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Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC), first to 5-hydroxymethylcytosine (5hmC), then to 5-formylcytosine (5fC), and finally to 5-carboxycytosine (5caC). Evidence suggests that changes in TET expression may impact cell function and the phenotype of aging. Proliferation, apoptosis, markers of autophagy and double-strand DNA break repair, and the expression of Fibulin 5 were assessed by flow cytometry in TET1 and TET2-overexpressing fibroblasts isolated from sun-unexposed skin of young (23–35 years) and age-advanced (75–94 years) individuals. In cells derived from young individuals, TET1 overexpression resulted in the inhibition of proliferation and apoptosis by 37% (p = 0.03) and 24% (p = 0.05), respectively, while the overexpression of TET2 caused a decrease in proliferation by 46% (p = 0.01). Notably, in cells obtained from age-advanced individuals, TETs exhibited different effects. Specifically, TET1 inhibited proliferation and expression of autophagy marker Beclin 1 by 45% (p = 0.05) and 28% (p = 0.048), respectively, while increasing the level of γH2AX, a marker of double-strand DNA breaks necessary for initiating the repair process, by 19% (p = 0.04). TET2 inhibited proliferation by 64% (p = 0.053) and increased the level of γH2AX and Fibulin 5 by 46% (p = 0.007) and 29% (p = 0.04), respectively. These patterns of TET1 and TET2 effects suggest their involvement in regulating various fibroblast functions and that some of their biological actions depend on the donor’s age.

MaroszSzymon, BorkowskaAleksandra, MikulskaPaulina,BorkowskaKatarzyna, Kowieska Jolanta. The treatment of diabetes with new generation drugs. Journal of Education, Health and Sport.2020;10(9):690-696. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.09.083 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.09.083 https://zenodo.org/record/4048524 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 10.09.2020. Revised: 24.09.2020. Accepted: 24.09.2020. The treatment of diabetes with new generation drugs Szymon Marosz1,Aleksandra Borkowska1, Paulina Mikulska2, Katarzyna Borkowska2, Jolanta Kowieska2 1Chair and Department of Epidemiology and Clinical Research Methodology, Medical University of Lublin 2Mazovian Regional Hospital of St. John Paul II in Siedlce Sp. z o.o. Corresponding author: Aleksandra Borkowska: borkowska.ola231@gmail.com ORICID ID: Szymon Marosz: https://orcid.org/0000-0003-4774-8449 Aleksandra Borkowska: https://orcid.org/0000-0002-0950-2176 Katarzyna Borkowska: https://orcid.org/0000-0002-2090-7887 Paulina Mikulska: https://orcid.org/0000-0003-0876-6150 Jolanta Kowieska: https://orcid.org/0000-0001-5257-686X Abstract Introduction:Diabetes is a global problem, affecting nearly 422 million people around the world. Pathogenesis includes a defect in secretion or insulin activity. This results in an increase in the glucose level, which is associated with the development of complications. These include changes in peripheral vessels and nerves that lead to their damage. It is necessary to introduce appropriate treatment in the earliest stages of the disease to prevent these effects. Materials and methods:The aim of this work is to present knowledge about the treatment based on the recommendations of the Polish Diabetes Association, American Diabetes Association, as well as a literature review and analysis of publications published on PubMed and Google Scholar platforms. Results:Over the years, the recommendations and recommendations for treatment change. Recently, a greater role has been given to the latest antidiabetic drugs. This group includes SGLT-2 inhibitors as well as incremental drugs, the main representatives of which are GLP-1 analogues. These drugs affect the level of glycemia, but also have a beneficial effect on weight reduction and reduce the risk of cardiovascular events. Recently, Poland has introduced reimbursement of some new generation antidiabetic drugs such as dapaglyphosin, empaglyphosin and canaglyphosin. Conclusions:Dynamic development of diabetes treatment helps to slow down the course of the disease and postpones the introduction of insulin therapy as the final treatment method. Reimbursement of some antidiabetic drugs enables patients to have better access to drugs that have not been within their reach so far. The changes introduced are, in a way, groundbreaking in the treatment of diabetes. Key words: diabetes, GLP-1 analogues, SGLT-2 inhibitors.

5-Hydroxymethylcytosine (5hmC) is a functionally active epigenetic modification. We analyzed whether changes in DNA 5-hydroxymethylation are an element of age-related epigenetic drift. We tested primary fibroblast cultures originating from individuals aged 22&ndash, 35 years and 74&ndash, 94 years. Global quantities of methylation-related DNA modifications were estimated by the dot blot and colorimetric methods. Regions of the genome differentially hydroxymethylated with age (DHMRs) were identified by hMeDIP-seq and the MEDIPS and DiffBind algorithms. Global levels of DNA modifications were not associated with age. We identified numerous DHMRs that were enriched within introns and intergenic regions and most commonly associated with the H3K4me1 histone mark, promoter-flanking regions, and CCCTC-binding factor (CTCF) binding sites. However, only seven DHMRs were identified by both algorithms and all of their settings. Among them, hypo-hydroxymethylated DHMR in the intron of Rab Escort Protein 1 (CHM) coexisted with increased expression in old cells, while increased 5-hydroxymethylation in the bodies of Arginine and Serine Rich Protein 1 (RSRP1) and Mitochondrial Poly(A) Polymerase (MTPAP) did not change their expression. These age-related differences were not associated with changes in the expression of any of the ten-eleven translocation (TET) enzymes or their activity. In conclusion, the distribution of 5hmC in DNA of in vivo aged human fibroblasts underwent age-associated modifications. The identified DHMRs are, likely, marker changes.

The elements creating friction pairs are described to be very difficult in terms of determining all optimal parameters in an unambiguous manner. The nowadays research on stability of friction pairs is focused on the surface and the top layer of surface. The main goal is find new design solutions and materials, achieving a lot of kilometers to main repair in combustion engines. The biggest structural difficulties are noticeable in friction pairs where can be observed sliding and returning motion, what is connected with sealing function. A typical example of such pair is piston ring – cylinder. Engineers work on defining an additional factor that would be able to gain the reduction of tangential force by reducing the friction coefficient in elements of friction pair. Molecular structure and nature of the bonds between the molecules presented in the material, result that the free surface energy may be such a factor, because determines the tribological properties of the material, what is reflected in the stability of the units. The work carries out of an analysis after research on the goniometer in the presence of water and diododomethane that allowed to measure wetting drops on the surface, thanks to which can be calculated surface energy. Within this work will be performed study of the energy state of the surface of piston rings with a coating including a diamond powder. After analysis on the basis of the collected measurements will be developed conclusion regarding the potential relationship between the free surface energy and wearing of the material.

Tłok wraz z pierścieniami oraz powierzchnią cylindra jest bardzo złożonym zamkniętym systemem trybologicznym. Pierścienie tłoka – cylinder jest jedną z najbardziej globalnie rozpowszechnionych par tarcia silników spalinowych. Para tarcia TPC jest rozwiązaniem wytwarzającym znaczące tarcie w silnikach spalinowych. Różne źródła naukowe określają straty na jeden węzeł spowodowane tarciem pary pierścień-ściana cylindra jako 19 do 60% wartości wszystkich strat tarcia w silniku spalinowym. W tym artykule omówiono część większego programu badawczego mającego na celu zmniejszenie zużycia pracujących elementów (tłok, pierścienie tłoka, powierzchnia cylindra). Projekt ten jest wdrażany w ramach rozwoju nowych konstrukcji pierścieni tłokowych z powłoką zapobiegającą zużyciu, zawierającą syntetyczny diament luźno zatopiony w powłoce chromu (TPC). Celem Autorów było przedstawienie metodologii stosowanej do obliczeń charakteryzującej się określoną procedurą. W praktyce wykorzystuje się oprogramowanie MES oraz MOS. Opracowany i wdrożony moduł obliczeniowy pierścieni tłokowych jest zgodny z ideą numerycznych metod obliczeniowych, to znaczy: funkcjonalnie polega na przeprowadzeniu obliczenia zamiaru uzyskania dokładnego wyniku (najbardziej zbliżonego rzeczywistości) poprzez uzyskanie i wykorzystanie wartości pośrednich.

Aim: To clarify mechanisms affecting the level and distribution of 5-hydroxymethylcytosine (5hmC) during aging. Materials & methods: We examined levels and genomic distribution of 5hmC along with the expression of ten–eleven translocation methylcytosine dioxygenases (TETs) in adipose stem cells in young and age-advanced individuals. Results: 5hmC levels were higher in adipose stem cells of age-advanced than young individuals (p = 0.0003), but were not associated with age-related changes in expression of TETs. 5hmC levels correlated with population doubling time (r = 0.62; p = 0.01). We identified 58 differentially hydroxymethylated regions. Hypo-hydroxymethylated differentially hydroxymethylated regions were approximately twofold enriched in CCCTC-binding factor binding sites. Conclusion: Accumulation of 5hmC in aged cells can result from inefficient active demethylation due to altered TETs activity and reduced passive demethylation due to slower proliferation.

Objectives To investigate the influence of overweight and obesity on general performance and mortality in seniors. Design Cross-sectional multidisciplinary study on ageing of the Polish population. Setting Community-dwelling individuals aged 65 years or older, selected using three-stage stratified, proportional draw. Participants 4944 Polish Caucasian seniors, aged 65 years or older recruited between October 2007 and October 2010. Measurements All study subjects underwent measurement of body mass index (BMI), waist circumference (WC), and arm circumference (AC). The physical and cognitive performance was evaluated using the Katz Activities of Daily Living (ADL) score and Mini-Mental State Examination (MMSE), respectively. Morbidity data were obtained from a medical questionnaire. Mortality data were obtained from the Population Register of Poland between October 2015 and October 2018. Results Increasing age was associated with a decreased prevalence of obesity (all p Conclusions Overweight and obesity in Caucasian seniors are not associated with deterioration of physical and cognitive function or with increased mortality.

Increased expression of sirtuins lowers the risk of age-related diseases, while their role in the regulation of longevity is not firmly established. Since aging is associated with immunosenescence, we tested whether sirtuin expression was modified in peripheral blood mononuclear cells (PBMC) in an age-related manner and whether this might result from altered expression of the selected miRNAs. The expression of seven SIRT genes and of SIRT1 mRNA-interacting miR-9, miR-34a, miR-132, and miR-199a-5p was evaluated by real-time PCR in PBMC originating from young (Y, n = 57, mean age 27 ± 4.3 years), elderly (E, n = 52, 65 ± 3.4 years), and long-lived (L, n = 56, 94 ± 3.5 years) individuals. Older age was associated with a decreased expression of the majority of the SIRT genes. Most severely affected were median expressions of SIRT1 ( P = 0.000001 for the whole studied group, Y vs. E: P Impact statement High expression of sirtuins, particularly SIRT1, lowers the risk of age-related diseases and probably slows down the rate of aging; therefore, their sustained expression should be one of the features of longevity. However, in this work we show that in peripheral blood mononuclear cells (PBMC) of long-lived individuals, expression of majority of the SIRT genes is significantly lower than in cells of young study subjects. In long-lived individuals, downregulation of SIRT1 coexists with upregulation of SIRT1 mRNA-interacting miR-34a and miR-9, indicating the role of epigenetic drift in age-dependent deregulation of SIRT1 expression. Such constellation of SIRT1, miR-34a, and miR-9 expression in PBMC of successfully aging long-lived individuals indicates that, at least in these individuals, it is not a risk factor for morbidity and mortality. It might however affect the function of the immune system and, therefore, aging individuals can profit from interventions increasing the level of SIRT1.

Background Aglepristone (RU534) is an antiprogestin used for pregnancy termination, parturition induction and conservative pyometra treatment in bitches. Its molecular structure is similar to mifepristone, an antiprogestin used in human medicine. Mifepristone has been shown to suppress proliferation and cytokine production by T cells, whereas the effect of aglepristone on T cell function remains elusive. The purpose of this project was to investigate the in vitro influence of RU534 on IFN-γ and IL-4 synthesis by peripheral blood T cells isolated from healthy bitches (N = 16) in luteal phase. The peripheral blood mononuclear cells (PBMCs) were incubated with three different dosages of aglepristone, or dimethyl sulfoxide (DMSO), with or without mitogen. The production of cytokines by resting or mitogen-activated T cells was determined by intercellular staining and flow cytometry analysis or ELISA assay, respectively. Results Our results showed no statistically significant differences in the percentage of IFN-γ and IL-4-synthesizing CD4+ or CD8+ resting T cells between untreated and aglepristone-treated cells at 24 and 48 hours post treatment. Moreover, mitogen-activated PBMCs treated with RU534 displayed similar concentration of IFN-γ and IL-4 in culture supernatants to those observed in mitogen-activated DMSO-treated PBMCs. Presented results indicate that administration of aglepristone for 48 hours has no influence on IFN-γ and IL-4 synthesis by resting and mitogen-activated T cells isolated from diestral bitches. Conclusions We conclude that antiprogestins may differentially affect T cell function depending on the animal species in which they are applied.