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1. Epigenetic modulation via the C-terminal tail of H2A.Z

Author

Imre, László, Nánási, Jr, Péter, Benhamza, Ibtissem, Enyedi, Kata Nóra, Mocsár, Gábor, Bosire, Rosevalentine, Hegedüs, Éva, Niaki, Erfaneh Firouzi, Csóti, Ágota, Darula, Zsuzsanna, Csősz, Éva, Póliska, Szilárd, Scholtz, Beáta, Mező, Gábor, Bacsó, Zsolt, Timmers, H. T. Marc, Kusakabe, Masayuki, Balázs, Margit, Vámosi, György, Ausio, Juan, Cheung, Peter, Tóth, Katalin, Tremethick, David, Harata, Masahiko, and Szabó, Gábor

Published
2024
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5. Analysis of Azathioprine Metabolites in Autoimmune Hepatitis Patient Blood—Method Development and Validation.

Author

Guba, Andrea, Kováts, Patrícia, Mezei, Zoltán A., Papp, Mária, Csősz, Éva, and Kalló, Gergő

Subjects
AUTOIMMUNE hepatitis, MASS spectrometry, LIVER diseases, BLOOD sampling, METABOLITES, LIQUID chromatography-mass spectrometry
Abstract

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease treated by steroids and immunomodulator thiopurine drugs such as azathioprine (AZA). AZA is metabolized in the human body into bioactive forms such as 6-thioguanine (6-TG) and 6-methyl-mercaptopurine (6-MMP). Monitoring the levels of bioactive AZA metabolites is very important for proper treatment of patients. In this study, our aim was to develop and validate a fast and sensitive ultra-high performance liquid chromatography–mass spectrometry (UHPLC–MS) method for the analysis of 6-TG and 6-MMP from blood samples of patients with AIH to monitor the level of these bioactive metabolites. The detection and quantification of the analytes was carried out by Selected Reaction Monitoring (SRM)-based targeted mass spectrometry. The method was validated according to the EMA guidelines. Blood samples from patients with AIH treated with AZA were analysed with the developed method. The method was successfully validated with appropriate accuracy and precision for the target biomolecules and their concentration in the samples from patients with AIH was determined. The developed and validated UHPLC–MS method enables the fast and precise analysis of AZA metabolites. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Embryonic exposure to low concentrations of aflatoxin B1 triggers global transcriptomic changes, defective yolk lipid mobilization, abnormal gastrointestinal tract development and inflammation in zebrafish

Author

Ivanovics, Bence, Gazsi, Gyongyi, Reining, Marta, Berta, Izabella, Poliska, Szilard, Toth, Marta, Domokos, Apolka, Nagy, Bela, Jr, Staszny, Adam, Cserhati, Matyas, Csosz, Eva, Bacsi, Attila, Csenki-Bakos, Zsolt, Acs, Andras, Urbanyi, Bela, and Czimmerer, Zsolt

Published
2021
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10. Examination of the Complex Molecular Landscape in Obesity and Type 2 Diabetes.

Author

Vadadokhau, Uladzislau, Varga, Imre, Káplár, Miklós, Emri, Miklós, and Csősz, Éva

Subjects
TYPE 2 diabetes, METABOLOMICS, OBESITY, PROTEOMICS, METABOLIC disorders, MULTIOMICS, BLOOD proteins, PRECISION farming
Abstract

The escalating prevalence of metabolic disorders, notably type 2 diabetes (T2D) and obesity, presents a critical global health challenge, necessitating deeper insights into their molecular underpinnings. Our study integrates proteomics and metabolomics analyses to delineate the complex molecular landscapes associated with T2D and obesity. Leveraging data from 130 subjects, including individuals with T2D and obesity as well as healthy controls, we elucidate distinct molecular signatures and identify novel biomarkers indicative of disease progression. Our comprehensive characterization of cardiometabolic proteins and serum metabolites unveils intricate networks of biomolecular interactions and highlights differential protein expression patterns between T2D and obesity cohorts. Pathway enrichment analyses reveal unique mechanisms underlying disease development and progression, while correlation analyses elucidate the interplay between proteomics, metabolomics, and clinical parameters. Furthermore, network analyses underscore the interconnectedness of cardiometabolic proteins and provide insights into their roles in disease pathogenesis. Our findings may help to refine diagnostic strategies and inform the development of personalized interventions, heralding a new era in precision medicine and healthcare innovation. Through the integration of multi-omics approaches and advanced analytics, our study offers a crucial framework for deciphering the intricate molecular underpinnings of metabolic disorders and paving the way for transformative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection

Author

Linkner, Tamás Richárd, primary, Ambrus, Viktor, additional, Kunkli, Balázs, additional, Szojka, Zsófia Ilona, additional, Kalló, Gergő, additional, Csősz, Éva, additional, Kumar, Ajneesh, additional, Emri, Miklós, additional, Tőzsér, József, additional, and Mahdi, Mohamed, additional

Published
2023
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14. Corrigendum: Human abdominal subcutaneous-derived active beige adipocytes carrying FTO rs1421085 obesity-risk alleles exert lower thermogenic capacity

Author

Vámos, Attila, primary, Arianti, Rini, additional, Vinnai, Boglárka Ágnes, additional, Alrifai, Rahaf, additional, Shaw, Abhirup, additional, Póliska, Szilárd, additional, Guba, Andrea, additional, Csősz, Éva, additional, Csomós, István, additional, Mocsár, Gábor, additional, Lányi, Cecilia, additional, Balajthy, Zoltán, additional, Fésüs, László, additional, and Kristóf, Endre, additional

Published
2023
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18. Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection.

Author

Linkner, Tamás Richárd, Ambrus, Viktor, Kunkli, Balázs, Szojka, Zsófia Ilona, Kalló, Gergő, Csősz, Éva, Kumar, Ajneesh, Emri, Miklós, Tőzsér, József, and Mahdi, Mohamed

Subjects
HIV, CELL analysis, CELL adhesion, TRANSCRIPTOMES, PROTEOMICS, COMPARATIVE studies, PROTEIN expression
Abstract

In spite of the similar structural and genomic organization of human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2), striking differences exist between them in terms of replication dynamics and clinical manifestation of infection. Although the pathomechanism of HIV-1 infection is well characterized, relatively few data are available regarding HIV-2 viral replication and its interaction with host–cell proteins during the early phase of infection. We utilized proteo-transcriptomic analyses to determine differential genome expression and proteomic changes induced by transduction with HIV-1/2 pseudovirions during 8, 12 and 26 h time-points in HEK-293T cells. We show that alteration in the cellular milieu was indeed different between the two pseudovirions. The significantly higher number of genes altered by HIV-2 in the first two time-points suggests a more diverse yet subtle effect on the host cell, preparing the infected cell for integration and latency. On the other hand, GO analysis showed that, while HIV-1 induced cellular oxidative stress and had a greater effect on cellular metabolism, HIV-2 mostly affected genes involved in cell adhesion, extracellular matrix organization or cellular differentiation. Proteomics analysis revealed that HIV-2 significantly downregulated the expression of proteins involved in mRNA processing and translation. Meanwhile, HIV-1 influenced the cellular level of translation initiation factors and chaperones. Our study provides insight into the understudied replication cycle of HIV-2 and enriches our knowledge about the use of HIV-based lentiviral vectors in general. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Cross-Linking Mass Spectrometry on P-Glycoprotein

Author

Gellen, Gabriella, primary, Klement, Eva, additional, Biwott, Kipchumba, additional, Schlosser, Gitta, additional, Kalló, Gergő, additional, Csősz, Éva, additional, Medzihradszky, Katalin F., additional, and Bacso, Zsolt, additional

Published
2023
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20. Hemoglobin oxidation generates globin-derived peptides in atherosclerotic lesions and intraventricular hemorrhage of the brain, provoking endothelial dysfunction

Author

Posta, Niké, Csősz, Éva, Oros, Melinda, Pethő, Dávid, Potor, László, Kalló, Gergő, Hendrik, Zoltán, Sikura, Katalin Éva, Méhes, Gábor, Tóth, Csaba, Posta, József, Balla, György, and Balla, József

