Biogenic selenium nanoparticles and selenium/chitosan-Nanoconjugate biosynthesized by Streptomyces parvulus MAR4 with antimicrobial and anticancer potential.

BACKGROUND: As antibiotics and chemotherapeutics are no longer as efficient as they once were, multidrug resistant (MDR) pathogens and cancer are presently considered as two of the most dangerous threats to human life. In this study, Selenium nanoparticles (SeNPs) biosynthesized by Streptomyces parvulus MAR4, nano-chitosan (NCh), and their nanoconjugate (Se/Ch-nanoconjugate) were suggested to be efficacious antimicrobial and anticancer agents. RESULTS: SeNPs biosynthesized by Streptomyces parvulus MAR4 and NCh were successfully achieved and conjugated. The biosynthesized SeNPs were spherical with a mean diameter of 94.2 nm and high stability. Yet, Se/Ch-nanoconjugate was semispherical with a 74.9 nm mean diameter and much higher stability. The SeNPs, NCh, and Se/Ch-nanoconjugate showed significant antimicrobial activity against various microbial pathogens with strong inhibitory effect on their tested metabolic key enzymes [phosphoglucose isomerase (PGI), pyruvate dehydrogenase (PDH), glucose-6-phosphate dehydrogenase (G6PDH) and nitrate reductase (NR)]; Se/Ch-nanoconjugate was the most powerful agent. Furthermore, SeNPs revealed strong cytotoxicity against HepG2 (IC50 = 13.04 µg/ml) and moderate toxicity against Caki-1 (HTB-46) tumor cell lines (IC50 = 21.35 µg/ml) but low cytotoxicity against WI-38 normal cell line (IC50 = 85.69 µg/ml). Nevertheless, Se/Ch-nanoconjugate displayed substantial cytotoxicity against HepG2 and Caki-1 (HTB-46) with IC50 values of 11.82 and 7.83 µg/ml, respectively. Consequently, Se/Ch-nanoconjugate may be more easily absorbed by both tumor cell lines. However, it exhibited very low cytotoxicity on WI-38 with IC50 of 153.3 µg/ml. Therefore, Se/Ch-nanoconjugate presented the most anticancer activity. CONCLUSION: The biosynthesized SeNPs and Se/Ch-nanoconjugate are convincingly recommended to be used in biomedical applications as versatile and potent antimicrobial and anticancer agents ensuring notable levels of biosafety, environmental compatibility, and efficacy.

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.

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.

Impact of Biogenic and Chemogenic Selenium Nanoparticles on Model Eukaryotic Lipid Membranes.

Microbial nanotechnology is an expanding research area devoted to producing biogenic metal and metalloid nanomaterials (NMs) using microorganisms. Often, biogenic NMs are explored as antimicrobial, anticancer, or antioxidant agents. Yet, most studies focus on their applications rather than the underlying mechanism of action or toxicity. Here, we evaluate the toxicity of our well-characterized biogenic selenium nanoparticles (bSeNPs) produced by the Stenotrophomonas maltophilia strain SeITE02 against the model yeast Saccharomyces cerevisiae comparing it with chemogenic SeNPs (cSeNPs). Knowing from previous studies that the biogenic extract contained bSeNPs in an organic material (OM) and supported here by Fourier transform infrared spectroscopy, we removed and incubated it with cSeNPs (cSeNPs_OM) to assess its influence on the toxicity of these formulations. Specifically, we focused on the first stages of the eukaryotic cell exposure to these samples─i.e., their interaction with the cell lipid membrane, which was mimicked by preparing vesicles from yeast polar lipid extract or phosphatidylcholine lipids. Fluidity changes derived from biogenic and chemogenic samples revealed that the bSeNP extract mediated the overall rigidification of lipid vesicles, while cSeNPs showed negligible effects. The OM and cSeNPs_OM induced similar modifications to the bSeNP extract, reiterating the need to consider the OM influence on the physical-chemical and biological properties of bSeNP extracts.

