Browsing by Author "Simic, Tatjana (6602094386)"

Purpose: We aimed to discern the role of glutathione (GSH) associated enzymes in maintaining high GSH levels in renal cell carcinoma (RCC) of the clear cell type and analyze RCC enzyme antioxidant capacity. Since changes in cellular redox balance in RCC might also be related to alterations of glutathione S-transferase (GST) phenotype, GST class α and π expression was also explored. Methods and materials: Human kidney specimens of tumor and distant nontumor regions were obtained from 15 patients with RCC at the time of surgery. The activities of GSH-replenishing enzymes, γ-glutamylcysteine synthetase (γ-GCS), γ-glutamyl transferase (γ-GT), and glutathione reductase (GR), as well as the activities of antioxidant enzymes glutathione peroxidase (GPX) and catalase (CAT) were determined spectrophotometrically. GST α and π class expression was determined by immunoblot. Results: In the course of renal cancerization, significant changes appear in the activities of GSH-replenishing and antioxidant enzymes. The activity of the key enzyme of GSH synthesis, γ-GCS, is up-regulated (P < 0.001), while the activities of γ-GT and GR are down-regulated in renal tumors compared to nontumor tissue (P < 0.001 and P < 0.05, respectively). Activities of GPX and CAT were also down-regulated (P < 0.001 and P < 0.05, respectively) in RCC. Changes in enzyme antioxidant capacity in RCC were associated with decreased GST class α (P < 0.001) and unchanged GST π expression at the protein level. Conclusions: Changes in redox status in RCC as a consequence of decreased enzyme antioxidant capacity, together with altered GST α expression, may be important factors in development and tumor growth. The up-regulation of γ-GCS and high levels of GSH in RCC may be an attempt to limit injury caused by oxidative stress. © 2008 Elsevier Inc. All rights reserved.

Purpose: Urothelial bladder cancer (UBC) is the most common malignancy of urinary tract in the developed world. In metastatic UBC, systemic chemotherapy still remains the mainstay of initial treatment. Inter-individual differences in treatment outcome partially may be the consequence of genetic variations in enzymes that modulate oxidative stress. Therefore, we aimed to determine the potential prognostic role of single nucleotide polymorphism (SNP) of the two antioxidant enzymes glutathione peroxidase 1 (GPX1) and superoxide dismutase 2 (SOD2) in metastatic UBC patients treated with cisplatin-based chemotherapy. Methods: This prospective single-center hospital-based case-control study included 33 patients with metastatic UBC treated with cisplatin-based chemotherapy and 227 healthy controls. GPX1 SNP (rs1050450) was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and SOD2 SNP (rs4880) was determined by quantitative PCR (q-PCR). Overall survival (OS) was evaluated using Kaplan–Meier survival analysis during 2-year follow up period, with the log-rank test for prognostic significance. Results: No significant difference was observed in the distributions of GPX1 and SOD2 gene variants between patients and controls (p>0.05). Regarding GPX1 polymorphism, no impact of GPX1 polymorphism on OS could be demonstrated (p>0.05). Finally, Kaplan-Meier survival analysis showed no association between SOD2 polymorphism and OS (p>0.05). Conclusions: No association was found between polymorphism of GPX1 and SOD2 and OS in patients with metastatic urothelial bladder cancer treated with cisplatin-based chemotherapy. © 2018 Zerbinis Publications. All Rights Reserved.

Purpose: Urothelial bladder cancer (UBC) is the most common malignancy of urinary tract in the developed world. In metastatic UBC, systemic chemotherapy still remains the mainstay of initial treatment. Inter-individual differences in treatment outcome partially may be the consequence of genetic variations in enzymes that modulate oxidative stress. Therefore, we aimed to determine the potential prognostic role of single nucleotide polymorphism (SNP) of the two antioxidant enzymes glutathione peroxidase 1 (GPX1) and superoxide dismutase 2 (SOD2) in metastatic UBC patients treated with cisplatin-based chemotherapy. Methods: This prospective single-center hospital-based case-control study included 33 patients with metastatic UBC treated with cisplatin-based chemotherapy and 227 healthy controls. GPX1 SNP (rs1050450) was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and SOD2 SNP (rs4880) was determined by quantitative PCR (q-PCR). Overall survival (OS) was evaluated using Kaplan–Meier survival analysis during 2-year follow up period, with the log-rank test for prognostic significance. Results: No significant difference was observed in the distributions of GPX1 and SOD2 gene variants between patients and controls (p>0.05). Regarding GPX1 polymorphism, no impact of GPX1 polymorphism on OS could be demonstrated (p>0.05). Finally, Kaplan-Meier survival analysis showed no association between SOD2 polymorphism and OS (p>0.05). Conclusions: No association was found between polymorphism of GPX1 and SOD2 and OS in patients with metastatic urothelial bladder cancer treated with cisplatin-based chemotherapy. © 2018 Zerbinis Publications. All Rights Reserved.

