Selenium deficiency induces irritable bowel syndrome: Analysis of UK Biobank data and experimental studies in mice.

Irritable bowel syndrome (IBS) patients exhibit significantly lower levels of serum selenium (Se) compared to healthy controls. This study integrates a prospective cohort analysis and animal experiments to investigate Se deficiency as a potential risk factor for IBS. Using data from the UK Biobank, a longitudinal analysis was conducted to explore the associations between dietary Se intake and the risk of incident IBS. In animal study, C57BL/6 mice were fed diets with normal (0.2 ppm) or low (0.02 ppm) Se levels to assess the impacts of Se deficiency on IBS symptoms. Furthermore, we performed 16 S rRNA sequencing, untargeted colonic fecal metabolomics analysis, and colon transcriptome profiling to uncover the regulatory mechanisms underlying Se deficiency-induced IBS. The analysis of UK Biobank data revealed a significant correlation between low dietary Se levels and an increased incidence of IBS. In the experimental study, a low Se diet induced IBS symptoms, evidenced by elevated abdominal withdrawal reflex scores, colon inflammation, and severe pathological damage to the colon. Additionally, the low Se diet caused disturbances in gut microbiota, characterized by an increase in Faecalibaculum and Helicobacter, and a decrease in Bifidobacterium and Akkermansia. Combined colonic fecal metabolomics and colon transcriptome analysis indicated that Se deficiency might trigger IBS through disruptions in pathways related to "bile excretion", "steroid hormone biosynthesis", "arachidonic acid metabolism", and "drug metabolism-cytochrome P450". These findings underscore the significant adverse effects of Se deficiency on IBS and suggest that Se supplementation should be considered for IBS patients.

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.

BPA exposure and Se deficiency caused spleen damage in chickens by nitrification stress-TNF-α.

With the increasing production and demand of plastic products in life, inescapable bisphenol A (BPA) exposure results in a threat to the health of organisms. Selenium (Se) is an essential trace element for living organisms. The insufficient Se intake can cause multi-tissue organ damage. In the process of production and life, the exposure of BPA is usually accompanied by Se deficiency. In this study, the models of chicken with BPA exposure and/or Se deficiency was duplicated, the status of nitrification stress, apoptosis, necroptosis, and changes in TNF-α/FADD signaling pathways in chicken spleen were examined. At the same time, nitrification stress inhibitor and TNF-α inhibitor were introduced into MSB-1 cell model tests in vitro, indicating that BPA exposure and Se deficiency up-regulated TNF-α/FADD signaling pathway through nitrification stress, inducing necroptosis and apoptosis, and heat shock protein was also involved in this process. This study provides a new control idea for healthy poultry breeding based on Se, and also provides a new reference for toxicity control of environmental pollutants.

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.

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 increased duodenal permeability and decreased expression of antimicrobial peptides by activating ROS/NF-κB signal pathway in chickens.

Selenium (Se) is an essential trace element for the body. Various organs of the body, including the intestine, are affected by its deficiency. Se deficiency can induce oxidative stress and inflammatory responses in the intestine. It can also increase intestinal permeability and decrease intestinal immune function in mammals. However, the detailed studies, conducted on the intestinal molecular mechanisms of Se deficiency-induced injury in poultry, are limited. This study explored the adverse effects of Se deficiency on intestinal permeability and its mechanism. A Se-deficient chicken model was established, and the morphological changes in the chicken duodenum tissues were observed using a light microscope and transmission electron microscope (TEM). Western blotting, qRT-PCR, and other methods were used to detect the expression levels of selenoproteins, oxidative stress indicators, inflammatory factors, tight junction (TJ) proteins, antimicrobial peptides, and other related indicators in intestinal tissues. The results showed that Se deficiency could decrease the expression levels of selenoproteins and antioxidant capacity, activate the nuclear factor kappa-B (NF-κB) pathway, cause inflammation, and decrease the expression levels of TJ proteins and antimicrobial peptides in the duodenum tissues. The study also demonstrated that Se deficiency could increase intestinal permeability and decrease antimicrobial peptides via reactive oxygen species (ROS)/NF-κB. This study provided a theoretical basis for the scientific prevention and control of Se deficiency in poultry. Se deficiency decreased the expression levels of selenoproteins and increased ROS levels to activate the NF-κB pathway, resulting in the production of pro-inflammatory cytokines, reducing the expression levels of TJ protein, and weakening the expression of antimicrobial peptides, which contributed to the higher intestinal permeability. Oxidative stress weakened the expression of antimicrobial peptides.

