@article{MTMT:34627084, title = {Rational Design of Antifungal Peptides Based on the γ-Core Motif of a Neosartorya (Aspergillus) fischeri Antifungal Protein to Improve Structural Integrity, Efficacy, and Spectrum}, url = {https://m2.mtmt.hu/api/publication/34627084}, author = {Váradi, Györgyi and Bende, Gábor and Borics, Attila and Dán, Kinga and Rákhely, Gábor and Tóth, Gábor and Galgóczi, László Norbert}, doi = {10.1021/acsomega.3c09377}, journal-iso = {ACS OMEGA}, journal = {ACS OMEGA}, volume = {9}, unique-id = {34627084}, issn = {2470-1343}, year = {2024}, eissn = {2470-1343}, pages = {7206-7214}, orcid-numbers = {Váradi, Györgyi/0000-0001-7907-8908; Rákhely, Gábor/0000-0003-2557-3641; Tóth, Gábor/0000-0002-3604-4385; Galgóczi, László Norbert/0000-0002-6976-8910} } @article{MTMT:34395398, title = {Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy}, url = {https://m2.mtmt.hu/api/publication/34395398}, author = {Dinh, Hoa and Kovács, Zsuzsanna and Kis, Merse and Kupecz, Klaudia and Sejben, Anita and Szűcs, Gergő and Márványkövi, Fanni and Siska, Andrea and Freiwan, Marah and Pósa, Szonja Polett and Galla, Zsolt and Ibos, Katalin Eszter and Bodnár, Éva and Lauber, Gülsüm Yilmaz and Goncalves, Ana Isabel Antunes and Acar, Eylem and Kriston, András and Kovács, Ferenc and Horváth, Péter and Bozsó, Zsolt and Tóth, Gábor and Földesi, Imre and Monostori, Péter and Cserni, Gábor and Podesser, Bruno K. and Lehoczki, Andrea Marianna and Pokreisz, Peter and Kiss, Attila and Dux, László and Csabafi, Krisztina and Sárközy, Márta}, doi = {10.1007/s11357-023-01017-8}, journal-iso = {GEROSCIENCE}, journal = {GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE)}, volume = {46}, unique-id = {34395398}, issn = {2509-2715}, abstract = {The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300–350 g) were randomized into four groups: (I) sham-operated, (II) 5/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction’s echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory ( Il6, Tnf ), fibrosis ( Col1 ), and apoptosis markers ( Bax/Bcl2 ) relative to the CKD group. In summary, KP-13’s influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle.}, year = {2024}, eissn = {2509-2723}, pages = {2463-2488}, orcid-numbers = {Kovács, Zsuzsanna/0000-0002-4197-4579; Sejben, Anita/0000-0002-9434-2989; Szűcs, Gergő/0000-0003-1874-2718; Márványkövi, Fanni/0000-0002-5114-1319; Pósa, Szonja Polett/0000-0002-7535-9689; Galla, Zsolt/0000-0002-9166-1212; Ibos, Katalin Eszter/0000-0001-5243-9945; Goncalves, Ana Isabel Antunes/0009-0009-3428-3321; Acar, Eylem/0000-0002-0599-6893; Kriston, András/0000-0001-8500-4315; Bozsó, Zsolt/0000-0002-5713-3096; Tóth, Gábor/0000-0002-3604-4385; Földesi, Imre/0000-0002-3329-8136; Monostori, Péter/0000-0003-3591-6054; Cserni, Gábor/0000-0003-1344-7744; Podesser, Bruno K./0000-0002-4641-7202; Lehoczki, Andrea Marianna/0000-0002-4285-7518; Pokreisz, Peter/0000-0003-2810-9000; Kiss, Attila/0000-0003-4652-1998; Dux, László/0000-0002-1270-1678; Csabafi, Krisztina/0000-0002-2008-7604; Sárközy, Márta/0000-0002-5929-2146} } @article{MTMT:34444233, title = {Impact Assessment of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and Hemostatic Sponge on Vascular Anastomosis Regeneration in Rats}, url = {https://m2.mtmt.hu/api/publication/34444233}, author = {Fazekas, László Ádám and Szabó, Balázs and Szegeczki, Vince and Fillér, Csaba and Varga , Ádám and Godó, Zoltán Attila and Tóth, Gábor and Reglődi, Dóra and Juhász, Tamás and Németh, Norbert}, doi = {10.3390/ijms242316695}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {34444233}, issn = {1661-6596}, abstract = {The proper regeneration of vessel anastomoses in microvascular surgery is crucial for surgical safety. Pituitary adenylate cyclase-activating polypeptide (PACAP) can aid healing by decreasing inflammation, apoptosis and oxidative stress. In addition to hematological and hemorheological tests, we examined the biomechanical and histological features of vascular anastomoses with or without PACAP addition and/or using a hemostatic