The enhancing effects of selenomethionine on harmine in attenuating pathological cardiac hypertrophy via glycolysis metabolism.

Pathological cardiac hypertrophy, a common feature in various cardiovascular diseases, can be more effectively managed through combination therapies using natural compounds. Harmine, a ß-carboline alkaloid found in plants, possesses numerous pharmacological functions, including alleviating cardiac hypertrophy. Similarly, Selenomethionine (SE), a primary organic selenium source, has been shown to mitigate cardiac autophagy and alleviate injury. To explores the therapeutic potential of combining Harmine with SE to treat cardiac hypertrophy. The synergistic effects of SE and harmine against cardiac hypertrophy were assessed in vitro with angiotensin II (AngII)-induced hypertrophy and in vivo using a Myh6R404Q mouse model. Co-administration of SE and harmine significantly reduced hypertrophy-related markers, outperforming monotherapies. Transcriptomic and metabolic profiling revealed substantial alterations in key metabolic and signalling pathways, particularly those involved in energy metabolism. Notably, the combination therapy led to a marked reduction in the activity of key glycolytic enzymes. Importantly, the addition of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) did not further potentiate these effects, suggesting that the antihypertrophic action is predominantly mediated through glycolytic inhibition. These findings highlight the potential of SE and harmine as a promising combination therapy for the treatment of cardiac hypertrophy.

Enhancing skeletal muscle fiber characteristics, intramuscular fat deposition and fatty acid composition in broilers under heat stress through combined selenomethionine and Bacillus subtilis supplementation in the diet.

Heat stress is the most common environmental stressor in poultry production, negatively affecting growth performance, meat quality, and welfare. Therefore, the aim of this study was to compare the nutritional effects of dietary supplementation with selenomethionine, BS, and a combination of selenomethionine and BS on broilers challenged with heat stress. A total of 300 21-day-old Ross 308 male broilers were randomly assigned to 5 groups with 6 replicates of 10 broilers per each: control group (CON, broilers raised at 22 ± 2℃); heat stress exposure group (HS, broilers raised at 32 ± 2℃ for 8 h/day); HSS group (HS group supplemented with 0.3 mg/kg selenomethionine); HSB group (HS group supplemented with 1 × 109 cfu/kg BS); and HSBS group (HS group supplemented with 0.3 mg/kg selenomethionine and × 109 cfu/kg BS). The experiment lasted for 21 days. The results indicated that, compared to the CON group, heat stress reduces (P < 0.05) broiler growth performance and damages the meat quality in breast and thigh muscles. Dietary supplementation with selenomethionine and BS did not improve the growth performance of broilers under heat stress. However, compared to the HS group, the HSS, HSB, and HSBS groups showed significantly increased (P < 0.05) pH45 min, redness (a*) and yellowness (b*), muscle fiber density, intramuscular fat (IMF), triglyceride content (TG), and expression levels of Myf5, CAPN 2, FM, SLC27A1, A-FABP, H-FABP, APOB-100, and ACC in breast and thigh muscles. Meanwhile, these groups showed reduced (P < 0.05) lightness (L*), drip loss, shear force, muscle fiber cross-sectional area, and FM gene expression level. The HSBS group showed greater improvement in the physicochemical quality of muscle and volatile substances compared to the HSS and HSB groups. In conclusion, selenomethionine and BS improved meat quality and flavor in broilers under heat stress by modulating muscle fiber composition and characteristics, as well as increasing intramuscular fat deposition.

Selenomethionine alleviates Aeromonas hydrophila-induced oxidative stress and ferroptosis via the Nrf2/HO1/GPX4 pathway in grass carp.

