TY - JOUR AU - Szlanka, Tamás AU - Lukacsovich, Tamás AU - Bálint, Éva AU - Virágh, Eszter Erika AU - Szabó, Kornélia AU - Hajdú, Ildikó AU - Molnár, Enikő AU - Lin, Yu-Hsien AU - Zvara, Ágnes AU - Kelemen-Valkony, Ildikó AU - Méhi, Orsolya Katinka AU - Török, István AU - Hegedűs, Zoltán AU - Kiss, Brigitta AU - Ramasz, Beáta AU - Magdalena, Laura M AU - Puskás, László AU - Mechler, Bernard M AU - Fónagy, Adrien AU - Asztalos, Zoltán Imre AU - Steinbach, Gábor AU - Žurovec, Michal AU - Boros, Imre Miklós AU - Kiss, István TI - Dominant suppressor genes of p53-induced apoptosis in Drosophila melanogaster JF - G3-GENES GENOMES GENETICS J2 - G3-GENES GENOM GENET VL - 14 PY - 2024 IS - 9 PG - 11 SN - 2160-1836 DO - 10.1093/g3journal/jkae149 UR - https://m2.mtmt.hu/api/publication/35135174 ID - 35135174 AB - One of a major function of programmed cell death (apoptosis) is the removal of cells which suffered oncogenic mutations, thereby preventing cancerous transformation. By making use of a Double-Headed-EP (DEP) transposon, a P element derivative made in our laboratory, we made an insertional mutagenesis screen in Drosophila melanogaster to identify genes which, when overexpressed, suppress the p53-activated apoptosis. The DEP element has Gal4-activatable, outward-directed UAS-promoters at both ends which can be deleted separately in vivo. In the DEP insertion mutants, we used the GMR-Gal4 driver to induce transcription from both UAS-promoters and tested the suppression effect on the apoptotic rough eye phenotype generated by an activated UAS-p53 transgene. By DEP insertions, seven genes were identified which suppressed the p53-induced apoptosis. In four mutants, the suppression effect resulted from single genes activated by one UAS-promoter (Pka-R2, Rga, crol, Spt5). In the other three (Orct2, Polr2M, stg), deleting either UAS-promoter eliminated the suppression effect. In qPCR experiments we found that the genes in the vicinity of the DEP insertion also showed an elevated expression level. This suggested an additive effect of the nearby genes on suppressing apoptosis. In the eucaryotic genomes there are co-expressed gene clusters. Three of the DEP insertion mutants are included and two are in close vicinity of separate co-expressed gene clusters. This raises the possibility that the activity of some of the genes in these clusters may help the suppression of the apoptotic cell death. LA - English DB - MTMT ER - TY - JOUR AU - Faragó, Anna AU - Zvara, Ágnes AU - Tiszlavicz, László AU - Hunyadi-Gulyás Éva, Csilla AU - Darula, Zsuzsanna AU - Hegedűs, Zoltán AU - Szabó, Enikő AU - Surguta, Sára Eszter AU - Tóvári, József AU - Puskás, László AU - Szebeni, Gábor TI - Lectin-Based Immunophenotyping and Whole Proteomic Profiling of CT-26 Colon Carcinoma Murine Model JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 7 PG - 21 SN - 1661-6596 DO - 10.3390/ijms25074022 UR - https://m2.mtmt.hu/api/publication/34790193 ID - 34790193 N1 - * Megosztott szerzőség A közlemény a Bolyai János Kutatási Ösztöndíj (BO/00582/22/8) segítségével jött létre. AB - A murine colorectal carcinoma (CRC) model was established. CT26 colon carcinoma cells were injected into BALB/c mice's spleen to study the primary tumor and the mechanisms of cell spread of colon cancer to the liver. The CRC was verified by the immunohistochemistry of Pan Cytokeratin and Vimentin expression. Immunophenotyping of leukocytes isolated from CRC-bearing BALB/c mice or healthy controls, such as CD19+ B cells, CD11+ myeloid cells, and