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.

Effects of selenium deficiency on biological results of X-ray and carbon-ion beam irradiation in mice.

The impact of radiation-induced hydrogen peroxide (H2O2) on the biological effects of X-rays and carbon-ion beams was investigated using a selenium-deficient (SeD) mouse model. Selenium is the active center of glutathione peroxidase (GSH-Px), and SeD mice lack the ability to degrade H2O2. Male and female SeD mice were prepared by feeding a torula yeast-based SeD diet and ultrapure water. Thirty-day survival rates after whole-body irradiation, radiation-induced leg contracture, and MRI-based redox imaging of the brain were assessed and compared between SeD and normal mice. Thirty-day lethality after whole-body 5.6 Gy irradiation with X-rays or carbon-ion beams was higher in the SeD mice than in the normal mice, while SeD did not give the notable difference between X-rays and carbon-ion beams. SeD also did not affect the maximum leg contracture level after irradiation with carbon-ion beams, but delayed the leg contraction rate. In addition, no marked effects of SeD were observed on variations in the redox status of the brain after irradiation. Collectively, the present results indicate that SeD slightly altered the biological effects of X-rays and/or carbon-ion beams. GSH-Px processes endogenous H2O2 generated through mitochondrial respiration, but does not have the capacity to degrade H2O2 produced by irradiation.

Bisphenol A aggravates renal apoptosis and necroptosis in selenium-deficient chickens via oxidative stress and PI3K/AKT pathway.

Bisphenol A (BPA) in the environment can have deleterious effects on humans and animals. BPA can exert nephrotoxicity by inducing oxidative stress. Selenium (Se) deficiency can specifically impair kidney tissues and additionally show a synergistic effect on the toxicity of several environmental chemicals. However, the toxic effects of BPA on the chicken kidney and whether Se deficiency produces synergistic effects on the toxicity of BPA remain poorly understood. Herein, we established BPA exposure models and Se deficiency model in vivo and in vitro, and described the discovery path of BPA aggravation on apoptosis and necroptosis in Se-deficient chicken kidneys via regulation of oxidative stress and phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. We found that BPA exposure increased reactive oxygen species and malondialdehyde levels, reduced activities of catalase, GPx, and superoxide dismutase, downregulated PI3K and AKT expressions, activated Bcl/Bax-Caspase 9-Caspase 3, and receptor-interacting protein kinase 1/mixed lineage kinase domain-like protein signaling pathways, resulting in apoptosis and necroptosis in the chicken kidney. In addition, Se deficiency significantly promoted the expression of renal apoptosis and necroptosis in BPA-exposed chicken kidneys. Altogether, our results showed that BPA aggravates apoptosis and necroptosis in Se-deficient chicken kidneys via regulation of oxidative stress and PI3K/AKT signaling pathway. Our findings elucidate the mechanism of BPA nephrotoxicity and Se deficiency exacerbation toxicity in chickens and will provide great significance for the protection of the ecological environment and animal health.

Multi-Omics Profiling Reveals Se Deficiency-Induced Redox Imbalance, Metabolic Reprogramming, and Inflammation in Pig Muscle.

BACKGROUND: Nutritional muscle dystrophy is associated with selenium (Se) deficiency; however, the underlying mechanism remains unclear. OBJECTIVES: This study aimed to understand the crosstalk among redox status, energy metabolism, and inflammation in nutritional muscle dystrophy induced by dietary Se deficiency. METHODS: Eighteen castrated male pigs (Yorkshire, 45 d old) were fed Se-deficient (Se-D; 0.007 mg Se/kg) or Se-adequate (Se-A; in the form of selenomethionine, 0.3 mg Se/kg) diets for 16 wk. The muscle Se concentrations; antioxidant capacity; and gene expression, transcriptome, global proteome, metabolome, and lipidome profiles were analyzed. The transcriptome, metabolome, and proteome profiles were analyzed with biostatistics, bioinformatics, and pathway enrichment analysis; other data were analyzed with Student's 2-sided t tests. RESULTS: The muscle Se content in the Se-D group was 96% lower than that in the Se-A group (P < 0.05). The activity of glutathione peroxidase (GPX) and thioredoxin reductase (TXNRD) in the Se-D group was 42%-69% lower than that in the Se-A group (P < 0.05). The mRNA levels of 10 selenoprotein genes were 25%-84% lower than those in the Se-A group (P < 0.05). Multi-omics analyses indicated that the levels of 1378 transcripts, 83 proteins, 22 metabolites, and 55 lipid molecules were significantly altered in response to Se deficiency. Se deficiency-induced redox imbalance led to muscle central carbon and lipid metabolism reprogramming, which enhanced the glycolysis pathway and decreased phospholipid synthesis. Inflammation and apoptosis were observed in response to Se deficiency-induced muscle oxidative stress, which may have been associated with extracellular matrix (ECM) remodeling, suppressed focal adhesion and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling, and activation of the NF-κB signaling pathway. CONCLUSIONS: These results contributed to understanding the crosstalk among redox, energy metabolism, and inflammation in Se deficiency-induced muscle dystrophy in pigs, and may provide intervention targets for muscle disease treatment.