Toxicity of repeated oral intake of organic selenium, inorganic selenium, and selenium nanoparticles: A review.

BACKGROUND: To protect from toxicity at supra-essential doses of selenium, it is important to determine dose levels at which adverse effects occur. METHODS: We identified relevant literature on the repeated dosage of selenium and extracted dose descriptors on reported endpoints, except on genotoxicity/carcinogenicity. RESULTS: Selenium forms with toxicological data were organic ones: selenomethionine, selenocystine/selenocysteine; and inorganic ones, including selenite (SeO32-), selenate (SeO42-), selenium sulphide (SeS2), selenide (Se2-) and selenium nanoparticles. Clinical signs of selenium toxicity in humans include a garlicky-smelling breath, hair loss, and nail changes. One human study showed increased mortality following daily ingestion of 300 µg Se per day for 5 years, equal to a lowest-observed-adverse-effect level (LOAEL) of ∼4.3 µg/kg bw/days. The corresponding no-observed-adverse-effect level (NOAEL) was ∼2.9 µg Se/kg bw/day. One study reported an increased risk of type 2 diabetes after ∼2.9 µg Se/kg bw/day, but other studies with similar doses found no increases in mortality or incidence of type 2 diabetes. NOAELs on affected body weight in animal studies were 0.24-1.2 mg Se/kg bw/day. Other endpoints of selenium toxicity in animals include hepatotoxicity with a NOAEL as low as 2 µg/kg bw/day in rats, as well as gastrointestinal, cardiovascular, and reproductive toxicities with NOAELs of 0.6 (gastrointestinal), 0.08, and 0.4 (cardiovascular) and ≥ 0.04 mg Se/kg bw/day (reproductive), respectively. CONCLUSIONS: Dose descriptors describing selenium toxicity were as low as 2-3 µg Se/kg bw/day.

Status of estrogen receptor expression and epigenetic methylation in Leydig cells after exposure to metalloestrogen - selenium.

The trace element selenium (Se) is essential for the maintenance of spermatogenesis and fertility. A growing volume of evidence shows that Se is necessary for testosterone synthesis, and Se can stimulate Leydig cell proliferation. However, Se can also act as a metalloestrogen, which can mimic estrogen and activate the estrogen receptors. This study aimed to investigate Se effect on estrogen signaling and the epigenetic status of Leydig cells. Mouse Leydig cells (MA-10) were cultured in a medium supplemented with different Se concentrations (4, 8 µM) for 24 h. Next, cells were assessed for morphological and molecular (qRT PCR, western blot, immunofluorescence) analyses. Immunofluorescence revealed strong immunosignal for 5-methylcytosine in both control and treated cells, with a stronger signal in the 8 µM treated group. qRT-PCR confirmed an increased expression of methyltransferase 3 beta (Dnmt3b) in 8 µM cells. Analysis of the expression of γH2AX (a marker for double-stranded DNA breaks) revealed an increase in the DNA breaks in cells exposed to 8 µM Se. Selenium exposure did not affect the expression of canonical estrogen receptors (ERα and ERß), however, an increase in membrane estrogen receptor G-protein coupled (GPER) protein expression was observed.To sum up, in a high concentration (8 µM) Se affects GPER expression (non-genomic estrogen signaling) in Leydig cells possibly via acting on receptor protein and/or its binding. This causes DNA breaks and induces changes in Leydig cell methylation status, especially in de novo methylation which is mediated by Dnmt3b.

The protective effect of N-acetyl cysteine against selenium toxicity and gamma irradiation in rats.

