Age-related influence on DNA damage, proteomic inflammatory markers and oxidative stress in hospitalized COVID-19 patients compared to healthy controls.

COVID-19 infections are accompanied by adverse changes in inflammatory pathways that are also partly influenced by increased oxidative stress and might result in elevated DNA damage. The aim of this case-control study was to examine whether COVID-19 patients show differences in oxidative stress-related markers, unconjugated bilirubin (UCB), an inflammation panel and DNA damage compared to healthy, age-and sex-matched controls. The Comet assay with and without the treatment of formamidopyrimidine DNA glycosylase (FPG) and H2O2 challenge was used to detect DNA damage in whole blood. qPCR was applied for gene expression, UCB was analyzed via HPLC, targeted proteomics were applied using Olink® inflammation panel and various oxidative stress as well as clinical biochemistry markers were analyzed in plasma. Hospitalized COVID-19 patients (n = 48) demonstrated higher serum levels of 55 inflammatory proteins (p < 0.001), including hs-C-reactive protein levels (p < 0.05), compared to healthy controls (n = 48). Interestingly, significantly increased age-related DNA damage (%-DNA in tail) after formamidopyrimidine DNA glycosylase (FPG) treatment was measured in younger (n = 24, average age 55.7 years; p < 0.05) but not in older COVID-19 patients (n = 24, average age 83.5 years; p > 0.05). Although various oxidative stress markers were not altered (e.g., FRAP, malondialdehyde, p > 0.05), a significant increased ratio of oxidized to reduced glutathione was detected in COVID-19 patients compared to healthy controls (p < 0.05). UCB levels were significantly lower in individuals with COVID-19, especially in younger COVID-19 patients (p < 0.05). These results suggest that COVID-19 infections exert effects on DNA damage related to age in hospitalized COVID-19 patients that might be driven by changes in inflammatory pathways but are not altered by oxidative stress parameters.

Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of MLH1 and DNMT1 Dose Dependently in Caco-2 Cells.

Obesity- or diabetes-induced oxidative stress is discussed as a major risk factor for DNA damage. Vitamin E and many polyphenols exhibit antioxidative activities with consequences on epigenetic regulation of inflammation and DNA repair. The present study investigated the counteraction of oxidative stress by vitamin E in the colorectal cancer cell line Caco-2 under normal (1 g/l) and high (4.5 g/l) glucose cell culture condition. Malondialdehyde (MDA) as a surrogate marker of lipid peroxidation and reactive oxygen species (ROS) was analyzed. Gene expression and promoter methylation of the DNA repair gene MutL homolog 1 (MLH1) and the DNA methyltransferase 1 (DNMT1) as well as global methylation by LINE-1 were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on H2O2-induced oxidative stress. Thereby, 10 µM vitamin E proved to be more efficient than did 50 µM in reducing MDA. Further, an induction of MLH1 and DNMT1 gene expression was noticed, accompanied by an increase in global methylation. Whether LINE-1 hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E in vitro exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair.

Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2.

BACKGROUND: Diabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration. METHODS: Female T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals. RESULTS: No significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group. CONCLUSION: BMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria.

Vibrational spectra and ab initio analysis of tert-butyl, trimethylsilyl, trimethylgermyl, trimethylstannyl and trimethylplumbyl derivatives of 3,3-dimethylcyclopropene. XII. 1,2-Di-tert-butyl-3,3-dimethylcyclopropene.

The synthesis of 1,2-di-tert-butyl-3,3-dimethylcyclopropene (I) is performed and its IR and Raman spectra are measured. Optimized geometries of I are obtained at the HF/6-31G* and CCSD/cc-pVDZ levels. The ab initio calculated spectra are used for the assignments of the experimental spectral data. The results obtained are compared with the corresponding data for 3,3-dimethylbut-1-ene and 3,3-dimethylcyclopropene. These experimental data and the total vibrational analysis of I supplement the information obtained in the series of investigations of tert-butyl, trimethylsilyl, trimethylgermyl, trimethylstannyl, and trimethylplumbyl derivatives of 3,3-dimethylcyclopropene.

Vibrational spectra and ab initio analysis of tert-butyl, trimethylsilyl, trimethylgermyl, trimethylstannyl and trimethylplumbyl derivatives of 3,3-dimethylcyclopropene. XI. Secondary periodicity.

Regularities of changes in the structural parameters and vibrational wavenumbers for certain moieties of the title compounds are presented. The optimized geometrical parameters and the force fields of the di- and monosubstituted 3,3-dimethylcyclopropenes were determined at the HF/3-21G* and HF/DDAll pseudopotential levels, respectively. These theoretical levels were chosen because of peculiarities of Gaussian 03 suite of programs for the Sn and Pb atoms. The theoretical vibrational wavenumbers were calculated using the corresponding scaled force fields. The regularities obtained in the form of zigzag lines for the properties as a function of the period number of X in the Mendeleyev Periodic Table are analogous to regularities that are characteristic of properties of the atoms of the 14 (IVA) group. This is known as the secondary periodicity phenomenon.