Background: Oxidative stress in patients with end-stage renal disease (ESRD) is associated with long-term cardiovascular complications. The cytosolic family of glutathione S-transferases (GSTs) is involved in the detoxication of various toxic compounds and antioxidant protection. GST omega class members, GSTO1 and GSTO2 possess, unlike other GSTs, dehydroascorbate reductase and deglutathionylation activities. The aim of this study was to clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) as risk determinants for ESRD development, as well as in the survival of these patients. Methods: A total of 199 patients and 199 healthy subjects were included in the study and genotyped for both GSTO1 and GSTO2 polymorphism. Protein thiol and carbonyl groups as markers of protein oxidative damage were determined spectrophotometrically. Cox proportional hazard model and Kaplan-Meier analysis were performed to investigate the role of GSTO1 and GSTO2 genetic polymorphism on mortality of ESRD patients during the follow-up period (36 month). Results: Individuals carrying the variant GSTO2 GG genotype were at 2.45-fold higher risk of ESRD development compared to the wild type GSTO2 AA genotype (OR=2.45; 95%CI=1.18-5.07; p=0.016). The results of GSTO1/GSTO2 haplotype analysis showed that the haplotype combi - nation of GSTO1 (∗A)/GSTO2 (∗A) (GSTO1 variant/GSTO2 wild type allele) was protective for ESRD (OR=0.23 95%CI=0.12-0.44, p=0.001). Patients carrying at least one GSTO1 reference allele have shorter mean overall (Log rank=2.844, p =0.241) and cardiovascular survival probability (Log rank=4.211, p=0.122). Conclusions: GSTO polymorphisms have been shown to act as significant markers in assessing the risk of ESRD development and patients' survival. © by Tatjana Simic 2016.

Background: Oxidative stress in patients with end-stage renal disease (ESRD) is associated with long-term cardiovascular complications. The cytosolic family of glutathione S-transferases (GSTs) is involved in the detoxication of various toxic compounds and antioxidant protection. GST omega class members, GSTO1 and GSTO2 possess, unlike other GSTs, dehydroascorbate reductase and deglutathionylation activities. The aim of this study was to clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) as risk determinants for ESRD development, as well as in the survival of these patients. Methods: A total of 199 patients and 199 healthy subjects were included in the study and genotyped for both GSTO1 and GSTO2 polymorphism. Protein thiol and carbonyl groups as markers of protein oxidative damage were determined spectrophotometrically. Cox proportional hazard model and Kaplan-Meier analysis were performed to investigate the role of GSTO1 and GSTO2 genetic polymorphism on mortality of ESRD patients during the follow-up period (36 month). Results: Individuals carrying the variant GSTO2 GG genotype were at 2.45-fold higher risk of ESRD development compared to the wild type GSTO2 AA genotype (OR=2.45; 95%CI=1.18-5.07; p=0.016). The results of GSTO1/GSTO2 haplotype analysis showed that the haplotype combi - nation of GSTO1 (∗A)/GSTO2 (∗A) (GSTO1 variant/GSTO2 wild type allele) was protective for ESRD (OR=0.23 95%CI=0.12-0.44, p=0.001). Patients carrying at least one GSTO1 reference allele have shorter mean overall (Log rank=2.844, p =0.241) and cardiovascular survival probability (Log rank=4.211, p=0.122). Conclusions: GSTO polymorphisms have been shown to act as significant markers in assessing the risk of ESRD development and patients' survival. © by Tatjana Simic 2016.

It is becoming increasingly evident that oxidative stress has a supporting role in pathophysiology and progression of primary open angle glaucoma (POAG). The aim of our study was to assess the association between polymorphisms in genes encoding enzymes involved in redox homeostasis, mitochondrial superoxide dismutase (SOD2), glutathione peroxidase (GPX1) and glutathione transferases (GSTs) with susceptibility to POAG. Single nucleotide polymorphisms in GST omega (GSTO1rs4925, GSTO2 rs156697), pi 1 (GSTP1 rs1695), as well as GPX1 (rs1050450) and SOD2 (rs4880) were determined by quantitative polymerase chain reaction (qPCR) in 102 POAG patients and 302 respective controls. The risk for POAG development was noted in carriers of both GSTO2*GG and GSTO1*AA variant genotypes (OR = 8.21, p = 0.002). Individuals who carried GPX1*TT and SOD2*CC genotypes had also an increased risk of POAG development but without significance after Bonferroni multiple test correction (OR = 6.66, p = 0.005). The present study supports the hypothesis that in combination, GSTO1/GSTO2, modulate the risk of primary open angle glaucoma. © 2021 Elsevier Ltd

It is becoming increasingly evident that oxidative stress has a supporting role in pathophysiology and progression of primary open angle glaucoma (POAG). The aim of our study was to assess the association between polymorphisms in genes encoding enzymes involved in redox homeostasis, mitochondrial superoxide dismutase (SOD2), glutathione peroxidase (GPX1) and glutathione transferases (GSTs) with susceptibility to POAG. Single nucleotide polymorphisms in GST omega (GSTO1rs4925, GSTO2 rs156697), pi 1 (GSTP1 rs1695), as well as GPX1 (rs1050450) and SOD2 (rs4880) were determined by quantitative polymerase chain reaction (qPCR) in 102 POAG patients and 302 respective controls. The risk for POAG development was noted in carriers of both GSTO2*GG and GSTO1*AA variant genotypes (OR = 8.21, p = 0.002). Individuals who carried GPX1*TT and SOD2*CC genotypes had also an increased risk of POAG development but without significance after Bonferroni multiple test correction (OR = 6.66, p = 0.005). The present study supports the hypothesis that in combination, GSTO1/GSTO2, modulate the risk of primary open angle glaucoma. © 2021 Elsevier Ltd

Background: Experimental data show that superoxide dismutase 2 (SOD2) is involved in ochratoxin (OTA)-induced nephrotoxicity, whereas clinical data indicate the role of SOD2 rs4880 or glutathione peroxidase 1 (GPX1) rs1050450 polymorphisms in end-stage renal disease and urothelial carcinoma risk, known to be the major complications of Balkan endemic nephropathy (BEN). Therefore, we hypothesized that SOD2 and GPX1 gene polymorphisms would influence the risk of BEN and its associated tumors. Materials and Methods: The study was conducted in 207 BEN patients and 86 controls from endemic areas. Results: Individuals with both copies of variant SOD2 allele, known for lower mitochondrial antioxidant protection, are at a significantly higher BEN risk (OR = 2.6, p = 0.021). No association was observed between GPX1 gene polymorphism and BEN risk. Combining SOD2 and GPX1 genotypes did not alter the risk of BEN development. Regarding the risk of urothelial tumors in BEN patients, none of the polymorphisms studied was significantly associated with the risk of these tumors. Conclusions: Polymorphism in SOD2 rs4880 gene affects the risk of BEN development. Hence, SOD2 genotyping could, together with a panel of other enzymes, be used as a biomarker of susceptibility in BEN areas. © 2019 by the authors. Licensee MDPI, Basel, Switzerland. T.

Background: The presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients. Methods. Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier. Results: GSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1*A/*A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1*0/GSTA1*A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1*B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1*B/*B genotype. Conclusions: Combined GSTM1*0/GSTA1*A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention. © 2014 Suvakov et al.; licensee BioMed Central Ltd.