N-acetyl cysteine (NAC) is a nutritional supplement and greatly applied as an antioxidant in vivo and in vitro. Therefore, this study aimed to assess the metabolic and antioxidant protective effect of NAC against selenium (Se) toxicity and gamma irradiation in rats by measuring biochemical and molecular parameters. This study was conducted on sixty rats divided into six equal different groups; control, NAC, Rad, Se, Rad + NAC, and Se + NAC groups. Oxidative/nitrosative makers (LPO, NO, and NOS), antioxidants status markers (GSH, GPx, and SOD), liver metabolic markers (LDH, SDH, and ATP), and plasma metabolic markers (Glucose, total cholesterol, and total proteins) were measured using commercial colorimetric kits while plasma corticosterone concentration was measured using commercial ELISA kit. Also, Levels of NR3C1 and Glut-2 genes expression using reverse transcription-quantitative polymerase chain reaction were done. Our results revealed that Se toxicity and gamma irradiation induced significant increases in oxidative/nitrosative stress markers and a significant decrease in antioxidant status markers in the liver and adrenal tissues. Moreover, metabolic disorders were recorded as manifested by elevation of plasma ALT, Albumin, glucose and cholesterol, and decrease in protein levels associated with a significant increase in corticosterone concentration. This was also accompanied by a significant decrease in SDH activity and ATP production in the hepatic tissue. Molecular analysis showed a marked increase in NR3C1 mRNA and decrease in Glut-2 mRNA in liver tissue. However, NAC supplementation attenuated the changes induced by these toxins. Finally, we could conclude that, oral supplementation of NAC can modulate the metabolic disturbances and has protective effects in rats exposed to Se toxicity and gamma irradiation.

Single and joint effects of cadmium and selenium on bioaccumulation, oxidative stress and metabolomic responses in the clam Scrobicularia plana.

Selenium (Se) is a vital trace element for many living organisms inclusive of aquatic species. Although the antagonistic action of this element against other pollutants has been previously described for mammals and birds, limited information on the join effects in bivalves is available. To this end, bivalves of the species Scrobicularia plana were exposed to Se and Cd individually and jointly. Digestive glands were analysed to determine dose-dependent effects, the potential influence of Se on Cd bioaccumulationas well as the possible recover of the oxidative stress and metabolic alterations induced by Cd. Selenium co-exposure decreased the accumulation of Cd at low concentrations. Cd exposure significantly altered the metabolome of clams such as aminoacyltRNA biosynthesis, glycerophospholipid and amino acid metabolism, while Se co-exposure ameliorated several altered metabolites such asLysoPC (14:0), LysoPE (20:4), LysoPE (22:6), PE (14:0/18:0), PE (20:3/18:4) andpropionyl-l-carnitine.Additionally, Se seems to be able to regulate the redox status of the digestive gland of clams preventing the induction of oxidativedamage in this organ. This study shows the potential Se antagonism against Cd toxicity in S. plana and the importance to study join effects of pollutants to understand the mechanism underlined the effects.

Associations of a metal mixture with iron status in U.S. adolescents: Evidence from the National Health and Nutrition Examination Survey.

Iron is needed for normal development in adolescence. Exposure to individual environmental metals (e.g., lead) has been associated with altered iron status in adolescence, but little is known about the cumulative associations of multiple metals with Fe status. We used data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) to examine associations between a metal mixture (lead, manganese, cadmium, selenium) and iron status in 588 U.S. adolescents (12-17 years). We estimated cumulative and interactive associations of the metal mixture with five iron status metrics using Bayesian Kernel Machine Regression (BKMR). Higher concentrations of manganese and cadmium were associated with lower log-transformed ferritin concentrations. Interactions were observed between manganese, cadmium, and lead for ferritin and the transferrin receptor, where iron status tended to be worse at higher concentrations of all metals. These results may reflect competition between environmental metals and iron for cellular uptake. Mixed metal exposures may alter normal iron function, which has implications for adolescent development.

Safety of selenium exposure and limitations of selenoprotein maximization: Molecular and epidemiologic perspectives.