Aeromonas hydrophila infection is a severe, acute, and life-threatening disease affecting grass carp (Ctenopharyngodon idella) in aquaculture. Ferroptosis is a novel form of cell death characterized by the accumulation of free iron and harmful lipid peroxides within cells. While selenomethionine (Se-Met) is known to effectively inhibit ferroptosis and alleviate cell damage, its ability to counteract oxidative stress and ferroptosis induced by A. hydrophila remains unclear. The objective of this study is to reveal the possible mechanism behind the ferroptosis phenomenon during A. hydrophila infection. We established a macrophage model of A. hydrophila invasion to monitor the dynamic changes in iron metabolism markers to evaluate the correlation between ferroptotic stress and A. hydrophila infection. A. hydrophila infection induces cytotoxicity and mitochondrial membrane damage via ferroptosis. This damage is attributed to the accumulation of lipid peroxides due to intracellular ferrous ion overload and glutathione depletion. Supplementation of Se-Met reduced mitochondrial damage, enhanced antioxidant enzyme activity and reduced ferroptosis by activating the Nrf2/HO1/GPX4 axis. These findings provide new insights into the regulatory mechanisms of A. hydrophila-induced ferroptosis in teleosts and suggest that targeted inhibition of ferroptosis may offer a novel therapeutic strategy for managing A. hydrophila infections.

Bioaccumulation and biotransformation of selenium nanoparticles in soybean and natto, and the bioaccessibility of multi-elements and amino acids.

Soybean is a food crop with strong selenium (Se) enrichment ability. Selenium nanoparticles (SeNPs) are a low-toxic Se source. To develop strategies in SeNPs biofortification of soybean and natto, the effects of Se enrichment and natto fermentation on selenoamino acids, mineral elements, free amino acids, γ-polyglutamic acid, nattokinase, and bioaccessibility were investigated. Soybean grains were able to convert SeNPs into selenomethionine (SeMet). Selenium enrichment and natto fermentation influenced the enrichment and distribution of multi-elements in soybean, as well as the composition of free and bound amino acids. Selenium enrichment had no significant effect on the bioaccessibility of amino acids. After natto fermentation, the bioaccessibility of SeMet, Fe, Mn, Cu, and Zn in the gastrointestinal tract increased significantly by 10.1-18.9 %. These findings indicate that SeNPs can enhance the Se content of soybean grains, and natto fermentation can further improve the nutritional quality of Se-enriched soybean.

Alleviation of cadmium toxicity in soybean (Glycine max L.): Up-regulating antioxidant capacity and enzyme gene expressions and down-regulating cadmium uptake by organic or inorganic selenium.

Although much interest has been focused on the role of selenium (Se) in plant nutrition over the last 20 years, the influences of organic selenium (selenomethionine; Se-Met) and inorganic selenium (potassium selenite; Se-K) on the growth and physiological characters of cadmium (Cd)-stressed Glycine max L.) seedlings have not yet been studied. In this study, the impacts of Se-Met or Se-K on the growth, water physiological parameters (gaseous exchange and leaf water content), photosynthetic and antioxidant capacities, and hormonal balance of G. max seedlings grown under 1.0 mM Cd stress were studied. The results showed that 30 µM Se-K up-regulates water physiological parameters, photosynthetic indices, antioxidant systems, enzymatic gene expression, total antioxidant activity (TAA), and hormonal balance. In addition, it down-regulates levels of reactive oxygen species (ROS; superoxide free radicals and hydrogen peroxide), oxidative damage (malondialdehyde content as an indicator of lipid peroxidation and electrolyte leakage), Cd translocation factor, and Cd content of Cd-stressed G. max seedlings. These positive findings were in favor of seedling growth and development under Cd stress. However, 50 µM Se-Met was more efficient than 30 µM Se-K in promoting the above-mentioned parameters of Cd-stressed G. max seedlings. From the current results, we conclude Se-Met could represent a promising strategy to contribute to the development and sustainability of crop production on soils contaminated with Cd at a concentration of up to 1.0 mM. However, further work is warranted to better understand the precise mechanisms of Se-Met action under Cd stress conditions.

Selenomethionine Promotes Milk Protein and Fat Synthesis and Proliferation of Mammary Epithelial Cells through the GPR37-mTOR-S6K1 Signaling.

