@article{MTMT:34790193, title = {Lectin-Based Immunophenotyping and Whole Proteomic Profiling of CT-26 Colon Carcinoma Murine Model.}, url = {https://m2.mtmt.hu/api/publication/34790193}, author = {Faragó, Anna and Zvara, Ágnes and Tiszlavicz, László and Hunyadi-Gulyás Éva, Csilla and Darula, Zsuzsanna and Hegedűs, Zoltán and Szabó, Enikő and Surguta, Sára Eszter and Tóvári, József and Puskás, László and Szebeni, Gábor}, doi = {10.3390/ijms25074022}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34790193}, issn = {1661-6596}, abstract = {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.}, keywords = {colorectal carcinoma; lectin binding sugar code; proteomic analysis of murine CRC}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Tóvári, József/0000-0002-5543-3204; Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:34486293, title = {Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC.}, url = {https://m2.mtmt.hu/api/publication/34486293}, author = {Gémes, Nikolett and Balog, József Ágoston and Neuperger, Patricia and Schlegl, Erzsébet and Barta, Imre and Fillinger, János and Antus, Balázs and Zvara, Ágnes and Hegedűs, Zoltán and Czimmerer, Zsolt and Manczinger, Máté and Balogh, Gergő Mihály and Tóvári, József and Puskás, László and Szebeni, Gábor}, doi = {10.3389/fimmu.2023.1297577}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {14}, unique-id = {34486293}, issn = {1664-3224}, abstract = {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.}, keywords = {Tobacco smoking; non-small cell lung cancer; single-cell mass cytometry; CD4 central memory T cells; CD4 effector memory T cells; exacerbating COPD; stable COPD}, year = {2023}, eissn = {1664-3224}, orcid-numbers = {Manczinger, Máté/0000-0003-0831-9617; Tóvári, József/0000-0002-5543-3204; Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:34446740, title = {Distinctive features of Zaprionus indianus hemocyte differentiation and function revealed by transcriptomic analysis}, url = {https://m2.mtmt.hu/api/publication/34446740}, author = {Cinege, Gyöngyi Ilona and Magyar, Lilla Brigitta and Kovács, Henrietta and Varga, Viktória and Bodai, László and Zsindely, Nóra and Nagy, Gábor and Hegedűs, Zoltán and Hultmark, Dan and Andó, István}, doi = {10.3389/fimmu.2023.1322381}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {14}, unique-id = {34446740}, issn = {1664-3224}, year = {2023}, eissn = {1664-3224}, orcid-numbers = {Bodai, László/0000-0001-8411-626X; Zsindely, Nóra/0000-0002-6189-3100; Nagy, Gábor/0000-0001-5464-1135; Andó, István/0000-0002-4648-9396} } @article{MTMT:34154918, title = {Fabry-betegséget okoz-e a GLA gén p.Ala143Thr variánsa? [Does the GLA p.Ala143Thr variant cause Fabry disease?]}, url = {https://m2.mtmt.hu/api/publication/34154918}, author = {Nagy, Viktória and Rácz, Gergely and Takács, Hedvig and Radics, Bence and Borbás, János and Kormányos, Árpád and Csányi, Beáta and Hategan, Lídia and Iványi, Béla and Nagy, István and Hegedűs, Zoltán and Sepp, Róbert}, doi = {10.26430/CHUNGARICA.2023.53.4.343}, journal-iso = {CARDIOL HUNG}, journal = {CARDIOLOGIA HUNGARICA}, volume = {53}, unique-id = {34154918}, issn = {0133-5596}, abstract = {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.}, year = {2023}, eissn = {1588-0230}, pages = {343-350}, orcid-numbers = {Kormányos, Árpád/0000-0002-7052-2184; Sepp, Róbert/0000-0003-4964-1661} } @article{MTMT:33708483, title = {Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy}, url = {https://m2.mtmt.hu/api/publication/33708483}, author = {Imre, Gergely and Takács, Bertalan Vilmos and Czipa, Erik and Drubi, Andrea and Jaksa, Gábor and Latinovics, Dóra and Nagy, Andrea and Karkas, Réka and Hudoba, Liza and Vásárhelyi, Bálint Márk and Pankotai-Bodó, Gabriella and Blastyák, András and Hegedűs, Zoltán and Germán, Péter and Bálint, Balázs and Ahmed Abdullah, Khaldoon Sadiq and Kopasz, Anna Georgina and Kovács, Anita Kármen and Nagy, László and Sükösd, Farkas and Pintér, Lajos and Rülicke, Thomas and Barta, Endre and Nagy, István and Haracska, Lajos and Mátés, Lajos}, doi = {10.1016/j.omtm.2023.03.003}, journal-iso = {MOL THER-METH CLIN D}, journal = {MOLECULAR