Browsing by Author "Munjas, Jelena (57194078742)"

Background: Chronic renal failure, particularly end-stage renal disease, is a serious health problem associated with a high mortality rate. Uremic syndrome leads to increased oxidative stress, inflammation, and dyslipidemia. Aims: To examine superoxide dismutase isoenzyme gene expression in peripheral blood mononuclear cells of patients on hemodialysis and to determine the associations between superoxide dismutase isoenzyme gene expression, oxidative stress, and non-enzymatic antioxidative protection. Study Design: Case control study. Methods: This study included 33 patients on hemodialysis (age, 55.33±15.31 years old) and 33 apparently healthy controls (age, 45.37±8.92 years old). Superoxide dismutase isoenzyme messenger ribonucleic acid levels were determined by real-time polymerase chain reaction. General biochemical parameters, high sensitivity C-reactive protein, total antioxidant status, thiobarbituric acid-reactive substances, and the superoxide anion radical were also determined. Results: Normalized Cu/Zn superoxide dismutase and Mn superoxide dismutase messenger ribonucleic acid levels were significantly higher in patients than controls (p<0.001 and p=0.011). A significant negative correlation was detected between normalized Cu/Zn superoxide dismutase messenger ribonucleic acid levels and total protein, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total antioxidant status. Normalized Mn superoxide dismutase messenger ribonucleic acid levels were negatively correlated with total protein and total antioxidant status. A multiple regression analysis revealed independent associations between total antioxidant status and normalized Cu/Zn superoxide dismutase (p=0.038) and between total antioxidant status and normalized Mn superoxide dismutase messenger ribonucleic acid levels (p=0.038 and p=0.018, respectively). Conclusion: The superoxide dismutase isoenzyme gene is expressed at a higher rate in patients with end-stage renal failure, probably due to increased oxidative stress and attenuated antioxidative defense. The plasma total antioxidant status is an independent predictor of normalized superoxide dismutase isoenzyme messenger ribonucleic acid levels. © 2018 by Trakya University Faculty of Medicine / The Balkan Medical Journal published by Galenos Publishing House.

Recurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls. The study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays. Our results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15-6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11-17.46, P=0.044). This is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings. © 2019 Society of Medical Biochemists of Serbia and Montenegro.

Recurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls. The study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays. Our results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15-6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11-17.46, P=0.044). This is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings. © 2019 Society of Medical Biochemists of Serbia and Montenegro.

Objectives: Gestational hypertension (GH) is one of the most common pregnancy-related complications, however, there is still insufficient knowledge about its development and molecular changes. The aim of our study was to examine the expression of miR-17, miR-29a and miR-181a, as well as TNF-α, IL-1β, IL-6 and IL-17 in women with GH and to investigate possible correlations between these parameters. Study design: The study included 64 pregnant women, placed either in the control or the GH group. Quantitative real-time PCR (qPCR) was used to determine expression levels of microRNAs and cytokines’ mRNAs. Main outcome measures: Expression levels of miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines mRNAs (TNF-α, IL-1β, IL-6 and IL-17) in women with gestational hypertension were compared to the control group (healthy pregnant women). Results: No significant changes in microRNAs expression level were found between compared groups. TNF-α was significantly upregulated in the GH group compared to controls. Expression levels of other investigated cytokines did not differ between examined groups. ROC curve analysis indicated that TNF-α does not show sufficient ability to discriminate between CG and GH patients. TNF-α was significantly positively correlated with IL-1β and IL-17 and negatively correlated with miR-181a. Conclusions: Our results point to the involvement of proinflamatory cytokines in gestational hypertension. Although increased expression of TNF-α was found in the GH group, this cytokine did not show sufficient ability to discriminate between GH and healthy pregnancies. © 2024 Elsevier B.V.

