@article{MTMT:34536265,
	title = {Sources of Variance in Human Tear Proteomic Samples: Statistical Evaluation, Quality Control, Normalization, and Biological Insight},
	url = {https://m2.mtmt.hu/api/publication/34536265},
	author = {Bruszel, Bella and Tóth-Molnár, Edit and Janáky, Tamás and Szabó, Zoltán},
	doi = {10.3390/ijms25031559},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34536265},
	issn = {1661-6596},
	abstract = {Human tear fluid contains numerous compounds, which are present in highly variable amounts owing to the dynamic and multipurpose functions of tears. A better understanding of the level and sources of variance is essential for determining the functions of the different tear components and the limitations of tear samples as a potential biomarker source. In this study, a quantitative proteomic method was used to analyze variations in the tear protein profiles of healthy volunteers. High day-to-day and inter-eye personal variances were observed in the tear volumes, protein content, and composition of the tear samples. Several normalization and outlier exclusion approaches were evaluated to decrease variances. Despite the intrapersonal variances, statistically significant differences and cluster analysis revealed that proteome profile and immunoglobulin composition of tear fluid present personal characteristics. Using correlation analysis, we could identify several correlating protein clusters, mainly related to the source of the proteins. Our study is the first attempt to achieve more insight into the biochemical background of human tears by statistical evaluation of the experimentally observed dynamic behavior of the tear proteome. As a pilot study for determination of personal protein profiles of the tear fluids of individual patients, it contributes to the application of this noninvasively collectible body fluid in personal medicine.},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {Tóth-Molnár, Edit/0000-0001-7989-1616; Janáky, Tamás/0000-0002-6466-8283; Szabó, Zoltán/0000-0001-8278-8038}
}

@book{MTMT:34407280,
	title = {Bevezetés a proteomikába : a fehérjék korszerű vizsgálata},
	url = {https://m2.mtmt.hu/api/publication/34407280},
	isbn = {9789633316009},
	author = {Csősz, Éva and Darula, Zsuzsanna and Drahos, László and Emri, Miklós and Hunyadi-Gulyás, Éva and Janáky, Tamás and Juhász, Gábor and Kalló, Gergő and Kékesi, Adrienna Katalin and Klement, Éva and Márk, László and Medzihradszky, F. Katalin and Pettkó-Szandtner, Aladár and Rokobné Révész, Ágnes and Schlosser, Gitta (Vácziné) and Szabó, Zoltán and Tóth, Gábor and Turiák, Lilla},
	publisher = {Semmelweis Egyetem},
	unique-id = {34407280},
	year = {2023},
	orcid-numbers = {Rokobné Révész, Ágnes/0000-0002-6221-1239; Schlosser, Gitta (Vácziné)/0000-0002-7637-7133; Szabó, Zoltán/0000-0001-8278-8038}
}

@article{MTMT:34231255,
	title = {Extracellular vesicle-mediated intercellular communication in cancer},
	url = {https://m2.mtmt.hu/api/publication/34231255},
	author = {Harmati, Mária and Bukva, Mátyás and Dobra, Gabriella and Gyukity-Sebestyén, Edina and Böröczky, Timea and Szabó, Zoltán and Kónya, Zoltán and Horvath, Peter and Klekner, Almos and Buzás, Krisztina},
	journal-iso = {EUR J IMMUNOL},
	journal = {EUROPEAN JOURNAL OF IMMUNOLOGY},
	volume = {53},
	unique-id = {34231255},
	issn = {0014-2980},
	year = {2023},
	eissn = {1521-4141},
	pages = {39-40},
	orcid-numbers = {Harmati, Mária/0000-0002-4875-5723; Bukva, Mátyás/0000-0002-5225-0285; Dobra, Gabriella/0000-0002-2814-7720; Gyukity-Sebestyén, Edina/0000-0003-1383-6301; Böröczky, Timea/0009-0009-3390-7809; Szabó, Zoltán/0000-0001-8278-8038; Kónya, Zoltán/0000-0002-9406-8596; Buzás, Krisztina/0000-0001-8933-2033}
}

