Selenoprotein Synthesis Research Articles

Biochemical strategy-based hybrid hydrogel dressing-mediated in situ synthesis of selenoproteins for DFU immunity-microbiota homeostasis regulation.

Chronic consequences of diabetes that are most commonly encountered are diabetic foot ulcers (DFUs), driven by microbiota-immune system dyshomeostasis, eventually leading to delayed wound healing. Available therapies, such as systemic or topical administration of anti-inflammatory or antimicrobial agents, are limited due to antibiotic resistance and immune dysfunction. Herein, a hybrid hydrogel dressing is developed as the artificial bioadhesive barrier at wound sites to maintain microbial and immunological homeostasis locally and have potent anti-inflammatory effects. Specifically, Zero-valent selenium nanoparticles are synthesized and encapsulated into the alginate-polyacrylamide interpenetrating hydrogel networks, during which trehalose is adopted to modify the network defects. Besides, as an anti-adhesion agent, trehalose has shown the ability to prevent immune degradation by reducing bacteria binding to HUVECs. The obtained hybrid hydrogel dressing serves as a physical barrier against microbiome invasion, further regulates the composition of the wound microbiome to restore microbial immune homeostasis at the wound site, and cooperatively relieves DFU-associated symptoms. Meanwhile, the hydrogel dressing can synthesize selenoproteins in situ based on biochemical strategies and significantly reduce the secretion of proinflammatory cytokines. The proposed biochemical strategy based on the hybrid hydrogel dressings can efficiently restore microbiota-immune homeostasis in the wounds, presenting a promising approach for DFU therapy in clinics.

Selenoprotein-Mediated Redox Regulation Shapes the Cell Fate of HSCs and Mature Lineages.

The maintenance of cellular redox balance is crucial for cell survival and homeostasis and is disrupted with aging. Selenoproteins, comprising essential antioxidant enzymes, raise intriguing questions about their involvement in hematopoietic aging and potential reversibility. Motivated by our observation of mRNA downregulation of key antioxidant selenoproteins in aged human hematopoietic stem cells (HSCs) and previous findings of increased lipid peroxidation in aged hematopoiesis, we employed tRNASec gene (Trsp) knockout (KO) mouse model to simulate disrupted selenoprotein synthesis. This revealed insights into the protective roles of selenoproteins in preserving HSC stemness and B-lineage maturation, despite negligible effects on myeloid cells. Notably, Trsp KO exhibited B lymphocytopenia and reduced HSCs' self-renewal capacity, recapitulating certain aspects of aged phenotypes, along with the upregulation of aging-related genes in both HSCs and pre-B cells. While Trsp KO activated an antioxidant response transcription factor NRF2, we delineated a lineage-dependent phenotype driven by lipid peroxidation, which was exacerbated with aging yet ameliorated by ferroptosis inhibitors such as vitamin E. Interestingly, the myeloid genes were ectopically expressed in pre-B cells of Trsp KO mice, and KO pro-B/pre-B cells displayed differentiation potential toward functional CD11b+ fraction in the transplant model, suggesting that disrupted selenoprotein synthesis induces the potential of B-to-myeloid switch. Given the similarities between the KO model and aged wild-type mice, including ferroptosis vulnerability, impaired HSC self-renewal and B-lineage maturation, and characteristic lineage switch, our findings underscore the critical role of selenoprotein-mediated redox regulation in maintaining balanced hematopoiesis and suggest the preventive potential of selenoproteins against aging-related alterations.

PRDX6 as an additional piece in the puzzle of selenoprotein synthesis

In this issue of Molecular Cell, Ito etal.1 and Chen etal.2 identify peroxiredoxin 6 (PRDX6) as member of the selenoprotein (re)synthesis machinery, thereby linking PRDX6 to ferroptosis susceptibility of cancer cells.

Intracellular Redox Environment Determines Cancer-normal Cell Selectivity of Selenium Nanoclusters.

