Browsing by Author "Stevanović, Ivana (57203529866)"

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-α and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2-0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target. © 2017 Milošević, Milicević, Božić, Lavrnja, Stevanović, Bijelić, Dubaić, Živković, Stević, Giniatullin and Andjus.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-α and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2-0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target. © 2017 Milošević, Milicević, Božić, Lavrnja, Stevanović, Bijelić, Dubaić, Živković, Stević, Giniatullin and Andjus.

ence (WC), blood pressure (BP), serum triglyceride (TG), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were also compared between the two groups. Results. PDG patients had statistically significantly higher TNF-α values compared to the HCG patients (73 pg/mL vs. 55 pg/mL, p = 0.024). A trend towards higher levels of IL-8 and IL-1β and lower levels of E-selectin, VEGF-A, and IL-18 was registered in PDG patients but without statistical significance. Furthermore, PDG patients had higher values of BMI, WC, systolic BP, serum TG, FPG, and HbA1c when compared to HCG. Conclusion. The results of our study suggest the importance of inflammation and some inflammatory mediators in the pathogenesis of early glycoregulation disorder. We believe that the main goal of future studies should focus on anti-inflammatory therapy in prediabetes.; Background/Aim. Prediabetes is a condition that refers to the state of hyperglycemia not sufficiently high to reach the diagnostic values for type 2 diabetes mellitus (T2DM). This condition often precedes the appearance of T2DM. The association between the development of early glycoregulation disorders and the state of low-grade chronic inflammation is still not sufficiently well understood. The aim of the study was to assess the values of different inflammatory mediators and biomarkers in individuals with prediabetes. Methods. This cross-sectional, observational study included 60 respondents divided into two groups: the prediabetes group (PDG) with 31 patients and the healthy control group (HCG) with 29 respondents. Serum values of seven selected cytokines/biomarkers were compared between the two groups. Examined biomarkers were: interleukin (IL)-1β, IL-6, IL-8, IL-18, tumor necrosis factor (TNF)-α, E-selectin, and vascular endothelial growth factor (VEGF)-A. In addition, the values of body mass index (BMI), waist circumfer-ence (WC), blood pressure (BP), serum triglyceride (TG), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were also compared between the two groups. Re-sults. PDG patients had statistically significantly higher TNF-α values compared to the HCG patients (73 pg/mL vs. 55 pg/mL, p = 0.024). A trend towards higher levels of IL-8 and IL-1β and lower levels of E-selectin, VEGF-A, and IL-18 was registered in PDG patients but without sta-tistical significance. Furthermore, PDG patients had higher values of BMI, WC, systolic BP, serum TG, FPG, and HbA1c when compared to HCG. Conclusion. The results of our study suggest the importance of inflammation and some inflammatory mediators in the pathogenesis of early glycoregulation disorder. We believe that the main goal of future studies should focus on anti-inflammatory therapy in prediabetes. © 2024 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.