Oleuropein, a Component of Extra Virgin Olive Oil, Improves Liver Steatosis and Lobular Inflammation by Lipopolysaccharides-TLR4 Axis Downregulation.

Gut-dysbiosis-induced lipopolysaccharides (LPS) translocation into systemic circulation has been suggested to be implicated in nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to assess if oleuropein (OLE), a component of extra virgin olive oil, lowers high-fat-diet (HFD)-induced endotoxemia and, eventually, liver steatosis. An immunohistochemistry analysis of the intestine and liver was performed in (i) control mice (CTR; n = 15), (ii) high-fat-diet fed (HFD) mice (HFD; n = 16), and (iii) HFD mice treated with 6 µg/day of OLE for 30 days (HFD + OLE, n = 13). The HFD mice developed significant liver steatosis compared to the controls, an effect that was significantly reduced in the HFD + OLE-treated mice. The amount of hepatocyte LPS localization and the number of TLR4+ macrophages were higher in the HFD mice in the than controls and were lowered in the HFD + OLE-treated mice. The number of CD42b+ platelets was increased in the liver sinusoids of the HFD mice compared to the controls and decreased in the HFD + OLE-treated mice. Compared to the controls, the HFD-treated mice showed a high percentage of intestine PAS+ goblet cells, an increased length of intestinal crypts, LPS localization and TLR4+ expression, and occludin downregulation, an effect counteracted in the HFD + OLE-treated mice. The HFD-fed animals displayed increased systemic levels of LPS and zonulin, but they were reduced in the HFD + OLE-treated animals. It can be seen that OLE administration improves liver steatosis and inflammation in association with decreased LPS translocation into the systemic circulation, hepatocyte localization of LPS and TLR4 downregulation in HFD-induced mouse model of NAFLD.

Food contamination and cardiovascular disease: a narrative review.

Cardiovascular disease is a significant cause of morbidity and mortality among non-communicable diseases worldwide. Evidence shows that a healthy dietary pattern positively influences many risk factors of cardiometabolic health, stroke, and heart disease, supported by the effectiveness of healthy diet and lifestyles for the prevention of CVD. High quality and safety of foods are prerequisites to ensuring food security and beneficial effects. Contaminants can be present in foods mainly because of contamination from environmental sources (water, air, or soil pollution), or artificially introduced by the human. Moreover, the cross-contamination or formation during food processing, food packaging, presence or contamination by natural toxins, or use of unapproved food additives and adulterants. Numerous studies reported the association between food contaminants and cardiovascular risk by demonstrating that (1) the cross-contamination or artificial sweeteners, additives, and adulterants in food processing can be the cause of the risk for major adverse cardiovascular events and (2) environmental factors, such as heavy metals and chemical products can be also significant contributors to food contamination with a negative impact on cardiovascular systems. Furthermore, oxidative stress can be a common mechanism that mediates food contamination-associated CVDs as substantiated by studies showing impaired oxidative stress biomarkers after exposure to food contaminants.This narrative review summarizes the data suggesting how food contaminants may elicit artery injury and proposing oxidative stress as a mediator of cardiovascular damage.

Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function.

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient ß: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient ß: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient ß:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient ß:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

Association between endotoxemia and blood no in the portal circulation of cirrhotic patients: results of a pilot study.

Pathophysiology of portal vein thrombosis (PVT) in cirrhosis is still not entirely understood. Elevated levels of lipopolysaccharides (LPS) in portal circulation are significantly associated with hypercoagulation, increased platelet activation and endothelial dysfunction. The aim of the study was to investigate if LPS was associated with reduced portal venous flow, the third component of Virchow's triad, and the underlying mechanism. Serum nitrite/nitrate, as a marker of nitric oxide (NO) generation, and LPS were measured in the portal and systemic circulation of 20 patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedure; portal venous flow velocity (PVV) was also measured in each patient and correlated with NO and LPS levels. Serum nitrite/nitrate and LPS were significantly higher in the portal compared to systemic circulation; a significant correlation was found between LPS and serum nitrite/nitrate (R = 0.421; p < 0.01). Median PVV before and after TIPS was 15 cm/s (6-40) and 31 cm/s (14-79), respectively. Correlation analysis of PVV with NO and LPS showed a statistically significant negative correlation of PVV with portal venous NO concentration (R = - 0.576; p = 0.020), but not with LPS. In vitro study with endothelial cells showed that LPS enhanced endothelial NO biosynthesis, which was inhibited by L-NAME, an inhibitor of NO synthase, or TAK-242, an inhibitor of TLR4, the LPS receptor; this effect was accomplished by up-regulation of eNOS and iNOS. The study shows that in cirrhosis, endotoxemia may be responsible for reduced portal venous flow via overgeneration of NO and, therefore, contribute to the development of PVT.

NOX2 as a Biomarker of Academic Performance: Evidence from University Students during Examination.

BACKGROUND: Cortisol levels, oxidative stress, and lower cerebral performance seem to be closely related. This study aimed to evaluate the question of whether exam stress affected oxidative stress and endothelial function parameters in the salivary samples of students. METHODS: A total of 114 healthy students were recruited. All students were subjected to a 21-item DASS questionnaire to assess perceived stress. Cortisol levels, biomarkers of oxidative stress, and endothelial function were evaluated at T0, during the semester, and T1, in the morning before the exam, in saliva samples. In vitro, HUVECs were stimulated with cortisol, and oxidative stress and endothelial function parameters were evaluated. RESULTS: At T1, cortisol levels were significantly increased compared with the levels during the semester. Moreover, exam results correlated inversely with the DASS score at T1. In addition, NOX2, H2O2 and endothelin-1 significantly increased, while NO bioavailability decreased. In vitro, HUVECs treatment with human cortisol determined the increase of oxidative stress and the decrease of endothelial function, in association with impaired eNOS phosphorylation. CONCLUSION: NOX2-mediated oxidative stress is a mechanism that could mediate cortisol-induced transient endothelial dysfunction during academic examination. Therefore, strategies to monitor or modulate oxidative stress could help students to reduce the impact of examination-related stress.