Publications by authors named "Daniel Zalewski"

9 Publications

  • Page 1 of 1

MicroRNAs in the aqueous humor of patients with different types of glaucoma.

Graefes Arch Clin Exp Ophthalmol 2021 Aug 30;259(8):2337-2349. Epub 2021 Apr 30.

Department of Diagnostics and Microsurgery of Glaucoma, Medical University of Lublin, ul. Chmielna 1, 20-079, Lublin, Poland.

Purpose: The aim of the study was to compare the frequency and the level of expression of selected miRNAs in the aqueous humor of patients with various types of glaucoma.

Methods: The studied group consisted of 42 patients with glaucoma: 19 with primary open-angle glaucoma (POAG), 14 with pseudoexfoliation glaucoma (PEXG), 9 with primary angle closure glaucoma (PACG), and the control group of 36 patients with senile cataract without glaucoma. The real-time polymerase chain reaction method was used to analyze the expression of miRNAs.

Results: There were no significant differences in the frequency and the level of miRNA expression between various types of glaucoma. There was a tendency for hsa-miR-6722-3p and hsa-miR-184 to be expressed more frequently in PEXG and hsa-miR-1260b in POAG. The expression levels of hsa-miR-1260b and hsa-miR-6515-3p were correlated with age in POAG. Target annotation and functional analyses showed that genes targeted by the most frequently expressed miRNAs (hsa-miR-1202, -1260b, -184, -187-5p, -6515-3p, -6722-3p, and hsa-mir-4634) are involved mainly in response to hypoxia, cardiovascular system development, and apoptosis.

Conclusion: Hsa-miR-1260b was the most abundantly expressed among studied miRNAs and may be a potential biomarker of clinical status in PEXG and PACG.
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http://dx.doi.org/10.1007/s00417-021-05214-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352835PMC
August 2021

Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens.

Int J Mol Sci 2021 Mar 21;22(6). Epub 2021 Mar 21.

Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.

Several human tissues are investigated in studies of molecular biomarkers associated with diseases development. Special attention is focused on the blood and its components due to combining abundant information about systemic responses to pathological processes as well as high accessibility. In the current study, transcriptome profiles of peripheral blood mononuclear cells (PBMCs) were used to compare differentially expressed genes between patients with lower extremities arterial disease (LEAD), abdominal aortic aneurysm (AAA) and chronic venous disease (CVD). Gene expression patterns were generated using the Ion S5XL next-generation sequencing platform and were analyzed using DESeq2 and UVE-PLS methods implemented in R programming software. In direct pairwise analysis, 21, 58 and 10 differentially expressed genes were selected from the comparison of LEAD vs. AAA, LEAD vs. CVD and AAA vs. CVD patient groups, respectively. Relationships between expression of dysregulated genes and age, body mass index, creatinine levels, hypertension and medication were identified using Spearman rank correlation test and two-sided Mann-Whitney U test. The functional analysis, performed using DAVID website tool, provides potential implications of selected genes in pathological processes underlying diseases studied. Presented research provides new insight into differences of pathogenesis in LEAD, AAA and CVD, and selected genes could be considered as potential candidates for biomarkers useful in diagnosis and differentiation of studied diseases.
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http://dx.doi.org/10.3390/ijms22063200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004090PMC
March 2021

The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer-A Preliminary Study.

Int J Mol Sci 2021 Feb 19;22(4). Epub 2021 Feb 19.

Chair and Department of Biology and Genetics, Medical University of Lublin, 20-093 Lublin, Poland.