Recent evidence from laboratory and epidemiologic studies has shed a different light on selenium health effects and its recommended range of environmental exposure, compared with earlier research. Specifically, epidemiologic studies in Western populations have shown adverse effects of selenium exposure at low levels, sometimes below or slightly above selenium intakes needed to maximize selenoprotein expression and activity. In addition, three recent lines of evidence in molecular and biochemical studies suggest some potential drawbacks associated with selenoprotein maximization: 1) the possibility that selenoprotein upregulation is a compensatory response to oxidative challenge, induced by selenium itself or other oxidants; 2) the capacity of selenoproteins to trigger tumor growth in some circumstances; and 3) the deleterious metabolic effects of selenoproteins and particularly of selenoprotein P. The last observation provides a toxicological basis to explain why in humans selenium intake levels as low as 60 µg/day, still in the range of selenium exposure upregulating selenoprotein expression, might start to increase risk of type 2 diabetes. Overall, these new pieces of evidence from the literature call into question the purported benefit of selenoprotein maximization, and indicate the need to reassess selenium dietary reference values and upper intake level. This reassessment should clarify which range of selenoprotein upregulation follows restoration of adequate selenium availability and which range is driven by a compensatory response to selenium toxicity and oxidative stress.

Comparison of selenite and selenate in alleviation of drought stress in Nicotiana tabacum L.

Exogenous selenium (Se) improves the tolerance of plants to abiotic stress. However, the effects and mechanisms of different Se species on drought stress alleviation are poorly understood. This study aims to evaluate and compare the different effects and mechanisms of sodium selenate (Na2SeO4) and sodium selenite (Na2SeO3) on the growth, photosynthesis, antioxidant system, osmotic substances and stress-responsive gene expression of Nicotiana tabacum L. under drought stress. The results revealed that drought stress could significantly inhibit growth, whereas both Na2SeO4 and Na2SeO3 could significantly facilitate the growth of N. tabacum under drought stress. However, compared to Na2SeO3, Se application as Na2SeO4 induced a significant increase in the root tip number and number of bifurcations under drought stress. Furthermore, both Na2SeO4 and Na2SeO3 displayed higher levels of photosynthetic pigments, better photosynthesis, and higher concentrations of osmotic substances, antioxidant enzymes, and stress-responsive gene (NtCDPK2, NtP5CS, NtAREB and NtLEA5) expression than drought stress alone. However, the application of Na2SeO4 showed higher expression levels of the NtP5CS and NtAREB genes than Na2SeO3. Both Na2SeO4 and Na2SeO3 alleviated many of the deleterious effects of drought in leaves, which was achieved by reducing stress-induced lipid peroxidation (MDA) and H2O2 content by enhancing the activity of antioxidant enzymes, while Na2SeO4 application showed lower H2O2 and MDA content than Na2SeO3 application. Overall, the results confirm the positive effects of Se application, especially Na2SeO4 application, which is markedly superior to Na2SeO3 in the role of resistance towards abiotic stress in N. tabacum.

Toxic arsenic in marketed aquatic products from coastal cities in China: Occurrence, human dietary exposure risk, and coexposure risk with mercury and selenium.

To improve the accuracy of dietary risk assessment of arsenic (As) from aquatic products, toxic As species (As(III), As(V), monomethylarsonic acid [MMA], and dimethylarsinic acid [DMA]) and total As were analyzed in 124 marketed aquatic products from eight coastal cities in China. Distribution characteristics of Toxic As (the sum of the four toxic As species) in the samples and associated risk of human dietary exposure were emphatically investigated. The impact of cooccurrence of As and other chemical elements in the aquatic products was assessed based on our former results of mercury (Hg) and selenium (Se). Toxic As contents (maximum value 0.358 mg kg-1 wet weight) in the samples accounted for at most 14.1% of total As. DMA was the major component (mean proportion 50.8% for shellfish, 100% for fish) of Toxic As in aquatic products. Shellfish contained more Toxic As than fish did. Mean estimated daily intakes of Toxic As for the residents with aquatic product consumption rates of 46.1-235 g day-1 ranged from 0.034 to 0.290 µg kg-1 day-1. Potential health risk was indicated among those who greatly consumed aquatic products, as their target hazard quotient (THQ) and target cancer risk (TR) values exceeded safety thresholds (1 for THQ, 10-4 for TR). DMA and MMA exposure contributed to 3.42-7.72% of the THQToxic As. Positive correlations between concentrations of As and Hg (Fish: r = 0.47, p < 0.01; Shellfish: r = 0.60, p < 0.01), as well as between that of As and Se (Fish: r = 0.69, p < 0.01; Shellfish: r = 0.37, p < 0.01) were found in the samples. It requires attentions urgently that As and Hg coexposure through aquatic product consumption rose the sum THQ of Toxic As and methylmercury (MeHg) to approximately two to eight times as high as the THQToxic As.

