Search Results (48)

It is known that a percentage of patients who undergo total thyroidectomy, approximately 16–34%, complain of symptoms of hypothyroidism or altered quality of life (QoL) despite achieving normal serum TSH values. The present study aimed to identify whether the level of selenium could be responsible for this phenomenon. This pilot cohort study included 44 thyroidectomized outpatients. All patients underwent surgery for benign disease. In this study, no patients with a history of autoimmunity, malignancy, or other conditions that could affect well-being, absorption, or selenium intake were included. Serum levels of TSH, fT3, fT4, Selenoprotein P (SelP), and glutathione peroxidase 3 (GPx3) were measured. The patients also completed the ThyPRO-39 questionnaire to assess their QoL. A strong and significant direct correlation was found between SelP and GPx3 (r = 0.88). However, no correlation was found between hormonal status and SelP or GPx3. Analysis of ThyPRO-39 results did not show clinically significant differences between items nor a correlation with thyroid hormone levels, except for symptoms of hypothyroidism. Interestingly, a significant direct correlation was observed between SelP and tiredness, as well as between GPx3 and tiredness. Furthermore, the fT3/fT4 ratio was correlated with worsening symptoms of hypothyroidism. The results suggest that the selenium status, in turn related to antioxidant activities, as reflected in SelP and GPx3 levels, may be associated with the QoL tiredness domain in thyroidectomized patients, despite normal levels of thyroid hormones. More research is needed to elucidate the role of selenium in the persistent symptoms experienced by some thyroidectomized patients. Full article

The objective of this study was to determine whether hydroxy-selenomethionine (OH-SeMet) exerts better protective effects on sows against heat stress than sodium selenite (SeNa) or seleno-yeast (SeY). A total of 60 sows (Landrace × Yorkshire) were randomly allocated into the three groups and fed a base diet supplemented with SeNa, SeY, or OH-SeMet at 0.3 mg Se/kg under a heat stress condition for a reproductive cycle. Compared to SeNa or SeY, OH-SeMet could more effectively sustain offspring growth performance, as evidenced by an increased number of live-born piglets, higher litter weight at day 21, and greater litter body weight gain from days 1 to 21. OH-SeMet was more effective in supporting endogenous redox systems, as shown by enhanced levels of TXNRD and GSH and reduced levels of GSSG in the serum of sows, improved T-AOC, TXNRD, and GSH alongside decreased MDA and GSSG in the serum of piglets, and heightened T-AOC in the jejunum of piglets. Furthermore, among the two tested organic Se sources, OH-SeMet was more effective than SeY in regulating immune responses compared to SeNa. OH-SeMet reduced inflammation-related markers CRP, HP, MAP, LPS, IL-1β, IL-6, and TNF-α, some or all of which were reduced in the serum of sows and their offspring. In addition, OH-SeMet also showed reduced glucose, TG, and NEFA levels, along with elevated insulin levels in the serum of sows. Correspondingly, among the two organic forms of Se, particularly those sows fed OH-SeMet showed better gut protection for the sows’ offspring, as indicated by a reduced crypt depth and increased villus height/crypt depth ratio in the duodenum, jejunum, and ileum than those fed SeNa. Specifically, compared to SeNa or SeY, OH-SeMet upregulated the expression of selenoproteins (GPX6, TXNRD3, GPX4, and SELENON), the tight junction protein (ZO-1), and host defense peptide gene (pBD1, pBD2, pBD3, NPG3, NPG4), along with downregulating levels of inflammation factor (IL-1β, IL-6 and TNF-α) and pro-apoptotic factor (P53) in the jejunum of piglets. Taken together, OH-SeMet more effectively mitigated the adverse effects induced by heat stress in sows and their offspring. Full article

Translation regulation is essential to the survival of hosts. Most translation initiation falls under the control of the mTOR pathway, which regulates protein production from mono-methyl-guanosine (m7G) cap mRNAs. However, mTOR does not regulate all translation; hosts and viruses alike employ alternative pathways, protein factors, and internal ribosome entry sites to bypass mTOR. Trimethylguanosine (TMG)-caps arise from hypermethylation of pre-existing m7G-caps by the enzyme TGS1 and are modifications known for snoRNA, snRNA, and telomerase RNA. New findings originating from HIV-1 research reveal that TMG-caps are present on mRNA and license translation via an mTOR-independent pathway. Research has identified TMG-capping of selenoprotein mRNAs, junD, TGS1, DHX9, and retroviral transcripts. TMG-mediated translation may be a missing piece for understanding protein synthesis in cells with little mTOR activity, including HIV-infected resting T cells and nonproliferating cancer cells. Viruses display a nuanced interface with mTOR and have developed strategies that take advantage of the delicate interplay between these translation pathways. This review covers the current knowledge of the TMG-translation pathway. We discuss the intimate relationship between metabolism and translation and explore how this is exploited by HIV-1 in the context of CD4+ T cells. We postulate that co-opting both translation pathways provides a winning strategy for HIV-1 to dictate the sequential synthesis of its proteins and balance viral production with host cell survival. Full article

