scholarly journals Regulation of neutrophil gelatinase-associated lipocalin in aortic valve stenosis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E Jover ◽  
L Matilla ◽  
M Garaikoetxea ◽  
A Fernandez-Celis ◽  
R Sabada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aortic Valve ◽  
Type I ◽  
Serum Samples ◽  
Alizarin Red ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Wide Range ◽  
Neutrophil Gelatinase ◽  
And Oxidative Stress

Abstract Background Aortic valve (AV) stenosis is the commonest form of adult valvular heart disease (VHD) and affects 4.5% of the general population aged over 60 years. Owing to multifactorial and complex molecular events, the valve interstitial cell (VIC) undergoes myofibroblast and osteoblast differentiation. Neutrophil gelatinase-associated lipocalin (NGAL) is a pleiotropic glycoprotein belonging to the lipocalin family and it is expressed in a wide range of tissues and cell types. It is deregulated in several diseases with both detrimental and beneficial effects. NGAL mainly signals towards 24p3R. Purpose We aimed to confirm the expression of NGAL in human AV stenosis and its association with inflammation, oxidative stress, fibrosis/remodeling and calcification, and its regulation in calcifying VICs. Methods Surgical AV leftovers were harvested from patients undergoing elective surgical valve replacement with no kidney disease. Serum samples were collected within the 24h before the surgery. AV were histologically assessed by hematoxylin-eosin, Movat, Alizarin Red and Alcian blue/Sirius Red staining and immunohistochemistry. Western blotting, ELISA and zymography were used in molecular biology studies. VICs were challenged for 2, 4 and 8 days with hyperphosphate (2.6mM, HP) media ± rhNGAL for in vitro validation studies. Results NGAL was quantified in AVs and serum samples from 126 donors (57.4% men). Circulating NGAL was associated with circulating inflammation (Tumor Necrosis Factor-α, Interleukin (IL)-6 and ICAM-1) and oxidative stress (Myeloperoxidase (MPO) and 8OHdG) markers. Likewise, tissue NGAL was correlated with inflammation (IL-6, RANTES and Galectin-3), oxidative stress (MPO, Endothelial Nitric Oxide Synthase, Malondialdehyde (MDA) and Carboxy Methyl Lysine (CML)) and fibrosis (Collagen type I). Osteoblast markers, metalloproteinase (MMP)-9 expression or its activity were not associated with NGAL. NGAL was greater expressed in men than women (217.70±23.41 vs. 119.5±11.31, p=0.0098). In vitro, intracellular NGAL and 24p3R were strongly down-regulated in calcifying men-derived VICs (n=6) whereas secretion of NGAL was enhanced from day 4 (0.55±0.15, p=0.0283; 0.32±0.09 p<0.0001; 8.00±2.32, p=0.0053 fold changes, respectively). This may reflect reduced 24p3R-dependent signalling in osteoblast-like VICs. Such effects were overall negated in women-derived VICs (n=3). RhNGAL endowed calcifying VICs with increased necrosis (52KDa-cPARP1), apoptosis (cCaspase 3) and oxidative stress (CML, MDA, nitrotyrosine and pNF-kB) at day 8. Conclusions NGAL is associated with inflammation, oxidative stress and fibrosis in AV stenosis, and promotes pro-apoptotic and necrotic phenotypes in vitro. Our results suggest that NGAL signaling may drive sex-dependent differences clinically relevant to the VHD pathogenesis. The challenge is now to understand how NGAL signals in men/women-derived VICs. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III

Astragalus Polysaccharide Nano-Liposomes Modulate the Inflammatory Response and Oxidative Stress in Stroke-Associated Pneumonia by Increasing OIP5-AS1 to Regulate the miR-128-3p/SIRT1 Pathway

2020 ◽  
Vol 12 (12) ◽  
pp. 1422-1430
Author(s):  
Weidong Zhu ◽  
Lifeng Yu ◽  
Ze Zhu ◽  
Dongmei Zhang ◽  
Yuyan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Lung Epithelial Cells ◽  
Herbal Extract ◽  
Therapeutic Effects ◽  
Serum Samples ◽  
Sirt1 Expression ◽  
Astragalus Polysaccharide ◽  
And Oxidative Stress

