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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.

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., (© 2024 Wiley Periodicals LLC.)

Selenium (Se) is an essential trace element for human health and plays an important role in the development and maintenance of central nervous system functions. Se deficiency has been associated with cognitive decline and increased oxidative stress. The increase in oxidative stress is one of the hypotheses for the emergence and worsening of neurodegenerative diseases, such as Alzheimer's disease (AD). To investigate the neuroprotective effects of organic Se compounds in human neuroblastoma cells (SH-SY5Y) differentiated into cholinergic neurons-like. The SH-SY5Y cells were differentiated into cholinergic neuron-like with retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). AD was mimicked exposing the cells to okadaic acid (OA) and beta-amyloid protein (Aβ). The neuroprotective effect of organic Se compounds, selenomethionine (SeMet) and Ebselen, was evaluated through cell viability tests, acetylcholinesterase and antioxidant enzyme activities, and detection of reactive oxygen species (ROS). None of the SeMet concentrations tested protected against the toxic effect of OA + Aβ. On the other hand, previous exposure to 0.1 and 1 µM Ebselen protected cells from the toxic effect of OA + Aβ. Cell differentiation induced by RA and BDNF exposure was effective, showing characteristics of neuronal cells, and pointing to a promising model of AD. Ebselen showed a protective effect, but more studies are needed to identify the mechanism of action., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Objective: Head and neck squamous cell carcinoma (HNSCC) is a histological type of cancer originating from the head and neck. Selenium complexes have been considered as a potential treatment for HNSCC. Therefore, the present work focused on probing the mechanism of L-selenomethionine (SeMet) in HNSCC treatment., Methods: MTT and colony formation assays were carried out to analyze the survival rate and proliferation of HNSCC cells, respectively. TUNEL staining was performed to examine apoptosis of HNSCC cells. Additionally, qRT-PCR and Western blotting assays were performed to measure mRNA and protein levels, separately., Results: SeMet treatment significantly hindered the survival and promoted the apoptosis of HNSCC cells in a dose- and time-dependently. SeMet administration promoted expression of TopBP1, ATR, H2AX, p-ATR and γ-H2AX, and suppressed that of TCAB1. Importantly, SeMet treatment suppressed the proliferation and facilitated the apoptosis of HNSCC cells, which were partly reversed by down-regulation of TopBP1 or up-regulation of TCAB1. The activation of SeMet to TopBP1/ATR signaling was rescued by TCAB1 up-regulating, and the inhibition of SeMet to TCAB1 expression was rescued by TopBP1 silencing., Conclusion: Our findings show that SeMet inhibits the proliferation of HNSCC cells and promotes their apoptosis by targeting TopBP1/ATR and TCAB1 signaling. SeMet is a potential method for HNSCC treatment., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Oxidative stress (OS) is widespread in animal husbandry, which causes edema in immune organs and suppresses immune function of animals. Selenium (Se) is an essential trace element involved in immune regulation and improves animals' immunity. In present study, growing and finishing pigs were used to determine the protective effects of the new organic Se (hydroxy selenomethionine, OH-SeMet) on dietary oxidative stress (DOS) induced inflammatory responses, and the corresponding response of selenotranscriptome in spleen and thymus. Forty castrated male pigs (25.0 ± 3.0 kg) were randomly grouped into 5 dietary treatments (n = 8) and fed on basal diet (formulated with normal corn and normal oils) or oxidized diet (formulated with aged corn and oxidized oils) supplied with 0.0, 0.3, 0.6, or 0.9 mg Se/kg OH-SeMet, after 16 weeks, the corresponding indicators were determined. Results showed that DOS moderately increased the spleen and thymus index, decreased the antioxidant capacity of serum, spleen and thymus, and increased the concentration of serum inflammatory cytokines (IL-6 and TNF-α). The inflammatory response in spleen and thymus under DOS were discrepancies, DOS increased the expression of inflammation-related gene (IFN-β and TNF-α) in thymus, while exhibited no impact on that of the spleen. Dietary OH-SeMet supplementation exhibited protective effects, which decreased the spleen and thymus index, improved the antioxidant capacity of serum, spleen and thymus, and decreased the serum IL-1β and IL-6 levels. Se supplementation exhibited limited impact on the inflammation-related genes in spleen, except decreased the mRNA expression of IL-8. On the contrary, Se supplementation showed more impact on that of the thymus, which decreased the mRNA expression of IL-8 and TNF-α, increased the expression of IFN-β, IL-6, IL-10, and MCP1. In addition, selenotranscriptome responsive to dietary Se levels in spleen and thymus were discrepancies. Se supplementation increased the mRNA expression of  the selenotranscriptome in thymus, while exhibited limited impact on that of in spleen. In conclusion, dietary OH-SeMet supplementation mitigates the DOS-induced immunological stress by increasing the antioxidant capacity and altering the expression of inflammation-related genes and selenotranscriptome in immune organs, and these response in spleen and thymus were discrepancies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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 nano‑selenium 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-1β (IL-1β), 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 F Parkin-/- and F + SeMet Parkin-/- groups closely resembled those in the F + SeMet WT group. Overall, the above results indicated that SeMet could alleviate fluoride-triggered inflammation and apoptosis in mice liver via blocking Parkin-mediated mitophagy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

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 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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.

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 (miR KD -Se-EVs) impeded the protective effects of Se-EVs, while overexpression of miR-125a-5p (miR OE -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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Fluoride, a global environmental pollutant, is ubiquitous in aquatic environments and coexists with selenium, which can cause complex effects on exposed organisms. However, data on the interaction of fluoride and selenium remain scarce. In this study, female zebrafish (Danio rerio) were exposed to fluoride (80 mg/L sodium fluoride) and/or dietary selenomethionine (Se-Met) for 30, 60 and 90 days, the effects on the liver of zebrafish were investigated. The results indicated that an increase in fluoride burden, inhibited growth and impaired liver morphology were recorded after fluoride exposure. Furthermore, fluoride alone caused oxidative stress and inflammation in the liver, as reflected by the increase in ROS and MDA contents, the reduction of anti-oxidative enzymes, the altered immune related enzymes (ACP, AKP, LZM and MPO) and the expression of IL-6, IL-1β, TNF-α, IL-10 and TGF-β. In contrast, co-exposure to fluoride and Se-Met decreased fluoride burden and restored growth. Furthermore, dietary Se-Met alleviated oxidative stress, inflammation and impaired morphology in liver trigger by fluoride. However, dietary Se-Met alone increased the activities of SOD and CAT. These results demonstrate that the protective effect of dietary Se-Met against chronic fluoride toxicity at a certain level., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Selenium (Se), as one of the essential trace elements, plays an anti-inflammatory, antioxidation, and immune-enhancing effect in the body. In addition, Se can also improve nervous system damage induced by various factors. Earlier studies have described the important role of mitochondrial dynamic imbalance in lipopolysaccharide (LPS)-induced nerve injury. The inositol 1,4,5-triphosphate receptor (IP3R)/glucose-regulated protein 75 (GRP75)/voltage-dependent anion channel 1 (VDAC1) complex is considered to be the key to regulating mitochondrial dynamics. However, it is not clear whether Selenomethionine (SeMet) has any influence on the IP3R/GRP75/VDAC1 complex. Therefore, the aim of this investigation was to determine whether SeMet can alleviate LPS-induced brain damage and to elucidate the function of the IP3R/GRP75/VDAC1 complex in it. We established SeMet and/or LPS exposure models in vivo and in vitro using laying hens and primary chicken nerve cells. We noticed that SeMet reversed endoplasmic reticulum stress (ERS) and the imbalance in mitochondrial dynamics and significantly prevented the occurrence of neuronal apoptosis. We made this finding by morphological observation of the brain tissue of laying hens and the detection of related genes such as ERS, the IP3R/GRP75/VDAC1 complex, calcium signal (Ca 2+ ), mitochondrial dynamics, and apoptosis. Other than that, we also discovered that the IP3R/GRP75/VDAC1 complex was crucial in controlling Ca 2+ transport between the endoplasmic reticulum and the mitochondrion when SeMet functions as a neuroprotective agent. In summary, our results revealed the specific mechanism by which SeMet alleviated LPS-induced neuronal apoptosis for the first time. As a consequence, SeMet has great potential in the treatment and prevention of neurological illnesses (like neurodegenerative diseases)., (© 2024 Wiley Periodicals LLC.)

