Theses (Faculty of Medicine)
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Tétel Korlátozottan hozzáférhető Cytometry analysis of lysosomal membrane stabilityAly, Reyad Ahmed Shaaban Mohamed; Bacsó, Zsolt József; Kipchumba, Biwott; Általános Orvostudományi Kar::Biofizikai és Sejtbiológiai Intézet; Gyógyszerésztudományi Kar; DE--Általános Orvostudományi KarLysosomal dysfunction is linked to various diseases, including neurodegenerative, cardiovascular, and cancerous conditions. Damage to the lysosomal membrane, causing lysosomal membrane permeabilization (LMP), can lead to autophagy, inflammation, or cell death. Cytotoxic T lymphocytes (CTLs) exhibit high lysosomal membrane stability and numerous lysosomes per cell, prompting analysis of whether this is due to lysosome quantity or membrane composition. The research aimed to utilize galectin puncta assays, the most sensitive method for LMP detection, on THP-1 and MCF-7 cell lines, as inducing lysosomal damage with LLOMe. We focused on detecting galectin-1 and galectin-3 through indirect immunofluorescence and LAMP-1 and LAMP-2 proteins as lysosomal markers, using confocal microscopy and flow cytometry to visualize and quantify the results. Both THP-1 and MCF-7 cell lines were used as references for these methods, which we plan to apply to CTL cells in the future.Tétel Korlátozottan hozzáférhető Investigation of the components of the 67-kDa laminin receptor-dependent protein phosphatase 2A activating signalling pathwayElsheikh, Emad R.A.; Kiss, Andrea; Általános Orvostudományi Kar::Orvosi Vegytani Intézet; DE--Általános Orvostudományi KarThe 67 kDa laminin receptor (67LR) is a non-integrin cell surface receptor derived from the 37 kDa precursor (37LRP) and is involved in cell adhesion. It also acts as a high-affinity receptor for epigallocatechin-3-gallate (EGCG), which can suppress tumor growth and induce apoptosis via various signaling pathways. One such pathway, involving the EGCG/67LR/cAMP/PKA/PP2A/MP cascade, activates tumor suppressor proteins through the dephosphorylation by protein phosphatase 2A (PP2A) and myosin phosphatase (MP). This study aims to elucidate the EGCG-67LR interaction and the role of B56 isoforms in MP activation. Using HEK293AD cells, the presence of the receptor in the plasma membrane was confirmed, making them suitable for interaction studies. An inducible CRISPR/Cas9 system in HeLa cells was employed to eliminate B56δ, revealing that its downregulation leads to increased phosphorylation of MYPT1, indicating that B56δ targets PP2A to MP.Tétel Korlátozottan hozzáférhető The effects of Danirixin, as a CXCR2 antagonist, on smooth muscle functionMesrati, Farah; Uray, Karen Lee; Általános Orvostudományi Kar::Orvosi Vegytani Intézet; DE--Általános Orvostudományi Kar; Szöllősi , Attila Gábor; Általános Orvostudományi Kar::Immunológiai IntézetThis research project was conducted in the frame of identifying the possibility of Danirixin use as a future treatment for ileus by proving the direct effect of danirixin on smooth muscle cell function through its signalling as a CXCR2 antagonist and investigating the effects of danirixin treatment on the overall proliferation and differentiation of the human smooth muscle cells.Tétel Korlátozottan hozzáférhető Comparative analysis of blood hic data across mammalsLodhi, Laiqa Zia; Barta, Endre; Általános Orvostudományi Kar::Biokémiai és Molekuláris Biológiai Intézet; DE--Általános Orvostudományi Kar; Kókai, Endre; Általános Orvostudományi Kar::Orvosi Vegytani IntézetThis project resulted in the successful development of a new pipeline for downloading and analyzing Mammalian Hi-C data. The analysis of blood hic data across mammals and how the conservation of syntenic region has been conserved across nine species. It highlights the effects of those conserved regions on 3D genomes of the selected species. Bash, Perl and several bioinformatics tools were utilized to run the analysis on the data.Tétel Korlátozottan hozzáférhető The role of HCN2 in macrophage cytokine releaseFrangu, Rrezon; Uray, Karen Lee; Általános Orvostudományi Kar::Orvosi Vegytani Intézet; DE--Általános Orvostudományi Kar; Koncz, Gábor; Általános Orvostudományi Kar::Immunológiai IntézetThis study explores the role of hyperpolarization-activated cyclic nucleotide-gated HCN channels in macrophage