Selenoproteins contain selenium (Se), which is included in the 21st proteinogenic amino acid selenocysteine (Sec). Selenium (Se) is an essential trace element that exerts its biological actions mainly through selenoproteins. Selenoproteins have crucial roles in maintaining healthy brain activity. At the same time, brain-function-associated selenoproteins may also be involved in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The selenoproteins GPx4 (glutathione peroxidase 4), GPx1 (glutathione peroxidase 1), SELENOP (selenoprotein P), SELENOK (selenoprotein K), SELENOS (selenoprotein S), SELENOW (selenoprotein W), and SELENOT (selenoprotein T) are highly expressed, specifically in AD-related brain regions being closely correlated to brain function. Only a few selenoproteins, mentioned above (especially SELENOP), can bind transition and heavy metals. Metal ion homeostasis accomplishes the vital physiological function of the brain. Dyshomeostasis of these metals induces and entertains neurodegenerative diseases. In this review, we described some of the proposed and established mechanisms underlying the actions and properties of the above-mentioned selenoproteins having the characteristic feature of binding transition or heavy metals. Full article

Lead (Pb), a heavy metal environmental pollutant, poses a threat to the health of humans and birds. Inflammation is one of the most common pathological phenomena in the case of illness and poisoning. However, the underlying mechanisms of inflammation remain unclear. The cerebellum and the thalamus are important parts of the nervous system. To date, there have been no reports of Pb inducing inflammation in animal cerebellums or thalami. Selenium (Se) can relieve Pb poisoning. Therefore, we aimed to explore the mechanism by which Se alleviates Pb toxicity to the cerebellums and thalami of chickens by establishing a chicken Pb or/and Se treatment model. Our results demonstrated that exposure to Pb caused inflammatory damage in cerebellums and thalami, evidenced by the characteristics of inflammation, the decrease in anti-inflammatory factors (interleukin (IL)-2 and interferon-γ (INF-γ)), and the increase in pro-inflammatory factors (IL-4, IL-6, IL-12β, IL-17, and nitric oxide (NO)). Moreover, we found that the IL-2/IL-17–NO pathway took part in Pb-caused inflammatory injury. The above findings were reversed by the supplementation of dietary Se, meaning that Se relieved inflammatory damage caused by Pb via the IL-2/IL-17–NO pathway. In addition, an up-regulated oxidative index malondialdehyde (MDA) and two down-regulated antioxidant indices (glutathione (GSH) and total antioxidant capacity (TAC)) were recorded after the chickens received Pb stimulation, indicating that excess Pb caused an oxidant/antioxidant imbalance and oxidative stress, and the oxidative stress mediated inflammatory damage via the GSH–IL-2 axis. Interestingly, exposure to Pb inhibited four glutathione peroxidase (GPx) family members (GPx1, GPx2, GPx3, and GPx4), three deiodinase (Dio) family members (Dio1, Dio2, and Dio3), and fifteen other selenoproteins (selenophosphate synthetase 2 (SPS2), selenoprotein (Sel)H, SelI, SelK, SelM, SelO, SelP1, SelPb, SelS, SelT, SelU, and selenoprotein (Sep)n1, Sepw1, Sepx1, and Sep15), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the SPS2–GPx1–GSH pathway. Se supplementation, as expected, reversed the changes mentioned above, indicating that Se supplementation improved antioxidant capacity and mitigated oxidative stress in chickens. For the first time, we discovered that the SPS2–GPx1–GSH–IL-2/IL-17–NO pathway is involved in the complex inflammatory damage mechanism caused by Pb in chickens. In conclusion, this study demonstrated that Se relieved Pb-induced oxidative stress and inflammatory damage via the SPS2–GPx1–GSH–IL-2/IL-17–NO pathway in the chicken nervous system. This study offers novel insights into environmental pollutant-caused animal poisoning and provides a novel theoretical basis for the detoxification effect of Se against oxidative stress and inflammation caused by toxic pollutants. Full article