Selenomethionine (SeMet) is an important nutrient, but its role in milk synthesis and the GPCR related to SeMet sensing is still largely unknown. Here, we determined the dose-dependent role of SeMet on milk protein and fat synthesis and proliferation of mammary epithelial cells (MECs), and we also uncovered the GPCR-mediating SeMet function. At 24 h postdelivery, lactating mother mice were fed a maintenance diet supplemented with 0, 5, 10, 20, 40, and 80 mg/kg SeMet, and the feeding process lasted for 18 days. The 10 mg/kg group had the best increase in milk production, weight gain of offspring mice, and mammary gland weight and acinar size, whereas a higher concentration of SeMet gradually decreased the weight gain of the offspring mice and showed toxic effects. Transcriptome sequencing was performed to find the differentially expressed genes (DEGs) between the mammary gland tissues of mother mice in the 10 mg/kg SeMet treatment group and the control group. A total of 258 DEGs were screened out, including 82 highly expressed genes including GPR37 and 176 lowly expressed genes. SeMet increased milk protein and fat synthesis in HC11 cells and cell proliferation, mTOR and S6K1 phosphorylation, and expression of GPR37 in a dose-dependent manner. GPR37 knockdown decreased milk protein and fat synthesis in HC11 cells and cell proliferation and blocked SeMet stimulation on mTOR and S6K1 phosphorylation. Taken together, our data demonstrate that SeMet can promote milk protein and fat synthesis and proliferation of MECs and functions through the GPR37-mTOR-S6K1 signaling pathway.

Selenomethionine supplementation mitigates fluoride-induced liver apoptosis and inflammatory reactions by blocking Parkin-mediated mitophagy in mice.

As an environmental pollutant, fluoride-induced liver damage is directly linked to mitochondrial alteration and oxidative stress. Selenium's antioxidant capacity has been shown to alleviate liver damage. Emerging research proves that E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy may be a therapeutic target for fluorosis. The current study explored the effect of diverse selenium sources on fluoride-caused liver injury and the role of Parkin-mediated mitophagy in this intervention process. Therefore, this study established a fluoride-different selenium sources co-intervention wild-type (WT) mouse model and a fluoride-optimum selenium sources co-intervention Parkin gene knockout (Parkin-/-) mouse model. Our results show that selenomethionine (SeMet) is the optimum selenium supplementation form for mice suffering from fluorosis when compared to sodium selenite and chitosan nano­selenium because mice from the F-SeMet group showed more closely normal growth and development levels of liver function, antioxidant capacity, and anti-inflammatory ability. Explicitly, SeMet ameliorated liver inflammation and cell apoptosis in fluoride-toxic mice, accomplished through downregulating the mRNA and protein expression levels associated with mitochondrial fusion and fission, mitophagy, apoptosis, inflammatory signalling pathway of nuclear factor-kappa B (NF-κB), reducing the protein expression levels of PARKIN, PTEN-induced putative kinase1 (PINK1), SQSTM1/p62 (P62), microtubule-associated protein light chain 3 (LC3), cysteinyl aspartate specific proteinase 3 (CASPAS3), as well as restraining the content of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ). The Parkin-/- showed comparable positive effects to the SeMet in the liver of fluorosis mice. The structure of the mitochondria, mRNA, protein expression levels, and the content of proinflammatory factors in mice from the FParkin-/- and F + SeMetParkin-/- groups closely resembled those in the F + SeMetWT group. Overall, the above results indicated that SeMet could alleviate fluoride-triggered inflammation and apoptosis in mice liver via blocking Parkin-mediated mitophagy.

p38MAPK/HSPB1 is involved in the regulatory effects of selenomethionine on the apoptosis, viability and testosterone secretion of sheep Leydig cells exposed to heat.

