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Background: Coronavirus infectious disease 2019 (COVID-19) is a significant public health problem worldwide. COVID-19 increases the risk of non-pulmonary complications such as acute myocardial injury, renal failure, thromboembolic events, and multi-organic damage. Several studies have documented increased inflammation molecules, endothelial dysfunction biomarkers, and dysregulation of coagulation factors in COVID-19 patients. In addition, endothelium dysfunction is exacerbated by the oxidative stress (OxS) promoted by endocrine and cardiovascular molecules. Our objective was to evaluate whether endothelial and OxS biomarkers were associated with mortality in hospitalized COVID-19 patients. Methods: A prospective cohort study was performed. Patients ≥18 years old with confirmed COVID-19 that required hospitalization were included in a prospective cohort study. Endothelium and oxidative stress biomarkers were collected between 3 and 5 days after admission. Results: A total of 165 patients were evaluated; 56 patients succumbed. The median follow-up was 71 days [23–129]. Regarding endothelial dysfunction and OxS biomarkers, patients who did not survive had higher levels of nitrates (0.4564 [0.1817–0.6761] vs. 0.2817 [0.0517–0.5], p = 0.014), total nitrates (0.0507 [−0.0342–0.1809] vs. −0.0041 [−0.0887–0.0909], p = 0.016), sE-Selectin (1.095 [0.86–1.495] vs. 0.94 [0.71–1.19], p = 0.004), and malondialdehyde (MDA) (0.50 [0.26–0.72] vs. 0.36 [0.23–0.52], p = 0.010) compared to patients who survived. Endothelial and OxS biomarkers independently associated with mortality were sE-selectin (HR:2.54, CI95%; from 1.11 to 5.81, p = 0.027), nitrates (HR:4.92, CI95%; from 1.23 to 19.63, p = 0.024), and MDA (HR: 3.05, CI95%; from 1.14 to 8.15, p = 0.025). Conclusions: Endothelial dysfunction (sE-selectin and nitrates) and OxS (MDA) are independent indicators of a worse prognosis in COVID-19 patients requiring hospitalization.

Background: The proximal tubule (PT) is the major target of cadmium (Cd2+) nephrotoxicity. Current dogma postulates that Cd2+ complexed to metallothionein (MT) (CdMT) is taken up through receptor-mediated endocytosis (RME) via the PT receptor megalin:cubilin, which is the predominant pathway for reuptake of filtered proteins in the kidney. Nevertheless, there is evidence that the distal parts of the nephron are also sensitive to damage induced by Cd2+. In rodent kidneys, another receptor for protein endocytosis, the 24p3 receptor (24p3R), is exclusively expressed in the apical membranes of distal tubules (DT) and collecting ducts (CD). Cell culture studies have demonstrated that RME and toxicity of CdMT and other (metal ion)–protein complexes in DT and CD cells is mediated by 24p3R. In this study, we evaluated the uptake of labeled CdMT complex through 24p3R after acute kidney injury (AKI) induced by gentamicin (GM) administration that disrupts PT function. Subcutaneous administration of GM at 10 mg/kg/day for seven days did not alter the structural and functional integrity of the kidney’s filtration barrier. However, because of PT injury, the concentration of the renal biomarker Kim-1 increased. When CdMT complex coupled to FITC was administered intravenously, both uptake of the CdMT complex and 24p3R expression in DT increased and also colocalized after PT injury induced by GM. Although megalin decreased in PT after GM administration, urinary protein excretion was not changed, which suggests that the increased levels of 24p3R in the distal nephron could be acting as a compensatory mechanism for protein uptake. Altogether, these results suggest that PT damage increases the uptake of the CdMT complex through 24p3R in DT (and possibly CD) and compensate for protein losses associated with AKI.

Osteopontin (OPN) is a protein involved in inflammatory illnesses such as fibrosis and cancer; its overexpression in cardiovascular diseases promotes the biomineralization of blood vessels and other soft tissues. Moreover, there is an active component of oxidative stress related with those diseases. The present study relates serum OPN levels with nutritional condition and oxidative stress in a group of adolescents. Anthropometric measurements were performed, and fasting blood samples were analyzed to determine OPN concentrations, blood chemistry parameters (glucose, triglycerides, total cholesterol, urea, uric acid, and creatinine) and oxidative stress biomarkers (Paraoxonase-1, Glutathione S-Transferase, Catalase, NAD(P)H Quinone Oxidoreductase, free carbonyl groups and malondialdehyde). Adolescents were categorized according to body mass index (BMI) and metabolic syndrome (MetS) criteria. We found increased OPN serum concentrations in overweight and obese adolescents, as well as in adolescents with MetS. Rises in OPN correlated with arm circumference and biomarkers of lipid peroxidation; with regard to serum glucose there was a trend to positive correlation. Our results suggest that serum OPN is associated to nutritional status and could be considered as an early biomarker of low-grade inflammation and probably the early biomineralization of soft tissues in adolescence.

Background: The child labor situation has been associated with precarious job conditions and poor health conditions because children are often exposed to unsafe work environments, stressful psycho-social work conditions, scarce or no access to protective services, and heavy work burdens. Objective: The aim of the study was to evaluate markers of exposure to benzene through the exposure biomarker trans, trans-muconic acid (tt-MA), and biomarkers of early renal damage in children who work in sites that are under precarious job conditions. Method: Samples of urine were obtained from children (aged 6–12 years old) who resided in Ticul, Yucatan, Mexico. Exposure to benzene was assessed through trans, trans-muconic acid (t,t-MA). Evaluated renal damage biomarkers were: Cystatin-C (Cys-C), Osteopontin (OPN), α1-Microglobulin (α1-MG) and Neutrophil Gelatinase-Associated Lipocalin (NGAL). Findings: Children who live where the workplace is inside the dwelling presented higher mean levels of tt-MA (0.59 mg/g creatinine) compared with those who live away from the workshops (0.19 mg/g creatinine). Likewise, mean levels of NGAL (4.7, 5.2 ng/ml), albuminuria (10, 10 ng/ml), Cys-C (11.8, 7.5 ng/ml), OPN (224.4, 226.5 ng/ml) and α1-MG (96.6, 73.6 ng/ml) were found in children where the workplace was inside the dwelling and outside, respectively. Conclusion: Our data indicate that the children who work under precarious job conditions are exposed to benzene, and they exhibit protein levels that suggest renal damage in a population in precarious working conditions. Therefore, the child population should be considered as the most vulnerable and susceptible to suffer adverse health effects.

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Our results show that compounds C5, C7, C10, C12 and C15 had the lowest IC50 of the series. C15 was the most active compound (IC50= 3.02 μg/mL), inducing caspase-dependent apoptotic cell death via the intrinsic pathway. QSAR and QPAR studies are discussed.

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