Elucidating the chemical structure and intracellular action mechanisms is still the critical limit for the clinical translation of nanomedicines. Intracellular redox environments originating from cell metabolism are key factors affecting internalized drug efficacy. Herein, we engineer Se-Se/Se-S bond to assemble selenium (Se) nanoclusters (SeClus) with intracellular redox environment-driven selective structure. Chemical structure analysis reveals that, the bonding of sulfur atom in intermediates to the two neighboring or interposition Se atoms in Se rings is the key internal driving force for SeClus formation. This nanocluster can be predominantly transformed to selenocysteine to facilitate selenoproteins synthesis in normal cells, while metabolize to cytotoxic SeO3 2- based on the oxidative intracellular redox environment of cancer cells. Resultantly, SeClus exhibit significant cell proliferation inhibition ability to cancer cells and impressive safety to normal cells. Taken together, this study not only clarifies the chemical nature of the atom engineering of SeClus, but also elucidates its intracellular redox environment-oriented anticancer mechanism.

Intracellular Redox Environment Determines Cancer‐normal Cell Selectivity of Selenium Nanoclusters

AbstractElucidating the chemical structure and intracellular action mechanisms is still the critical limit for the clinical translation of nanomedicines. Intracellular redox environments originating from cell metabolism are key factors affecting internalized drug efficacy. Herein, we engineer Se−Se/Se−S bond to assemble selenium (Se) nanoclusters (SeClus) with intracellular redox environment‐driven selective structure. Chemical structure analysis reveals that, the bonding of sulfur atom in intermediates to the two neighboring or interposition Se atoms in Se rings is the key internal driving force for SeClus formation. This nanocluster can be predominantly transformed to selenocysteine to facilitate selenoproteins synthesis in normal cells, while metabolize to cytotoxic SeO32− based on the oxidative intracellular redox environment of cancer cells. Resultantly, SeClus exhibit significant cell proliferation inhibition ability to cancer cells and impressive safety to normal cells. Taken together, this study not only clarifies the chemical nature of the atom engineering of SeClus, but also elucidates its intracellular redox environment‐oriented anticancer mechanism.

TRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory

Post-transcriptional modification of RNA regulates gene expression at multiple levels. ALKBH8 is a tRNA-modifying enzyme that methylates wobble uridines in a subset of tRNAs to modulate translation. Through methylation of tRNA-selenocysteine, ALKBH8 promotes selenoprotein synthesis and regulates redox homeostasis. Pathogenic variants in ALKBH8 have been linked to intellectual disability disorders in the human population, but the role of ALKBH8 in the nervous system is unknown. Through in vivo studies in Drosophila, we show that ALKBH8 controls oxidative stress in the brain to restrain synaptic growth and support learning and memory. ALKBH8 null animals lack wobble uridine methylation and exhibit reduced protein synthesis in the nervous system, including a specific decrease in selenoprotein levels. Either loss of ALKBH8 or independent disruption of selenoprotein synthesis results in ectopic synapse formation. Genetic expression of antioxidant enzymes fully suppresses synaptic overgrowth in ALKBH8 null animals, confirming oxidative stress as the underlying cause of dysregulation. ALKBH8 null animals also exhibit associative memory impairments that are reversed by pharmacological antioxidant treatment. Together, these findings demonstrate the critical role of tRNA wobble uridine modification in redox homeostasis in the developing nervous system and reveal antioxidants as a potential therapy for ALKBH8-associated intellectual disability.

Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis

The limited availability of therapeutic options for patients with triple-negative breast cancer (TNBC) contributes to the high rate of metastatic recurrence and poor prognosis. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation and counteracted by the antioxidant activity of the selenoprotein GPX4. Here, we show that TNBC cells secrete an anti-ferroptotic factor in the extracellular environment when cultured at high cell densities but are primed to ferroptosis when forming colonies at low density. We found that secretion of the anti-ferroptotic factors, identified as monounsaturated fatty acid (MUFA) containing lipids, and the vulnerability to ferroptosis of single cells depends on the low expression of stearyl-CoA desaturase (SCD) that is proportional to cell density. Finally, we show that the inhibition of Sec-tRNAsec biosynthesis, an essential step for selenoprotein production, causes ferroptosis and impairs the lung seeding of circulating TNBC cells that are no longer protected by the MUFA-rich environment of the primary tumour.

Human selenocysteine synthase, SEPSECS, has evolved to optimize binding of a tRNA-based substrate.

