Selenium Deficiency as a Risk Factor for Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a multifactorial disease. Although the specific aetiology and pathogenesis of PPCM are unknown, several hypotheses have been proposed, including selenium deficiency. However, the risk of PPCM from selenium deficiency was not previously quantified. This posthoc analysis of peripartum cardiomyopathy in Nigeria (PEACE) registry data aimed to determine if selenium deficiency is an independent risk factor for PPCM. METHODS: Apparently healthy women who delivered within the previous 8 weeks and PPCM patients in Kano, Nigeria, were compared for selenium deficiency (<70µg/L) and other relevant socio-demographic and clinical characteristics. Selenium level was measured at recruitment for each subject. Independent predictors of PPCM were determined using logistic regression models. RESULTS: 159 PPCM patients and 90 age-matched controls were consecutively recruited. 84.9% of the patients and 3.3% of controls had selenium deficiency. Selenium deficiency independently increased the odds for PPCM by 167-fold while both unemployment and lack of formal education independently increased the odds by 3.4-fold. CONCLUSION: Selenium deficiency was highly prevalent among PPCM patients in Kano, Nigeria, and significantly increased the odds for PPCM. These results could justify screening of women in their reproductive years for selenium deficiency, particularly those living in regions with high incidence of PPCM. The results also call for the setting up of a definitive clinical trial of selenium supplementation in PPCM patients with selenium deficiency, to further define its benefits in the treatment of PPCM.

CONTEXTE: La cardiomyopathie péripartum (CMPP) est une maladie multifactorielle. Bien que l'étiologie spécifique et la pathogenèse de la CMPP soient inconnues, plusieurs hypothèses ont été proposées, notamment la carence en sélénium. Cependant, le risque de CMPP lié à la carence en sélénium n'a pas été précédemment quantifié. Cette analyse post-hoc des données du registre de la cardiomyopathie péripartum au Nigéria (PEACE) visait à déterminer si la carence en sélénium est un facteur de risque indépendant de la CMPP. MÉTHODES: Des femmes apparemment en bonne santé ayant accouché dans les 8 semaines précédentes et des patientes atteintes de CMPP à Kano, au Nigéria, ont été comparées pour la carence en sélénium (<70µg/L) et d'autres caractéristiques socio-démographiques et cliniques pertinentes. Le taux de sélénium a été mesuré au recrutement pour chaque sujet. Les prédicteurs indépendants de la CMPP ont été déterminés à l'aide de modèles de régression logistique. RÉSULTATS: 159 patientes atteintes de CMPP et 90 témoins appariés selon l'âge ont été recrutés consécutivement. 84,9% des patientes et 3,3% des témoins présentaient une carence en sélénium. La carence en sélénium augmentait indépendamment les chances de CMPP de 167 fois, tandis que le chômage et le manque d'éducation formelle augmentaient indépendamment les chances de 3,4 fois. CONCLUSION: La carence en sélénium était très répandue parmi les patientes atteintes de CMPP à Kano, au Nigéria, et augmentait significativement les chances de CMPP. Ces résultats pourraient justifier le dépistage de la carence en sélénium chez les femmes en âge de procréer, en particulier celles vivant dans des régions à forte incidence de CMPP. Les résultats appellent également à la mise en place d'un essai clinique définitif sur la supplémentation en sélénium chez les patientes atteintes de CMPP présentant une carence en sélénium, afin de définir davantage ses avantages dans le traitement de la CMPP. MOTS-CLÉS: Cardiomyopathie Péripartum; Carence en Sélénium; Facteur de Risque.

Comparative Analysis of Differentially Expressed Genes in Chondrocytes from Rats Exposed to Low Selenium and T-2 Toxin.

The aim of this study was to construct rat models of environmental risk factors for Kashin-Beck disease (KBD) with low selenium and T-2 toxin levels and to screen the differentially expressed genes (DEGs) between the rat models exposed to environmental risk factors. The Se-deficient (SD) group and T-2 toxin exposure (T-2) group were constructed. Knee joint samples were stained with hematoxylin-eosin, and cartilage tissue damage was observed. Illumina high-throughput sequencing technology was used to detect the gene expression profiles of the rat models in each group. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were performed and five differential gene expression results were verified by quantitative real-time polymerase chain reaction (qRT‒PCR). A total of 124 DEGs were identified from the SD group, including 56 upregulated genes and 68 downregulated genes. A total of 135 DEGs were identified in the T-2 group, including 68 upregulated genes and 67 downregulated genes. The DEGs were significantly enriched in 4 KEGG pathways in the SD group and 9 KEGG pathways in the T-2 group. The expression levels of Dbp, Pc, Selenow, Rpl30, and Mt2A were consistent with the results of transcriptome sequencing by qRT‒PCR. The results of this study confirmed that there were some differences in DEGs between the SD group and the T-2 group and provided new evidence for further exploration of the etiology and pathogenesis of KBD.

Synergistic effects of T-2 toxin and selenium deficiency exacerbate renal fibrosis through modulation of the ERα/PI3K/Akt signaling pathway.

As common pathogenic agents in the world and widely distributed globally, T-2 toxin and selenium deficiency might exacerbate toxic effects by combined exposure, posing a dramatic health hazard to humans and animals. In this study, we aim to elucidate the underlying mechanisms of renal fibrosis triggered by T-2 toxin and selenium deficiency exposure. A total of thirty-two rats are randomly divided into the normal control, T-2 toxin, selenium deficiency, and combined intervention groups. T-2 toxin (100 ng/g) is intragastric gavaged to the rats in compliance with the body weight. Both the standard (containing selenium 0.20 mg/Kg) and selenium-deficient (containing selenium 0.02 mg/Kg) diets were manufactured adhering to the AIN-93 formula. After 12 weeks of intervention, renal tissue ultrastructural and pathological changes, inflammatory infiltration, epithelial mesenchymal transition (EMT), and extracellular matrix (ECM) deposition are evaluated, respectively. Metabolomics analysis is conducted to explore the underlying pathology of renal fibrosis, followed by the validation of potential mechanisms at gene and protein levels. T-2 toxin and selenium deficiency exposure results in podocyte foot process elongation or fusion, tubular vacuolization and dilatation, and collagen deposition in the kidneys. Additionally, it also increases inflammatory infiltration, EMT conversion, and ECM deposition. Metabolomics analysis suggests that T-2 toxin and selenium deficiency influence amino acid and cholesterol metabolism, respectively, and the estrogen signaling pathway is probably engaged in renal fibrosis progression. Moreover, T-2 toxin and selenium deficiency are found to regulate the expressions of the ERα/PI3K/Akt signaling pathway. In conclusion, T-2 toxin and selenium deficiency synergistically exacerbate renal fibrosis through regulating the ERα/PI3K/Akt signaling pathway, and inflammatory infiltration, EMT and ECM deposition are involved in this process.

Bisphenol A Regulates the TNFR1 Pathway and Excessive ROS Mediated by miR-26a-5p/ADAM17 Axis to Aggravate Selenium Deficiency-Induced Necroptosis in Broiler Veins.

Selenium (Se) deficiency can affect the expression of microRNA (miRNA) and induce necroptosis, apoptosis, etc., resulting in damage to various tissues and organs. Bisphenol A (BPA) exposure can cause adverse consequences such as oxidative stress, endothelial dysfunction, and atherosclerosis. The toxic effects of combined treatment with Se-deficiency and BPA exposure may have a synergistic effect. We replicated the BPA exposure and Se-deficiency model in broiler to investigate whether the combined treatment of Se-deficiency and BPA exposure induced necroptosis and inflammation of chicken vascular tissue via the miR-26A-5p/ADAM17 axis. We found that Se deficiency and BPA exposure significantly inhibited the expression of miR-26a-5p and increased the expression of ADAM17, thereby increasing reactive oxygen species (ROS) production. Subsequently, we discovered that the tumor necrosis factor receptor (TNFR1), which was highly expressed, activated the necroptosis pathway through receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed-lineage kinase domain-like (MLKL), and regulated the heat shock proteins-related genes expressions and inflammation-related genes expressions after exposure to BPA and selenium deficiency. In vitro, we found that miR-26a-5p knockdown and increased ADAM17 can induce necroptosis by activating the TNFR1 pathway. Similarly, both N-Acetyl-L-cysteine (NAC), Necrostatin-1 (Nec-1), and miR-26a-5p mimic prevented necroptosis and inflammation caused by BPA exposure and Se deficiency. These results suggest that BPA exposure activates the miR-26a-5p/ADAM17 axis and exacerbates Se deficient-induced necroptosis and inflammation through the TNFR1 pathway and excess ROS. This study lays a data foundation for future ecological and health risk assessments of nutrient deficiencies and environmental toxic pollution.