Klebsiella pneumoniae (K. pneumoniae) is one of the major pathogens causing bovine clinical mastitis. Autophagy maintains cellular homeostasis and resists excessive inflammation in eukaryotic organisms. Selenomethionine (Se-Met) is commonly used as a source of selenium supplementation for dairy cows. This study aimed to investigate the effects of Se-Met on inflammatory responses mediated by nuclear factor-kappa B (NF-κB) through autophagy. We infected bovine mammary epithelial cell line (MAC-T) with K. pneumoniae and examined the expression of autophagy-related proteins and changes in autophagic vesicles, LC3 puncta, and autophagic flux at various intervals. The results showed that K. pneumoniae activated the early-stage autophagy of MAC-T cells. The levels of LC3-II, Beclin1, and ATG5, as well as the number of LC3 puncta and autophagic vesicles, increased after 2 h post-treatment. However, the late-stage autophagic flux was blocked. Furthermore, the effect of autophagy on NF-κB-mediated inflammation was investigated with different autophagy levels. The findings showed that enhanced autophagy inhibited the K. pneumoniae-induced inflammatory responses of MAC-T cells. The opposite results were found with the inhibition of autophagy. Finally, we examined the effect of Se-Met on NF-κB-mediated inflammation based on autophagy. The results indicated that Se-Met alleviated K. pneumoniae-induced autophagic flux blockage, inhibited NF-κB-mediated inflammation, and decreased the adhesion of K. pneumoniae to MAC-T cells. The inhibitory effect of Se-Met on NF-κB-mediated inflammation could be partially blocked by the autophagy inhibitor chloroquine (CQ). Overall, Se-Met attenuated K. pneumoniae-induced NF-κB-mediated inflammatory responses by enhancing autophagic flux., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Selenium (Se) is involved in many physiopathologic processes in humans and animals and is strongly associated with the development of heart disease. Lipopolysaccharides (LPS) are cell wall components of gram-negative bacteria that are present in large quantities during environmental pollution. To investigate the mechanism of LPS-induced cardiac injury and the efficacy of the therapeutic effect of SeMet on LPS, a chicken model supplemented with selenomethionine (SeMet) and/or LPS treatment, as well as a primary chicken embryo cardiomyocyte model with the combined effect of SeMet / JAK2 inhibitor (INCB018424) and/or LPS were established in this experiment. CCK8 kit, Trypan blue staining, DCFH-DA staining, oxidative stress kits, immunofluorescence staining, LDH kit, real-time fluorescence quantitative PCR, and western blot were used. The results proved that LPS exposure led to ROS explosion, hindered the antioxidant system, promoted the expression of the JAK2 pathway, and increased the expression of genes involved in the pyroptosis pathway, inflammatory factors, and heat shock proteins (HSPs). Upon co-treatment with SeMet and LPS, SeMet reduced LPS-induced pyroptosis and inflammation and restored the expression of HSPs by inhibiting the ROS burst and modulating the antioxidant capacity. Co-treatment with INCB018424 and LPS resulted in inhibited of the JAK2 pathway, attenuating pyroptosis, inflammation, and high expression of HSPs. Thus, LPS induced pyroptosis, inflammation, and changes in HSPs activity by activating of the JAK2 / STAT3 / A20 signaling axis in chicken hearts. Moreover, SeMet has a positive effect on LPS-induced injury. This work further provides a theoretical basis for treating cardiac injury by SeMet., Competing Interests: Declaration of competing interest We declare that we have no financial or personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service, and company. The authors claim that none of the material in the paper has been published or is being considered for publication elsewhere. All authors have read the manuscript and have agreed to submit it in its current form for consideration for publication in BBA-general subjects., (Copyright © 2023. Published by Elsevier B.V.)

Rice is an important food in the world, and selenium (Se) is a necessary trace element for the human. So the effects of selenomethionine (SeMet) on photosynthetic capacity, yield and quality of rice at different stages were studied. The results show that SeMet can increase the Ppotosynthetic capacity of rice leaves during each growth stage, the effect of 5 mg/L SeMet treatment was the most significant. At the mature stage of rice, SeMet significantly increased rice yield and total plant biomass, 7.5and 5 mg/L SeMet treatments had the most significant effects, respectively. In addition, SeMet significantly improved the content of Se and processing quality of rice, decreased chalkiness, inhibited amylose synthesis, and optimized flavor. The above indices showed the best results after treatment with 5 mg/L SeMet. It is hoped that this study will provide a theoretical basis for the application of organic selenium in rice production., Competing Interests: Declaration of competing interest In consideration of the publication, we hereby warrant and undertake:, (Copyright © 2024. Published by Elsevier Masson SAS.)

This study aimed to compare the effects of various selenium (Se) sources (2 mg/kg) on the performance, quality, and antioxidant capacity of laying hens as well as the Se content in their eggs and blood. We selected 720 34-wk-old Lohmann pink-shell laying hens were randomly assigned into 6 groups and fed a basal diet (control) or a basal diet supplemented with various Se sources (Se-enriched yeast, SY-A, SY-C, SY-N; selenomethionine SM, nano-Se SN) for 16 wk. There were 10 replicates of 120 hens per group. Dietary Se supplementation increased the egg production rate of all laying hens. Egg and serum Se deposition was highest in the SM group. Yolk color scores of SY-A and SY-N groups were significantly lower than those of other groups (P < 0.01). The protein height and Haugh unit were significantly lower in the SN group than in the other groups (P < 0.05). The yolk height was significantly higher in the SN and SY-N groups than in the SY-A group (P < 0.05). Dietary supplementation of selenium can improve the antioxidant capacity of laying hens. The SOD content of SM group was significantly lower than that of SY-A and SN group (P < 0.05). The malondialdehyde (MDA) content was significantly higher in the SM group than in the SY-A group (P < 0.05). The present work empirically demonstrated that the production performance of laying hens supplemented with 2 mg/kg Se was superior to that of the hens receiving only a basal diet. The SY-C group exhibited the best production performance, the SY-A group had the highest antioxidant capacity, and the SM group produced eggs with the highest level of Se enrichment., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Selenomethionine (SeMet) as the main form of daily dietary selenium, occupies essential roles in providing antioxidant and anti-inflammatory properties, which alleviates inflammatory liver damage. N6-methyladenosine (m 6 A) is one of the most prevalent and abundant internal transcriptional modifications that regulate gene expression. To investigate the protective mechanism of SeMet on liver injury and the regulatory effect of m 6 A methylation modification, we established the model by supplementing dietary SeMet, and LPS as stimulus in laying hens. LMH cells were intervened with SeMet (0.075 µM) and/or LPS (60 µg/mL). Subsequently, histopathology and ultrastructure of liver were observed. Western Blot, qRT-PCR, colorimetry, MeRIP-qPCR, fluorescent probe staining and AO/EB were used to detect total m 6 A methylation level, m 6 A methylation level of Nrf2, ROS, inflammatory and necroptosis factors. Studies showed that SeMet suppressed LPS-induced upregulation of total m 6 A methylation levels and METTL3 expression. Interestingly, SeMet reduced the m 6 A methylation level of Nrf2, activated antioxidant pathways and alleviated oxidative stress. LMH cells were transfected with 50 µm siMETTL3. SeMet/SiMETTL3 reversed the LPS-induced reduction in Nrf2 mRNA stability, slowed down its degradation rate. Moreover, LPS induced oxidative stress, led to necroptosis and activated NF-κB to promote the expression of inflammatory factors. SeMet/SiMETTL3 alleviated LPS-induced necroptosis and inflammation. Altogether, SeMet enhanced antioxidant and anti-inflammatory capacity by reducing METTL3-mediated m 6 A methylation levels of Nrf2, ultimately alleviating liver damage. Our findings provided new insights and therapeutic target for the practical application of dietary SeMet in the treatment and prevention of liver inflammation, and supplied a reference for comparative medicine., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Poorly differentiated thyroid cancer (PDTC) is a special type of thyroid cancer that threatens the life of the patients. Unfortunately, there are no effective treatments for PDTC right now, so it is urgent to search for new efficacious drugs. This experiment was designed to elucidate the effects of selenomethionine (SeMet) on PDTC in vitro and vivo., Methods: A xenograft animal model was used to assay the volume and weight of PDTC. LncRNA NOMMMUT014201 expression was detected by fluorescence in situ hybridization and Real-time quantitative PCR (qRT-PCR). In vitro experiments were carried on in WRO cells. The Cell Counting Kit-8 assay was performed to test the effect of SeMet on the proliferation of cells. And the migration and invasion of WRO cells by the wound-healing assay, Transwell migration and invasion assays. The cell apoptosis was measured by flow cytometry. In addition, genes related to proliferation, migration, invasion and apoptosis were detected through qRT-PCR and Western Blot., Results: SeMet inhibited the proliferation, migration and invasion and promoted the apoptosis of WRO cells in a dose-dependent manner. Then vivo , SeMet significantly suppressed the volume and weight of PDTC. And SeMet downregulated the expressions of Ki67, PCNA, MMP2, MMP9 and BCL2, but upregulated that of BAX and Cleaved-Caspase 3. Moreover, SeMet upregulated the level of LncRNA NOMMMUT014201 both vivo and in vitro . In addition, repression of LncRNA NOMMMUT014201 removed the inhibition effect of SeMet on WRO cell growth significantly (p<0.05). Further investigation showed that LncRNA NOMMMUT014201 downregulated the expression of miR-6963-5p in PDTC cells, but miR-6963-5p inhibited the level of Srprb. In addition, sh-LncRNA NOMMMUT014201 enhanced the proliferation, migration and invasion but inhibited the apoptosis of WRO cells. However, inhibited miR-6963-5p or overexpressed Srprb relieved the effects of sh-LncRNA NOMMMUT014201on WRO cells., Conclusion: Collectively, SeMet inhibits the growth of PDTC in a dose-dependent manner through LncRNA NONMMUT014201/miR-6963-5p/Srprb signal pathway, thus suggesting that SeMet might be a potential drug for PDTC treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Previously, insulin resistance and hepatic oxidative stress with increased expressions of glutathione peroxidase (GPx) 1 and selenoprotein P (SelP) were induced in NSY mice, a diabetic mouse model, by administrating a high fat diet (HFD) and seleno-L-methionine (SeMet) for 12 weeks. In this study we developed an analysis method for serum selenoproteins using LC-tandem mass spectrometry (LC-MS/MS) and investigated the effects of supplementary selenium on serum concentrations of selenoproteins as well as protein expression in skeletal muscle as a major insulin target tissue under the same experimental condition. The glucose area under the curves for oral glucose tolerance and insulin tolerance tests indicated that the HFD induced insulin resistance, whereas the treatment of SeMet + HFD showed insignificant promotion compared with the HFD-induced insulin resistance. Although the expressions of GPx1 in gastrocnemius and soleus were not significantly induced by supplementary SeMet nor HFD administration, the expressions of SelP in both skeletal muscles were significantly induced by the treatment of SeMet + HFD. There were also significant increases in serum concentrations of SelP by supplementary SeMet + HFD administration, whereas GPx3 was augmented by supplementary SeMet only. These results indicated that the HFD intake under the sufficient selenium status augmented the blood secretion of SelP, which may participate in the reduction of insulin sensitivity in skeletal muscles as well as liver or adipose tissues, and it is a better indicator of deterioration than GPx3 as it is a major selenoprotein in serum.