Selenium-sensitive histone deacetylase 2 is required for forkhead box O3A and regulates extracellular matrix metabolism in cartilage.

INTRODUCTION: Selenium (Se) as well as selenoproteins are vital for osteochondral system development. Se deficiency (SeD) has a definite impact on the expression and activity of histone deacetylases (HDACs). Abnormal expression of some HDACs affects cartilage development. This current study aims to explore the relationship between differentially expressed HDACs and cartilage development, especially extracellular matrix (ECM) homeostasis maintenance, under SeD conditions. MATERIALS AND METHODS: Dark Agouti rats and C28/I2 cell line under SeD states were used to detect the differently expressed HDAC by RT-qPCR, western blotting and IHC staining. Meanwhile, the biological roles of the above HDAC in cartilage development and homeostasis maintenance were confirmed by siRNA transfection, western blotting, RNA sequence and inhibitor treatment experiments. RESULTS: HDAC2 exhibited lower expression at protein level in both animals and chondrocytes during SeD condition. The results of cell-level experiments indicated that forkhead box O3A (FOXO3A), which was required to maintain metabolic homeostasis of cartilage matrix, was reduced by HDAC2 knockdown. Meanwhile, induced HDAC2 was positively associated with FOXO3A in rat SeD model. Meanwhile, knockdown of HDAC2 and FOXO3A led to an increase of intracellular ROS level, which activated NF-κB pathway. Se supplementary significantly inhibited the activation of NF-κB pathway with IL-1ß treatment. CONCLUSION: Our results suggested that low expression of HDAC2 under SeD condition increased ROS content by decreasing FOXO3A in chondrocytes, which led to the activation of NF-κB pathway and ECM homeostasis imbalance.

Selenium deficiency aggravates bisphenol A-induced autophagy in chicken kidney through regulation of nitric oxide and adenosine monophosphate activated protein kinase/mammalian target of rapamycin signaling pathway.

Bisphenol A (BPA), a phenolic compound, is harmful to humans and animals as its residue in the water threatens multiple organs, especially the kidney. Low selenium (Se) diets are consumed in many regions of the world, and poor Se status has exacerbating effect on toxicity of several environmental chemicals. Here, we described the discovery path of Se deficiency aggravation on autophagy in BPA treated chicken kidney through regulating nitric oxide (NO) and adenosine monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathways. The actual dietary Se intake for chickens was 0.30 mg/kg in control group and 0.03 mg/kg in Low-Se group, and BPA exposure concentration for chickens was 0.05 g/kg. Chicken embryo kidney (CEK) cells were used in vitro and the BPA exposure concentration for CEK cells was 150 nM. We found that BPA significantly increased levels of NO and inducible nitric oxide synthase, activated AMPK/mTOR signaling pathways, thereby triggering p62/LC3/Beclin1 signaling, resulting in formations of autophagosome and autolysosome, and finally stimulating autophagy in the chicken kidney. Additionally, Se deficiency promoted the occurrence of autophagy in BPA-treated kidneys. Altogether, our findings showed that Se deficiency exacerbates BPA-induced renal autophagy in chickens via regulation of NO and AMPK/mTOR signaling pathways. These findings will improve our understandings of the mechanisms of nephrotoxicity of BPA and detoxification by Se in chickens. In addition, further work is required to determine if Se status of exposed populations needs to be considered in future epidemiological assessments.

