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A decrease in M2-subtype macrophages associated with a decrease in collagen deposition was observed. Using LLC-PK1 cells, a model of PTECs, we observed that (1) these cells express IL-4 receptor α chain associated with activation of the JAK3/STAT6 pathway; (2) IL-4 alone did not change albumin endocytosis but did reverse the inhibitory effect of higher albumin concentration. This effect was abolished by JAK3 inhibitor. A further increase in urinary protein and creatinine levels was observed in the KO + BSA group compared with the BSA group, but not compared with the CONT group. These observations indicate that IL-4 has a protective role in the development of TII induced by albumin overload that is correlated with modulation of the pro-inflammatory response. We propose that megalin-mediated albumin endocytosis in PTECs could work as a sensor, transducer, and target during the genesis of TII. Copyright © 2020 Peruchetti, Silva-Filho, Silva-Aguiar, Teixeira, Takiya, Souza, Henriques, Pinheiro and Caruso-Neves.It is widely acknowledged that achieving and maintaining a healthier lifestyle can be enhanced through regular participation in sport and physical activity. Coevally, a growing number of health professionals regard exercise as a legitimate intervention strategy for those who have lost their health. Exercise has been shown to be effective for overweight or obese individuals, who are at risk to lose their health due to development of type II diabetes, cardiovascular disease, as well as, infiltration of muscles, bone and other organs with fat, so it can be considered medicine. However, exercise and associated mobility likely also have a strong prevention component that can effectively contribute to the maintenance of the integrity of multiple biological systems for those who do not have overt risk factors or ongoing disease. While prevention is preferred over intervention in the context of disease, it is clear that exercise and associated mobility, generally, can be an effective influence, although overtraining and excessive loading can be deleterious to health. The basis for the generally positive influence of exercise likely lies in the fact that many of our physiological systems are designed to function in the mechanically dynamic and active 1g environment of Earth (e.g., muscles, cartilage, ligaments, tendons, bones, and cardiovascular system, and neuro-cognitive function), and nearly all these systems subscribe to the "use it or lose it" paradigm. This conclusion is supported by the changes observed over the more than 50 years of space flight and exposure to microgravity conditions. Therefore, the premise advanced is "exercise is preventative for loss of health due to age-related decline in the integrity of several physiological systems via constant reinforcement of those systems, and thus, optimal levels of exercise and physical activity are endemic to, essential for, and intrinsic to optimal health and wellbeing." Copyright © 2020 Hart and Zernicke.Accumulating epidemiological evidence supports that chronic exposure to ambient fine particular matters of less then 2.5 μm (PM2.5) predisposes both children and adults to Alzheimer's disease (AD) and age-related brain damage leading to dementia. There is also experimental evidence to show that PM2.5 exposure results in early onset of AD-related pathologies in transgenic AD mice and development of AD-related and age-related brain pathologies in healthy rodents. Studies have also documented that PM2.5 exposure causes AD-linked molecular and cellular alterations, such as mitochondrial dysfunction, synaptic deficits, impaired neurite growth, neuronal cell death, glial cell activation, neuroinflammation, and neurovascular dysfunction, in addition to elevated levels of amyloid β (Aβ) and tau phosphorylation. Oxidative stress and the oxidative stress-sensitive TRPM2 channel play important roles in mediating multiple molecular and cellular alterations that underpin AD-related cognitive dysfunction. Documented evidence suggests critical engagement of oxidative stress and TRPM2 channel activation in various PM2.5-induced cellular effects. Here we discuss recent studies that favor causative relationships of PM2.5 exposure to increased AD prevalence and AD- and age-related pathologies, and raise the perspective on the roles of oxidative stress and the TRPM2 channel in mediating PM2.5-induced predisposition to AD and age-related brain damage. Copyright © 2020 Wang, Wei, Ding, Feng, Li, Li, Malko, Syed Mortadza, Wu, Yin and Jiang.Background Sickle cell disease (SCD) patients with asthma have an increased rate of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) episodes when compared to those without asthma. We hypothesized that either asthma diagnosis or bronchodilator treatment might aggravate SCD via their modulating effect on the autonomic nervous system (ANS). learn more Methods Cross-sectional evaluation of heart rate variability (HRV) during pulmonary function tests, including salbutamol administration, in children with SCD receiving asthma treatment or not when compared to asthmatic children without SCD matched for ethnicity. Results SCD children with asthma (n = 30, median age of 12.9 years old) were characterized by a reduced FEV1/FVC ratio, an increased bronchodilator response, and a greater incidence of VOC and ACS when compared to SCD children without asthma (n = 30, 12.7 years). Children with asthma without SCD (n = 29, 11.4 years) were characterized by a higher exhaled NO fraction than SCD children. SCD children when compared to non-SCD children showed reduced HRV [total power, low (LF) and high (HF, vagal tone) frequencies], which was further worsened by salbutamol administration in all the groups reduction in total power and HF with an increase in LF/HF ratio. After salbutamol, the LF/HF ratio of the SCD children was higher than that of the non-SCD children. The two groups of SCD children were similar, suggesting that asthma diagnosis per se did not modify ANS functions. Conclusion SCD children are characterized by impaired parasympathetic control and sympathetic overactivity that is worsened by salbutamol administration. Clinical Trial Registration www.ClinicalTrials.gov, identifier NCT04062409. Copyright © 2020 Bokov, El Jurdi, Denjoy, Peiffer, Medjahdi, Holvoet, Benkerrou and Delclaux.