Association of Plasma Selenium and Its Untargeted Metabolomic Profiling with Cervical Cancer Prognosis.

Selenium is an essential trace element that shows beneficial or adverse health effects depending on the dose. However, its role in the prognosis of cervical cancer (CC) has been less reported. We aimed to explore the association between selenium status and prognosis in CC patients with different prognoses and to elucidate the underlying mechanism of selenium in CC prognosis. This cross-sectional observational study had a case-control design at the Harbin Medical University Cancer Hospital and was conducted using 29 CC cases with poor prognosis and 29 CC cases with good prognosis. Plasma selenium levels were measured using an atomic fluorescence spectrometer. Untargeted metabolomics was used to identify metabolites. Plasma selenium levels of the poor prognosis group (49.90 ± 13.81 µg/L) were lower than that of the good prognosis group (59.38 ± 13.00 µg/L, t = 2.69, P = 0.009). In the logistic regression analysis, plasma selenium levels were associated with lower poor prognosis risk [odds ratio (OR) = 0.952, 95% CI: 0.909-0.998]. Receiver operating characteristic curve analysis revealed an optimal cut-off point of plasma selenium levels ≤ 47.68 µg/L for poor prognosis of CC. Based on the cut-off selenium levels, patients with different prognoses were divided into high and low selenium groups. Metabolomic analysis revealed six differential metabolites among different prognoses with low and high selenium levels, and the glycerophospholipid (GPL) metabolism was enriched. Plasma selenium levels were positively correlated with metabolite levels. Our findings provided evidence that low plasma selenium levels may associate with a poor prognosis of CC. Low plasma selenium levels might suppress GPL metabolism and influence the prognosis of CC. This finding requires confirmation in future prospective cohort studies.

Methylation of melatonin receptors in patients with unipolar and bipolar depression.

Disturbances of melatonin secretion alter the circadian rhythm and sleep-wake cycle, which is observed among patients with depression. Melatonin acts via melatonin receptors MT1 and MT2, which are present in many tissues, including peripheral blood mononuclear cells (PBMC). We assume that disturbances of the melatonin pathway in the brain may be reflected by molecular changes in peripheral organs. The study objective was to evaluate the methylation profile of CpG island in the promoter region of melatonin receptor genes MTNR1A and MTNR1B in PBMC of patients with depression and compare it with healthy volunteers. The study group comprised 85 patients with unipolar (UP) and bipolar disorders (BP) and 83 controls. The methylation pattern of CpG island in the promoter region was analyzed using the quantitative methylation-specific real-time PCR (qMSP-PCR) method. We found that the methylation profile of the patients with depression varied in comparison to the control group. The methylation level of MTNR1A was significantly lower among depressed patients compared to controls. Additionally, melatonin concentration was negatively correlated with MTNR1B methylation level among the UP patients. The study may suggest that the methylation profile of melatonin receptors in PBMC may be used as a complementary molecular marker in depression diagnosis.

Sodium selenite inhibits cervical cancer growth via ROS mediated AMPK/FOXO3a /GADD45a axis.

Selenium is a trace element that has been shown to inhibit the growth of various cancer cell types. However, its role in cervical cancer and its underlying mechanisms remains largely unknown. Herein, we explored the anti-cervical cancer effect of selenium and its potential mechanisms through xenograft and in vitro experiments. HeLa cell xenografts in female nude mice showed tumor growth retardation, with no obvious liver and kidney toxicity, after being intraperitoneally injected with 3 mg/kg sodium selenite (SS) for 14 days. Compared to the control group, selenium levels in the tumor tissue increased significantly after SS treatment. In vitro experiments, SS inhibited the viability of HeLa and SiHa cells, blocked the cell cycle at the S phase, and enhanced apoptosis. RNA-sequencing, Kyoto encyclopedia of genes and genomes pathway analysis showed that forkhead box protein O (FOXO) was a key regulatory signaling pathway for SS to exhibit anticancer effects. Gene Ontology analysis filtered multiple terms associated with apoptosis, anti-proliferation, and cell cycle arrest. Further research revealed that SS increased intracellular reactive oxygen species (ROS) and impaired mitochondrial function, which activated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) via phosphorylation at Thr172, resulting in activation of FOXO3a and its downstream growth arrest and DNA damage-inducible alpha (GADD45a). In summary, SS exhibited anti-cervical cancer effects, and their mechanisms may be that SS is involved in inducing cell cycle arrest and potentiating cell apoptosis caused by ROS-dependent activation of the AMPK/FOXO3a/GADD45a axis.