LncRNA 0003250 accelerates heart autophagy and binds to miR-17-5p as a competitive endogenous RNA in chicken induced by selenium deficiency.

Long noncoding RNAs (LncRNAs) have been demonstrated to be associated with a variety of myocardial diseases, but how LncRNAs regulate autophagy in selenium (Se)-deficient myocardial injury is infrequently reported. Here, we screened out a novel long noncoding RNA, microRNA, and ATG7 through transcriptomic results. We employed a Se-deficient chicken model in vivo, and primary cultured cardiomyocytes treated by correlation in vitro. The results showed that Se deficiency upregulated the expression of ATG7, and miR-17-5p inhibited cardiomyocyte autophagy by targeting ATG7. Furthermore, we found that LncRNA 0003250 regulated miR-17-5p, and thus affected the expression of ATG7 and autophagic cell death. Our present study proposed a novel model for the regulation of cardiomyocytes autophagy, which includes LncRNA 0003250, miR-17-5p and ATG7 in the chicken heart. Our conclusions may provide a feasible diagnostic tool for Se-deficient cardiomyocyte injury.

Sulfur Amino Acid Status Controls Selenium Methylation in Pseudomonas tolaasii: Identification of a Novel Metabolite from Promiscuous Enzyme Reactions.

Selenium (Se) deficiency affects many millions of people worldwide, and the volatilization of methylated Se species to the atmosphere may prevent Se from entering the food chain. Despite the extent of Se deficiency, little is known about fluxes in volatile Se species and their temporal and spatial variation in the environment, giving rise to uncertainty in atmospheric transport models. To systematically determine fluxes, one can rely on laboratory microcosm experiments to quantify Se volatilization in different conditions. Here, it is demonstrated that the sulfur (S) status of bacteria crucially determines the amount of Se volatilized. Solid-phase microextraction gas chromatography mass spectrometry showed that Pseudomonas tolaasii efficiently and rapidly (92% in 18 h) volatilized Se to dimethyl diselenide and dimethyl selenyl sulfide through promiscuous enzymatic reactions with the S metabolism. However, when the cells were supplemented with cystine (but not methionine), a major proportion of the Se (∼48%) was channeled to thus-far-unknown, nonvolatile Se compounds at the expense of the previously formed dimethyl diselenide and dimethyl selenyl sulfide (accounting for <4% of total Se). Ion chromatography and solid-phase extraction were used to isolate unknowns, and electrospray ionization ion trap mass spectrometry, electrospray ionization quadrupole time-of-flight mass spectrometry, and microprobe nuclear magnetic resonance spectrometry were used to identify the major unknown as a novel Se metabolite, 2-hydroxy-3-(methylselanyl)propanoic acid. Environmental S concentrations often exceed Se concentrations by orders of magnitude. This suggests that in fact S status may be a major control of selenium fluxes to the atmosphere. IMPORTANCE Volatilization from soil to the atmosphere is a major driver for Se deficiency. "Bottom-up" models for atmospheric Se transport are based on laboratory experiments quantifying volatile Se compounds. The high Se and low S concentrations in such studies poorly represent the environment. Here, we show that S amino acid status has in fact a decisive effect on the production of volatile Se species in Pseudomonas tolaasii. When the strain was supplemented with S amino acids, a major proportion of the Se was channeled to thus-far-unknown, nonvolatile Se compounds at the expense of volatile compounds. This hierarchical control of the microbial S amino acid status on Se cycling has been thus far neglected. Understanding these interactions-if they occur in the environment-will help to improve atmospheric Se models and thus predict drivers of Se deficiency.

Preparation of an experimental mouse model lacking selenium-dependent glutathione peroxidase activities by feeding a selenium-deficient diet.