@article{MTMT:34131836,
	title = {Antiproliferative and Antimetastatic Properties of 16-Azidomethyl Substituted 3-O-Benzyl Estrone Analogs},
	url = {https://m2.mtmt.hu/api/publication/34131836},
	author = {Senobar Tahaei, Seyyed Ashkan and Kulmány, Ágnes Erika and Minorics, Renáta and Kiss, Anita and Szabó, Zoltán and Germán, Péter and Szebeni, Gábor and Gémes, Nikolett and Mernyák, Erzsébet and Zupkó, István},
	doi = {10.3390/ijms241813749},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {34131836},
	issn = {1661-6596},
	abstract = {Four diastereomers of 16-azidomethyl substituted 3-O-benzyl estradiol (1–4) and their two estrone analogs (16AABE and 16BABE) were tested for their antiproliferative properties against human gynecological cancer cell lines. The estrones were selected for additional experiments based on their outstanding cell growth-inhibiting activities. Both compounds increased hypodiploid populations of breast cancer cells, and 16AABE elicited cell cycle disturbance as evidenced by flow cytometry. The two analogs substantially increased the rate of tubulin polymerization in vitro. 16AABE and 16BABE inhibited breast cancer cells’ migration and invasive ability, as evidenced by wound healing and Boyden chamber assays. Since both estrone analogs exerted remarkable estrogenic activities, as documented by a luciferase reporter gene assay, they can be considered as promising drug candidates for hormone-independent malignancies.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Minorics, Renáta/0000-0001-9685-813X; Kiss, Anita/0000-0003-3352-0996; Szabó, Zoltán/0000-0001-8278-8038; Szebeni, Gábor/0000-0002-6998-5632; Mernyák, Erzsébet/0000-0003-4494-1817; Zupkó, István/0000-0003-3243-5300}
}

@article{MTMT:33712712,
	title = {Structural Adaptation of the Single-Stranded DNA-Binding Protein C-Terminal to DNA Metabolizing Partners Guides Inhibitor Design},
	url = {https://m2.mtmt.hu/api/publication/33712712},
	author = {Tököli, Attila and Bodnár, Brigitta and Bogár, Ferenc and Paragi, Gábor and Hetényi, Anasztázia and Bartus, Éva and Wéber, Edit and Hegedüs, Zsófia and Szabó, Zoltán and Kecskeméti, Gábor and Szakonyi, Gerda and Martinek, Tamás},
	doi = {10.3390/pharmaceutics15041032},
	journal-iso = {PHARMACEUTICS},
	journal = {PHARMACEUTICS},
	volume = {15},
	unique-id = {33712712},
	issn = {1999-4923},
	abstract = {Single-stranded DNA-binding protein (SSB) is a bacterial interaction hub and an appealing target for antimicrobial therapy. Understanding the structural adaptation of the disordered SSB C-terminus (SSB-Ct) to DNA metabolizing enzymes (e.g., ExoI and RecO) is essential for designing high-affinity SSB mimetic inhibitors. Molecular dynamics simulations revealed the transient interactions of SSB-Ct with two hot spots on ExoI and RecO. The residual flexibility of the peptide–protein complexes allows adaptive molecular recognition. Scanning with non-canonical amino acids revealed that modifications at both termini of SSB-Ct could increase the affinity, supporting the two-hot-spot binding model. Combining unnatural amino acid substitutions on both segments of the peptide resulted in enthalpy-enhanced affinity, accompanied by enthalpy–entropy compensation, as determined by isothermal calorimetry. NMR data and molecular modeling confirmed the reduced flexibility of the improved affinity complexes. Our results highlight that the SSB-Ct mimetics bind to the DNA metabolizing targets through the hot spots, interacting with both of segments of the ligands.},
	year = {2023},
	eissn = {1999-4923},
	orcid-numbers = {Tököli, Attila/0000-0001-8413-3182; Bogár, Ferenc/0000-0002-0611-1452; Paragi, Gábor/0000-0001-5408-1748; Hetényi, Anasztázia/0000-0001-8080-6992; Bartus, Éva/0000-0001-9976-6978; Wéber, Edit/0000-0002-5904-0619; Hegedüs, Zsófia/0000-0002-5546-8167; Szabó, Zoltán/0000-0001-8278-8038; Kecskeméti, Gábor/0000-0002-5584-6869; Szakonyi, Gerda/0000-0002-4366-4283; Martinek, Tamás/0000-0003-3168-8066}
}