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.

Association of allelic combinations in selenoprotein and redox related genes with markers of lipid metabolism and oxidative stress - multimarkers analysis in a cross-sectional study.

BACKGROUND: Selenium (Se) and selenoproteins have been shown to be involved in lipid metabolism mainly due to their ability to modulate redox homeostasis in adipose tissue. The underlying mechanisms are yet to be evaluated. In the light of few data related to the association between polymorphic variants of selenoprotein encoding genes and metabolic syndrome or obesity in humans, the role of selenoprotein polymorphisms in lipid metabolism remains unclear. The aim of this study was to investigate the impact of allelic combination within selenoprotein and redox related genes on the markers of lipid metabolism and oxidative stress. METHODS: The study comprised 441 healthy individuals from Poland, in the 18-74 year age group. Allelic combinations were investigated within the polymorphic variants of four selenoprotein encoding genes (GPX1 rs1050450, GPX4 rs713041, SELENOP rs3877899 and SELENOF rs5859) and the redox related gene (SOD2 rs4880). The impact of the most common allelic GPX1-GPX4-SELENOP-SELENOF-SOD2 combinations was assessed on the following markers: triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glutathione peroxidase activities (GPX1, GPX3), lipid peroxidation (as TBARS), ceruloplasmin (Cp) and superoxide dismutase 1 (SOD1). RESULTS: Multivariable analysis revealed significant associations between three allelic combinations and markers of lipid metabolism, including HDL-C and TC/HDL-C ratio (AAAAa), LDL-C (aaAaa), and triglycerides (aaaaA), whereas two allelic combinations (aAaAA, aaaAA) were associated with GPX3 activity. CONCLUSION: This study confirms the possible implication of selenoproteins in lipid metabolism and warrants further research on specific allele combinations within selenoprotein and redox related genes in order to identify functional genetic combinations linked to metabolic phenotype.

Determinants of the Essential Elements and Vitamins Intake and Status during Pregnancy: A Descriptive Study in Polish Mother and Child Cohort.

The study objective was to identify determinants of essential elements and vitamins intake, and microelements and vitamins concentration in blood among pregnant women from Poland. Based on the data from food frequency questionnaires and information about supplements taken (n = 1252), daily supply of six elements (calcium, magnesium, iron, zinc, copper, selenium) and nine vitamins (folate, vitamins A, E, C, B1, B2, B3, B6, B12) was calculated. Zinc, copper, selenium (n = 340), vitamin A and E (n = 358) concentration was determined in blood collected during pregnancy. Most of the women did not meet the demand for essential elements and vitamins with a diet. About 94% of the respondents declared supplements use. The women with higher education, indicating leisure-time, physical activity and multiparity had a higher chance of meeting the average demand for the majority of the analyzed nutrients. On the other hand, factors such as BMI < 18.5kg/m2, a higher level of stress, and late first medical-care visit were associated with a lower chance of meeting the recommendations. Higher socio-economic status was a determinant of a higher selenium concentration in plasma (ß = 3.1; 95%CI: 0.2-5.9), whereas BMI ≥ 25 kg/m2, and multiparity of a higher copper concentration in plasma (ß = 0.2; 95%CI: 0.03-0.4; ß = 0.2; 95%CI: 0.1-0.4). Higher plasma concentration of vitamin E was noted among women older than 30 years of age comparing to those who were 30 or younger (ß = 1.5; 95%CI: 0.6-2.4). Although more studies are required, especially such based on laboratory measures, our results indicate target groups for dietary interventions during pregnancy for children's optimal health and development.

