Selenium and viral infection: are there lessons for COVID-19?

Selenium (Se) is a micronutrient that is essential for human health. Sub-optimal Se status is common, occurring in a significant proportion of the population across the world, including parts of Europe and China. Human and animal studies have shown that Se status is a key determinant of the host response to viral infections. In this review, we address the question whether Se intake is a factor in determining the severity of response to COVID-19. Emphasis is placed on epidemiological and animal studies which suggest that Se affects host response to RNA viruses and on the molecular mechanisms by which Se and selenoproteins modulate the inter-linked redox homeostasis, stress response and inflammatory response. Together these studies indicate that Se status is an important factor in determining the host response to viral infections. Therefore, we conclude that Se status is likely to influence human response to the SARS-CoV-2 infection and that Se status is one (of several) risk factors which may impact on the outcome of SARS-CoV-2 infection, particularly in populations where Se intake is suboptimal or low. We suggest the use of appropriate markers to assess the Se status of COVID-19 patients and possible supplementation may be beneficial in limiting the severity of symptoms, especially in countries where Se status is regarded as sub-optimal

Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk.

Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases and 975 controls matched for age and hormone replacement therapy (HRT) use was genotyped for five functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast cancer risk was assessed using conditional logistic regression. Additionally pre-diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the population. A 60% reduction in risk of developing overall BC and ductal BC was observed in women who were homozygous Thr carriers for SEPP1 rs3877899. Additionally, Leu carriers for GPX1 Pro198Leu polymorphism (rs1050450) were at ∼2 fold increased risk of developing a non-ductal BC. Pre-diagnosis eGPx activity was found to depend on genotype for rs713041 (GPX4), rs3877899 (SEPP1), and rs1050450 (GPX1) and on HRT use. Moreover, depending on genotype and HRT use, eGPx activity was significantly lower in women who developed BC later in life compared with controls. Furthermore, GPx1 protein levels increased in human breast adenocarcinoma MCF7 cells exposed to β-estradiol and sodium selenite.In conclusion, our data provide evidence that SNPs in SEPP1 and GPX1 modulate risk of BC and that eGPx activity is modified by SNPs in SEPP1, GPX4 and GPX1 and by estrogens. Our data thus suggest a role of selenoproteins in BC development

Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status

Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (P-ACT = 0.10; P-ACT significance threshold was P <0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.Peer reviewe

A novel technique to characterize conformational state of the proteins: p53 analysis

4noAs the technology is advancing, biotechnologist and pharmacologist seems more interested and focused towards the development of innovative sensing solution/technology capable of evaluating proteins without any limitations of time and cost which were encountered/offered by conventional/traditional methods such as ELISA used for protein quantification. To allow continuous monitoring and attain protein sample information in a non-invasive way, spectrophotometry might be considered as an alternate method which analyzes different conformational states of proteins by closely observing the variation in optical properties of the sample. The work presented studies p53 protein conformational dynamics and their involvement in various pathophysiological and neurodegenerative disease/disorders using the spectrophotometer-based method. By utilizing the technique of spectrophotometry, investigations were carried out on three samples containing varied molecular state of p53 (Wild p53, Denatured p53, and Oxidized p53), to detect the difference in light absorption. Overall, this proposes the possibility of a simple, non-invasive and optical based method capable of detecting and identifying different structural states of p53 while overcoming the complexities offered by the conventional procedures.nonenoneAbdullah, Saad*; Serpelloni, Mauro; Abate, Giulia; Uberti, DanielaAbdullah, Saad; Serpelloni, Mauro; Abate, Giulia; Uberti, Daniel

Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 µg/L and 4.3 mg/L in cases and 85.6 µg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95%CI: 0.82-1.03 per 25 µg/L increase). However, sub-group analyses by sex showed a statistically significant association for women (Ptrend = 0.032; per 25 µg/L Se increase, IRR = 0.83, 95%CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (Ptrend = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95%CI: 0.82-0.98) with the association more apparent in women (Ptrend = 0.004; IRR = 0.82, 95%CI: 0.72-0.94 per 0.806 mg/L increase) than men (Ptrend = 0.485; IRR = 0.98, 95%CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women

Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 g/L and 4.3 mg/L in cases and 85.6 g/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR=0.92, 95% CI: 0.82-1.03 per 25 g/L increase). However, sub-group analyses by sex showed a statistically significant association for women (p(trend)=0.032; per 25 g/L Se increase, IRR=0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (p(trend)=0.009; per 0.806 mg/L increase, IRR=0.89, 95% CI: 0.82-0.98) with the association more apparent in women (p(trend)=0.004; IRR=0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (p(trend)=0.485; IRR=0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women. What's new? Selenium is an essential micronutrient with anti-carcinogenic properties, but its association with the development of colorectal cancer is controversial. In the present study, the authors find that the selenium status in many Western Europeans is suboptimal. Higher selenium levels were inversely associated with the risk to develop colorectal carcinoma, a finding more evident in women than in men. The authors argue that in populations where the selenium status is sub-optimal (e.g. Western Europe) increasing selenium intake may reduce colorectal carcinoma risk, while contrasting results may be obtained in regions with higher selenium intake

Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 g/L and 4.3 mg/L in cases and 85.6 g/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR=0.92, 95% CI: 0.82-1.03 per 25 g/L increase). However, sub-group analyses by sex showed a statistically significant association for women (p(trend)=0.032; per 25 g/L Se increase, IRR=0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (p(trend)=0.009; per 0.806 mg/L increase, IRR=0.89, 95% CI: 0.82-0.98) with the association more apparent in women (p(trend)=0.004; IRR=0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (p(trend)=0.485; IRR=0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women. What's new? Selenium is an essential micronutrient with anti-carcinogenic properties, but its association with the development of colorectal cancer is controversial. In the present study, the authors find that the selenium status in many Western Europeans is suboptimal. Higher selenium levels were inversely associated with the risk to develop colorectal carcinoma, a finding more evident in women than in men. The authors argue that in populations where the selenium status is sub-optimal (e.g. Western Europe) increasing selenium intake may reduce colorectal carcinoma risk, while contrasting results may be obtained in regions with higher selenium intake