CD3+ T cells, was carried out using fluorochrome-labeled lectins. The binding of six lectins to white blood cells, such as galectin-1 (Gal1), siglec-1 (Sig1), Sambucus nigra lectin (SNA), Aleuria aurantia lectin (AAL), Phytolacca americana lectin (PWM), and galectin-3 (Gal3), was assayed. Flow cytometric analysis of the splenocytes revealed the increased binding of SNA, and AAL to CD3 + T cells and CD11b myeloid cells; and increased siglec-1 and AAL binding to CD19 B cells of the tumor-bearing mice. The whole proteomic analysis of the established CRC-bearing liver and spleen versus healthy tissues identified differentially expressed proteins, characteristic of the primary or secondary CRC tissues. KEGG Gene Ontology bioinformatic analysis delineated the established murine CRC characteristic protein interaction networks, biological pathways, and cellular processes involved in CRC. Galectin-1 and S100A4 were identified as upregulated proteins in the primary and secondary CT26 tumor tissues, and these were previously reported to contribute to the poor prognosis of CRC patients. Modelling the development of liver colonization of CRC by the injection of CT26 cells into the spleen may facilitate the understanding of carcinogenesis in human CRC and contribute to the development of novel therapeutic strategies. LA - English DB - MTMT ER - TY - JOUR AU - Gémes, Nikolett AU - Balog, József Ágoston AU - Neuperger, Patricia AU - Schlegl, Erzsébet AU - Barta, Imre AU - Fillinger, János AU - Antus, Balázs AU - Zvara, Ágnes AU - Hegedűs, Zoltán AU - Czimmerer, Zsolt AU - Manczinger, Máté AU - Balogh, Gergő Mihály AU - Tóvári, József AU - Puskás, László AU - Szebeni, Gábor TI - Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC. JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 14 PY - 2023 PG - 16 SN - 1664-3224 DO - 10.3389/fimmu.2023.1297577 UR - https://m2.mtmt.hu/api/publication/34486293 ID - 34486293 N1 - * Megosztott szerzőség AB - Tobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC).Smoker controls without chronic illness were recruited as controls. Through extensive mapping of single cells, surface receptor quantification was achieved by single-cell mass cytometry (CyTOF) with 29 antibodies. The CyTOF characterized 14 main immune subsets such as CD4+, CD8+, CD4+/CD8+, CD4-/CD8-, and γ/δ T cells and other subsets such as CD4+ or CD8+ NKT cells, NK cells, B cells, plasmablasts, monocytes, CD11cdim, mDCs, and pDCs. The CD4+ central memory (CM) T cells (CD4+/CD45RA-/CD45RO+/CD197+) and CD4+ effector memory (EM) T cells (CD4+/CD45RA-/CD45RO+/CD197-) were FACS-sorted for RNA-Seq analysis. Plasma samples were assayed by Luminex MAGPIX® for the quantitative measurement of 17 soluble immuno-oncology mediators (BTLA, CD28, CD80, CD27, CD40, CD86, CTLA-4, GITR, GITRL, HVEM, ICOS, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, TLR-2) in the four studied groups.Our focus was on T-cell-dependent differences in COPD and NSCLC, where peripheral CD4+ central memory and CD4+ effector memory cells showed a significant reduction in exCOPD and CD4+ CM showed elevation in NSCLC. The transcriptome analysis delineated a perfect correlation of differentially expressed genes between exacerbating COPD and NSCLC-derived peripheral CD4+ CM or CD4+ EM cells. The measurement of 17 immuno-oncology soluble mediators revealed a disease-associated phenotype in the peripheral blood of stCOPD, exCOPD, and NSCLC patients.The applied single-cell mass cytometry, the whole transcriptome profiling