THERAPY-METHODS AND CLINICAL DEVELOPMENT}, volume = {29}, unique-id = {33708483}, year = {2023}, eissn = {2329-0501}, pages = {145-159}, orcid-numbers = {Vásárhelyi, Bálint Márk/0000-0003-1782-8691; Kovács, Anita Kármen/0000-0001-9805-1647} } @inproceedings{MTMT:33563542, title = {Depthwise Convolutions using Physicochemical Features of DNA for Transcription Factor Binding Site Classification. Physicochemical Features for DNA-Protein Classification with Depthwise Convolutions}, url = {https://m2.mtmt.hu/api/publication/33563542}, author = {Pap, Gergely and Ádám, Krisztián and Györgypál, Zoltán and Tóth, László and Hegedűs, Zoltán}, booktitle = {ICAAI '22: Proceedings of the 6th International Conference on Advances in Artificial Intelligence}, doi = {10.1145/3571560.3571563}, unique-id = {33563542}, year = {2022}, pages = {15-21}, orcid-numbers = {Tóth, László/0000-0003-0161-1375} } @article{MTMT:33125064, title = {Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease}, url = {https://m2.mtmt.hu/api/publication/33125064}, author = {Boros, Éva and Hegedűs, Zoltán and Kellermayer, Zoltán and Balogh, Péter and Nagy, István}, doi = {10.3389/fimmu.2022.991346}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {33125064}, issn = {1664-3224}, abstract = {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.}, year = {2022}, eissn = {1664-3224} } @article{MTMT:32849807, title = {Distinct Cellular Tools of Mild Hyperthermia-Induced Acquired Stress Tolerance in Chinese Hamster Ovary Cells.}, url = {https://m2.mtmt.hu/api/publication/32849807}, author = {Tiszlavicz, Ádám and Gombos, Imre and Péter, Mária and Hegedűs, Zoltán and Hunya, Ákos and Dukic, Barbara and Nagy, István and Peksel, Begüm and Balogh, Gábor and Horváth, Ibolya and Vigh, László and Török, Zsolt}, doi = {10.3390/biomedicines10051172}, journal-iso = {BIOMEDICINES}, journal = {BIOMEDICINES}, volume = {10}, unique-id = {32849807}, abstract = {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.}, keywords = {MEMBRANE; STRESS; heat shock response; transcriptomics; LIPIDOMICS; Unfolded protein response; Chinese hamster ovary cells; acquired stress tolerance; membrane lipid metabolism}, year = {2022}, eissn = {2227-9059}, orcid-numbers = {Hunya, Ákos/0000-0002-4547-9284} } @article{MTMT:32804523, title = {The Genetic Architecture of Hypertrophic Cardiomyopathy in Hungary: Analysis of 242 Patients with a Panel of 98 Genes}, url = {https://m2.mtmt.hu/api/publication/32804523}, author = {Sepp, Róbert and Hategan, Lídia and Csányi, Beáta and Borbás, János and Tringer, Annamária and Pálinkás, Eszter Dalma and Nagy, Viktória and Takács, Hedvig and Latinovics, Dóra and Nyolczas, Noémi and Pálinkás, Attila and Faludi, Réka and Rábai, Miklós and Szabó, Gábor Tamás and Czuriga, Dániel and Balogh, László and Halmosi, Róbert and Borbély, Attila and Habon, Tamás and Hegedűs, Zoltán and Nagy, István}, doi = {10.3390/diagnostics12051132}, journal-iso = {DIAGNOSTICS}, journal = {DIAGNOSTICS}, volume = {12}, unique-id = {32804523}, issn = {2075-4418}, year = {2022}, eissn = {2075-4418}, orcid-numbers = {Sepp, Róbert/0000-0003-4964-1661; Pálinkás, Eszter Dalma/0000-0003-0713-3909; Nyolczas, Noémi/0000-0001-9466-0939; Szabó, Gábor Tamás/0000-0001-9880-0425; Czuriga, Dániel/0000-0002-6972-0781; Habon, Tamás/0000-0002-4816-857X} } @article{MTMT:32524824, title = {Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids}, url = {https://m2.mtmt.hu/api/publication/32524824}, author = {Cinege, Gyöngyi Ilona and Magyar, Lilla Brigitta and Kovács, Attila Lajos and Lerner, Zita and Juhász, Gábor and Lukacsovich, David and Winterer, Jochen and Lukacsovich, Tamás and Hegedűs, Zoltán and Kurucz, Judit Éva and Hultmark, Dan and Földy, Csaba and Andó, István}, doi = {10.1159/000520110}, journal-iso = {J INNATE IMMUN}, journal = {JOURNAL OF INNATE IMMUNITY}, volume = {14}, unique-id = {32524824}, issn = {1662-811X}, year = {2022}, eissn = {1662-8128}, pages = {335-354}, orcid-numbers = {Juhász, Gábor/0000-0001-8548-8874; Winterer, Jochen/0000-0002-6800-6594; Lukacsovich, Tamás/0000-0001-5908-9861; Hultmark, Dan/0000-0002-6506-5855; Andó, István/0000-0002-4648-9396} }