Therapeutic Potential of Selenium and Selenium Compounds in Cervical Cancer.

Cervical cancer is a common female cancer. It is strongly associated with human papillomavirus (HPV) infection. However, HPV infection alone is not sufficient to induce cervical cancer because its development is dependent on the coexistence of several factors that enable the virus to overcome the host immune system. These include individual genetic background, environmental factors, or diet, including dietary selenium intake. Selenium is an essential trace element with antiviral properties and has been shown to exert antitumor effects. Surprisingly, the role of selenium in cervical cancer has not been studied as intensively as in other cancers. Here, we have summarized the existing experimental data on selenium and cervical cancer. It may be helpful in evaluating the role of this nutrient in treatment of the mentioned malignancy as well as in planning further studies in this area.

Controversy around parabens: Alternative strategies for preservative use in cosmetics and personal care products.

Parabens usage as preservatives in cosmetics and personal care products have been debated among scientists and consumers. Parabens are easy to production, effective and cheap, but its safety status remains controversial. Other popular cosmetics preservatives are formaldehyde, triclosan, methylisothiazolinone, methylchloroisothiazolinone, phenoxyethanol, benzyl alcohol and sodium benzoate. Although their high antimicrobial effectiveness, they also exhibit some adverse health effects. Lately, scientists have shown that natural substances such as essential oils and plant extracts present antimicrobial potential. However, their use in cosmetic is a challenge. The present review article is a comprehensive summary of the available methods to prevent microbial contamination of cosmetics and personal care products, which can allow reducing the use of parabens in these products.

A Proliferation-Inducing Ligand Regulation in Polymorphonuclear Neutrophils by Panax ginseng.

A proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor superfamily that was first identified as a factor favoring tumorigenesis. APRIL is important fitness and survival factors for B cells and plasma cells in the periphery. Considering this, as well as the quantitative predominance of neutrophils among the peripheral blood leukocytes, we carried out the first study assessing the influence of the transforming growth factor (TGF)-ß signaling pathway on APRIL expression in these cells. Furthermore, as the Rb1 ginsenoside is known to exhibit multiple pharmacological activities, we verified if the saponin is capable of modulating the process. The present study shows that TGF-ß increased the expression of APRIL and the level of phospho-p38, phospho-Akt(T308), and phospho-Akt(S473) in the cytoplasmic fraction, as well as the expression of Fra1, c-Fos, and c-Jun in the nuclear fraction, of neutrophils. However, exposure of these cells to Rb1 reduced the expression and level of the investigated proteins. No changes were found in the expression of APRIL and the level of p-p38 in the cytoplasmic fraction of neutrophils following the application of Rb1 alone, as well as in the neutrophils incubated first with Rb1 and then with TGF-ß, whereas a higher level of phosphorylation was observed for Akt and PI3 kinases in the cells. Moreover, a higher expression of all the studied transcription factors was observed in the nuclear fraction of neutrophils. Based on the observed changes, it may be assumed that the expression of APRIL molecule in TGF-ß-induced neutrophils and its regulation by Rb1 are associated with PI3K/AKT signaling pathways and transcription factors Fra-1, Fra-2, c-Jun, and c-Fos. Rb1 appears to be a favorable factor that may be potentially used in the modulation of tumor-promoting APRIL expression.

Wetland buffer zones for nitrogen and phosphorus retention: Impacts of soil type, hydrology and vegetation.

