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The exponential growth of the aged population worldwide is followed by an increase in the prevalence of age-related disorders. Oxidative stress plays central role in damage accumulation during ageing and cell senescence. Thus, a major target of today's anti-ageing research has been focused on antioxidants counteracting senescence. In the current work, six novel 5,7,8-trimethyl-1,4-benzoxazine/catechol or resorcinol hybrids were synthesized connected through a methoxymethyl-1,2,3-triazolyl or a 1,2,3-triazoly linker. The compounds were evaluated for their antioxidant capacity in a cell-free system and for their ability to reduce intracellular ROS levels in human skin fibroblasts, both young (early-passage) and senescent. The most efficient compounds were further tested in these cells for their ability to induce the expression of the gene heme oxygenase-1 (ho-1), known to regulate redox homeostasis, and cellular glutathione (GSH) levels. Overall, the two catechol derivatives were found to be more potent than the resorcinol analogues. Furthermore, these two derivatives were shown to act coordinately as radical scavengers, ROS inhibitors, ho-1 gene expression inducers, and GSH enhancers. Interestingly, one of the two catechol derivatives was also found to enhance human skin fibroblast viability. The properties of the synthesized compounds support their potential use in cosmetic applications, especially in products targeting skin ageing. [ABSTRACT FROM AUTHOR]

Novel metabolites of the anabolic androgenic steroid 17α‐methyltestosterone have been detected in HepG2 cell in vitro metabolic model and in human urine. Their detection was accomplished through targeted gas chromatography–(tandem) mass spectrometry analysis that has been based on microscale synthesized standards. The related synthesis and the gas chromatography–(tandem) mass spectrometry characterization of the analytical standards are described. All newly presented metabolites have a fully reduced steroid A‐ring with either an 17,17‐dimethyl‐18‐nor‐Δ13 structure or they have been further oxidized at position 16 of the steroid backbone. Metabolites with 17,17‐dimethyl‐18‐nor‐Δ13 structure may be considered as side products of phase II metabolic sulfation of the 17β‐hydroxy group of methyltestosterone or its reduced tetrahydro‐methyltestosterone metabolites 17α‐methyl‐5β‐androstane‐3α,17β‐diol and 17α‐methyl‐5α‐androstane‐3α,17β‐diol that produce the known epimeric 17β‐methyl‐5β‐androstane‐3α,17α‐diol and 17β‐methyl‐5α‐androstane‐3α,17α‐diol metabolites. The prospective of these new metabolites to increase detection time windows and improve identification was investigated by applying the World Anti‐doping Agency TD2021IDCR criteria. The new metabolites, presented herein, complement the current knowledge on the 17α‐methyltestosterone metabolism and in some cases can be used as additional long‐term markers in the frame of sport doping drug testing. [ABSTRACT FROM AUTHOR]

Background/Aim: Myocardial infarction, an acute medical situation with a high mortality rate worldwide, has been extensively studied in modern cardiovascular research, using different experimental models. However, a deep understanding of myocardial activity loss has not been fully investigated. We have developed a novel experimental rat model for noninvasive assessment of myocardial ischemia based on single photon emission computed tomography (SPECT/CT), in order to further understand and evaluate myocardial activity before and after surgical induction of myocardial ischemia. Materials and Methods: Thirty adult female Wistar rats underwent open thoracotomy with (n=20) or without (n=10) surgical ligation of the left anterior descending coronary artery (LAD). The myocardial ischemia was confirmed with ECG and myocardial viability was evaluated via SPECT/CT at 7 days before as well as at 7 and 14 days post-surgery, after which animals were sacrificed and myocardial ischemic injury was further assessed histologically. Results: All animals were evaluated with anatomical and functional criteria based on the SPECT/CT imaging results. A successful surgical technique causing ischemia and loss of myocardial function in all animals undergoing a LAD ligation was established. Furthermore, evaluation of the viable myocardium with SPECT/CT confirmed the reduction of functional myocardial cells of the left ventricle post-infarction, which was also documented histologically. Conclusion: Using our technique, the validity of this animal model to induce and evaluate myocardial ischemia was demonstrated. Our choice to apply SPECT-CT qualitative and quantitative evaluation of myocardial function leads to a new approach in experimentation with an anticipated significant impact in the ongoing cardiovascular laboratory research. [ABSTRACT FROM AUTHOR]