Exposure to lipopolysaccharide (LPS) can lead to inflammation in a variety of tissues and organs. Selenium (Se) plays a crucial role in mitigating inflammatory damage. Compared with inorganic selenium, organic selenium, such as selenomethionine (SeMet), has the advantages of a higher absorption rate and lower toxicity in animals. This study examined the protective effects of SeMet on eggshell gland tissue damage caused by LPS. Hy-Line Brown laying hens were chosen as the experimental animals and were randomly assigned to four groups: control group (C), lipopolysaccharide group (LPS), SeMet group (Se), and SeMet + lipopolysaccharide group (Se + LPS). H&E staining and transmission electron microscope were performed to observe the pathological changes of eggshell glands, oxidative stress related indicators were measured using relevant kits, qRT‒PCR and western blotting were used to evaluate the mRNA and protein levels of the Nrf2 pathway, necroptosis, and inflammation related indicators. The results showed that LPS treatment increased the content of malondialdehyde (MDA), decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and decreased the content of glutathione (GSH). LPS increased the levels of Keap1, RIPK1, RIPK3, MLKL, TNF-α, COX-2, and NF-κB, while decreasing the levels of HO-1, NQO1, Nrf2, and Caspase-8. However, SeMet treatment effectively reversed the changes of the above indicators, indicating that SeMet alleviates eggshell gland cell necroptosis-mediated inflammation induced by LPS via regulating the Keap1/Nrf2/HO-1 pathway. This study elucidated the mechanism by which SeMet alleviates LPS-induced eggshell gland tissue damage in Hy-Line Brown laying hens and provided a new direction for expanding the application of SeMet in the feeding and production of laying hens., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The purpose of this study was to explore the protective effect of SeMet on renal injury induced by AFB 1 in rabbits and its molecular mechanism. Forty rabbits of 35 days old were randomly divided into control group, AFB 1 group (0.3 mg AFB 1 /kg b.w), 0.2 mg/kg Se + AFB 1 group (0.3 mg AFB 1 /kg b.w + 0.2 mg SeMet/kg feed) and 0.4 mg/kg Se + AFB 1 group (0.3 mg AFB 1 /kg b.w + 0.4 mg SeMet/kg feed). The SeMet treatment group was fed different doses of SeMet diets every day for 21 days. On the 17-21 day, the AFB 1 treatment group, the 0.2 mg/kg Se + AFB 1 group and the 0.4 mg/kg Se + AFB 1 group were administered 0.3 mg AFB 1 /kg b.w by gavage (dissolved in 0.5 ml olive oil) respectively. The results showed that AFB 1 poisoning resulted in the changes of renal structure, the increase of renal coefficient and serum biochemical indexes, the ascent of ROS and MDA levels, the descent of antioxidant enzyme activity, and the significant down-regulation of Nrf2, HO-1 and NQO1. Besides, AFB 1 poisoning increased the number of renal apoptotic cells, rised the levels of PTEN, Bax, Caspase-3 and Caspase-9, and decreased the levels of PI3K, AKT, p-AKT and Bcl-2. In summary, SeMet was added to alleviate the oxidative stress injury and apoptosis of kidney induced by AFB 1 , and the effect of 0.2 mg/kg Se + AFB 1 is better than 0.4 mg/kg Se + AFB 1 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Deoxynivalenol (DON) is a significant Fusarium toxin that has gained global attention due to its high frequency of contamination in food and feed. It was reported to have hepatotoxicity, immunotoxicity, and reproduction toxicity in organs. On the other hand, Selenomethionine (SeMet) was proven to have anti-oxidation, tissue repairing, immunity improvement, and antifungal mycotoxin infection functions. However, the molecular mechanism by which SeMet alleviates DON damage is not yet clear. C57BL/6 mice were randomly divided into three groups, Se-A and Se-A+DON were fed with a diet containing 0.2 mg/kg Se whereas Se-S+DON were fed with a diet of 1.0 mg/kg Se. After feeding for four weeks, the mice were gavaged for 21 days with DON (2.0 mg/kg BW) or ultrapure water once per day. In the present study, we showed that SeMet significantly decreased the lipid peroxidation product malondialdehyde, and increased activities of antioxidant enzymes superoxide dismutase and total antioxidant capacity after DON exposure. In addition, our investigation revealed that SeMet regulated pathways related to lipid synthesis and metabolisms, and effectively mitigated DON-induced liver damage. Moreover, we have discovered that SeMet downregulation of N-acylethanolamine and HexCer accumulation induced hepatic lipotoxicity. Further study showed that SeMet supplementation increased protein levels of glutathione peroxidase 4 (GPX4), peroxisome proliferator-activated receptor γ (PPARγ), nuclear erythroid 2-related factor 2 (Nrf2), and upregulated target proteins, indicating suppression of oxidative stress in the liver. Meanwhile, we found that SeMet significantly reduced the DON-induced protein abundances of Bcl2, Beclin1, LC3B and proteins related to ferroptosis (Lpcat3, and Slc3a2), and downregulation of Slc7a11. In conclusion, SeMet protected the liver from damage by enhancing the Nrf2/PPARγ-GPX4-ferroptosis pathway, inhibiting lipid accumulation and hepatic lipotoxicity. The findings of this study indicated that SeMet has a positive impact on liver health by improving antioxidant capacity and relieving lipotoxicity in toxin pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

