Stabilization by Chaperone GroEL in Biogenic Selenium Nanoparticles Produced from Bifidobacterium animalis H15 for the Treatment of DSS-Induced Colitis.

Inflammatory bowel diseases have a high rate of mortality and pose a serious threat to global public health. Selenium is an essential trace element, which has been shown to play important roles in redox control and antioxidant defense. Microorganisms play important roles in the reduction of toxic inorganic selenium (selenite and selenate) to less-toxic biogenic selenium nanoparticles (Bio-SeNPs), which have higher biocompatibility. In the present study, novel Bio-SeNPs with high stability were synthesized using probiotic Bifidobacterium animalis subsp. lactis H15, which was isolated from breastfed infant feces. The Bio-SeNPs with a size of 122 nm showed stability at various ionic strengths, temperatures, and in simulated gastrointestinal fluid, while chemosynthetic SeNPs underwent aggregation. The main surface protein in the Bio-SeNPs was identified as chaperone GroEL by liquid chromatography-tandem mass spectrometry. The overexpression and purification of GroEL demonstrated that GroEL controlled the assembly of Bio-SeNPs both in vitro and in vivo. In vivo, oral administration of Bio-SeNPs could alleviate dextran sulfate sodium-induced colitis by decreasing cell apoptosis, increasing antioxidant capacity and the number of proliferating cells, and improving the function of the intestinal mucosal barrier. In vitro experiments verified that Bio-SeNPs inhibited lipopolysaccharide-induced toll-like receptor 4/NF-κB signaling pathway activation. These results suggest that the Bio-SeNPs with high stability could have potential as a nutritional supplement for the treatment of colitis in nanomedicine applications.

Advances in the Study of Selenium-Enriched Probiotics: From the Inorganic Se into Se Nanoparticles.

Selenium (Se) is a momentous metallic element that plays an irreplaceable role in biochemical activities. Se deficiency remains a nutritional challenge across the world. Organic Se supplementation is the most effective treatment means for Se deficiency. Organic Se transformed from Se-enriched probiotics show outstanding excellent properties in antibacteria, anti-oxidation, anti-inflammation, and immunoregulation. Studying the influencing factors for Se enrichment capacity and enrichment mechanisms of Se-enriched probiotics is conducive to the exploit of more potent Se-enriched probiotics. Se-enriched probiotics transform inorganic Se into Se nanoparticles (SeNPs), which have been widely used in animal husbandry and biomedical field. In this paper, the novel development of Se-enriched probiotics is reviewed, and the bioactivities of SeNPs are assessed, so as to display their potential application prospects. The excellent role of SeNPs in anti-oxidation is summarized, and the mechanism by which SeNPs improve Se deficiency and boost animal health is explained.

Eucommia ulmoides polysaccharide modified nano-selenium effectively alleviated DSS-induced colitis through enhancing intestinal mucosal barrier function and antioxidant capacity.

Ulcerative colitis (UC) is currently the most common inflammatory bowel disease (IBD). Due to its diverse and complex causes, there is no cure at present, and researchers are constantly exploring new therapies. In recent years, nano-selenium particle(SeNP) has attracted wide attention due to excellent biological activities. Therefore, in this study, for the first time, we used a natural polysaccharide, Eucommia ulmoides polysaccharide (EUP), modified SeNP to get EUP-SeNP with a size of about 170 nm, and its effect on 3% dextran sulphate sodium (DSS) induced colitis was explored. Our results showed that colon intestinal histology, intestinal mucosal barrier, inflammatory cytokines and intestinal microbiome composition were changed after EUP-SeNP treatment in colitis mice. Specifically, it was also shown that oral treatment of EUP-SeNP could relieve the degree of DSS-induced colitis in mice by restoring weight loss, reducing disease activity index (DAI), enhancing colon antioxidant capacity and regulating intestinal microbiome composition. In addition, we verified the mechanism in intestinal epithelial cell lines, showing that EUP-SeNP inhibited LPS-induced activation of the TRL-4/NF-κB signaling pathway in intestinal epithelial cell lines. To some extend, our study provides therapeutic reference for the treatment of IBD.

