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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.
Daniel Zalewski; Karol Ruszel; Andrzej Stępniewski; Dariusz Gałkowski; Jacek Bogucki; Przemysław Kołodziej; Jolanta Szymańska; Bartosz Płachno; Tomasz Zubilewicz; Marcin Feldo; Janusz Kocki; Anna Bogucka-Kocka. Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens. International Journal of Molecular Sciences 2021, 22, 3200 .
AMA StyleDaniel Zalewski, Karol Ruszel, Andrzej Stępniewski, Dariusz Gałkowski, Jacek Bogucki, Przemysław Kołodziej, Jolanta Szymańska, Bartosz Płachno, Tomasz Zubilewicz, Marcin Feldo, Janusz Kocki, Anna Bogucka-Kocka. Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens. International Journal of Molecular Sciences. 2021; 22 (6):3200.
Chicago/Turabian StyleDaniel Zalewski; Karol Ruszel; Andrzej Stępniewski; Dariusz Gałkowski; Jacek Bogucki; Przemysław Kołodziej; Jolanta Szymańska; Bartosz Płachno; Tomasz Zubilewicz; Marcin Feldo; Janusz Kocki; Anna Bogucka-Kocka. 2021. "Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens." International Journal of Molecular Sciences 22, no. 6: 3200.
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 PIK3CA and AKT1 genes was 29.63%. It was stated that the average expression level of the PIK3CA, PIK3R1, PTEN genes in the group of breast cancer patients is lower in comparison to the control group, while the average expression level of the AKT1 and mTOR 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 PIK3CA and AKT1 genes, the PIK3CA 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 AKT1 and mTOR gene expression in the case of patients with mutations and without mutations.
Przemysław Kołodziej; Marcin Nicoś; Paweł A. Krawczyk; Jacek Bogucki; Agnieszka Karczmarczyk; Daniel Zalewski; Tomasz Kubrak; Elżbieta Kołodziej; Anna Makuch-Kocka; Barbara Madej-Czerwonka; Bartosz J. Płachno; Janusz Kocki; Anna Bogucka-Kocka. The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer—A Preliminary Study. International Journal of Molecular Sciences 2021, 22, 2061 .
AMA StylePrzemysław Kołodziej, Marcin Nicoś, Paweł A. Krawczyk, Jacek Bogucki, Agnieszka Karczmarczyk, Daniel Zalewski, Tomasz Kubrak, Elżbieta Kołodziej, Anna Makuch-Kocka, Barbara Madej-Czerwonka, Bartosz J. Płachno, Janusz Kocki, Anna Bogucka-Kocka. The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer—A Preliminary Study. International Journal of Molecular Sciences. 2021; 22 (4):2061.
Chicago/Turabian StylePrzemysław Kołodziej; Marcin Nicoś; Paweł A. Krawczyk; Jacek Bogucki; Agnieszka Karczmarczyk; Daniel Zalewski; Tomasz Kubrak; Elżbieta Kołodziej; Anna Makuch-Kocka; Barbara Madej-Czerwonka; Bartosz J. Płachno; Janusz Kocki; Anna Bogucka-Kocka. 2021. "The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer—A Preliminary Study." International Journal of Molecular Sciences 22, no. 4: 2061.
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.
Daniel Zalewski; Karol Ruszel; Andrzej Stępniewski; Dariusz Gałkowski; Jacek Bogucki; Łukasz Komsta; Przemysław Kołodziej; Paulina Chmiel; Tomasz Zubilewicz; Marcin Feldo; Janusz Kocki; Anna Bogucka-Kocka. Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm. Journal of Clinical Medicine 2020, 9, 1974 .
AMA StyleDaniel Zalewski, Karol Ruszel, Andrzej Stępniewski, Dariusz Gałkowski, Jacek Bogucki, Łukasz Komsta, Przemysław Kołodziej, Paulina Chmiel, Tomasz Zubilewicz, Marcin Feldo, Janusz Kocki, Anna Bogucka-Kocka. Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm. Journal of Clinical Medicine. 2020; 9 (6):1974.
Chicago/Turabian StyleDaniel Zalewski; Karol Ruszel; Andrzej Stępniewski; Dariusz Gałkowski; Jacek Bogucki; Łukasz Komsta; Przemysław Kołodziej; Paulina Chmiel; Tomasz Zubilewicz; Marcin Feldo; Janusz Kocki; Anna Bogucka-Kocka. 2020. "Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm." Journal of Clinical Medicine 9, no. 6: 1974.
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.
Daniel P. Zalewski; Karol P. Ruszel; Andrzej Stępniewski; Dariusz Gałkowski; Jacek Bogucki; Łukasz Komsta; Przemysław Kołodziej; Paulina Chmiel; Tomasz Zubilewicz; Marcin Feldo; Janusz Kocki; Anna Bogucka-Kocka. Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease. Journal of Clinical Medicine 2020, 9, 1251 .