The evolution of the genetic code to incorporate selenocysteine (Sec) enabled the development of a selenoproteome in all domains of life. O-phosphoseryl-tRNASec selenium transferase (SepSecS) catalyzes the terminal reaction of Sec synthesis on tRNASec in archaea and eukaryotes. Despite harboring four equivalent active sites, human SEPSECS binds no more than two tRNASec molecules. Though, the basis for this asymmetry remains poorly understood. In humans, an acidic, C-terminal, α-helical extension precludes additional tRNA-binding events in two of the enzyme monomers, stabilizing the SEPSECS•tRNASec complex. However, the existence of a helix exclusively in vertebrates raised questions about the evolution of the tRNA-binding mechanism in SEPSECS and the origin of its C-terminal extension. Herein, using a comparative structural and phylogenetic analysis, we show that the tRNA-binding motifs in SEPSECS are poorly conserved across species. Consequently, in contrast to mammalian SEPSECS, the archaeal ortholog cannot bind unacylated tRNASec and requires an aminoacyl group. Moreover, the C-terminal α-helix 16 is a mammalian innovation, and its absence causes aggregation of the SEPSECS•tRNASec complex at low tRNA concentrations. Altogether, we propose SEPSECS evolved a tRNASec binding mechanism as a crucial functional and structural feature, allowing for additional levels of regulation of Sec and selenoprotein synthesis.

Severe neurodevelopmental phenotype, diagnostic, and treatment challenges in patients with SECISBP2 deficiency

PurposeDefects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited. MethodsGenetic and laboratory investigations were performed in affected members from 6 families presenting with short stature and failure to thrive. ResultsFour probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in 2 cases. Thyroid hormone treatment improved motor development, whereas speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20 years because SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted antithyroid treatment instead. ConclusionThis syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in 4 patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy.

The role of selenium in the functioning of immune system components and the incidence of allergies: a content analysis of recent literature

Selenium is an essential trace element. Adequate intake of selenium is necessary for optimal functioning of cellular and humoral processes in the body. Lack of selenium in the diet can lead to aggravation of infectious and allergic diseases and also increase the risk of tumor formation. This review article provides data on the metabolic pathways of selenium and its role in the immune system, as well as the occurrence of allergies and antitumor and antioxidant protection. In detail, the role of selenium is discussed in relation to the implementation of body antiviral defenses. Under conditions of selenium deficiency, numerous viral infections are linked to an unfavorable prognosis, and this article specifically considers the problem of myocarditis occurring during viral infections, summarizing data on the pathogenesis of the condition and possible connections with selenium deficiency. The results of content analysis demonstrate that selenium, participating in the synthesis of selenium-containing enzymes and selenoproteins, ensures the functioning and activity of innate and acquired immunity, antitumour and antioxidant defence, which indirectly affects the course of allergic diseases. Selenium deficiency increases the incidence of allergies, tumours and infections, especially viral infections. In case of viral infections, not only the course of immune reactions depends on sufficient amount of selenium in the organism, but also the possibility of increasing the virulence of the pathogen in case of selenium deficiency. In the case of a severe course of the disease, the main symptoms of infection may be joined by other, more serious manifestations, such as myocarditis. The antioxidant, immunostimulant and antiviral properties of selenium ensure its modifying role in the development of diseases and the percentage of fatalities. Rational consumption of selenium may be of great importance in the prevention, course and determination of outcomes of many diseases, including allergopathology.

PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis.

Ferroptosis is a form of regulated cell death induced by iron-dependent accumulation of lipid hydroperoxides. Selenoprotein glutathione peroxidase 4 (GPX4) suppresses ferroptosis by detoxifying lipid hydroperoxides via a catalytic selenocysteine (Sec) residue. Sec, the genetically encoded 21st amino acid, is biosynthesized from a reactive selenium donor on its cognate tRNA[Ser]Sec. It is thought that intracellular selenium must be delivered 'safely' and 'efficiently' by a carrier protein owing to its high reactivity and very low concentrations. Here, we identified peroxiredoxin 6 (PRDX6) as a novel selenoprotein synthesis factor. Loss of PRDX6 decreases the expression of selenoproteins and induces ferroptosis via a reduction in GPX4. Mechanistically, PRDX6 increases the efficiency of intracellular selenium utilization by transferring selenium between proteins within the selenocysteyl-tRNA[Ser]Sec synthesis machinery, leading to efficient synthesis of selenocysteyl-tRNA[Ser]Sec. These findings highlight previously unidentified selenium metabolic systems and provide new insights into ferroptosis.

