application strategies in pea sprouts production. (<b>C</b>) Comparison of HJ with different selenium fertilizers. In the Figure, HA refers to humic acid, COS denotes chitosan oligosaccharides, and PEG400 denotes polyethylene glycol 400. HJ is the experimental group, and P1, P2 and P3 of the positive control group represent three kinds of commercial selenium fertilizers, “KaiJin”, “ZhenXi” and “SiJiFeng”.</p>
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<p>Pea seeds soaking experiment. (<b>A</b>) Flow chart of the experiment, (<b>B</b>) Graph of the imbibing solution, (<b>C</b>) Results of seed germination potential and germination rate, and (<b>D</b>) Results of fresh weight and dry weight of pea sprouts after imbibition. Different lowercase letters indicate significant differences (<span class="html-italic">p</span> &lt; 0.05) between the two groups.</p>
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<p>Optimization of HJ application strategies in pea sprouts production. (<b>A</b>) Shoot length, (<b>B</b>) Root length, (<b>C</b>) Edibility rate, (<b>D</b>) Total Se content, (<b>E</b>) Soluble protein content, (<b>F</b>) Soluble sugar content, (<b>G</b>) Chlorophyll a content, (<b>H</b>) Chlorophyll b content, (<b>I</b>) Total chlorophyll content, and (<b>J</b>) Carotenoids content. Different lowercase letters indicate significant differences (<span class="html-italic">p</span> &lt; 0.05) between the two groups.</p>
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<p>Comparison of the effects of different application methods for selenium concentration of 8 μg/mL HJ. (<b>A</b>) Shoot length, (<b>B</b>) Root length, (<b>C</b>) Edibility rate, (<b>D</b>) Total Se content, (<b>E</b>) Soluble protein content, (<b>F</b>) Soluble sugar content, (<b>G</b>) Chlorophyll a content, (<b>H</b>) Chlorophyll b content, (<b>I</b>) Total chlorophyll content, and (<b>J</b>) Carotenoids content. Different lowercase letters indicate significant differences (<span class="html-italic">p</span> &lt; 0.05) between the two groups.</p>
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<p>Effects of various selenium fertilizers on growth indexes, total Se content and physiological indexes of pea sprouts. (<b>A</b>) Comparison of pea sprouts in each treatment group, (<b>B</b>) Shoot length, (<b>C</b>) Root length, (<b>D</b>) Edibility rate, (<b>E</b>) Fresh weight, (<b>F</b>) Dry weight, (<b>G</b>) Water content, (<b>H</b>) Total Se content, (<b>I</b>) Soluble protein content, (<b>J</b>) Soluble sugar content, (<b>K</b>) Chlorophyll b content, (<b>L</b>) Chlorophyll a content, (<b>M</b>) Total chlorophyll content, and (<b>N</b>) Carotenoids content. In the Figure, HJ is the experimental group and P1, P2 and P3 of the positive control group represent three kinds of commercial selenium fertilizers, “KaiJin”, “ZhenXi” and “SiJiFeng”. Different lowercase letters indicate significant differences (<span class="html-italic">p</span> &lt; 0.05) between the two groups.</p>
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<p>Effect of various selenium fertilizers on antioxidant enzyme activities and nutritional quality of pea sprouts. (<b>A</b>) SOD activity, (<b>B</b>) POD activity, (<b>C</b>) CAT activity, (<b>D</b>) MDA content, (<b>E</b>) free amino acids, (<b>F</b>) vitamin C, and (<b>G</b>) nitrate nitrogen. In the Figure, HJ is the experimental group and P1, P2 and P3 of the positive control group represent three kinds of commercial selenium fertilizers, “KaiJin”, “ZhenXi” and “SiJiFeng”. Different lowercase letters indicate significant differences (<span class="html-italic">p</span> &lt; 0.05) between the two groups.</p>
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<p>Radar analysis of the effects of different selenium fertilizers on various indicators of pea sprouts. In the Figure, HJ is the experimental group, and P1, P2 and P3 of the positive control group represent three kinds of commercial selenium fertilizers, “KaiJin”, “ZhenXi” and “SiJiFeng”.</p>
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16 pages, 719 KiB  
Article
Nutritional Characterisation of Childhood Chronic Kidney Disease: Trace Element Malnutrition in Paediatric Renal Disease (TeMPeReD) Study
by Matthew J. Harmer, Stephen A. Wootton, Rodney D. Gilbert and Caroline E. Anderson
Nutrients 2025, 17(3), 535; https://doi.org/10.3390/nu17030535 - 31 Jan 2025
Viewed by 779
Abstract
Background/Objectives: In chronic kidney disease (CKD), poor nutrition is associated with poorer clinical outcomes. There are limited data on milder stages of childhood CKD. Methods: This study characterised the nutritional state of a cohort of children with CKD. Results: Within the cohort (mean [...] Read more.
