Publications by authors named "Miroslava Rabajdova"

12 Publications

  • Page 1 of 1

The role of physical activity and miRNAs in the vascular aging and cardiac health of dialysis patients.

Physiol Rep 2021 May;9(10):e14879

Department of Health Psychology and Research Methodology, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovakia.

Cardiovascular comorbidities are independent risk factors for mortality in dialysis patients. MicroRNA signaling has an important role in vascular aging and cardiac health, while physical activity is a primary nonpharmacologic treatment for cardiovascular comorbidities in dialysis patients. To identify the relationships between muscle function, miRNA signaling pathways, the presence of vascular calcifications and the severity of cardiovascular comorbidities, we initially enrolled 90 subjects on hemodialysis therapy and collected complete data from 46 subjects. A group of 26 subjects inactiv group (INC) was monitored during 12 weeks of physical inactivity and another group of 20 patients exercise group (EXC) was followed during 12 weeks of intradialytic, moderate intensity, resistance training intervention applied three times per week. In both groups, we assessed the expression levels of myo-miRNAs, proteins, and muscle function (MF) before and after the 12-week period. Data on the presence of vascular calcifications and the severity of cardiac comorbidities were collected from the patients' EuCliD records. Using a full structural equitation modelling of the total study sample, we found that the higher the increase in MF was observed in patients, the higher the probability of a decrease in the expression of miR-206 and TRIM63 and the lower severity of cardiac comorbidities. A reduced structural model in INC patients showed that the higher the decrease in MF, the higher the probability of the presence of calcifications and the higher severity of cardiac comorbidities. In EXC patients, we found that the higher the increase in MF, the lower the probability of higher severity of cardiovascular comorbidities.
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http://dx.doi.org/10.14814/phy2.14879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157788PMC
May 2021

Effect of hypoxia factors gene silencing on ROS production and metabolic status of A375 malignant melanoma cells.

Sci Rep 2021 May 14;11(1):10325. Epub 2021 May 14.

Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04011, Košice, Slovakia.

The innate response of melanocytes to exogenous or endogenous stress stimuli like extreme pH and temperature, metabolite and oxygen deficiency or a high UV dose initiates a cellular stress response. This process activates adaptive processes to minimize the negative impact of the stressor on the pigment cell. Under physiological conditions, a non-cancer cell is directed to apoptosis if the stressor persists. However, malignant melanoma cells will survive persistent stress thanks to distinct "cancerous" signaling pathways (e.g. MEK) and transcription factors that regulate the expression of so-called "survival genes" (e.g. HIF, MITF). In this survival response of cancer cells, MEK pathway directs melanoma cells to deregulate mitochondrial metabolism, to accumulate reduced species (NADH), and to centralize metabolism in the cytosol. The aim of this work was to study the effect of gene silencing in malignant melanoma A375 cells on metabolic processes in cytosol and mitochondria. Gene silencing of HIF-1α, and miR-210 in normoxia and pseudohypoxia, and analysis of its effect on MITF-M, and PDHA1 expression. Detection of cytosolic NADH by Peredox-mCherry Assay. Detection of OCR, and ECAR using Seahorse XF96. Measurement of produced O with MitoTracker Red CMXRos. H NMR analysis of metabolites present in cell suspension, and medium. By gene silencing of HIF-1α and miR-210 the expression of PDHA1 was upregulated while that of MITF-M was downregulated, yielding acceleration of mitochondrial respiratory activity and thus elimination of ROS. Hence, we detected a significantly reduced A375 cell viability, an increase in alanine, inositol, nucleotides, and other metabolites that together define apoptosis. Based on the results of measurements of mitochondrial resipiratory activity, ROS production, and changes in the metabolites obtained in cells under the observed conditions, we concluded that silencing of HIF-1α and miR-210 yields apoptosis and, ultimately, apoptotic cell death in A375 melanoma cells.
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http://dx.doi.org/10.1038/s41598-021-89792-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121821PMC
May 2021

Comparison in detection of prodromal Parkinson's disease patients using original and updated MDS research criteria in two independent cohorts.

Parkinsonism Relat Disord 2021 Apr 30;87:48-55. Epub 2021 Apr 30.

Department of Neurology, P. J. Safarik University, Trieda SNP 1, 04011, Kosice, Slovak Republic; Department of Neurology, University Hospital L. Pasteur, Rastislavova 43, 04190, Kosice, Slovak Republic.

Introduction: MDS research criteria for prodromal Parkinson's disease (pPD) were published in 2015 and updated in 2019. We aimed to determine the difference in pPD patient detection rates in two cohorts recruited via gastrointestinal symptoms (PARCAS study) and the presence of a probable REM sleep behaviour disorder (PDBIOM study) using the original and updated criteria.