Testosterone derived from testicular Leydig cells (LCs) is important for male sheep, and the testis is susceptible to external temperature. The present study aimed to explore the alleviating effect of selenomethionine (Se-Met) on heat-induced injury in Hu sheep LCs. Isolated LCs were exposed to heat (41.5°C, heat exposure, HE) or not (37°C, nonheat exposure, NE), and cells in NE and HE were treated with 0 (C) or 8 µmol/L (S) Se-Met for 6 h. Cell viability, testosterone level, and the expression of GPX1, HSD3B, apoptosis-related genes and p38 mitogen-activated protein kinase (p38MAPK)/heat shock protein beta-1 (HSPB1) pathway were examined. The results showed that Se-Met increased GPX1 expression (NE-S vs. NE-C: 2.28-fold; HE-S vs. HE-C: 2.36-fold, p < 0.05) and alleviated heat-induced decrease in cell viability (HE-S vs. HE-C: 1.41-fold; HE-C vs. NE-C: 0.61-fold, p < 0.01), although the viability was still lower than that in the NE-C cells (HE-S vs. NE-C: 0.85-fold) and Se-Met-treated cells (HE-S vs. NE-S: 0.81-fold). Se-Met relieved heat-induced decrease in testosterone level (HE-S vs. HE-C: 1.84-fold, p < 0.05) and HSD3B expression (HE-S vs. HE-C: 1.67-fold, p < 0.05). Se-Met alleviated heat-induced increase in Bcl2-associated protein X (BAX) expression (HE-C vs. HE-S: 2.4-fold, p < 0.05), and decrease in B-cell lymphoma-2 (BCL2) expression (HE-S vs. HE-C: 2.62-fold, p < 0.05), resulting in increased BCL2/BAX ratio in the HE-S cells (HE-S vs. HE-C: 5.24-fold, p < 0.05). Furthermore, Se-Met alleviated heat-induced activation of p-p38MAPK/p38MAPK (HE-C vs. HE-S: 1.79-fold, p < 0.05) and p-HSPB1/HSPB1 (HE-C vs. HE-S: 2.72-fold, p < 0.05). In conclusion, p38MAPK/HSPB1 might be involved in Se-Met-mediated alleviation of heat-induced cell apoptosis, cell viability and testosterone secretion impairments in sheep LCs.

The effect of hydroxy-selenomethionine on the productive and reproductive performance of old broiler breeders.

BACKGROUND: Selenium (Se) is a rare essential element that plays a vital role in the health and performance of animals. By interfering in the production of antioxidant enzymes such as glutathione peroxidase, thioredoxin reductase and methionine sulfoxide, Se plays a role in reducing the effects of oxidative stress and animal performance. OBJECTIVES: This study aimed to investigate the effect of hydroxy-selenomethionine (OH-SeMet) in the diet of broiler breeder and old broiler breeder roosters on productive performance, reproduction and sperm quality parameters. METHODS: For this purpose, 260 broiler breeders of the Ross 308 strain were used in a completely randomized design with four treatments and five replications (13 hens and one rooster in each replication). Experimental treatments included: (1) a basal diet without OH-SeMet (T1:control), (2) a broiler breeder diet without OH-SeMet and a rooster diet containing 0.1 mg/kg OH-SeMet (T2), (3) broiler breeder diet containing 0.1 mg/kg OH-SeMet and rooster diet without OH-SeMet (T3) and (4) broiler breeder and rooster diet contained 0.1 mg/kg OH-SeMet (T4). RESULTS: The results showed that T3 and T4 treatments improved egg production, egg weight, egg mass and feed conversion ratio (FCR) compared to the control treatment (p < 0.05). The fertility and hatchability percentages of T4 and T2 treatments increased compared to T1 and T3 treatments (p < 0.05). The rate of embryonic losses in T1 was higher than in other treatments. However, grade one chickens were higher in T4 than in other treatments (p < 0.05). Total motility and viability of sperms were significantly higher in T2 and T4 treatments than in T1 and T3 treatments. The sperm abnormality percentage and sperm MDA concentration decreased in T2 and T4 treatments. CONCLUSIONS: Therefore, using OH-SeMet may be a practical approach to help old broiler breeders' production and reproduction performance.