Background/Objectives: In chronic kidney disease (CKD), poor nutrition is associated with poorer clinical outcomes. There are limited data on milder stages of childhood CKD. Methods: This study characterised the nutritional state of a cohort of children with CKD. Results: Within the cohort (mean age 10.5 years, mean eGFR = 57 mL/min/1.73 m2), obesity defined by body mass index rates was comparable to that in the general population, but central obesity (waist-to-height ratio > 0.5) was evident in 44% of children. Although average nutrient intakes for the cohort were acceptable, there was marked variability in the risk of poor nutrient intake (<LRNI): selenium (35%), magnesium (35%), iodine (30%), and zinc (30%). No child met the recommended dietary fibre intake. The prevalence of frank deficiency of vitamins and minerals in blood concentrations was low. Blood concentrations of vitamins A and E were near-universally elevated. In those who had a decline in kidney function at the 12-month follow-up, dietary intake of fibre correlated with the degree of decline. Conclusions: Much work is needed to optimise the nutritional status of children with CKD as an important modifiable risk factor for disease progression and other important outcomes. Full article
(This article belongs to the Section Pediatric Nutrition)
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<p>Baseline Anthropometry SDS. Standardised deviation scores for height, weight, body mass index, mid-upper arm circumference, and height velocity are shown for the entire cohort. Median scores with interquartile ranges are shown in red. The black dotted lines represent the normal reference range of −2 to +2 SD. Most children lay within the normal reference range for measurements, but compared to the reference standard, the group was shorter, with a large variation in height velocity. The variation in height velocity may represent the shifting of the normal growth curve to the right, with a delayed pubertal growth spurt and/or catch-up growth following. Abbreviations: BMI—body mass index; Ht—height; Ht Vel—height velocity; MUAC—mid-upper arm circumference; SDS—standardised deviation score; Wt—weight.</p>
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<p>Distributions of blood concentrations of vitamins A and E. Reports the distribution of vitamin A (total retinol) and vitamin E (total tocopherols) in the cohort, with the normal reference ranges indicated by the dotted lines. Both vitamins were elevated in the majority of children, with a range of values up to 3 times the upper normal reference range. The clinical significance of this has yet to be determined in children with chronic kidney disease.</p>
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28 pages, 2730 KiB  
Review
Minerals and Human Health: From Deficiency to Toxicity
by Mohammed S. Razzaque and Sunil J. Wimalawansa
Nutrients 2025, 17(3), 454; https://doi.org/10.3390/nu17030454 - 26 Jan 2025
Cited by 1 | Viewed by 2431
Abstract
Minerals are essential nutrients that play critical roles in human health by regulating various physiological functions. Examples include bone development, enzyme function, nerve signaling, and the immune response. Both the deficiencies and toxicities of minerals can have significant health implications. Deficiencies in macrominerals [...] Read more.
Minerals are essential nutrients that play critical roles in human health by regulating various physiological functions. Examples include bone development, enzyme function, nerve signaling, and the immune response. Both the deficiencies and toxicities of minerals can have significant health implications. Deficiencies in macrominerals such as calcium, magnesium, and phosphate can lead to osteoporosis (associated with falls and fractures), cardiovascular events, and neuromuscular dysfunction. Trace mineral deficiencies, such as iron and zinc. Selenium deficiency impairs oxygen transport, immune function, and antioxidant defenses, contributing to anemia, delaying wound healing, and increasing susceptibility to infectious diseases. Conversely, excessive intake of minerals can have severe health consequences. Hypercalcemia can cause kidney stones and cardiac arrhythmias as well as soft-tissue calcification, whereas excessive iron deposition can lead to oxidative stress and organ/tissue damage. Maintaining adequate mineral levels through a balanced diet, guided supplementation, and monitoring at-risk populations is essential for good health and preventing disorders related to deficiencies and toxicities. Public health interventions and education about dietary sources of minerals are critical for minimizing health risks and ensuring optimal well-being across populations. While a comprehensive analysis of all macro and micronutrients is beyond the scope of this article, we have chosen to focus on calcium, magnesium, and phosphate. We summarize the consequences of deficiency and the adverse events associated with the overconsumption of other minerals. Full article
(This article belongs to the Special Issue Mineral Nutrition on Human Health and Disease)
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<p>The figure depicts essential minerals with primary functions.</p>
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<p>Major physiological and biological regulators and controls are illustrated [Fibroblast growth factor 23 (FGF23)].</p>
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<p>Different body systems, tissues, and diseases require varying steady-state serum 25(OH)D concentrations to prevent initiation and progression. The left side of the figure presents the minimum (average) serum 25(OH)D concentrations needed to obtain optimum clinical outcomes. In contrast, the right side depicts the percentage risk reduction for each disease entity [25(OH)D;25-hydroxyvitamin D] (modified from Wimalawansa) [<a href="#B94-nutrients-17-00454" class="html-bibr">94</a>].</p>
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<p>A few important nutrients with approximate total (diet plus supplements) daily requirements during pregnancy and lactation.</p>
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15 pages, 16929 KiB  
Article
Non-Targeted Metabolome Analysis with Low-Dose Selenate-Treated Arabidopsis
by Hongqiao Li, Tetsuya Mori, Rintaro Moriyama, Moeka Fujita, Genki Hatanaka, Naoki Shiotsuka, Ryota Hosomi and Akiko Maruyama-Nakashita
Plants 2025, 14(3), 322; https://doi.org/10.3390/plants14030322 - 22 Jan 2025
Viewed by 690
Abstract
Selenate, the most common form of selenium (Se) in soil environments, is beneficial for higher plants. Selenate is similar to sulfate in terms of the structure and the manner of assimilation by plants, which involves the reduction of selenate to selenide and the [...] Read more.