With the increasing of global mean surface air temperature, heat stress (HS) induced by extreme high temperature has become a key factor restricting the poultry industry. Liver is the main metabolic organ of broilers, HS induces liver damage and metabolic disorders, which impairs the health of broilers and affects food safety. As an essential trace element for animals, selenium (Se) involves in the formation of antioxidant system, and its biological functions are generally mediated by selenoproteins. However, the mechanism of Se against HS induced liver damage and metabolic disorders in broilers is inadequate. Therefore, we developed the chronic heat stress (CHS) broiler model and investigated the potential protection mechanism of organic Se (selenomethionine, SeMet) on CHS induced liver damage and metabolic disorders. In present study, CHS caused liver oxidative damage, and induced hepatic lipid accumulation and glycogen infiltration of broilers, which are accompanied by mitochondrial dysfunction, abnormal mitochondrial tricarboxylic acid (TCA) cycle and endoplasmic reticulum (ER) stress. Dietary SeMet supplementation increased the hepatic Se concentration and exhibited protective effects via promoting the expression of selenotranscriptome and several key selenoproteins (GPX4, TXNRD2, SELENOK, SELENOM, SELENOS, SELENOT, GPX1, DIO1, SELENOH, SELENOU and SELENOW). These key selenoproteins synergistically improved the antioxidant capacity, and mitigated the mitochondrial dysfunction, abnormal mitochondrial TCA cycle and ER stress, thus recovered the hepatic triglyceride and glycogen concentration. What's more, SeMet supplementation suppressed lipid and glycogen biosynthesis and promoted lipid and glycogen breakdown in liver of broilers exposed to CHS though regulating the AMPK signals. Overall, our present study reveals a potential mechanism that Se alleviates environment HS induced liver damage and glycogen and lipid metabolism disorders in broilers, which provides a preventive and/or treatment measure for environment HS-dependent hepatic metabolic disorders in poultry industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Se is an essential trace element associated with animal growth and antioxidant and metabolic processes. However, whether Se, especially organic Se with higher bioavailability, can alleviate the adverse effects of low salinity stress on marine economic crustacean species has not been investigated. Accordingly, juvenile Pacific white shrimp ( Litopenaeus vannamei ) were reared in two culture conditions (low and standard salinity) fed diets supplemented with increasing levels of l-selenomethionine (0·41, 0·84 and 1·14 mg/kg Se) for 56 d, resulting in four treatments: 0·41 mg/kg under standard seawater (salinity 31) and 0·41, 0·84 and 1·14 mg/kg Se under low salinity (salinity 3). The diet containing 0·84 mg/kg Se significantly improved the survival and weight gain of shrimp under low salinity stress and enhanced the antioxidant capacity of the hepatopancreas. The increased numbers of B and R cells may be a passive change in hepatopancreas histology in the 1·14 mg/kg Se group. Transcriptomic analysis found that l-selenomethionine was involved in the regulatory pathways of energy metabolism, retinol metabolism and steroid hormones. In conclusion, dietary supplementation with 0·84 mg/kg Se (twice the recommended level) effectively alleviated the effects of low salinity stress on L. vannamei by regulating antioxidant capacity, hormone regulation and energy metabolism.

Renal ischemia-reperfusion injuries (IRIs) are one of the leading causes of acute kidney injuries (AKIs). Selenium, as an essential trace element, is able to antioxidant stress and reduces inflammatory responses. The regulation mechanism of selenomethionine, one of the major forms of selenium intake by humans, is not yet clear in renal IRIs. Therefore, we aimed to explore the key targets and related mechanisms of selenomethionine regulation in renal IRIs and provide new ideas for the treatment of selenomethionine with renal IRIs. We used transcriptome sequencing data from public databases as well as animal experiments to explore the key target genes and related mechanisms regulated by selenomethionine in renal IRI. We found that selenomethionine can effectively alleviate renal IRI by a mechanism that may be achieved by inhibiting the MAPK signaling pathway. Meanwhile, we also found that the key target of selenomethionine regulation in renal IRI might be selenoprotein GPX3 based on the PPI protein interaction network and machine learning. Through a comprehensive analysis of bioinformatic techniques and animal experiments, we found that Gpx3 might serve as a key gene for the regulation of selenomethionine in renal IRIs. Selenomethionine may exert a protective effect against renal IRI by up-regulating GPX3, inhibiting the MAPK signaling pathway, increased production of antioxidants, decreasing inflammation levels, mitigation of apoptosis in renal tubular epithelial cells, this reduces renal histopathological damage and protects renal function. Providing a theoretical basis for the mechanism of selenomethionine actions in renal IRIs., (© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Conditions associated with selenium (Se) and/or vitamin E (VitE) deficiency are still being reported in high-yielding pigs fed the recommended amounts. Here, the dietary effects of Se source (sodium selenite, NaSe, 0.40 or 0.65 mg Se/kg; L-selenomethionine, SeMet, 0.19 or 0.44 mg Se/kg; a NaSe-SeMet mixture, SeMix, 0.44-0.46 mg Se/kg) and VitE concentration (27, 50-53 or 101 mg/kg) on the antioxidant status of finisher pigs were compared with those in pigs fed non-Se-supplemented diets (0.08-0.09 mg Se/kg). Compared to NaSe-enriched diets, SeMet-supplemented diets resulted in significantly (p < 0.0018) higher plasma concentrations of total Se (14-27%) and selenospecies (GPx3, SelP, SeAlb; 7-83%), significantly increased the total Se accumulation in skeletal muscles, myocardium, liver and brain (10-650%), and enhanced the VitE levels in plasma (15-74%) and tissues (8-33%) by the end of the 80-day trial, proving better Se distribution and retention in pigs fed organic Se. Injecting lipopolysaccharide (LPS) intravenously half-way into the trial provoked a pyrogenic response in the pigs followed by a rapid increase of inorganic Se after 5-12 h, a drastic drop of SeMet levels between 12 and 24 h that recovered by 48 h, and a small increase of SeCys by 24-48 h, together with a gradual rise of GPx3, SelP and SeAlb in plasma up to 48 h. These changes in Se speciation in plasma were particularly significant (0.0024 > p > 0.00007) in pigs receiving SeMet- (0.44 mg Se/kg, above EU-legislated limits) or SeMix-supplemented (SeMet and NaSe both at 0.2 mg Se/kg, within EU-legislated limits) diets, which demonstrates Se metabolism upregulation to counteract the LPS-induced oxidative stress and a strengthened antioxidant capacity in these pigs. Overall, a Se source combination (without exceeding EU-legislated limits) and sufficient VitE supplementation (≥ 50 mg/kg) improved the pigs' antioxidant status, while doubling the allowed dietary organic Se increased the Se in tissues up to sixfold without compromising the animal's health due to toxicity. This study renders valuable results for revising the current dietary SeMet limits in swine rations., (© 2022. The Author(s).)