Peripheral blood lymphocytes (PBLs), which play a pivotal role in orchestrating the immune system, garner minimal attention in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The impact of primary liver cancers on PBLs remains unexplored. In this study, flow cytometry facilitated the quantification of cell populations, while transcriptome of PBLs was executed utilizing 10× single-cell sequencing technology. Additionally, pertinent cases were curated from the GEO database. Subsequent bioinformatics and statistical analyses were conducted utilizing R (4.2.1) software. Elevated counts of NK cells and CD8+ T cells were observed in both ICC and HCC when compared to benign liver disease (BLD). In the multivariate Cox model, NK cells and CD8+ T cells emerged as independent risk factors for recurrence-free survival. Single-cell sequencing of PBLs uncovered the downregulation of TGFβ signaling in tumor-derived CD8+ T cells. Pathway enrichment analysis, based on differential expression profiling, highlighted aberrations in selenium metabolism. Proteomic analysis of preoperative and postoperative peripheral blood samples from patients undergoing tumor resection revealed a significant upregulation of SELENBP1 and a significant downregulation of SEPP1. Primary liver cancer has a definite impact on PBLs, manifested by alterations in cellular quantities and selenoprotein metabolism. Full article

Selenocysteine (Sec) was discovered as the 21st genetically encoded amino acid. In nature, site-directed incorporation of Sec into proteins requires specialized biosynthesis and recoding machinery that evolved distinctly in bacteria compared to archaea and eukaryotes. Many organisms, including higher plants and most fungi, lack the Sec-decoding trait. We review the discovery of Sec and its role in redox enzymes that are essential to human health and important targets in disease. We highlight recent genetic code expansion efforts to engineer site-directed incorporation of Sec in bacteria and yeast. We also review methods to produce selenoproteins with 21 or more amino acids and approaches to delivering recombinant selenoproteins to mammalian cells as new applications for selenoproteins in synthetic biology. Full article

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. Full article

Selenium (Se) is a metalloid that is recognized as one of the vital trace elements in our body and plays multiple biological roles, largely mediated by proteins containing selenium—selenoproteins. Selenoproteins mainly have oxidoreductase functions but are also involved in many different molecular signaling pathways, physiological roles, and complex pathogenic processes (including, for example, teratogenesis, neurodegenerative, immuno-inflammatory, and obesity development). All of the selenoproteins contain one selenocysteine (Sec) residue, with only one notable exception, the selenoprotein P (SELENOP), which has 10 Sec residues. Although these mechanisms have been studied intensely and in detail, the characteristics and functions of many selenoproteins remain unknown. This review is dedicated to the recent data describing the identity and the functions of several selenoproteins that are less known than glutathione peroxidases (Gpxs), iodothyronine deiodinases (DIO), thioredoxin reductases (TRxRs), and methionine sulfoxide reductases (Msrs) and which are named after alphabetical letters (i.e., F, H, I, K, M, N, O, P, R, S, T, V, W). These “alphabet” selenoproteins are involved in a wide range of physiological and pathogenetic processes such as antioxidant defense, anti-inflammation, anti-apoptosis, regulation of immune response, regulation of oxidative stress, endoplasmic reticulum (ER) stress, immune and inflammatory response, and toxin antagonism. In selenium deficiency, the “alphabet” selenoproteins are affected hierarchically, both with respect to the particular selenoprotein and the tissue of expression, as the brain or endocrine glands are hardly affected by Se deficiency due to their equipment with LRP2 or LRP8. Full article