The Regulation of Selenoproteins in Diabetes: A New Way to Treat Diabetes.

Selenium is an essential micronutrient required for the synthesis and function of selenoproteins, most of which are enzymes involved in maintaining oxidative balance in the body. Diabetes is a group of metabolic disorders characterized by high blood glucose levels over a prolonged period of time. There are three main types of diabetes: type 1, type 2, and gestational diabetes. This review summarizes recent advances in the field of diabetes research with an emphasis on the roles of selenoproteins on metabolic disturbance in diabetes. We also discuss the interaction between selenoproteins and glucose and lipid metabolism to provide new insights into the prevention and treatment of diabetes.

Selenotranscriptome network in Alzheimer’s disease

The interplay between selenoproteins, oxidative stress, and cell death pathways holds promise in unravelling novel therapeutic targets for Alzheimer’s disease (AD) in the future. Nonetheless, further comprehensive investigations are warranted to fully comprehend the precise contributions of selenoproteins in the aetiology and potential therapeutic strategies for Alzheimer’s disease. Previous work into gene expression networks in AD has included analysis of the entire transcriptome and, as of yet, has not yielded consistent insight into pathological pathways.1 Despite the comprehensive assessment of the transcriptome enabled by current technologies, one drawback of the whole transcriptome analysis is the risk of overlooking subtle yet significant variations in metabolic pathways.2 Thus, we aimed to assess gene expression of known selenoprotein and selenium-containing pathways in two different brain regions (dorsolateral prefrontal cortex (DPC) and posterior cingulate cortex (PCC)) across the AD spectrum. We used RNA sequencing data from The Rush University’s Religious Orders Study and Memory and Aging Project (ROSMAP) cohort available in the AD Knowledge Portal (https://www.synapse.org/).3 This study included data available for a total of 889 DPC and 647 PCC samples. Four pathological phenotypes were determined based on pathology (CERAD) and clinical (CDR) status: AD ([(+) pathology, (+) clinical], prodromal disease, corresponding to donors that have not received a clinical diagnosis despite the presence of pathological alterations ([(+) pathology, (−) clinical], controls ([(−) pathology, (−) clinical] and non-AD dementia [(+) pathology, (+) clinical]. This last group was excluded from the analysis as it is assumed they may have been misdiagnosed or presented with non-AD dementia. Six selenium or AD-related pathways were assessed, accounting for 421 unique genes. Group comparisons were performed using linear mixed modelling adjusted for age, sex, APOEe4 status and batch via DESeq2 package with Benjamini-Hochberg adjustment for multiple testing. A total of 18 genes significantly differed between AD and controls in both brain areas (same direction in both brain areas; P < 0.05), including eight selenoprotein genes or genes directly associated with selenoprotein synthesis. Fifteen of them were also different (same direction) in PCC (seven selenoprotein/selenoprotein synthesis genes), and four were different in DPC (four selenoprotein/selenoprotein synthesis genes) between AD and prodromal. Only three genes significantly differed between prodromal and control samples (DPC), including the selenoprotein DIO3 and the transcription factor SP3. Our findings indicate a progressive change in gene expression across the different stages of AD. These findings shed light on critical genes involved in selenoprotein synthesis that play a role in AD pathogenesis. Restricting the analysis to a subset of pathways enabled the detection of smaller alterations between groups, which is particularly appropriate in trace element homeostasis, where small alterations may have significant downstream effects.

Promising aryl selenoate derivatives as antileishmanial agents and their effects on gene expression.