Selenium (Se) is an essential element and antioxidant that catalyzes the destruction of hydrogen peroxide formed during cellular oxidative metabolism. Doses of Se as selenomethionine (SeMe) by oral route are 0.1-0.3 mgSe/kg DM, while the dose by parenteral route with sodium selenite (Na 2 SeO 3 ) is 0.1 mgSe/BW. The effects of supranutritional Se supplementation on normal kids have rarely been studied. The objective of the study was to evaluate both Se sources on growth performance, Se in tissues, histopathological findings, and meat characteristics. Forty-five kids of the Pastoreña breed with 25-day age were distributed (4.7 ± 1.13 kg) in three treatments: a) control group, C: consumption with goat milk (GM: containing 0.135 mgSe/g); b) NaSe: GM plus Na 2 SeO 3 injectable, 0.25 mgSe/kg BW; c) SeMe: GM plus oral dosage, 0.3 mgSe as SeMe daily. Fifteen animals per treatment were slaughtered at 7, 14, and 21 days. Feed conversion improved (P < 0.05) with Se supplement (P < 0.05) at 7 and 14 days. SeMe had higher protein and fat meat content (P < 0.05). SeMe increased Se liver at 14 and 21 days. NaSe and SeMe had higher (P < 0.05) levels of Se kidney. SeMe-21d showed 42% mononuclear and periportal cell infiltration lesions. In conclusion, Se administered through milk in goat kids was insufficient to prevent nutritional muscular dystrophy. The supranutritional dose of 0.25 mg/kg as NaSe was sufficient to maintain the Se level in tissues. SeMe increased Se liver and kidney efficiently. Both Se sources improved the bioavailability of the mineral in kids., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The current study was designed to evaluate the effects of chronic dietary arsenic exposure on the cognitive performance of adult zebrafish and uncover probable pathways by which arsenic mediates such neurotoxic effects. Adult zebrafish were treated with 3 different dietary arsenic concentrations (30, 60, and 100 μg/g dry weight (dw), as arsenite) in addition to control for 60 days. A latent learning paradigm, which employs a complex maze, was used to assess the cognitive performance of fish. Our results demonstrated that dietary treatment with arsenic, especially at medium (60 μg/g dw) and high (100 μg/g dw) exposure dose levels, significantly impaired the performance of fish in various latent learning tasks evaluated in the present study. Concomitant with cognitive dysfunction, chronic dietary exposure to arsenic was also found to increase arsenic accumulation and dopamine levels, and induce oxidative stress (reduced thiol redox, increased lipid peroxidation and expression of antioxidant enzyme genes) in the brain of zebrafish in a dose-dependent manner. Dopaminergic system in the brain is known to play a critical role in regulating cognitive behaviours in fish, and our observations suggested that chronic dietary treatment with medium and high arsenic doses leads to significant alterations in the expression of genes involved in dopamine signaling (dopamine receptors), synthesis (thyroxine hydroxylase) and metabolism (monoamine oxidase) in the zebrafish brain. Moreover, we also recorded significant downregulation of genes such as the brain-derived neurotrophic factor (BDNF) and ectonucleotidases (entpd2&#95;mg, entpd2&#95;mq, and 5'-nucleotidase), which are critical for learning and memory functions, in the zebrafish brain following chronic dietary exposure to arsenic. Overall, the present study suggests that chronic environmentally relevant dietary exposure to arsenic can impair the cognitive performance in zebrafish, essentially by inducing oxidative stress and disrupting the dopaminergic neurotransmission in the brain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

T-2 toxin and selenium deficiency are considered important etiologies of Kashin-Beck disease (KBD), although the exact mechanism is still unclear. To identify differentially expressed microRNAs (DE-miRNAs) in the articular cartilage of rats exposed to T-2 toxin and selenomethionine (SeMet) supplementation, thirty-six 4-week-old Sprague Dawley rats were divided into a control group (gavaged with 4% anhydrous ethanol), a T-2 group (gavaged with 100 ng/g·bw/day T-2 toxin), and a T-2 + SeMet group (gavaged with 100 ng/g·bw/day T-2 toxin and 0.5 mg/kg·bw/day SeMet), respectively. Toluidine blue staining was performed to detect the pathological changes of articular cartilage. Three rats per group were randomly selected for high-throughput sequencing of articular cartilage. Target genes of DE-miRNAs were predicted using miRanda and RNAhybrid databases, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were enriched. The network map of miRNA-target genes was constructed using Cytoscape software. The expression profiles of miRNAs associated with KBD were obtained from the Gene Expression Omnibus database. Additionally, the DE-miRNAs were selected for real-time quantitative PCR (RT-qPCR) verification. Toluidine blue staining demonstrated that T-2 toxin damaged articular cartilage and SeMet effectively alleviated articular cartilage lesions. A total of 50 DE-miRNAs (28 upregulated and 22 downregulated) in the T-2 group vs. the control group, 18 DE-miRNAs (6 upregulated and 12 downregulated) in the T-2 + SeMet group vs. the control group, and 25 DE-miRNAs (5 upregulated and 20 downregulated) in the T-2 + SeMet group vs. the T-2 group were identified. Enrichment analysis showed the target genes of DE-miRNAs were associated with apoptosis, and in the MAPK and TGF-β signaling pathways in the T-2 group vs. the control group. However, the pathway of apoptosis was not significant in the T-2 + SeMet group vs. the control group. These results indicated that T-2 toxin induced apoptosis, whereas SeMet supplementation antagonized apoptosis. Apoptosis and autophagy occurred simultaneously in the T-2 + SeMet group vs. T-2 group, and autophagy may inhibit apoptosis to protect cartilage. Compared with the GSE186593 dataset, the evidence of miR-133a-3p involved in apoptosis was more abundant. The results of RT-qPCR validation were consistent with RNA sequencing results. Our findings suggested that apoptosis was involved in articular cartilage lesions induced by T-2 toxin, whereas SeMet supplementation antagonized apoptosis, and that miR-133a-3p most probably played a central role in the apoptosis process.

Ammonia is a significant pollutant in the livestock houses and the atmospheric environment, and excessive ammonia would harm the health of livestock and breeders. Previous studies have shown that ammonia exposure could damage the tissue structure of the nervous system, but the molecular mechanism of ammonia-induced hypothalamus damage was still unclear. The purpose of this study was to determine the role of excessive ammonia in abnormal autophagy of pig hypothalamus and whether selenomethionine would have a mitigating effect on ammonia toxicity. Twenty-four 18-week pigs were randomly divided into four groups: the control group (C group), the selenium group (Se group), the ammonia + selenium group (A + Se group), and the ammonia group (A group). In our study, the expression levels of NF-κB, IL-1β, iNOS, TNF-α, IKK-α, p-IKK-α, Nrf2, ATG5, ATG 10, ATG 12, LC3 I/II, HSP60, HSP70, and HSP90 were increased after ammonia exposure; meanwhile, IFN-γ, IKB-α, p-IKB-α, Keap1, P62, mTOR, AKT, p-AKT, PI3K, SQSTM, and Beclin1 showed decreasing trends. The results indicated that excessive ammonia inhalation inhibited the AKT/mTOR pathway to acclerated autophagy through oxidative stress-mediated inflammation in the porcine hypothalamus. L-selenomethionine could alleviate hypothalamus injury induced by ammonia exposure., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ammonia could be regarded as one detrimental pollutant with an acrid smell in livestock sheds. So far, the pig breeding industry became the main source of atmospheric ammonia. Previous literature demonstrated that excessive ammonia inhalation might cause a series of physiological damage to multiple organs. Unfortunately, the toxicity mechanisms of gaseous ammonia to the porcine nervous system need further research to elucidate. Selenium (Se) involves in many essential physiological processes and has a mitigative effect on the exogenous toxicant. There were scant references that corroborated whether organic Se could intervene in the underlying toxicity of ammonia to the hypothalamus. In the present study, multi-omics tools, ethology, and molecular biological techniques were performed to clarify the detailed mechanisms of relaxation effects of L-selenomethionine on ammonia poisoning. Our results showed that ammonia inhalation caused the clinical symptoms and the increment of positive apoptosis rate in the hypothalamus with the dysfunction of mitochondrial dynamics factors, while obvious mitochondria structure defects were observed. In parallel, the inflammation medium levels and gut microbes-driven metabolism function were altered to mediate the neurotoxicity in fattening pigs through the initiation of inflammation development. Interestingly, L-selenomethionine could attenuate ammonia toxicity by activating the PI3K/Akt/PPAR-γ pathway to inhibit the mitochondria-mediated apoptosis process, blocking the abnormal immune response and the accumulation of reactive oxygen species in the nucleus. Meanwhile, Se could enhance the production performance of fattening sows. Taken together, our study verified the novel hypothesis for the toxicity identification of aerial ammonia and provided a therapeutic strategy for the treatment of occupational poisoning., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

(1) In this study we determined the effect of long-term selenomethionine administration on the oxidative stress level and changes in antioxidant protein/enzyme activity; mRNA expression; and the levels of iron, zinc, and copper. (2) Experiments were performed on 4-6-week-old BALB/c mice, which were given selenomethionine (0.4 mg Se/kg b.w.) solution for 8 weeks. The element concentration was determined via inductively coupled plasma mass spectrometry. mRNA expression of SelenoP , Cat , and Sod1 was quantified using real-time quantitative reverse transcription. Malondialdehyde content and catalase activity were determined spectrophotometrically. (3) After long-term SeMet administration, the amount of Se increased by 12-fold in mouse blood, 15-fold in the liver, and 42-fold in the brain, as compared to that in the control. Exposure to SeMet decreased amounts of Fe and Cu in blood, but increased Fe and Zn levels in the liver and increased the levels of all examined elements in the brain. Se increased malondialdehyde content in the blood and brain but decreased it in liver. SeMet administration increased the mRNA expression of selenoprotein P, dismutase, and catalase, but decreased catalase activity in brain and liver. (4) Eight-week-long selenomethionine consumption elevated Se levels in the blood, liver, and especially in the brain and disturbed the homeostasis of Fe, Zn, and Cu. Moreover, Se induced lipid peroxidation in the blood and brain, but not in the liver. In response to SeMet exposure, significant up-regulation of the mRNA expression of catalase, superoxide dismutase 1, and selenoprotein P in the brain, and especially in the liver, was determined.