Wetland buffer zones (WBZs) are riparian areas that form a transition between terrestrial and aquatic environments and are well-known to remove agricultural water pollutants such as nitrogen (N) and phosphorus (P). This review attempts to merge and compare data on the nutrient load, nutrient loss and nutrient removal and/or retention from multiple studies of various WBZs termed as riparian mineral soil wetlands, groundwater-charged peatlands (i.e. fens) and floodplains. Two different soil types ('organic' and 'mineral'), four different main water sources ('groundwater', 'precipitation', 'surface runoff/drain discharge', and 'river inundation') and three different vegetation classes ('arboraceous', 'herbaceous' and 'aerenchymous') were considered separately for data analysis. The studied WBZs are situated within the temperate and continental climatic regions that are commonly found in northern-central Europe, northern USA and Canada. Surprisingly, only weak differences for the nutrient removal/retention capability were found if the three WBZ types were directly compared. The results of our study reveal that for example the nitrate retention efficiency of organic soils (53 ± 28%; mean ± sd) is only slightly higher than that of mineral soils (50 ± 32%). Variance in load had a stronger influence than soil type on the N retention in WBZs. However, organic soils in fens tend to be sources of dissolved organic N and soluble reactive P, particularly when the fens have become degraded due to drainage and past agricultural usage. The detailed consideration of water sources indicated that average nitrate removal efficiencies were highest for ground water (76 ± 25%) and lowest for river water (35 ± 24%). No significant pattern for P retention emerged; however, the highest absolute removal appeared if the P source was river water. The harvesting of vegetation will minimise potential P loss from rewetted WBZs and plant biomass yield may promote circular economy value chains and provide compensation to land owners for restored land now unsuitable for conventional farming.

Environmental mercury exposure and selenium-associated biomarkers of antioxidant status at molecular and biochemical level. A short-term intervention study.

Mercury (Hg) is a potent toxicant. In the field of public health a chronic-low-level environmental Hg exposure resulting from fish consumption in general population is still being discussed. The objective of the study was to assess the influence of real Hg exposure on biomarkers of selenium (Se) status and selected biomarkers of pro-oxidant/anti-oxidant effects in healthy men (n = 67) who participated in the short-term intervention study consisting in daily fish consumption for two weeks. The analysis included Se level, Se-associated antioxidants at molecular (profile of 7 genes encoding selected proteins related to antioxidant defense) and biochemical levels (Se-dependent glutathione peroxidases activities and plasma selenoprotein P concentration). A pro-oxidant/anti-oxidant balance was explored using a biomarker of plasma lipid peroxidation and total antioxidant activity. The study revealed significant correlations (p < 0.05) between the biomarkers of exposure to Hg, Se level and Se-dependent antioxidants. Even though the risk of adverse effects of Hg for volunteers was substantially low, biomarkers of Hg altered levels of circulation selenoproteins and their genes expression. Changes in genes expression during study differed between the main enzymes involved in two systems: downregulation of thioredoxin reductase1 and upregulation of glutathione peroxidases. Hg exposure caused imbalance between the biomarkers of pro-oxidant/anti-oxidant effects.

Biomarkers of selenium status and antioxidant effect in workers occupationally exposed to mercury.

The present observation based research was designed to evaluate the influence of occupational human exposure to metallic mercury (Hg°) vapor on the biomarkers of selenium status involved in the antioxidant defense system. For this purpose we determined Hg and selenium (Se) concentrations in body fluids, the markers of antioxidant effect measured as an activity of Se-dependent enzymes (red blood cell and plasma glutathione peroxidase: GPx1-RBC and GPx3-P), concentration of selenoprotein P in the plasma (SeP-P) and total antioxidant activity in the plasma (TAA-P) in 131 male workers from a chloralkali plant exposed to Hg° and 67 non-exposed males (control group). The mRNA expression levels of glutathione peroxidases (GPX1, GPX3), selenoprotein P (SEPP1), thioredoxin reductase 1 (TRXR1), thioredoxin 1 (TRX1), peroxiredoxins (PRDX1, PRDX2) were also examined in the leukocytes of peripheral blood. Hg concentration in the blood (Hg-B) and urine (Hg-U) samples was determined using the thermal decomposition amalgamation/atomic absorption spectrometry (TDA-AAS) method and Se concentrations in plasma (Se-P) and urine (Se-U) using the inductively coupled plasma mass spectrometry (ICP-MS) method. Activities of GPx1-RBC, GPx3-P and TAA-P were determined using the kinetic and spectrophotometric method, respectively. Gene expression analysis was performed using the quantitative Real-Time PCR. The results showed significant higher Hg levels among the Hg°-exposed workers in comparison to control group (12-times higher median for Hg-B and almost 74-times higher median for Hg-U concentration in chloralkali workers). Se-P was also significantly higher (Me (median): 82.85 µg/L (IQR (interquartile range) 72.03-90.28 µg/L) for chloralkali workers vs. Me: 72.74 µg/L (IQR 66.25-80.14 µg/L) for control group; p = 0.0001) but interestingly correlated inversely with Hg-U in chloralkali workers suggesting depletion of the Se protection among the workers with the highest Hg-U concentration. The mRNA level for GPX1, PRXD1 were markedly but significantly higher in the workers compared to the control group. Moreover, concentrations of Hg-B and Hg-U among the workers were significantly positively correlated with the levels of selenoprotein P at both the mRNA and selenoprotein levels. In the multivariate model, after adjusting to cofounders (dental amalgam fillings, age, BMI, job seniority time, smoking), we confirmed that Hg-U concentration was inversely correlated with genes expression of TRXR1. This is the first comprehensive assessment of the impact of occupational exposure of workers to Hg° at both the mRNA and selenoprotein levels, with investigation of fish intake obtained by means of a questionnaire. These findings suggest that exposure to Hg° alters gene expression of the antioxidant enzymes and the level of Se-containing selenoproteins.

The Association Between Long-Term Acenocoumarol Treatment and Vitamin D Deficiency.

OBJECTIVE: Both vitamin D and K2 are involved in a number of metabolic processes, including bone metabolism; however, associations between the vitamins are not fully understood. The aim of the study was to evaluate serum concentrations of 25-hydroxyvitamin D [25(OH)D] in adult patients receiving long-term acenocoumarol (AC) treatment. PARTICIPANTS AND METHODS: In this cross-sectional study, 58 Caucasian patients (31 women, 27 men) with a median age of 65 years receiving long-term AC therapy were evaluated and compared with 35 age- and gender-matched healthy controls. The AC treatment was used due to recurrent venous thromboembolism (34.5%), atrial fibrillation (31%), or mechanical heart valve prostheses (34.5%). Medical records and a questionnaire were used to obtain information about chronic diseases, smoking habits, and the duration of therapy and weekly dose of AC. Anthropometric measurements were performed, and serum concentration of 25(OH)D and total alkaline phosphatase (ALP) activity were measured. RESULTS: Among the 58 patients receiving long-term AC treatment, a high proportion (46.6%) demonstrated significant vitamin D deficiency with concentrations of 25(OH)D lower than 20 ng/mL. The median concentration of 25(OH)D in subjects receiving AC was significantly lower compared to the control group [20.4 (17.4; 26.1) vs. 28.2 (24; 32.7); p < 0.001]. No differences were found between women and men receiving AC therapy. In patients receiving AC, a negative correlation was found between the concentration of 25(OH)D and the weekly dose of AC (r = -0.337, p = 0.01). Patients with concentrations of 25(OH)D < 20 ng/mL were found to have a significantly higher median dose of AC, compared to those with concentrations of 25(OH)D ≥ 20 ng/mL [21 (17; 31) vs. 17 (12; 28); p = 0.045]. CONCLUSION: In conclusion, treatment with AC is associated with low 25-hydroxyvitamin D levels, although the path leading to this phenomenon is not entirely clear. Long-term administration of AC in adults may increase the risk of chronic vitamin D deficiency, thus, effective supplementation of vitamin D in these individuals needs careful consideration.

Selenium and Epigenetics in Cancer: Focus on DNA Methylation.

Chemopreventive activity of selenium (Se) may influence epigenome. In this review, we have discussed two aspects of Se and epigenetics in cancer, related to (1) the association between Se and epigenetic regulation in cancer development and prevention; (2) epigenetic modification of selenoprotein-encoding genes in different cancers. In both issues, we focused on DNA methylation as the most investigated epigenetic mechanism. The existing evidence from experimental data in human cancer cell lines, rodents, and human studies in cancer-free subjects indicates that: high Se exposure leads to the inhibition of DNA methyltransferase expression/activity; the association between Se and global methylation remains unclear and requires further investigation with respect to the underlying mechanisms and possible nonlinear character of this relationship; Se affects methylation of specific tumor suppressor genes, possibly in a sex-dependent manner; and cancer phenotype is often characterized by altered methylation of selenoprotein-encoding genes, mainly glutathione peroxidase 3.

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism.

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

Selenium and Human Health: Witnessing a Copernican Revolution?

In humans, selenium was hypothesized to lower the risk of several chronic diseases, mainly due to the antioxidant activity of selenium-containing proteins. Recent epidemiologic and laboratory studies, however, are changing our perception of the biological effects of this nutritionally essential trace element. We reviewed the most recent epidemiologic and biochemical literature on selenium, synthesizing the findings from these studies into a unifying view. Randomized trials have shown that selenium did not protect against cancer and other chronic diseases, but even increased the risk of specific neoplasms such as advanced prostate cancer and skin cancer, in addition to type 2 diabetes. Biochemical studies indicate that selenium may exert a broad pattern of toxic effects at unexpectedly low concentrations. Furthermore, its upregulation of antioxidant proteins (selenium-dependent and selenium-independent) may be a manifestation of self-induced oxidative stress. In conclusion, toxic effects of selenium species occur at lower concentrations than previously believed. Those effects may include a large range of proteomic changes and adverse health effects in humans. Since the effects of environmental exposure to this element on human health still remain partially unknown, but are potentially serious, the toxicity of selenium exposure should be further investigated and considered as a public health priority.

Association between plasma selenium level and NRF2 target genes expression in humans.

Animal studies in rodent and in vitro studies indicate compensatory role of nuclear factor (erythroid-derived 2)-like (Nrf2) and Nrf2-regulated antioxidant and phase II biotransformation enzymes for the dietary selenium (Se) deficiency or for the loss of selenoproteins. To explore associations between plasma Se level and NRF2-regulated cytoprotective genes expression, an observational study was conducted in a population of 96 healthy non-smoking men living in Central Poland aged 18-83 years with relatively low plasma Se level. NRF2, KEAP2, CAT, EPHX1, GCLC, GCLM, GPX2, GSR, GSTA1, GSTM1, GSTP1, GSTT1, HMOX1, NQO1, PRDX1, SOD1, SOD2, TXNRD1 transcript levels in peripheral blood leukocytes and polymorphism of NRF2-617C/A (rs6721961) in blood genomic DNA were determined by means of quantitative real-time PCR. Mean plasma Se level was found to be 51.10±15.25µg/L (range 23.86-96.18µg/L). NRF2 mRNA level was positively correlated with expression of investigated NRF2-target genes. The multivariate linear regression adjusting for selenium status showed that plasma Se level was significantly inversely associated only with expression of GSTP1 (ß-coef.=-0.270, p=0.009), PRDXR1 (ß-coef.=-0.245, p=0.017) and SOD2 with an inverse trend toward significance (ß-coef.=-0.186, p=0.074), but without an effect of NRF2 gene variants. NRF2 expression was inversely associated with age (r=-0.23, p=0.03) and body mass index (r=-0.29, p<0.001). The findings may suggest a possible link between plasma Se level and cytoprotective response at gene level in humans.