Cardiac lipotoxicity is an important contributor to cardiovascular complications during obesity. Given the fundamental role of the endoplasmic reticulum (ER)-resident Selenoprotein T (SELENOT) for cardiomyocyte differentiation and protection and for the regulation of glucose metabolism, we took advantage of a small peptide (PSELT), derived from the SELENOT redox-active motif, to uncover the mechanisms through which PSELT could protect cardiomyocytes against lipotoxicity. To this aim, we modeled cardiac lipotoxicity by exposing H9c2 cardiomyocytes to palmitate (PA). The results showed that PSELT counteracted PA-induced cell death, lactate dehydrogenase release, and the accumulation of intracellular lipid droplets, while an inert form of the peptide (I-PSELT) lacking selenocysteine was not active against PA-induced cardiomyocyte death. Mechanistically, PSELT counteracted PA-induced cytosolic and mitochondrial oxidative stress and rescued SELENOT expression that was downregulated by PA through FAT/CD36 (cluster of differentiation 36/fatty acid translocase), the main transporter of fatty acids in the heart. Immunofluorescence analysis indicated that PSELT also relieved the PA-dependent increase in CD36 expression, while in SELENOT-deficient cardiomyocytes, PA exacerbated cell death, which was not mitigated by exogenous PSELT. On the other hand, PSELT improved mitochondrial respiration during PA treatment and regulated mitochondrial biogenesis and dynamics, preventing the PA-provoked decrease in PGC1-α and increase in DRP-1 and OPA-1. These findings were corroborated by transmission electron microscopy (TEM), revealing that PSELT improved the cardiomyocyte and mitochondrial ultrastructures and restored the ER network. Spectroscopic characterization indicated that PSELT significantly attenuated infrared spectral-related macromolecular changes (i.e., content of lipids, proteins, nucleic acids, and carbohydrates) and also prevented the decrease in membrane fluidity induced by PA. Our findings further delineate the biological significance of SELENOT in cardiomyocytes and indicate the potential of its mimetic PSELT as a protective agent for counteracting cardiac lipotoxicity. Full article

Selenium is an essential trace element for health that can only be obtained through food. However, the pathological processes of selenium deficiency in cattle have received little attention. This study investigated the effects of selenium deficiency on oxidative stress, apoptosis, inflammation, and necroptosis in the lungs of weaning calves compared with healthy calves as controls. The lung selenium content and the expression of 11 selenoproteins mRNA in selenium-deficient calves were substantially reduced compared with the controls. Pathological results showed engorged alveolar capillaries, thickened alveolar septa, and diffuse interstitial inflammation throughout the alveolar septa. The levels of GSH and T-AOC, as well as the CAT, SOD, and TrxR activities, were significantly decreased compared with healthy calves. MDA and H₂O₂ were significantly elevated. Meanwhile, the apoptosis activation in the Se-D group was validated. Next, in the Se-D group, several pro-inflammatory cytokines showed higher expression. Further research revealed that the lungs in the Se-D group experienced inflammation via hyperactive NF-κB and MAPK pathways. The high level of expression of c-FLIP, MLKL, RIPK1, and RIPK3 indicated that necroptosis also causes lung damage during selenium deficiency. Full article

As a selenium-enriched plant, Cardamine violifolia (SEC) has an excellent antioxidant function. The edibility of SEC is expected to develop new sources of organic Se supplementation for human and animal nutrition. This study was conducted to investigate the effects of SEC on laying performance and ovarian antioxidant capacity in aging laying hens. A total of 450 laying hens were assigned to five treatments. Dietary treatments included the following: a basal diet (diet without Se supplementation, CON) and basal diets supplemented with 0.3 mg/kg Se from sodium selenite (SS), 0.3 mg/kg Se from Se-enriched yeast (SEY), 0.3 mg/kg Se from SEC, or 0.3 mg/kg Se from SEC and 0.3 mg/kg Se from SEY (SEC + SEY). Results showed that supplementation with SEC tended to increase the laying rate, increased the Haugh unit of eggs, and reduced the FCR. SEC promoted ovarian cell proliferation, inhibited apoptosis, and ameliorated the maintenance of follicles. SEC, SEY, or SEC + SEY increased ovarian T-AOC and decreased MDA levels. SEC increased the mRNA abundance of ovarian selenoproteins. SEC and SEC + SEY increased the mRNA abundance of Nrf2, HO-1, and NQO1, and decreased the mRNA abundance of Keap1. These results indicate that SEC could potentially to improve laying performance and egg quality via the enhancement of ovarian antioxidant capacity. SEC exerts an antioxidant function through the modulation of the Nrf2/Keap1 signaling pathway. Full article

