Search Results (118)

Selenium, a crucial trace element, has garnered significant attention in functional food development due to its effective conversion into organic forms. This study systematically investigated the selenium enrichment potential and metabolic regulation mechanisms of 50 lactic acid bacteria (LAB) strains from Xinjiang. Through sodium selenite tolerance tests, eight core strains with over 80% selenium enrichment were selected, with optimal enrichment conditions being a 37 °C temperature, 2% sodium chloride concentration, and pH of 6.0 in MRS medium. Functional tests demonstrated that selenium-enriched strains exhibited a significantly enhanced antioxidant capacity (demonstrated by DPPH and ABTS free radical scavenging activities) and improved gastrointestinal fluid tolerance, with strain No.41 showing the most outstanding performance. Scanning electron microscopy combined with energy-dispersive X-ray spectroscopy (SEM-EDX) revealed nanoscale selenium (1.34 keV) on cell surfaces. Further characterization showed that 68.94% of selenium was incorporated into selenoproteins, 7.61% into nucleic acids, and 7.02% into polysaccharides. Integrated metabolomic and proteomic studies have shown that selenium reduces the content of L-cysteine primarily by replacing sulfur and competing for key sites in cysteine-S-conjugate-β-lyase, S-adenosyl-L-cysteine hydrolase, and homocysteine synthase, ultimately leading to the synthesis of selenocysteine and selenomethionine. A correlation analysis between differential metabolites and proteins revealed selenium’s significant impacts on the metabolic networks of LAB, antioxidant mechanisms, energy metabolism, and membrane stability. This research provides new insights for developing selenium-enriched probiotics for functional dairy products and health supplements. Full article

Selenium-enriched Dendrobium huoshanense C. Z. Tang et S. J. Cheng is a precious medicinal herb that combines traditional therapeutic value with modern nutritional benefits. However, its wild populations primarily inhabit special habitats like cliffs and rock crevices, resulting in limited yield and low selenium content. This study optimized an in vitro selenium-enriched cultivation system for D. huoshanense, investigating the regulatory mechanisms of selenium on physiological metabolism by modulating exogenous selenium concentrations, and determining the spatiotemporal distribution and speciation of selenium in plantlets. The results showed the optimal medium composition was as follows: MS + IBA (0.1 mg/L) + NAA (0.6 mg/L) + 7% agar + 30% sucrose + 100 g/L banana homogenate + 3 mg/L sodium selenite (pH 5.8). Under these conditions, roots served as the primary selenium accumulation sites at 30 and 60 days of cultivation. After 90 days, selenium redistribution occurred from storage organs (roots) to metabolically active organs (leaves). Organic selenium constituted 83.70% of total selenium, comprising 44.90% selenoproteins, 29.20% selenopolysaccharides, and 9.60% other organic forms. The contents of selenomethionine (SeMet), methylselenocysteine (MeSeCys), and selenocysteine (SeCys₂) were 0.63 ± 0.04, 0.20 ± 0.11, and 0.28 ± 0.06 mg/kg, respectively. Using plant tissue culture technology, we successfully cultivated selenium-enriched D. huoshanense, and investigated its growth metabolism, selenium translocation mechanisms, and selenium speciation. These findings provide theoretical foundations for developing selenium-enriched medicinal materials and have significant implications for enhancing the medicinal value of D. huoshanense. Full article

Background/Objectives: Selenoproteins play indispensable roles in embryonic development, with their dysregulation linked to various metabolic and neurological disorders. This study aims to systematically quantify the mRNA expression levels of all 24 selenoprotein genes in murine heart, brain, liver, and kidney tissues across embryonic (E8.5, E12.5, E18.5) and postnatal (P7, P30, P90) developmental stages, in order to elucidate the regulatory landscape of selenium metabolism during development. Methods: We collected tissues from mice at six developmental stages and performed RNA extraction followed by quantitative real-time PCR (qPCR) to measure the expression of all 24 selenoprotein genes. Data were normalized using the geometric mean of ActB and Gapdh, and statistical analyses were conducted using one-way ANOVA with Duncan’s post hoc test. Results: Our analysis reveals three principal findings: (1) Distinct expression patterns emerge among selenoprotein families—deiodinases (Dio1-3) and thioredoxin reductases (Txnrd1-3) exhibit limited embryonic expression (<20-fold changes), while glutathione peroxidases (Gpx1, Gpx3, Gpx4) and biosynthesis-related genes (Selenop, Msrb1) show substantial postnatal upregulation (up to 600-fold increases); (2) Selenoproteins essential for embryonic survival (Gpx4, Txnrd1, Txnrd2, Selenoi, Selenot) display expression profiles concordant with their essential developmental functions; (3) Selenop and Msrb1, involved in selenium transport and redox regulation, demonstrate early embryonic upregulation with further increases during postnatal development. Conclusions: These spatiotemporal expression patterns elucidate the regulatory landscape of selenium metabolism during development and provide mechanistic insights into the phenotypes associated with selenium deficiency. The findings offer valuable implications for human nutritional interventions and developmental health. Full article