Selenate, the most common form of selenium (Se) in soil environments, is beneficial for higher plants. Selenate is similar to sulfate in terms of the structure and the manner of assimilation by plants, which involves the reduction of selenate to selenide and the replacement of an S moiety in the organic compounds such as amino acids. The nonspecific incorporation of seleno-amino acids into proteins induce Se toxicity in plants. Selenate alters the plant metabolism, particularly the S metabolism, which is comparable to the responses to S deficiency (−S). However, previous analyses involved high concentrations of selenate, and the effects of lower selenate doses have not been elucidated. In this study, we analyzed the metabolic changes induced by selenate treatment through a non-targeted metabolome analysis and found that 2 µM of selenate decreased the S assimilates and amino acids, and increased the flavonoids, while the glutathione levels were maintained. The results suggest that the decrease in amino acid levels, which is not detected under −S, along with the disruptions in S assimilation, amino acid biosynthesis pathways, and the energy metabolism, present the primary metabolic influences of selenate. These results suggest that selenate targets the energy metabolism and S assimilation first, and induces oxidative stress mitigation, represented by flavonoid accumulation, as a key adaptive response, providing a novel, possible mechanism in plant stress adaptation. Full article
(This article belongs to the Special Issue Advances in Plant and Food Metabolomics)
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<p>The effects of different concentrations of selenate on plant growth and low-S-inducible gene expressions. Plants were grown for 2 weeks on an agar medium supplemented with various concentrations of K<sub>2</sub>SeO<sub>4</sub> (0, 2, 10, 20, and 50 μM). RNA was extracted from the plants exposed to 0, 2, and 10 μM of selenate and analyzed via quantitative RT-PCR. (<b>A</b>) Representative plant image (top). Shoot (left graph) and root (middle graph) fresh weights, and root-to-shoot ratios (right graph). Bars represent mean ± SE (n = 3). One-way ANOVA followed by the Tukey–Kramer test was performed; significant differences (<span class="html-italic">p</span> &lt; 0.05) are indicated by distinct letters. (<b>B</b>) Transcript levels of <span class="html-italic">BGLU28</span>, <span class="html-italic">APR3</span>, <span class="html-italic">SULTR1;1</span>, and <span class="html-italic">SULTR1;2</span> in the shoots and roots with different treatments. Relative mRNA levels were calculated using the ΔΔCt method, with <span class="html-italic">ACT2</span> as an internal control. Bars represent mean ± SE (n = 3). Asterisks denote significant differences compared to the control (0 μM) (Dunnett’s test; * 0.05 ≤ <span class="html-italic">p</span> &lt; 0.1).</p>
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<p>Metabolomic changes caused by selenate. Plants were grown for 2 weeks on agar media supplemented with 0 or 2 μM of selenate (K<sub>2</sub>SeO<sub>4</sub>). After freeze-drying, the samples were subjected to non-targeted metabolome analysis using LCMS. Peak picking and peak annotation to a metabolite were performed as described in the Materials and Methods section. (<b>A</b>) PCA of the metabolites detected in the plants grown in the presence of 0 and 2 μM of selenate. (<b>B</b>) Metabolites significantly influenced by the 2 μM selenate treatment. We selected the metabolites with PC1 loading values of &gt;0.5 or &lt;−0.5 and curated them for their identities. P and N in the metabolite ID column represent positive and negative ion modes; RT, retention time (min); PC1, loading values for PC1 with the color gradient from magenta to blue representing most minus to most plus values; MSI level [<a href="#B18-plants-14-00322" class="html-bibr">18</a>], metabolites defined by the authentic standard or the MS/MS spectra from the references [<a href="#B19-plants-14-00322" class="html-bibr">19</a>,<a href="#B20-plants-14-00322" class="html-bibr">20</a>,<a href="#B21-plants-14-00322" class="html-bibr">21</a>,<a href="#B22-plants-14-00322" class="html-bibr">22</a>,<a href="#B23-plants-14-00322" class="html-bibr">23</a>]; Ref, reference. −Se, +Se, average of the metabolite intensities when plants were grown 0, 2 µM of selenate with the color gradient from blue to orange representing the lowest to the highest; +Se/−Se, The ratio of intensities between +Se and −Se with the color gradient from green to orange representing the lowest to the highest.</p>
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<p>Effects of selenate on the S-, Se-, N-containing metabolite levels in <span class="html-italic">Arabidopsis thaliana</span>. Plants were grown for 2 weeks on agar media supplemented with 0 or 2 μM of selenate (K<sub>2</sub>SeO<sub>4</sub>). After freeze-drying, the samples were used for the metabolite analysis, as described in the Materials and Methods section. (<b>A</b>) The total S and S contents in protein fractions of the plants grown under 0 or 2 μM of selenate. (<b>B</b>) Sulfate, cysteine, and glutathione contents in the plants. (<b>C</b>) Glucosinolate contents in the plants. (<b>D</b>) Camalexin content in the plants. (<b>E</b>) Amino acid content in the plants. (<b>F</b>) Total Se, Se contents in the protein fractions, and selenocysteine (SeCys), selenite, and selenate contents in the plants. Bars and error bars represent the mean and standard error (n = 3), respectively. Asterisks indicate significant differences between the two conditions, as determined by Student’s <span class="html-italic">t</span>-test (*** <span class="html-italic">p</span> &lt; 0.01).</p>
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<p>Changes in the metabolite profiles in plants induced by the selenate treatment. Metabolites exhibiting significantly increased and decreased levels are indicated by orange boxes and green boxes, respectively, and the fold changes are indicated by the color gradient, as shown with the boxes on the bottom. Metabolites that were not changed or detected are indicated by open boxes or no background, respectively. Asp and Glu were categorized in the no-change group, as their increase and decrease were not identical between the LCMS and HPLC analyses (<a href="#plants-14-00322-f002" class="html-fig">Figure 2</a>B and <a href="#plants-14-00322-f003" class="html-fig">Figure 3</a>E; <a href="#app1-plants-14-00322" class="html-app">Tables S1 and S2</a>). Continuous arrows represent one-step reactions and dashed arrows indicate a series of biochemical reactions.</p>
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21 pages, 3275 KiB  
Article
Diet, Advanced Maternal Age, and Neonatal Outcomes: Results from the GESTAGE Study
by Maria Puche-Juarez, Juan M. Toledano, Daniel Hinojosa-Nogueira, Catalina de Paco Matallana, Javier Sánchez-Romero, Julio J. Ochoa, Maria Paz Carrillo, Estefanía Martín-Álvarez, Javier Diaz-Castro and Jorge Moreno-Fernandez
Nutrients 2025, 17(2), 321; https://doi.org/10.3390/nu17020321 - 17 Jan 2025
Viewed by 1404
Abstract
Maternal nutrition during pregnancy plays a pivotal role in influencing both maternal and fetal health, impacting neonatal anthropometric outcomes and long-term disease susceptibility. An advanced maternal age (AMA ≥ 35 years) has been linked to increased risks of obstetric complications and adverse neonatal [...] Read more.