Abstract

The lysis of red blood cells was shown to occur in human ruptured atherosclerotic lesions and intraventricular hemorrhage (IVH) of the brain. Liberated cell-free hemoglobin was found to undergo oxidation in both pathologies. We hypothesize that hemoglobin-derived peptides are generated during hemoglobin oxidation both in complicated atherosclerotic lesions and IVH of the brain, triggering endothelial cell dysfunction. Oxidized hemoglobin and its products were followed with spectrophotometry, LC–MS/MS analysis and detection of the cross-linking of globin chains in complicated atherosclerotic lesions of the human carotid artery and the hemorrhaged cerebrospinal liquid of preterm infants. The vascular pathophysiologic role of oxidized hemoglobin and the resultant peptides was assessed by measuring endothelial integrity, the activation of endothelial cells and the induction of proinflammatory genes. Peptide fragments of hemoglobin (VNVDEVGGEALGRLLVVYPWTQR, LLVVYPWTQR, MFLSFPTTK, VGAHAGEYGAELERMFLSFPTTK, and FLASVSTVLTSKYR) were identified in ruptured atherosclerotic lesions and in IVH of the human brain. Fragments resulting from the oxidation of hemoglobin were accompanied by the accumulation of ferryl hemoglobin. Similar to complicated atherosclerotic lesions of the human carotid artery, a high level of oxidized and cross-linked hemoglobin was observed in the cerebrospinal fluid after IVH. Haptoglobin inhibited hemoglobin fragmentation provoked by peroxide. The resultant peptides failed to bind haptoglobin or albumin. Peptides derived from hemoglobin oxidation and ferryl hemoglobin induced intercellular gap formation, decreased junctional resistance in the endothelium, and enhanced monocyte adhesion to endothelial cells. Enhanced expression of TNF and the activation of NLRP3 and CASP1 followed by the increased generation of IL-1β and nuclear translocation of the NF-κβ transcription factor occurred in response to hemoglobin-derived peptides, and ferryl hemoglobin in endothelium was upregulated in both pathologies. We conclude that the oxidation of hemoglobin in complicated atherosclerotic lesions and intraventricular hemorrhage of the brain generates peptide fragments and ferryl hemoglobin with the potential to trigger endothelial cell dysfunction.

Published
2024
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24. Human Abdominal Subcutaneous-Derived Active Beige Adipocytes CarryingFTOrs1421085 Obesity-Risk Alleles Exert Lower Thermogenic Capacity

Author

Vámos, Attila, primary, Arianti, Rini, additional, Vinnai, Boglárka Ágnes, additional, Alrifai, Rahaf, additional, Shaw, Abhirup, additional, Póliska, Szilárd, additional, Guba, Andrea, additional, Csősz, Éva, additional, Csomós, István, additional, Mocsár, Gábor, additional, Lányi, Cecilia, additional, Balajthy, Zoltán, additional, Fésüs, László, additional, and Kristóf, Endre, additional

Published
2023
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31. Tissue Transglutaminase Knock-Out Preadipocytes and Beige Cells of Epididymal Fat Origin Possess Decreased Mitochondrial Functions Required for Thermogenesis

Author

Lénárt, Kinga, primary, Bankó, Csaba, additional, Ujlaki, Gyula, additional, Póliska, Szilárd, additional, Kis, Gréta, additional, Csősz, Éva, additional, Miklós, Antal, additional, Bacso, Zsolt, additional, Bai, Péter, additional, Fésüs, László, additional, and Mádi, András, additional

Published
2022
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32. Metabolomic Analysis of Serum and Tear Samples from Patients with Obesity and Type 2 Diabetes Mellitus

Author

Nokhoijav, Erdenetsetseg, primary, Guba, Andrea, additional, Kumar, Ajneesh, additional, Kunkli, Balázs, additional, Kalló, Gergő, additional, Káplár, Miklós, additional, Somodi, Sándor, additional, Garai, Ildikó, additional, Csutak, Adrienne, additional, Tóth, Noémi, additional, Emri, Miklós, additional, Tőzsér, József, additional, and Csősz, Éva, additional