Effect of Trace Element Selenium on the Intestinal Microbial Community in Nude Mice with Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. The role of intestinal microbiota in carcinogenesis has also become an important research topic, and CRC is closely related to the intestinal microbiota. Selenium-containing compounds have attracted more attention as anticancer drugs as they can have minimal side effects. The purpose of this study was to determine and compare the effect of sodium selenite and selenomethionine on the microbial communities of nude mice with CRC. A CRC ectopic tumorigenesis model was established by subcutaneously injecting HCT116 cells into nude mice. The mice were then intraperitoneally injected with sodium selenite and selenomethionine for 24 days to regulate their intestinal microbiota. Compared with sodium selenite, selenomethionine resulted in a greater reduction in the richness and diversity of intestinal microbiota in nude mice with CRC, and the richness and diversity were closer to healthy levels. Selenomethionine also regulated a wider variety of flora. Additionally, sodium selenite and selenomethionine produced different microorganisms, changed function and metabolic pathways in the intestinal microbiota. Both sodium selenite and selenomethionine have certain effects on restoring the intestinal microbial diversity in nude mice with CRC, and the effect of selenomethionine is better than that of sodium selenite.

The Effects of Seleno-Methionine in Cadmium-Challenged Human Primary Chondrocytes.

Cadmium (Cd) is a potentially toxic element able to interfere with cellular functions and lead to disease or even death. Cd accumulation has been demonstrated in cartilage, where it can induce damage in joints. The aim of this study was to evaluate the effect of CdCl2 on primary cultures of human chondrocytes and the possible protective effect of seleno-methionine (Se-Met). Human primary articular chondrocytes were cultured and treated as follows: control groups, cells challenged with 7.5 µM and 10 µM CdCl2 alone, and cells pretreated with 10 and 20 µM Se-Met and then challenged with 7.5 µM and 10 µM CdCl2. Twenty-four hours after incubation, cell viability, histological evaluation with hematoxylin-eosin stain, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed. Furthermore, reverse transcription-PCR was carried out to evaluate mRNA levels of BAX, BAK1, CASP-3, and CASP-9. After CdCl2 challenge at both doses, a reduced cell viability and an overexpression of BAX, BAK1, CASP-3, and CASP-9 genes, as well as a high number of TUNEL-positive cells, were demonstrated, all parameters becoming higher as the dose of CdCl2 was increased. The pretreatment with Se-Met lowered the expression of all considered genes, improved cell viability and morphological changes, and reduced the number of TUNEL-positive cells. It was concluded that Se-Met plays a protective role against CdCl2-induced structural and functional changes in chondrocytes in vitro, as it improved cell viability and showed a positive role in the context of the apoptotic pathways. It is therefore suggested that a translational, multifaceted approach, with plant-based diets, bioactive functional foods, nutraceuticals, micronutrients, and drugs, is possibly advisable in situations of environmental pollution caused by potentially toxic elements.

Selenomethionine Inhibited HADV-Induced Apoptosis Mediated by ROS through the JAK-STAT3 Signaling Pathway.

Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.

The Influence of N-Acetyl-selenomethionine on Two RONS-Generating Cancer Cell Lines Compared to N-Acetyl-methionine.

N-acetyl-selenomethionine (NASeLM), a representative of the selenium compounds, failed to convince in clinical studies and cell cultures that it neither inhibits cancer growth nor has a chemoprotective effect. This study aims to find out whether NASeLM shows a growth-inhibiting property compared to the carrier substance N-Acetyl-L-methionine (NALM) on two different cancer cells, namely Jurkat cells and MTC-SK cells. METHODS: Jurkat and MTC-SK cells were cultured in the absence or presence of varying concentrations (0-500 µg/mL) of NASeLM and NALM solutions. After 0, 24, 48, and 72 h, mitochondrial activity, cancer cell membrane CP levels, cell growth, and caspase-3 activity were assessed in aliquots of Jurkat and MTC-SK cells. RESULTS: Both substances, NASeLM and NALM, were similarly able to inhibit cell growth and mitochondrial activity of Jurkat cells in a concentration-dependent and time-dependent manner up to 70%. Only the determination of caspase activity showed that only NASeLM was able to increase this to almost 40% compared to the control as well as the same lack of NALM. However, the experiments on MTC-SK cells showed a clear difference in favor of NASeLM compared to NALM. While NASeLM was able to reduce cell growth to up to 55%, the same amount of NALM was only at around 15%, which turned out to be highly significant (p < 0.001). The same could also be measured for the reduction in MTC-SK mitochondrial activity. Time dependence could also be recognized: the longer both substances, NASeLM and NALM, were incubated, the higher the effect on cell growth and mitochondrial activity, in favour of NASeLM. Only NASeLM was able to increase caspase-3 activity in MTC-SK cells: at 250 µg/mL NASeLM, caspase-3 activity increased significantly to 28% after 24 and 48 h compared to the control (14%) or the same NALM concentration (14%). After 72 h, this could still increase to 37%. A further increase in the NASeLM concentration did not result in higher caspase-3 activity. CONCLUSION: NASeLM could clearly increase caspase-3 activity in both cell types, Jurkat or MTC-SK cells, and thus induce cell death. NALM and NASeLM showed a reduction in cell growth and mitochondrial activity in both cell lines: While NALM and NASeLM showed almost identical measurements on Jurkat cells, NASeLM was much more effective on MTC-SK than the non-selenium-containing carrier, indicating that it has additional anti-chemoprotective effects.