Leishmaniasis remains one of the main public health problems worldwide, with special incidence in the poorest populations. Selenium and its derivatives can be potent therapeutic options against protozoan parasites. In this work, 17 aryl selenoates were synthesized and screened against three species of Leishmania (Leishmania major, Leishmania amazonensis, and Leishmania infantum). Initial screening in promastigotes showed L. infantum species was more sensitive to selenoderivatives than the others. The lead Se-(2-selenocyanatoethyl) thiophene-2-carboselenoate (16) showed a half-maximal effective concentration of 3.07 µM and a selectivity index > 32.57 against L. infantum promastigotes. It was also the most effective of all 17 compounds, decreasing the infection ratio by 90% in L. infantum-infected macrophages with amastigotes at 10 µM. This aryl selenoate did not produce a hemolytic effect on human red blood cells at the studied doses (10-100 µM). Furthermore, the gene expression of infected murine macrophages related to cell death, the cell cycle, and the selenoprotein synthesis pathway in amastigotes was altered, while no changes were observed in their murine homologs, supporting the specificity of Compound 16 against the parasite. Therefore, this work reveals the possible benefits of selenoate derivatives for the treatment of leishmaniasis.

Biomonitoring of mercury and selenium in commercially important shellfish: Distribution pattern, health benefit assessment and consumption advisories.

This study aims to explore the concentrations of Se and Hg in shellfish along the Gulf of Mannar (GoM) coast (Southeast India) and to estimate related risks and risk-based consumption limits for children, pregnant women, and adults. Se concentrations in shrimp, crab, and cephalopods ranged from 0.256 to 0.275mgkg-1, 0.182 to 0.553mgkg-1, and 0.176 to 0.255mgkg-1, respectively, whereas Hg concentrations differed from 0.009 to 0.014mgkg-1, 0.022 to 0.042mgkg-1 and 0.011 to 0.024mgkg-1, respectively. Se and Hg content in bamboo shark (C. griseum) was 0.242mgkg-1 and 0.082mgkg-1, respectively. The lowest and highest Se concentrations were found in C. indicus (0.176mgkg-1) and C. natator (0.553mgkg-1), while Hg was found high in C. griseum (0.082mgkg-1) and low in P. vannamei (0.009mgkg-1). Se shellfishes were found in the following order: crabs > shrimp > shark > cephalopods, while that of Hg were shark > crabs > cephalopods > shrimp. Se in shellfish was negatively correlated with trophic level (TL) and size (length and weight), whereas Hg was positively correlated with TL and size. Hg concentrations in shellfish were below the maximum residual limits (MRL) of 0.5mgkg-1 for crustaceans and cephalopods set by FSSAI, 0.5mgkg-1 for crustaceans and 1.0mgkg-1 for cephalopods and sharks prescribed by the European Commission (EC/1881/2006). Se risk-benefit analysis, the AI (actual intake):RDI (recommended daily intake) ratio was > 100%, and the AI:UL (upper limit) ratio was < 100%, indicating that all shellfish have sufficient level of Se to meet daily requirements without exceeding the upper limit (UL). The target hazard quotient (THQ < 1) and hazard index (HI < 1) imply that the consumption of shellfish has no non-carcinogenic health impacts for all age groups. However, despite variations among the examined shellfish, it was consistently observed that they all exhibited a Se:Hg molar ratio > 1. This finding implies that the consumption of shellfish is generally safe in terms of Hg content. The health benefit indexes, Se-HBV and HBVse, consistently showed high positive values across all shellfish, further supporting the protective influence of Se against Hg toxicity and reinforcing the overall safety of shellfish consumption. Enhancing comprehension of food safety analysis, it is crucial to recognize that the elevated Se:Hg ratio in shellfish may be attributed to regular selenoprotein synthesis and the mitigation of Hg toxicity by substituting Se bound to Hg.

The Role of the Trace Element Selenium in Inflammatory Bowel Disease.

One set of chronic gastrointestinal disorders called inflammatory bowel disease (IBD) is defined by persistent, non-specific inflammation. Abdominal pain, hematochezia, diarrhea, and other symptoms are among its clinical signs. Currently, managing and treating IBD remains a significant challenge. Patients with IBD frequently have deficits in trace elements. Selenium (Se) is one of the necessary trace elements for normal organismal function. It has several regulatory effects, including anti-oxidation, anti-inflammatory, and defensive properties, via inducing the synthesis of selenoproteins. Patients with IBD have been shown to have lower Se levels in epidemiologic research studies. Several experimental models of IBD suggest that Se or selenoproteins play a key role in microinflammation. We discuss the relationship between Se and IBD in this review, with an emphasis on a summary of potential mechanisms of action and applications of Se in IBD.