Stroke-associated pneumonia (SAP) is major reason for the poor prognosis of stroke patients. Astragalus polysaccharide (APS) is a commonly used Chinese herbal extract that regulates the inflammatory response, however, its therapeutic effects on APS as well as its underlying mechanism of action are unclear. In this study, we evaluated the effects of APS nano-liposomes on SAP, including regulation of the inflammatory response and oxidative stress, as well as the underlying molecular mechanism. Serum samples of SPA were collected from patients and healthy controls and the expression of OIP5-AS1 and miR-128-3p was measured. Lipopolysaccharide (LPS) was used to construct an in vitro lung injury model using RLE-6TN lung epithelial cells and APS nanoliposomes were used for treatment. Several cellular processes were evaluated including OIP5-AS1, miR-128-3p, and SIRT1 expression by RT-PCR, SIRT1 protein expression by western blot analysis, IL-1β, TNF-α, and IL-6 expression by ELISA, a bioinformatics analysis for downstream molecular targets of OIP5-AS1, and dual luciferase and RNA immunoprecipitation (RIP) assays to identify interactions between miR-128-3p, OIP5-AS1, and SIRT1. Our results revealed low expression of OIP5-AS1 and high expression of miR-128-3p in SAP. Treatment with APS nano-liposomes reduced LPS-induced apoptosis of RLE-6TN cells, inhibited the inflammatory response and oxidative stress, and increased OIP5-AS1 and SIRT1 expression. Furthermore, the overexpression of miR-128-3p reversed the protective effect of APS nano-liposomes on LPS-induced RLE-6TN cells. In summary, OIP5-AS1 is an endogenous competitor that inhibits miR-128-3p targeting of SIRT1. APS nanoliposomes significantly reduced miR-128-3p expression resulting in increased OIP5-AS1 expression.

scholarly journals Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo
Keyword(s):  
Oxidative Stress ◽  
Food Sources ◽  
Preventive Action ◽  
Nutritional Interventions ◽  
Beneficial Effects ◽  
Age Related ◽  
Macromolecular Damage ◽  
And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

Pirfenidone mediates cigarette smoke extract induced inflammation and oxidative stress in vitro and in vivo

2021 ◽  
Vol 96 ◽  
pp. 107593
Author(s):  
Yiming Ma ◽  
Lijuan Luo ◽  
Xiangming Liu ◽  
Herui Li ◽  
Zihang Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Cigarette Smoke Extract ◽  
And Oxidative Stress

In vitro study on the effects of iron sucrose, ferric gluconate and iron dextran on redox-active iron and oxidative stress

2011 ◽  
Vol 60 (07) ◽  
pp. 459-465
Author(s):  
Brigitte Sturm ◽  
Hannes Steinkellner ◽  
Nina Ternes ◽  
Hans Goldenberg ◽  
Barbara Scheiber-Mojdehkar
Keyword(s):  
Oxidative Stress ◽  
In Vitro Study ◽  
Iron Sucrose ◽  
Vitro Study ◽  
Iron Dextran ◽  
Active Iron ◽  
Redox Active ◽  
And Oxidative Stress

scholarly journals Tamoxifen and oxidative stress: an overlooked connection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nermin S. Ahmed ◽  
Marek Samec ◽  
Alena Liskova ◽  
Peter Kubatka ◽  
Luciano Saso
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Gold Standard ◽  
Pharmacological Activities ◽  
Standard Drug ◽  
Menopausal Women ◽  
Wide Range ◽  
Post Menopausal ◽  
Apoptotic Effects ◽  
And Oxidative Stress

AbstractTamoxifen is the gold standard drug for the treatment of breast cancer in pre and post-menopausal women. Its journey from a failing contraceptive to a blockbuster is an example of pharmaceutical innovation challenges. Tamoxifen has a wide range of pharmacological activities; a drug that was initially thought to work via a simple Estrogen receptor (ER) mechanism was proven to mediate its activity through several non-ER mechanisms. Here in we review the previous literature describing ER and non-ER targets of tamoxifen, we highlighted the overlooked connection between tamoxifen, tamoxifen apoptotic effects and oxidative stress.

The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
High Dose ◽  
Protective Effects ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

scholarly journals Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 114
Author(s):  
Pahriya Ashrap ◽  
Deborah J. Watkins ◽  
Ginger L. Milne ◽  
Kelly K. Ferguson ◽  
Rita Loch-Caruso ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostaglandin F2α ◽  
Urine Samples ◽  
Oxidative Stress Marker ◽  
Essential Metals ◽  
Male Fetus ◽  
Metal Concentrations ◽  
Fetal Sex ◽  
Wide Range ◽  
And Oxidative Stress

Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9% for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.

Sign in / Sign up

Export Citation Format

Share Document