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Selenium (Se) is an essential element in human and animal diets, based upon a widespread range of beneficial effects that are primarily due to its antioxidant properties. While Se can be associated to anti-cancer and anti-diabetic activities, reproductive efficiency, and enhancement of the immune system, the mechanistic details of the corresponding biological processes are still largely elusive. To avoid deficiencies and increase bioavailability, Se it is generally supplied to livestock through Se-supplemented feeds or forage plants fertilized with inorganic Se. While the relationship between Ca.sup.2+ and ROS (reactive oxygen species) is well known, only a few studies have addressed the possible involvement of Se in the control of cytosolic Ca.sup.2+ in oxidative stress. The results on Ca.sup.2+ homeostasis were obtained adding exogenous Se in the form of SeO.sub.4 .sup.2- to sheep lymphomonocytes cultured in vitro. In particular, Se strongly attenuated 1mM H.sub.2 O.sub.2 -induced alteration of intracellular [Ca.sup.2+ ].sub.C as well as the entry of extracellular Ca.sup.2+ into the cells with comparable EC50 values for sodium selenate accounting to 1.72 and 2.28 mM, respectively. In an ex vivo trial, it was observed that Ca.sup.2+ homeostasis can effectively be rescued in sheep lymphomonocytes exposed in vivo to a Se concentration of approximately 1.9 mM, that was achieved by feeding sheep with olive leaves previously sprayed with 500 mg/plant Na-selenate. Thus the results obtained suggest that the mode of action of selenium markedly influenced Ca.sup.2+ -related signaling events. Furthermore, results clearly reveal that the protective effect of Se on Ca.sup.2+ homeostasis under oxidative challenge can be clearly and effectively achieved through an appropriate dietary regimen obtained also in a circular economy logic using pruning of olive trees treated to reduce tree drought stress.

AIMS: Although the global importance of selenium (Se) deficiency to human and animal health has been recognized for decades, strategic Se fertilization interventions addressing agro-ecosystem specific conditions have not been developed. This research aims to identify such strategies based on an inventory of production-ecological factors controlling the potential impact of Se fertilizers on crop performance and nutritional content. METHODS: The effect of agro-ecosystem properties on crop response to Se fertilization was assessed using a meta-analysis approach based on 243 experiments performed during 1960 to 2014. RESULTS: The meta-analysis confirms the high impact of fertilization as an effective agronomic biofortification strategy. Site specific properties strongly affect crop responses to Se fertilization implying the need for tailor-made solutions. However, the minor influence of soil organic matter, total soil Se levels and acidity suggests that consideration of other agro-ecosystem properties like climate and bioavailable Se measurements is also required to optimize fertilizer strategies. CONCLUSIONS: Fertilization characteristics including formulation, dose and timing were found to be driving variables enhancing crop Se uptake. The highest uptake efficiencies are found for foliar and selenate based fertilizers. The current low recoveries and the scarce resource availability challenges the fertilizer approach to develop strategies that maximize the uptake efficiency of Se.

Glutathione peroxidase 4 (GPx4) is an antioxidant enzyme reported as an inhibitor of ferroptosis, a recently discovered non-apoptotic form of cell death. This pathway was initially described in cancer cells and has since been identified in hippocampal and renal cells. In this Perspective, we propose that inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration. In addition, we suggest that selenium deficiency enhances susceptibility to ferroptotic processes, as well as other programmed cell death pathways due to a reduction in GPx4 activity. We review recent studies of GPx4 with an emphasis on neuronal protection, and discuss the relevance of selenium levels on its enzymatic activity.