Published
2022
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35. Oxidation of Hemoglobin Drives a Proatherogenic Polarization of Macrophages in Human Atherosclerosis

Author

Potor, László, primary, Hendrik, Zoltán, additional, Patsalos, Andreas, additional, Katona, Éva, additional, Méhes, Gábor, additional, Póliska, Szilárd, additional, Csősz, Éva, additional, Kalló, Gergő, additional, Komáromi, István, additional, Combi, Zsolt, additional, Posta, Niké, additional, Sikura, Katalin Éva, additional, Pethő, Dávid, additional, Oros, Melinda, additional, Vereb, György, additional, Tóth, Csaba, additional, Gergely, Péter, additional, Nagy, László, additional, Balla, György, additional, and Balla, József, additional

Published
2021
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36. ASC‐1 transporter‐dependent amino acid uptake is required for the efficient thermogenic response of human adipocytes to adrenergic stimulation

Author

Arianti, Rini, primary, Vinnai, Boglárka Ágnes, additional, Tóth, Beáta B., additional, Shaw, Abhirup, additional, Csősz, Éva, additional, Vámos, Attila, additional, Győry, Ferenc, additional, Fischer‐Posovszky, Pamela, additional, Wabitsch, Martin, additional, Kristóf, Endre, additional, and Fésüs, László, additional

Published
2021
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40. Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres

Author

Alvarado, Gerardo, Tóth, Attila, Csősz, Éva, Kalló, Gergő, Dankó, Katalin, Csernátony, Zoltán, Smith, Ann, Gram, Magnus, Akerström, Bo, Édes, István, Balla, György, Papp, Zoltán, and Balla, József

Subjects
contractile dysfunction, hemopexin, oxidation, Muscle Fibers, Skeletal, skeletal muscle myopathy, Muscle Proteins, α1-microglobulin, sulfhydryl groups, Mass Spectrometry, Article, sulfenic acid formation, chronic heart failure, lcsh:Chemistry, Myofibrils, skeletal muscle fibre, lcsh:Biology (General), lcsh:QD1-999, Humans, Calcium, Amino Acid Sequence, Cysteine, heme, Oxidation-Reduction, lcsh:QH301-705.5, Muscle Contraction
Abstract

Background: Heme released from red blood cells targets a number of cell components including the cytoskeleton. The purpose of the present study was to determine the impact of free heme (20&ndash, 300 &micro, M) on human skeletal muscle fibres made available during orthopedic surgery. Methods: Isometric force production and oxidative protein modifications were monitored in permeabilized skeletal muscle fibre segments. Results: A single heme exposure (20 &micro, M) to muscle fibres decreased Ca2+-activated maximal (active) force (Fo) by about 50% and evoked an approximately 3-fold increase in Ca2+-independent (passive) force (Fpassive). Oxidation of sulfhydryl (SH) groups was detected in structural proteins (e.g., nebulin, &alpha, actinin, meromyosin 2) and in contractile proteins (e.g., myosin heavy chain and myosin-binding protein C) as well as in titin in the presence of 300 &micro, M heme. This SH oxidation was not reversed by dithiothreitol (50 mM). Sulfenic acid (SOH) formation was also detected in the structural proteins (nebulin, &alpha, actinin, meromyosin). Heme effects on SH oxidation and SOH formation were prevented by hemopexin (Hpx) and &alpha, 1-microglobulin (A1M). Conclusions: These data suggest that free heme has a significant impact on human skeletal muscle fibres, whereby oxidative alterations in structural and contractile proteins limit contractile function. This may explain and or contribute to the weakness and increase of skeletal muscle stiffness in chronic heart failure, rhabdomyolysis, and other hemolytic diseases. Therefore, therapeutic use of Hpx and A1M supplementation might be effective in preventing heme-induced skeletal muscle alterations.