Background: Autism spectrum disorders (ASD) are complex psychiatric disorders, with gene environment interaction being in the basis of their etiology. The association of perinatal complications and ASD is well established. Recent findings suggested that oxidative stress and polymorphism in genes encoding antioxidant enzymes might be involved in the development of ASD. Glutathione transferases (GSTs) have an important role in the antioxidant defense system. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms. Methods: The study included 113 ASD cases and 114 age-and sex group-matched healthy controls. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The questionnaire regarding prenatal and perinatal risk factors and complications was administered for all the subjects in the study. Results: The evaluated perinatal complications as a group significantly increased the risk of ASD [odds ratio (OR) = 9.415; p = 0.000], as well as individual perinatal complications, such as prematurity (OR = 11.42; p = 0.001), neonatal jaundice (OR = 8.774; p = 0.000), respiratory distress syndrome (OR = 4.835; p = 0.047), and the use of any medication during pregnancy (OR = 2.413; p = 0.03). In logistic regression model, adding GST genotypes did not modify the significant effects found for prematurity and neonatal jaundice as risk factors in ASD. However, there was a significant interaction of GST genotype with medication use during pregnancy and the use of tocolytics during pregnancy, which was predictive of ASD risk only in carriers of GSTM1-null, as opposed to carriers of GSTM1-active genotype. Conclusion: Specific perinatal complications may be significant risk factors for ASD. GSTM1 genotype may serve as a moderator of the effect of some prenatal factors on the risk of ASD such as using medication during pregnancy. It may be speculated that different oxidative stress-related genetic and environmental factors could lead to development of ASD. Apart from etiological mechanisms, possible therapeutic implications in ASD are also discussed. © 2019 Mandic-Maravic, Mitkovic-Voncina, Pljesa-Ercegovac, Savic-Radojevic, Djordjevic, Pekmezovic, Grujicic, Ercegovac, Simic, Lecic-Tosevski and Pejovic-Milovancevic.

Purpose: To get more insight into molecular mechanisms underlying oxidative stress and its role in different types of seizure, in this study, oxidative byproducts of proteins, lipids and DNA, as well as, antioxidant enzyme activities were studied in adult patients with epilepsy. Methods: Study was performed in 60 patients with epilepsy and in 25 healthy controls. Plasma protein reactive carbonyl derivatives (RCD) and protein thiol groups (P-SH), byproducts of oxidative protein damage, as well as antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), representative byproducts of lipid and DNA oxidative damage, respectively, were determined by enzyme immunoassay. Results: RCD levels were significantly increased (p = 0.001), while P-SH content was decreased in patients with first seizure (p = 0.052) compared to controls, independently of the seizure type. Urinary 8-epi-PGF2α and 8-OHdG were significantly increased in patients with epilepsy (p = 0.001 and p = 0.001). Rise in 8-epi-PGF2α was more pronounced in patients with generalized tonic-clonic seizure (GTCS) compared to those with partial seizure (PS). Both SOD and GPX activity were significantly increased in epileptic patients compared to controls (p = 0.001 and p = 0.001), but only SOD activity was significantly higher in patients with GTCS than in those with PS. Conclusions: Data on enhanced protein, lipid and DNA oxidation, together with upregulated antioxidant enzyme activities, confirm the existence of systemic oxidative stress in patients with epilepsy. It might be speculated that post-translational modification to existing functional proteins, particularly alterations to ion channels, might be at least partially responsible for acute early changes in neuronal networks. © 2010 British Epilepsy Association.

Purpose: To get more insight into molecular mechanisms underlying oxidative stress and its role in different types of seizure, in this study, oxidative byproducts of proteins, lipids and DNA, as well as, antioxidant enzyme activities were studied in adult patients with epilepsy. Methods: Study was performed in 60 patients with epilepsy and in 25 healthy controls. Plasma protein reactive carbonyl derivatives (RCD) and protein thiol groups (P-SH), byproducts of oxidative protein damage, as well as antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), representative byproducts of lipid and DNA oxidative damage, respectively, were determined by enzyme immunoassay. Results: RCD levels were significantly increased (p = 0.001), while P-SH content was decreased in patients with first seizure (p = 0.052) compared to controls, independently of the seizure type. Urinary 8-epi-PGF2α and 8-OHdG were significantly increased in patients with epilepsy (p = 0.001 and p = 0.001). Rise in 8-epi-PGF2α was more pronounced in patients with generalized tonic-clonic seizure (GTCS) compared to those with partial seizure (PS). Both SOD and GPX activity were significantly increased in epileptic patients compared to controls (p = 0.001 and p = 0.001), but only SOD activity was significantly higher in patients with GTCS than in those with PS. Conclusions: Data on enhanced protein, lipid and DNA oxidation, together with upregulated antioxidant enzyme activities, confirm the existence of systemic oxidative stress in patients with epilepsy. It might be speculated that post-translational modification to existing functional proteins, particularly alterations to ion channels, might be at least partially responsible for acute early changes in neuronal networks. © 2010 British Epilepsy Association.