inflammation and their potential impact on intestinal motility. While HCN2 inhibition is known to decrease intestinal motility, its involvement in the development of ileus remains unclear. The research focused on HCN channels, particularly HCN2, which are crucial for cellular excitability and pacemaking, and are now recognized for their role in immune modulation. THP1 cells were treated with the HCN channel blocker ZD7288 or a vehicle control (DMSO) and subjected to cyclic stretch, with cytokine release measured to assess inflammation. Using the FlexCell system to apply mechanical stretch to activated THP1 cells, results showed a significant reduction in macrophage cytokine release following HCN2 inhibition. These findings enhance our understanding of HCN2 channels in macrophage inflammation and suggest their potential as therapeutic targets.Tétel Korlátozottan hozzáférhető IRF4 Negatively Regulates The Myeloid Blood Cell Development From Pluripotent Stem CellsMalik, Abdul; Szatmári, István; Általános Orvostudományi Kar::Biokémiai és Molekuláris Biológiai Intézet; DE--Általános Orvostudományi KarThe thesis explores the impact of the transcription factor IRF4 on the differentiation of mouse embryonic stem cells (ESCs) into myeloid dendritic cell (DC) progenitors. For this study, I used two chemically inducible ESC clones carrying the IRF4 transgene. This investigation explores the role of IRF4 in regulating this developmental process. Through flow cytometry analysis and gene expression profiling, it was observed that enforced expression of IRF4 led to a decreased percentage of CD45+ and CD34+ cells, indicative of suppression in ESC-derived myeloid blood cell development. Additionally, the results from RT-PCR analyzes revealed an increased expression of IRF4 when the cells were induced by doxycycline both at their undifferentiated stage and during the differentiation process. Together these results suggest that IRF4 suppresses ESC-derived myeloid blood cell development and exerts a general inhibitory effect on ES-DC development.Tétel Korlátozottan hozzáférhető The role of TPH1 in the regulation of breast tumor cell proliferation.Abad Sojos, Andrea Gabriela; Uray, Iván; Lengyel, Máté; Általános Orvostudományi Kar::Onkológiai Tanszék; Általános Orvostudományi Kar::Biokémiai és Molekuláris Biológiai Intézet; DE--Általános Orvostudományi KarStudies show that serotonin (5-hydroxytryptamine, 5HT) may interact with tumor cell proliferation and tumorigenic signaling pathways. Tryptophan hydroxilase-1 (TPH1), is the rate-limiting enzyme for serotonin production. We determined that the reduction of cellular 5HT levels in MCF7 breast cancer cells by the pharmacological inhibition of the TPH1 enzyme, was associated with growth suppression. To study the relationship between serotonin levels and its proliferative activity we conducted a cloning experiment for the TPH1 gene. The TPH1 gene DNA was cloned in 3 fragments that will be assembled in an expression vector for transfection.Tétel Korlátozottan hozzáférhető Pharmacogenomic investigation of SETMAR fusion gene on near-Haploid Lymphoblastoid Leukemia (HAP1) cell lineEsmandar, Zeina; Székvölgyi, Lóránt; Gyógyszerésztudományi Kar; DE--Általános Orvostudományi Kar; Uray, Karen Lee; Általános Orvostudományi Kar::Orvosi Vegytani IntézetGiven the lack of studied knowledge on the effects of SETMAR expression on drug sensitivity, we aimed to investigate various FDA-approved drugs impacting the viability of various genetically modified near-haploid human cell lines (HAP1) by applying high-content screening on the FDA-approved drug libraries in order to choose hits of active compounds for further analysis. HAP1 cells were treated with the hits (drugs) to evaluate how these drugs might influence cellular processes if we manipulated SETMAR expression levels in these cell lines.Tétel Korlátozottan hozzáférhető Analysis of mRNA Expression of Genes Commonly Regulated by RAR and VDR Agonists in Differentiated THP1 CellsAlHaman, Farah Hisham Ahmad; Széles, Lajos; Mianesaz, Hamidreza; Szirák, Krisztina; Általános Orvostudományi Kar::Humángenetikai Tanszék; Általános Orvostudományi Kar::Humángenetikai Tanszék; DE--Általános Orvostudományi KarRetinoic acid receptor (RAR) and vitamin D receptor (VDR) are nuclear receptors that form heterodimers with RXR and regulate the