Selenoprotein thioredoxin reductase 1 (TXNRD1) is frequently upregulated in various cancer cells to sustain cellular redox homeostasis, and its inhibition has emerged as a promising anti-cancer strategy. In this study, we identified PK11007, a thiol-modifying compound previously characterized as a p53 reactivator, as a potent inhibitor of TXNRD1. PK11007 irreversibly inhibited recombinant TXNRD1 in a time- and dose-dependent manner. Using differential scanning fluorimetry (DSF) and LC–MS/MS analysis, we confirmed that PK11007 covalently modifies the C-terminal redox motif (Cys⁴⁹⁷-Sec⁴⁹⁸) of TXNRD1. In non-small cell lung cancer (NSCLC) H1299 cells, PK11007-induced TXNRD1 inhibition disrupted cellular redox balance, leading to impaired autophagy flux and cell death. Similar autophagy suppression was observed in TXNRD1-knockdown cells, as well as pharmacological inhibition of TXNRD1 by Auranofin (AF) and TXNRD1 inhibitor 1 (TRi-1). Taken together, these findings highlight that oxidative stress contributes to the cytotoxic effects of PK11007 and uncover autophagy disorder as a downstream consequence of TXNRD1 inhibition. Full article

Background: Pregnancy-induced hypertension (PIH) affects approximately 10% of pregnancies worldwide, representing a leading cause of maternal and perinatal morbidity and mortality. The relationship between plasma selenium levels and PIH remains controversial, with observational studies limited by confounding factors. Selenoprotein S (SELENOS) has emerged as a potential biomarker for PIH risk. As one of the carrier proteins for dietary selenium, SELENOS plays a crucial role in oxidative stress and inflammatory pathways. However, the causal relationship between the plasma levels of the SELENOS and PIH development remains unclear. This study employed Mendelian randomization (MR) to investigate the causal link between the plasma levels of the SELENOS and PIH risk, providing evidence for preventive strategies. Methods: We conducted a two-sample MR analysis using genome-wide association study (GWAS) summary statistics from the INTERVAL study and FinnGen consortium. The analysis included individuals of European ancestry, utilizing the inverse-variance weighted (IVW) method as the primary approach. Comprehensive sensitivity analyses were performed to address potential pleiotropy and strengthen causal inference. Results: The analysis encompassed 3301 samples for the plasma levels of the SELENOS and 7686 PIH cases, 1109 pre-existing hypertension (PEH) cases, 4255 gestational hypertension (GH) cases, and 83 preeclampsia (PE) cases superimposed on chronic hypertension, alongside approximately 115,000 controls. Genetic variabilities that have been found to be accompanied by elevated levels of plasma selenioprotein levels showed significant associations with increased risk of PIH [odds ratio (OR) 1.078, 95% confidence interval (CI) 1.031–1.126, p = 0.001], PEH (OR 1.232, 95% CI 1.105–1.373, p < 0.001), and GH (OR 1.111, 95% CI 1.047–1.180, p = 0.001), with suggestive associations for preeclampsia superimposed on chronic hypertension (OR 1.590, 95% CI 1.078–2.344, p = 0.019). Conclusions: This study provides robust genetic evidence for a causal relationship between the plasma levels of the SELENOS and PIH risk, establishing SELENOS as a potential modifiable risk factor with significant clinical implications. These findings support the development of personalized selenium management strategies during pregnancy and highlight the potential for early screening and targeted interventions to improve maternal and fetal outcomes. Full article