Investigation on selenium and mercury interactions and the distribution patterns in mice organs with LA-ICP-MS imaging.

It is the first time to investigate local distribution patterns of mercury (Hg) in mice organs after Hg and Se exposure with detection of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Two batch of adult mice were employed to be exposed to inorganic mercury (iHg) and methylmercury (MeHg) with or without Se at the dose of 55 µmol kg-1. Tissue sections of brain, kidney, liver, and spleen from one batch mice were prepared to get local imaging of Hg by LA-ICP-MS. Tissues from another batch mice were used to quantify Hg and Se in tissues with ICP-MS after acid digestion. The results indicated that, for mice exposed to iHg, Hg mainly distributed in kidney, a little in liver, and hardly in brain and spleen; for mice exposed to MeHg, lower amount of Hg was found in kidney, liver and spleen, and almost no Hg was found in brain. It was interesting that for Hg and Se co-administration groups, higher level of Hg was observed in kidney, liver, spleen and even in brain than single Hg administration groups. In addition, Se level in organ tissues increased obviously not only in Se exposure group but also in MeHg exposure group, while the phenomenon was not observed in iHg exposure group. HepG2 cells were employed to investigate Se and Hg interactions in single cell level, similar bioaccumulation behavior of Hg was found between cells and mice organs. Higher level of Hg was observed in cells cultured with Se and Hg medium than cells cultured with single Hg medium. The results are expected to provide new insight to investigate Hg and Se interactions in animal bodies and in-vitro cells.

Oral Administration of Resveratrol-Selenium-Peptide Nanocomposites Alleviates Alzheimer's Disease-like Pathogenesis by Inhibiting Aß Aggregation and Regulating Gut Microbiota.

Alzheimer's disease (AD) is a neurodegenerative disease associated with amyloid-ß (Aß) deposition, leading to neurotoxicity (oxidative stress and neuroinflammation) and gut microbiota imbalance. Resveratrol (Res) has neuroprotective properties, but its bioavailability in vivo is very low. Herein, we developed a small Res-selenium-peptide nanocomposite to enable the application of Res for eliminating Aß aggregate-induced neurotoxicity and mitigating gut microbiota disorder in aluminum chloride (AlCl3) and d-galactose(d-gal)-induced AD model mice. Res functional selenium nanoparticles (Res@SeNPs) (8 ± 0.34 nm) were prepared first, after which the surface of Res@SeNPs was decorated with a blood-brain barrier transport peptide (TGN peptide) to generate Res-selenium-peptide nanocomposites (TGN-Res@SeNPs) (14 ± 0.12 nm). Oral administration of TGN-Res@SeNPs improves cognitive disorder through (1) interacting with Aß and decreasing Aß aggregation, effectively inhibiting Aß deposition in the hippocampus; (2) decreasing Aß-induced reactive oxygen species (ROS) and increasing activity of antioxidation enzymes in PC12 cells and in vivo; (3) down-regulating Aß-induced neuroinflammation via the nuclear factor kappa B/mitogen-activated protein kinase/Akt signal pathway in BV-2 cells and in vivo; and (4) alleviating gut microbiota disorder, particularly with respect to oxidative stress and inflammatory-related bacteria such as Alistipes, Helicobacter, Rikenella, Desulfovibrio, and Faecalibaculum. Thus, we anticipate that Res-selenium-peptide nanocomposites will offer a new potential strategy for the treatment of AD.