sponge (HS). End-to-end anastomoses were established on the right femoral arteries of rats. On the 21st postoperative day, femoral arteries were surgically removed for evaluation of tensile strength and for histological and molecular biological examination. Effects of PACAP were also investigated in tissue culture in vitro to avoid the effects of PACAP degrading enzymes. Surgical trauma and PACAP absorption altered laboratory parameters; most notably, the erythrocyte deformability decreased. Arterial wall thickness showed a reduction in the presence of HS, which was compensated by PACAP in both the tunica media and adventitia in vivo. The administration of PACAP elevated these parameters in vitro. In conclusion, the application of the neuropeptide augmented elastin expression while HS reduced it, but no significant alterations were detected in collagen type I expression. Elasticity and tensile strength increased in the PACAP group, while it decreased in the HS decreased. Their combined use was beneficial for vascular regeneration.}, keywords = {PACAP; Biomechanics; Microsurgery; tensile strength; Hemorheology; Vascular anastomosis; Vascular regeneration}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Tóth, Gábor/0000-0002-3604-4385; Németh, Norbert/0000-0002-1162-3778} } @article{MTMT:34145694, title = {Conjugation with Tris Decreases the Risk of Ketoprofen-Induced Mucosal Damage and Reduces Inflammation-Associated Methane Production in a Rat Model of Colitis}, url = {https://m2.mtmt.hu/api/publication/34145694}, author = {Ugocsai, Melinda and Bársony, Anett and Varga, Réka A. and Gajda, Ámos and Vida, Noémi and Lajkó, Norbert and Rónaszéki, Benedek and Tóth, Gábor and Boros, Mihály and Érces, Dániel and Varga, Gabriella}, doi = {10.3390/pharmaceutics15092329}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {15}, unique-id = {34145694}, issn = {1999-4923}, abstract = {We have designed a new compound from the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (Ket) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors, with the aim to reduce the gastrointestinal (GI) side effects of NSAID therapies. We investigated mucosal reactions in a standard rat model of colitis together with methane generation as a possible indicator of pro-inflammatory activation under this condition (approval number: V./148/2013). Whole-body methane production (photoacoustic spectroscopy) and serosal microcirculation (intravital videomicroscopy) were measured, and mucosal damage was assessed (conventional histology; in vivo laser-scanning endomicroscopy). Inflammatory markers were measured from tissue and blood samples. Colitis induced an inflammatory response, morphological colonic damage and increased methane output. Ket treatment lowered inflammatory activation and colonic mucosal injury, but macroscopic gastric bleeding and increased methane output were present. Ket-Tris reduced inflammatory activation, methane emission and colonic mucosal damage, without inducing gastric injury. Conjugation with Tris reduces the GI side effects of Ket and still decreases the inflammatory response in experimental colitis. Methane output correlates with the mucosal inflammatory response and non-invasively demonstrates the effects of anti-inflammatory treatments.}, keywords = {Inflammation; MICROCIRCULATION; MUCOSA; TNBS colitis; Non-steroid anti-inflammatory drugs; methane generation; rat}, year = {2023}, eissn = {1999-4923}, orcid-numbers = {Tóth, Gábor/0000-0002-3604-4385; Boros, Mihály/0000-0003-1410-1999; Érces, Dániel/0000-0002-4283-2441; Varga, Gabriella/0000-0003-1888-8629} } @article{MTMT:34117220, title = {Protective Effects of Pituitary Adenylate-Cyclase-Activating Polypeptide on Retinal Vasculature and Molecular Responses in a Rat Model of Moderate Glaucoma}, url = {https://m2.mtmt.hu/api/publication/34117220}, author = {Patkó, Evelin Viktória and Szabó, Edina and Váczy, Alexandra and Molitor, Dorottya and Tari, Eniko and Li, Lina and Csutak, Adrienne and Tóth, Gábor and Reglődi, Dóra and Atlasz, Tamás}, doi = {10.3390/ijms241713256}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {34117220}, issn = {1661-6596}, abstract = {Despite the high probability of glaucoma-related blindness, its cause is not fully understood and there is no efficient therapeutic strategy for neuroprotection. Vascular factors have been suggested to play an important role in glaucoma development and progression. Previously, we have proven the neuroprotective effects of pituitary adenylate-cyclase-activating polypeptide (PACAP) eye drops in an inducible, microbeads model in rats that is able to reproduce many clinically relevant features of human glaucoma. In the present study, we examined the potential protective effects of PACAP1-38 on the retinal vasculature and the molecular changes in hypoxia. Ocular hypertension was induced by injection of microbeads into the anterior chamber, while control rats received PBS. PACAP dissolved in vehicle (1 µg/drop) or vehicle treatment was started one day after the injections for four weeks three times a day. Retinal degeneration was assessed with optical coherence tomography (OCT), and vascular and molecular changes were assessed by immunofluorescence labeling. HIF1-α and VEGF-A protein levels were measured by Western blot. OCT images proved severe retinal degeneration in the glaucomatous group, while PACAP1-38 eye drops had a retinoprotective effect. Vascular parameters were deteriorated and molecular analysis suggested hypoxic conditions in glaucoma. PACAP treatment exerted a positive effect against these alterations. In summary, PACAP could prevent the severe damage to the retina and its vasculature induced by ocular hypertension in a microbeads model.}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Tóth, Gábor/0000-0002-3604-4385; Atlasz, Tamás/0000-0002-8112-8633} } @article{MTMT:34043893, title = {Hard nut to crack: Solving the disulfide linkage pattern of the Neosartorya (Aspergillus) fischeri antifungal protein 2}, url = {https://m2.mtmt.hu/api/publication/34043893}, author = {Váradi, Györgyi and Kele, Zoltán and Czajlik, András and Borics, Attila and Bende, Gábor and Papp, Csaba Gergő and Rákhely, Gábor and Tóth, Gábor and Batta, Gyula and Galgóczi, László Norbert}, doi = {10.1002/pro.4692}, journal-iso = {PROTEIN SCI}, journal = {PROTEIN SCIENCE}, volume = {32}, unique-id = {34043893}, issn = {0961-8368}, abstract = {As a consequence of the fast resistance spreading, a limited number of drugs are available to treat fungal infections. Therefore, there is an urgent need to develop new antifungal treatment strategies. The features of a disulfide bond-stabilized antifungal protein, NFAP2 secreted by the mold Neosartorya (Aspergillus) fischeri render it to be a promising template for future protein-based antifungal drug design, which requires knowledge about the native disulfide linkage pattern as it is one of the prerequisites for biological activity. However, in the lack of tryptic and chymotryptic proteolytic sites in the ACNCPNNCK sequence, the determination of the disulfide linkage pattern of NFAP2 is not easy with traditional mass spectrometry-based methods. According to in silico predictions working with a preliminary nuclear magnetic resonance (NMR) solution structure, two disulfide isomers of NFAP2 (abbacc and abbcac) were possible. Both were chemically synthesized; and comparative reversed-phase high-performance liquid chromatography, electronic circular dichroism and NMR spectroscopy analyses, and antifungal susceptibility and efficacy tests indicated that the abbcac is the native pattern. This knowledge allowed rational modification of NAFP2 to improve the antifungal efficacy and spectrum through the modulation of the evolutionarily conserved gamma-core region, which is responsible for the activity of several antimicrobial peptides. Disruption of the steric structure of NFAP2 upon gamma-core modification led to the conclusions that this motif may affect the formation of the biologically active three-dimensional structure, and that the gamma-core modulation is not an efficient tool to improve the antifungal efficacy or to change the antifungal spectrum of NFAP2.