@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 = {Tiszlavicz, László/0000-0003-1134-6587; Tóvári, József/0000-0002-5543-3204; Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:34865380, title = {Az ACTC1 gén novel p.Asn94Ile mutációja extrém fokú szívizom fi brózist okoz hypertrophiás cardiomyopathiával és progresszív ingerületvezetési zavarral járó fenotípusban = Extreme myocardial fibrosis caused by a novel cardiac actin gene (ACTC1) p.Asn94Ile mutation leading to hypertrophic cardiomyopathy and progressive conduction disease}, url = {https://m2.mtmt.hu/api/publication/34865380}, author = {Tringer, Annamária and Borbás, János and Nagy, Viktória and Takács, Hedvig and Rácz, Gergely and Kormányos, Árpád and Schvartz, Noémi and Polestyuk, Bianka Petra and Hategan, Lídia and Csányi, Beáta and Pap, Róbert and Hegedűs, Zoltán and Nagy, István and Szili-Török, Tamás and Sepp, Róbert}, journal-iso = {CARDIOL HUNG}, journal = {CARDIOLOGIA HUNGARICA}, volume = {54}, unique-id = {34865380}, issn = {0133-5596}, year = {2024}, eissn = {1588-0230}, pages = {C337-C337}, orcid-numbers = {Kormányos, Árpád/0000-0002-7052-2184; Pap, Róbert/0000-0002-7009-5063; Szili-Török, Tamás/0000-0002-7165-8243; Sepp, Róbert/0000-0003-4964-1661} } @article{MTMT:34867807, title = {A dilatatív cardiomyopathia genetikai mintázata magyarországon: 135 beteg vizsgálata új generációs szekvenálással = The genetic landscape of dilated cardiomyopathy in Hungary}, url = {https://m2.mtmt.hu/api/publication/34867807}, author = {Csányi, Beáta and Hategan, Lídia and Borbás, János and Nagy, Viktória and Takács, Hedvig and Pálinkás, Attila and Pálinkás, Eszter Dalma and Rábai, Miklós and Balogh, László and Halmosi, Róbert and Borbély, Attila and Habon, Tamás and Nyolczas, Noémi and Nagy, István and Hegedűs, Zoltán and Sepp, Róbert}, journal-iso = {CARDIOL HUNG}, journal = {CARDIOLOGIA HUNGARICA}, volume = {54}, unique-id = {34867807}, issn = {0133-5596}, year = {2024}, eissn = {1588-0230}, pages = {C450-C450}, orcid-numbers = {Sepp, Róbert/0000-0003-4964-1661} } @article{MTMT:35135174, title = {Dominant suppressor genes of p53-induced apoptosis in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/35135174}, author = {Szlanka, Tamás and Lukacsovich, Tamás and Bálint, Éva and Virágh, Eszter Erika and Szabó, Kornélia Ágnes and Hajdú, Ildikó and Molnár, Enikő and Lin, Yu-Hsien and Zvara, Ágnes and Kelemen-Valkony, Ildikó and Méhi, Orsolya Katinka and Török, István and Hegedűs, Zoltán and Kiss, Brigitta and Ramasz, Beáta and Magdalena, Laura M and Puskás, László and Mechler, Bernard M and Fónagy, Adrien and Asztalos, Zoltán Imre and Steinbach, Gábor and Žurovec, Michal and Boros, Imre Miklós and Kiss, István}, doi = {10.1093/g3journal/jkae149}, journal-iso = {G3-GENES GENOM GENET}, journal = {G3-GENES GENOMES GENETICS}, volume = {14}, unique-id = {35135174}, issn = {2160-1836}, abstract = {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.}, keywords = {APOPTOSIS; DROSOPHILA; SUPPRESSION; p53; activating insertional mutagenesis}, year = {2024}, eissn = {2160-1836}, orcid-numbers = {Szabó, Kornélia Ágnes/0000-0002-6231-3251; Méhi, Orsolya Katinka/0009-0004-7918-913X; Steinbach, Gábor/0000-0001-7137-7030; Boros, Imre Miklós/0000-0001-8504-9687} } @article{MTMT:35503610, title = {Identification of a novel actin gene mutation, ACTC1 p.Asn94Ile, in a family with cardiomyopathy and conduction disease}, url = {https://m2.mtmt.hu/api/publication/35503610}, author = {Sepp, Róbert and Tringer, Annamária and Nagy, Viktória and Radics, Bence and Hategan, Lídia and Takács, Hedvig and Palinkas, A. and Borbás, János and Csányi, Beáta and Rácz, Gergely and Kormányos, Árpád and Pálinkás, Eszter Dalma and Hegedűs, Zoltán and Nagy, István}, journal-iso = {EUR J HEART FAIL}, journal = {EUROPEAN JOURNAL OF HEART FAILURE}, volume = {26}, unique-id = {35503610}, issn = {1388-9842}, year = {2024}, eissn = {1879-0844}, pages = {518-518}, orcid-numbers = {Sepp, Róbert/0000-0003-4964-1661; Kormányos, Árpád/0000-0002-7052-2184; Pálinkás, Eszter Dalma/0000-0003-0713-3909} } @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 Abdullah, Khaldoon Sadiq Ahmed 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}, abstract = {DNA transposon-based gene delivery vectors represent a promising new branch of randomly integrating vector development for gene therapy. For the side-by-side evaluation of the piggyBac and Sleeping Beauty systems—the only DNA transposons currently employed in clinical trials—during therapeutic intervention, we treated the mouse model of tyrosinemia type I with liver-targeted gene delivery using both transposon vectors. For genome-wide