of peripheral CD4+ memory cells, and the quantification of 17 plasma mediators provided complex data that may contribute to the understanding of the disbalance in immune homeostasis generated or sustained by tobacco smoking in COPD and NSCLC. LA - English DB - MTMT ER - TY - JOUR AU - Cinege, Gyöngyi Ilona AU - Magyar, Lilla Brigitta AU - Kovács, Henrietta AU - Varga, Viktória AU - Bodai, László AU - Zsindely, Nóra AU - Nagy, Gábor AU - Hegedűs, Zoltán AU - Hultmark, Dan AU - Andó, István TI - Distinctive features of Zaprionus indianus hemocyte differentiation and function revealed by transcriptomic analysis JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 14 PY - 2023 PG - 14 SN - 1664-3224 DO - 10.3389/fimmu.2023.1322381 UR - https://m2.mtmt.hu/api/publication/34446740 ID - 34446740 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Viktória AU - Rácz, Gergely AU - Takács, Hedvig AU - Radics, Bence AU - Borbás, János AU - Kormányos, Árpád AU - Csányi, Beáta AU - Hategan, Lídia AU - Iványi, Béla AU - Nagy, István AU - Hegedűs, Zoltán AU - Sepp, Róbert TI - Fabry-betegséget okoz-e a GLA gén p.Ala143Thr variánsa? [Does the GLA p.Ala143Thr variant cause Fabry disease?] JF - CARDIOLOGIA HUNGARICA J2 - CARDIOL HUNG VL - 53 PY - 2023 IS - 4 SP - 343 EP - 350 PG - 8 SN - 0133-5596 DO - 10.26430/CHUNGARICA.2023.53.4.343 UR - https://m2.mtmt.hu/api/publication/34154918 ID - 34154918 N1 - Szegedi Tudományegyetem, Kardiológiai Centrum, Szeged, Hungary Szegedi Tudományegyetem, Patológiai Intézet, Szeged, Hungary Biokémiai Intézet, Szegedi Biológiai Központ, Szeged, Hungary Seqomics Biotechnológiai Kft., Mórahalom, Hungary Biofizikai Intézet, Szegedi Biológiai Központ, Szeged, Hungary Pécsi Tudományegyetem, Biokémiai és Orvosi Kémiai Intézet, Pécs, Hungary Export Date: 21 March 2024 Correspondence Address: Róbert, S.; Szegedi Tudományegyetem, Semmelweis u 8, Hungary; email: sepprobert@gmail.com AB - Háttér: A hipertrófiás cardiomyopathia (HCM), és annak fenotípusát utánzó HCM-fenokópiák, pl. a Fabry-betegség kardiális manifesztációjának differenciáldiagnosztikai elkülönítése jelentős nehézséget okozhat a mindennapi klinikai gyakorlatban. Esetismertetés: A jelen észlelésekor 55 éves férfi beteg korábbi anamnézisében hipertónia, több alkalommal hipertenzív excessus miatti kórházi felvétel, ateroszklerózis, COPD, veseérintettség és stroke szerepelt. Egyre fokozódó fulladás és kifejezett terhelési intolerancia miatt indított kardiológiai kivizsgálása során jelentős balkamra-hipertrófia (IVS: 21 mm, PW: 17 mm) igazolódott, szignifikáns vitium vagy bal kamra kiáramlási pálya obstrukció nélkül. A bal kamra ejekciós frakció megtartott (EF: 64%) volt, csökkent bal kamrai globális longitudinális strain (GLS: –11,8 %) mellett, a bal kamrai töltőnyomás nem volt emelkedett. Szív-MRI-vizsgálat megerősítette a súlyos balkamra-hipertrófia (LVmax: 22 mm) jelenlétét, diffúz, kiterjedt késői kontraszthalmozással, amely a basalis, inferolateralis falon volt a legkifejezettebb. A beteg laborvizsgálata mérsékelten emelkedett NT-proBNP (427 pg/ml) és troponin T (41 ng/ml) értéket, csökkent vesefunkciót (eGFR: 59 ml/min/m2 ) és enyhe proteinuriát igazolt. A felmerülő Fabry-betegség irányában végzett specifikus vizsgálatok normális lyso-Gb3 értéket és mérsékelten csökkent alfa-galaktozidáz enzimszintet (a normális referenciaérték 45%-a) mutatott. A GLA gén genetikai vizsgálata egy bizonytalan hatású variánsként klasszifikált p.Ala143Thr variánst igazolt (NM_000169.2:c.427G>A, rs104894845). Tekintettel