Introduction: The treatment preserving the kidney for upper urinary tract (UUT) transitional cell carcinoma (TCC) is still controversial. We aimed to elucidate the results of open conservative surgery and compare them with the results of radical nephroureterectomy (RNU). Patients and Methods: The study included 107 patients with UUT TCC treated by open conservative surgery (21 patients) or nephroureterectomy (86 patients). Epidemiological, clinical and pathological characteristics of patients as well as 5-year survival rates were compared between groups. Results: Patients treated by conservative surgery had a significantly higher rate of bilateral tumors (38% vs. 3%, p = 0.0001) and smaller tumor size than those treated by radical operations (2.60 ± 1.24 vs. 3.99 ± 3.94 cm, p = 0.060). Five-year survival rates for patients treated by conservative and radical surgery were 59 and 55%, respectively. Within the group of patients treated by conservative surgery, 5-year overall survival rates of patients operated due to imperative and elective indications were 41 and 75%, respectively. In univariate analysis, RNU was a statistically significant predictor of poorer outcome of the disease in comparison with conservative surgery (HR = 2.2, 95% CI 1.1-4.6, p = 0.030). Conclusions: The mode of operation affects the outcome of UUT TCC patients, in addition to factors such as tumor grade, stage and size. © 2009 S. Karger AG, Basel.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment. © 2016 Elsevier Inc.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment. © 2016 Elsevier Inc.

Objectives: Glutathione S-transferase P1 (GSTP1) provides an important link between activity of regulatory stress kinases and apoptotic pathways. It can be hypothesized that up-regulated GSTP1, in TCC, might enhance apoptosis inhibition. We aimed to establish whether relationship between GSTP1 expression and executive (pro-caspase 3, cleaved caspase 3) and regulatory (Bcl-2) apoptotic pathways in TCC exists. Materials and Methods: Samples were obtained from 84 TCC patients (41 consecutive patient with muscle noninvasive and 43 consecutive patients with muscle invasive TCC tumors), who underwent surgery at the Institute of Urology and Nephrology, Clinical Centre of Serbia, during 2006 and 2007. Expression of GSTP1, pro-caspase 3 (CPP32), and Bcl-2, as well as cleaved caspase-3 labeling index (LI) were determined by immunocytochemistry. Levels of expression were correlated with tumor stage, grade, and invasiveness. Results: GSTP1 protein expression was demonstrated in all tumor samples examined. According to GSTP1 status, all tumors were divided into groups with low, moderate, or high GSTP1 status. Expression of CPP32 and cleaved caspase 3 was positive in 80% of TCC patients. Their levels differed significantly between groups with various GSTP1 expression (P < 0.05), with the lowest CPP32 expression and cleaved caspase 3 LI in tumors with high GSTP1 status. Moreover, significant negative correlation was found between GSTP1 level and cleaved caspase 3 LI (r = -0.459, P = 0.041). The positive rate of Bcl-2 protein expression was 48%. Most of the Bcl-2 positive patients exhibited at the same time high GSTP1 positivity (P = 0.078). Significant association with tumor grade and stage was found for all examined parameters except for CPP32 regarding tumor grade. Conclusions: Based on results obtained, we conclude that enhanced GSTP1 expression in TCC of urinary bladder is associated with altered apoptotic pathways. Molecular interplay between GSTP1 and members of apoptotic cascade might, at least partially, play a role in development of invasive characteristics of TCC. © 2011 Elsevier Inc.

The efficiency of human recombinant epoetin in alleviating anemia in hemodialyzed patients has been well documented. However, the effects of rhEPO therapy in correction of antioxidant capacity are not completely explained. In this study we examined both extracellular (plasma) and intracellular (red blood cells) antioxidant potential in hemodialyzed patients before and after three and six months of epoetin treatment by evaluating markers of oxidative stress (malondialdehyde) and antioxidant capacity (thiol groups, superoxide dismutase, and glutathione peroxidase). Six months of treatment with epoetin was followed by significant increases in thiol groups, superoxide dismutase and glutathione peroxidase activities in both plasma and red blood cells of hemodialyzed patients. Hence, during accelerated erythropoiesis, an increase in the number of young hematopoietic cells may replenish erythrocyte superoxide dismutase and glutathione peroxidase activity. However, the consequences of an imbalance between enzymatic antioxidant system (higher superoxide dismutase and lower glutathione peroxidase activity) that exists in these patients are the very high red blood cell and plasma malondialdehyde levels. These results suggest that, in spite of epoetin treatment and improvement in red blood cells and plasma antioxidant capacity, the production of reactive oxygen species overwhelms the intracellular and extracellular antioxidant capacity.