Maternal nutrition during pregnancy plays a pivotal role in influencing both maternal and fetal health, impacting neonatal anthropometric outcomes and long-term disease susceptibility. An advanced maternal age (AMA ≥ 35 years) has been linked to increased risks of obstetric complications and adverse neonatal outcomes, yet its specific nutritional profile remains underexplored. Background/Objectives: This study aimed to evaluate the nutrient and polyphenol intakes of women at an AMA compared to those of a younger control group and to investigate associations with neonatal anthropometric measures. Methods: A cohort of 200 pregnant women, stratified into AMA and control groups, completed a food frequency questionnaire during the second trimester. Neonatal anthropometric data were collected at delivery. Results: Intakes of fiber, zinc, copper, selenium, vitamins E, B1, B3 and folate were lower in the AMA group in comparison with the control values. Negative correlations were found between fiber, vitamin A and vitamin E and the head circumference of the newborn, with fiber being identified as a potential predictor of this parameter. Conclusions: Despite some limitations, such as the fact that the FFQ was completed only once during pregnancy and the cross-sectional design of the study, the findings highlight notable nutritional deficiencies among AMA women, which may influence neonatal outcomes such as head circumference. These results underscore the need for nutritional guidelines and supplementation strategies tailored to pregnant women over 35 years of age. Full article
(This article belongs to the Section Nutrition in Women)
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<p>AMA: advanced maternal age; ns: not significant. Comparison between control and AMA at groups of food level, assessed by a food frequency questionnaire.</p>
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<p>AMA: advanced maternal age; ns: not significant. Comparison between groups of the mean intake macronutrients, evaluated by <span class="html-italic">t</span>-test or U-Mann–Whitney (*** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>AMA: advanced maternal age; DRV: dietary reference value. Comparison of the mean intake of nutrients by group, with the dietary reference values (DRVs) from the AESAN.</p>
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<p>Correlations between energy and macronutrients, including fiber, and anthropometric measures of the newborn (* <span class="html-italic">p</span> &lt; 0.05, in red square).</p>
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<p>Correlations between vitamins and anthropometric measures of the newborn (* <span class="html-italic">p</span> &lt; 0.05, in red square).</p>
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<p>Regression model and linear regression found between fiber and head circumference.</p>
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19 pages, 5945 KiB  
Article
The Inhibitory Effects of NCT503 and Exogenous Serine on High-Selenium Induced Insulin Resistance in Mice
by Shuo Zhan, Jianrong Wang, Mingyu Zhu, Yiqun Liu, Feng Han, Licui Sun, Qin Wang and Zhenwu Huang
Nutrients 2025, 17(2), 311; https://doi.org/10.3390/nu17020311 - 16 Jan 2025
Viewed by 664
Abstract
Objective: This study aims to identify whether the development of insulin resistance (IR) induced by high selenium (Se) is related to serine deficiency via the inhibition of the de novo serine synthesis pathway (SSP) by the administrations of 3-phosphoglycerate dehydrogenase (PHGDH) inhibitor (NCT503) [...] Read more.