Selenomethionine (Se-Met) has many beneficial effects on higher animals and human, and can regulate cellular physiology through distinct signaling pathways. However, the role and molecular mechanism of Se-Met in skeletal muscle growth remains unclear. In this study, we observed the effects of Se-Met on C2C12 myoblasts and skeletal muscle growth of mice, and explored the corresponding molecular mechanism. Se-Met affected proliferation and protein synthesis of C2C12 myoblasts in a hormesis type of relationship, and had an optimal stimulatory effect at 50 µM concentration. Se-Met also affected mTOR, ANXA2, and PKCα phosphorylation in the same manner. ANXA2 knockdown blocked the stimulation of Se-Met on cell proliferation and protein synthesis and inhibition of Se-Met on autophagy of C2C12 myoblasts. Western blotting analysis showed that PI3K inhibition blocked the stimulation of Se-Met on mTOR phosphorylation. ANXA2 knockdown further blocked the stimulation of Se-Met on PI3K and mTOR phosphorylation. Point mutation experiment showed that ANXA2 mediated the stimulation of Se-Met on the PI3K-mTOR signaling through phosphorylation at Ser26. PKCα interacted with ANXA2, and PKCα knockdown blocked the stimulation of Se-Met on ANXA2 phosphorylation at Ser26. Se-Met addition (7.5mg/kg diet, 4 weeks) increased mouse carcass weight, promoted gastrocnemius skeletal muscle growth and ANXA2 and mTOR phosphorylation in this tissue. Collectively, our findings reveal that Se-Met can promote proliferation and protein synthesis of myoblasts and skeletal muscle growth through ANXA2 phosphorylation., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ammonia (NH 3 ) is a harmful gas in livestock houses. So far, many researchers have demonstrated that NH 3 is detrimental to animal and human organs. Selenium (Se) is one of the essential trace elements in the body and has a good antioxidant effect. However, there was little conclusive evidence that Se alleviated NH 3 poisoning. To investigate the toxic mechanism of NH 3 on pig spleen and the antagonistic effect of L-selenomethionine, a porcine NH 3 -poisoning model and an L-selenomethionine intervention model were established in this study. Our results showed that NH 3 exposure increased the apoptosis rate, while L-selenomethionine supplementation alleviated the process of excessive apoptosis. Immunofluorescence staining, real-time quantitative polymerase chain reaction (qRT-PCR), and western blot results confirmed that exposure to NH 3 changed the expression levels of interleukin family factors, apoptosis, death receptor, and oxidative stress factors. Our study further confirmed that excessive NH 3 induced inflammatory response and mediated necroptosis leading to cell apoptosis by activating the Nrf2 signaling pathway. Excessive NH 3 could mediate spleen injury through oxidative stress-induced mitochondrial dynamics disorder. L-Selenomethionine could alleviate inflammation and abnormal apoptosis by inhibiting the IL-17/TNF-α/FADD axis. Our study would pave the way for comparative medicine and environmental toxicology., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this study, we aimed to determine the amount of Se transferred to milk and blood of mid- to late-lactation dairy cows when supplemental Se from hydroxy-selenomethionine (OH-SeMet) was fed compared with an unsupplemented group and a group supplemented with a seleno-yeast (SY). Twenty-four lactating Holstein cows (178 ± 43 d in milk) were used in a complete randomized block design for 91 d (7-d covariate period and 84-d treatment period). Treatments were (1) basal diet with an analyzed Se background of 0.2 mg of Se per kg as-fed (control); (2) basal diet + 0.3 mg of Se/kg as-fed from SY (SY-0.3); (3) basal diet + 0.1 mg of Se/kg as-fed from OH-SeMet (OH-SeMet-0.1); and (4) basal diet + 0.3 mg of Se/kg as-fed from OH-SeMet (OH-SeMet-0.3). During the trial, plasma and milk were analyzed for total Se, and plasma was analyzed for glutathione peroxidase activity. The mean plasma and milk Se concentrations exhibited the same relationship, where OH-SeMet-0.3 resulted in the highest values (142 µg/L of plasma and 104 µg/kg of milk), followed by SY-0.3 (134 µg/L and 85 µg/kg), OH-SeMet-0.1 (122 µg/L and 67 µg/kg), and the control group had the lowest values (120 µg/L and 50 µg/kg). The increment of Se in milk induced by OH-SeMet-0.3 (+54 µg/kg) was 54% higher than that induced by SY-0.3 (+35 µg/kg). Additionally, dietary supplementation of 0.2 mg/kg Se from OH-SeMet in the total mixed ration was estimated to be similar to 0.3 mg/kg Se from SY in the total mixed ration when considering the level of Se in the milk. There was no difference in plasma glutathione peroxidase activity between groups; however, OH-SeMet-0.3 significantly decreased somatic cell count. The results confirmed that supplementation with organic Se increases milk and plasma Se concentrations. Moreover, when administered at the same level of supplementation, OH-SeMet was shown to be more efficient than SY in improving milk quality by increasing Se content and decreasing milk somatic cell count., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Chronic heat stress (CHS) compromised the immunity and spleen immunological function of pigs, which may associate with antioxidant suppression and splenocyte apoptosis and splenic inflammation. Selenium (Se) exhibited antioxidant function and immunomodulatory through selenoprotein. Thus, this study aimed to investigate the protective effect of dietary hydroxy-selenomethionine (Selisso ® , SeO) on chronic heat stress (CHS)-induced porcine splenic oxidative stress, apoptosis and inflammation. Growing pigs were raised in the thermoneutral environment (22 ± 2 °C) with the basal diet (BD), or raised in hyperthermal conditions (33 ± 2 °C) with BD supplied with 0.0, 0.2, 0.4 and 0.6 mg Se/kg SeO for 28 d, respectively. The results showed that dietary SeO supplementation recovered the spleen mass and enhanced the splenic antioxidant capacity of CHS growing pigs. Meanwhile, SeO activated the Nrf2/Keap1 signal, downregulated p38, caspase 3 and Bax, inhibited the activation of NFκb and STAT3, and enhanced the protein expression level of GPX1, GPX3, GPX4, SELENOS and SELENOF. In summary, SeO supplementation mitigates the CHS-induced splenic oxidative damages, apoptosis and inflammation in pigs, and the processes are associated with the activation of Nrf2/Keap1 signal and the suppression of NFκb, p38(MAPK) and STAT signal. It seems that the antioxidant-related selenoproteins (GPXs) and functional selenoproteins (SELENOS and SELENOF) play important roles in the alleviation processes.

