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This work presents the first systematic comparison of selenium (Se) speciation in plasma from cancer patients treated orally with three Se compounds (sodium selenite, SS; L-selenomethionine, SeMet; or Se-methylselenocysteine, MSC) at 400 µg/day for 28 days. The primary goal was to investigate how these chemical forms of Se affect the plasma Se distribution, aiming to identify the most effective Se compound for optimal selenoprotein expression. This was achieved using methodology based on HPLC-ICP-MS after sample preparation/fractionation approaches. Measurements of total Se in plasma samples collected before and after 4 weeks of treatment showed that median total Se levels increased significantly from 89.6 to 126.4 µg kg−1 Se (p < 0.001), particularly when SeMet was administered (190.4 µg kg−1 Se). Speciation studies showed that the most critical differences between treated and baseline samples were seen for selenoprotein P (SELENOP) and selenoalbumin after administration with MSC (p = 5.8 × 10−4) and SeMet (p = 6.8 × 10−5), respectively. Notably, selenosugar-1 was detected in all low-molecular-weight plasma fractions following treatment, particularly with MSC. Two different chromatographic approaches and spiking experiments demonstrated that about 45% of that increase in SELENOP levels (to ~ 8.8 mg L−1) with SeMet is likely due to the non-specific incorporation of SeMet into the SELENOP affinity fraction. To the authors’ knowledge, this has not been reported to date. Therefore, SELENOP is probably part of both the regulated (55%) and non-regulated (45%) Se pools after SeMet administration, whereas SS and MSC mainly contribute to the regulated one.

The chemical and physical resemblance between selenium (Se) and sulfur (S) establishes that both these elements share common metabolic pathways in plants. The presence of isologous Se and S compounds indicates that these elements compete in biochemical processes that affect uptake, translocation and assimilation throughout plant development. Yet, minor but crucial differences in reactivity and other metabolic interactions infer that some biochemical processes involving Se may be excluded from those relating to S. This review examines the current understanding of physiological and biochemical relationships between S and Se metabolism by highlighting their similarities and differences in relation to uptake, transport and assimilation pathways as observed in Se hyperaccumulator and non-accumulator plant species. The exploitation of genetic resources used in bioengineering strategies of plants is illuminating the function of sulfate transporters and key enzymes of the S assimilatory pathway in relation to Se accumulation and final metabolic fate. These strategies are providing the basic framework by which to resolve questions relating to the essentiality of Se in plants and the mechanisms utilized by Se hyperaccumulators to circumvent toxicity. In addition, such approaches may assist in the future application of genetically engineered Se accumulating plants for environmental renewal and human health objectives.

Selenocysteine methyltransferase (SMT) is a key enzyme involved in the Se metabolism pathway, and it is responsible for the catalysis of Se-methylselenocysteine (SeMSC) compound formation. Previous studies showed that selenium treatment activated SMT expression and promoted the accumulation of glucosinolates (GSLs) and sulforaphane, but the roles and functional mechanisms of SMT in mediating GSLs and sulforaphane synthesis remain unclear. In this study, we identified the BoSMT gene in broccoli and uncovered its roles in mediating GSLs biosynthesis. Transgenic assays revealed that BoSMT is involved in SeMSC biosynthesis in broccoli. More importantly, the contents of GSLs and sulforaphane were significantly increased in the BoSMT-overexpressing broccoli lines but decreased in the knockdown lines, suggesting that BoSMT played a positive role in regulating GSLs and sulforaphane synthesis. Further evidence indicated that BoSMT-mediated overaccumulation of GSLs and sulforaphane might be due to the increase in the endogenous SeMSC content. Compared with the mock (water) treatment, selenite-induced significantly increases of the SeMSC content in the BoSMT-knockdown plants partially compensated the phenotype of GSLs and sulforaphane loss. Compared with the mock treatment, exogenous SeMSC treatment significantly increased the contents of GSL and sulforaphane and activated GSL synthesis-related gene expression, suggesting that SeMSC acted as a positive regulator for GSL and sulforaphane production. Our findings provided novel insights into selenium-mediated GSLs and sulforaphane accumulation. The genetic manipulation of BoSMT might be a useful strategy for improving the dietary nutritional values of broccoli.