@article{MTMT:33592853,
	title = {MMP-9 as Prognostic Marker for Brain Tumours: A Comparative Study on Serum-Derived Small Extracellular Vesicles},
	url = {https://m2.mtmt.hu/api/publication/33592853},
	author = {Dobra, Gabriella and Gyukity-Sebestyén, Edina and Bukva, Mátyás and Harmati, Mária and Nagy, Valentina and Szabó, Zoltán and Pankotai, Tibor and Klekner, Álmos and Buzás, Krisztina},
	doi = {10.3390/cancers15030712},
	journal-iso = {CANCERS},
	journal = {CANCERS},
	volume = {15},
	unique-id = {33592853},
	abstract = {Matrix metalloproteinase-9 (MMP-9) degrades the extracellular matrix, contributes to tumour cell invasion and metastasis, and its elevated level in brain tumour tissues indicates poor prognosis. High-risk tissue biopsy can be replaced by liquid biopsy; however, the blood–brain barrier (BBB) prevents tumour-associated components from entering the peripheral blood, making the development of blood-based biomarkers challenging. Therefore, we examined the MMP-9 content of small extracellular vesicles (sEVs)—which can cross the BBB and are stable in body fluids—to characterise tumours with different invasion capacity. From four patient groups (glioblastoma multiforme, brain metastases of lung cancer, meningioma, and lumbar disc herniation as controls), 222 serum-derived sEV samples were evaluated. After isolating and characterising sEVs, their MMP-9 content was measured by ELISA and assessed statistically (correlation, paired t-test, Welch’s test, ANOVA, ROC). We found that the MMP-9 content of sEVs is independent of gender and age, but is affected by surgical intervention, treatment, and recurrence. We found a relation between low MMP-9 level in sEVs (<28 ppm) and improved survival (8-month advantage) of glioblastoma patients, and MMP-9 levels showed a positive correlation with aggressiveness. These findings suggest that vesicular MMP-9 level might be a useful prognostic marker for brain tumours.},
	year = {2023},
	eissn = {2072-6694},
	orcid-numbers = {Dobra, Gabriella/0000-0002-2814-7720; Gyukity-Sebestyén, Edina/0000-0003-1383-6301; Bukva, Mátyás/0000-0002-5225-0285; Harmati, Mária/0000-0002-4875-5723; Szabó, Zoltán/0000-0001-8278-8038; Pankotai, Tibor/0000-0001-9810-5465; Buzás, Krisztina/0000-0001-8933-2033}
}

@article{MTMT:33046603,
	title = {An Extensive Study of Phenol Red Thread as a Novel Non-Invasive Tear Sampling Technique for Proteomics Studies: Comparison with Two Commonly Used Methods},
	url = {https://m2.mtmt.hu/api/publication/33046603},
	author = {Kecskeméti, Gábor and Tóth-Molnár, Edit and Janáky, Tamás and Szabó, Zoltán},
	doi = {10.3390/ijms23158647},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {33046603},
	issn = {1661-6596},
	abstract = {Tear samples are considered in recent publications as easily, noninvasively collectible information sources for precision medicine. Their complex composition may aid the identification of biomarkers and the monitoring of the effectiveness of treatments for the eye and systemic diseases. Sample collection and processing are key steps in any analytical method, especially if subtle personal differences need to be detected. In this work, we evaluate the usability of a novel sample collection technique for human tear samples using phenol red threads (cotton thread treated with the pH indicator phenol red), which are efficiently used to measure tear volume in clinical diagnosis. The low invasiveness and low discomfort to the patients have already been demonstrated, but their applicability for proteomic sample collection has not yet been compared to other methods. We have shown, using various statistical approaches, the qualitative and quantitative differences in proteomic samples collected with this novel and two traditional methods using either glass capillaries or Schirmer’s paper strips. In all parameters studied, the phenol red threads proved to be equally or even more suitable than traditional methods. Based on detectability using different sampling methods, we have classified proteins in tear samples.},
	keywords = {Mass spectrometry; proteomics; LC-MS; tear; data independent analysis},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Kecskeméti, Gábor/0000-0002-5584-6869; Tóth-Molnár, Edit/0000-0001-7989-1616; Janáky, Tamás/0000-0002-6466-8283; Szabó, Zoltán/0000-0001-8278-8038}
}

