Inter-individual variation in nucleotide excision repair in young adults: effects of age, adiposity, micronutrient supplementation and genotype

Nucleotide excision repair (NER) is responsible for repairing bulky helix-distorting DNA lesions and is essential for the maintenance of genomic integrity. Severe hereditary impairment of NER leads to cancers such as those in xeroderma pigmentosum, and more moderate reductions in NER capacity have been associated with an increased cancer risk. Diet is a proven modifier of cancer risk but few studies have investigated the potential relationships between diet and NER. In the present study, the plasmid-based host cell reactivation assay was used to measure the NER capacity in peripheral blood mononuclear cells from fifty-seven volunteers aged 18–30 years before and after 6 weeks of supplementation with micronutrients (selenium and vitamins A, C and E). As a control, nine individuals remained unsupplemented over the same period. Volunteers were genotyped for the following polymorphisms in NER genes: ERCC5 Asp1104His (rs17655); XPC Lys939Gln (rs2228001); ERCC2 Lys751Gnl (rs13181); XPC PAT (an 83 bp poly A/T insertion–deletion polymorphism in the XPC gene). NER capacity varied 11-fold between individuals and was inversely associated with age and endogenous DNA strand breaks. For the first time, we observed an inverse association between adiposity and NER. No single polymorphism was associated with the NER capacity, although significant gene–gene interactions were observed between XPC Lys939Gln and ERCC5 Asp1104His and XPC Lys939Gln and ERCC2 Lys751Gnl. While there was no detectable effect of micronutrient supplementation on NER capacity, there was evidence that the effect of fruit intake on the NER capacity may be modulated by the ERCC2 Lys751Gnl single nucleotide polymorphism

Invited letter to editor in response to: Finland’s handling of selenium is a model in these times of coronavirus infections.

This response by the authors is in reply to a letter from Ulfberg and Stehlik (https://doi.org/10.1017/S0007114520003827) in comment to the authors' orginal article (https://doi.org/10.1017/S0007114520003128) that suggested that SE status was an important factor in determining the host response to viral infections

Expression profiling indicating low selenium-sensitive microRNA levels linked to cell cycle and cell stress response pathways in the CaCo-2 cell line

Se is an essential micronutrient for human health, and fluctuations in Se levels and the potential cellular dysfunction associated with it may increase the risk for disease. Although Se has been shown to influence several biological pathways important in health, little is known about the effect of Se on the expression of microRNA (miRNA) molecules regulating these pathways. To explore the potential role of Se-sensitive miRNA in regulating pathways linked with colon cancer, we profiled the expression of 800 miRNA in the CaCo-2 human adenocarcinoma cell line in response to a low-Se (72 h at <40 nm) environment using nCounter direct quantification. These data were then examined using a range of in silico databases to identify experimentally validated miRNA-mRNA interactions and the biological pathways involved. We identified ten Se-sensitive miRNA (hsa-miR-93-5p, hsa-miR-106a-5p, hsa-miR-205-5p, hsa-miR-200c-3p, hsa-miR-99b-5p, hsa-miR-302d-3p, hsa-miR-373-3p, hsa-miR-483-3p, hsa-miR-512-5p and hsa-miR-4454), which regulate 3588 mRNA in key pathways such as the cell cycle, the cellular response to stress, and the canonical Wnt/β-catenin, p53 and ERK/MAPK signalling pathways. Our data show that the effects of low Se on biological pathways may, in part, be due to these ten Se-sensitive miRNA. Dysregulation of the cell cycle and of the stress response pathways due to low Se may influence key genes involved in carcinogenesis

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 maternal micronutrient status, oxidative stress and common genetic variants in antioxidant enzymes at 15 weeks’ gestation in nulliparous women who subsequently develop pre-eclampsia

Aims: Pre-eclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality. Deficiencies of specific micronutrient antioxidant activities associated with copper, selenium, zinc and manganese, have previously been linked to pre-eclampsia at time of disease. Our aims were to investigate whether maternal plasma micronutrient concentrations and related antioxidant enzyme activities are altered prior to pre-eclampsia onset and to examine the dependence on genetic variations in these antioxidant enzymes. Methods: Pre-disease plasma samples (15+1 weeks’ gestation) were obtained from women enrolled in the international SCreening fOr Pregnancy Endpoints (SCOPE) study who subsequently developed pre-eclampsia (n=244), and age- and BMI-matched normotensive controls (n=472). Micronutrient concentrations were measured by inductively coupled plasma mass spectrometry; associated antioxidant enzyme activities, selenoprotein-P, caeruloplasmin concentrations and activities, antioxidant capacity and markers of oxidative stress were measured by colorimetric assays. Sixty four tagSNPs within genes encoding the antioxidant enzymes and selenoprotein-P were genotyped using allele-specific competitive PCR. Results: Plasma copper and caeruloplasmin concentrations were modestly, but significantly elevated in women who subsequently developed pre-eclampsia (both P<0.001) compared to controls (median [IQR], copper: 1957.4 [1787, 2177.5] vs. 1850.0 [1663.5, 2051.5] µg/L; caeruloplasmin: 2.5[1.4, 3.2] vs. 2.2[1.2, 3.0] µg/ml). There were no differences in other micronutrients or enzymes between groups. No relationship was observed between genotype for single nucleotide polymorphisms (SNPs) and antioxidant enzyme activity. Conclusions: This analysis of a prospective cohort study reports maternal micronutrient concentrations in combination with associated antioxidant enzymes and SNPs in their encoding genes in women at 15 weeks’ gestation that subsequently developed pre-eclampsia. The modest elevation in copper may contribute to oxidative stress, later in pregnancy, in those women that go on to develop pre-eclampsia. The lack of evidence to support the hypothesis that functional SNPs influence antioxidant enzyme activity in pregnant women argues against a role for these genes in the aetiology of pre-eclampsia

