1,720,985 research outputs found

    Empagliflozin does not reverse lipotoxicity-induced impairment in human myeloid angiogenic cell bioenergetics

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    Background: Empagliflozin can curb inflammation and oxidative stress, through sodium-proton exchanger (NHE) inhibition, in a model of lipotoxicity in human myeloid angiogenic cells (MAC), which mediate endothelial repairing processes. Aim of this study is to assess in human MAC whether: (1) Stearic acid (SA) induced inflammation and increase in oxidant stress is accompanied by bioenergetic alterations; (2) empagliflozin anti-lipotoxic action is concomitant with coherent changes in bioenergetic metabolism, possibly via NHE blockade. Methods: MAC were isolated from peripheral blood of healthy volunteers and incubated in the presence/absence of SA (100 μM for 3 h) with/without empagliflozin (EMPA 100 μM) or amiloride (Ami 100 μM) for 1 h. Cell respiration (oxygen consumption rate OCR) and anaerobic glycolysis (measured as proton production rate) were recorded in real-time by Seahorse technology, and ATP production (anaerobic glycolysis- and oxphos-derived) rates were calculated. Results: SA, at the concentration causing inflammation and increased oxidant stress, altered cell bioenergetics of human MAC, with overall reductions in basal OCR and oxphos-derived ATP production (all p < 0.05), pointing to mitochondrial alterations. EMPA, at the concentration counteracting SA-induced lipotoxicity, both alone and in the presence of SA, caused NHE-independent extensive bioenergetic alterations (from p < 0.05 to p < 0.01), greater than those induced by SA alone. Conclusions: In human MAC: (1) SA altered cell bioenergetics, concomitantly with inflammation and oxidant stress; (2) EMPA possibly inhibited mitochondrial respiration, (3) the protective effect of EMPA against SA-induced lipotoxicity was unlikely to be mediated through bioenergetic metabolism

    Performance and antrhropometric characteristics of Elite Rugby Players.

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    Summary. Background and aim of the study: Physical performance is the result of a complex combination of several factors such as genetic and anthropometric aspects, nutrition and hormonal status. In the past few years many studies have considered the impact of vitamin D on muscular strength and athletic performance. e aim of the present study was to assess the anthropometric measures impacting on physical performance in a group of professional rugby athletes. As a secondary aim we investigated a possible relationship between baseline vitamin D status and athletic performance status in these subjects. Methods: All rugby players com- pleted a test–retest reliability study on performance measures, as 70kg jump squat and body weight (BW) jump squat to assess musculoskeletal performance. Additionally at the time point we collected a blood sample of every athletes for the assessment of serum vitamin D. Results: We found that lean mass was an important independent predictor of performance score in 70kg jump squat (p=0.007, R2=0.74) and BW jump squat (p=0.010, R2=0.66) in these well trained athletes. No statistically significant association was present between performance score and serum vitamin D in this specific setting. Conclusions: We demonstrate a positive in- teraction between lower limb lean mass and performance score, but we have not been able to identify any statistically significant association between worsening in performance measures and decrease of serum 25 OH Vitamin D

    SARS-CoV-2 Spike protein is not pro-inflammatory in human primary macrophages: endotoxin contamination and lack of protein glycosylation as possible confounders

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    Introduction: The inflammatory potential of SARS-CoV-2 Spike S1 (Spike) has never been tested in human primary macrophages (MΦ). Different recombinant Spikes might display different effects in vitro, according to protein length and glycosylation, and endotoxin (lipopolysaccharide, LPS) contamination. Objectives: To assess (1) the effects of different Spikes on human primary MΦ inflammation; (2) whether LPS contamination of recombinant Spike is (con)cause in vitro of increased MΦ inflammation. Methods: Human primary MΦ were incubated in the presence/absence of several different Spikes (10 nM) or graded concentrations of LPS. Pro-inflammatory marker expression (qPCR and ELISA) and supernatant endotoxin contamination (LAL test) were the main readouts. Results: LPS-free, glycosylated Spike (the form expressed in infected humans) caused no inflammation in human primary MΦ. Two (out of five) Spikes were contaminated with endotoxins ≥ 3 EU/ml and triggered inflammation. A non-contaminated non-glycosylated Spike produced in E. coli induced MΦ inflammation. Conclusions: Glycosylated Spike per se is not pro-inflammatory for human MΦ, a feature which may be crucial to evade the host innate immunity. In vitro studies with commercially available Spike should be conducted with excruciating attention to potential LPS contamination. Graphical abstract: [Figure not available: see fulltext.
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