Obesity and type 2 diabetes (T2D) show an increased risk for a severe COVID-19 disease. Treatment with DPP4 inhibitor (DPP4i) results in reduced mortality and better clinical outcome. Here, we aimed ...to identify potential mechanisms for the observed DPP4i effect in COVID-19. Comparing T2D subjects with and without DPP4i treatment, we identified a significant increase of the anti-inflammatory adipokine sFRP5 in relation to DPP4 inhibition. sFRP5 is a specific antagonist to Wnt5a, a glycopeptide secreted by adipose tissue macrophages acting pro-inflammatory in various diseases. We therefore examined sFRP5 levels in patients hospitalised for severe COVID-19 and found significant lower levels compared to healthy controls. Since sFRP5 might consequently be a molecular link for the beneficial effects of DPP4i in COVID-19, we further aimed to identify the exact source of sFRP5 in adipose tissue on cellular level. We therefore isolated pre-adipocytes, mature adipocytes and macrophages from adipose tissue biopsies and performed western-blotting. Results showed a sFRP5 expression specifically in mature adipocytes of subcutaneous and omental adipose tissue. In summary, our data suggest that DPP4i increase serum levels of anti-inflammatory sFRP5 which might be beneficial in COVID-19, reflecting a state of sFRP5 deficiency.
The molecular foundation of chronic inflammatory diseases (CIDs) can differ markedly between individuals. As our understanding of the biochemical mechanisms underlying individual disease ...manifestations and progressions expands, new strategies to adjust treatments to the patient's characteristics will continue to profoundly transform clinical practice. Nutrition has long been recognized as an important determinant of inflammatory disease phenotypes and treatment response. Yet empirical work demonstrating the therapeutic effectiveness of patient-tailored nutrition remains scarce. This is mainly due to the challenges presented by long-term effects of nutrition, variations in inter-individual gastrointestinal microbiota, the multiplicity of human metabolic pathways potentially affected by food ingredients, nutrition behavior, and the complexity of food composition. Historically, these challenges have been addressed in both human studies and experimental model laboratory studies primarily by using individual nutrition data collection in tandem with large-scale biomolecular data acquisition (e.g. genomics, metabolomics, etc.). This review highlights recent findings in the field of precision nutrition and their potential implications for the development of personalized treatment strategies for CIDs. It emphasizes the importance of computational approaches to integrate nutritional information into multi-omics data analysis and to predict which molecular mechanisms may explain how nutrients intersect with disease pathways. We conclude that recent findings point towards the unexhausted potential of nutrition as part of personalized medicine in chronic inflammation.
The German Government’s Integrated Energy and Climate Programme (IEKP) and the National Biomass Action Plan set ambitious targets for the further development of bioenergy until 2020. The share of ...energy from biomass is supposed to reach 8 % and 9.7 % of the total power consumption and of the total heat usage, respectively. The share of biofuels on the total consumption of fuels for transportation should rise up to 12 % (energetic) by 2020. This project aims to assess the possibilities of achieving the IEKP targets for bioenergy in a regional and global context. On a regional as well as global level, the potentials of different biomasses were determined in different development scenarios until 2020. Furthermore, the extent to which remote sensing could contribute in improving the spatial specification of biomass resources and whether it could be used as a monitoring system for the early detection of land use changes was investigated. On the regional level, the spatial implications of energetic biomass use was analysed with regard to environmental impacts and land use conflicts. Depending on their significance of spatial impacts, instruments of spatial planning were assessed in order to steer the supply of bioenergy. ... from Executive Summary
The German Government’s Integrated Energy and Climate Programme (IEKP) and the National Biomass Action Plan set ambitious targets for the further development of bioenergy until 2020. The share of ...energy from biomass is supposed to reach 8 % and 9.7 % of the total power consumption and of the total heat usage, respectively. The share of biofuels on the total consumption of fuels for transportation should rise up to 12 % (energetic) by 2020. This project aims to assess the possibilities of achieving the IEKP targets for bioenergy in a regional and global context. On a regional as well as global level, the potentials of different biomasses were determined in different development scenarios until 2020. Furthermore, the extent to which remote sensing could contribute in improving the spatial specification of biomass resources and whether it could be used as a monitoring system for the early detection of land use changes was investigated. On the regional level, the spatial implications of energetic biomass use was analysed with regard to environmental impacts and land use conflicts. Depending on their significance of spatial impacts, instruments of spatial planning were assessed in order to steer the supply of bioenergy. ... from Executive Summary
Oxidized phospholipids (oxPAPC) induce endothelial dysfunction and atherosclerosis. Here we show that oxPAPC induce a gene network regulating serine-glycine metabolism with the mitochondrial ...methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) as a causal regulator using integrative network modeling and Bayesian network analysis in human aortic endothelial cells. The cluster is activated in human plaque material and by atherogenic lipoproteins isolated from plasma of patients with coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) within the MTHFD2-controlled cluster associate with CAD. The MTHFD2-controlled cluster redirects metabolism to glycine synthesis to replenish purine nucleotides. Since endothelial cells secrete purines in response to oxPAPC, the MTHFD2-controlled response maintains endothelial ATP. Accordingly, MTHFD2-dependent glycine synthesis is a prerequisite for angiogenesis. Thus, we propose that endothelial cells undergo MTHFD2-mediated reprogramming toward serine-glycine and mitochondrial one-carbon metabolism to compensate for the loss of ATP in response to oxPAPC during atherosclerosis.