mapping of transposon insertion sites we developed a new next-generation sequencing procedure called streptavidin-based enrichment sequencing, which allowed us to identify approximately one million integration sites for both systems. We revealed that a high proportion of piggyBac integrations are clustered in hot regions and found that they are frequently recurring at the same genomic positions among treated animals, indicating that the genome-wide distribution of Sleeping Beauty-generated integrations is closer to random. We also revealed that the piggyBac transposase protein exhibits prolonged activity, which predicts the risk of oncogenesis by generating chromosomal double-strand breaks. Safety concerns associated with prolonged transpositional activity draw attention to the importance of squeezing the active state of the transposase enzymes into a narrower time window.}, year = {2023}, eissn = {2329-0501}, pages = {145-159}, orcid-numbers = {Vásárhelyi, Bálint Márk/0000-0003-1782-8691; Pankotai-Bodó, Gabriella/0000-0001-5548-6026; Kovács, Anita Kármen/0000-0001-9805-1647; Barta, Endre/0000-0002-6753-0714} } @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: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}, abstract = {Background: Insects have specialized cell types that participate in the elimination of parasites, for instance, the lamellocytes of the broadly studied species Drosophila melanogaster. Other drosophilids, such as Drosophila ananassae and the invasive Zaprionus indianus, have multinucleated giant hemocytes, a syncytium of blood cells that participate in the encapsulation of the eggs or larvae of parasitoid wasps. These cells can be formed by the fusion of hemocytes in circulation or originate from the lymph gland. Their ultrastructure highly resembles that of the mammalian megakaryocytes. Methods: Morphological, protein expressional, and functional features of blood cells were revealed using epifluorescence and confocal microscopy. The respective hemocyte subpopulations were identified using monoclonal antibodies in indirect immunofluorescence assays. Fluorescein isothiocyanate (FITC)-labeled Escherichia coli bacteria were used in phagocytosis tests. Gene expression analysis was performed following mRNA sequencing of blood cells. Results: D. ananassae and Z. indianus encapsulate foreign particles with the involvement of multinucleated giant hemocytes and mount a highly efficient immune response against parasitoid wasps. Morphological, protein expressional, and functional assays of Z. indianus blood cells suggested that these cells could be derived from large plasmatocytes, a unique cell type developing specifically after parasitoid wasp infection. Transcriptomic analysis of blood cells, isolated from naïve and wasp-infected Z. indianus larvae, revealed several differentially expressed genes involved in signal transduction, cell movements, encapsulation of foreign targets, energy production, and melanization, suggesting their role in the anti-parasitoid response. A large number of genes that encode proteins associated with coagulation and wound healing, such as phenoloxidase activity factor-like proteins, fibrinogen-related proteins, lectins, and proteins involved in the differentiation and function of platelets, were constitutively expressed. The remarkable ultrastructural similarities between giant hemocytes and mammalian megakaryocytes, and presence of platelets, and giant cell- derived anucleated fragments at wound sites hint at the involvement of this cell subpopulation in wound healing processes, in addition to participation in the encapsulation reaction. Conclusion: Our observations provide insights into the broad repertoire of blood cell functions required for efficient defense reactions to maintain the homeostasis of the organism. The analysis of the differentiation and function of multinucleated giant hemocytes gives an insight into the diversification of the immune mechanisms.}, 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: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:34557941, title = {No variant tranythyretin amyloidosis is found in a large non-red-flag selected cardiomyopathy population}, url = {https://m2.mtmt.hu/api/publication/34557941}, author = {Takács, Hedvig and Nagy, Viktória and Borbás, János and Csányi, Beáta and Hategan, Lídia and Nagy, I. and Hegedűs, Zoltán and Sepp, Róbert}, journal-iso = {EUR J HEART FAIL}, journal = {EUROPEAN JOURNAL OF HEART FAILURE}, volume = {25}, unique-id = {34557941}, issn = {1388-9842}, year = {2023}, eissn = {1879-0844}, pages = {378-379}, orcid-numbers = {Sepp, Róbert/0000-0003-4964-1661} }