Protective Effects of Selenium Nanoparticles against Bisphenol A-Induced Toxicity in Porcine Intestinal Epithelial Cells.

Bisphenol A (BPA) is widely used to harden plastics and polycarbonates and causes serious toxic effects in multiple organs, including the intestines. Selenium, as an essential nutrient element for humans and animals, exhibits a predominant effect in various physiological processes. Selenium nanoparticles have attracted more and more attention due to their outstanding biological activity and biosafety. We prepared chitosan-coated selenium nanoparticles (SeNPs) and further compared the protective effects, and investigated the underlying mechanism of SeNPs and inorganic selenium (Na2SeO3) on BPA-induced toxicity in porcine intestinal epithelial cells (IPEC-J2). The particle size, zeta potential, and microstructure of SeNPs were detected by using a nano-selenium particle size meter and a transmission electron microscope. IPEC-J2 cells were exposed to BPA alone or simultaneously exposed to BPA and SeNPs or Na2SeO3. The CCK8 assay was performed to screen the optimal concentration of BPA exposure and the optimal concentration of SeNPs and Na2SeO3 treatment. The apoptosis rate was detected by flow cytometry. Real-time PCR and Western blot methods were used to analyze the mRNA and protein expression of factors related to tight junctions, apoptosis, inflammatory responses and endoplasmic reticulum stress. Increased death and morphological damage were observed after BPA exposure, and these increases were attenuated by SeNPs and Na2SeO3 treatment. BPA exposure disturbed the tight junction function involved with decreased expression of tight junction protein Zonula occludens 1 (ZO-1), occludin, and claudin-1 proteins. Proinflammatory response mediated by the transcription factor nuclear factor-k-gene binding (NF-κB), such as elevated levels of interleukin-1ß(IL-1ß), interleukin-6 (IL-6), interferon-γ (IFN-γ), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) expression was induced at 6 and 24 h after BPA exposure. BPA exposure also disturbed the oxidant/antioxidant status and led to oxidative stress. IPEC-J2 cell apoptosis was induced by BPA exposure, as indicated by increased BCL-2-associated X protein (Bax), caspase 3, caspase 8, and caspase 9 expression and decreased B-cell lymphoma-2 (Bcl-2) and Bcl-xl expression. BPA exposure activated the endoplasmic reticulum stress (ERS) mediated by the receptor protein kinase receptor-like endoplasmic reticulum kinase (PERK), Inositol requiring enzyme 1 (IRE1α), and activating transcription factor 6 (ATF6). We found that treatment with SeNPs and Na2SeO3 can alleviate the intestinal damage caused by BPA. SeNPs were superior to Na2SeO3 and counteracted BPA-induced tight junction function injury, proinflammatory response, oxidative stress, apoptosis, and ERS stress. Our findings suggest that SeNPs protect intestinal epithelial cells from BPA-induced damage, partly through inhibiting ER stress activation and subsequently attenuating proinflammatory responses and oxidative stress and suppressing apoptosis, thus enhancing the intestinal epithelial barrier function. Our data indicate that selenium nanoparticles may represent an effective and reliable tool for preventing BPA toxicity in animals and humans.

Selenium deficiency-induced multiple tissue damage with dysregulation of immune and redox homeostasis in broiler chicks under heat stress.

Broiler chicks are fast-growing and susceptible to dietary selenium (Se) deficiency. This study sought to reveal the underlying mechanisms of how Se deficiency induces key organ dysfunctions in broilers. Day-old male chicks (n=6 cages/diet, 6 chicks/cage) were fed with a Se-deficient diet (Se-Def, 0.047 mg Se/kg) or the Se-Def+0.3 mg Se/kg (Control, 0.345 mg Se/kg) for 6 weeks. The serum, liver, pancreas, spleen, heart, and pectoral muscle of the broilers were collected at week 6 to assay for Se concentration, histopathology, serum metabolome, and tissue transcriptome. Compared with the Control group, Se deficiency induced growth retardation and histopathological lesions and reduced Se concentration in the five organs. Integrated transcriptomics and metabolomics analysis revealed that dysregulation of immune and redox homeostasis related biological processes and pathways contributed to Se deficiency-induced multiple tissue damage in the broilers. Meanwhile, four metabolites in the serum, daidzein, epinephrine, L-aspartic acid and 5-hydroxyindoleacetic acid, interacted with differentially expressed genes with antioxidative effects and immunity among all the five organs, which contributed to the metabolic diseases induced by Se deficiency. Overall, this study systematically elucidated the underlying molecular mechanisms in the pathogenesis of Se deficiency-related diseases, which provides a better understanding of the significance of Se-mediated heath in animals.

Advances in the Study of the Mechanism by Which Selenium and Selenoproteins Boost Immunity to Prevent Food Allergies.

Selenium (Se) is an essential micronutrient that functions in the body mainly in the form of selenoproteins. The selenoprotein contains 25 members in humans that exhibit a number of functions. Selenoproteins have immunomodulatory functions and can enhance the ability of immune system to regulate in a variety of ways, which can have a preventive effect on immune-related diseases. Food allergy is a specific immune response that has been increasing in number in recent years, significantly reducing the quality of life and posing a major threat to human health. In this review, we summarize the current understanding of the role of Se and selenoproteins in regulating the immune system and how dysregulation of these processes may lead to food allergies. Thus, we can explain the mechanism by which Se and selenoproteins boost immunity to prevent food allergies.

The Role and Mechanism of Essential Selenoproteins for Homeostasis.

Selenium (Se) is one of the essential trace elements that plays a biological role in the body, mainly in the form of selenoproteins. Selenoproteins can be involved in the regulation of oxidative stress, endoplasmic reticulum (ER) stress, antioxidant defense, immune and inflammatory responses and other biological processes, including antioxidant, anti-inflammation, anti-apoptosis, the regulation of immune response and other functions. Over-loading or lack of Se causes certain damage to the body. Se deficiency can reduce the expression and activity of selenoproteins, disrupt the normal physiological function of cells and affect the body in antioxidant, immunity, toxin antagonism, signaling pathways and other aspects, thus causing different degrees of damage to the body. Se intake is mainly in the form of dietary supplements. Due to the important role of Se, people pay increasingly more attention to Se-enriched foods, which also lays a foundation for better research on the mechanism of selenoproteins in the future. In this paper, the synthesis and mechanism of selenoproteins, as well as the role and mechanism of selenoproteins in the regulation of diseases, are reviewed. Meanwhile, the future development of Se-enriched products is prospected, which is of great significance to further understand the role of Se.

Trace Element Selenium Effectively Alleviates Intestinal Diseases.

Selenium (Se) is an essential trace element in the body. It is mainly used in the body in the form of selenoproteins and has a variety of biological functions. Intestinal diseases caused by chronic inflammation are among the most important threats to human health, and there is no complete cure at present. Due to its excellent antioxidant function, Se has been proven to be effective in alleviating intestinal diseases such as inflammatory bowel diseases (IBDs). Therefore, this paper introduces the role of Se and selenoproteins in the intestinal tract and the mechanism of their involvement in the mediation of intestinal diseases. In addition, it introduces the advantages and disadvantages of nano-Se as a new Se preparation and traditional Se supplement in the prevention and treatment of intestinal diseases, so as to provide a reference for the further exploration of the interaction between selenium and intestinal health.

Selenoproteins Protect Against Avian Liver Necrosis by Metabolizing Peroxides and Regulating Receptor Interacting Serine Threonine Kinase 1/Receptor Interacting Serine Threonine Kinase 3/Mixed Lineage Kinase Domain-Like and Mitogen-Activated Protein Kinase Signaling.

Liver necroptosis of chicks is induced by selenium (Se)/vitamin E (VE) deficiencies and may be associated with oxidative cell damage. To reveal the underlying mechanisms of liver necrosis, a pool of the corn-soy basal diet (10 µg Se/kg; no VE added), a basal diet plus all-rac-α-tocopheryl acetate (50 mg/kg), Se (sodium selenite at 0.3 mg/kg), or both of these nutrients were provided to day-old broiler chicks (n = 40/group) for 6 weeks. High incidences of liver necrosis (30%) of chicks were induced by -SE-VE, starting at day 16. The Se concentration in liver and glutathione peroxidase (GPX) activity were decreased (P < 0.05) by dietary Se deficiency. Meanwhile, Se deficiency elevated malondialdehyde content and decreased superoxide dismutase (SOD) activity in the liver at weeks 2 and 4. Chicks fed with the two Se-deficient diets showed lower (P < 0.05) hepatic mRNA expression of Gpx1, Gpx3, Gpx4, Selenof, Selenoh, Selenok, Selenom, Selenon, Selenoo, Selenop, Selenot, Selenou, Selenow, and Dio1 than those fed with the two Se-supplemented diets. Dietary Se deficiency had elevated (P < 0.05) the expression of SELENOP, but decreased the downregulation (P < 0.05) of GPX1, GPX4, SELENON, and SELENOW in the liver of chicks at two time points. Meanwhile, dietary Se deficiency upregulated (P < 0.05) the abundance of hepatic proteins of p38 mitogen-activated protein kinase, phospho-p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, phospho-c-Jun N-terminal kinase, extracellular signal-regulated kinase, phospho-mitogen-activated protein kinase, receptor-interacting serine-threonine kinase 1 (RIPK1), receptor-interacting serine-threonine kinase 3 (RIPK3), and mixed lineage kinase domain-like (MLKL) at two time points. In conclusion, our data confirmed the differential regulation of dietary Se deficiency on several key selenoproteins, the RIPK1/RIPK3/MLKL, and mitogen-activated protein kinase signaling pathway in chicks and identified new molecular clues for understanding the etiology of nutritional liver necrosis.

Dietary Selenium Regulates microRNAs in Metabolic Disease: Recent Progress.

Selenium (Se) is an essential element for the maintenance of a healthy physiological state. However, due to environmental and dietary factors and the narrow safety range of Se, diseases caused by Se deficiency or excess have gained considerable traction in recent years. In particular, links have been identified between low Se status, cognitive decline, immune disorders, and increased mortality, whereas excess Se increases metabolic risk. Considerable evidence has suggested microRNAs (miRNAs) regulate interactions between the environment (including the diet) and genes, and play important roles in several diseases, including cancer. MiRNAs target messenger RNAs to induce changes in proteins including selenoprotein expression, ultimately generating disease. While a plethora of data exists on the epigenetic regulation of other dietary factors, nutrient Se epigenetics and especially miRNA regulated mechanisms remain unclear. Thus, this review mainly focuses on Se metabolism, pathogenic mechanisms, and miRNAs as key regulatory factors in Se-related diseases. Finally, we attempt to clarify the regulatory mechanisms underpinning Se, miRNAs, selenoproteins, and Se-related diseases.

Lactoferrin Is a Potential Activator of the Vitamin D Receptor in Its Regulation of Osteogenic Activities in C57BL/6J Mice and MC3T3-E1 Cells.

BACKGROUND: Lactoferrin (LF) has been shown to promote bone anabolism, and the vitamin D receptor (VDR) mediates the effects of vitamin D on bone. We hypothesized that LF improves bone health by increasing VDR expression. OBJECTIVES: We sought to determine the role of VDR activation in LF-induced osteogenic activity in vivo and in vitro and the underlying molecular mechanisms. METHODS: Sixty male C57BL/6J mice (aged 4 wk) were randomly assigned into 6 groups and fed vitamin D-deficient (VDD; 0 IU/kg) or vitamin D-normal diet (VDN; 1000 IU cholecalciferol/kg) and administered placebo or LF (100 or 1000 mg/kg body weight) by gavage for 24 wk. Trabecular bone structure was analyzed using micro-CT, and VDR expression was assessed by immunohistochemistry. In vitro, MC3T3-E1 cells were treated with 100 µg LF/mL to evaluate its effect on VDR expression. Finally, the direct recruitment of LF to the Vdr promoter was confirmed by chromatin immunoprecipitation assay. In addition, cells were transfected with pGL3-basic Vdr vector for monitoring Vdr promoter activation using luciferase assays. RESULTS: LF supplementation at 100 and 1000 mg/kg revealed an ∼6.5% (P < 0.05) increase in bone mineral density in mice on VDD diet and exhibited an enhanced expression of VDR in bone compared with control. This increased expression of VDR was also observed in the bone of mice on the VDN diet, but the effect was more pronounced in VDD diet. In vitro, compared with the control group, Vdr mRNA expression was 18 times greater (P < 0.05) and peaked at 2 h posttreatment of LF. By cotransfection of the pGL3-basic Vdr vector, LF induced luciferase activity by 30% (P < 0.05) in MC3T3-E1 cells. CONCLUSIONS: In vivo and in vitro, LF, a potential activator of VDR, promotes osteogenesis. This suggests that dairy products, which are rich in LF, may serve as a functional food to improve bone health.

Exploring the structure evolution of MoS2 upon Li/Na/K ion insertion and the origin of the unusual stability in potassium ion batteries.

The recent revival of research on Na and K ion batteries has two benefits. It not only provides alternate energy storage technologies to Li ion batteries with potential cost advantages but also enhances our understanding of charge storage through systematic studies on alkali-metal ion batteries with increasing insertion ion sizes. Using MoS2 as a model material, the structure evolution upon the uptake of Li, Na, and K ions are compared through in situ TEM. Despite their larger size, insertion of K ions shows both the better electrochemical and structural stability. To understand this paradoxical and counter-intuitive phenomenon, in situ XRD is carried out to examine the phase transitions of MoS2 upon ion insertion, while ex situ TEM is further applied to closely examine the structures at the nanoscale. Complementary DFT calculations are performed to understand the kinetic/thermodynamic origins of the unusual stability. The result reveal that the less electrovalent K-S bond favors the intercalation process, resulting in preservation of the layered structure for stable cycling. This study provides a structural insight to design stable electrodes for the K-ion batteries.

Knockout of Selenoprotein V Affects Regulation of Selenoprotein Expression by Dietary Selenium and Fat Intakes in Mice.

BACKGROUND: The metabolic function of selenoprotein V (SELENOV) remains unknown. OBJECTIVES: Two experiments were conducted to determine effects of the Selenov knockout (KO) on selenium concentration and mRNA, protein, and/or activity of 4 major selenoproteins [glutathione peroxidase (GPX) 1, GPX4, thioredoxin reductase-1 (TXNRD1), and selenoprotein P (SELENOP)] in the serum, liver, testis, and/or white adipose tissue (WAT) of mice fed different dietary selenium and fat concentrations. METHODS: In Experiment (Expt) 1, 40 KO and 40 wild-type (WT) mice (males, 8 wk old) were fed (n = 10/genotype) a casein-sucrose basal diet plus 0, 0.3, 1, or 3 mg Se/kg (as sodium selenite) for 32 wk . In Expt 2, 20 KO and 20 WT mice (males, 8 wk old) were fed (n  = 10/genotype) a normal-fat diet (NF; 10% calories from fat) or a high-fat diet (HF; 60% calories from fat) for 19 wk. RESULTS: In Expt 1, the KO caused consistent or substantial decreases (P < 0.05) of mRNA amounts of Gpx1, Txnrd1, and Selenop in the testis (≤52%), but selenium concentrations (19-29%) and GPX activities (≤ 50%) were decreased in the liver across different dietary selenium concentrations . Hepatic and testis GPX1 protein was elevated (≤31%) and decreased (≤45%) by the KO, respectively. In Expt 2, the genotype and dietary fat intake exerted interaction effects ( P < 0.05) on Gpx1 mRNA amounts in the WAT; Gpx1, Txnrd1, and Selenop mRNA amounts and TXNRD activities in the testis; and selenium concentrations in the serum and liver. However, these 2 treatments produced largely independent or additive effects (P < 0.05) on the GPX1 and SELENOP protein amounts in the liver and testis (up to ± 50% changes). CONCLUSIONS: The KO-mediated changes in the tissue selenium concentrations and functional expression of 3 major selenoproteins implied potential for SELENOV in regulating body selenium metabolism in the mouse.

The underestimated charge storage capability of carbon cathodes for advanced alkali metal-ion capacitors.

Li-ion capacitors (LICs) are emerging as complementary energy storage devices to Li-ion batteries to satisfy some specific applications where high power density and long cycle life are required. Due to the wide usage of LICs, LICs with promising energy density are urgently needed; however, at this stage, the achievement of this type of LICs is the main challenge. In this study, we increased the energy density of LICs via both material optimization and charge storage mechanism exploration. Moreover, porous carbon with a high surface area of over 2800 m2 g-1 was fabricated from alkali lignin via a traditional KOH activation method assisted by self-activation. A wide voltage window of 1.0-4.8 V was applied where the synergistic storage of anions and cations was achieved. This shows that a deep discharge down to 1.0 V is necessary for the complete desorption of anions, which also triggers the adsorption of cations (Li+), resulting in increased capacity. However, a compromise must be made in the energy efficiency due to intensified battery polarization upon deep discharging. Furthermore, considering the natural abundance of sodium and potassium over lithium, Na- and K-ion capacitors have been investigated for sustainable development using the as-prepared carbon materials.

Avian selenogenome: response to dietary Se and vitamin E deficiency and supplementation.

Selenium (Se) is an essential nutrient for humans and all food-producing animal species. Nutritional deficiencies of Se and (or) vitamin E induce exudative diathesis, nutritional pancreatic atrophy, and nutritional muscular dystrophy in chicks. Although these diseases are presumably associated with the need of Se for the synthesis of the 21st amino acid, selenocysteine (Sec, U) in selenoproteins, metabolic functions of the 25 selenoproteins identified in avian species remain largely unknown. This paper reviews regulations of the whole selenogenome and selected selenoproteins by different concentrations and chemical forms of dietary Se and (or) vitamin E in various affected tissues. The avian selenogenome may be divided into 2 groups: responders and non-responders, based on its response to dietary Se and vitamin E changes. Mechanisms for the gene-, tissue-, and age-dependent responses and the correlation with the stress and cell death signaling are explored. Overall, this review intends to link the novel regulation and function of avian selenogenome to the protection by Se against oxidative insults associated with the classical Se/vitamin E deficiency diseases in chicks.

A Novel Organic Selenium Compound Exerts Unique Regulation of Selenium Speciation, Selenogenome, and Selenoproteins in Broiler Chicks.

Background: A new organic selenium compound, 2-hydroxy-4-methylselenobutanoic acid (SeO), displayed a greater bioavailability than sodium selenite (SeNa) or seleno-yeast (SeY) in several species.Objective: This study sought to determine the regulation of the speciation of selenium, expression of selenogenome and selenocysteine biosynthesis and degradation-related genes, and production of selenoproteins by the 3 forms of selenium in the tissues of broiler chicks.Methods: Day-old male chicks (n = 6 cages/diet, 6 chicks/cage) were fed a selenium-deficient, corn and soy-based diet [base diet (BD), 0.05 mg Se/kg] or the BD + SeNa, SeY, or SeO at 0.2 mg Se/kg for 6 wk. Plasma, livers, and pectoral and thigh muscles were collected at weeks 3 and 6 to assay for total selenium, selenomethionine, selenocysteine, redox status, and selected genes, proteins, and enzymes.Results: Although both SeY and SeO produced greater concentrations (P < 0.05) of total selenium (20-172%) and of selenomethionine (≤15-fold) in the liver, pectoral muscle, and thigh than those of SeNa, SeO further raised (P < 0.05) these concentrations by 13-37% and 43-87%, respectively, compared with SeY. Compared with the BD, only SeO enhanced (P < 0.05) the mRNA of selenoprotein (Seleno) s and methionine sulfoxide reductase B1 (Msrb1) in the liver and thigh (62-98%) and thioredoxin reductase (TXRND) activity in the pectoral and thigh muscles (20-37%) at week 3. Furthermore, SeO increased (P < 0.05) the expression of glutathione peroxidase (Gpx) 3, GPX4, SELENOP, and SELENOU relative to the SeNa group by 26-207%, and the expression of Selenop, O-phosphoseryl-transfer RNA (tRNA):selenocysteinyl-tRNA synthase, GPX4, and SELENOP relative to the SeY group by 23-55% in various tissues.Conclusions: Compared with SeNa or SeY, SeO demonstrated a unique ability to enrich selenomethionine and total selenium depositions, to induce the early expression of Selenos and Mrsb1 mRNA and TXRND activity, and to enhance the protein production of GPX4, SELENOP, and SELENOU in the tissues of chicks.

Selenium Deficiency-Induced Apoptosis of Chick Embryonic Vascular Smooth Muscle Cells and Correlations with 25 Selenoproteins.

Selenium deficiency is the major cause of exudative diathesis in chicks. Subcutaneous hemorrhage is one of the typical symptoms of the disease. However, the reason for the occurrence of blood exudation remains unknown. In the present study, the vascular smooth muscle cells (VSMCs) were isolated from 17-day-old broiler chick embryos. Cell viability, cell apoptosis, and intracellular reactive oxygen species level under different concentrations of selenium (0-0.9 µM) were investigated. The mRNA expression levels of 25 selenoproteins and apoptosis-related genes (p53, CytC, Caspase-3, Caspase-8, Bcl-2, and Bax) were also measured. Selenium deficiency significantly decreased cell viability and increased cell apoptosis (p < 0.05). Supplementation with selenium could alleviate these changes. In general, at all levels of selenium addition, Gpx1, Gpx3, Gpx4, SepW1, and Sep15 mRNAs were all highly expressed in VSMCs, whereas Gpx2, Dio1, SepN1, SelO, and SelPb were at lower levels. There was a high correlation between Gpx2, Gpx3, Gpx4, Dio1, Txnrd1, Txnrd2, and Txnrd3 gene expression. Additionally, Gpx3, Gpx4, Dio1, Txnrd1, Txnrd2, Txnrd3, SelS, and SelPb showed a strong negative correlation with pro-apoptotic gene Caspase-3 as well as a strong positive correlation with anti-apoptotic gene Bcl-2, especially SelI (r = 0.913 and r = 0.929, p < 0.01). These results suggest that selenium deficiency could induce VSMC apoptosis, and several selenoproteins may be involved in the development of apoptosis. Our findings provide information on the molecular mechanism of vascular injury by selenium deficiency.

Characterization of Selenoprotein M and Its Response to Selenium Deficiency in Chicken Brain.

Selenoprotein M (SelM) may function as thiol disulfide oxidoreductase that participates in the formation of disulfide bonds and can be implicated in calcium responses. SelM may have a functional role in catalyzing free radicals and has been associated with Alzheimer's disease (AD). However, studies of SelM in chicken remain very limited. In this study, two groups of day-old broiler chicks (n = 40/group) were fed a corn-soy basal diet (BD, 13 µg Se/kg) and BD supplemented with Se (as sodium selenite) at 0.3 mg/kg. The brain was collected at 14, 21, 28, and 42 days of age. We performed a sequence analysis and predicted the structure and function of SelM. We also investigated the effects of Se deficiency on the expression of Selt, Selw, and Selm and the Se status in the chicken brain. The results show that Se deficiency induced the lower (P < 0.05) Se content, glutathione peroxidase (GPx), and catalase (CAT) activities; increased (P < 0.05) malondialdehyde (MDA) content; and reduced (P < 0.05) the expression of Selm messenger RNA (mRNA) and protein abundance of SelM in the brain. However, there were no significant brain Selt and Selw mRNA levels by dietary Se deficiency in chicks. The different regulations of these three redox (Rdx) protein expressions by Se deficiency represent a novel finding of the present study. Our results demonstrated that SelM may have an important role in protecting against oxidative damage in the brain of chicken, which might shed light on the role of SelM in human neurodegenerative disease. More studies are needed to confirm our conclusion.

Selenoproteins protect against avian nutritional muscular dystrophy by metabolizing peroxides and regulating redox/apoptotic signaling.

Nutritional muscular dystrophy (NMD) of chicks is induced by dietary selenium (Se)/vitamin E (Vit. E) deficiencies and may be associated with oxidative cell damage. To reveal the underlying mechanisms related to the presumed oxidative cell damage, we fed four groups of 1-day-old broiler chicks (n = 40/group) with a basal diet (BD; 10 µg Se/kg; no Vit. E added, -Se -Vit. E) or the BD plus all-rac-α-tocopheryl acetate at 50mg/kg (-Se +Vit. E), Se (as sodium selenite) at 0.3mg/kg (+Se -Vit. E), or both of these nutrients (+Se +Vit. E) for 6 weeks. High incidences of NMD (93%) and mortality (36%) of the chicks were induced by the BD, starting at week 3. Dietary Se deficiency alone also induced muscle fiber rupture and coagulation necrosis in the pectoral muscle of chicks at week 3 and thereafter, with increased (P < 0.05) malondialdehyde, decreased (P < 0.05) total antioxidant capacity, and diminished (P < 0.05) glutathione peroxidase activities in the muscle. To link these oxidative damages of the muscle cells to the Se-deficiency-induced NMD, we first determined gene expression of the potential 26 selenoproteins in the muscle of the chicks at week 2 before the onset of symptoms. Compared with the +Se chicks, the -Se chicks had lower (P < 0.05) muscle mRNA levels of Gpx1, Gpx3, Gpx4, Sepp1, Selo, Selk, Selu, Selh, Selm, Sepw1, and Sep15. The -Se chicks also had decreased (P < 0.05) production of 6 selenoproteins (long-form selenoprotein P (SelP-L), GPx1, GPx4, Sep15, SelW, and SelN), but increased levels (P < 0.05) of the short-form selenoprotein P in muscle at weeks 2 and 4. Dietary Se deficiency elevated (P < 0.05) muscle p53, cleaved caspase 3, cleaved caspase 9, cyclooxygenase 2 (COX2), focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), phospho-Akt, nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, phospho-JNK, and phospho-ERK and decreased (P < 0.05) muscle procaspase 3, procaspase 9, and NF-κB inhibitor α. In conclusion, the downregulation of SelP-L, GPx1, GPx4, Sep15, SelW, and SelN by dietary Se deficiency might account for induced oxidative stress and the subsequent peroxidative damage of chick muscle cells via the activation of the p53/caspase 9/caspase 3, COX2/FAK/PI3K/Akt/NF-κB, and p38 MAPK/JNK/ERK signaling pathways. Metabolism of peroxides and redox regulation are likely to be the mechanisms whereby these selenoproteins prevented the onset of NMD in chicks.

Porcine serum can be biofortified with selenium to inhibit proliferation of three types of human cancer cells.

Our objectives were to determine if porcine serum could be enriched with selenium (Se) by feeding pigs with high concentrations of dietary Se and if the Se-biofortified serum inhibited proliferation of 3 types of human cancer cells. In Expt. 1, growing pigs (8 wk old, n = 3) were fed 0.02 or 3.0 mg Se/kg (as sodium selenite) for 16 wk and produced serum with 0.5 and 5.4 µmol/L Se, respectively. In Expt. 2, growing pigs (5 wk old, n = 6) were fed 0.3 or 1.0 mg Se/kg (as Se-enriched yeast) for 6 wk and produced serum with 2.6 and 6.2 µmol/L Se, respectively. After the Se-biofortified porcine sera were added at 16% in RPMI 1640 to treat NCI-H446, DU145, and HTC116 cells for 144 h, they decreased (P < 0.05) the viability of the 3 types of human cancer cells by promoting apoptosis, compared with their controls. This effect was replicated only by adding the appropriate amount of methylseleninic acid to the control serum and was mediated by a downregulation of 8 cell cycle arrest genes and an upregulation of 7 apoptotic genes. Along with 6 previously reported selenoprotein genes, selenoprotein T (Selt), selenoprotein M (Selm), selenoprotein H (Selh), selenoprotein K (Selk), and selenoprotein N (Sepn1) were revealed to be strongly associated with the cell death-related signaling induced by the Se-enriched porcine serum. In conclusion, porcine serum could be biofortified with Se to effectively inhibit the proliferation of 3 types of human cancer cells and the action synchronized with a matrix of coordinated functional expression of multiple selenoprotein genes.