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 N1 - Seqomics Biotechnology Ltd, Mórahalom, Hungary Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Pécs, Hungary Department of Immunology and Biotechnology, University of Pécs, Pécs, Hungary Lymphoid Organogenesis Research Group, Szentágothai János Research Center, University of Pécs, Pécs, Hungary Cited By :4 Export Date: 17 December 2024 Correspondence Address: Nagy, I.; Seqomics Biotechnology LtdHungary; email: nagyi@baygen.hu 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 - Veres, Balázs AU - Erős, Krisztián AU - Antus, Csenge Petra AU - Kálmán, Nikoletta AU - Fónai, Fruzsina AU - Jakus, Péter AU - Boros, Éva AU - Hegedűs, Zoltán AU - Nagy, István AU - Tretter, László AU - Gallyas, Ferenc AU - Sümegi, Balázs TI - Cyclophilin D-dependent mitochondrial permeability transition amplifies inflammatory reprogramming in endotoxemia JF - FEBS OPEN BIO J2 - FEBS OPEN BIO VL - 11 PY - 2021 IS - 3 SP - 684 EP - 704 PG - 21 SN - 2211-5463 DO - 10.1002/2211-5463.13091 UR - https://m2.mtmt.hu/api/publication/31822211 ID - 31822211 N1 - Department of Biochemistry and Medical Chemistry, Medical School, University of Pecs, Hungary MTA-PTE Nuclear-Mitochondrial Interactions Research Group, Pecs, Hungary Szentagothai Janos Research Center, University of Pecs, Hungary Institute of Biochemistry, Biological Research Centre, Szeged, Hungary Institute of Biophysics, Biological Research Centre, Szeged, Hungary SeqOmics Biotechnology Ltd, Morahalom, Hungary Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary Cited By :14 Export Date: 10 October 2024 Correspondence Address: Veres, B.; Department of Biochemistry and Medical Chemistry, Hungary; email: balazs.veres@aok.pte.hu AB - Microorganisms or LPS (lipopolysaccharide), an outer membrane component of Gram-negative bacteria, can induce a systemic inflammatory response that leads to sepsis, multiple organ dysfunction, and mortality. Here, we investigated the role of cyclophilin D (CypD)-dependent mitochondrial permeability transition (mPT) in the immunosuppressive phase of LPS-induced endotoxic shock. The liver plays an important role in immunity and organ dysfunction; therefore, we used liver RNA sequencing (RNAseq) data, Ingenuity® Pathway Analysis (IPA ® ) to investigate the complex role of mPT formation in inflammatory reprogramming and disease progression. LPS induced significant changes in the expression of 2844 genes, affecting 179 pathways related to mitochondrial dysfunction, defective oxidative phosphorylation, nitric oxide (NO) and reactive oxygen species (ROS) accumulation, nuclear factor, erythroid 2 like 2 (Nrf2), Toll-like receptors (TLRs), and tumor necrosis factor α receptor (TNFR)-mediated processes in wild-type mice. The disruption of CypD reduced LPS-induced alterations in gene expression and pathways involving TNFRs and TLRs, in addition to improving survival and attenuating oxidative liver damage and the related NO- and ROS-producing pathways. CypD deficiency diminished the suppressive effect of LPS on mitochondrial function, nuclear- and mitochondrial-encoded genes, and mitochondrial DNA (mtDNA) quantity, which could be critical in improving survival. Our data propose that CypD-dependent mPT is an amplifier in inflammatory reprogramming and promotes disease progression. The mortality in human sepsis and shock is associated with mitochondrial dysfunction. Prevention of mPT by CypD disruption reduces inflammatory reprogramming, mitochondrial dysfunction, and lethality; therefore, CypD can be a novel drug target in endotoxic shock and related inflammatory diseases. LA - English DB - MTMT ER - TY - JOUR AU - Boros, Éva AU - Prontvai, Bence AU - Kellermayer, Zoltán AU - Balogh, Péter AU - Sarlós, Patrícia AU - Vincze, Áron AU - Varga, Csaba AU - Maróti, Zoltán AU - Bálint, Balázs AU - Nagy, István TI - Transcriptome Based Profiling of the Immune Cell Gene Signature in Rat Experimental Colitis and Human IBD Tissue Samples JF - BIOMOLECULES J2 - BIOMOLECULES VL - 10 PY - 2020 IS - 7 PG - 21 SN - 2218-273X DO - 10.3390/biom10070974 UR - https://m2.mtmt.hu/api/publication/31368904 ID - 31368904 N1 - Institute of Biochemistry, Biological Research Centre, Szeged, 6726, Hungary Department of Immunology and Biotechnology, University of Pécs, Pécs, 7624, Hungary Lymphoid Organogenesis Research Group, Szentágothai János Research Center, University of Pécs, Pécs, 7624, Hungary 1st Department of Internal Medicine, Medical School, University of Pécs, Pécs, 7624, Hungary Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, 6726, Hungary Institute of Pediatrics and Pediatric Health Center, University of Szeged, Szeged, 6720, Hungary Seqomics Biotechnology Ltd., Mórahalom, 