Selenium methionine (SeMet) is an essential micronutrient required for normal body function and is associated with additional health benefits. However, oral administration of SeMet can be challenging due to its purported narrow therapeutic index, low oral bioavailability, and high susceptibility to oxidation. To address these issues, SeMet was entrapped in zein-coated nanoparticles made from chitosan using an ionic gelation formulation. The high stability of both the SeMet and selenomethionine nanoparticles (SeMet-NPs) was established using cultured human intestinal and liver epithelial cells, rat liver homogenates, and rat intestinal homogenates and lumen washes. Minimal cytotoxicity to Caco-2 and HepG2 cells was observed for SeMet and SeMet-NPs. Antioxidant properties of SeMet were revealed using a Reactive Oxygen Species (ROS) assay, based on the observation of a concentration-dependent reduction in the build-up of peroxides, hydroxides and hydroxyl radicals in Caco-2 cells exposed to SeMet (6.25-100 μM). The basal apparent permeability coefficient (P app ) of SeMet across isolated rat jejunal mucosae mounted in Ussing chambers was low, but the P app was increased when presented in NP. SeMet had minimal effects on the electrogenic ion secretion of rat jejunal and colonic mucosae in Ussing chambers. Intra-jejunal injections of SeMet-NPs to rats yielded increased plasma levels of SeMet after 3 h for the SeMet-NPs compared to free SeMet. Overall, there is potential to further develop SeMet-NPs for oral supplementation due to the increased intestinal permeability, versus free SeMet, and the low potential for toxicity.

Selenium plays a vital role in cancer prevention, antioxidation, and the growth of humans and other vertebrates. Excessive selenium can cause liver injury and metabolic disorders, which can lead to hepatic disease, but few studies have shown the effects of excessive selenium on liver development and its mechanism in zebrafish embryos. In this study, liver development and glucolipid metabolism were investigated in selenium-stressed zebrafish embryos. Under selenium treatment, transgenic fabp10a-eGFP zebrafish embryos showed reduced liver size, and wild-type zebrafish embryos exhibited steatosis and altered lipid metabolism-related indexes and glucose metabolism-related enzyme activities. In addition, selenium-stressed embryos exhibited damaged mitochondria and inhibited autophagy in the liver. An autophagy inducer (rapamycin) alleviated selenium-induced liver injury and restored the expression of some genes related to liver development and glucolipid metabolism. In summary, our research evaluated liver developmental toxicity and metabolic disorders under selenium stress, and confirmed that autophagy and oxidative stress might involve in the selenium-induced hepatic defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Imbalanced nutrient intake causes abnormal energy metabolism, which results in obesity. There is feasible evidence that selenium-rich (Se-rich) foods may alleviate obesity and enhance general public health, but the underlying mechanisms remain elusive. Herein we examined the effect of Se supplementation on white adipose tissue beiging process. The mice were fed with a normal diet or a Se-deficient high-fat diet (DHFD) until significant differences in terms of body weight, glucose tolerance and insulin sensitivity. Next, mice in the DHFD group were changed to a high-fat diet (HFD) containing specified amounts of selenomethionine (SeMet) (0, 150, 300, and 600 μg/kg) and continued to feed for 14 weeks. Notably, 150 μg/kg SeMet supplement highly protected mice from DHFD-induced obesity, insulin resistance, and lipid deposits in the liver and kidney, and featured by the enhanced beiging process in white adipose tissue and increased energy expenditure. Moreover, upon cold challenge, 150 μg/kg SeMet supplement enhanced cold tolerance in mice by inducing adipose beiging to promote energy expenditure, as evidenced by the increased expression of uncoupling protein-1 (UCP1) in adipocytes. Similarly, SeMet (10 μM) promoted the differentiation of beige adipocytes from the stromal vascular fraction. Collectively, our data support that optimal supplementation of SeMet could enhance the beiging process to attenuate HFD-induced obesity, which provides new insights into the relationship between dietary SeMet and type 2 diabetes., Competing Interests: Declaration of competing interests The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The purpose of this study was to investigate the protective effect and mechanism of selenomethionine (SeMet) on ochratoxin A (OTA)-induced nephrotoxicity in rabbits. In total, sixty Ira rabbits were randomly divided into 5 groups (the control group, OTA group, 0. 2 mg/kg SeMet + OTA group, 0. 4 mg/kg SeMet + OTA group, and 0. 6 mg/kg SeMet + OTA group). The rabbits were fed diets supplemented with different doses of SeMet for 21 days and given 0. 2 mg/kg OTA starting on day 15 for a week. The results showed that the SeMet supplementation could improve the changes in blood physiological indices and renal function decline caused by OTA poisoning, and alleviate pathological kidney injury in the rabbits. SeMet also increased the activities of total antioxidant capacity, superoxide dismutase, and glutathione peroxidase, and decreased the contents of malondialdehyde and reactive oxygen species and the expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the damaged kidneys of the rabbits. In addition, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream gene heme oxygenase 1 (HO-1) was also inhibited after OTA poisoning, while SeMet activated the Nrf2 signaling pathway and enhanced the expression of Nrf2 and the downstream gene HO-1. In conclusion, SeMet protected against kidney injury caused by OTA in rabbits, and the mechanism may be the activation of the Nrf2 signaling pathway., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Oxidative stress significantly compromises the production efficiency of laying hens. It has been reported in literature that selenium (Se) in poultry diets has a positive effect on mitigating these effects. This study has been carried out to evaluate the effects of Se supplementation in feeds, from either an inorganic or a hydroxy-selenomethionine (OH-SeMet) source, on the performance and physiological traits of 50- to 70-wk-old Dekalb Brown laying hens under heat stress, and on their egg quality after different storage durations. The treatments consisted in supplementing 0.3 ppm of Se as sodium selenite (SS; 45%-0.7g/ton) or OH-SeMet (2%-15g/ton) in twelve 16-bird replicates. Supplementation with OH-SeMet resulted in a better performance of the laying hens than with SS: -5% feed conversion ratio and +3.6% of egg mass. A reduction in egg quality was observed with prolonged egg storage, which was mitigated with the use of OH-SeMet in laying hen diets. The use of OH-SeMet increased the antioxidant capacity of the birds, which showed higher glutathione peroxidase levels in the blood, kidneys, liver, and intestinal mucosa, in addition to a higher Se content in the eggs and a greater bone resistance. Thus, supplementing feeds with 0.3 ppm of OH-SeMet to 50- to 70-wk-old semi-heavy laying hens enhances their antioxidant capacity and leads to a higher egg quality and productivity than SS supplementation., Competing Interests: DISCLOSURES Naiara Simarro Fagundes and Garros Fontinhas-Netto are employees of Adisseo. The other authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Selenium (Se) is an essential micronutrient known to play an important role in the antioxidant system that can potentially influence tumor growth. We aimed to investigate the effects of dietary Se supplementation after detection of 4T1 mammary tumor growth in BALB/c mice. Thirty female mice received subcutaneous inoculation of 4T1 cells. After five days, all animals presenting palpable tumors were randomly assigned to three groups: a control group (Se-control) receiving a diet with adequate Se (0.15 mg/kg) and two other groups that received Se-supplemented diets (1.4 mg/kg of total Se) with either Brazilian nuts (Se-Nuts) or selenomethionine (SeMet). Data were assessed by either One or Two-way ANOVA followed by Tukey's HSD or Bonferroni's post hoc tests, respectively. Both Se-supplemented diets reduced tumor volume from the thirteenth day of feeding compared with the Se-adequate (control) diet (p < 0.05). The SeMet group presented a higher Se blood concentration (p < 0.05) than the Se-control group, with the Se-Nuts group presenting intermediate values. Selenoprotein P gene expression in the liver was higher in the Se-Nuts group than in the Se-control group (p < 0.05), while the SeMet group presented intermediate expression. Dietary Se supplementation, starting after detection of 4T1 palpable lesions, reduced tumor volume in mice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pereira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The small intestinal epithelium is regulated in response to various beneficial or harmful environmental information. Deoxynivalenol (DON), a mycotoxin widely distributed in cereal-based feeds, induces oxidative stress damage in the intestine due to the mitochondrial stress. As a functional nutrient, selenomethionine (Se-Met) is involved in synthesizing several antioxidant enzymes, yet whether it can replenish the intestinal epithelium upon DON exposure remains unknown. Therefore, the in vivo model C57BL/6 mice and the in vitro model MODE-K cells were treated with l-Se-Met and DON alone or in combination to confirm the status of intestinal stem cell (ISC)-driven epithelial regeneration. The results showed that 0.1 mg/kg body weight (BW) Se-Met reinstated the growth performance and integrity of jejunal structure and barrier function in DON-challenged mice. Moreover, Lgr5 + ISCs and PCNA + mitotic cells in crypts were prominently increased by Se-Met in the presence of DON, concomitant with a significant increase in absorptive cells, goblet cells, and Paneth cells. Simultaneously, crypt-derived jejunal organoids from the Se-Met + DON group exhibited more significant growth advantages ex vivo . Furthermore, Se-Met-stimulated Keap1/Nrf2-dependent antioxidant system (T-AOC and GSH-Px) to inhibit the accumulation of ROS and MDA in the jejunum and serum. Moreover, Se-Met failed to rescue the DON-triggered impairment of cell antioxidant function after Nrf2 perturbation using its specific inhibitor ML385 in MODE-K cells. In conclusion, Se-Met protects ISC-driven intestinal epithelial integrity against DON-induced oxidative stress damage by modulating Keap1/Nrf2 signaling.