Foliar selenium biofortification of soybean: the potential for transformation of mineral selenium into organic forms.

Introduction: Selenium (Se) deficiency, stemming from malnutrition in humans and animals, has the potential to disrupt many vital physiological processes, particularly those reliant on specific selenoproteins. Agronomic biofortification of crops through the application of Se-containing sprays provides an efficient method to enhance the Se content in the harvested biomass. An optimal candidate for systematic enrichment, guaranteeing a broad trophic impact, must meet several criteria: (i) efficient accumulation of Se without compromising crop yield, (ii) effective conversion of mineral Se fertilizer into usable organically bound Se forms (Seorg), (iii) acceptance of a Se-enriched crop as livestock feed, and (iv), interest from the food processing industry in utilization of Se-enriched outputs. Hence, priority should be given to high-protein leafy crops, such as soybean. Methods: A three-year study in the Czech Republic was conducted to investigate the response of field-grown soybean plants to foliar application of Na2SeO4 solutions (0, 15, 40, and 100 g/ha Se); measured outcomes included crop yield, Se distribution in aboveground biomass, and the chemical speciation of Se in seeds. Results and Discussion: Seed yield was unaffected by applied SeO4 2-, with Se content reaching levels as high as 16.2 mg/kg. The relationship between SeO4 2-dose and Se content in seeds followed a linear regression model. Notably, the soybeans demonstrated an impressive 73% average recovery of Se in seeds. Selenomethionine was identified as the predominant species of Se in enzymatic hydrolysates of soybean, constituting up to 95% of Seorg in seeds. Minor Se species, such as selenocystine, selenite, and selenate, were also detected. The timing of Se spraying influenced both plant SeO4 2- biotransformation and total content in seeds, emphasizing the critical importance of optimizing the biofortification protocol. Future research should explore the economic viability, long-term ecological sustainability, and the broad nutritional implications of incorporating Se-enriched soybeans into food for humans and animals.

Exposure to Selenomethionine and Selenocystine Induces Redox-Mediated ER Stress in Normal Breast Epithelial MCF-10A Cells.

Selenium is an essential trace element co-translationally incorporated into selenoproteins with important biological functions. Health benefits have long been associated with selenium supplementation. However, cytotoxicity is observed upon excessive selenium intake. The aim of this study is to investigate the metabolic pathways underlying the response to the selenium-containing amino acids selenomethionine and selenocysteine in a normal human breast epithelial cell model. We show that both selenomethionine and selenocystine inhibit the proliferation of non-cancerous MCF-10A cells in the same concentration range as cancerous MCF-7 and Hela cells, which results in apoptotic cell death. Selenocystine exposure in MCF-10A cells caused a severe depletion of free low molecular weight thiols, which might explain the observed upregulation of the expression of the oxidative stress pathway transcription factor NRF2. Both selenomethionine and selenocystine induced the expression of target genes of the unfolded protein response (GRP78, ATF4, CHOP). Using a redox-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we show that both selenoamino acids shifted the ER redox balance towards an even more oxidizing environment. These results suggest that alteration of the redox state of the ER may disrupt protein folding and cause ER stress-induced apoptosis in MCF-10A cells exposed to selenoamino acids.