expression of multiple genes. many genes are regulated by both RAR and VDR agonists (e.g. AM850 and 1α,25-dihydroxyvitamin D3, respectively) in multiple cell types. This study examines genes regulated by both AM580 (RARα specific agonist) and 1α,25-dihydroxyvitamin D3 (VDR agonist) in differentiated THP-1 cells focusing on mRNA induction kinetics and additive effects on gene activation.Tétel Korlátozottan hozzáférhető Study of miRNAs as biomarker in lung Adenocarcinoma associated brain tumorAftab Khan, Ruqayya; Hádáné Birkó, Zsuzsanna; Torner, Bernadett; Általános Orvostudományi Kar::Humángenetikai Tanszék; DE--Általános Orvostudományi KarWe aimed to compare the miRNA expression pattern in malignant tissue samples with lung adenocarcinoma-associated brain tumors and control brain tissue samples from healthy individuals, to develop a miRNA panel that can help reliably distinguish between tumor and healthy samples, potentially serving as biomarkers for adenocarcinoma-associated brain tumors. Two miRNAs, hsa-miR-200c-5p and hsa-miR-141-5p, were identified as significantly upregulated in adenocarcinoma associated brain tumor samples compared to control samples. The identification of hsa-miR-200c-5p and hsa-miR-141-5p as potential biomarkers for lung adenocarcinoma-associated brain tumors opens avenues for early diagnosis of metastatic brain tumors from lung adenocarcinoma and to distinguish it from other brain tumors.Tétel Korlátozottan hozzáférhető Genotyping and analysis of the HLA region of whole genome sequencing data from two Hungarian families affected with coeliac diseaseValerio Aguilar, Kenneth Alejandro; Barta, Endre; Általános Orvostudományi Kar::Biokémiai és Molekuláris Biológiai Intézet; DE--Általános Orvostudományi Kar; Polgár , Zsuzsanna; Általános Orvostudományi Kar::Orvosi Vegytani IntézetIn this study, we used whole genome sequencing data from two Hungarian families affected by CD to analyze the HLA-related genetic mechanisms behind it. We used bash scripting to run an open-source genotyping algorithm to predict the alleles of the different HLA genetic regions. After this, we extracted, analyzed, and compared the haplotype frequencies in CD-affected individuals against non-affected ones. We found that, in line with previous findings, the HLADQ2.5 haplotype was predominant in our study group, and there was almost no evidence of the HLADQ8 haplotype. Using descriptive statistics methods, we found evidence of a strong linkage disequilibrium factor in our population. Affected individuals might be carrying the ancestral haplotype AH 8.1, composed of HLA-A1, Cw7, B8, DRB1*0301, DRB3*0101, DQA1*0501, and DQB1*0201 alleles.Tétel Korlátozottan hozzáférhető Membrane localization of Kv1.3 channels in synapse-engaged CD19-CAR T-cellsHijaz, Marwa Mahmoud Mohammad; Hajdu, Péter Béla; Fogorvostudományi Kar; DE--Általános Orvostudományi Kar; Mótyán , János András; Általános Orvostudományi Kar::Biokémiai és Molekuláris Biológiai IntézetCAR T cells are genetically modified cells engineered to recognize CD19 on tumor cells. The immune synapse formed between a CAR T cell and a target antigen-presenting cell (APC) has unique characteristics, one of which is the accumulation of Kv1.3. By generating CAR T cells with retroviral transduction, and the activation of B cells with the engineered T cells, Kv1.3 accumulation at the synapse was captured with confocal microscopy and further analyzed with flow cytometry.Tétel Korlátozottan hozzáférhető Study of the Nuclear Function of Transglutaminase-2 in Acute Promyelocytic Leukemia CellsAysha, Afnan Hossain; Balajthy, Zoltán; Jambrovics, Károly; Általános Orvostudományi Kar::Biokémiai és Molekuláris Biológiai Intézet; Általános Orvostudományi Kar::Biokémiai és Molekuláris Biológiai Intézet; DE--Általános Orvostudományi Kar; Kovács, Katalin; Általános Orvostudományi Kar::Orvosi Vegytani IntézetThis thesis investigates the role of Transglutaminase-2 (TG2) in acute promyelocytic leukemia (APL), particularly how it interacts with the PML-RARα fusion protein and affects retinoic acid (RA) signaling pathways. By treating NB4 cells with all-trans retinoic acid (ATRA), we were able to trigger the movement of TG2 into the nucleus, which allowed us to detect, isolate, and study it. We used various biochemical methods like cell fractionation, co-immunoprecipitation, and