Altered microRNAs (miRNAs1) and cytokines expression levels are associated with several pregnancy-induced complications. We evaluated the profile of circulating miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-17) in women with gestational diabetes mellitus (GDM2), as well as their potential use as GDM biomarkers. The case-control study included 65 pregnant women divided into 2 groups - GDM and control. Expression levels of miRNAs in plasma samples and cytokines mRNA isolated from peripheral blood buffy coat were analyzed by quantitative real-time PCR (qPCR3). Significant miR-29a downregulation was found in GDM compared to the control group, and was even more significant after adjustments for covariates. miR-17 and miR-181a expression levels did not differ between the examined groups. Expression levels of IL-1β were significantly higher in GDM group compared to controls, while TNF-α, IL-6 and IL-17 did not show significant changes in expression between the two groups. As jugded from the ROC curve analysis, miR-29a and IL-1β had a significant capacity to discriminate between CG and GDM. Additionally, a positive correlation was established between IL-1β and TNF-α in the GDM group. GDM appeared to be associated with altered levels of miR-29a and IL-1β making them markers of this condition. © 2024 Elsevier B.V.

Altered microRNAs (miRNAs1) and cytokines expression levels are associated with several pregnancy-induced complications. We evaluated the profile of circulating miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-17) in women with gestational diabetes mellitus (GDM2), as well as their potential use as GDM biomarkers. The case-control study included 65 pregnant women divided into 2 groups - GDM and control. Expression levels of miRNAs in plasma samples and cytokines mRNA isolated from peripheral blood buffy coat were analyzed by quantitative real-time PCR (qPCR3). Significant miR-29a downregulation was found in GDM compared to the control group, and was even more significant after adjustments for covariates. miR-17 and miR-181a expression levels did not differ between the examined groups. Expression levels of IL-1β were significantly higher in GDM group compared to controls, while TNF-α, IL-6 and IL-17 did not show significant changes in expression between the two groups. As jugded from the ROC curve analysis, miR-29a and IL-1β had a significant capacity to discriminate between CG and GDM. Additionally, a positive correlation was established between IL-1β and TNF-α in the GDM group. GDM appeared to be associated with altered levels of miR-29a and IL-1β making them markers of this condition. © 2024 Elsevier B.V.

Coronary artery disease (CAD) is one of the most important causes of mortality and morbidity in wide world population. Dyslipidemia, inflammation and oxidative stress may contribute to disruption of endothelium structure and function, atherosclerosis and CAD. Our study was aimed to determine whether Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) gene expression could be modulated by oxidative stress in CAD patients. This study included 77 CAD patients and 31 apparently healthy persons. Serum lipid levels, high sensitivity C-reactive protein (hsCRP), total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS) were measured. SOD isoenzymes gene expression was determined in peripheral blood mononuclear cells using quantitative polymerase chain reaction. Mn SOD messenger ribonucleic acid (mRNA) levels were significantly lower in CAD patients than in controls (p=0.011), while Cu/Zn SOD mRNA levels did not change significantly between tested groups (p=0.091). We found significantly lower high-density lipoprotein-cholesterol (HDL-c) (p<0.001) and TAS (p<0.001) levels and significantly higher hsCRP (p=0.002) and TBARS (p<0.001) in CAD patients than in controls. There were significant positive correlations between TAS and Mn SOD mRNA (ρ=0.243, p=0.020) and TAS and Cu/Zn SOD mRNA (r=0.359, p<0.001). TBARS negatively correlated only with Cu/Zn SOD mRNA (ρ=-0.215, p=0.040). TAS levels remained independent predictor for Mn SOD mRNA levels (OR=2.995, p=0.034). Results of this study showed that Mn SOD gene expression were decreased in CAD patients compared to controls and can be modulated by non-enzymatic antioxidant status in blood. © 2019 Ana Ninić, Nataša Bogavac-Stanojević, Miron Sopić, Jelena Munjas, Jelena Kotur-Stevuljević, Milica Miljković, Tamara Gojković, Dimitra Kalimanovska-Oštrić, Vesna Spasojević-Kalimanovska.