Selenomethionine preconditioned mesenchymal stem cells derived extracellular vesicles exert enhanced therapeutic efficacy in intervertebral disc degeneration.

Extracellular vesicles (EVs) derived from Mesenchymal Stromal Cells (MSCs) have shown promising therapeutic potential for multiple diseases, including intervertebral disc degeneration (IDD). Nevertheless, the limited production and unstable quality of EVs hindered the clinical application of EVs in IDD. Selenomethionine (Se-Met), the major form of organic selenium present in the cereal diet, showed various beneficial effects, including antioxidant, immunomodulatory and anti-apoptotic effects. In the current study, Se-Met was employed to treat MSCs to investigate whether Se-Met can facilitate the secretion of EVs by MSCs and optimize their therapeutic effects on IDD. On the one hand, Se-Met promoted the production of EVs by enhancing the autophagy activity of MSCs. On the other hand, Se-Met pretreated MSC-derived EVs (Se-EVs) exhibited an enhanced protective effects on alleviating nucleus pulposus cells (NPCs) senescence and attenuating IDD compared with EVs isolated from control MSCs (C-EVs) in vitro and in vivo. Moreover, we performed a miRNA microarray sequencing analysis on EVs to explore the potential mechanism of the protective effects of EVs. The result indicated that miR-125a-5p is markedly enriched in Se-EVs compared to C-EVs. Further in vitro and in vivo experiments revealed that knockdown of miR-125a-5p in Se-EVs (miRKD-Se-EVs) impeded the protective effects of Se-EVs, while overexpression of miR-125a-5p (miROE-Se-EVs) boosted the protective effects. In conclusion, Se-Met facilitated the MSC-derived EVs production and increased miR-125a-5p delivery in Se-EVs, thereby improving the protective effects of MSC-derived EVs on alleviating NPCs senescence and attenuating IDD.

Selenized non-Saccharomyces yeasts and their potential use in fish feed.

Selenium (Se) is a vital trace element, essential for growth and other biological functions in fish. Its significance lies in its role as a fundamental component of selenoproteins, which are crucial for optimal functioning of the organism. The inclusion of Se in the diets of farmed animals, including fish, has proved invaluable in mitigating the challenges arising from elemental deficiencies experienced in captivity conditions due to limitations in the content of fishmeal. Supplementing diets with Se enhances physiological responses, particularly mitigates the effects of the continuous presence of environmental stress factors. Organic Se has been shown to have higher absorption rates and a greater impact on bioavailability and overall health than inorganic forms. A characteristic feature of yeasts is their rapid proliferation and growth, marked by efficient mineral assimilation. Most of the selenized yeasts currently available in the market, and used predominantly in animal production and aquaculture, are based on Saccharomyces cerevisiae, which contains selenomethionine (Se-Met). The object of this review is to highlight the importance of selenized yeasts. In addition, it presents metabolic and productive aspects of other yeast genera that are important potential sources of organic selenium. Some yeast strains discussed produce metabolites of interest such as lipids, pigments, and amino acids, which could have applications in aquaculture and further enrich their usefulness.

Protective effect of selenomethionine on rabbit testicular injury induced by Aflatoxin B1.