Selenium deficiency exacerbated Bisphenol A-induced intestinal toxicity in chickens: Apoptosis and cell cycle arrest mediated by ROS/P53.

Bisphenol A (BPA) is a phenolic organic synthetic compound that is used as the raw material of polycarbonate plastics, and its safety issues have recently attracted wide attention. Selenium (Se) deficiency has gradually developed into a global disease affecting intestinal function via oxidative stress and apoptosis. However, the toxic effects and potential mechanisms of BPA exposure and Se deficiency in the chicken intestines have not been studied. In this study, BPA exposure and/or Se deficiency models were established in vivo and in vitro to investigate the effects of Se deficiency and BPA on chicken jejunum. The results showed that BPA exposure and/or Se deficiency increased jejunum oxidative stress and DNA damage, activated P53 pathway, led to mitochondrial dysfunction, and induced apoptosis and cell cycle arrest. Using protein-protein molecular docking, we found a strong binding ability between P53 and peroxisome proliferator-activated receptor γ coactivator-1, thereby regulating mitochondrial dysfunctional apoptosis. In addition, we used N-acetyl-L-cysteine and pifithrin-α for in vitro intervention and found that N-acetyl-L-cysteine and pifithrin-α intervention reversed the aforementioned adverse effects. This study clarified the potential mechanism by which Se deficiency exacerbates BPA induced intestinal injury in chickens through reactive oxygen species/P53, which provides a new idea for the study of environmental combined toxicity of Se deficiency, and insights into animal intestinal health from a new perspective.

Extracellular Vesicles Derived from Selenium-Deficient MAC-T Cells Aggravated Inflammation and Apoptosis by Triggering the Endoplasmic Reticulum (ER) Stress/PI3K-AKT-mTOR Pathway in Bovine Mammary Epithelial Cells.

Selenium (Se) deficiency disrupts intracellular REDOX homeostasis and severely deteriorates immune and anti-inflammatory function in high-yielding periparturient dairy cattle. To investigate the damage of extracellular vesicles derived from Se-deficient MAC-T cells (SeD-EV) on normal mammary epithelial cells, an in vitro model of Se deficiency was established. Se-deficient MAC-T cells produced many ROS, promoting apoptosis and the release of inflammatory factors. Extracellular vesicles were successfully isolated by ultrahigh-speed centrifugation and identified by transmission electron microscopy, particle size analysis, and surface markers (CD63, CD81, HSP70, and TSG101). RNA sequencing was performed on exosomal RNA. A total of 9393 lncRNAs and 63,155 mRNAs transcripts were identified in the SeC and SeD groups, respectively, of which 126 lncRNAs and 955 mRNAs were differentially expressed. Furthermore, SeD-EV promoted apoptosis of normal MAC-T cells by TUNEL analysis. SeD-EV significantly inhibited Bcl-2, while Bax and Cleaved Caspase3 were greatly increased. Antioxidant capacity (CAT, T-AOC, SOD, and GSH-Px) was inhibited in SeD-EV-treated MAC-T cells. Additionally, p-PERK, p-eIF2α, ATF4, CHOP, and XBP1 were all elevated in MAC-T cells supplemented with SeD-EV. In addition, p-PI3K, p-Akt, and p-mTOR were decreased strikingly by SeD-EV. In conclusion, SeD-EV caused oxidative stress, thus triggering apoptosis and inflammation through endoplasmic reticulum stress and the PI3K-Akt-mTOR signaling pathway, which contributed to explaining the mechanism of Se deficiency causing mastitis.

Comparative Analysis of Gut Microbiota from Rats Induced by Se Deficiency and T-2 Toxin.