AMA StyleDaniel P. Zalewski, Karol P. Ruszel, Andrzej Stępniewski, Dariusz Gałkowski, Jacek Bogucki, Łukasz Komsta, Przemysław Kołodziej, Paulina Chmiel, Tomasz Zubilewicz, Marcin Feldo, Janusz Kocki, Anna Bogucka-Kocka. Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease. Journal of Clinical Medicine. 2020; 9 (5):1251.
Chicago/Turabian StyleDaniel P. Zalewski; Karol P. Ruszel; Andrzej Stępniewski; Dariusz Gałkowski; Jacek Bogucki; Łukasz Komsta; Przemysław Kołodziej; Paulina Chmiel; Tomasz Zubilewicz; Marcin Feldo; Janusz Kocki; Anna Bogucka-Kocka. 2020. "Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease." Journal of Clinical Medicine 9, no. 5: 1251.
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 (AK5, CD248, CDS2, FAM129A, FBLN2, GGT1, NOG, NRCAM, PDE7A, RP11-545E17.3, SLC12A2, SLC16A10, SLC4A10, and ZSCAN18) 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 in silico 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.
Anna Bogucka-Kocka; Daniel P. Zalewski; Karol P. Ruszel; Andrzej Stępniewski; Dariusz Gałkowski; Jacek Bogucki; Łukasz Komsta; Przemysław Kołodziej; Tomasz Zubilewicz; Marcin Feldo; Janusz Kocki. Dysregulation of MicroRNA Regulatory Network in Lower Extremities Arterial Disease. Frontiers in Genetics 2019, 10, 1200 .
AMA StyleAnna Bogucka-Kocka, Daniel P. Zalewski, Karol P. Ruszel, Andrzej Stępniewski, Dariusz Gałkowski, Jacek Bogucki, Łukasz Komsta, Przemysław Kołodziej, Tomasz Zubilewicz, Marcin Feldo, Janusz Kocki. Dysregulation of MicroRNA Regulatory Network in Lower Extremities Arterial Disease. Frontiers in Genetics. 2019; 10 ():1200.
Chicago/Turabian StyleAnna Bogucka-Kocka; Daniel P. Zalewski; Karol P. Ruszel; Andrzej Stępniewski; Dariusz Gałkowski; Jacek Bogucki; Łukasz Komsta; Przemysław Kołodziej; Tomasz Zubilewicz; Marcin Feldo; Janusz Kocki. 2019. "Dysregulation of MicroRNA Regulatory Network in Lower Extremities Arterial Disease." Frontiers in Genetics 10, no. : 1200.
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 Chelidonium majus L. and Berberis thunbergii 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 Chelidonium majus L. extract exhibit significant cytotoxicity against all studied cell lines. Lower cytotoxic activity was demonstrated for berberine. Berberis thunbergii DC. extract had no influence on cell viability. Berberine, sanguinarine, and Chelidonium majus 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 Chelidonium majus L. extract toward the studied hematopoietic cell lines, which indicates the utility of these substances in anticancer therapy.
Anna Och; Daniel Zalewski; Łukasz Komsta; Przemysław Kołodziej; Janusz Kocki; Anna Bogucka-Kocka. Cytotoxic and Proapoptotic Activity of Sanguinarine, Berberine, and Extracts of Chelidonium majus L. and Berberis thunbergii DC. toward Hematopoietic Cancer Cell Lines. Toxins 2019, 11, 485 .
AMA StyleAnna Och, Daniel Zalewski, Łukasz Komsta, Przemysław Kołodziej, Janusz Kocki, Anna Bogucka-Kocka. Cytotoxic and Proapoptotic Activity of Sanguinarine, Berberine, and Extracts of Chelidonium majus L. and Berberis thunbergii DC. toward Hematopoietic Cancer Cell Lines. Toxins. 2019; 11 (9):485.
Chicago/Turabian StyleAnna Och; Daniel Zalewski; Łukasz Komsta; Przemysław Kołodziej; Janusz Kocki; Anna Bogucka-Kocka. 2019. "Cytotoxic and Proapoptotic Activity of Sanguinarine, Berberine, and Extracts of Chelidonium majus L. and Berberis thunbergii DC. toward Hematopoietic Cancer Cell Lines." Toxins 11, no. 9: 485.
Anna Bogucka-Kocka; Daniel Zalewski. Qualitative and quantitative determination of main alkaloids of Chelidonium majus L. using thin-layer chromatographic-densitometric method. Acta Chromatographica 2017, 29, 385 -397.
AMA StyleAnna Bogucka-Kocka, Daniel Zalewski. Qualitative and quantitative determination of main alkaloids of Chelidonium majus L. using thin-layer chromatographic-densitometric method. Acta Chromatographica. 2017; 29 (3):385-397.
Chicago/Turabian StyleAnna Bogucka-Kocka; Daniel Zalewski. 2017. "Qualitative and quantitative determination of main alkaloids of Chelidonium majus L. using thin-layer chromatographic-densitometric method." Acta Chromatographica 29, no. 3: 385-397.