6782, Hungary Cited By :5 Export Date: 17 December 2024 Correspondence Address: Nagy, I.; Institute of Biochemistry, Hungary; email: nagyi@baygen.hu Correspondence Address: Nagy, I.; Seqomics Biotechnology Ltd.Hungary; email: nagyi@baygen.hu AB - Chronic intestinal inflammation is characteristic of Inflammatory Bowel Disease (IBD) that is associated with the exaggerated infiltration of immune cells. A complex interplay of inflammatory mediators and different cell types in the colon are responsible for the maintenance of tissue homeostasis and affect pathological conditions. Gene expression alteration of colon biopsies from IBD patients and an in vivo rat model of colitis were examined by RNA-Seq and QPCR, while we used in silico methods, such as Ingenuity Pathway Analysis (IPA) application and the Immune Gene Signature (ImSig) package of R, to interpret whole transcriptome data and estimate immune cell composition of colon tissues. Transcriptome profiling of in vivo colitis model revealed the most significant activation of signaling pathways responsible for leukocyte recruitment and diapedesis. We observed significant alteration of genes related to glycosylation or sensing of danger signals and pro- and anti-inflammatory cytokines and chemokines, as well as adhesion molecules. We observed the elevated expression of genes that implies the accumulation of monocytes, macrophages, neutrophils and B cells in the inflamed colon tissue. In contrast, the rate of T-cells slightly decreased in the inflamed regions. Interestingly, natural killer and plasma cells do not show enrichment upon colon inflammation. In general, whole transcriptome analysis of the in vivo experimental model of colitis with subsequent bioinformatics analysis provided a better understanding of the dynamic changes in the colon tissue of IBD patients. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Liliána AU - Váradi, Györgyi AU - Boros, Éva AU - Borics, Attila AU - Ficze, Hargita AU - Nagy, István AU - Tóth, Gábor AU - Rákhely, Gábor AU - Marx, Florentine AU - Galgóczi, László Norbert TI - Biofungicidal Potential of Neosartorya (Aspergillus) Fischeri Antifungal Protein NFAP and Novel Synthetic γ-Core Peptides JF - FRONTIERS IN MICROBIOLOGY J2 - FRONT MICROBIOL VL - 11 PY - 2020 PG - 13 SN - 1664-302X DO - 10.3389/fmicb.2020.00820 UR - https://m2.mtmt.hu/api/publication/31312066 ID - 31312066 AB - Because of enormous crop losses worldwide due to pesticide-resistant plant pathogenic fungi, there is an increasing demand for the development of novel antifungal strategies in agriculture. Antifungal proteins (APs) and peptides are considered potential biofungicides; however, several factors limit their direct agricultural application, such as the high cost of production, narrow antifungal spectrum, and detrimental effects to plant development and human/animal health. This study evaluated the safety of the application of APs and peptides from the ascomycete Neosartorya fischeri as crop preservatives. The full-length N. fischeri AP (NFAP) and novel rationally designed γ-core peptide derivatives (PDs) γNFAP-opt and γNFAP-optGZ exhibited efficacy by inhibiting the growth of the agriculturally relevant filamentous ascomycetes in vitro. A high positive net charge, however, neither the hydrophilicity nor the primary structure supported the antifungal efficacy of these PDs. Further testing demonstrated that the antifungal activity did not require a conformational change of the β-pleated NFAP or the canonically ordered conformation of the synthetic PDs. Neither hemolysis nor cytotoxicity was observed when the NFAP and γNFAP-opt were applied at antifungally effective concentrations in human cell lines. Similarly, the Medicago truncatula plants that served as toxicity model and were grown from seedlings that were treated with NFAP, γNFAP-opt, or γNFAP-optGZ failed to exhibit morphological aberrations, reduction in primary root length, or the number of lateral roots. Crop protection experiments demonstrated that NFAP and associated antifungal active γ-core PDs were able to protect tomato fruits against the postharvest fungal pathogen Cladosporium herbarum. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Liliána AU - Boros, Éva AU - Poór, Péter AU - Ördög, Attila AU - Kele, Zoltán AU - Váradi, Györgyi AU - Holzknecht, Jeanett AU - Bratschun-Khan, Doris AU - Nagy, István AU - Tóth, Gábor AU - Rákhely, Gábor AU - Marx, Florentine AU - Galgóczi, László Norbert TI - The potential use of the Penicillium chrysogenum antifungal protein PAF, the designed variant PAFopt and its γ-core peptide Pγopt in plant protection. JF - MICROBIAL BIOTECHNOLOGY J2 - MICROB BIOTECHNOL VL - 13 PY - 2020 IS - 5 SP - 1403 EP - 1414 PG - 12 SN - 1751-7907 DO - 10.1111/1751-7915.13559 UR - https://m2.mtmt.hu/api/publication/31259936 ID - 31259936 AB - The prevention of enormous crop losses caused by pesticide-resistant fungi is a serious challenge in agriculture. Application of alternative fungicides, such as antifungal proteins and peptides, provides a promising basis to overcome this problem; however, their direct use in fields suffers limitations, such as high cost of production, low stability, narrow antifungal spectrum and toxicity on plant or mammalian cells. Recently, we demonstrated that a Penicillium chrysogenum-based expression system provides a feasible tool for economic production of P. chrysogenum antifungal protein (PAF) and a rational designed variant (PAFopt ), in which the evolutionary conserved γ-core motif was modified to increase antifungal activity. In the present study, we report for the first time that γ-core modulation influences the antifungal spectrum and efficacy of PAF against important plant pathogenic ascomycetes, and the synthetic γ-core peptide Pγopt , a derivative of PAFopt , is antifungal active against these pathogens in vitro. Finally, we proved the protective potential of PAF against Botrytis cinerea infection in tomato plant leaves. The lack of any toxic effects on mammalian cells and plant seedlings, as well as the high tolerance to harsh environmental conditions and proteolytic degradation further strengthen our concept for applicability of these proteins and peptide in agriculture. LA - English DB - MTMT ER - TY - JOUR AU - Boros, Éva AU - Nagy, István TI - The Role of MicroRNAs upon Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease JF - CELLS J2 - CELLS-BASEL VL - 8 PY - 2019 IS - 11 PG - 20 SN - 2073-4409 DO - 10.3390/cells8111461 UR - https://m2.mtmt.hu/api/publication/30924452 ID - 30924452 AB - Increasing evidence suggest the significance of inflammation in the progression of cancer, for example the development of colorectal cancer in Inflammatory Bowel Disease (IBD) patients. Long-lasting inflammation in the gastrointestinal tract causes serious systemic complications and breaks the homeostasis of the intestine, where the altered expression of regulatory genes and miRNAs trigger malignant transformations. Several steps lead from acute inflammation to malignancies: epithelial-to-mesenchymal transition (EMT) and inhibitory microRNAs (miRNAs) are known factors during multistage carcinogenesis and IBD pathogenesis. In this review, we outline the interactions between EMT components and miRNAs that may affect cancer development during IBD. LA - English DB - MTMT ER - TY - CHAP AU - Tóth, Liliána AU - Váradi, Györgyi AU - Boros, Éva AU - Ficze, Hargita AU - Nagy, I AU - Marx, F AU - Galgóczi, László Norbert ED - Monostori, Tamás TI - Agricultural Applicability of Neosartorya Fischeri Antifungal Protein and De Novo Designed Peptide Derivatives T2 - 17th Wellmann International Scientific Conference PB - University of Szeged Faculty of Agriculture C1 - Hódmezővásárhely SN - 9789633066539 PY - 2019 SP - 75 EP - 76 PG - 2 UR - https://m2.mtmt.hu/api/publication/30736794 ID - 30736794 LA - English DB - MTMT ER - TY - CHAP AU - Tóth, Liliána AU - Sonderegger, C AU - Boros, Éva AU - Nagy, I AU - Bratschun-Khan, D AU - Marx, F AU - Galgóczi, László Norbert ED - Monostori, Tamás TI - Applicability of Penicillium Chrysogenum Antifungal Protein and Its Rational Designed Variant in Plant Protection T2 - 17th Wellmann International Scientific Conference PB - University of Szeged Faculty of Agriculture C1 - Hódmezővásárhely SN - 9789633066539 PY - 2019 SP - 73 EP - 74 PG - 2 UR - https://m2.mtmt.hu/api/publication/30736772 ID - 30736772 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Liliána AU - Váradi, Györgyi AU - Boros, Éva AU - Nagy, I AU - Marx, F. AU - Galgóczi, László Norbert TI - In Vitro Cytotoxic Effect of Penicillium Chysogenum Antifungal Protein, Its De Novo Rational Designed Protein Variant and Peptide Derivative on Mammalian Cells and Plants JF - ACTA MICROBIOLOGICA ET IMMUNOLOGICA HUNGARICA J2 - ACTA MICROBIOL IMMUNOL HUNG VL - 66 PY - 2019 IS - Suppl. 1 SP - 203 EP - 203 PG - 1 SN - 1217-8950 UR - https://m2.mtmt.hu/api/publication/30735459 ID - 30735459 LA - English DB - MTMT ER - TY - JOUR AU - Boros, Éva AU - Kellermayer, Z AU - Balogh, P AU - Sarlos, P AU - Vincze, A AU - Varga, Csaba AU - Nagy, I TI - Interdependent Gene- and Microrna-Expression Pattern Contributes to the Epithelial to Mesenchymal Transition in Inflammatory Bowel Disease JF - IMMUNOLÓGIAI SZEMLE J2 - IMMUNOLÓGIAI SZEMLE VL - 10 PY - 2018 IS - 3 SP - 9 EP - 9 PG - 1 SN - 2061-0203 UR - https://m2.mtmt.hu/api/publication/30604007 ID - 30604007 LA - English DB - MTMT ER -