The aim of this study was to analyze the differences in gut microbiota between selenium deficiency and T-2 toxin intervention rats. Knee joint and fecal samples of rats were collected. The pathological characteristics of knee cartilage were observed by safranin O/fast green staining. DNA was extracted from fecal samples for PCR amplification, and 16S rDNA sequencing was performed to compare the gut microbiota of rats. At the phylum level, Firmicutes (81.39% vs. 77.06%) and Bacteroidetes (11.11% vs. 14.85%) were dominant in the Se-deficient (SD) group and T-2 exposure (T-2) groups. At the genus level, the relative abundance of Ruminococcus_1 (12.62%) and Ruminococcaceae_UCG-005 (10.31%) in the SD group were higher. In the T-2 group, the relative abundance of Lactobacillus (11.71%) and Ruminococcaceae_UCG-005 (9.26%) were higher. At the species level, the high-quality bacteria in the SD group was Ruminococcus_1_unclassified, and Ruminococcaceae_UCG-005_unclassified in the T-2 group. Lactobacillus_sp__L_YJ and Lactobacillus_crispatus were the most significant biomarkers in the T-2 group. This study analyzed the different compositions of gut microbiota in rats induced by selenium deficiency and T-2 toxin, and revealed the changes in gut microbiota, so as to provide a certain basis for promoting the study of the pathogenesis of Kashin-Beck disease (KBD).

Selenium in Infants and Preschool Children Nutrition: A Literature Review.

Selenium (Se), an essential trace element, is fundamental to human health, playing an important role in the formation of thyroid hormones, DNA synthesis, the immune response, and fertility. There is a lack of comprehensive epidemiological research, particularly the serum Se concetration in healthy infants and preschool children compared to the estimated dietary Se intake. However, Se deficiencies and exceeding the UL have been observed in infants and preschool children. Despite the observed irregularities in Se intake, there is a lack of nutritional recommendations for infants and preschool children. Therefore, the main objective of this literature review was to summarize what is known to date about Se levels and the risk of deficiency related to regular consumption in infants and preschool children.

Widespread selenium deficiency in the brain of cases with Huntington's disease presents a new potential therapeutic target.

BACKGROUND: Huntington or Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterised by both progressive motor and cognitive dysfunction; its pathogenic mechanisms remain poorly understood and no treatment can currently slow, stop, or reverse its progression. There is some evidence of metallomic dysfunction in limited regions of the HD brain; we hypothesised that these alterations are more widespread than the current literature suggests and may contribute to pathogenesis in HD. METHODS: We measured the concentrations of eight essential metals (sodium, potassium, magnesium, calcium, iron, zinc, copper, and manganese) and the metalloid selenium across 11 brain regions in nine genetically confirmed, clinically manifest cases of HD and nine controls using inductively-coupled plasma mass spectrometry. Case-control differences were assessed by non-parametric Mann-Whitney U test (p < 0.05), risk ratios, E-values, and effect sizes. FINDINGS: We observed striking decreases in selenium levels in 11 out of 11 investigated brain regions in HD, with risk ratios and effect sizes ranging 2.3-9.0 and 0.7-1.9, respectively. Increased sodium/potassium ratios were observed in every region (risk ratio = 2.5-8.0; effect size = 1.2-5.8) except the substantia nigra (risk ratio = 0.25; effect size = 0.1). Multiple regions showed increased calcium and/or zinc levels, and localised decreases in iron, copper, and manganese were present in the globus pallidus, cerebellum, and substantia nigra, respectively. INTERPRETATION: The observed metallomic alterations in the HD brain may contribute to several pathogenic mechanisms, including mitochondrial dysfunction, oxidative stress, and blood-brain barrier dysfunction. Selenium supplementation may represent a potential, much-needed therapeutic pathway for the treatment of HD that would not require localised delivery in the brain due to the widespread presence of selenium deficiency in regions that show both high and low levels of neurodegeneration. FUNDING: In Acknowledgments, includes the Lee Trust, the Endocore Research Trust, Cure Huntington's Disease Initiative, the Oakley Mental Health Research Foundation, the Medical Research Council (MRC), the New Zealand Neurological Foundation, and others.

The effect of selenium supplementation in pregnant women on maternal, fetal, and newborn outcomes: a systematic review and meta-analysis.