Coronary artery disease (CAD) is one of the most important causes of mortality and morbidity in wide world population. Dyslipidemia, inflammation and oxidative stress may contribute to disruption of endothelium structure and function, atherosclerosis and CAD. Our study was aimed to determine whether Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) gene expression could be modulated by oxidative stress in CAD patients. This study included 77 CAD patients and 31 apparently healthy persons. Serum lipid levels, high sensitivity C-reactive protein (hsCRP), total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS) were measured. SOD isoenzymes gene expression was determined in peripheral blood mononuclear cells using quantitative polymerase chain reaction. Mn SOD messenger ribonucleic acid (mRNA) levels were significantly lower in CAD patients than in controls (p=0.011), while Cu/Zn SOD mRNA levels did not change significantly between tested groups (p=0.091). We found significantly lower high-density lipoprotein-cholesterol (HDL-c) (p<0.001) and TAS (p<0.001) levels and significantly higher hsCRP (p=0.002) and TBARS (p<0.001) in CAD patients than in controls. There were significant positive correlations between TAS and Mn SOD mRNA (ρ=0.243, p=0.020) and TAS and Cu/Zn SOD mRNA (r=0.359, p<0.001). TBARS negatively correlated only with Cu/Zn SOD mRNA (ρ=-0.215, p=0.040). TAS levels remained independent predictor for Mn SOD mRNA levels (OR=2.995, p=0.034). Results of this study showed that Mn SOD gene expression were decreased in CAD patients compared to controls and can be modulated by non-enzymatic antioxidant status in blood. © 2019 Ana Ninić, Nataša Bogavac-Stanojević, Miron Sopić, Jelena Munjas, Jelena Kotur-Stevuljević, Milica Miljković, Tamara Gojković, Dimitra Kalimanovska-Oštrić, Vesna Spasojević-Kalimanovska.

Context: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage. Objectives: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. Materials and methods: Eighteen male Wistar albino rats were divided into three groups (n=6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1 mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin. Results: Normalized HO-1 [0.11 (0.04-0.24)] and MCP-1 [0.29 (0.21-0.47)] mRNA levels and DNA scores [12.50 (4.50-36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35-2.51)], p=0.021 for HO-1 [0.85 (0.61-3.45)], p=0.047 for MCP-1 and [176.5 (66.50-221.25)], p=0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21-0.71), p=0.049]. Conclusions: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage. © 2018 The Author(s).

Context: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage. Objectives: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. Materials and methods: Eighteen male Wistar albino rats were divided into three groups (n=6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1 mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin. Results: Normalized HO-1 [0.11 (0.04-0.24)] and MCP-1 [0.29 (0.21-0.47)] mRNA levels and DNA scores [12.50 (4.50-36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35-2.51)], p=0.021 for HO-1 [0.85 (0.61-3.45)], p=0.047 for MCP-1 and [176.5 (66.50-221.25)], p=0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21-0.71), p=0.049]. Conclusions: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage. © 2018 The Author(s).

Introduction: Sphingolipids, essential to trophoblast and endothelial function, may impact inflammation in preeclampsia. However, their specific role in late-onset preeclampsia remains unclear. To address this research gap, we analyzed sphingolipid profiles in pregnancies at high risk for preeclampsia development to identify potential biomarkers and clarify their role in disease pathogenesis. Materials and methods: We monitored 90 pregnant women at high risk for preeclampsia development across four gestational points. These women were later categorized into the group of women with high risk who did not develop preeclampsia (HRG) (70 women) or the preeclampsia group (PG) (20 women). Sphingolipids (sphingosine, sphinganine, sphingosine-1-phosphate (S1P), ceramides C16:0/C24:0, and sphingomyelin C16:0) were quantified via liquid chromatography-tandem mass spectrometry. Results: Sphingolipid profiles revealed distinct patterns between groups. Concentrations of S1P in the HRG increased from the 1st trimester to delivery (P < 0.001). We did not notice significant changes in S1P during pregnancy in the PG but compared with the HRG we found significantly lower concentrations at each test point from the 2nd trimester until delivery (P = 0.020, P = 0.013, P = 0.011, respectively). Ceramides C16:0 and C24:0 demonstrated significant increases over time in HRG (P < 0.001, both). Sphingomyelin C16:0 increased significantly across pregnancy in both groups (P < 0.001 in HRG and P = 0.006 in PG), with no significant differences between groups. Conclusions: We identified S1P as a potential biomarker for late-onset preeclampsia, with lower concentrations observed in PG compared to HRG. Rising sphingomyelin concentrations in both cohorts might serve as a relevant cardiovascular risk indicator in pregnancies at high risk for preeclampsia. © by Croatian Society of Medical Biochemistry and Laboratory Medicine.