Aim: The single-nucleotide polymorphism (SNP) rs713041, located in the regulatory region, is required to incorporate selenium into the selenoprotein glutathione peroxidase 4 (GPX4) and has been found to have functional consequences. This systematic review aimed to conduct a meta-analysis to determine whether there is an association between GPX4 (rs713041) SNP and the risk of diseases in humans and its correlation with selenium status. Material and methods: A systematic search for English-language manuscripts published between January 1990 and November 2022 was carried out using six databases: CINAHL, Cochrane, Medline, PubMed, Scopus and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess a relationship between GPX4 (rs713041) SNP and the risk of different diseases based on three genetic models. Review Manager 5.4 and Comprehensive Meta-Analysis 4 software were used to perform the meta-analysis and carry out Egger’s test for publication bias. Results: Data from 21 articles were included in the systematic review. Diseases were clustered according to the physiological system affected to understand better the role of GPX4 (rs713041) SNP in developing different diseases. Carriers of the GPX4 (rs173041) T allele were associated with an increased risk of developing colorectal cancer in additive and dominant models (p = 0.02 and p = 0.004, respectively). In addition, carriers of the T allele were associated with an increased risk of developing stroke and hypertension in the additive, dominant and recessive models (p = 0.002, p = 0.004 and p = 0.01, respectively). On the other hand, the GPX4 (rs713041) T allele was associated with a decreased risk of developing pre-eclampsia in the additive, dominant and recessive models (p < 0.0001, p = 0.002 and p = 0.0005, respectively). Moreover, selenium levels presented lower mean values in cancer patients relative to control groups (SMD = −0.39 µg/L; 95% CI: −0.64, −0.14; p = 0.002, I² = 85%). Conclusion: GPX4 (rs713041) T allele may influence colorectal cancer risk, stroke, hypertension and pre-eclampsia. In addition, low selenium levels may play a role in the increased risk of cancer. Full article

This study aimed to discover the immunomodulatory effect of selenium nanoparticles (SeNPs) on the functional state of neutrophils in vivo. Intraperitoneal injections of SeNPs (size 100 nm) 2.5 mg/kg/daily to BALB/c mice for a duration of 7–28 days led to the development of an inflammatory reaction, which was registered by a significant increase in the number of neutrophils released from the peritoneal cavity, as well as their activated state, without additional effects. At the same time, subcutaneous injections of the same SeNPs preparations at concentrations of 0.1, 0.5, and 2.5 mg/kg, on the contrary, modulated the functional state of neutrophils depending on the concentration and duration of SeNPs administration. With the use of fluorescence spectroscopy, chemiluminescence, biochemical methods, and PCR analysis, it was found that subcutaneous administration of SeNPs (0.1, 0.5, and 2.5 mg/kg) to mice for a short period of time (7–14 days) leads to modification of important neutrophil functions (adhesion, the number of migrating cells into the peritoneal cell cavity, ROS production, and NET formation). The obtained results indicated the immunostimulatory and antioxidant effects of SeNPs in vivo during short-term administration, while the most pronounced immunomodulatory effects of SeNPs were observed with the introduction of a low concentration of SeNPs (0.1 mg/kg). Increase in the administration time of SeNPs (0.1 mg/kg or 2.5 mg/kg) up to 28 days led to a decrease in the adhesive abilities of neutrophils and suppression of the expression of mRNA of adhesive molecules, as well as proteins involved in the generation of ROS, with the exception of NOX2; there was a tendency to suppress gene expression pro-inflammatory factors, which indicates the possible manifestation of immunosuppressive and anti-inflammatory effects of SeNPs during their long-term administration. Changes in the expression of selenoproteins also had features depending on the concentration and duration of the administered SeNPs. Selenoprotein P, selenoprotein M, selenoprotein S, selenoprotein K, and selenoprotein T were the most sensitive to the introduction of SeNPs into the mouse organism, which indicates their participation in maintaining the functional status of neutrophils, and possibly mediated the immunomodulatory effect of SeNPs. Full article

Co-translational incorporation of selenocysteine (Sec) into selenoproteins occurs at UGA codons in a process in which translational elongation competes with translational termination. Selenocysteine insertion sequence-binding protein 2 (SECISBP2) greatly enhances Sec incorporation into selenoproteins by interacting with the mRNA, ribosome, and elongation factor Sec (EFSEC). Ribosomal profiling allows to study the process of UGA re-coding in the physiological context of the cell and at the same time for all individual selenoproteins expressed in that cell. Using HAP1 cells expressing a mutant SECISBP2, we show here that high-resolution ribosomal profiling can be used to assess read-through efficiency at the UGA in all selenoproteins, including those with Sec close to the C-terminus. Analysis of ribosomes with UGA either at the A-site or the P-site revealed, in a transcript-specific manner, that SECISBP2 helps to recruit tRNA^Sec and stabilize the mRNA. We propose to assess the effect of any perturbation of UGA read-through by determining the proportion of ribosomes carrying UGA in the P-site, pUGA. An additional, new observation is frameshifting that occurred 3′ of the UGA/Sec codon in SELENOF and SELENOW in SECISBP2-mutant HAP1 cells, a finding corroborated by reanalysis of neuron-specific Secisbp2^R543Q-mutant brains. Full article