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Everett Rosa posted an update 2 months ago
Acute kidney injury (AKI) is a common clinical problem that is associated with high mortality due to multiple complex mechanisms. Cisplatin is the most important and highly effective chemotherapeutic agent used for the treatment of various solid tumors; however, it is associated with dose-dependent adverse effects, particularly in the kidney where it can cause severe nephrotoxicity. The pathophysiological basis of cisplatin-induced nephrotoxicity has been investigated over the last few decades, and the key pathological occurrences in cisplatin nephrotoxicity include renal tubular cell injury and death. Necrostatin-1 (Nec-1) has been confirmed to act as a specific and potent small-molecule inhibitor of necroptosis. However, the effects of three structurally distinct necrostatins on cisplatin-induced nephrotoxicity remain ambiguous. The aim of this study was to determine if three types of necrostatins (Nec-1, Nec-3-A, and/or Nec-3-B) can exert protective effects in regard to the AKI induced by cisplatin. Our results indicated that necrostatins can prevent cisplatin induced nephrotoxicity via modulating apoptotic pathways through the suppression of cleaved caspase-3 and also by influencing the function of mitogen-activated protein kinase pathway members, including extracellular signal-regulated kinases, c-Jun N-terminal kinases, and p38, in the renal tubular epithelial cell line LLC-PK1. These findings suggest that necrostatins exert beneficial anti-apoptotic effects in the context of AKI induced by cisplatin.Immune system function changes during aging, but the molecular mechanisms of this phenomenon are not fully understood. The present study identified pathways that are associated with age-associated changes in human B lymphocytes. Initial in silico analysis of 1355 genes involved in aging revealed the strongest association (p = 4.36E-21) with the gonadotropin-releasing hormone receptor (GnRHR) pathway. Extended analysis of 2736 aging-related genes using updated databases confirmed such association (p = 2.41E-16). Genes involved in both aging and the GnRHR pathway were significantly involved in lymphocyte B and T activation and aging-related phenotypes, including hyperinsulinemia and diabetes, arthritis, cerebrovascular disease, and cancers. We, therefore, examined non-tumorigenic Epstein-Barr virus (EBV)-transformed B-lymphocyte cell lines that originated from 12 young subjects (20-31 years old) and 10 centenarians (100-102 years old). Gonadotropin-releasing hormone I (GnRH-I) and GnRHR levels did not depend on the age of the cell donors. Inhibition of the GnRHR pathway age-independently decreased cell proliferation (p less then 0.001) and increased apoptosis (p less then 0.001). However, the decrease in immunoglobulin G synthesis (p less then 0.01) was twice as high in centenarian cells than in young cells. In conclusion, the GnRHR pathway regulated essential properties of B lymphocytes. However, upon EBV transformation, memory class-switched B cells became the dominant cell subpopulation. Therefore, the observed effects of GnRHR inhibition were attributable to this subpopulation.In the present study, we characterized the aberration in Nrf2 signaling in macrophages under a hyperglycemic microenvironment that reflects diabetic wounds in vitro and studied the effect of an Nrf2 activator pterostilbene (PTS) in these experimental conditions. Macrophages were exposed to pro-inflammatory cytokines TNFα and IFNγ with (HG+) or without high glucose (NG+) followed by the treatment with or without PTS. Western blotting was undertaken to assess the Nrf2 translocation from cytosol to nucleus followed by its downstream and upstream mediators, heme oxygenase-1 and Akt, respectively, the latter via phosphorylation. Quantitative PCR was also carried out to check the expression of macrophage mannose receptor CD206. We found a 2-fold reduction in the activation of Nrf2 in the HG+ group at 24 h compared to NG+, which was significantly improved by the treatment with PTS. Reduction in the levels of heme oxygenase-1 and phosphorylation of Akt in the HG+ group was also ameliorated by PTS. Furthermore, the gene expression of CD206 that was significantly reduced in the HG+ group was also restored by PTS treatment. The disruption of Nrf2 signaling in macrophages in a hyperglycemic microenvironment in vitro may indeed reflect diabetic wounds, as opposed to other non-diabetic wounds.Ageing is associated with chronic low-grade inflammation and with a decrease in muscle mass and strength. The aim of the study was to evaluate the effect of a resistance training programme in conditions of intermittent hypoxia on inflammatory biomarkers in older people. A total of 54 older adults (aged 65-75 years), who voluntarily participated in the study, were randomly divided into three groups the control (CON) group, the resistance training normoxia (RTN) group that performed resistance training in normoxia and resistance training hypoxia (RTH) group that trained under hypoxic conditions at a simulated altitude of 2500 m above sea level. The training programme that was carried out during 24 weeks was similar in both experimental groups and consisted of a full-body workout with elastic bands and kettlebells (three sets x 12-15 reps). Blood inflammatory parameters (CRP, VCAM-1, IL-6, IL-8 and IL-10) were analysed before and after the intervention. After the resistance training programme, a significant decrease in CRP and IL-8 levels was observed, as well as an increase in IL-10 levels, both in normoxia and hypoxia. These results show that resistance training, either in conditions of normoxia or hypoxia, is useful to deal with the chronic inflammation associated with ageing.Anthropometry (derived from the Greek Anthropos human, and metron measure) refers to the systematic collection, and measurement of the physical characteristics of the human body, primarily body weight, body size, and shape. Anthropometric values are closely related to genetic factors, environmental characteristics, social, and cultural conditions, lifestyle, functional status, and health. Anthropometric measurements can be used to assess risk of malnutrition, obesity, muscle wasting, increased fat mass, and maldistribution of adipose tissue. Potential modifiable factors include circumferences, skinfolds, and body weight. While are height, and the bone diameters are non-modifiable. Selleck SAR405 Kinanthropometry is the study of size, shape, proportionality, composition, biological maturation, and body function, in order to understand the process of growth, exercise, sports performance, and nutrition. Aging of the population, which is associated with increased risk of chronic disease, and disability, is one of the most important demographic changes facing many countries.