OBJECTIVE: Low maternal selenium status has been associated with poor pregnancy outcomes, including preterm birth. This study aimed to evaluate available evidence of the effects of selenium supplementation during pregnancy on preterm birth and related maternal, fetal, and newborn outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, Global Index Medicus, and the Cochrane Library were systematically searched on June 23, 2022, without language or time restrictions. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and nonrandomized interventional studies were included if they compared the effects of selenium supplementation with placebo or no treatment among pregnant women. The review protocol was registered in the International Prospective Register of Systematic Reviews (identification number: CRD42022383669). METHODS: For outcomes reported by ≥1 study, a meta-analysis was conducted. Because of the small number of studies and high clinical heterogeneity between populations, random-effects models were used. The Risk of Bias 2 and Risk Of Bias In Non-randomized Studies - of Interventions tools were used to assess study quality, and Grading of Recommendations Assessment, Development, and Evaluation analysis was used to determine the certainty of evidence for each outcome. RESULTS: Literature searches identified 5105 unique records, and 32 studies met the eligibility criteria. Of note, 11 reports were not included for analysis following research integrity assessments. Moreover, 10 trials and 3 observational studies met the inclusion criteria; however, only 8 trials (1851 women) and 1 prospective cohort study (71,728 women) reported on at least 1 review outcome. Our results could not determine the effect of selenium supplementation on preterm birth at <37 weeks of gestation (relative risk, 0.65; 95% confidence interval, 0.26-1.63; very low certainty evidence) and <34 weeks of gestation (relative risk, 1.05; 95% confidence interval, 0.59-1.44; very low certainty evidence). CONCLUSION: There is limited evidence on the effects of selenium supplementation during pregnancy. Further trials, with larger sample sizes, more representative populations, and reliable assessment of maternal selenium status at trial entry, are required.

New insights into brain injury in chickens induced by bisphenol A and selenium deficiency-Mitochondrial reactive oxygen species and mitophagy-apoptosis crosstalk homeostasis.

Bisphenol A (BPA), a component of plastic products, can penetrate the blood-brain barrier and pose a threat to the nervous system. Selenium (Se) deficiency can also cause nervous system damage. Resulting from the rapid industrial development, BPA pollution and Se deficiency often coexist. However, it is unclear whether brain damage in chickens caused by BPA exposure and Se deficiency is related to the crosstalk disorder between mitophagy and apoptosis. In this study, 60 chickens (1 day old) were fed with a diet that contained 20 mg/kg BPA but was insufficient in Se (only 0.039 mg/kg) for 42 days to establish a chicken brain injury model. In vitro, the primary chicken embryo brain neurons were treated for 24 h with Se-deficient medium containing 75 µM BPA. The results showed that BPA exposure and Se deficiency inhibited the expression of the mitochondrial respiratory chain complex in brain neurons, and a large number of mitochondrial reactive oxygen species were released. Furthermore, the expression levels of mitochondrial fusion proteins (OPA1, Mfn1, and Mfn2) decreased, while the expression levels of mitochondrial fission proteins (Drp1, Mff, and Fis1) increased, thus exacerbating mitochondrial division. In addition, the results of immunofluorescence and flow cytometry analysis, as well as the elevated expressions of mitophagy related genes (PINK1, Parkin, ATG5, and LC3II/I) and pro-apoptotic markers (Bax, Cytc, Caspase3, and Caspase9) indicated that BPA exposure and Se deficiency disrupted the crosstalk homeostasis between mitophagy and apoptosis. However, this crosstalk homeostasis was restored after Mito-Tempo and Rapamycin treatment. In contrast, 3-methyladenine treatment exacerbated this crosstalk disorder. In conclusion, BPA exposure and Se deficiency can induce mitochondrial reactive oxygen species bursts and disorders of mitochondrial dynamics by destroying the mitochondrial respiratory chain complex. The result is indicative of an imbalance in mitochondrial autophagy and apoptosis crosstalk homeostasis, which damages the chicken brain.

Proposal to Screen for Zinc and Selenium in Patients with IgA Deficiency.