Selenium (Se), an essential antioxidant trace element, is reported to play a role in Parkinson's disease (PD). However, there is a lack of systematic studies on different Se forms against PD. Our study is designed to compare the neuroprotective effects of inorganic and organic Se in two classical PD mice models and investigate the underlying mechanisms for their potentially differential actions against PD. In this study, different dosages of inorganic sodium selenite (Se-Na) or organic seleno-L-methionine (Se-Met) were fed to either acute or chronic PD mice models, and their neuroprotective effects and mechanisms were explored and compared. Se-Na provided better neuroprotective effects in PD mice than Se-Met administered at the same but at a relatively low Se dosage. Se-Na treatment could influence GPX activities but not their mRNA expressions in the midbrains of PD mice. The enhanced GPX activities caused by Se-Na, but not Se-Met, in PD mice could be the major reason for the positive actions of inorganic Se to prevent dopaminergic neuronal loss in this study. In vivo bio-distribution experiments found MPTP injection greatly changed Se bio-distribution in mice, which led to reversed alterations in the bioavailability of Se-Met and Se-Na. Se-Na had higher bioavailability than Se-Met in PD mice, which could explain its better neuroprotective effects compared to Se-Met. Our results proved that Se forms and dosages determined their biological actions in mouse models of PD. Our study will provide valuable scientific evidence to researchers and/or medical professionals in using Se for PD prevention or therapy.

Ammonia has been reported to have a variety of toxicity to aquatic animals, farm animals and humans. However, its potential toxicity on the intestines remains unknown. L-selenomethionine is one of the important organic selenium sources. However, the mitigating effect of L-selenomethionine on ammonia exposure toxicity is still lacking. Therefore, in this study, the mechanism of toxic action of ammonia on intestinal tract and the detoxification effect of L-selenomethionine were examined. We evaluated the intestinal toxicity of ammonia and the alleviating effect of L-selenomethionine in an in vivo model, and then verified it in vitro model by a variety of cutting-edge experimental techniques. Our results showed that ammonia exposure causes oxidative stress, necroptosis, Th1/Th2 imbalance and inflammation in the intestinal tissue and the intestinal cells, and L-selenomethionine had a significant mitigation effect on the changes of these indexes induced by ammonia. In conclusion, ammonia exposure caused oxidative stress and Th1/Th2 imbalance in the porcine small intestine and IPEC-J2 cells, and that excessive ROS accumulation-mediated necroptosis targeted inflammatory responses, resulting in the destruction of tight connections of intestinal cells, thereby causing intestinal barrier dysfunction. L-selenomethionine could effectively reduce the intestinal injury caused by ammonia exposure and antagonize the toxic effect of ammonia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Heat stress (HS) in summer has caused huge economic losses to animal husbandry production recently. When mammary gland is exposed to high temperatures, it will cause blood-milk barrier damage. Hydroxy-selenomethionine (HMSeBA) is a new selenium source with better guarantee of animals' production performance under stress, but whether it has protective effect on heat stress-induced blood-milk damage is still unclear. We established mammary epithelial cells and mice heat stress injury models to fill this research gap, and hope to provide theoretical basis for using HMSeBA to alleviate heat stress damage mammary gland. The results showed that (1) Heat stress significantly decreases in vitro transepithelial electrical resistance (TEER) and cell viability ( P < 0.01), and significantly decreases clinical score, histological score, and total alveoli area of mice mammary gland tissue ( P < 0.01). (2) HMSeBA significantly increases TEER and fluorescein sodium leakage of HS-induced monolayer BMECs ( P < 0.01), significantly improves the milk production and total area of alveoli ( P < 0.01), and reduces clinical score, histological score, mRNA expression of heat stress-related proteins, and inflammatory cytokines release of heat-stressed mice ( P < 0.01). (3) HMSeBA significantly improves tight junction structure damage, and significantly up-regulated the expression of tight junction proteins (ZO-1, claudin 1, and occludin) as well as signal molecules PI3K, AKT, and mTOR ( P < 0.01) in heat-stressed mammary tissue. (4) HMSeBA significantly increases glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and superoxide dismutase release (SOD) ( P < 0.01) and significantly reduce malondialdehyde (MDA) expression ( P < 0.01) in heat-stressed mammary tissue. In conclusion, this study implemented heat-stressed cell and mice model and showed that HMSeBA significantly regulate antioxidant capacity, inhibited inflammation, and regulate tight junction proteins expression in blood-milk barrier via PI3K/AKT/mTOR signaling pathway, so as to alleviate mammary gland damage and ensure its structure and function integrity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Zhao, He, Wang, Cao, Yang, Wang and Li.)

L-Selenomethionine is one of the important organic selenium sources. The supplementation of L-selenomethionine in diets is significant to improve the health of pigs. Ammonia is a major pollutant in the atmosphere and piggery, posing a threat to human and animal health. Although ammonia exposure can damage the heart, the mechanism of cardiac toxicity by ammonia is still unknown. In this study, we investigated the mechanism of cardiac injury induced by ammonia exposure in pigs and the protective effect of L-selenomethionine on its cardiotoxicity. The results showed that the blood ammonia content of pig increased significantly in ammonia group, the expressions of energy metabolism-related genes (LDHA, PDK4, HK2, and CPTIB) and the oxidative stress indexes were significantly changed (P < 0.05), the AMPK/PPAR-γ/NF-κB signaling pathways were activated, the chromatin edge aggregation and nuclear pyknosis were observed in ultrastructure, the apoptotic cells were significantly increased (P < 0.05), and the mRNA and protein expressions of apoptosis-related genes (Bcl-2, Bax, Cyt-c, caspase-3, and caspase-9) were significantly affected (P < 0.05). The above changes were significantly alleviated in ammonia + L-selenomethionine group, but there were still significant differences compared with the C group (P < 0.05). Our results indicated that ammonia exposure could cause energy metabolism disorder and oxidative stress and induce apoptosis of cardiomyocytes through AMPK/PPAR-γ/NF-κB pathways, which could lead to cardiac injury and affect cardiac function. L-Selenomethionine could effectively alleviate the cardiac damage caused by ammonia and antagonize the cardiotoxicity of ammonia., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Methylmercury (MeHg) is a well-known environmental contaminant, particularly harmful to the developing brain. The main human dietary exposure to MeHg occurs through seafood consumption. However, seafood also contains several nutrients, including selenium, which has been shown to interact with MeHg and potentially ameliorate its toxicity. The aim of this study was to investigate the combined effects of selenium (as selenomethionine; SeMet) and MeHg on mercury accumulation in tissues and the effects concomitant dietary exposure of these compounds exert on the hippocampal proteome and transcriptome in mice. Adolescent male BALB/c mice were exposed to SeMet and two different doses of MeHg through their diet for 11 weeks. Organs, including the brain, were sampled for mercury analyses. Hippocampi were collected and analyzed using proteomics and transcriptomics followed by multi-omics bioinformatics data analysis. The dietary presence of SeMet reduced the amount of mercury in several organs, including the brain. Proteomic and RNA-seq analyses showed that both protein and RNA expression patterns were inversely regulated in mice receiving SeMet together with MeHg compared to MeHg alone. Several pathways, proteins and RNA transcripts involved in conditions such as immune responses and inflammation, oxidative stress, cell plasticity and Alzheimer's disease were affected inversely by SeMet and MeHg, indicating that SeMet can ameliorate several toxic effects of MeHg in mice.