@article{MTMT:32924828,
	title = {Diet-Induced Hypercholesterolemia Leads to Cardiac Dysfunction and Alterations in the Myocardial Proteome},
	url = {https://m2.mtmt.hu/api/publication/32924828},
	author = {Szabó, Márton Richárd and Pipicz, Márton and Sárközy, Márta and Bruszel, Bella and Szabó, Zoltán and Csont, Tamás Bálint},
	doi = {10.3390/ijms23137387},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {32924828},
	issn = {1661-6596},
	abstract = {Elevated blood cholesterol is a major risk factor for coronary heart disease. Moreover, direct effects on the myocardium also contribute to the adverse effects of hypercholesterolemia. Here, we investigated the effect of hypercholesterolemia on the cardiac proteome. Male Wistar rats were fed with a laboratory rodent chow supplemented with 2% cholesterol for 8 weeks to induce hypercholesterolemia. The protein expression data obtained from the proteomic characterization of left ventricular samples from normo- and hypercholesterolemic animals were subjected to gene ontology (GO) and protein interaction analyses. Elevated circulating cholesterol levels were accompanied by diastolic dysfunction in cholesterol-fed rats. The proteomic characterization of left ventricular samples revealed altered expression of 45 proteins due to hypercholesterolemia. Based on the Gene Ontology analysis, hypercholesterolemia was associated with disturbed expression of cytoskeletal and contractile proteins. Beta-actin was downregulated in the hypercholesterolemic myocardium, and established a prominent hub of the protein interaction network. Analysis of the unfiltered dataset revealed concordant downregulated expression patterns in proteins associated with the arrangement of the contractile system (e.g., cardiac-specific troponins and myosin complex), and in subunits of the mitochondrial respiratory chain. We conclude that the observed changes in the cardiac proteome may contribute to the development of diastolic dysfunction in hypercholesterolemia.},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Szabó, Márton Richárd/0000-0003-0415-5192; Pipicz, Márton/0000-0002-0944-1684; Sárközy, Márta/0000-0002-5929-2146; Szabó, Zoltán/0000-0001-8278-8038; Csont, Tamás Bálint/0000-0001-5792-2768}
}