isoelectric focusing to explore TG2’s interactions with other nuclear proteins. Our findings show that TG2 plays a significant role in the differentiation and apoptosis of APL cells, rendering it a therapeutic target. This research adds to our understanding of TG2’s importance in both APL and broader cellular functions.Tétel Korlátozottan hozzáférhető The immunomodulatory effects of ivermectin on human monocyte-derived dendritic cellsAl-Bayati, Ibrahim Faisal Ibrahim; Bacsi, Attila; Varga, Aliz; Általános Orvostudományi Kar::Immunológiai Intézet; Általános Orvostudományi Kar::Immunológiai Intézet; DE--Általános Orvostudományi Kar; Szalmas, Anita; Általános Orvostudományi Kar::Orvosi Mikrobiológiai IntézetIvermectin, a drug used to treat parasitic infections, has gained attention for its possible immune system-modulating effects beyond its usual medical applications. This research aims to investigate the effect of ivermectin as immunomodulatory through its impact on moDCs by studying the amount of HLA-DQ molecules and CD86 molecules on moDCs by flow cytometry and their production of proinflammatory cytokines (IL-6 and TNF-a) by ELISA, by analysing the impacts of different treatments (control, DMSO, ivermectin, pIC+DMSO, pIC+LyoVec+DMSO, pIC+Ivermectin, pIC+LyoVec+Ivermectin) on moDCs and their role in immune regulation during viral infections. The results, meticulously obtained through the flow cytometry method, revealed no significant differences in cell vitality under various experimental conditions. This indicates that the concentration of 2.5 micromolar, whether used alone or in combination with other treatments, did not exhibit any toxic effects on the cells, reinforcing the safety of the experimental setup.Tétel Korlátozottan hozzáférhető One health approach: dynamics of antibiotics resistance within the context of human-animal relationshipsWarutho, Bitrum Hinga; Papp, Dalma; Tóth, Renáta; Metagenomikai Intézet; Metagenomikai Intézet; DE--Általános Orvostudományi KarThis pilot investigation explored antibiotic resistance dynamics in the human-animal relationship, focusing on ESBL+, AmpC+, CRP+ Enterobacteriaceae, and vancomycin-resistant Enterococci. Stool samples from 19 pet-owner groups revealed that out of 128 bacterial strains, only 11 displayed the resistance mechanisms of interest, with a minor phenotypic overlap between human and pet strains. Genetic analysis confirmed phenotypic resistance but did not find identical or similar strains between humans and animals. Plasmid-encoded resistance was identified in 50% of resistant animal strains. External factors like recent hospitalization of owners might influence resistance occurrence, though the small sample size limits significant conclusions.Tétel Korlátozottan hozzáférhető Aortic Stenosis, TAVI Treatment and the Role of Cardiac Computed TomographyKurabayashi, Makiko; Kolozsvári, Rudolf; Általános Orvostudományi Kar::Kardiológiai Intézet::Kardiológiai Tanszék; DE--Általános Orvostudományi Kar; Zöld, Éva; Ladányi, Lilla; Általános Orvostudományi Kar::Belgyógyászati Intézet; Általános Orvostudományi Kar::Orvosi Képalkotó Intézet::Radiológiai TanszékAortic stenosis (AS) is a common valvular disorder, especially in the elderly, when the aortic valve does not open enough during systole. Main symptoms are chest pain, heart failure and syncope. Etiologies are calcification, congenital and rheumatic change of the valve. The gold standard method for evaluation of AS is echocardiography. The definitive treatment for AS is aortic valve replacement. The valve replacement is performed by open heart surgery or transcatheter method. Transcatheter aortic valve implantation (TAVI) is one of the interventions in which aortic valve is replaced to the biological prosthetic valve by catheter. This is less invasive method than open heart surgery and it is used for the elderly and patients previously considered difficult to operate on. Which intervention to use is discussed and determined based on the patient's condition and risk factors.Tétel Korlátozottan hozzáférhető Medical treatment of psychotic diseasesChae, Jeongyun; Pórszász, Róbert; Általános Orvostudományi Kar::Farmakológiai és Farmakoterápiai Intézet; DE--Általános Orvostudományi Kar; László; Megyeri, Attila; Általános Orvostudományi Kar::Aneszteziológiai és Intenzív