Relatively young (4-week-old) selenium deficient (SeD) mice, which lack the activity of selenium-dependent glutathione peroxidase (GSH-Px) isomers, were prepared using torula yeast-based SeD diet. Mice were fed the torula yeast-based SeD diet and ultra-pure water. Several different timings for starting the SeD diet were assessed. The weekly time course of liver comprehensive GSH-Px activity after weaning was monitored. Protein expression levels of GPx1 and 4 in the liver were measured by Western blot analysis. Gene expression levels of GPx1, 2, 3, 4, and 7 in the liver were measured by quantitative real-time PCR. Apoptotic activity of thymocytes after hydrogen peroxide (H2O2) exposure was compared. Thirty-day survival rates after whole-body X-ray irradiation were estimated. Pre-birth or right-after-birth starting of the SeD diet in dams was unable to lead to creation of SeD mice due to neonatal death. This suggests that Se is necessary for normal birth and healthy growing of mouse pups. Starting the mother on the SeD diet from 2 weeks after giving birth (SeD-trial-2w group) resulted in a usable SeD mouse model. The liver GSH-Px activity of the SeD-trial-2w group was almost none from 4 week olds, but the mice survived for more than 63 weeks. Protein and gene expression of GPx1 was suppressed in the SeD-trial-2w group, but that of GPx4 was not. The thymocytes of the SeD-trial-2w group were sensitive to H2O2-induced apoptosis. The SeD-trial-2w group was sensitive to whole-body X-ray irradiation compared with control mice. The SeD-trial-2w model may be a useful animal model for H2O2/hydroperoxide-induced oxidative stress.

Abnormal expression of chondroitin sulfate sulfotransferases in the articular cartilage of pediatric patients with Kashin-Beck disease.

The objective of this study is to investigate the expression of enzymes involved in the sulfation of articular cartilage from proximal metacarpophalangeal (PMC) joint cartilage and distal metacarpophalangeal (DMC) joint cartilage in children with Kashin-Beck disease (KBD). The finger cartilage samples of PMC and DMC were collected from KBD and normal children aged 5-14 years old. Hematoxylin and eosin staining as well as immunohistochemical staining were used to observe the morphology and quantitate the expression of carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 12 (CHST-12), carbohydrate sulfotransferase 13 (CHST-13), uronyl 2-O-sulfotransferase (UST), and aggrecan. In the results, the numbers of chondrocyte decreased in all three zones of PMC and DMC in the KBD group. Less positive staining cells for CHST-3, CHST-12, CHST-13, UST, and aggrecan were observed in almost all three zones of PMC and DMC in KBD. The positive staining cell rates of CHST-12 were higher in superficial and middle zones of PMC and DMC in KBD, and a significantly higher rate of CHST-13 was observed only in superficial zone of PMC in KBD. In conclusion, the abnormal expression of chondroitin sulfate sulfotransferases in chondrocytes of KBD children may provide an explanation for the cartilage damage, and provide therapeutic targets for the treatment.

Bioavailability of selenium (Se) in cattle population in Sri Lanka based on qualitative determination of glutathione peroxidase (GSH-Px) activities.

Glutathione Peroxidase activity in whole blood is well correlated with the Selenium (Se) levels in cattle hence can be used effectively to assess the supply of Se to farm animals. In this study, Se status of cattle from five different geographic regions of Sri Lanka were assessed based on glutathione peroxidase (GSH-Px) activity. The GSH-Px activity was determined in whole blood samples collected from 80 cattle from 31 different farms in five districts viz. Kandy, Anuradhapura, Batticoloa, Trincomalee and Jaffna using photometric method. Mean GSH-Px activity was found to be 825, 1239, 1039, 849 and 1307 µkat L-1 in above districts, respectively while the reference value was considered as 665.4 µkat L-1. Among the studied animals, insufficient Se levels were detected in 50%, 17%, 9%, 27% and 5%, respectively, from above districts. Kruskal Wallis test indicated a significant variation among the sampled locations with respect to the GSH-Px activity (p = 0.001). Selenium content in pasture and water collected from studied locations varied from 6.0 to 554 µg kg-1 and < 0.03-1.14 µg L-1, respectively. The lower Se levels in feeds recorded from Kandy region infer the lower GSH-Px activity in the animals from the same region. This variability may be due to differences in nutrient supply, age and species of cattle, and lactation stage. Although the assessing method has some limitations, the activity of GSH-Px of the samples indirectly confirms that considerable numbers of cattle from Sri Lanka are with insufficient selenium levels.

Oxidative stress, inflammation, and glycometabolism disorder-induced erythrocyte hemolysis in selenium-deficient exudative diathesis broilers.