@article{MTMT:31646463,
	title = {Inhibition of ABCG2/BCRP-mediated transport–correlation analysis of various expression systems and probe substrates},
	url = {https://m2.mtmt.hu/api/publication/31646463},
	author = {Sáfár, Zsolt and Kecskeméti, Gábor and Molnár, Judit and Kurunczi, Anita and Szabó, Zoltán and Janáky, Tamás and Kis, Emese and Krajcsi, Péter},
	doi = {10.1016/j.ejps.2020.105593},
	journal-iso = {EUR J PHARM SCI},
	journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES},
	volume = {156},
	unique-id = {31646463},
	issn = {0928-0987},
	abstract = {BCRP / ABCG2 is a key determinant of pharmacokinetics of substrate drugs. Several BCRP substrates and inhibitors are of low passive permeability, and the vesicular transport assay works well in this permeability space. Membranes were prepared from BCRP-HEK293, MCF-7/MX, and baculovirus-infected Sf9 cells with (BCRP-Sf9-HAM), and without (BCRP-Sf9) cholesterol loading. Km values for three substrates - estrone-3-sulfate, sulfasalazine, topotecan - correlated well between the four expression systems. In contrast, a 10-20-fold range in Vmax values was observed, with BCRP-HEK293 membranes possessing the largest dynamic range. IC50 values of the different test systems were similar to each other, with 94.4% of pairwise comparisons being within 3-fold. Substrate dependent inhibition showed somewhat greater variation, as 81.4% of IC50 values in the BCRP-HEK293 membranes were within 3-fold in pairwise comparisons. Overall, BCRP-HEK293 membranes demonstrated the highest activity. The IC50 values showed good concordance but substrate dependent inhibition was observed for some drugs.},
	keywords = {ABCG2; Vesicular transport; BCRP; HEK293-BCRP; substrate-dependent inhibition},
	year = {2021},
	eissn = {1879-0720},
	orcid-numbers = {Kecskeméti, Gábor/0000-0002-5584-6869; Szabó, Zoltán/0000-0001-8278-8038; Janáky, Tamás/0000-0002-6466-8283; Krajcsi, Péter/0000-0002-4450-5954}
}

@article{MTMT:31666189,
	title = {O-GlcNAcylation Suppresses the Ion Current IClswell by Preventing the Binding of the Protein ICln to α-Integrin},
	url = {https://m2.mtmt.hu/api/publication/31666189},
	author = {Costa, Roberta and Remigante, Alessia and Civello, Davide A. and Bernardinelli, Emanuele and Szabó, Zoltán and Morabito, Rossana and Marino, Angela and Sarikas, Antonio and Patsch, Wolfgang and Paulmichl, Markus and Janáky, Tamás and Miseta, Attila János and Nagy, Tamás and Dossena, Silvia},
	doi = {10.3389/fcell.2020.607080},
	journal-iso = {FRONT CELL DEV BIOL},
	journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY},
	volume = {8},
	unique-id = {31666189},
	issn = {2296-634X},
	abstract = {O-GlcNAcylation is a post-translational modification of proteins that controls a variety of cellular processes, is chronically elevated in diabetes mellitus, and may contribute to the progression of diabetic complications, including diabetic nephropathy. Our previous work showed that increases in the O-GlcNAcylation of cellular proteins impair the homeostatic reaction of the regulatory volume decrease (RVD) after cell swelling by an unknown mechanism. The activation of the swelling-induced chloride current IClswell is a key step in RVD, and ICln, a ubiquitous protein involved in the activation of IClswell, is O-GlcNAcylated. Here, we show that experimentally increased O-GlcNAcylation of cellular proteins inhibited the endogenous as well as the ICln-induced IClswell current and prevented RVD in a human renal cell line, while decreases in O-GlcNAcylation augmented the current magnitude. In parallel, increases or decreases in O-GlcNAcylation, respectively, weakened or stabilized the binding of ICln to the intracellular domain of α-integrin, a process that is essential for the activation of IClswell. Mutation of the putative YinOYang site at Ser67 rendered the ICln-induced IClswell current unresponsive to O-GlcNAc variations, and the ICln interaction with α-integrin insensitive to O-GlcNAcylation. In addition, exposure of cells to a hypotonic solution reduced the O-GlcNAcylation of cellular proteins. Together, these findings show that O-GlcNAcylation affects RVD by influencing IClswell and further indicate that hypotonicity may activate IClswell by reducing the O-GlcNAcylation of ICln at Ser67, therefore permitting its binding to α-integrin. We propose that disturbances in the regulation of cellular volume may contribute to disease in settings of chronically elevated O-GlcNAcylation, including diabetic nephropathy.},
	year = {2020},
	eissn = {2296-634X},
	orcid-numbers = {Szabó, Zoltán/0000-0001-8278-8038; Janáky, Tamás/0000-0002-6466-8283; Miseta, Attila János/0000-0002-7984-3347; Nagy, Tamás/0000-0001-5437-1411}
}