There is an urgent need to seek new molecular biomarkers helpful in diagnosing and treating breast cancer. In this elaboration, we performed a molecular analysis of mutations and expression of genes within the PI3K/Akt/mTOR pathway in patients with ductal breast cancer of various malignancy levels. We recognized significant correlations between the expression levels of the studied genes. We also performed a bioinformatics analysis of the data available on the international database TCGA and compared them with our own research. Studies on mutations and expression of genes were conducted using High-Resolution Melt PCR (HRM-PCR), Allele-Specific-quantitative PCR (ASP-qPCR), Real-Time PCR molecular methods in a group of women with ductal breast cancer. Bioinformatics analysis was carried out using web source Ualcan and bc-GenExMiner. In the studied group of women, it was observed that the prevalence of mutations in the studied and genes was 29.63%. It was stated that the average expression level of the , , genes in the group of breast cancer patients is lower in comparison to the control group, while the average expression level of the and genes in the studied group was higher in comparison to the control group. It was also indicated that in the group of patients with mutations in the area of the and genes, the gene expression level is statistically significantly lower than in the group without mutations. According to our knowledge, we demonstrate, for the first time, that there is a very strong positive correlation between the levels of and gene expression in the case of patients with mutations and without mutations.
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http://dx.doi.org/10.3390/ijms22042061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922286PMC
February 2021

Salivary Carbohydrate-Deficient Transferrin in Alcohol- and Nicotine-Dependent Males.

J Clin Med 2020 Dec 15;9(12). Epub 2020 Dec 15.

Experimental Dentistry Laboratory, Medical University of Bialystok, 15-222 Bialystok, Poland.

Serum carbohydrate-deficient transferrin (CDT), an 80 kDa glycoprotein, is one of the most commonly employed biomarkers to detect alcohol dependence. Some salivary glycoproteins such as α-amylase, clusterin, haptoglobin, light/heavy-chain immunoglobulin, and transferrin, which alter glycosylation in alcohol-dependent persons, have been suggested to be potential alcohol markers. However, their identification is based on indirect analysis of lectin glycosidic bonds and molecular weight. We investigated the CDT content in the saliva of alcohol- and nicotine-dependent men. The CDT concentration (ng/mL, ng/mg protein) was determined by an Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit in 55 men: 20 healthy social drinkers (C), 10 chronic cigarette smokers (S), 10 alcohol-dependent non-smokers (A), and 15 alcohol-dependent smokers (AS). Surprisingly, there were no differences in the concentrations of CDT between the studied groups. Salivary pH was the lowest in the AS and the highest in the A group. Therefore, salivary CDT cannot be used as an alcohol dependence marker as measured by ELISA. We suggest that direct identification of glycoproteins is necessary to search for potential salivary alcohol biomarkers. Molecules smaller than 40 kDa, which easily translocate from blood to the saliva, might be preferred as salivary alcohol markers.
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http://dx.doi.org/10.3390/jcm9124054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765464PMC
December 2020

Peripheral Markers of Depression.

J Clin Med 2020 Nov 24;9(12). Epub 2020 Nov 24.

Department of Psychiatry, Medical University of Bialystok, pl. Brodowicza 1, 16-070 Choroszcz, Poland.

Major Depressive Disorder (MDD) is a leading cause of disability worldwide, creating a high medical and socioeconomic burden. There is a growing interest in the biological underpinnings of depression, which are reflected by altered levels of biological markers. Among others, enhanced inflammation has been reported in MDD, as reflected by increased concentrations of inflammatory markers-C-reactive protein, interleukin-6, tumor necrosis factor-α and soluble interleukin-2 receptor. Oxidative and nitrosative stress also plays a role in the pathophysiology of MDD. Notably, increased levels of lipid peroxidation markers are characteristic of MDD. Dysregulation of the stress axis, along with increased cortisol levels, have also been reported in MDD. Alterations in growth factors, with a significant decrease in brain-derived neurotrophic factor and an increase in fibroblast growth factor-2 and insulin-like growth factor-1 concentrations have also been found in MDD. Finally, kynurenine metabolites, increased glutamate and decreased total cholesterol also hold promise as reliable biomarkers for MDD. Research in the field of MDD biomarkers is hindered by insufficient understanding of MDD etiopathogenesis, substantial heterogeneity of the disorder, common co-morbidities and low specificity of biomarkers. The construction of biomarker panels and their evaluation with use of new technologies may have the potential to overcome the above mentioned obstacles.
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http://dx.doi.org/10.3390/jcm9123793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760788PMC
November 2020

Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm.

J Clin Med 2020 Jun 24;9(6). Epub 2020 Jun 24.

Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.

Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.
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http://dx.doi.org/10.3390/jcm9061974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355415PMC
June 2020

Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease.

J Clin Med 2020 Apr 25;9(5). Epub 2020 Apr 25.

Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.
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http://dx.doi.org/10.3390/jcm9051251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287878PMC
April 2020

Dysregulation of MicroRNA Regulatory Network in Lower Extremities Arterial Disease.

Front Genet 2019 22;10:1200. Epub 2019 Nov 22.

Department of Clinical Genetics, Chair of Medical Genetics, Medical University of Lublin, Lublin, Poland.

Atherosclerosis and its comorbidities are the major contributors to the global burden of death worldwide. Lower extremities arterial disease (LEAD) is a common manifestation of atherosclerotic disease of arteries of lower extremities. MicroRNAs belong to epigenetic factors that regulate gene expression and have not yet been extensively studied in LEAD. We aimed to indicate the most promising microRNA and gene expression signatures of LEAD, to identify interactions between microRNA and genes and to describe potential effect of modulated gene expression. High-throughput sequencing was employed to examine microRNAome and transcriptome of peripheral blood mononuclear cells of patients with LEAD, in relation to controls. Statistical significance of microRNAs and genes analysis results was evaluated using DESeq2 and uninformative variable elimination by partial least squares methods. Altered expression of 26 microRNAs (hsa-let-7f-1-3p, hsa-miR-34a-5p, -122-5p, -3591-3p, -34a-3p, -1261, -21-5p, -15a-5p, -548d-5p, -34b-5p, -424-3p, -548aa, -548t-3p, -4423-3p, -196a-5p, -330-3p, -766-3p, -30e-3p, -125b-5p, -1301-3p, -3184-5p, -423-3p, -339-3p, -138-5p, -99a-3p, and -6087) and 14 genes (, , , , , , , , , , , , , and ) were the most significantly differentially expressed in LEAD group compared to controls. Discriminative value of revealed microRNAs and genes were confirmed by receiver operating characteristic analysis. Dysregulations of 26 microRNAs and 14 genes were used to propose novel biomarkers of LEAD. Regulatory interactions between biomarker microRNAs and genes were studied using R multiMiR package. Functional analysis of genes modulated by proposed biomarker microRNAs was performed using DAVID 6.8 tools and revealed terms closely related to atherosclerosis and, interestingly, the processes involving nervous system. The study provides new insight into microRNA-dependent regulatory mechanisms involved in pathology of LEAD. Proposed microRNA and gene biomarkers of LEAD may provide new diagnostic and therapeutic opportunities.
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http://dx.doi.org/10.3389/fgene.2019.01200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892359PMC
November 2019

Cytotoxic and Proapoptotic Activity of Sanguinarine, Berberine, and Extracts of L. and DC. toward Hematopoietic Cancer Cell Lines.

Toxins (Basel) 2019 08 23;11(9). Epub 2019 Aug 23.

Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.

Isoquinoline alkaloids belong to the toxic secondary metabolites occurring in plants of many families. The high biological activity makes these compounds promising agents for use in medicine, particularly as anticancer drugs. The aim of our study was to evaluate the cytotoxicity and proapoptotic activity of sanguinarine, berberine, and extracts of L. and DC. IC10, IC50, and IC90 doses were established toward hematopoietic cancer cell lines using trypan blue staining. Alterations in the expression of 18 apoptosis-related genes in cells exposed to IC10, IC50, and IC90 were evaluated using real-time PCR. Sanguinarine and L. extract exhibit significant cytotoxicity against all studied cell lines. Lower cytotoxic activity was demonstrated for berberine. DC. extract had no influence on cell viability. Berberine, sanguinarine, and L. extract altered the expression of apoptosis-related genes in all tested cell lines, indicating the induction of apoptosis. The presented study confirmed the substantial cytotoxicity and proapoptotic activity of sanguinarine, berberine, and L. extract toward the studied hematopoietic cell lines, which indicates the utility of these substances in anticancer therapy.
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http://dx.doi.org/10.3390/toxins11090485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784183PMC
August 2019
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