Published
2020

48. Comparative analysis of cytokine profiles of glaucomatous tears and aqueous humour reveals potential biomarkers for trabeculectomy complications

Author

Csősz, Éva, Deák, Eszter, Tóth, Noémi, Traverso, Carlo Enrico, Csutak, Adrienne, and Tőzsér, József

Subjects
Adult, Male, genetic structures, tear, trabeculectomy, aqueous humour, biomarker, cytokine profile, glaucoma, Orvostudományok, Middle Aged, eye diseases, Aqueous Humor, Postoperative Complications, Tears, Cytokines, Humans, Female, Elméleti orvostudományok, sense organs, Biomarkers, Research Articles, Aged, Research Article
Abstract

Glaucoma is a multifactorial neurodegenerative disease that causes impaired vision and, in advanced cases, blindness. The increasing prevalence of glaucoma due to an ageing population has necessitated the identification of suitable biomarkers for the early detection of the disease. Aqueous humour (AH) has been proposed as a source of biomarkers, but it can only be collected using a minor, yet invasive surgical intervention. Tears, however, are constantly available and can be collected any time via noninvasive methods. In order to examine the utility of tear as a surrogate for aqueous humour in biomarker development, we compared the levels of 27 cytokines and chemokines in paired samples of tear and aqueous humour using a Luminex multiplex immunobead‐based technique. Significantly higher levels of cytokines in tear compared to aqueous humour were detected suggesting that tear and aqueous humour are not identical in terms of inflammation response. Furthermore, the levels of IFN‐γ, GM‐CSF and IL‐5 in tear were significantly lower in patients who developed complications after one year, but no statistically significant changes in cytokine levels were observed in aqueous humour. These three molecules may have potential as predictive biomarkers for the appearance of late flap‐related complications of trabeculectomy.

Published
2019

49. Additional file 4: of Analysis of networks of host proteins in the early time points following HIV transduction

Author

Csősz, Éva, Tóth, Ferenc, Mahdi, Mohamed, Tsaprailis, George, Emri, Miklós, and Tőzsér, József

Abstract

Network parameters calculated for functional sub-networks. The y axis show the mean value characteristic for each parameter, and the x axis indicates the time points. Blue color refers to the control, while the yellow color to the HIV-1 treated conditions. N refers to the number of nodes, E to the number of edges, S show network strength, D represents the edge density and R the edge ratio. The f refers to the functional sub-network, the n to the non-functional subnetwork containing the proteins not present in the functional sub-network, while the c refers to the interactions between the functional and the non-functional sub-networks. (PDF 9676 kb)

Published
2019
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50. Wound-Healing Markers Revealed by Proximity Extension Assay in Tears of Patients following Glaucoma Surgery

Author

Csősz, Éva, Tóth, Noémi, Deák, Eszter, Csutak, Adrienne, and Tőzsér, József

Subjects
Aged, 80 and over, Male, tear, Interleukin-6, food and beverages, Trabeculectomy, wound healing, Middle Aged, eye diseases, Article, lcsh:Chemistry, glaucoma, Gene Expression Regulation, lcsh:Biology (General), lcsh:QD1-999, inflammation, Tears, Humans, proximity extension assay, Female, Matrix Metalloproteinase 1, lcsh:QH301-705.5, Biomarkers, Aged
Abstract

Tears are a constantly available and highly valuable body fluid collectable by non-invasive techniques. Although it can give information on ocular status and be used for follow-ups, tear analysis is challenging due to the low amount of sample that is available. Proximity extension assay (PEA) allows for a sensitive and scalable analysis of multiple proteins in a single run from a one-&micro, L sample, so we applied this technique and examined the amount of 184 proteins in tears collected at different time points after trabeculectomy. The success rate of this surgical intervention highly depends on proper wound healing, therefore, information on the process is indispensable. We observed significantly higher levels of IL-6 and MMP1 at the early time points (day one, two, and four) following trabeculectomy, and the protein amounts went back to the level observed before the surgery three months after the intervention. Patients with or without complications were tested, and proteins that have roles in the immune response and wound healing could be observed with altered frequency and amounts in the cases of patients with complications. Our results highlight the importance of inflammation in wound-healing complications, and at the same time, indicate the utility of PEA in tear analysis.

Published
2018

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