Revealing novel biomarkers for diagnosing chronic kidney disease in pediatric patients.

Pediatric chronic kidney disease (CKD) is a clinical condition characterized by progressive renal function deterioration. CKD diagnosis is based on glomerular filtration rate, but its reliability is limited, especially at the early stages. New potential biomarkers (citrulline (CIT), symmetric dimethylarginine (SDMA), S-adenosylmethionine (SAM), n-butyrylcarnitine (nC4), cis-4-decenoylcarnitine, sphingosine-1-phosphate and bilirubin) in addition to creatinine (CNN) have been proposed for early diagnosis. To verify the clinical value of these biomarkers we performed a comprehensive targeted metabolomics study on a representative cohort of CKD and healthy pediatric patients. Sixty-seven children with CKD and forty-five healthy children have been enrolled in the study. Targeted metabolomics based on liquid chromatography-triple quadrupole mass spectrometry has been used for serum and plasma samples analysis. Univariate data analysis showed statistically significant differences (p < 0.05) in the concentration of CNN, CIT, SDMA, and nC4 among healthy and CKD pediatric patients. The predictive ability of the proposed biomarkers was also confirmed through specificity and sensitivity expressed in Receiver Operating Characteristic curves (AUC = 0.909). In the group of early CKD pediatric patients, AUC of 0.831 was obtained, improving the diagnostic reliability of CNN alone. Moreover, the models built on combined CIT, nC4, SDMA, and CNN allowed to distinguish CKD patients from healthy control regardless of blood matrix type (serum or plasma). Our data demonstrate potential biomarkers in the diagnosis of early CKD stages.

High-Fat Diet Affects Ceramide Content, Disturbs Mitochondrial Redox Balance, and Induces Apoptosis in the Submandibular Glands of Mice.

This is the first study to investigate the relationship between ceramides, the mitochondrial respiratory system, oxidative stress, inflammation, and apoptosis in the submandibular gland mitochondria of mice with insulin resistance (IR). The experiment was conducted on 20 male C57BL/6 mice divided into two equal groups: animals fed a high-fat diet (HFD; 60 kcal% fat) and animals fed a standard diet (10 kcal% fat). We have shown that feeding mice HFD induces systemic IR. We noticed that HFD feeding was accompanied by a significant increase in ceramide production (C18 1Cer, C18 Cer, C22 Cer, C24 1Cer, C24 Cer), higher activity of pro-oxidant enzymes (NADPH oxidase and xanthine oxidase), and weakened functioning of mitochondrial complexes in the submandibular glands of IR mice. In this group, we also observed a decrease in catalase and peroxidase activities, glutathione concentration, redox status, increased concentration of protein (advanced glycation end products, advanced oxidation protein products) and lipid (malondialdehyde, lipid hydroperoxide) peroxidation products, and enhanced production of tumor necrosis factor alpha (TNFα) and interleukin 2 (IL-2) as well as pro-apoptotic Bax in the submandibular gland mitochondria. In summary, HFD impairs salivary redox homeostasis and is responsible for enhanced oxidative damage and apoptosis in the submandibular gland mitochondria. The accumulation of some ceramides could boost free radical formation by affecting pro-oxidant enzymes and the mitochondrial respiratory chain.

Exposure to Ti4Al4V Titanium Alloy Leads to Redox Abnormalities, Oxidative Stress, and Oxidative Damage in Patients Treated for Mandible Fractures.

Due to the high biotolerance, favourable mechanical properties, and osseointegration ability, titanium is the basic biomaterial used in maxillofacial surgery. The passive layer of titanium dioxide on the surface of the implant effectively provides anticorrosive properties, but it can be damaged, resulting in the release of titanium ions to the surrounding tissues. The aim of our work was to evaluate the influence of Ti6Al4V titanium alloy on redox balance and oxidative damage in the periosteum surrounding the titanium miniplates and screws as well as in plasma and erythrocytes of patients with mandibular fractures. The study included 31 previously implanted patients (aged 21-29) treated for mandibular fractures and 31 healthy controls. We have demonstrated increased activity/concentration of antioxidants both in the mandibular periosteum and plasma/erythrocytes of patients with titanium mandibular fixations. However, increased concentrations of the products of oxidative protein and lipid modifications were only observed in the periosteum of the study group patients. The correlation between the products of oxidative modification of the mandible and antioxidants in plasma/erythrocytes suggests a relationship between the increase of oxidative damage at the implantation site and central redox disorders in patients with titanium miniplates and screws.