The aim of this study was to investigate the alleviating effect of selenomethionine (SeMet) on aflatoxin B1 (AFB1)-induced testicular injury in rabbits. Twenty-five 90-d-old rabbits were randomly divided into 5 groups (the control group, the AFB1 group, the 0.2 mg/kg SeMet + AFB1 group, the 0.4 mg/kg SeMet + AFB1 group and the 0.6 mg/kg SeMet + AFB1 group). After 1 d of the experiment, the SeMet-treated groups were fed 0.2 mg/kg SeMet, 0.4 mg/kg SeMet, or 0.6 mg/kg SeMet daily, and the remaining two groups were fed a normal diet for 30 d. On Day 31, all rabbits in the model group and the three treatment groups were fed 0.5 mg/kg AFB1 for 21 d. The levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rabbit plasma were detected. Rabbit semen was collected, and its quality was evaluated. Pathological changes in rabbit testes were observed by hematoxylin-eosin (HE) staining. The expression of related proteins in testicular tissue was detected by immunohistochemistry, immunofluorescence and western blot (WB) analysis. Enzyme-linked immunosorbent assays (ELISAs) were used to detect oxidative stress-related indices and inflammatory factors in testicular tissue. The results showed that AFB1 can induce oxidative stress and inflammation to activate the p38/MSK/NF-κB signalling pathway, mediate apoptosis, inhibit the proliferation and differentiation of testicular cells, destroy the integrity of the blood-testis barrier (BTB) and the normal structure of the testis, and reduce the content of sex hormones and semen quality. SeMet pretreatment significantly alleviated testicular injury oxidative stress, and the inflammatory response in rabbits. Thus, we demonstrated that SeMet restores AFB1-induced testicular toxicity by inhibiting the p38/MSK/NF-κB signalling pathway. In addition, in this study, 0.4 mg/kg SeMet had the most impactful effect.

Genome-wide identification of HMT gene family explores BpHMT2 enhancing selenium accumulation and tolerance in Broussonetia papyrifera.

Broussonetia papyrifera, a valuable feed resource, is known for its fast growth, wide adaptability, high protein content and strong selenium enrichment capacity. Selenomethionine (SeMet), the main selenium form in selenium fortification B. papyrifera, is safe for animals and this enhances its nutritional value as a feed resource. However, the molecular mechanisms underlying SeMet synthesis remain unclear. This study identified three homocysteine S-methyltransferase genes from the B. papyrifera genome. The phylogenetic tree demonstrated that BpHMTs were divided into two classes, and BpHMT2 in the Class 2-D subfamily evolved earlier and possesses more fundamental functions. On the basis of the correlation between gene expression levels and selenium content, BpHMT2 was identified as a key candidate gene associated with selenium tolerance. Subcellular localization experiments confirmed the targeting of BpHMT2 in nucleus, cell membrane and chloroplasts. Moreover, three BpHMT2 overexpression Arabidopsis thaliana lines were confirmed to enhance plant selenium tolerance and SeMet accumulation. Overall, our finding provides insights into the molecular mechanisms of selenium metabolism in B. papyrifera, highlighting the potential role of BpHMT2 in SeMet synthesis. This research contributes to our understanding of selenium-enriched feed resources, with increased SeMet content contributing to the improved nutritional value of B. papyrifera as a feed resource.

Induction of Oxidative Stress and Ferroptosis in Triple-Negative Breast Cancer Cells by Niclosamide via Blockade of the Function and Expression of SLC38A5 and SLC7A11.

The amino acid transporters SLC38A5 and SLC7A11 are upregulated in triple-negative breast cancer (TNBC). SLC38A5 transports glutamine, methionine, glycine and serine, and therefore activates mTOR signaling and induces epigenetic modifications. SLC7A11 transports cystine and increases the cellular levels of glutathione, which protects against oxidative stress and lipid peroxidation via glutathione peroxidase, a seleno (Se)-enzyme. The primary source of Se is dietary Se-methionine (Se-Met). Since SLC38A5 transports methionine, we examined its role in Se-Met uptake in TNBC cells. We found that SLC38A5 interacts with methionine and Se-Met with comparable affinity. We also examined the influence of Se-Met on Nrf2 in TNBC cells. Se-Met activated Nrf2 and induced the expression of Nrf2-target genes, including SLC7A11. Our previous work discovered niclosamide, an antiparasitic drug, as a potent inhibitor of SLC38A5. Here, we found SLC7A11 to be inhibited by niclosamide with an IC50 value in the range of 0.1-0.2 µM. In addition to the direct inhibition of SLC38A5 and SLC7A11, the pretreatment of TNBC cells with niclosamide reduced the expression of both transporters. Niclosamide decreased the glutathione levels, inhibited proliferation, suppressed GPX4 expression, increased lipid peroxidation, and induced ferroptosis in TNBC cells. It also significantly reduced the growth of the TNBC cell line MB231 in mouse xenografts.