Methods: We evaluated all risk and prodromal markers, except genetic testing, plasma urate and physical inactivity, in both cohorts and DaT scan, diabetes mellitus type II and cognitive deficit in the PARCAS cohort. Thresholds of 50% probability for possible pPD and 80% for probable pPD were used.

Results: PPD status as identified by the original/updated criteria showed differences for probable pPD (n = 8/9; original/updated criteria) and possible pPD (n = 9/13) in the PARCAS cohort (total n = 158), as well as for probable pPD (n = 19/21) and possible pPD (n = 6/3) in the PDBIOM cohort (total n = 48). A high concordance rate was found between the two criteria sets (p < 0.001 for all groups).

Conclusion: All probable pPD cases remained in the same category after evaluation with both criteria; three possible pPD cases based on the original criteria exceeded the threshold for probable pPD based on the updated criteria, and five possible new pPD cases were detected, with only one shift in the opposite direction. The updated MDS pPD research criteria tend to identify more patients as positive, yet their accuracy needs to be determined in prospective studies.
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http://dx.doi.org/10.1016/j.parkreldis.2021.04.028DOI Listing
April 2021

Development of novel parameter for monitoring of malignant melanoma progression.

Pract Lab Med 2020 Nov 21;22:e00182. Epub 2020 Oct 21.

Department of Medical and Clinical Biochemistry, Pavol Jozef Šafárik University in Košice, Medical Faculty, Slovakia.

Objective: Increasing HIFs in malignant melanoma, the highly aggressive skin tumour, results in the stimulation of invasiveness. Increased HIF-1α fallouts in inhibition of the activity of some mitochondrial enzymes and leads to preference of cytosol energetic metabolism. Increase of aerobic glycolysis is reflected in an increase of free NADH (Warburg effect) and develops the malignant melanoma.Our goal was to find a link between hypoxia, or hypoxia mimicking factors and the stage of malignant melanoma. Furthermore, we focused on the finding of the experimental parameter which could monitor melanoma patients.

Patients And Methods: We targeted HIF-1α gene expression and VDR rs2107301 gene polymorphism by PCR analysis. We detected the level of NADH in blood plasma by fluorescence spectroscopy (excitation and emission spectra).

Results: Analysis of the obtained data from patient samples has shown an increase in HIF-1α which correlates with the disease stage. Investigation VDR rs2107301 polymorphism of patient samples does not show any significant changes in single nucleotide polymorphism, and the low vitamin D level in blood is not a result of VDR mutation in mitochondria. NADH levels vary under hypoxic and pseudohypoxic conditions and refer to the cancer stage.

Conclusions: The apparent mismatch between HIF-1α expression and NADH fluorescence has become the basis for the design of an algorithm for monitoring malignant melanoma based on the sensing of NADH fluorescence and the determination of HIF-1α.
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http://dx.doi.org/10.1016/j.plabm.2020.e00182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586240PMC
November 2020

MicroRNA molecules as predictive biomarkers of adaptive responses to strength training and physical inactivity in haemodialysis patients.

Sci Rep 2020 09 24;10(1):15597. Epub 2020 Sep 24.

Department of Community and Occupational Medicine, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands.

The miRNA-206 and miRNA-23a play an important role in muscle tissue hypertrophy, regeneration and atrophy. Both of these miRNAs have been highlighted as promising adaptation predictors; however, the available evidence on associations is inconclusive. Therefore, our aim was to assess the expression levels of these two miRNAs as predictors of change in muscle function during strength training and physical inactivity among dialysed patients. For this purpose, 46 haemodialysis patients were monitored for 12-weeks of either intradialytic strength training (EXG, n = 20) or physical inactivity during dialysis (CON, n = 26). In both groups of patients, we assessed the baseline expression levels of miRNA-23a and miRNA-206 and the isometric force generated during hip flexion (HF) contraction before and after the 12-week period. Among the EXG group, the expression of miRNA-206 predicted the change in HF (R = 0.63, p = 0.0005) much more strongly than the expression of miRNA-23a (R = 0.21, p = 0.027). Interestingly, baseline miRNA-23a (R = 0.30, p = 0.006) predicted the change in HF much more than miRNA-206 (p = ns) among the CON group. Our study indicates that the baseline expression of miRNA-206 could predict the response to strength training, while miRNA-23a could serve as a potential predictive marker of functional changes during physical inactivity in dialysis patients.
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http://dx.doi.org/10.1038/s41598-020-72542-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519115PMC
September 2020

The effects of intradialytic resistance training on muscle strength, psychological well-being, clinical outcomes and circulatory micro-ribonucleic acid profiles in haemodialysis patients: Protocol for a quasi-experimental study.

Medicine (Baltimore) 2019 May;98(19):e15570

Department of Community and Occupational Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein, Groningen, Netherlands.