A263 IRONING OUT THE DETAILS: CROHN’S DISEASE PATIENT DERIVED MACROPHAGES ARE MORE SUSCEPTIBLE TO FERROPTOSIS

Abstract Background Death of intestinal epithelial cells is ubiquitous in Crohn’s disease (CD) but the death of immune cells such as macrophages is less explored. We have found that monocyte derived macrophages from patients with active CD are more susceptible to H2O2-induced cytotoxicity but the form of regulated cell death these cells undergo remains to be elucidated. Selenium (Se)—a common micronutrient deficiency in patients with CD—is used in the synthesis of selenoproteins that have antioxidant properties (e.g., glutathione peroxidases (GPx)) and are highly expressed in macrophages. Whether Se deficiency plays a role in the increased cytotoxicity also remains to be elucidated. Aims To determine the form of cell death of macrophages in response to H2O2-induced cytotoxicity and whether selenium deficiency plays a role in the increased susceptibility to H2O2-induced cytotoxicity. Methods Blood collected from healthy volunteers and patients with active CD was analyzed for serum GPx activity. Monocytes isolated by plastic adherence were treated with M-CSF (10ng/ml, 7d) to derive macrophages. Macrophages were treated with H2O2 (500μm, 2h) and lactate dehydrogenase release was measured. GPX1, SLC7A11 and PTGS2 mRNA expression were determined by qPCR. The presence of cleaved caspase 3 was determined by immunoblotting and IL-1β by ELISA. Lipid peroxidation a marker of ferroptosis was assessed by staining macrophages with Bodipy C-11 (± liproxstatin-1, an inhibitor of ferroptosis). Results CD macrophages were two times more susceptible to H2O2-evoked cell death. In response to H2O2 macrophages did not express cleaved caspase 3 or IL-1β, but there was an induction of ferroptosis markers (SLC7A11 and PTGS2). Moreover, lipid peroxidation was induced and could be blocked with liproxstatin-1. Dietary Se intake did not differ between groups but serum GPx activity was greater in patients with CD compared to control. In contrast, GPX1 mRNA expression and GPx1 protein expression were decreased in CD macrophages compared to healthy controls. Conclusions Macrophages derived from patients with CD are inherently more sensitive to ferroptosis potentially through reduced GPx1 expression. Future studies warrant testing if GPx1 prevents ferroptotic macrophage cell death and if it holds therapeutic relevance in CD pathophysiology. Funding Agencies Helmsley Charitable Trust, Crohn's and Colitis Foundation of America

Emerging evidence on selenoneine and its public health relevance in coastal populations: a review and case study of dietary Se among Inuit populations in the Canadian Arctic.

Selenium is an essential mineral yet both deficiency and excess are associated with adverse health effects. Dietary intake of Se in humans varies greatly between populations due to food availability, dietary preferences, and local geological and ecosystem processes impacting Se accumulation into agricultural products and animal populations. We argue there is a need to evaluate and reconsider the relevance of public health recommendations on Se given recent evidence, including the metabolic pathways and health implications of Se. This argument is particularly pertinent for Inuit populations in Northern Canada, who often exceed dietary tolerable upper intake levels and exhibit very high whole blood Se concentrations due to their dependence on local country foods high in the newly discovered Se compound, selenoneine. Since selenoneine appears to have lower toxicity compared to other Se species and does not contribute to the circulating pools of Se for selenoprotein synthesis, we argue that total dietary Se or total Se in plasma or whole blood are poor indicators of Se adequacy for human health in these populations. Overall, this review provides an overview of the current evidence of Se speciation, deficiency, adequacy, and excess and implications for human health and dietary recommendations, with particular reference to Inuit populations in the Canadian Arctic and other coastal populations consuming marine foods.