Introduction: Sphingolipids, essential to trophoblast and endothelial function, may impact inflammation in preeclampsia. However, their specific role in late-onset preeclampsia remains unclear. To address this research gap, we analyzed sphingolipid profiles in pregnancies at high risk for preeclampsia development to identify potential biomarkers and clarify their role in disease pathogenesis. Materials and methods: We monitored 90 pregnant women at high risk for preeclampsia development across four gestational points. These women were later categorized into the group of women with high risk who did not develop preeclampsia (HRG) (70 women) or the preeclampsia group (PG) (20 women). Sphingolipids (sphingosine, sphinganine, sphingosine-1-phosphate (S1P), ceramides C16:0/C24:0, and sphingomyelin C16:0) were quantified via liquid chromatography-tandem mass spectrometry. Results: Sphingolipid profiles revealed distinct patterns between groups. Concentrations of S1P in the HRG increased from the 1st trimester to delivery (P < 0.001). We did not notice significant changes in S1P during pregnancy in the PG but compared with the HRG we found significantly lower concentrations at each test point from the 2nd trimester until delivery (P = 0.020, P = 0.013, P = 0.011, respectively). Ceramides C16:0 and C24:0 demonstrated significant increases over time in HRG (P < 0.001, both). Sphingomyelin C16:0 increased significantly across pregnancy in both groups (P < 0.001 in HRG and P = 0.006 in PG), with no significant differences between groups. Conclusions: We identified S1P as a potential biomarker for late-onset preeclampsia, with lower concentrations observed in PG compared to HRG. Rising sphingomyelin concentrations in both cohorts might serve as a relevant cardiovascular risk indicator in pregnancies at high risk for preeclampsia. © by Croatian Society of Medical Biochemistry and Laboratory Medicine.

Purpose: Obstructive sleep apnea (OSA) is characterised by increased systemic inflammation, and is often accompanied with type 2 diabetes mellitus (T2DM) and cardiovascular disease. The aim of this investigation was to evaluate gene expression of resistin, its receptor CAP1 and CD36 as the indicators of the inflammatory changes in PBMCs in relation to the severity of OSA, and the presence of type 2 diabetes mellitus (T2DM) in OSA. Methods: Severity of OSA was defined by the apnea/hypopnea index (AHI): AHI < 30: mild to moderate OSA (MM-OSA), AHI ≥ 30: severe OSA (S-OSA). Presence of T2DM was captured: OSA with T2DM (OSA + T2DM), OSA without T2DM (OSA-T2DM). PBMC resistin, CAP1, and CD36 mRNA were determined by real-time PCR. Results: Resistin mRNA was significantly upregulated in S-OSA (N = 54) compared to the MM-OSA (N = 52, P = 0.043); CAP1 and CD36 mRNA levels did not differ between the groups (P = 0.302; P = 0.166, respectively). Resistin mRNA was significantly upregulated in OSA + T2DM (N = 29) compared to the OSA-T2DM (N = 77, P = 0.029); CAP1 and CD36 mRNA levels did not differ between the groups (P = 0.662; P = 0.108, respectively). AHI and T2DM were independent predictors of resistin mRNA above the 75th percentile (OR = 3.717 [1.152–11.991]; OR = 3.261 [1.000–10.630], P = 0.042 respectively). Conclusion: Resistin gene upregulation in S-OSA indicates its possible contribution to increased inflammation in S-OSA and makes it a possible marker of the disease severity. Resistin gene upregulation in OSA + T2DM suggests that a joint effect of these two comorbidities may have a major contribution to increased inflammation and complications that arise from this state. © 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.