Background: Intradialytic resistance training (IRT) protects patients' muscle mass and functions against protein-energy wasting, malnutrition and cachexia. However, the evidence of the effects of such an intervention in haemodialysis patients is limited and not conclusive. To improve the applicability of such interventions, we need a better understanding of molecular, functional and psycho-social adaptation in dialysed patients following a physical training. Therefore, the aim of this study is to investigate the effects of IRT on lower extremity muscle functions, quality of life, and anxiety and depression, clinical outcomes and circulatory micro-ribonucleic acid (miRNA) profiles in patients on chronic haemodialysis therapy.

Methods: We will perform a quasi-experimental study in 3 dialysis centres. Patients will be recruited via their nephrologists and will be allocated to an experimental and a control group based on the location of the patients' dialysis centre. Patients allocated to the experimental group will undergo a 12-week IRT, while the control group will remain physically inactive during dialysis. The primary outcome is the change in the maximal force produced during an isometric contraction of lower extremity muscles. Secondary outcomes regard quality of life, anxiety and depression, clinical outcomes and circulatory miRNA profiles. Patients' level of health literacy defined as the ability to get and understand health information will be also measured in the study as a potential modifier of effects.

Discussion: This quasi-experimental study can add in an important way to our understanding of the effects of resistance training on dialysis patients' muscle strength, quality of life and disease-specific outcomes.
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http://dx.doi.org/10.1097/MD.0000000000015570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531031PMC
May 2019

Detection of Pathological Changes in the Aorta during Thoracic Aortic Aneurysm Progression on Molecular Level.

Dis Markers 2017 12;2017:9185934. Epub 2017 Oct 12.

Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Šafárik University, Košice, Slovakia.

The progression of thoracic aortic aneurysm depends on regulation of aortic wall homeostasis and on changes in the structural components of the extracellular matrix, which are affected by multiple molecular signalling pathways. We decided to correlate the diameter of ascending thoracic aneurysm with gene expression of inflammation markers (IL-6, CRP), cytokine receptors (IL-6R, TNFR1, and TNFR2), and extracellular matrix components (Emilin-1, MMP9, and TIMP) for detection of the degree of pathological process of TAA formation. The experimental group was divided into three groups according to the diameter of the aortic aneurysm. Whole blood and tissue samples were properly collected and used for nucleic acid, chromatin, and protein isolation. The mRNA levels were detected by qRT-PCR. For the detection of protein levels a Cytokine Array IV assay kit was used in combination with a biochip analyzer. In aortic tissue, significant positive correlations were found between increased mRNA levels of inflammatory cytokines (CRP and IL-6) on both mRNA levels in tissue and protein from the blood with maximum in stage 3. Changes of gene expression of selected genes can be used for the experimental study of the inflammatory receptor inhibitors during trials targeted on slowing down the progress of aortic wall aneurysm.
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http://dx.doi.org/10.1155/2017/9185934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660829PMC
July 2018

Novel zinc complexes of a non-steroidal anti-inflammatory drug, niflumic acid: Structural characterization, human-DNA and albumin binding properties.

Eur J Med Chem 2018 Jun 5;153:131-139. Epub 2017 May 5.

Department of Medical and Clinical Biochemistry, Faculty of Medicine, P. J. Šafárik University in Košice, Trieda SNP 1, 04011 Košice, Slovakia.

Three novel Zn(II) complexes of NSAID niflumic acid (Hnif) were prepared and studied, namely; [Zn(MeOH)(nif)] (1), [Zn(cyclam)(nif)] (2) and [Zn(nif)(tmen)] (3), where nif is deprotonated niflumic acid, cyclam is 1,4,8,11-Tetraazacyclotetradecane and tmen is N,N,N',N'-Tetramethylethylenediamine. The complexes have been characterized by infrared spectroscopy, elemental and thermal analysis and single-crystal X-ray structure analysis. All three complexes contain two deprotonated niflumato anions monodentately coordinated via carboxylato groups. Furthermore, fluorescence binding studies of the prepared compounds with human genomic DNA-EB (ethidium bromide) were carried out, which suggest that all complexes are able to bind to DNA via intercalation. Moreover, from the obtained results it followed that complexes 2 and 3 bind to DNA from the tissue with aortic aneurysm (aDNA) and control (cDNA) with a different strength. Additionally, complexes 1-3 exhibit good binding affinity to human serum albumin with high binding constant.
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http://dx.doi.org/10.1016/j.ejmech.2017.05.009DOI Listing
June 2018

Perspectives and challenges of antioxidant therapy for atrial fibrillation.

Naunyn Schmiedebergs Arch Pharmacol 2017 Jan 29;390(1):1-14. Epub 2016 Nov 29.

Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with significant morbidity and mortality. The mechanisms underlying the pathogenesis of AF are poorly understood, although electrophysiological remodeling has been described as an important initiating step. There is growing evidence that oxidative stress is involved in the pathogenesis of AF. Many known triggers of oxidative stress, such as age, diabetes, smoking, and inflammation, are linked with an increased risk of arrhythmia. Numerous preclinical studies and clinical trials reported the importance of antioxidant therapy in the prevention of AF, using vitamins C and E, polyunsaturated fatty acids, statins, or nitric oxide donors. The aim of our work is to give a current overview and analysis of opportunities, challenges, and benefits of antioxidant therapy in AF.
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http://dx.doi.org/10.1007/s00210-016-1320-9DOI Listing
January 2017

The crucial role of emilin 1 gene expression during progression of tumor growth.

J Cancer Res Clin Oncol 2016 Nov 31;142(11):2397-402. Epub 2016 Aug 31.

Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Safarik University, Trieda SNP 1, 040 11, Kosice, Slovakia.

Background: This study describes the effect of rapid tumor growth of patients suffering from various grades of malignant ductal breast carcinoma associated with the gene expression of ECM protein emilin 1, in correlation with the number of gene copies of emilin 1 and degradation of tumor tissue proteins.

Methods: A total of 40 examined patients participated in the experiment (controls, n = 10, grades GI-GIII, each n = 10). After isolation of total mRNA, transcription of mRNA into the cDNA was performed. Quantification of gene expression changes was detected by the real-time PCR method. Analysis at the protein level was performed via Western blot method.

Results: During the detection of changes at the mRNA level, a significantly decreased level of emilin 1 in tumor tissues with grade II (about 54 ± 8 % lower than control) was identified. Protein-level analysis indicated an increased level of emilin 1 in tumors with grade I in comparison with control samples (about 10 ± 3 %).

Conclusion: Obtained results demonstrated that the suppressive role of emilin 1 is related to the grade of growing breast tumors, and associated with increased hypoxia in the tumor microenvironment followed by elevated unfolding and degradation of tissue proteins.
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http://dx.doi.org/10.1007/s00432-016-2226-0DOI Listing
November 2016

Transcription facilitates sister chromatid cohesion on chromosomal arms.

Nucleic Acids Res 2016 08 15;44(14):6676-92. Epub 2016 Apr 15.

Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK

Cohesin is a multi-subunit protein complex essential for sister chromatid cohesion, gene expression and DNA damage repair. Although structurally well studied, the underlying determinant of cohesion establishment on chromosomal arms remains enigmatic. Here, we show two populations of functionally distinct cohesin on chromosomal arms using a combination of genomics and single-locus specific DNA-FISH analysis. Chromatin bound cohesin at the loading sites co-localizes with Pds5 and Eso1 resulting in stable cohesion. In contrast, cohesin independent of its loader is unable to maintain cohesion and associates with chromatin in a dynamic manner. Cohesive sites coincide with highly expressed genes and transcription inhibition leads to destabilization of cohesin on chromatin. Furthermore, induction of transcription results in de novo recruitment of cohesive cohesin. Our data suggest that transcription facilitates cohesin loading onto chromosomal arms and is a key determinant of cohesive sites in fission yeast.
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http://dx.doi.org/10.1093/nar/gkw252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001582PMC
August 2016

Vascular marker expression during the development of various types of gynaecological malignancy.

Tumour Biol 2014 Nov 12;35(11):11229-35. Epub 2014 Aug 12.

Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic.

Clinical diagnosis of gynaecological malignancies is usually successful in the advanced stages of the tumour, and this has a major impact on the success of therapy. Therefore, in the last few years, cancer research has tried to identify and characterise new biochemical and molecular markers needed as predictive indicators for the diagnosis of cancer. Our aim has been to search the molecular changes in gene expression of death receptor 6, glycoprotein M6B (Gpm6B) and genes associated with tumours of the female genital system. After isolation of messenger RNA (mRNA), transcription of mRNA into the cDNA was performed. The quantification of gene expression changes was detected using the reverse transcription polymerase chain reaction (RT-PCR) method. Analysis at the protein level was performed using the Western blot method. In both methods, we used actin as a housekeeping gene for normalisation. Numerical quantification of changes in expression and in the level of the specific proteins was evaluated using the Data Syngene program. Significant changes in the levels of protein and mRNA expression were detected, mainly in the death receptor 6 (Dr6) gene of patients suffering from cancer of the corpus and cervix uteri and ovarian cancer, which also corresponded with the level of protein Dr6. At the level of transcription, a significant increase in the expression levels of mRNA for the Gpm6B gene was detected, which led to an increase in corresponding protein in the peripheral blood of patients with gynaecological tumours against the healthy control group. This article could help to find an adequate marker for clinical application that will enable more sensitive detection of the early stages of gynaecological malignancies from the peripheral blood of patients.
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http://dx.doi.org/10.1007/s13277-014-2447-2DOI Listing
November 2014