The increase in life expectancy can be a consequence of the world's socioeconomic, sanitary and nutritional conditions. Some studies have demonstrated that individuals with a satisfactory diet variety score present a lower risk of malnutrition and better health status. Zinc and selenium are important micronutrients that play a role in many biochemical and physiological processes of the immune system. Deficient individuals can present both innate and adaptive immunity abnormalities and increased susceptibility to infections. Primary immunodeficiency diseases, also known as inborn errors of immunity, are genetic disorders classically characterized by an increased susceptibility to infection and/or dysregulation of a specific immunologic pathway. IgA deficiency (IgAD) is the most common primary antibody deficiency. This disease is defined as serum IgA levels lower than 7 mg/dL and normal IgG and IgM levels in individuals older than four years. Although many patients are asymptomatic, selected patients suffer from different clinical complications, such as pulmonary infections, allergies, autoimmune diseases, gastrointestinal disorders and malignancy. Knowing the nutritional status as well as the risk of zinc and selenium deficiency could be helpful for the management of IgAD patients. OBJECTIVES: to investigate the anthropometric, biochemical, and nutritional profiles and the status of zinc and selenium in patients with IgAD. METHODS: in this descriptive study, we screened 16 IgAD patients for anthropometric and dietary data, biochemical evaluation and determination of plasma and erythrocyte levels of zinc and selenium. RESULTS: dietary intake of zinc and selenium was adequate in 75% and 86% of the patients, respectively. These results were consistent with the plasma levels (adequate levels of zinc in all patients and selenium in 50% of children, 25% of adolescents and 100% of adults). However, erythrocyte levels were low for both micronutrients (deficiency for both in 100% of children, 75% of adolescents and 25% of adults). CONCLUSION: our results highlight the elevated prevalence of erythrocyte zinc and selenium deficiency in patients with IgAD, and the need for investigation of these micronutrients in their follow-up.

Comparative Assessment of Serum Selenium Status in HIV-Infected and Non-infected Children: A Pilot Study in a Tertiary Hospital in Nigeria.

Background Selenium is an essential micronutrient that plays a crucial role in a wide range of physiological processes, including immune responses. Selenium deficiency has been recognized as an associated factor in the progression of HIV to advanced HIV disease and/or mortality. Although selenium supplementation has been shown to reduce hospitalizations and improve cellular immunity, the evidence remains mixed. This study aimed to determine the prevalence of selenium deficiency and its relationship with HIV disease markers in HIV-infected children at the Lagos University Teaching Hospital. Methodology This is a cross-sectional, comparative, pilot study of plasma concentrations of selenium in HIV-infected (n = 30) and non-infected (n = 20) children enrolled in the pediatric HIV clinic of the Lagos University Teaching Hospital, Lagos, Nigeria, from May 2019 to May 2021. HIV-infected children were on stable antiretroviral therapy (ART) with an undetectable viral load. The serum concentration of selenium was measured using the automated atomic absorption spectrophotometer (hydride generation method). Logistic regression was used to study the effect of selenium status on the levels of HIV disease markers (CD4 count, viral load, weight, opportunistic infections) in the study participants. Results The median age of all participants was nine (4-12) years, with 74% being boys. The mean selenium concentrations were lower in HIV-infected children (91.1 ± 12.0 µg/L) compared to the comparison group without HIV (147.8 ± 4.9 µg/L) (p = 0.001). After controlling for age, ART duration, markers of HIV infection, and other potentially confounding variables, participants with selenium deficiency had approximately 11-fold odds of increased hospital admissions (adjusted odds ratio = 10.57, 95% confidence interval = 1.58 to 70.99; p = 0.015). Conclusions In this study, selenium concentrations were significantly lower in HIV-infected children than in the HIV-negative comparison group. Lower serum selenium concentrations were associated with increased hospitalizations. Although our findings suggest the potential need for selenium supplementation for children living with HIV in Nigeria, further studies are warranted to determine the safety and efficacy of selenium supplementation in this key population.

Selenium deficiency causes oxidative stress and activates inflammation, apoptosis, and necroptosis in the intestine of weaned calves.