Low investment in sexual reproduction threatens plants adapted to phosphorus limitation.

Plant species diversity in Eurasian wetlands and grasslands depends not only on productivity but also on the relative availability of nutrients, particularly of nitrogen and phosphorus. Here we show that the impacts of nitrogen:phosphorus stoichiometry on plant species richness can be explained by selected plant life-history traits, notably by plant investments in growth versus reproduction. In 599 Eurasian sites with herbaceous vegetation we examined the relationship between the local nutrient conditions and community-mean life-history traits. We found that compared with plants in nitrogen-limited communities, plants in phosphorus-limited communities invest little in sexual reproduction (for example, less investment in seed, shorter flowering period, longer lifespan) and have conservative leaf economy traits (that is, a low specific leaf area and a high leaf dry-matter content). Endangered species were more frequent in phosphorus-limited ecosystems and they too invested little in sexual reproduction. The results provide new insight into how plant adaptations to nutrient conditions can drive the distribution of plant species in natural ecosystems and can account for the vulnerability of endangered species.

Selenium supplementation to chronic kidney disease patients on hemodialysis does not induce the synthesis of plasma glutathione peroxidase.

BACKGROUND: Numerous authors have shown that selenium (Se) concentration and glutathione peroxidase (GSH-Px) activity in plasma of chronic kidney disease (CKD) patients are lower than in healthy subjects, but there are only few publications on the level of GSH-Px protein in those patients and no reports on the effect of Se supplementation to HD patients on the level of this enzyme. SUBJECTS AND METHODS: Se concentration and GSH-Px protein level in plasma were measured in a group of 30 CKD patients on hemodialysis (HD) supplemented with 200 microg Se/day for 3 months, and 28 patients on HD administered with placebo. Se concentration was measured by graphite furnace atomic absorption spectrometry and plasma GSH-Px protein level by the sandwich ELISA method using polyclonal antibody specific for human plasma GSH-Px. RESULTS: Se concentration in patients on placebo did not change throughout the 3-month study period, but increased significantly in Se supplemented group. Se supplementation to CKD patients on HD had no effect on the level of GSH-Px protein. CONCLUSIONS: The lack of GSH-Px protein in CKD patients on HD is not linked to Se deficiency since the level of this element increased after Se supplementation while enzyme protein level did not change. The damaged kidney of HD patients is unable to synthesize GSH-Px, even after induction with selenium.

Expression of selenoprotein-coding genes SEPP1, SEP15 and hGPX1 in non-small cell lung cancer.

Aim of the study was to investigate the mRNA expression level of selenoprotein P (SEPP1), 15-kDa selenoprotein (SEP15) and glutathione peroxidase 1 (hGPX1) in paired malignant and non-malignant tissue. To achieve this goal, the quantitative real-time PCR technique was utilized in paired tissue samples from 33 non-small cell lung cancer (NSCLC) patients. Simultaneously, the activity of glutathione peroxidases (GPX) and the level of thiobarbituric acid-reactive species (TBARS) in paired tissue specimens and the blood plasma selenium level was measured. We found significant down-regulation of SEPP1 expression level in tumorous lung tissue (2.732-fold; p<0.001). The expression of hGPX1 and SEP15 in tumorous tissue remained unchanged compared to healthy tissue. The level of TBARS in malignant tissue was significantly increased (p<0.005) and negatively correlated with SEPP1 expression level (R(S)=-0.3238; p<0.05). The activity of GPX in malignant tissue was significantly increased compared to the non-malignant one (p<0.005) and negatively correlated with the expression level of SEPP1. It seems possible, that the down-regulation of SEPP1 expression may lead to an increased oxidative stress possibly resulting in lung carcinogenesis. Increased activity of GPX in tumorous lung tissue seems to be a feedback mechanism.