Bi/Se-Based Nanotherapeutics Sensitize CT Image-Guided Stereotactic Body Radiotherapy through Reprogramming the Microenvironment of Hepatocellular Carcinoma.

The particular characteristics of hypoxia, immune suppression in the tumor microenvironment, and the lack of accurate imaging guidance lead to the limited effects of stereotactic body radiotherapy (SBRT) in reducing the recurrence rate and mortality of hepatocellular carcinoma (HCC). This research developed a novel theranostic agent based on Bi/Se nanoparticles (NPs), synthesized by a simple reduction reaction method for in vivo CT image-guided SBRT sensitization in mice. After loading Lenvatinib (Len), the obtained Bi/Se-Len NPs had excellent performance in reversing hypoxia and the immune suppression status of HCC. In vivo CT imaging results uncovered that the radiotherapy (RT) area could be accurately labeled after the injection of Bi/Se-Len NPs. Under Len's unique and robust properties, in vivo treatment was then carried out upon injection of Bi/Se-Len NPs, achieving excellent RT sensitization effects in a mouse HCC model. Comprehensive tests and histological stains revealed that Bi/Se-Len NPs could reshape and normalize tumor blood vessels, reduce the hypoxic situation of the tumor, and upregulate tumor-infiltrating CD4+ and CD8+ T lymphocytes around the tumors. Our work highlights an excellent proposal of Bi/Se-Len NPs as theranostic nanoparticles for image-guided HCC radiotherapy.

The toxicity of selenium and mercury in Suaeda salsa after 7-days exposure.

Mercury is one of the major pollutants in the ocean, selenium causes toxicity beyond a certain limit, but there are few comparative toxic studies between them in halophytes. The study was to investigate the toxic effects of selenium (Se4+) and mercury (Hg2+) in halophyte Suaeda salsa at the level of genes, proteins and metabolites after exposure for 7 days. By integrating the results of proteomics and metabolomics, the pathway changed under different treatments were revealed. In Se4+-treated group, the changed 3 proteins and 10 metabolites participated in the process of substance metabolism (amino acid, pyrimidine), citrate cycle, pentose phosphate pathway, photosynthesis, energy, and protein biosynthesis. In Hg2+-treated group, the changed 10 proteins and 10 metabolites were related to photosynthesis, glycolysis, substance metabolism (cysteine and methionine, amino acid, pyrimidine), ATP synthesis and binding, tolerance, sugar-phosphatase activity, and citrate cycle. In Se4++ Hg2+-treated group, the changed 5 proteins an 12 metabolites involved in stress defence, iron ion binding, mitochondrial respiratory chain, structural constituent of ribosome, citrate cycle, and amino acid metabolism. Furthermore, the separate and combined selenium and mercury both inhibited growth of S. salsa, enhanced activity of antioxidant enzymes (superoxide dismutase, peroxidase and catalase), and disturbed osmotic regulation through the genes of choline monoxygenase and betaine aldehyde dehydrogenase. Our experiments also showed selenium could induce synergistic effects in S. salsa. In all, we successfully characterized the effects of selenium and mercury in plant which was helpful to evaluate the toxicity and interaction of marine pollutants.

Advances in Research on the Toxicological Effects of Selenium.

Selenium is a trace element necessary for the growth of organisms. Moreover, selenium supplementation can improve the immunity and fertility of the body, as well as its ability to resist oxidation, tumors, heavy metals, and pathogenic microorganisms. However, owing to the duality of selenium, excessive selenium supplementation can cause certain toxic effects on the growth and development of the body and may even result in death in severe cases. At present, increasing attention is being paid to the development and utilization of selenium as a micronutrient, but its potential toxicity tends to be neglected. This study systematically reviews recent research on the toxicological effects of selenium, aiming to provide theoretical references for selenium toxicology-related research and theoretical support for the development of selenium-containing drugs, selenium-enriched dietary supplements, and selenium-enriched foods.

Metabolic, immunologic, and histopathologic responses on premetamorphic American bullfrog (Lithobates catesbeianus) following exposure to lithium and selenium.