Selenium (Se) deficiency causes injury of diversified tissues and cells, including livers, hearts, skeletal muscles, and erythrocytes. The aim of the present study is to explore the molecular mechanism of erythrocyte hemolysis due to Se deficiency in broilers. One hundred and eighty broilers (male/female, 1 day old) were randomly divided into two groups and fed with either a normal Se content diet (C group, 0.2 mg Se/kg) or a Se-deficient diet (ED group, 0.008 mg Se/kg) for 45 days. During the trial period of 15-30 days, biological properties such as osmotic fragility, fluidity, phospholipid components of cell membrane, adenosine triphosphatase activities, and antioxidant function of erythrocytes in broilers were examined. Moreover, the messenger RNA (mRNA) expressions of genes associated with inflammation, glycometabolism, and avian uncoupling protein (avUCP) were detected. We found that compared with the C group, hemolysis rate, degree of polarization, and microviscosity of erythrocytes were increased in broilers of the ED group. The composition of erythrocyte membrane lipids was changed. Meanwhile, the antioxidant function of erythrocytes was weakened and mRNA levels of inflammatory genes were stimulated by Se deficiency (p < 0.05). In addition, mRNA expressions of rate-limiting enzymes in glycometabolism were effected and avUCP mRNA level was downregulated (p < 0.05) in the ED group. It has been concluded from the results that oxidative stress, inflammatory response, and glycometabolism disorder lead to erythrocyte hemolysis by changing the structure and function of erythrocyte membrane in ED broilers suffered from Se deficiency.

microRNA-33-3p involved in selenium deficiency-induced apoptosis via targeting ADAM10 in the chicken kidney.

Selenium (Se) deficiency induces typical clinical and pathological changes and causes various pathological responses at the molecular level in several different chicken organs; the kidney is one of the target organs of Se deficiency. To explore the mechanisms that underlie the effects of microRNA-33-3p (miR-33-3p) on Se deficiency-induced kidney apoptosis, 60 chickens were randomly divided into two groups (30 chickens per group). We found that Se deficiency increased the expression of miR-33-3p in the chicken kidney. A disintegrin and metalloprotease domain 10 (ADAM10) was verified to be a target of miR-33-3p in the chicken kidney. The overexpression of miR-33-3p decreased the expression levels of ß-catenin, cyclinD1, T-cell factor (TCF), c-myc, survivin, and Bcl-2; it increased the expression levels of E-cadherin, Bak, Bax, and caspase-3; and it increased the number of chicken kidney cells in the G0/G1 phase. In addition, Se deficiency caused the ultrastructure of the kidney to develop apoptotic characteristics. The results of flow cytometry analysis and AO/EB staining showed that the number of apoptotic chicken kidney cells increased in the miR-33-3p mimic group. All these results suggest that Se deficiency-induced cell cycle arrest and apoptosis in vivo and in vitro in the chicken kidney via the regulation of miR-33-3p, which targets ADAM10.

Maintenance of SOX9 stability and ECM homeostasis by selenium-sensitive PRMT5 in cartilage.

OBJECTIVES: Selenium (Se) plays pivotal roles in maintaining optimal health. Nevertheless, how Se influences the metabolism of extracellular matrix (ECM) in cartilage remains unclear. The aim of the present study was to observe protein dimethylation by certain Se-sensitive PRMT and to elucidate its effects on the key transcriptional factor in cartilage. METHODS: We observed the expression of selenoproteins and markers of ECM metabolism in chondrocytes and articular cartilage of the rats under Se-deficiency by RT-qPCR, immunoblotting and immunohistochemistry. Then, we analyzed the expression of total dimethylated protein by using specific antibody under different Se statuses. After Se sensitive PRMT was identified, we used siRNA or PRMT inhibitor or stably overexpressing vector to intervene in the PRMT expression and identified the key transcriptional factor. Co-immunoprecipitation was applied to verify the interaction between PRMT and the key transcriptional factor. Finally, we measured the half-life time of the key transcriptional factor by immunoblotting after cycloheximide treatment. RESULTS: In chondrocytes and cartilage of the rats with Se deficiency, we found an aberrant metabolism manifesting decreased expression of Col2a1 and increased expression of Mmp-3. Then, we identified that PRMT5 was the unique type II PRMT, sensitive to Se status. PRMT5 upregulation led to the increased COL2A1 expression but decreased MMP-3 expression in chondrocytes. Furthermore, we revealed that PRMT5 improved SOX9 stability by dimethylating the protein, which contributed to maintain the matrix metabolic homeostasis of the chondrocytes. CONCLUSIONS: Se-sensitive PRMT5 increases the half-life of SOX9 protein via PTM and helps to maintain ECM homeostasis of the articular cartilage.