arra, hogy a képalkotó vizsgálatok a felmerült tárolási és infiltratív szívizom-betegségeket egyértelműen sem kizárni, sem megerősíteni nem tudták, szívizom-biopsziát végeztünk, amely Fabry-betegséget vagy infiltratív betegséget egyértelműen kizárt, hipertrófiás cardiomyopathiára jellemző eltéréseket (fibrosis, myofiber disarray) mutatott. Következtetés: A hipertrófiás cardiomyopathiát utánzó fenokópiák kardiális manifesztációjának elkülönítésére multidiszciplináris megközelítés, részletes képalkotó vizsgálatok, szükség esetén szívizom-biopszia és genetikai vizsgálat nyújthat segítséget. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Imre, Gergely AU - Takács, Bertalan Vilmos AU - Czipa, Erik AU - Drubi, Andrea AU - Jaksa, Gábor AU - Latinovics, Dóra AU - Nagy, Andrea AU - Karkas, Réka AU - Hudoba, Liza AU - Vásárhelyi, Bálint Márk AU - Pankotai-Bodó, Gabriella AU - Blastyák, András AU - Hegedűs, Zoltán AU - Germán, Péter AU - Bálint, Balázs AU - Abdullah, Khaldoon Sadiq Ahmed AU - Kopasz, Anna Georgina AU - Kovács, Anita Kármen AU - Nagy, László AU - Sükösd, Farkas AU - Pintér, Lajos AU - Rülicke, Thomas AU - Barta, Endre AU - Nagy, István AU - Haracska, Lajos AU - Mátés, Lajos TI - Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy JF - MOLECULAR THERAPY-METHODS AND CLINICAL DEVELOPMENT J2 - MOL THER-METH CLIN D VL - 29 PY - 2023 SP - 145 EP - 159 PG - 15 SN - 2329-0501 DO - 10.1016/j.omtm.2023.03.003 UR - https://m2.mtmt.hu/api/publication/33708483 ID - 33708483 LA - English DB - MTMT ER - TY - CHAP AU - Pap, Gergely AU - Ádám, Krisztián AU - Györgypál, Zoltán AU - Tóth, László AU - Hegedűs, Zoltán ED - Anon, A TI - Depthwise Convolutions using Physicochemical Features of DNA for Transcription Factor Binding Site Classification. Physicochemical Features for DNA-Protein Classification with Depthwise Convolutions TS - Physicochemical Features for DNA-Protein Classification with Depthwise Convolutions T2 - ICAAI '22: Proceedings of the 6th International Conference on Advances in Artificial Intelligence PB - Association for Computing Machinery (ACM) CY - New York, New York SN - 9781450396943 PY - 2022 SP - 15 EP - 21 PG - 7 DO - 10.1145/3571560.3571563 UR - https://m2.mtmt.hu/api/publication/33563542 ID - 33563542 LA - English DB - MTMT ER - TY - JOUR AU - Boros, Éva AU - Hegedűs, Zoltán AU - Kellermayer, Zoltán AU - Balogh, Péter AU - Nagy, István TI - Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 13 PY - 2022 PG - 14 SN - 1664-3224 DO - 10.3389/fimmu.2022.991346 UR - https://m2.mtmt.hu/api/publication/33125064 ID - 33125064 AB - Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that associates with, among others, increased risk of colorectal cancer. There is a growing evidence that miRNAs have important roles in pathological processes, such as inflammation or carcinogenesis. Understanding the molecular mechanisms such as alterations in microRNAome upon chronic intestinal inflammation is critical for understanding the exact pathomechanism of IBD. Hence, we conducted a genome wide microRNAome analysis by applying miRNA-Seq in a rat model of experimental colitis, validated the data by QPCR, examined the expression of a selection of precursor and mature miRNAs, performed in depth biological interpretation using Ingenuity Pathway Analysis and tested the obtained results on samples derived from human patients. We identified specific, interdependent expression pattern of activator/repressor transcription factors, miRNAs and their direct targets in the inflamed