Heart failure (HF) is one of the major cardiovascular causes of death worldwide. In this study, we explored the Effects of folic acid (FA) on cardiometabolic, oxidative stress biomarker changes, and the activity of proliferation marker Ki67 in monocrotaline-induced HF. The research was conducted during a 4 week period using five experimental groups (eight animals per group): Blank solution exposed controls (C1: 1 mL/kg physiological saline, 1 day; C2: 1 mL/kg physiological saline, 28 days), monocrotaline (MCT) induced HF (50 mg/kg MCT), FA (5 mg·kg−1·day−1 FA), and MCT+FA (50 mg/kg MCT, 5 mg·kg−1·day−1 FA). Superoxide dismutase and glutathione peroxidase activities together with total glutathione and parameters of oxidative damage of proteins were determined in cardiac tissue as well as cardiometabolic parameters in plasma or serum. The total glutathionylation was determined by Western blot and proliferation marker Ki67 was assessed by immunohistochemistry. The right ventricular (RV) wall hypertrophy and Ki67 positivity, accompanied by a significant increase of troponin T, has been shown in MCT-induced HF. The antioxidant effect of FA was reflected through superoxide dismutase activity, reduced Ki67 positivity in the RV wall, and a slightly decreased total glutathionylation level. © 2020, Canadian Science Publishing. All rights reserved.

Heart failure (HF) is one of the major cardiovascular causes of death worldwide. In this study, we explored the Effects of folic acid (FA) on cardiometabolic, oxidative stress biomarker changes, and the activity of proliferation marker Ki67 in monocrotaline-induced HF. The research was conducted during a 4 week period using five experimental groups (eight animals per group): Blank solution exposed controls (C1: 1 mL/kg physiological saline, 1 day; C2: 1 mL/kg physiological saline, 28 days), monocrotaline (MCT) induced HF (50 mg/kg MCT), FA (5 mg·kg−1·day−1 FA), and MCT+FA (50 mg/kg MCT, 5 mg·kg−1·day−1 FA). Superoxide dismutase and glutathione peroxidase activities together with total glutathione and parameters of oxidative damage of proteins were determined in cardiac tissue as well as cardiometabolic parameters in plasma or serum. The total glutathionylation was determined by Western blot and proliferation marker Ki67 was assessed by immunohistochemistry. The right ventricular (RV) wall hypertrophy and Ki67 positivity, accompanied by a significant increase of troponin T, has been shown in MCT-induced HF. The antioxidant effect of FA was reflected through superoxide dismutase activity, reduced Ki67 positivity in the RV wall, and a slightly decreased total glutathionylation level. © 2020, Canadian Science Publishing. All rights reserved.

Prostate cancer (PCa) is the second most diagnosed cancer type globally and is one of the leading causes of death in men. Genetic susceptibility plays a sig nificant role in PCa development with a reported heritability of 57%. Mutations in the different DNA damage repair (DDR) genes (BRCA1, BRCA2, CHEK2, ATM, and PALB2) and in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) are hallmark of hereditary prostate cancer (HPCa) and are included in National Comprehensive Cancer Network (NCCN) guidelines for PCa germline genetic testing. In addition to rare high-risk mutations in susceptibility genes, poly genetic inheritance of low-risk germline variants in the form of single-nucleotide polymorphisms (SNPs) may be utilized to distinguish an individual’s susceptibility to PCa onset and progression. Over the past decade, the number of detected variants has increased to 269, due to the genome-wide association studies (GWAS). The large number of identified variants led to the development of polygenic risk scores (PRS) that aggregates common PCa-associated genetic variants into a single mea sure. The incorporation of diverse genetic analyses and PRS is highly anticipated to those individuals with positive PCa family history and may lead to improvements in clinical outcomes for this population through early prevention screening efforts. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2024.