The presence of chemicals and the destruction of freshwater habitats have been addressed as one of the reasons for the decline in the amphibians' populations worldwide. Considering the threat that these animals have been suffering in tropical regions, the present study tested if the Brazilian legislation, concerning the permissive levels of lithium and selenium in water bodies and effluents, warrants the protection of aquatic life. To do so, we assessed the metabolic, immunologic, and histopathologic alterations in liver samples of American bullfrog (Lithobates catesbeianus), at the premetamorphic stage, through biomarkers indicative of general energetic status, i.e., glucose, lipid, and protein metabolism using biochemical and histochemical approaches. The immunologic responses were assessed by the quantification of melanomacrophage centres (MMCs); the histopathologic evaluation of the liver sections was also performed. The assay was carried out over 21 days with two periods of sampling (after 7 and 21 days) to assess the effects of exposure over time. The animals were exposed to the considered safe levels of lithium (2.5 mg L-1) and selenium (10 µg L-1), both, isolated and mixed. The exposed animals showed alterations in glucose and lipid metabolism throughout the experiment. The intense presence of MMCs and histopathological responses are compatible with hepatotoxicity. The toxicity expressed by the employed animal model indicates that the Brazilian environmental legislation for the protection of aquatic life needs to be updated. With this study, we intend to provide data for better environmental policies and bring attention to sublethal effects triggered by the presence of contaminants in the aquatic environment.

LncRNA MIAT regulated by selenium and T-2 toxin increases NF-κB-p65 activation, promoting the progress of Kashin-Beck Disease.

LncRNA myocardial infarction associated transcript (MIAT) has been shown to be involved in osteoarthritis (OA), but its role in Kashin-Beck Disease (KBD) has rarely been reported. In this study, rats were administered with low selenium and/or T-2 toxin for 4 weeks to establish a KBD animal model. The serum selenium level, TNF-α and IL-1ß contents, phosphorylated p65 (p-p65) and MIAT expression were increased in each intervention group. Next, we isolated the primary epiphyseal chondrocytes, and found that selenium treatment reversed the effects of T-2 toxin on chondrocyte injury, p-p65 and MIAT expression. In addition, MIAT overexpression or T-2 toxin treatment led to increased cell death, apoptosis, inflammation, NF-κB-p65 pathway activation and MIAT expression, which was rescued by selenium treatment or MIAT siRNA transfection. Our results suggested that lncRNA MIAT regulated by selenium and T-2 toxin increased the activation of NF-κB-p65, thus being involved in the progress of KBD.

Transcriptome, proteome, and metabolome reveal the mechanism of tolerance to selenate toxicity in Cardamine violifolia.

Cardamine violifolia was found here to accumulate selenium (Se) to over 9000 mg kg-1 dry weight. To investigate the mechanism of Se accumulation and tolerance in C. violifolia, metabolome, transcriptome, and proteome technologies were applied to C. violifolia seedlings treated with selenate. Several sulfate transporter (Sultr) genes (Sultr1;1, Sultr1;2, and Sultr2;1) and sulfur assimilatory enzyme genes showed high expression levels in response to selenate. Many calcium protein and cysteine-rich kinase genes of C. violifolia were downregulated, whereas selenium-binding protein 1 (SBP1) and protein sulfur deficiency-induced 2 (SDI2) of C. violifolia were upregulated by selenate. The expression of genes involved in the ribosome and posttranslational modifications and chaperones in C. violifolia were also detected in response to selenate. Based on the results of this study and previous findings, we suggest that the downregulated expression of calcium proteins and cysteine-rich kinases, and the upregulated expression of SBP1 and SDI2, were important contributors to the Se tolerance of C. violifolia. The downregulation of cysteine-rich kinases and calcium proteins would enhance Se tolerance of C. violifolia is a novel proposition that has not been reported on other Se hyperaccumulators. This study provides us novel insights to understand Se accumulation and tolerance in plants.