colon samples. Particularly, decreased expression of the miR-200 family members (miR-200a/b/c,-141, and -429) and miR-27b correlates with the reduced level of their enhancers (HNF1B, E2F1), elevated expression of their repressors (ZEB2, NFKB1) and increased expression of their target genes (ZEB2, RUNX1). Moreover, the marked upregulation of six miR-27b target genes (IFI16, GCA, CYP1B1, RUNX1, MEF2C and MMP13) in the inflamed colon tissues is a possible direct consequence of the lack of repression due to the downregulated miRNA-27b expression. Our data indicate that changes in microRNAome are associated with the pathophysiology of IBD, consequently, microRNAs offer potential targets for the diagnosis, prognosis and treatment of IBD. LA - English DB - MTMT ER - TY - JOUR AU - Tiszlavicz, Ádám AU - Gombos, Imre AU - Péter, Mária AU - Hegedűs, Zoltán AU - Hunya, Ákos AU - Dukic, Barbara AU - Nagy, István AU - Peksel, Begüm AU - Balogh, Gábor AU - Horváth, Ibolya AU - Vigh, László AU - Török, Zsolt TI - Distinct Cellular Tools of Mild Hyperthermia-Induced Acquired Stress Tolerance in Chinese Hamster Ovary Cells. JF - BIOMEDICINES J2 - BIOMEDICINES VL - 10 PY - 2022 IS - 5 PG - 24 SN - 2227-9059 DO - 10.3390/biomedicines10051172 UR - https://m2.mtmt.hu/api/publication/32849807 ID - 32849807 AB - Mild stress could help cells to survive more severe environmental or pathophysiological conditions. In the current study, we investigated the cellular mechanisms which contribute to the development of stress tolerance upon a prolonged (0-12 h) fever-like (40 °C) or a moderate (42.5 °C) hyperthermia in mammalian Chinese Hamster Ovary (CHO) cells. Our results indicate that mild heat triggers a distinct, dose-dependent remodeling of the cellular lipidome followed by the expression of heat shock proteins only at higher heat dosages. A significant elevation in the relative concentration of saturated membrane lipid species and specific lysophosphatidylinositol and sphingolipid species suggests prompt membrane microdomain reorganization and an overall membrane rigidification in response to the fluidizing heat in a time-dependent manner. RNAseq experiments reveal that mild heat initiates endoplasmic reticulum stress-related signaling cascades resulting in lipid rearrangement and ultimately in an elevated resistance against membrane fluidization by benzyl alcohol. To protect cells against lethal, protein-denaturing high temperatures, the classical heat shock protein response was required. The different layers of stress response elicited by different heat dosages highlight the capability of cells to utilize multiple tools to gain resistance against or to survive lethal stress conditions. LA - English DB - MTMT ER - TY - JOUR AU - Sepp, Róbert AU - Hategan, Lídia AU - Csányi, Beáta AU - Borbás, János AU - Tringer, Annamária AU - Pálinkás, Eszter Dalma AU - Nagy, Viktória AU - Takács, Hedvig AU - Latinovics, Dóra AU - Nyolczas, Noémi AU - Pálinkás, Attila AU - Faludi, Réka AU - Rábai, Miklós AU - Szabó, Gábor Tamás AU - Czuriga, Dániel AU - Balogh, László AU - Halmosi, Róbert AU - Borbély, Attila AU - Habon, Tamás AU - Hegedűs, Zoltán AU - Nagy, István TI - The Genetic Architecture of Hypertrophic Cardiomyopathy in Hungary: Analysis of 242 Patients with a Panel of 98 Genes JF - DIAGNOSTICS J2 - DIAGNOSTICS VL - 12 PY - 2022 IS - 5 PG - 12 SN - 2075-4418 DO - 10.3390/diagnostics12051132 UR - https://m2.mtmt.hu/api/publication/32804523 ID - 32804523 N1 - * Megosztott szerzőség LA - English DB - MTMT ER -