Objective: This study aims to identify whether the development of insulin resistance (IR) induced by high selenium (Se) is related to serine deficiency via the inhibition of the de novo serine synthesis pathway (SSP) by the administrations of 3-phosphoglycerate dehydrogenase (PHGDH) inhibitor (NCT503) or exogenous serine in mice. Method: forty-eight male C57BL/6J mice were randomly divided into four groups: adequate-Se (0.1 mgSe/kg), high-Se (0.8 mgSe/kg), high-Se +serine (240 mg/kg/day), and high-Se +NCT503 (30 mg/kg, twice a week) for 5 months. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to confirm the development of IR in mice with high-Se intake, and fasting blood glucose levels were measured monthly. The Se contents in plasma and tissues were detected by ICP-MS. The levels of insulin (INS), homocysteine (HCY), and serine in plasma were tested by ELISA. Western blot analyses were conducted to evaluate the protein expressions of glutathione peroxidase 1 (GPX1), selenoprotein P (SELENOP) and PHGDH, the PI3K-AKT-mTOR pathway, folate cycle (SHMT1, MTHFR), and methionine cycle (MS). Results: An IR model was developed in mice from the high-Se group with elevated fasting blood glucose and INS levels, impaired glucose tolerance, and reduced insulin sensitivity, but not in both the high-Se +serine group and the high-Se +NCT503 group. Compared with the high-Se and high-Se +serine groups, the expressions of GPX1 and SELENOP significantly decreased for the high-Se +NCT503 group in the liver, muscle, and pancreas tissues. The expression of PHGDH of high-Se group was significantly higher than that of the adequate-Se group in the liver (p < 0.05) and pancreas (p < 0.001). Also, the expected high expression of PHGDH was effectively inhibited in mice from the high-Se +serine group but not from the high-Se +NCT503 group. The expression of p-AKT (Ser-473) for the high-Se group was significantly lower than that of the adequate-Se group in the liver, muscle, and pancreas. Conclusions: The IR induced by high-Se intake in the body has been confirmed to be partially due to serine deficiency, which led to the initiation of SSP to produce endogenous serine. The supplementations of exogenous serine or inhibitors of PHGDH in this metabolic pathway could be used for the intervention. Full article
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<p>Animal experiment flowchart.</p>
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<p>Effects of selenium levels (0.1, 0.8 mg Se/kg) and interventions (Ser, NCT503) on weight, glucose metabolism, GTT, and ITT in C57BL/6J mice. (<b>a</b>) Changes in body weight over 5 months. (<b>b</b>) Fasting blood glucose levels measured monthly. (<b>c</b>) Glucose tolerance assessed at the end of the fourth month. (<b>d</b>) Insulin tolerance evaluated at the end of the fourth month. (Data are expressed as mean ± SD, n = 10–12). (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001; two-way ANOVA). Both Ser and NCT503 effectively mitigate Se-induced metabolic disturbances, with Ser showing a more substantial improvement in body weight and blood glucose regulation.</p>
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<p>Effects of selenium levels (0.1 mg and 0.8 mg Se/kg) and interventions (Ser, NCT503) on plasma biochemical markers in C57BL/6J mice. (<b>a</b>–<b>c</b>) Changes in plasma biochemical markers: (<b>a</b>) insulin (INS, mIU/L), (<b>b</b>) homocysteine (Hcy, µmol/L), amd (<b>c</b>) serine (Ser, µmol/L). (<b>d</b>) Selenium levels in plasma, liver, muscle, and pancreas. (<b>e</b>) PHGDH enzyme activity in plasma, liver, muscle, and pancreas. (Data are expressed as mean ± SD, n = 7). (*** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001; two-way ANOVA). Supplementation with Ser and NCT503 modulates biochemical markers and PHGDH enzyme activity. Ser supplementation lowers INS and HCY levels, while NCT503 decreases INS and serine levels, and increases HCY levels. The NCT503 inhibitor has a stronger inhibitory effect on PHGDH enzyme activity.</p>
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<p>Effect of 0.1, 0.8 mg Se/kg and Ser or NCT503 intervention group on the Expressions of selenoproteins and enzymes in Liver Tissue. (<b>a</b>) WB images. (<b>b</b>–<b>g</b>) grayscale analysis. (Mean ± SD, n = 3, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; two-way ANOVA). NCT503 and Ser differentially modulate liver enzyme expression, with NCT503 enhancing PHGDH activity and reducing SELENOP, while Ser primarily decreases MS expression.</p>
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<p>Effect of 0.1, 0.8 mg Se/kg and Ser or the NCT503 intervention group on the expressions of selenoproteins and enzymes in muscle Tissue. (<b>a</b>) WB images. (<b>b</b>–<b>g</b>) grayscale analysis. (Mean ± SD, n = 3, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; two-way ANOVA). NCT503 reduces GPX1 and SELENOP expression in muscle, while Ser mainly reduces MS expression.</p>
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<p>Effect of 0.1, 0.8 mg Se/kg and Ser or the NCT503 intervention group on the expression of selenoproteins and enzymes in Mouse pancreas Tissue. (<b>a</b>) WB images. (<b>b</b>–<b>f</b>) grayscale analysis. (Mean ± SD, n = 3, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; two-way ANOVA). NCT503 increases PHGDH expression in the pancreas, while Ser primarily reduces SHMT1 expression.</p>
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<p>Effects of 0.1, 0.8 mg Se/kg, and Ser or the NCT503 intervention group on the PI3K-AKT-mTOR pathway in mice liver. (<b>a</b>) WB images. (<b>b</b>–<b>f</b>) Pathway grayscale analysis (Mean ± SD, n = 3, * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001; two-way ANOVA). Ser and NCT503 supplementation modulate mTOR expression in the liver, with NCT503 and Ser both enhancing mTOR signaling.</p>