Background: Varicocele is a common condition involving the dilation of veins in the scrotum, often linked to male infertility and testicular dysfunction. This study aimed to elucidate the molecular effects of successful varicocele treatment on sperm proteomes following percutaneous sclero-embolization. Methods: High-resolution tandem mass spectrometry was performed for proteomic profiling of pooled sperm lysates from five patients exhibiting improved semen parameters before and after (3 and 6 months) varicocele sclero-embolization. Data were validated by Western blot analysis. Results: Seven proteins were found exclusively in varicocele patients before surgery—such as stathmin, IFT20, selenide, and ADAM21—linked to inflammation and oxidative stress. After sclero-embolization, 55 new proteins emerged, including antioxidant enzymes like selenoprotein P and GPX3. Thioredoxin (TXN) and peroxiredoxin (PRDX3) were upregulated, indicating restoration of key antioxidant pathways. Additionally, the downregulation of some histones and the autophagy-related protein ATG9A suggests a shift toward an improved chromatin organization and a healthier cellular environment post-treatment. Conclusions: Varicocele treatment that improves sperm quality and fertility parameters leads to significant proteome modulation. These changes include reduced oxidative stress and broadly restored sperm maturation. Despite the limited patient cohort analyzed, these preliminary findings provide valuable insights into how varicocele treatment might enhance male fertility and suggest potential biomarkers for improved male infertility treatment strategies. Full article

Metabolic syndrome (MetS), characterized by obesity, insulin resistance, and dyslipidemia, is a major risk factor for renal injury. Oxidative stress (OxS) plays a pivotal role in its progression; however, the underlying molecular mechanisms are not fully understood. In this study, we established a rat model of MetS using a high-fat diet combined with a single-dose streptozotocin injection in male Wistar rats. MetS rats exhibited systemic OxS, evidenced by elevated circulating levels of free oxygen radicals and decreased antioxidant defense capacity, as well as hypertension, renal lipid peroxidation, glomerular hyperfiltration, and renal tubular injury. Transcriptomic profiling of renal tissue revealed significant downregulation of six OxS-related genes: C-C motif chemokine ligand 5 (CCL5), glutamate-cysteine ligase catalytic subunit, glutathione peroxidase 6, recombination activating gene 2, NAD(P)H: quinone oxidoreductase 1, and selenoprotein P-1. Among these downregulated genes, CCL5 was further confirmed to be repressed at both mRNA and protein levels across intrarenal and systemic compartments. Given its documented functions in immune signaling and redox homeostasis, CCL5 downregulation may contribute to enhanced oxidative damage in MetS-associated renal injury. These findings highlight the role of redox gene dysregulation in the pathogenesis of MetS-related kidney disease and support the potential of CCL5 as a biomarker for oxidative renal injury. Full article

It is known that a percentage of patients who undergo total thyroidectomy, approximately 16–34%, complain of symptoms of hypothyroidism or altered quality of life (QoL) despite achieving normal serum TSH values. The present study aimed to identify whether the level of selenium could be responsible for this phenomenon. This pilot cohort study included 44 thyroidectomized outpatients. All patients underwent surgery for benign disease. In this study, no patients with a history of autoimmunity, malignancy, or other conditions that could affect well-being, absorption, or selenium intake were included. Serum levels of TSH, fT3, fT4, Selenoprotein P (SelP), and glutathione peroxidase 3 (GPx3) were measured. The patients also completed the ThyPRO-39 questionnaire to assess their QoL. A strong and significant direct correlation was found between SelP and GPx3 (r = 0.88). However, no correlation was found between hormonal status and SelP or GPx3. Analysis of ThyPRO-39 results did not show clinically significant differences between items nor a correlation with thyroid hormone levels, except for symptoms of hypothyroidism. Interestingly, a significant direct correlation was observed between SelP and tiredness, as well as between GPx3 and tiredness. Furthermore, the fT3/fT4 ratio was correlated with worsening symptoms of hypothyroidism. The results suggest that the selenium status, in turn related to antioxidant activities, as reflected in SelP and GPx3 levels, may be associated with the QoL tiredness domain in thyroidectomized patients, despite normal levels of thyroid hormones. More research is needed to elucidate the role of selenium in the persistent symptoms experienced by some thyroidectomized patients. Full article