Selenium performs a variety of biological functions in organisms, including antioxidant and anti-inflammatory effects. This study investigated how selenium deficiency affects weaned calves' intestines. According to Inductively coupled plasma mass spectrometry (ICP-MS) analysis of intestinal selenium concentrations in calves, the Se-D group had a significantly lower concentration of selenium. Hematoxylin-eosin staining showed that the intestinal epithelial cells were detached, the goblet cells were lost, and the intestinal villi were fragmented and loosely arranged in the Se-D group, along with hyperemia and inflammatory infiltration. Of the 22 selenoprotein genes, 9 were downregulated in response to selenium deficiency in Reverse transcription-PCR (RT-PCR), whereas 6 genes were upregulated. In the Se-D group, oxidative stress was detected by measuring redox levels in the intestines. Furthermore, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, RT-PCR, and Western blotting (WB) results indicated that both intrinsic and extrinsic apoptosis pathways are activated in the intestine during selenium deficiency. Selenium deficiency also induced necroptosis in the intestine through upregulation of MLKL, RIPK1, and RIPK3 mRNA levels. In addition, according to hematoxylin-eosin staining and ELISA, selenium-deficient calves had severe inflammation in their intestines. As a result of RT-PCR and WB analyses, we found that selenium deficiency was associated with nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Our study suggested that weaned calves' intestines are affected by selenium deficiency, which causes oxidative stress, inflammation, apoptosis, and necroptosis.

Bisphenol A aggravate selenium deficiency-induced apoptosis via miR-215-3p/Dio1 to activate ROS/PI3K/AKT pathway in chicken arterial.

Both bisphenol A (BPA) and selenium (Se) deficiency can affect the expression of microRNAs (miRNAs), which can specifically regulate its target mRNA and induce apoptosis, and play a significant role in cardiovascular injury diseases. To explore the mechanism of apoptosis induced by BPA and Se deficiency in chicken arterial endothelial tissue and the role of miRNAs in this process, the model of BPA exposure/Se deficiency in chicken and PAEC cells have been employed. The targeting relationship between miR-215-3p and iodothyronine deiodinase 1 (Dio1) in PAEC was verified by double luciferase gene report. The level of miR-215-3p was detected by qRT-PCR. The oxidative stress level of arterial endothelial cells was detected by oxidative stress kit and DCFH-DA probe method. The PI3K/AKT pathway, mitochondrial dynamics, and apoptosis-related genes were detected by qRT-PCR and western blot. The mitochondrial ATP level and nitric oxide synthases (NOSs) level were detected with the kit. TUNEL, acridine orange/ethidium bromide, and flow cytometry were used to detect the level of apoptosis. The results showed that BPA exposure and Se deficiency led to overexpression of miR-215-3p, aggravated oxidative stress, inhibited activation of PI3K/AKT pathway, promoted mitochondrial division, increased expression of apoptosis related genes, and finally led to apoptosis of chicken arterial endothelial cells. We also established knockdown/overexpression models of miR-215-3p and Dio1 in vitro, and found that overexpression of miR-215-3p and knockout of Dio1 can induce apoptosis. Interestingly, miR-215-3p-Inhibitor and N-acetyl- l-cysteine (NAC) partially prevented apoptosis caused by BPA exposure and Se deficiency, and LY294002 aggravated apoptosis. These results suggest that BPA exposure aggravates the apoptosis of Se deficient arterial endothelial cells in chickens by regulating the ROS/PI3K/AKT pathway activated by miR-215-3p/Dio1. The miR-215-3p/Dio1 axis provides a new way to understand the toxic mechanism of BPA exposure and Se deficiency, and reveals a new regulatory model of apoptosis damage in vascular diseases.

Selenium deficiency causes hypertension by increasing renal AT1 receptor expression via GPx1/H2O2/NF-κB pathway.

