Improved cardiovascular health by supplementation with selenium and coenzyme Q10: applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective randomized double-blind placebo-controlled intervention project in Sweden

Purpose Selenium and coenzyme Q10 have synergistic antioxidant functions. In a four-year supplemental trial in elderly Swedes with a low selenium status, we found improved cardiac function, less cardiac wall tension and reduced cardiovascular mortality up to 12 years of follow-up. Here we briefly review the main results, including those from studies on biomarkers related to cardiovascular risk that were subsequently conducted. In an effort, to explain underlying mechanisms, we conducted a structured analysis of the inter-relationship between biomarkers. Methods Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/ day), or placebo was given to 443 elderly community-living persons, for 48 months. Structural Equation Modelling (SEM) was used to investigate the statistical inter-relationships between biomarkers related to inflammation, oxidative stress, insulin-like growth factor 1, expression of microRNA, fibrosis, and endothelial dysfunction and their impact on the clinical effects. The main study was registered at Clinicaltrials.gov at 30th of September 2011, and has the identifier NCT01443780. Results In addition to positive clinical effects, the intervention with selenium and coenzyme Q10 was also associated with favourable effects on biomarkers of cardiovascular risk. Using these results in the SEM model, we showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress influencing the factors, fibrosis (β = 0.74; p < 0.001) and myocardium (β = 0.65; p < 0.001). According to the model, the intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced CV mortality. Conclusion Selenium reduced inflammation and oxidative stress. According to the SEM analysis, these effects reduced fibrosis and improved myocardial function pointing to the importance of supplementation in those low on selenium and coenzyme Q10. © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/Improved cardiovascular health by supplementation with selenium and coenzyme Q10: applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective randomized double-blind placebo-controlled intervention project in SwedenpublishedVersio

Erythrocytes as Messengers for Information and Energy Exchange between Cells

Evolution has created a hierarchy of systems for information and energy using different cells according to messages generated from DNA, RNA, and other sources. Erythrocytes are formed in high speed at about 2 × 106/s to balance dying or not working erythrocytes to maintain optimal energy and information transfer. Important information is handled by nucleotides and distribution of metal ions and phosphates when starting synthesis process. Handling of these processes needs kinases known to be magnesium-dependent. Oxygen delivered by erythrocytes is used by other cells to synthesize ATP and to increase reaction capacity. Complex signals to bone marrow balance erythroblasts before developing into reticulocytes and erythrocytes. We discuss some aspects of erythrocyte communication with other cells of the body with special focus on magnesium and selenium in this process

Erythrocytes as Biomarkers of Virus and Bacteria in View of Metal Ion Homeostasis

The erythrocyte contributes to the immune system in several ways. It sequesters interferons, interleukins or chemokines and by binding nucleic acid. It binds virus and bacteria and may deliver bacteria to macrophages for phagocytosis. It may also kill bacteria directly with oxygen. For proper function of the erythrocyte, homeostasis of reactive oxygen species, selenium, metal ions and trace elements is important. Erythrocytes display morphological and metabolic changes in diseases like sepsis, and in several genetic diseases. Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), giving rise to the coronavirus disease 2019 (Covid-19), show many erythrocyte changes as compared to healthy controls. The erythrocyte responds to hemolysins by purinergic signaling leading to hemolysis or phosphatidylserine exposure on the plasma membrane. Phosphatidylserine marks erythrocytes for clearance by spleen macrophages. Regulated erythrocyte cell death, also called eryptosis, can be induced by oxidative stress, pathogen infection, and certain diseases like sepsis. Erythrocytes may, in the future, contribute more to diagnosis based on research and diagnostic technological development

Sickness Behavior in Community-Dwelling Elderly: Associations with Impaired Cardiac Function and Inflammation