The objective of this study was to determine whether hydroxy-selenomethionine (OH-SeMet) exerts better protective effects on sows against heat stress than sodium selenite (SeNa) or seleno-yeast (SeY). A total of 60 sows (Landrace × Yorkshire) were randomly allocated into the three groups and fed a base diet supplemented with SeNa, SeY, or OH-SeMet at 0.3 mg Se/kg under a heat stress condition for a reproductive cycle. Compared to SeNa or SeY, OH-SeMet could more effectively sustain offspring growth performance, as evidenced by an increased number of live-born piglets, higher litter weight at day 21, and greater litter body weight gain from days 1 to 21. OH-SeMet was more effective in supporting endogenous redox systems, as shown by enhanced levels of TXNRD and GSH and reduced levels of GSSG in the serum of sows, improved T-AOC, TXNRD, and GSH alongside decreased MDA and GSSG in the serum of piglets, and heightened T-AOC in the jejunum of piglets. Furthermore, among the two tested organic Se sources, OH-SeMet was more effective than SeY in regulating immune responses compared to SeNa. OH-SeMet reduced inflammation-related markers CRP, HP, MAP, LPS, IL-1β, IL-6, and TNF-α, some or all of which were reduced in the serum of sows and their offspring. In addition, OH-SeMet also showed reduced glucose, TG, and NEFA levels, along with elevated insulin levels in the serum of sows. Correspondingly, among the two organic forms of Se, particularly those sows fed OH-SeMet showed better gut protection for the sows’ offspring, as indicated by a reduced crypt depth and increased villus height/crypt depth ratio in the duodenum, jejunum, and ileum than those fed SeNa. Specifically, compared to SeNa or SeY, OH-SeMet upregulated the expression of selenoproteins (GPX6, TXNRD3, GPX4, and SELENON), the tight junction protein (ZO-1), and host defense peptide gene (pBD1, pBD2, pBD3, NPG3, NPG4), along with downregulating levels of inflammation factor (IL-1β, IL-6 and TNF-α) and pro-apoptotic factor (P53) in the jejunum of piglets. Taken together, OH-SeMet more effectively mitigated the adverse effects induced by heat stress in sows and their offspring. Full article

Selenium (Se) has important anti-inflammatory and antioxidant activities, plays an important role in the immune system through redox balance, and is part of selenoproteins. In patients who are critically ill, Se supplementation causes alterations in inflammatory markers such as procalcitonin, leukocyte count, albumin, prealbumin, C-reactive protein (CRP), inflammatory cytokines, and cholesterol. The decrease in Se levels leads to a reduction in the levels of various selenoenzymes, in particular glutathione peroxidase and selenoprotein P. These antioxidant selenoproteins play a protective role against the lipoperoxidation of cell membranes and also participate in the process of regulating the inflammatory response. Currently, there are no conclusive data that allow us to affirm the existence of a significant reduction in mortality with the use of Se in intensive care. Selenium nanoparticles (SeNPs) can be used as dietary supplements or therapeutic agents due to their low toxicity and better bioavailability compared to traditional Se supplementation. In this review, we focus on the current state of research on SeNPs and their anti-inflammatory and antioxidant properties as a therapy for patients who are seriously ill, without the toxic effects of other Se species. Full article

Background: Selenium (Se), a vital trace element, plays a neuroprotective role by mitigating oxidative stress through selenoproteins and regulating metal balance. The apolipoprotein E ε4 allele (APOE4), a significant genetic risk factor for Alzheimer’s disease (AD), has been linked to reduced Se levels and weakened antioxidant capacity. This research explores the association between serum Se concentrations and cognitive performance, with an emphasis on how APOE4 status influences this relationship. Methods: This study included 196 older adults from community and memory clinic settings, who underwent assessments for episodic memory, global cognition, and non-memory functions using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery, with serum selenium levels analyzed via inductively coupled plasma–mass spectrometry (ICP-MS) and APOE genotyping conducted to determine allele status. Results: Higher serum Se levels were associated with better episodic memory score (EMS) (B = 0.065, 95% CI = 0.020–0.110, p = 0.005) and CERAD total score (TS) (B = 0.119, 95% CI = 0.046–0.193, p = 0.002). However, the interaction between Se and APOE4 status significantly affected EMS (B = −0.074, 95% CI = −0.109 to −0.039, p < 0.001), with significant benefits observed in APOE4-negative participants. Conclusions: This study highlights the genotype-specific impact of Se on cognitive health, emphasizing the need for personalized nutritional interventions targeting Se levels, particularly for APOE4-negative individuals. Future research should further elucidate the mechanisms of Se’s effects and assess its therapeutic potential in aging populations. Full article

Selenoproteins contain selenium (Se), which is included in the 21st proteinogenic amino acid selenocysteine (Sec). Selenium (Se) is an essential trace element that exerts its biological actions mainly through selenoproteins. Selenoproteins have crucial roles in maintaining healthy brain activity. At the same time, brain-function-associated selenoproteins may also be involved in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The selenoproteins GPx4 (glutathione peroxidase 4), GPx1 (glutathione peroxidase 1), SELENOP (selenoprotein P), SELENOK (selenoprotein K), SELENOS (selenoprotein S), SELENOW (selenoprotein W), and SELENOT (selenoprotein T) are highly expressed, specifically in AD-related brain regions being closely correlated to brain function. Only a few selenoproteins, mentioned above (especially SELENOP), can bind transition and heavy metals. Metal ion homeostasis accomplishes the vital physiological function of the brain. Dyshomeostasis of these metals induces and entertains neurodegenerative diseases. In this review, we described some of the proposed and established mechanisms underlying the actions and properties of the above-mentioned selenoproteins having the characteristic feature of binding transition or heavy metals. Full article

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

South American camelids inhabit high-altitude environments characterized by hypoxia, influencing embryonic, fetal, and placental development. This study examined the term placenta morphology of alpacas (Vicugna pacos, N = 12) and the immunoexpression of antioxidant selenoproteins (SP). We hypothesize that the placenta of alpacas, adapted to high altitudes, has characteristics with other species also adapted to altitude. Placentas were paraffin-embedded, sectioned (3–5 µm), stained with hematoxylin–eosin (H&E), Masson’s trichrome, and picrosirius red, and analyzed via light and polarized light microscopy. The chorion showed simple cuboidal epithelium with binucleated cells, a subepithelial mesenchyme rich in blood capillaries (area: 124.90 ± 9.82 µm²), and type III collagen fibers. The chorionic villi measured 2740.22 ± 132.75 µm. The allantois contained a simple columnar epithelium and mesenchyme with type I collagen fibers. Immunohistochemistry localized SP-N, SP-P, Dio-3, and GPx-3 in the blood capillaries and mesenchymal tissue of the chorion but not in the allantois. These findings were compared to human and sheep placentas from different altitudes due to a lack of camelid data at low levels. The morphological features resembled adaptations to hypoxia observed in other species. This preliminary study suggests a potential role for selenoproteins in hypoxia adaptation, providing a basis for future functional studies. Full article

Background/Objectives: In recent years, there has been a growing interest in precision nutrition and its potential for disease prevention. Differences in individual responses to diet, especially among populations of different ancestry, have underlined the importance of understanding the effects of genetic variations on nutrient intake (nutrigenomics). Since humans generally cannot synthesize essential vitamins, the maintenance of healthy bodily functions depends on dietary vitamin intake. Understanding the differences in vitamin uptake and metabolism across diverse populations may allow for targeted treatment plans and improved overall health. We assessed the current scientific evidence on genetic variations (such as single-nucleotide polymorphisms (SNPs)) affecting vitamin metabolism in humans. Methods: A systematic literature review of primary studies on genetic variations associated with (personalized) nutrition was conducted. Using key terms related to personalized nutrition, nutrigenomics, SNPs, and genetic variations, three online databases were searched for studies published between 2007 and 2023 that included healthy adult subjects. Only results that were confirmed at least once were included. Study quality was assessed with the Joanna Briggs Institute (JBI) critical appraisal tool. Results: Eighty-six articles were included in this review. Our analysis revealed associations with homocysteine metabolism and B Vitamins, Vitamin D, and components of Vitamin E. Genetic associations with Vitamin D, particularly with the GC gene, were extensively researched and linked to lower 25(OH)D concentrations, with sunlight exposure as a contributing factor. Most variants had a negative effect on homocysteine levels. Additionally, we observed general increases in carotenoid levels in the presence of SNPs, although more research on Selenium and Selenoprotein P concentrations is warranted. No studies on Vitamin C were obtained, indicating an area for further methodological improvement. Ancestry is believed to be a significant factor influencing SNP associations and significance. Conclusions: The current review emphasizes the importance of genetics in targeted disease prevention and health care. Our comprehensive findings may provide healthcare practitioners with reliable information to make recommendations in precision nutrition, specifically vitamin supplementation. Full article