Selenoprotein‐Regulated Hydrogel for Ultrasound‐Controlled Microenvironment Remodeling to Promote Bone Defect Repair

AbstractAbnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede bone repair processes. Herein, an innovative ultrasound‐modulatable hydrogel platform with selenoprotein‐mediated antioxidant effects to promote bone injury repair is presented. This hydrogel platform encapsulates oxygen‐enriched selene‐incorporated thin‐shell silicon within methacrylate gelatin (O2‐PSSG). The resultant construct orchestrates the modulation of the bone‐defect microenvironment, thereby expediting the course of bone regeneration. Ultrasound (US) is used to regulate the pore size of the hydrogel to release selenium‐containing nanoparticles and promote the in situ synthesis of efficient intracellular selenoproteins and hydrogen peroxide consumption. As expected, O2‐PSSG rapidly releases selenocystine ([Sec]2) under US control to scavenge reactive oxygen species and maintain the homeostasis of bone marrow mesenchymal stem cells (BMSCs). Over time, the action of the system by selenoprotein increases the activation of Wnt/β‐catenin pathways and promotes the differentiation of BMSCs. Consequently, O2‐PSSG potentiates the antioxidant proficiency of BMSCs both in vitro and in vivo, alleviates hypoxic environments, promotes osteogenic differentiation, and expedites cranial bone repair in rat models. In summary, this study suggests that the designed and constructed US‐responsive antioxidant hydrogel is a promising prospective strategy for addressing bone defects and fostering bone regeneration.

Biogenic Selenium Nanoparticles Synthesized Using Alginate Oligosaccharides Attenuate Heat Stress-Induced Impairment of Breast Meat Quality via Regulating Oxidative Stress, Metabolome and Ferroptosis in Broilers.

Selenium (Se) is an indispensable trace element with versatile functions in antioxidant defense in poultry. In our previous study, we synthesized a novel type of biogenic selenium nanoparticle based on alginate oligosaccharides (SeNPs-AOS), and found that the particles are sized around 80 nm with an 8% Se content, and the dietary addition of 5 mg/kg of SeNPs-AOS could effectively alleviate the deleterious effects of heat stress (HS) in broilers, but it is still unclear whether SeNPs-AOS can improve the meat quality. Therefore, the aim of this study was to evaluate the protective effects of SeNPs-AOS on breast meat quality in heat-stressed broilers, and explore the relevant mechanisms. Birds at the age of 21 days were randomly divided into four groups with six replicates per group (eight broilers per replicate) according to a 2 × 2 experimental design, using HS (33 ± 2 °C, 10 h/day vs. thermoneutral, TN, under 23 ± 1.5 °C) and SeNPs-AOS (5 mg/kg feed vs. no inclusion) as variables. The results showed that dietary SeNPs-AOS decreased the cooking loss (p < 0.05), freezing loss (p < 0.001), and shear force (p < 0.01) of breast muscle in heat-stressed broilers. The non-targeted metabolomics analysis of the breast muscle identified 78 differential metabolites between the HS and HS + SeNPs-AOS groups, mainly enriched in the arginine and proline metabolism, β-alanine metabolism, D-arginine and D-ornithine metabolism, pantothenate, and CoA biosynthesis pathways (p < 0.05). Meanwhile, supplementation with SeNPs-AOS increased the levels of the total antioxidant capacity (T-AOC), the activities of catalase (CAT) and glutathione peroxidase (GSH-Px), and decreased the content of malondialdehyde (MDA) in the breast muscle (p < 0.05) in broilers under HS exposure. Additionally, SeNPs-AOS upregulated the mRNA expression of CAT, GPX1, GPX3, heme oxygenase-1 (HO-1), masculoaponeurotic fibrosarcoma G (MafG), MafK, selenoprotein W (SELENOW), SELENOK, ferritin heavy polypeptide-1 (FTH1), Ferroportin 1 (Fpn1), and nuclear factor erythroid 2-related factor 2 (Nrf2) (p < 0.05), while it downregulated Kelch-like ECH-associated pro-36 tein 1 (Keap1) and prostaglandin-endoperoxide Synthase 2 (PTGS2) expression (p < 0.05) in broilers under HS. These findings demonstrated that the dietary addition of SeNPs-AOS mitigated HS-induced oxidative damage and metabolite changes in the breast muscle of broilers, which may be related to the regulation of the Nrf2 signaling pathway and selenoprotein synthesis. In addition, SeNPs-AOS upregulated the breast muscle gene expression of anti-ferroptosis-related molecules in broilers under HS, suggesting that SeNPs-AOS can be used as novel Se supplements against HS in broilers.