Epidemiological studies show an association between low body selenium and the risk of hypertension. However, whether selenium deficiency causes hypertension remains unknown. Here, we report that Sprague-Dawley rats fed a selenium-deficient diet for 16 weeks developed hypertension, accompanied with decreased sodium excretion. The hypertension of selenium-deficient rats was associated with increased renal angiotensin II type 1 receptor (AT1R) expression and function that was reflected by the increase in sodium excretion after the intrarenal infusion of the AT1R antagonist candesartan. Selenium-deficient rats had increased systemic and renal oxidative stress; treatment with the antioxidant tempol for 4 weeks decreased the elevated blood pressure, increased sodium excretion, and normalized renal AT1R expression. Among the altered selenoproteins in selenium-deficient rats, the decrease in renal glutathione peroxidase 1 (GPx1) expression was most prominent. GPx1, via regulation of NF-κB p65 expression and activity, was involved in the regulation of renal AT1R expression because treatment with dithiocarbamate (PDTC), an NF-κB inhibitor, reversed the up-regulation of AT1R expression in selenium-deficient renal proximal tubule (RPT) cells. The up-regulation of AT1R expression with GPx1 silencing was restored by PDTC. Moreover, treatment with ebselen, a GPX1 mimic, reduced the increased renal AT1R expression, Na+-K+-ATPase activity, hydrogen peroxide (H2O2) generation, and the nuclear translocation of NF-κB p65 protein in selenium-deficient RPT cells. Our results demonstrated that long-term selenium deficiency causes hypertension, which is due, at least in part, to decreased urine sodium excretion. Selenium deficiency increases H2O2 production by reducing GPx1 expression, which enhances NF-κB activity, increases renal AT1R expression, causes sodium retention and consequently increases blood pressure.

Biological Activity of Selenium and Its Impact on Human Health.

Selenium (Se) is a naturally occurring metalloid element essential to human and animal health in trace amounts but it is harmful in excess. Se plays a substantial role in the functioning of the human organism. It is incorporated into selenoproteins, thus supporting antioxidant defense systems. Selenoproteins participate in the metabolism of thyroid hormones, control reproductive functions and exert neuroprotective effects. Among the elements, Se has one of the narrowest ranges between dietary deficiency and toxic levels. Its level of toxicity may depend on chemical form, as inorganic and organic species have distinct biological properties. Over the last decades, optimization of population Se intake for the prevention of diseases related to Se deficiency or excess has been recognized as a pressing issue in modern healthcare worldwide. Low selenium status has been associated with an increased risk of mortality, poor immune function, cognitive decline, and thyroid dysfunction. On the other hand, Se concentrations slightly above its nutritional levels have been shown to have adverse effects on a broad spectrum of neurological functions and to increase the risk of type-2 diabetes. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important issue to elucidate its effect on human diseases. This review gives an overview of the role of Se in human health highlighting the effects of its deficiency and excess in the body. The biological activity of Se, mainly performed through selenoproteins, and its epigenetic effect is discussed. Moreover, a brief overview of selenium phytoremediation and rhizofiltration approaches is reported.

Single and Combined Effects of Short-Term Selenium Deficiency and T-2 Toxin-Induced Kidney Pathological Injury Through the MMPs/TIMPs System.

The single and combined effects of short-term selenium (Se) deficiency and T-2 toxin-induced kidney pathological injury through the MMPs/TIMPs system were investigated. Forty-eight rats were randomly divided into control, 10 ng/g T-2 toxin, 100 ng/g T-2 toxin, Se-deficient, 10 ng/g T-2 toxin and Se deficiency combined, and 100 ng/g T-2 toxin and Se deficiency combined groups for a 4-week intervention. The kidney Se concentration was measured to evaluate the construction of animal models of Se deficiency. Kidney tissues were analyzed by hematoxylin-eosin staining, Masson staining, and transmission electron microscope to observe the pathological changes, the severity of kidney fibrosis, and ultrastructural changes, respectively. Meanwhile, quantitative polymerase chain reaction and immunohistochemical staining were used to analyze the gene and protein expression levels of matrix metallopeptidase 2/3 (MMP2/3) and tissue inhibitor of metalloproteinase 1 (TIMP1). The results showed that short-term Se deficiency and T-2 toxin exposure can cause kidney injury through tubular degeneration and even lead to kidney fibrosis. And the combination of T-2 toxin and Se deficiency had a synergistic effect on the kidney. A dose-response effect of the T-2 toxin was also observed. At the gene and protein levels, the expression of MMP2/3 in the intervention group increased, while the expression of TIMP1 decreased compared with the control group. In conclusion, short-term Se deficiency and T-2 toxin exposure might lead to injury and even the development of fibrosis in the kidneys, and combined intervention can increase the severity with a dose-dependent trend. MMP2/3 and TIMP1 likely play a significant role in the development of kidney fibrosis.