The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions of selenium-containing compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, as well as selenoproteins and selenium nanoparticles in the regulation of defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description of the available data for each of the above selenium compounds and the mechanisms underlying the regulation of immune processes with the active participation of these selenium agents, as well as their therapeutic and pharmacological potential, is presented. The main purpose of this review is to systematize the available information, supplemented by data obtained in our laboratory, on the important role of selenium compounds in all of these processes. In addition, the presented information makes it possible to understand the key differences in the mechanisms of action of these compounds, depending on their chemical and physical properties, which is important for obtaining a holistic picture and prospects for creating drugs based on them.

Selenite can be a dominant form of selenium (Se) in aerobic soils; however, unlike selenate, the mechanism of selenite uptake by plants remains unclear. Uptake, translocation and Se speciation in wheat (Triticum aestivum) supplied with selenate or selenite, or both, were investigated in hydroponic experiments. The kinetics of selenite influx was determined in short-term (30 min) experiments. Selenium speciation in the water-extractable fraction of roots and shoots was determined by HPLC-ICPMS. Plants absorbed similar amounts of Se within 1 d when supplied with selenite or selenate. Selenate and selenite uptake were enhanced in sulphur-starved and phosphorus-starved plants, respectively. Phosphate markedly increased Km of the selenite influx. Selenate and selenite uptake were both metabolically dependent. Selenite was rapidly converted to organic forms in roots, with limited translocation to shoots. Selenomethionine, selenomethionine Se-oxide, Se-methyl-selenocysteine and several other unidentified Se species were detected in the root extracts and xylem sap from selenite-treated plants. Selenate was highly mobile in xylem transport, but little was assimilated to organic forms in 1 d. The presence of selenite decreased selenate uptake and xylem transport. Selenite uptake is an active process likely mediated, at least partly, by phosphate transporters. Selenite and selenate differ greatly in the ease of assimilation and xylem transport.

Owing to the strong antioxidant capacity of selenium (Se) in vivo, a variety of Se compounds have been shown to have great potential for improving the main pathologies and cognitive impairment in Alzheimer’s disease (AD) models. However, the differences in the anti-AD effects and mechanisms of different Se compounds are still unclear. Theoretically, the absorption and metabolism of different forms of Se in the body vary, which directly determines the diversification of downstream regulatory pathways. In this study, low doses of Se-methylselenocysteine (SMC), selenomethionine (SeM), or sodium selenate (SeNa) were administered to triple transgenic AD (3× Tg-AD) mice for short time periods. AD pathology, activities of selenoenzymes, and metabolic profiles in the brain were studied to explore the similarities and differences in the anti-AD effects and mechanisms of the three Se compounds. We found that all of these Se compounds significantly increased Se levels and antioxidant capacity, regulated amino acid metabolism, and ameliorated synaptic deficits, thus improving the cognitive capacity of AD mice. Importantly, SMC preferentially increased the expression and activity of thioredoxin reductase and reduced tau phosphorylation by inhibiting glycogen synthase kinase-3 beta (GSK-3β) activity. Glutathione peroxidase 1 (GPx1), the selenoenzyme most affected by SeM, decreased amyloid beta production and improved mitochondrial function. SeNa improved methionine sulfoxide reductase B1 (MsrB1) expression, reflected in AD pathology as promoting the expression of synaptic proteins and restoring synaptic deficits. Herein, we reveal the differences and mechanisms by which different Se compounds improve multiple pathologies of AD and provide novel insights into the targeted administration of Se-containing drugs in the treatment of AD.

Background Selenium (Se) deficiency causes a series of health disorders in humans, and Se concentrations in the edible parts of crops can be improved by altering exogenous Se species. However, the uptake, transport, subcellular distribution and metabolism of selenite, selenate and SeMet (selenomethionine) under the influence of phosphorus (P) has not been well characterized. Results The results showed that increasing the P application rate enhanced photosynthesis and then increased the dry matter weight of shoots with selenite and SeMet treatment, and an appropriate amount of P combined with selenite treatment increased the dry matter weight of roots by enhancing root growth. With selenite treatment, increasing the P application rate significantly decreased the concentration and accumulation of Se in roots and shoots. P 1 decreased the Se migration coefficient, which could be attributed to the inhibited distribution of Se in the root cell wall, but increased distribution of Se in the root soluble fraction, as well as the promoted proportion of SeMet and MeSeCys (Se-methyl-selenocysteine) in roots. With selenate treatment, P 0.1 and P 1 significantly increased the Se concentration and distribution in shoots and the Se migration coefficient, which could be attributed to the enhanced proportion of Se (IV) in roots but decreased proportion of SeMet in roots. With SeMet treatment, increasing the P application rate significantly decreased the Se concentration in shoots and roots but increased the proportion of SeCys 2 (selenocystine) in roots. Conclusion Compared with selenate or SeMet treatment, treatment with an appropriate amount of P combined with selenite could promote plant growth, reduce Se uptake, alter Se subcellular distribution and speciation, and affect Se bioavailability in wheat.