GRADE-ADOLOPMENT process to develop 24-hour movement behavior recommendations and physical activity guidelines for the under 5s in the United Kingdom, 2019

Background: This article summarizes the approach taken to develop UK Chief Medical Officers' physical activity guidelines for the Under 5s, 2019. Methods: The Grading of Recommendations Assessment, Development and Evaluation (GRADE)- Adaptation, Adoption, De Novo Development (ADOLOPMENT) approach was used, based on the guidelines from Canada and Australia, with evidence updated to February 2018. Recommendations were based on the associations between (1) time spent in sleep, sedentary time, physical activity, and 10 health outcomes and (2) time spent in physical activity and sedentary behavior on sleep outcomes (duration and latency). Results: For many outcomes, more time spent in physical activity and sleep (up to a point) was beneficial, as was less time spent in sedentary behavior. The authors present, for the first time, evidence in GRADE format on behavior type-outcome associations for infants, toddlers, and preschoolers. Stakeholders supported all recommendations, but recommendations on sleep and screen time were not accepted by the Chief Medical Officers; UK guidelines will refer only to physical activity. Conclusions: This is the first European use of GRADE-ADOLOPMENT to develop physical activity guidelines. The process is robust, rapid, and inexpensive, but the UK experience illustrates a number of challenges that should help development of physical activity guidelines in future

Role of parental and environmental characteristics in toddlers\u27 physical activity and screen time: Bayesian analysis of structural equation models

BACKGROUND: Guided by the Socialization Model of Child Behavior (SMCB), this cross-sectional study examined direct and indirect associations of parental cognitions and behavior, the home and neighborhood environment, and toddlers\u27 personal attributes with toddlers\u27 physical activity and screen time. METHODS: Participants included 193 toddlers (1.6&thinsp;&plusmn;&thinsp;0.2&nbsp;years) from the Parents\u27 Role in Establishing healthy Physical activity and Sedentary behavior habits (PREPS) project. Toddlers\u27 screen time and personal attributes, physical activity- or screen time-specific parental cognitions and behaviors, and the home and neighborhood environment were measured via parental-report using the PREPS questionnaire. Accelerometry-measured physical activity was available in 123 toddlers. Bayesian estimation in structural equation modeling (SEM) using the Markov Chain Monte Carlo algorithm was performed to test an SMCB hypothesized model. Covariates included toddlers\u27 age, sex, race/ethnicity, main type of childcare, and family household income. RESULTS: In the SMCB hypothesized screen time model, higher parental barrier self-efficacy for limiting toddlers\u27 screen time was associated with higher parental screen time limiting practices (&beta;&thinsp;=&thinsp;0.451), while higher parental negative outcome expectations for limiting toddlers\u27 screen time was associated with lower parental screen time limiting practices (&beta;&thinsp;=&thinsp;-&thinsp;0.147). In turn, higher parental screen time limiting practices was associated with lower screen time among toddlers (&beta;&thinsp;=&thinsp;-&thinsp;0.179). Parental modeling of higher screen time was associated with higher screen time among toddlers directly (&beta;&thinsp;=&thinsp;0.212) and indirectly through the home environment. Specifically, higher screen time among parents was associated with having at least one electronic device in toddlers\u27 bedrooms (&beta;&thinsp;=&thinsp;0.146) and, in turn, having electronics in the bedroom, compared to none, was associated with higher screen time among toddlers (&beta;&thinsp;=&thinsp;0.250). Neighborhood safety was not associated with toddlers\u27 screen time in the SEM analysis. No significant correlations were observed between the SMCB variables and toddlers\u27 physical activity; thus, no further analyses were performed for physical activity. CONCLUSIONS: Parents and their interactions with the home environment may play an important role in shaping toddlers\u27 screen time. Findings can inform family-based interventions aiming to minimize toddlers\u27 screen time. Future research is needed to identify correlates of toddlers\u27 physical activity

Selenoprotein gene nomenclature

The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates