Zobrazení zdroje stránky Driscollditlevsen7396

We ruled out the GATA3 transcription factor as being responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicated in NK cell exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells' exhaustion might contribute to immunopathogenesis in SARS-CoV-2 infection.Metabolic regulation of immune cells has arisen as a critical set of processes required for appropriate response to immunological signals. While our knowledge in this area has rapidly expanded in leukocytes, much less is known about the metabolic regulation of brain-resident microglia. In particular, the role of alternative nutrients to glucose remains poorly understood. Here, we use stable-isotope (13C) tracing strategies and metabolomics to characterize the oxidative metabolism of β-hydroxybutyrate (BHB) in human (HMC3) and murine (BV2) microglia cells and the interplay with glucose in resting and LPS-activated BV2 cells. We found that BHB is imported and oxidised in the TCA cycle in both cell lines with a subsequent increase in the cytosolic NADHNAD+ ratio. In BV2 cells, stimulation with LPS upregulated the glycolytic flux, increased the cytosolic NADHNAD+ ratio and promoted the accumulation of the glycolytic intermediate dihydroxyacetone phosphate (DHAP). The addition of BHB enhanced LPS-induced accumulation of DHAP and promoted glucose-derived lactate export. [https://www.selleckchem.com/products/jhu395.html selleck chemical] BHB also synergistically increased LPS-induced accumulation of succinate and other key immunometabolites, such as α-ketoglutarate and fumarate generated by the TCA cycle. Finally, BHB upregulated the expression of a key pro-inflammatory (M1 polarisation) marker gene, NOS2, in BV2 cells activated with LPS. In conclusion, we identify BHB as a potentially immunomodulatory metabolic substrate for microglia that promotes metabolic reprogramming during pro-inflammatory response.Depression is a psychiatric disorder, and oxidative stress is a significant mechanism of damage in this mood disorder. It is characterized by an enhancement of oxidative stress markers and low concentrations of endogenous antioxidants, or antioxidants enzymes. This suggests that antioxidants could have an antidepressant effect. S-allyl cysteine (SAC) is a compound with antioxidant action or free radical scavenger capacity. The purpose of the current research was to evaluate the antidepressant-like effect as well as the antioxidant role of SAC on a preclinical test, using the Porsolt forced swim test (FST). SAC (30, 70, 120, or 250 mg/kg, ip) was administered to male BALB/c mice daily for 17 days, followed by the FST at day 18. Oxidative stress markers (reactive oxygen species, superoxide production, lipid peroxidation, and antioxidant enzymes activities) were analyzed in the midbrain, prefrontal cortex, and hippocampus. SAC (120 mg/kg) attenuated the immobility scores (44%) in the FST, and protection was unrelated to changes in locomotor activity. This antidepressant-like effect was related to decreased oxidative stress, as indicated by lipid peroxidation and manganese-superoxide dismutase (Mn-SOD) activity in the hippocampus. SAC exerts an antidepressant-like effect that correlated, in part, with preventing oxidative damage in hippocampus.The study examines the effects of a preschool-based family-involving multicomponent intervention on children's energy balance-related behaviors (EBRBs) such as food consumption, screen time and physical activity (PA), and self-regulation (SR) skills, and whether the intervention effects differed among children with low or high parental educational level (PEL) backgrounds. The Increased Health and Wellbeing in Preschools (DAGIS) intervention was conducted as a clustered randomized controlled trial, clustered at preschool level, over five months in 2017-2018. Altogether, 802 children aged 3-6 years in age participated. Parents reported children's consumption of sugary everyday foods and beverages, sugary treats, fruits, and vegetables by a food frequency questionnaire, and screen time by a 7-day diary. Physical activity was assessed by a hip-worn accelerometer. Cognitive and emotional SR was reported in a questionnaire by parents. General linear mixed models with and without repeated measures were used as statistical methods. At follow-up, no differences were detected in EBRBs or SR skills between the intervention and control group, nor did differences emerge in children's EBRBs between the intervention and the control groups when stratified by PEL. The improvement in cognitive SR skills among low PEL intervention children differed from low PEL control children, the significance being borderline. The DAGIS multicomponent intervention did not significantly affect children's EBRBs or SR. Further sub-analyses and a comprehensive process evaluation may shed light on the non-significant findings.The macroscopic properties of novel liquid crystal (LC) systems-LCs with unconventional molecular structure as well as conventional LCs in unconventional geometries-directly descend from their mesoscopic structural organization. While X-ray diffraction (XRD) is an obvious choice to investigate their nanoscale structure, conventional diffractometry is often hampered by experimental difficulties the low scattering power and short-range positional order of the materials, resulting in weak and diffuse diffraction features; the need to perform measurements in challenging conditions, e.g., under magnetic and/or electric fields, on thin films, or at high temperatures; and the necessity to probe micron-sized volumes to tell the local structural properties from their macroscopic average. Synchrotron XRD allows these problems to be circumvented thanks to the superior diffraction capabilities (brilliance, q-range, energy and space resolution) and advanced sample environment available at synchrotron beamlines. Here, we highlight the potentiality of synchrotron XRD in the field of LCs by reviewing a selection of experiments on three unconventional LC systems the potentially biaxial and polar nematic phase of bent-core mesogens; the very high-temperature nematic phase of all-aromatic LCs; and polymer-dispersed liquid crystals. In all these cases, synchrotron XRD unveils subtle nanostructural features that are reflected into macroscopic properties of great interest from both fundamental and technological points of view.