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<p>Effects of 0.1, 0.8 mg Se/kg, and Ser or the NCT503 intervention group on the PI3K-AKT-mTOR pathway in mice muscle. (<b>a</b>) WB images. (<b>b</b>–<b>f</b>) Pathway grayscale analysis (Mean ± SD, n = 3, * <span class="html-italic">p</span> &lt; 0.05; two-way ANOVA). While Ser and NCT503 supplementation slightly increased Akt/mTOR pathway markers in muscle, these changes were not significant.</p>
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<p>Effects of 0.1, 0.8 mg Se/kg, and Ser or the NCT503 intervention group on the PI3K-AKT-mTOR pathway in mice muscle pancreas. (<b>a</b>) WB images. (<b>b</b>–<b>f</b>) Pathway grayscale analysis (Mean ± SD, n = 3, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; two-way ANOVA). Both Ser and NCT503 supplementation restored Akt/mTOR signaling in the pancreas, with significant increases in mTOR and phosphorylated Akt levels compared to the high-Se group.</p>
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<p>The SSP supports selenium detoxification and metabolic balance. The SSP plays a pivotal role in maintaining redox balance, supporting methylation reactions, and facilitating selenium detoxification under high selenium conditions. Increased PHGDH expression drives serine production, replenishing SAM for methylation and promoting GSH synthesis to combat oxidative stress. Excessive SSP activation burdens the methionine and folate cycles, depleting SAM and disrupting methylation homeostasis. Serine supplementation alleviates these effects by restoring one-carbon metabolism and enhancing selenium detoxification. Similarly, pharmacological inhibition of PHGDH (e.g., NCT-503) reduces SSP overactivation, highlighting its potential as a therapeutic target in Se-induced metabolic dysregulation.</p>
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<p>Integration of mTOR signaling, oxidative stress, and IR. The figure delineates the intricate mechanisms by which mTOR signaling integrates oxidative stress, energy homeostasis, and insulin sensitivity. Oxidative stress activates AMPK, which inhibits mTORC1 via TSC2 phosphorylation and suppresses Rheb, a key mTOR activator. Reduced mTOR signaling impairs AKT activation, disrupting GLUT4 translocation and diminishing glucose uptake. Concurrently, impaired AKT fails to suppress FOXO1 nuclear activity, leading to enhanced gluconeogenesis through the upregulation of key enzymes like PEPCK. Elevated oxidative stress and inflammation further aggravate IR by activating pathways, inducing aberrant IRS1 phosphorylation, and reducing insulin receptor sensitivity. These combined effects underscore the centrality of mTOR in maintaining redox balance, metabolic stability, and insulin signaling integrity.</p>
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13 pages, 5179 KiB  
Article
Coenzyme Q and Selenium Co-Supplementation Alleviate Methionine Choline-Deficient Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Mice
by Hyewon Choi, Jiwon Choi, Yula Go and Jayong Chung
Nutrients 2025, 17(2), 229; https://doi.org/10.3390/nu17020229 - 9 Jan 2025
Viewed by 1088
Abstract
Background/Objectives: The pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) is closely associated with increased oxidative stress and lipid peroxidation. Coenzyme Q (CoQ) and selenium (Se) are well-established antioxidants with protective effects against oxidative damage. This study aimed to investigate the effects of CoQ and [...] Read more.
Background/Objectives: The pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) is closely associated with increased oxidative stress and lipid peroxidation. Coenzyme Q (CoQ) and selenium (Se) are well-established antioxidants with protective effects against oxidative damage. This study aimed to investigate the effects of CoQ and Se in ameliorating MASH induced by a methionine choline-deficient (MCD) diet in mice. Methods: C57BL/6J male mice were fed either a methionine choline-sufficient (MCS) or MCD diet and treated with vehicle, CoQ (100 mg/kg), Se (158 μg/kg), or their combination (CoQ + Se) for 4 weeks. Results: The MCD diet significantly increased hepatic steatosis, inflammation, and fibrosis compared to MCS controls. Treatment with CoQ and Se, particularly in combination, markedly reduced the MAFLD activity score, hepatic inflammation, and fibrosis. Combined supplementation of CoQ and Se significantly decreased serum alanine aminotransferase and aspartate aminotransferase levels and hepatic TG and cholesterol concentrations. CoQ and Se effectively mitigated hepatic oxidative stress by enhancing catalase and superoxide dismutase activities, increasing glutathione peroxidase (GPX) activity, and restoring the GSH/GSSG ratio. Lipid peroxidation markers, such as malondialdehyde and 4-hydroxynonenal, were significantly reduced. Furthermore, the expression of ferroptosis-related markers, including acyl-CoA synthetase long-chain family member 4, arachidonate 12-lipoxygenase, and hepatic non-heme iron content, was significantly downregulated, while GPX4 expression was upregulated by combined CoQ and Se treatment. Conclusions: CoQ and Se synergistically alleviate MASH progression by reducing oxidative stress and lipid peroxidation, which may contribute to the suppression of ferroptosis. Combined CoQ and Se supplementation demonstrates therapeutic potential for managing MASH and related liver injury. Full article
(This article belongs to the Special Issue Effects of Selenium and Other Micronutrient Intake on Human Health)
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<p>Effects of CoQ and Se treatment on liver injury in MCD diet-induced MASH mice. (<b>a</b>) Liver sections stained with H&amp;E (steatosis (Δ), lobular inflammation (*), and ballooning degeneration (<tt>→</tt>)), (<b>b</b>) MAS score, (<b>c</b>) Serum ALT activity, (<b>d</b>) Serum AST activity, (<b>e</b>) Hepatic TG concentration, (<b>f</b>) Hepatic total cholesterol (TC) concentration. Data are shown as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. MCS vehicle, <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. MCD vehicle, <sup><span>$</span></sup> <span class="html-italic">p</span> &lt; 0.05 vs. MCD + CoQ.</p>
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<p>Effects of CoQ and Se treatment on liver injury in MCD diet-induced MASH mice. (<b>a</b>) Liver sections stained with H&amp;E (steatosis (Δ), lobular inflammation (*), and ballooning degeneration (<tt>→</tt>)), (<b>b</b>) MAS score, (<b>c</b>) Serum ALT activity, (<b>d</b>) Serum AST activity, (<b>e</b>) Hepatic TG concentration, (<b>f</b>) Hepatic total cholesterol (TC) concentration. Data are shown as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. MCS vehicle, <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. MCD vehicle, <sup><span>$</span></sup> <span class="html-italic">p</span> &lt; 0.05 vs. MCD + CoQ.</p>
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<p>Effects of CoQ and Se treatment on hepatic inflammation and fibrosis in MCD diet-induced MASH mice. (<b>a</b>): Liver sections stained with Sirius Red staining (200× magnification); The arrow indicates collagen staining, (<b>b</b>) % Fibrotic area, (<b>c</b>) the mRNA levels of fibrotic markers, (<b>d</b>) Hepatic mRNA levels of pro-inflammatory cytokines, (<b>e</b>) Hepatic protein levels of COX2 with representative blot (upper panel). Data are shown as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. MCS vehicle, <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. MCD vehicle, <sup><span>$</span></sup> <span class="html-italic">p</span> &lt; 0.05 vs. MCD + CoQ.</p>
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<p>Effects of CoQ and Se treatment on hepatic lipid peroxidation in MCD diet-induced MASH mice. (<b>a</b>) Hepatic MDA concentration, (<b>b</b>) Hepatic protein levels of 4-HNE with representative blot (upper panel). Data are shown as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. MCS vehicle, <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. MCD vehicle.</p>
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<p>Effects of CoQ and Se treatment on hepatic ferroptosis markers in MCD diet-induced MASH mice. Hepatic protein levels of (<b>a</b>) ACSL4, (<b>b</b>) LOX, and (<b>c</b>) GPX4. Data are shown as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. MCS vehicle, <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. MCD vehicle.</p>
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<p>Effects of CoQ and Se treatment on hepatic non-heme iron concentrations and hepatic ferritin protein level in MCD diet-induced MASH mice. (<b>a</b>) Hepatic non-heme iron concentration, (<b>b</b>) Hepatic protein levels of ferritin. Data are shown as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. MCS vehicle, <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. MCD vehicle.</p>
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13 pages, 249 KiB  
Article
Assessing the Nutrient Composition of a Carnivore Diet: A Case Study Model
by Sylvia Goedeke, Tamzyn Murphy, Amy Rush and Caryn Zinn
Nutrients 2025, 17(1), 140; https://doi.org/10.3390/nu17010140 - 31 Dec 2024
Cited by 1 | Viewed by 10979
Abstract
Background/Objectives: The rise in chronic metabolic diseases has led to the exploration of alternative diets. The carnivore diet, consisting exclusively of animal products, has gained attention, anecdotally, for imparting benefit for inflammatory conditions beyond that possible by other restrictive dietary approaches. The aim [...] Read more.
Background/Objectives: The rise in chronic metabolic diseases has led to the exploration of alternative diets. The carnivore diet, consisting exclusively of animal products, has gained attention, anecdotally, for imparting benefit for inflammatory conditions beyond that possible by other restrictive dietary approaches. The aim was to assess the micronutrient adequacy of four versions of the carnivore diet against national nutrient reference values (NRVs). Methods: This study assessed the nutrient adequacy of the carnivore diet against national NRVs from the Australian National Health and Medical Research Council (NHMRC) and New Zealand Ministry of Health. Four meal plans for hypothetical average Australian adults were developed and analysed using Foodworks.online (Version 1, Xyris Pty Ltd., Brisbane, Australia, 2024), dietary software. Two female and two male plans were included; one set including dairy products and the other set including offal. Results: The carnivore diet met several NRV thresholds for nutrients such as riboflavin, niacin, phosphorus, zinc, Vitamin B6, Vitamin B12, selenium, and Vitamin A, and exceeded the sodium threshold. However, it fell short in thiamin, magnesium, calcium, and Vitamin C, and in iron, folate, iodine and potassium in some cases. Fibre intake was significantly below recommended levels. Conclusion: The carnivore diet may offer benefits for managing certain chronic conditions. Whether the metabolic contexts from consuming such a diet facilitates a lower requirement of certain nutrients, or whether it poses risks of micronutrient inadequacies remains to be determined. Tailored nutritional guidance and supplementation strategies are recommended to ensure careful consideration of micronutrient intake to prevent deficiencies. Full article
(This article belongs to the Section Micronutrients and Human Health)
11 pages, 524 KiB  
Article
Micronutrient Deficiencies in Heart Failure and Relationship with Exocrine Pancreatic Insufficiency
by Marlene A. T. Vijver, Nils Bomer, Robert C. Verdonk, Peter van der Meer, Dirk J. van Veldhuisen and Olivier C. Dams
Nutrients 2025, 17(1), 56; https://doi.org/10.3390/nu17010056 - 27 Dec 2024
Viewed by 1116
Abstract
Background: Micronutrient deficiencies are common and play a significant role in the prognosis of many chronic diseases, including heart failure (HF), but their prevalence in HF is not well known. As studies have traditionally focused on causes originating within the intestines, exocrine pancreatic [...] Read more.
Background: Micronutrient deficiencies are common and play a significant role in the prognosis of many chronic diseases, including heart failure (HF), but their prevalence in HF is not well known. As studies have traditionally focused on causes originating within the intestines, exocrine pancreatic insufficiency (EPI) has been overlooked as a potential contributor. The exocrine pancreas enables the absorption of various (fat-soluble) micronutrients and may be insufficient in HF. We hypothesize that EPI contributes to micronutrient deficiencies in HF. Objectives: To evaluate micronutrient concentrations in HF cases and their association with clinical characteristics and EPI. Materials and Methods: Plasma samples from 59 consecutive hospitalized patients with HF were analyzed for vitamins A, D, and E and the minerals selenium and zinc. EPI was defined as fecal elastase 1 level < 206 μg/g. Results: The mean age of patients was 59 ± 14 years, with 24 (41%) being women, and a median NT-proBNP concentration of 3726 [2104–6704] pg/mL was noted. Vitamin A deficiency occurred in eight (14%) of the patients, and 12 (20%) exceeded the upper limit. More than half (51%) were vitamin D-deficient. No patients showed vitamin E deficiency, but 14 (24%) had elevated levels. Selenium deficiency was common, affecting 36 (61%) patients, while zinc was below the normal range in seven patients (12%). Micronutrient levels did not differ significantly based on the presence of EPI. Conclusions: This study provides novel insights into the micronutrient status of patients with HF. Deficiencies in vitamins A and D, selenium, and zinc are prevalent in HF, but these findings are not associated with exocrine pancreatic function. Full article
(This article belongs to the Section Micronutrients and Human Health)
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<p>Visual representation of distribution of nutrients in patients with HF compared to population-based reference values. Distribution of nutrients is indicated by the upper blue boxplot, displaying the median and interquartile ranges for vitamins A and D and the means with standard deviations for vitamin E, selenium, and zinc. The black lines refer to the minimum and maximum values. Reference values (0.025–0.975 of the population range) are indicated by the green bar. The red arrow bars indicate the number of patients who exceeded the lower or upper limit of normality. (<b>A</b>) Distribution of vitamin A. (<b>B</b>) Distribution of vitamin D. (<b>C</b>) Distribution of vitamin E. (<b>D</b>) Distribution of selenium. (<b>E</b>) Distribution of zinc.</p>
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22 pages, 2936 KiB  
Review
Effects and Impact of Selenium on Human Health, A Review
by Song Bai, Miaohe Zhang, Shouying Tang, Miao Li, Rong Wu, Suran Wan, Lijun Chen, Xian Wei and Shuang Feng
Molecules 2025, 30(1), 50; https://doi.org/10.3390/molecules30010050 - 26 Dec 2024
Viewed by 1486
Abstract
Selenium (Se) is an essential trace element that is crucial for human health. As a key component of various enzymes and proteins, selenium primarily exerts its biological functions in the form of selenoproteins within the body. Currently, over 30 types of selenoproteins have [...] Read more.
Selenium (Se) is an essential trace element that is crucial for human health. As a key component of various enzymes and proteins, selenium primarily exerts its biological functions in the form of selenoproteins within the body. Currently, over 30 types of selenoproteins have been identified, with more than 20 of them containing selenocysteine residues. Among these, glutathione peroxidases (GPXs), thioredoxin reductases (TrxRs), and iodothyronine deiodinases (DIOs) have been widely studied. Selenium boasts numerous biological functions, including antioxidant properties, immune system enhancement, thyroid function regulation, anti-cancer effects, cardiovascular protection, reproductive capability improvement, and anti-inflammatory activity. Despite its critical importance to human health, the range between selenium’s nutritional and toxic doses is very narrow. Insufficient daily selenium intake can lead to selenium deficiency, while excessive intake carries the risk of selenium toxicity. Therefore, selenium intake must be controlled within a relatively precise range. This article reviews the distribution and intake of selenium, as well as its absorption and metabolism mechanisms in the human body. It also explores the multiple biological functions and mechanisms of selenium in maintaining human health. The aim is to provide new insights and evidence for further elucidating the role of selenium and selenoproteins in health maintenance, as well as for future nutritional guidelines and public health policies. Full article
(This article belongs to the Special Issue Organosulfur and Organoselenium Chemistry II)
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<p>Structural formulas of selenocysteine (SeCys) and selenomethionine (SeMet).</p>
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<p>Distribution of selenium [<a href="#B35-molecules-30-00050" class="html-bibr">35</a>,<a href="#B36-molecules-30-00050" class="html-bibr">36</a>]. (<b>A</b>) Selenium distribution at the global scale: in the world map, red indicates sufficient selenium, pink indicates selenium deficiency, and white indicates no selenium content data. (<b>B</b>) Distribution pattern of soil selenium concentration in China.</p>
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<p>The concentration of selenium in blood and human health (range of blood selenium concentrations with possible related health effects from deficiency to toxicity) [<a href="#B55-molecules-30-00050" class="html-bibr">55</a>].</p>
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<p>Metabolic pathway of selenium.</p>
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<p>The role of catalase and glutathione peroxidase in the removal of hydrogen peroxide in the human body [<a href="#B55-molecules-30-00050" class="html-bibr">55</a>].</p>
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<p>Role of thioredoxin in the reduction of ribonucleosides-5′-diphosphates to deoxyribonucleosides-5′-diphosphate.</p>
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<p>Formulae of thyroxine and triiodothyronine.</p>
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<p>The process of thyroid hormone synthesis.</p>
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<p>The role of deiodinases in the conversion between different thyroid hormones.</p>
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