Terápiás Tanszék; Általános Orvostudományi Kar::Farmakológiai és Farmakoterápiai IntézetThe population at risk for mental illness and psychotic diseases has grown significantly in the last several years. There has been a steady rise in the risk factors for psychotic disorders, including stress, alcoholism, and drug abuse. Furthermore, the significance of safe treatment of psychotic diseases and prevention of any potential consequences of psychotic diseases or pharmacological side effects of antipsychotic drugs has increased along with the number of complications linked to various psychiatric problems, and drug usage. This thesis examines various hypotheses regarding the pathophysiology of psychotic disorders, classification, features, and diagnosis of psychotic disorders, basic therapeutic modalities, particularly pharmacological means, side effects of medications, and recent adjuvant treatment options.Tétel Korlátozottan hozzáférhető ADVANTAGEOUS EFFECTS OF TOFACITINIB ON COMORBIDITIES OBSERVED IN COMPLETE FREUND’S ADJUVANT- INDUCED RHEUMATOID ARTHRITIS IN A ZSF1 RAT MODELVietrov, Tymur; Bombicz, Mariann; Általános Orvostudományi Kar::Farmakológiai és Farmakoterápiai Intézet; DE--Általános Orvostudományi KarThe study aimed to examine the effects of the antirheumatic drug tofacitinib on metabolic syndrome associated with Rheumatoid Arthritis (RA) in a rodent model. 50 male ZSF1 rats were divided into eight groups, four lean and four obese, and treated with combinations of Complete Freund’s Adjuvant (CFA) and tofacitinib. Inflammation severity, glucose homeostasis, blood pressure, and body weight were measured, and FDG-PET scans were used to assess metabolic activity. Obese rats had worse OGTT results, higher HgbA1C levels, blood pressure, and body weight than lean ones. Tofacitinib treatment resulted in significant differences, including a decrease in the thermo-mechanical nociceptive threshold. The study suggests that tofacitinib may alleviate metabolic syndrome’s consequences, such as insulin resistance, without affecting blood pressure.Tétel Korlátozottan hozzáférhető INCORPORATION OF ALPHA2- PLASMIN INHIBITOR INTO PLASMA CLOTS OF HEALTHY CONTROLS AND PATIENTS WITH VENOUS THROMBOEMBOLISMDauda, Marriam Akua Amprofua; Katona, Éva; Általános Orvostudományi Kar::Laboratóriumi Medicina Intézet; DE--Általános Orvostudományi KarAlpha2-plasmin inhibitor (A2PI) is the main physiological inhibitor of plasmin. In the final phase of coagulation, activated factor XIII (FXIIIa) cross-links A2PI to fibrin and it has been shown that only cross-linked A2PI can efficiently inhibit fibrinolysis. After secretion into the plasma, full length A2PI contains a C-terminal plasminogen-binding site (PB-A2PI), which is lost due to cleavage by an as yet unknown protease. The truncated form (NPB-A2PI) remains enzymatically active, but it is a slow plasmin inhibitor. FXIIIa primarily cross-links PB-A2PI to fibrin. The binding of the truncated form to the clot and the effect of the ratio of the two C-terminal forms on the incorporation of PB-A2PI have not yet been investigated in detail. The study aims to investigate the incorporation of PB-A2PI and NPB-A2PI into the plasma clots of controls and patients with venous thromboembolism (VTE).Tétel Korlátozottan hozzáférhető Pharmacology of immunosuppressants in transplantation surgeriesFisher, Ofer; Pórszász, Róber; Általános Orvostudományi Kar::Farmakológiai és Farmakoterápiai Intézet; DE--Általános Orvostudományi Kar; Drimba, László; Megyeri, Attila; Általános Orvostudományi Kar::Aneszteziológiai és Intenzív Terápiás Tanszék; Általános Orvostudományi Kar::Farmakológiai és Farmakoterápiai IntézetThe purpose of this study is to review and learn the connection between the immunospressive drugs treatment and its effects on the success of the solid organ transplantation and the dangers it withholds (opportunistic infections), plus understanding the importance of an accurate dose of those drugs given to the patients and finding the right balance in order to have a successful transplantation as well as a healthy patient. Furthermore, learning about the importance of searching for novel drugs, capable of increasing the tolerance (increasing graft survivability), while keeping the immune system of the patient functioning (protect patient from opportunistic infections).