Geislerelgaard4681

Mechanism studies revealed that PL171 upregulated SIRT3 and its upstream peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) under basal and Aβ 42O-treated conditions. The inhibition of SIRT3 activity could eliminate the protective effects of PL171. Further, long-term treatment with Aβ 42O increased the number of senescent neuronal cell, which was also alleviated by PL171 in a SIRT3-dependent manner. Taken together, our results indicated that PL171 rescued Aβ 42O-induced oxidative stress, mitochondrial dysfunction, and cell senescence via upregulating SIRT3 and might be a potential drug candidate against AD. Copyright © 2020 Yi Li et al.Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of death in neonates with no effective treatments. Recent advancements in hydrogen (H2) gas offer a promising therapeutic approach for ischemia reperfusion injury; however, the impact of this approach for HIE remains a subject of debate. We assessed the therapeutic effects of H2 gas on HIE and the underlying molecular mechanisms in a rat model of neonatal hypoxic-ischemic brain injury (HIBI). H2 inhalation significantly attenuated neuronal injury and effectively improved early neurological outcomes in neonatal HIBI rats as well as learning and memory in adults. This protective effect was associated with initiation time and duration of sustained H2 inhalation. Furthermore, H2 inhalation reduced the expression of Bcl-2-associated X protein (BAX) and caspase-3 while promoting the expression of Bcl-2, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1 (HO-1). H2 activated extracellular signal-regulated kinase and c-Jun N-terminal pro responses. HO-1 plays an important role in H2-mediated protection through the MAPK/HO-1/PGC-1α pathway. Our results support further assessment of H2 as a potential therapeutic for neurological conditions in which oxidative stress and apoptosis are implicated. Copyright © 2020 Peipei Wang et al.Taken into consideration that oxidative stress response after preconditioning with phosphodiesterase inhibitors (PDEIs) and moderate physical activity has still not been clarified, the aim of this study was to assess the effects of PDEIs alone or in combination with physical activity, on systemic redox status. The study was carried out on 96 male Wistar albino rats classified into two groups. The first group included animals exposed only to pharmacological preconditioning (PreC) maneuver (sedentary control (CTRL, 1 ml/day saline, n = 12), nicardipine (6 mg/kg/day of NIC, n = 12), vinpocetine (10 mg/kg/day of VIN, n = 12), and nimodipine (NIM 10 mg/kg/day of, n = 12). The second included animals exposed to preconditioning with moderate-intensity training (MIT) on treadmill for 8 weeks. After 5 weeks from the start of training, the animals were divided into four subgroups depending on the medication to be used for pharmacological PreC moderate-intensity training (MIT+ 1 ml/day saline, n = 12), nicardipine (MIT+ 6 mg/kg/day of NIC, n = 12), vinpocetine (MIT+ 10 mg/kg/day of VIN, n = 12), and nimodipine (MIT+ 10 mg/kg/day of NIM, n = 12). After three weeks of pharmacological preconditioning, the animals were sacrificed. The following oxidative stress parameters were measured spectrophotometrically nitrites (NO2 -), superoxide anion radical (O2 -), hydrogen peroxide (H2O2), index of lipid peroxidation (TBARS), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Our results showed that PDE1 and MIT preconditioning decreased the release of prooxidants and improved the activity of antioxidant enzymes thus preventing systemic oxidative stress. Copyright © 2020 Jelena Ristic et al.This study was conducted to evaluate the effect of dietary supplementation with Lactobacillus delbrueckii (LAB) on intestinal morphology, barrier function, immune response, and antioxidant capacity in weaned piglets challenged with lipopolysaccharide (LPS). A total of 36 two-line crossbred (Landrace × large Yorkshire) weaned piglets (28 days old) were divided into three groups (1) nonchallenged control (CON); (2) LPS-challenged control (LPS); and (3) LAB+LPS treatment (0.2% LAB+LPS). check details Compared to the LPS piglets, the LAB+LPS piglets improved intestinal morphology, indicated by greater (P less then 0.05) villus height in the duodenum and ileum; villus height  crypt depth ratio in the duodenum, jejunum, and ileum, as well as decreased (P less then 0.05) crypt depth in the jejunum and ileum; and better intestinal barrier function, indicated by upregulated (P less then 0.05) mRNA expression of tight junction proteins in the intestinal mucosa. Moreover, compared to the LPS piglets, LAB significantly decreased (P less then 0.05) concentrations of TNF-α and IL-1β in the small intestine and increased (P less then 0.05) IL-10 levels in the jejunum and ileum. Additionally, LAB increased (P less then 0.05) T-AOC activities of the colon, GSH concentrations of the jejunum, and mRNA expression of CAT and Cu/Zn-SOD, while reduced (P less then 0.05) MDA concentrations in the jejunum and ileum in LPS-changed piglets. Collectively, our results indicate that supplementation of LAB improved intestinal integrity and immune response and alleviated intestinal oxidative damage in LPS-challenged piglets. Copyright © 2020 Fengming Chen et al.Treatments on neoplastic diseases and cancer using genotoxic drugs often cause long-term health problems related to premature aging. The underlying mechanism is poorly understood. Based on the study of a long-lasting senescence-like growth arrest (10-12 weeks) of human dermal fibroblasts induced by psoralen plus UVA (PUVA) treatment, we here revealed that slowly repaired bulky DNA damages can serve as a "molecular scar" leading to reduced cell proliferation through persistent endogenous production of reactive oxygen species (ROS) that caused accelerated telomere erosion. The elevated levels of ROS were the results of mitochondrial dysfunction and the activation of NADPH oxidase (NOX). A combined inhibition of DNA-PK and PARP1 could suppress the level of ROS. Together with a reduced expression level of BRCA1 as well as the upregulation of PP2A and 53BP1, these data suggest that the NHEJ repair of DNA double-strand breaks may be the initial trigger of metabolic changes leading to ROS production. Further study showed that stimulation of the pentose phosphate pathway played an important role for NOX activation, and ROS could be efficiently suppressed by modulating the NADP/NADPH ratio.