Epigenetic marks critically control gene expression and thus the cellular activity state. The functions of many epigenetic modifiers in the vascular system have not yet been studied. We screened for ...histone modifiers in endothelial cells and observed a fairly high expression of the histone plant homeodomain finger protein 8 (PHF8). Given its high expression, we hypothesize that this histone demethylase is important for endothelial cell function. Overexpression of PHF8 catalyzed the removal of methyl-groups from histone 3 lysine 9 (H3K9) and H4K20, whereas knockdown of the enzyme increased H3K9 methylation. Knockdown of PHF8 by RNAi also attenuated endothelial proliferation and survival. As a functional readout endothelial migration and tube formation was studied. PHF8 siRNA attenuated the capacity for migration and developing of capillary-like structures. Given the impact of PHF8 on cell cycle genes, endothelial E2F transcription factors were screened, which led to the identification of the gene repressor E2F4 to be controlled by PHF8. Importantly, PHF8 maintains E2F4 but not E2F1 expression in endothelial cells. Consistently, chromatin immunoprecipitation revealed that PHF8 reduces the H3K9me2 level at the E2F4 transcriptional start site, demonstrating a direct function of PHF8 in endothelial E2F4 gene regulation. Conclusion: PHF8 by controlling E2F4 expression maintains endothelial function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine the accuracy of the recently proposed landmark-method ‘nostril-to-tragus minus 10 mm’ and compare with ERC-recommended distances for nasopharyngeal airway length sizing in children.
We ...conducted a prospective observational study in sedated children < 12 years. Nasopharyngeal airways were inserted following ‘nostril-to-tragus minus 10 mm’. Primary outcome was the rate of nasopharyngeal airway tips between soft palate and epiglottis on magnetic resonance imaging (MRI) indicated for medical reasons. An optimal placement was defined when the tip lied within 25–75% of the total soft palate-to-epiglottis distance. Between 0–100% of this distance, placement was still considered acceptable, below 0% too proximal or above 100% too distal. Secondary outcomes were the rate of adverse events, the qualitative positions of airway tips, and the comparison of ́nostril-to-tragus minus 10 mḿ with the ERC-recommended distances ‘nostril-to-angle of the mandible’ and ‘nostril-to-tragus’ with objective MRI measurements.
We analysed 92 patients with a mean age of 4.3 years. Nasopharyngeal airways were optimally placed in 37.0% (8.7% too proximal-77.2% acceptable-14.1% too distal). Three qualitative malpositions, but no airway-associated adverse event occurred. Objective measurements on MRI revealed the probability of 40.2% optimally placed nasopharyngeal airways (5.4%–67.4%–27.2%) for ‘nostril-to-tragus minus 10 mm’, 38.0% (17.4%–58.7%–23.9%) for ‘nostril-to-mandible’ and 13.0% (0%–28.3%–71.7%) for ‘nostril-to-tragus’, respectively.
No landmark-method predicted nasopharyngeal airway position reliably. ‘Nostril-to-tragus minus 10 mm’ seems the least inaccurate one and could be a valuable approximation until another estimation-formula proves more accurate. During insertion, careful clinical evaluation of airway patency is crucial.
German Clinical Trials Register; DRKS00021007.
PDF