The aim of this study was to synthesize selenium nanoparticles (SeNPs) using cell suspension and total cell protein of sp. SW30 and optimize its synthesis by studying the influence of physiological and physicochemical parameters. Also, we aimed to compare its anticancer activity with that of chemically synthesized SeNPs in breast cancer cells. Cell suspension of sp. SW30 was exposed to various physiological and physicochemical conditions in the presence of sodium selenite to study their effects on the synthesis and morphology of SeNPs. Breast cancer cells (4T1, MCF-7) and noncancer cells (NIH/3T3, HEK293) were exposed to different concentrations of SeNPs. The 18 h grown culture with 2.7×10 cfu/mL could synthesize amorphous nanospheres of size 78 nm at 1.5 mM and crystalline nanorods at above 2.0 mM Na SeO concentration. Polygonal-shaped SeNPs of average size 79 nm were obtained in the supernatant of 4 mg/mL of total cell protein of sp. SW30. Chemical SeNPs showed more anticancer activity than SeNPs synthesized by sp. SW30 (BSeNPs), but they were found to be toxic to noncancer cells also. However, BSeNPs were selective against breast cancer cells than chemical ones. Results suggest that BSeNPs are a good choice of selection as anticancer agents.

Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 μg Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. The mean serum selenium concentration among participants at baseline was low, 67.1 μg/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; <65 μg/L, 65-85 μg/L, and >85 μg/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of >85 μg/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group. In this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 μg/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations <65 μg/L in comparison with those having a selenium concentration >85 μg/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, ≤85 at inclusion. In those with serum selenium>85 μg/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted. Clinicaltrials.gov NCT01443780.

The adverse influences of elevated ambient temperatures during the summer season on the rabbit industry have received increased global attention. Therefore, this study intended to compare the potential effects of nano-selenium (nano-Se) synthesized by biological (BIO) and chemical (CH) methods on growth performance, carcass variables, serum metabolites, and inflammatory cytokines responses of growing rabbits in the summer season. Two hundred and fifty weaned rabbits (males, 35 days of age) were randomly divided into five treatment groups of 50 rabbits each (each group had five replicates with ten male rabbits). Treatment groups were fed a control diet and four controlled diets supplemented with nano-Se synthesized by biological method (BIO25 and BIO50, with a 25 and 50 mg of nano-Se/kg diet, respectively) and chemical method (CH25 and CH50, with a 25 and 50 mg of nano-Se/kg diet, respectively) for eight weeks. During 11 to 13 weeks of age, a gradual enhancement in live body weight (LBW), feed intake (FI) and feed conversion ratio (FCR) was noticed with BIO25 and BIO50 treatments compared to those in the other groups. The carcass percentage was significantly higher (p < 0.01) for animals fed with BIO25 than the other groups. The other organ functions were significantly higher (p < 0.01) in heat-stressed groups compared to that of nano-Se groups. Increasing the level of only BIO from a 25 to a 50 mg/kg diet gave more improvement in the studied parameters. Additionally, the concentrations of serum urea, triglycerides (TG), and glutamyl transferase (GGT) were lower (p < 0.01) in both treated and untreated groups. Likewise, the supplementation with nano-Se (BIO25, BIO50, or CH25) significantly improved the antioxidant indices and inflammatory cytokines responses as indicated from serum metabolites. Based on the study results, nano-Se especially synthesized by the biological method at diet levels of 25 or 50 mg/kg improved the growth performance, kidney and liver functions, carcass traits, antioxidants indices, and inflammatory cytokines of growing rabbits during thermal stress.

Background Several studies indicated that dietary organic selenium (Se) usually absorbed better than an inorganic source, with high retention and bioavailability. Dietary Se as an antioxidant element affects the immune system and hematological status in animals. Therefore, the aim of this study was to evaluate the effect of dietary supplementation of bacterial selenium as an organic source on hematology, immunity response, selenium retention, and gut morphology in broiler chickens. Results The present results revealed that supplementation of inorganic Se was associated with the lowest level of RBC, HB, and PCV with significant difference than ADS18-Se. In the starter stage, both T2 and T5 were associated with the significantly highest IgG level compared to the basal diet, while all supplemented groups showed higher IgM levels compared to the control group. In the finisher phase, all Se supplemented groups showed significant ( P ˂ 0.05) increases in IgG, IgA, and IgM levels compared to T1. Birds fed bacterial-Se showed high intestinal villus height and better Se retention more than sodium selenite. The organic selenium of ADS18 had a superior action in improving Se retention compared to ADS1 and ADS2 bacterial Se. Conclusions Bacterial organic Se had a beneficial effect on the villus height of small intestine led to high Se absorption and retention. Thus, it caused a better effect of Se on hematological parameters and immunity response.

Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95%CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified. Since this was a small study, the observations should be regarded as hypothesis-generating. Clinicaltrials.gov NCT01443780.

Selenium (Se) is an essential oligonutrient, as a component of several Se-containing proteins (selenoproteins), which exert important biological functions within an organism. In livestock, Se-enriched products have been proposed as dietary supplements to be included into functional feeds for animal preventive health care. To this end, it is important to understand the optimal range of concentrations for supplementation and how long it takes to be assimilated into the organism. In this study, rainbow trout (Oncorhynchus mykiss) were fed a control diet containing 0.9 g Kg-1 Se or the same diet supplemented with a Se-Yeast product (Sel-Plex) to achieve Se concentrations ranging from 1.5-8.9 g Kg-1 for a period of ten weeks. Fish were sampled every two weeks for analysis. The kinetics of Se bioaccumulation and the effects on fish selenoprotein expression was determined in different tissues combining chemical and bimolecular techniques. The Sel-Plex enriched diets did not have any effect on survival and growth performance. The highest Se levels were found in liver and kidney followed by muscle and blood cells. Analysis of the Se concentration factor showed that liver is able to initially regulate the amount of Se accumulated. However, with higher dietary Se level (4.8 and 8.9 g Kg-1) and longer times of exposure (10 weeks), regulation is ineffective and the Se tissue concentration increases. The expression of the selected trout selenoprotein transcripts showed an inverse correlation with Sel-Plex augmentation in most cases. In liver, kidney and blood cells the highest up-regulation of the trout selenoprotein genes was seen mostly in the group fed the diet enriched with the lowest concentration of Sel-Plex (0.5 g Kg-1) for 10 weeks. Sel-Plex may represent an excellent Se supplement to deliver a high level of Se without provoking harm to the fish and to guarantee the maximal absorption of the element. According to our results, a dietary supplementation of Sel-Plex between 0.5 and 4 g Kg-1 may allow maximal benefits, whereas 8 g Kg-1 may be excessive for the purpose of supplementation.

Tea plant (Camellia sinensis) has strong enrichment ability for selenium (Se). Selenite is the main form of Se absorbed and utilized by tea plant. However, the mechanism of selenite absorption and accumulation in tea plant is still unknown. In this study, RNA sequencing (RNA-seq) was used to perform transcriptomic analysis on the molecular mechanism of selenite absorption and accumulation in tea plant. 397.98 million high-quality reads were obtained and assembled into 168,212 unigenes, 89,605 of which were extensively annotated. There were 60,582 and 1,362 differentially expressed genes (DEGs) in roots and leaves, respectively. RNA-seq results were further validated by quantitative RT-PCR. Based on GO terms, the unigenes were mainly involved in cell, binding and metabolic process. KEGG pathway enrichment analysis showed that predominant pathways included ribosome and protein processing in endoplasmic reticulum. Further analysis revealed that sulfur metabolism, glutathione metabolism, selenocompound metabolism and plant hormone signal transduction responded to selenite in tea plant. Additionally, a large number of genes of higher expressions associated with phosphate transporters, sulfur assimilation, antioxidant enzymes, antioxidant substances and responses to ethylene and jasmonic acid were identified. Stress-related plant hormones might play a signaling role in promoting sulfate/selenite uptake and assimilation in tea plant. Moreover, some other Se accumulation mechanisms of tea plant were found. Our study provides a possibility for controlling Se accumulation in tea plant through bio-technologies and will be helpful for breeding new tea cultivars.