}, keywords = {DYNAMICS; PREDICTION; DRUG DESIGN; BONDS; protein structure; ANTIFUNGAL PROTEIN; disulfide linkage pattern}, year = {2023}, eissn = {1469-896X}, orcid-numbers = {Váradi, Györgyi/0000-0001-7907-8908; Kele, Zoltán/0000-0002-4401-0302; Papp, Csaba Gergő/0000-0003-4450-0667; Rákhely, Gábor/0000-0003-2557-3641; Tóth, Gábor/0000-0002-3604-4385; Batta, Gyula/0000-0002-0442-1828; Galgóczi, László Norbert/0000-0002-6976-8910} } @article{MTMT:34043118, title = {Proline cis/trans Isomerization in Intrinsically Disordered Proteins and Peptides}, url = {https://m2.mtmt.hu/api/publication/34043118}, author = {Sebák, Fanni and Szolomájer, János and Papp, Nándor and Tóth, Gábor and Bodor, Andrea}, doi = {10.31083/j.fbl2806127}, journal-iso = {FRONT BIOSCI-LANDMARK}, journal = {FRONTIERS IN BIOSCIENCE-LANDMARK}, volume = {28}, unique-id = {34043118}, issn = {2768-6701}, year = {2023}, eissn = {2768-6698}, orcid-numbers = {Sebák, Fanni/0000-0001-9252-9961; Szolomájer, János/0000-0003-1458-6156; Tóth, Gábor/0000-0002-3604-4385; Bodor, Andrea/0000-0002-7422-298X} } @article{MTMT:33773509, title = {A 80 éves Penke Botond köszöntése}, url = {https://m2.mtmt.hu/api/publication/33773509}, author = {Szűcs, Mária and Tóth, Gábor}, journal-iso = {MAGY KEM LAP}, journal = {MAGYAR KÉMIKUSOK LAPJA}, volume = {78}, unique-id = {33773509}, issn = {0025-0163}, year = {2023}, eissn = {1588-1199}, pages = {95} } @CONFERENCE{MTMT:33748284, title = {Biocontrol ability of rationally designed peptide derivatives of a novel Solanum lycopersicum L. antifungal defensin}, url = {https://m2.mtmt.hu/api/publication/33748284}, author = {Hilda, Vass and Váradi, Györgyi and Kele, Zoltán and Gábor, Rákhely and Poór, Péter and Tóth, Gábor and Galgóczi, László Norbert and Tóth, Liliána}, booktitle = {16th European Conference on Fungal Genetics: Programme & Abstracts}, unique-id = {33748284}, year = {2023}, pages = {478-479}, orcid-numbers = {Váradi, Györgyi/0000-0001-7907-8908; Kele, Zoltán/0000-0002-4401-0302; Poór, Péter/0000-0002-4539-6358; Tóth, Gábor/0000-0002-3604-4385; Galgóczi, László Norbert/0000-0002-6976-8910; Tóth, Liliána/0000-0003-1400-6174} } @article{MTMT:33676645, title = {Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Aspergillus giganteus Antifungal Protein, AFP}, url = {https://m2.mtmt.hu/api/publication/33676645}, author = {Váradi, Györgyi and Batta, Gyula and Galgóczi, László Norbert and Hajdu, Dorottya Zsuzsanna and Fizil, Ádám and Czajlik, András and Virágh, Máté and Kele, Zoltán and Meyer, Vera and Jung, Sascha and Marx, Florentine and Tóth, Gábor}, doi = {10.1021/acs.jnatprod.2c00954}, journal-iso = {J NAT PROD}, journal = {JOURNAL OF NATURAL PRODUCTS}, volume = {86}, unique-id = {33676645}, issn = {0163-3864}, abstract = {Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from Aspergillus giganteus with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared using native chemical ligation. The native protein was synthesized via oxidative folding with uniform protection for cysteine thiols. AFP's biological activity depends heavily on the pattern of natural disulfide bonds. Enzymatic digestion and MS analysis provide proof for interlocking disulfide topology (abcdabcd) that was previously assumed. With this knowledge, a semi-orthogonal thiol protection method was designed. By following this strategy, out of a possible 105, only 6 disulfide isomers formed and 1 of them proved to be identical with the native protein. This approach allows the synthesis of analogs for examining structure-activity relationships and, thus, preparing AFP variants with higher antifungal activity.}, year = {2023}, eissn = {1520-6025}, pages = {782-790}, orcid-numbers = {Váradi, Györgyi/0000-0001-7907-8908; Batta, Gyula/0000-0002-0442-1828; Galgóczi, László Norbert/0000-0002-6976-8910; Fizil, Ádám/0000-0002-4815-5744; Virágh, Máté/0000-0002-2278-1288; Kele, Zoltán/0000-0002-4401-0302; Meyer, Vera/0000-0002-2298-2258; Tóth, Gábor/0000-0002-3604-4385} }