Sickness behavior is a cluster of symptoms that occur as a response to an infection and alterations in the inflammatory response. Under normal circumstances, sickness behavior is fully reversible once the pathogen has been cleared. Aging and chronic illness such as heart failure are associated with enhanced inflammatory activity that lasts for a long duration and no longer represents an adaptive response. The aim of this study was to explore whether inflammation mediates the relationship between impaired cardiac function and a symptom cluster including anhedonia, fatigue, and sleepiness, which might represent sickness behavior in community-dwelling elders. Structural equation modeling (SEM) showed that the factor impaired cardiac function (i.e., N-terminal fragment of pro-brain natriuretic peptide, left ventricular ejection fraction, and the heart failure medications angiotensin converting enzyme inhibitor, angiotensin receptor blockade, β-blocker, and diuretics) was associated with both inflammation (i.e., C-reactive protein; β = .26) and the symptom cluster (β = .31). Inflammation had a significant direct, but smaller, association with the symptom cluster (β = .21). By this pathway, inflammation also mediated an indirect association between impaired cardiac function and the symptom cluster (β = .05). Including creatinine, blood glucose, ischemic heart disease, previous and current tumor, respiratory disease, age, and body mass index in the SEM model did not change these associations. Our results imply that some aspects of the symptom panorama in elderly individuals with impaired cardiac function or heart failure could represent sickness behavior

The Contribution of Heart Failure to Sleep Disturbances and Depressive Symptoms in Older Adults

Background: The aim of this study was to explore the associations between physical symptoms, sleep disturbances, and depressive symptoms in community-dwelling elderly individuals, comparing persons with and without heart failure (HF). Methods: A total of 613 older adults (mean age 78 years) underwent clinical and echocardiographic examinations. Questionnaires were used to evaluate sleep disturbances and depressive symptoms. A model was developed in those with HF (n = 107) and compared with those without HF (n = 506). Results: Cardiopulmonary symptoms (ie, dyspnea and nighttime palpitations) and pain had significant direct associations with sleep disturbances, which indirectly affected depressive symptoms. The model was essentially the same in those with and without HF except that the effect of sleep disturbances on depressive symptoms was stronger in those with HF (β = 0.64 vs β = 0.45, P = .006). Conclusion: In community-dwelling older adults, regardless of their diagnosis, physical symptoms had a direct effect on sleep disturbances and an indirect effect on depressive symptoms

Divergence in gene expression related to variation in host specificity of an ectomycorrhizal fungus

Ectomycorrhizae are formed by mutualistic interactions between fungi and the roots of woody plants. During symbiosis the two organisms exchange carbon and nutrients in a specific tissue that is formed at the contact between a compatible fungus and plant. There is considerable variation in the degree of host specificity among species and strains of ectomycorrhizal fungi. In this study, we have for the first time shown that this variation is associated with quantitative differences in gene expression, and with divergence in nucleotide sequences of symbiosis-regulated genes. Gene expression and sequence evolution were compared in different strains of the ectomycorrhizal fungus Paxillus involutus; the strains included Nau, which is not compatible with birch and poplar, and the two compatible strains Maj and ATCC200175. On a genomic level, Nau and Maj were very similar. The sequence identity was 98.9% in the 16 loci analysed, and only three out of 1075 genes analysed by microarray-based hybridizations had signals indicating differences in gene copy numbers. In contrast, 66 out of the 1075 genes were differentially expressed in Maj compared to Nau after contact with birch roots. Thirty-seven of these symbiosis-regulated genes were also differentially expressed in the ATCC strain. Comparative analysis of DNA sequences of the symbiosis-regulated genes in different strains showed that two of them have evolved at an enhanced rate in Nau. The sequence divergence can be explained by a decreased selection pressure, which in turn is determined by lower functional constraints on these proteins in Nau as compared to the compatible strains

Comparison of Erythrocytes for Individual Indications of Metabolism Changes in Parkinson’s and Alzheimer’s Diseases

Alzheimer’s and Parkinson’s diseases are neurodegenerative diseases where several biomarkers have suggested that a single measurement is not a sufficient biomarker. The observation of increased concentration of cadmium (Cd), lead (Pb), and silver (Ag) in erythrocytes by inductively coupled plasma mass spectrometry (ICP-MS) shows a need to look for new approaches to understand the complex synchronistic effects of the cell metabolism. We have used a simplified scheme to follow some of the effects by following a hierarchy of reactions simplified to monitor elements in peripheral blood cells, e.g., erythrocytes. Erythrocytes carry oxygen to cells and carbon dioxide and waste to the lungs and back when passing from different organs including the brain. Erythrocytes also have the capacity to carry metal ions, which may be transferred to other organs, e.g., brain, despite the blood-brain barrier (BBB) and choroid plexus filter. If transfer of Cd, Pb, and Ag is continued too long, the repair systems may not be sufficient, and epigenetic effects on DNA and RNA may begin. Peripheral blood cells, e.g., erythrocytes, may help get earlier individual indications of changes at the cell level by using ICP-MS

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente