An understanding directly into Aging Senescence and Their Effects upon Injury Healing

Background Exercise induced health benefits are limited by the overaccumulation of reactive oxygen species (ROS). ROS and further oxidative stress could potentially induce muscle damage which could result in poor exercise performance. However, predicting ROS induced oxidative stress in response to endurance training has several limitations in terms of selecting biomarkers that are used to measure oxidative stress. Objective The purpose of this study was to systematically investigate the suitable biomarkers that predict oxidative stress status among runners. learn more Methods According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a search for relevant articles was carried out on PubMed/Medline, ISI Web of Science, and Google Scholar using related search terms such as oxidative damage, ROS, exercise, physical training, running, marathon, and ultramarathon. Results Outcomes included (1) running programs like a half-marathon, ultramarathon, and iron-man race, (2) measuring biochemical assessment of oxidative damage markers such as malondialdehyde (MDA), protein carbonyl (PC), total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), 8-Oxo-2'-deoxyguanosine (8-OH-dG), 4-hydroxynonenal (HNE), and F1-isoprostones, and enzymatic and non-enzymatic antioxidants level. Conclusions This study concluded that a running exercise does not elicit a response to specific biomarkers of oxidative stress, instead, oxidative damage markers of lipids, proteins, and various enzymatic and non-enzymatic antioxidants are expressed according to the training status of the individual.This study examined acute cerebral hemodynamic and circulating neurotrophic factor responses to moderate intensity continuous exercise (MICT), guideline-based high intensity interval exercise (HIIT), and sprint interval exercise (SIT). We hypothesized that the pattern of middle cerebral artery velocity (MCAv) response would differ between interval and continuous exercise, with SIT inducing the smallest increase from rest, while increases in neurotrophic factors would be intensity-dependent. In a randomized crossover design, 24 healthy adults (nine females) performed three exercise protocols (i) MICT (30 min), (ii) HIIT (4 × 4 min at 85% HRmax), and (iii) SIT (4 × 30 s supramaximal). MCAv significantly increased from rest across MICT (Δ13.1 ± 8.5 cm⋅s-1, p 5-fold greater in SIT, p less then 0.001), alongside a small significant reduction at the end of active recovery in insulin-like growth factor 1 (IGF-1, Δ22 ± 21%, p = 0.002). In conclusion, while the nature of the response may differ, both guideline-based and sprint-based interval exercise have the potential to induce significant changes in factors linked to improved cerebrovascular and brain health.Pyruvate kinase deficiency (PKD) is a rare congenital hemolytic anemia caused by mutations in the PKLR gene. Here, we review pathophysiological aspects of PKD, focusing on the interplay between pyruvate kinase (PK)-activity and reticulocyte maturation in the light of ferroptosis, an iron-dependent process of regulated cell death, and in particular its key player glutathione peroxidase 4 (GPX4). GPX4 plays an important role in mitophagy, the key step of peripheral reticulocyte maturation and GPX4 deficiency in reticulocytes results in a failure to fully mature. Mitophagy depends on lipid oxidation, which is under physiological conditions controlled by GPX4. Lack of GPX4 leads to uncontrolled auto-oxidation, which will disrupt autophagosome maturation and thereby perturb mitophagy. Based on our review, we propose a model for disturbed red cell maturation in PKD. A relative GPX4 deficiency occurs due to glutathione (GSH) depletion, as cytosolic L-glutamine is preferentially used in the form of α-ketoglutarate as fuel for the tricarboxylic acid (TCA) cycle at the expense of GSH production. The relative GPX4 deficiency will perturb mitophagy and, subsequently, results in failure of reticulocyte maturation, which can be defined as late stage ineffective erythropoiesis. Our hypothesis provides a starting point for future research into new therapeutic possibilities, which have the ability to correct the oxidative imbalance due to lack of GPX4.Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease that appeared at the end of 2019. As of July 2020, the cumulative number of infections and deaths have exceeded 15 million and 630,000, respectively. And new cases are increasing. There are still many difficulties surrounding research on the mechanism and development of therapeutic vaccines. It is urgent to explore the pathogenic mechanism of viruses to help prevent and treat COVID-19. In our study, we downloaded two datasets related to COVID-19 (GSE150819 and GSE147507). By analyzing the high-throughput expression matrix of uninfected human bronchial organoids and infected human bronchial organoids in the GSE150819, 456 differentially expressed genes (DEGs) were identified, which were mainly enriched in the cytokine-cytokine receptor interaction pathway and so on. We also constructed the protein-protein interaction (PPI) network of DEGs to identify the hub genes. Then we analyzed GSE147507, which contained lung adenocarcinoma cell lines (A549 and Calu3) and the primary bronchial epithelial cell line (NHBE), obtaining 799, 460, and 46 DEGs, respectively. The results showed that in human bronchial organoids, A549, Calu3, and NHBE samples infected with SARS-CoV-2, only one upregulated gene CSF3 was identified. Interestingly, CSF3 is one of the hub genes we previously screened in GSE150819, suggesting that CSF3 may be a potential drug target. Further, we screened potential drugs targeting CSF3 by MOE; the top 50 drugs were screened by flexible docking and rigid docking, with 37 intersections. Two antiviral drugs (Elbasvir and Ritonavir) were included; Elbasvir and Ritonavir formed van der Waals (VDW) interactions with surrounding residues to bind with CSF3, and Elbasvir and Ritonavir significantly inhibited CSF3 protein expression.Kv7.4 (KCNQ4) voltage-gated potassium channels control excitability in the inner ear and the central auditory pathway. Mutations in Kv7.4 channels result in inherited progressive deafness in humans. Calmodulin (CaM) is crucial for regulating Kv7 channels, but how CaM affects Kv7 activity has remained unclear. Here, based on electrophysiological recordings, we report that the third EF hand (EF3) of CaM controls the calcium-dependent regulation of Kv7.4 activation and that the S2-S3 loop of Kv7.4 is essential for the regulation mediated by CaM. Overexpression of the mutant CaM1234, which loses the calcium binding ability of all four EF hands, facilitates Kv7.4 activation by accelerating activation kinetics and shifting the voltage dependence of activation leftwards. The single mutant CaM3, which loses the calcium binding ability of the EF3, phenocopies facilitating effects of CaM1234 on Kv7.4 activation. Kv7.4 channels co-expressed with wild-type (WT) CaM show inhibited activation when intracellular calcium levels increase, while Kv7.