Se-methylselenocysteine (MeSeCys) is a natural organic selenium (Se) supplement. However, its effects on animal nutrition are poorly understood. This study compared the effects of sodium selenite (SeNa), MeSeCys, and selenomethionine (SeMet) on immune function, tissue Se concentration, meat quality, and selenoprotein gene expression in pigs. A total of 72 finishing pigs were divided into four groups, which received a basal diet (BD, 0.1 mg Se/kg) without Se supplementation or one supplemented with SeNa, MeSeCys, or SeMet at a concentration of 0.25 mg Se/kg. Organic Se supplementation significantly increased the immune globulin A (IgA), IgG, and IgM serum levels compared with BD and SeNa groups (P < 0.05). There were no statistically significant differences in growth performance among the four groups. SeMet was more efficient in increasing Se concentrations in the heart, muscle, and liver than MeSeCys and SeNa (P < 0.05), while no statistically significant differences were observed between MeSeCys and SeNa. Se supplementation significantly decreased the pressing muscle loss compared with the BD group (P < 0.05). Meat color and pH were not significantly affected. Se supplement effects on liver selenoprotein gene mRNA level enhancement were ranked as follows: MeSeCys > SeMet > SeNa (P < 0.05). In muscle tissues, only the SELENOW mRNA level was significantly increased by the MeSeCys and SeMet treatment, compared with the SeNa group. In conclusion, SeMet was more efficient in increasing Se concentrations than MeSeCys and SeNa in pigs, while MeSeCys was more efficient in enhancing selenoprotein gene expression than SeMet and SeNa.

Seleno-methylselenocysteine (SeMCys) is an effective component for selenium supplementation with anti-carcinogenic potential and can ameliorate neuropathology and cognitive deficits. In this study, we aimed to engineer Bacillus subtilis 168 for the microbial production of SeMCys. First, the accumulation of intracellular selenocysteine (SeCys) as the precursor of SeMCys was enhanced through overexpression of serine O-acetyltransferase, which was desensitized against feedback inhibition by cysteine. Next, the S-adenosylmethionine (SAM) synthetic pathway was optimized to improve methyl donor availability through expression of S-adenosylmethionine synthetase. Further, SeMCys was successfully produced through expression of the selenocysteine methyltransferase in SeCys and SAM-producing strain. The increased expression level of selenocysteine methyltransferase benefited the SeMCys production. Finally, all the heterologous genes were integrated into the genome of B. subtilis, and the strain produced SeMCys at a titer of 18.4 μg/L in fed-batch culture. This is the first report on the metabolic engineering of B. subtilis for microbial production of SeMCys and provides a good starting point for future pathway engineering to achieve the industrial-grade production of SeMCys.Key points• Expression of the feedback-insensitive serine O-acetyltransferase provided B. subtilis the ability of accumulating SeCys.• SAM production was enhanced through expressing S-adenosylmethionine synthetase in B. subtilis.• Expression of selenocysteine methyltransferase in SeCys and SAM-accumulating strain facilitated SeMCys production.

Cyclocarya paliurus (CP) contains triterpene acids that can improve glucose and lipid metabolism disorders. However, controlling the composition and content of these active ingredients in CP extracts is challenging. The main active components in CP triterpene acids, including ursolic acid (UA), oleanolic acid (OA), and betulinic acid (BA), exhibit antihyperglycemic and antihypertensive effects. The response surface methodology was utilized to design and optimize the ratio of UA, OA, and BA based on the inhibition rate of pancrelipase and α-amylase. The proportional mixture of UA, OA, and BA resulted in the formation of a complex known as Cyclocarya paliurus triterpenoid acid (TAC). Se-methylselenocysteine (MSC), a compound with various physiological functions such as antioxidant properties and tumor inhibition, has been used in combination with TAC to form the TAC/MSC complex. Our data demonstrate that TAC/MSC improved palmitic acid (PA)-induced insulin resistance in HepG2 cells through activating the phosphoinositide 3-kinase (PI3K) /protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) pathway. Moreover, TAC/MSC effectively improved hyperglycemia, glucose intolerance, insulin resistance, and lipid metabolism disorder in mice with type 2 diabetes mellitus (T2DM), attenuated hepatic steatosis, and reduced oxidative stress to alleviate T2DM characteristics.