Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson's Disease at the Prodromal Stage.

Parkinson's disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains the low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD. The aim of this study was to search for changes in the blood of patients at risk of developing PD, which are considered potential diagnostic biomarkers. Out of 1835 patients, 26 patients were included in the risk group and 20 patients in the control group. The primary criteria for inclusion in a risk group were the impairment of sleep behavior disorder and sense of smell, and the secondary criteria were neurological and mental disorders. In patients at risk and in controls, the composition of plasma and the expression of genes of interest in lymphocytes were assessed by 27 indicators. The main changes that we found in plasma include a decrease in the concentrations of l-3,4-dihydroxyphenylalanine (L-DOPA) and urates, as well as the expressions of some types of microRNA, and an increase in the total oxidative status. In turn, in the lymphocytes of patients at risk, an increase in the expression of the DA D3 receptor gene and the lymphocyte activation gene 3 (LAG3), as well as a decrease in the expression of the Protein deglycase DJ-1 gene (PARK7), were observed. The blood changes we found in patients at risk are considered candidates for diagnostic biomarkers at the prodromal stage of PD.

New facets of nanozyme activity of ceria: lipo- and phospholipoperoxidase-like behaviour of CeO2 nanoparticles.

Cerium dioxide nanoparticles have a special place among engineered nanomaterials due to the wide range of their enzyme-like activities. They possess SOD-, catalase- and peroxidase-like properties, as well as recently discovered phosphatase-, photolyase-, phospholipase- and nuclease-like properties. Advancing biomedical applications of CeO2-based nanozymes requires an understanding of the features and mechanisms of the redox activity of CeO2 nanoparticles when entering the vascular bed, especially when interacting with lipid-protein supramolecular complexes (biomembranes and lipoproteins). In this paper, CeO2 nanoparticles are shown to possess two further types of nanozyme activity, namely lipo- and phospholipoperoxidase-like activities. Compared to a strong blood prooxidant, hemoglobin, CeO2 nanoparticles act as a mild oxidising agent, since they exhibit a 106 times lower, and 20 times lower, prooxidant capacity towards linoleic acid and phosphatidylcholine hydroperoxides, respectively. Compared to the widespread pharmacological preparation of iron, Fe(iii) carboxymaltose (antianemic preparation Ferinject®), the prooxidant capacity of CeO2 nanoparticles towards lipid and phospholipid substrates has been shown to be 102 times lower, and 4 times higher, respectively. The data obtained on the mechanism of the interaction of nanodisperse CeO2 with the main components of biological membranes, lipids and phospholipids enable the substantial expansion of the scope of biomedical applications of CeO2 nanozymes.

Prognosis and cardiovascular morbidity and mortality in prospective study of hypertensive patients with obstructive sleep apnea syndrome in St Petersburg, Russia.

BACKGROUND: To assess the impact of obstructive sleep apnea-hypopnea syndrome (OSAHS) on prognosis and cardiovascular morbidity and mortality in relation to other major cardiovascular risk factors. MATERIAL/METHODS: This prospective study recruited 234 patients from an out-patient clinic. Based on the Berlin questionnaire, 147 patients (90 males, mean age 52.1 ± 10.4 years) with highly suspected sleep breathing disorders were included in the study. Based on cardiorespiratory monitoring, patients were divided into 2 groups: 42 patients without sleep breathing disorders (SBD), and 105 patients with OSAHS. Among these, 12 patients started CPAP therapy and formed the third group. RESULTS: The mean follow-up period was 46.4 ± 14.3 months. Event-free survival was lowest in the untreated OSAHS patients (log rank test 6.732, p = 0.035). In the non-adjusted regression model, OSAHS was also associated with a higher risk of cardiovascular events (OR = 8.557, 95% CI 1.142-64.131, p = 0.037). OSAHS patients demonstrated higher rates of hospitalization compared to the control group without SBD (OR 2.750, 95%CI 1.100-6.873, p = 0.04). CONCLUSIONS: OSAHS hypertensive patients, and in particular, according to our model, patients with severe OSAHS (AHI ≥ 30/h), are at higher risk of fatal and non-fatal cardiovascular events. Moreover, untreated OSAHS patients demonstrate higher rates of hospitalization caused by the onset or deterioration of cardiovascular disease.