TY - JOUR AU - Karkas, Réka AU - Abdullah, Khaldoon Sadiq Ahmed AU - Kaizer, László AU - Ürmös, A AU - Raya, May AU - Tiszlavicz, Lilla Györgyi AU - Pankotai, Tibor AU - Nagy, István AU - Mátés, Lajos AU - Sükösd, Farkas TI - LINE-1 ORF1p is a Promising Biomarker in Cervical Intraepithelial Neoplasia Degree Assessment JF - INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY J2 - INT J GYNECOL PATHOL VL - 44 PY - 2025 IS - 1 SP - 22 EP - 30 PG - 9 SN - 0277-1691 DO - 10.1097/PGP.0000000000001035 UR - https://m2.mtmt.hu/api/publication/34883229 ID - 34883229 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Fund, Hungary [2021-1.1.4-GYORSITOSAV- 2022-00018]; New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund, Hungary [UNKP-23-3] Funding text: The project was, in part, funded by the 2021-1.1.4-GYORSITOSAV- 2022-00018 project of the National Research, Development and Innovation Fund, Hungary. R.K. was supported by the UNKP-23-3 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund, Hungary. AB - Cervical intraepithelial neoplasia (CIN) represents a spectrum of preinvasive squamous lesions within the cervical epithelium, whose identification is a diagnostic challenge due to subtle histomorphological differences among its categories. This study explores ORF1p, a nucleic acid-binding protein derived from long interspersed nuclear element-1 (LINE-1), as a potential biomarker for enhancing CIN diagnosis. A comprehensive analysis of 143 cervical specimens, encompassing CIN I (n=20), CIN II (n=46), CIN III (n=14), invasive cancer (n=32), and nondysplastic cases (normal cervical epithelia (n=24) and atrophy (n=7) were conducted. ORF1p, Ki67, and p16 expressions were evaluated using immunohistochemistry. ORF1p immunopositivity was detected in the vast majority [110/112 (98.2%)] of dysplastic and neoplastic (CIN and invasive cancer) specimens, whereas 19/24 (79.2%) of normal cervical specimens lacked ORF1p expression. The observed pattern of ORF1p expression showed a progressively increasing extent and intensity with advancing CIN grades. CIN I exhibited mild ORF1p expression in the lower one or two-thirds of the cervical epithelium [14/16 (87.5%)], whereas CIN II demonstrated moderate to strong ORF1p expression spanning the lower two-thirds [29/46 (63.0%)]. Pronounced transepithelial ORF1p immunopositivity characterized CIN III cases [13/14 (92.8%)] and cervical cancer [30/32 (93.8%)]. These findings propose ORF1p as a valuable indicator even for detecting CIN I, effectively discerning them from normal cervical tissue (p < 0.0001). Our findings underscore the potential of ORF1p as an early diagnostic marker for cervical neoplasia. LA - English DB - MTMT ER - TY - THES AU - Zombori-Tóth, Noémi TI - Current clinicopathological challenges of lung cancer [A tüdődaganatok aktuális klinikopatológiai kihívásai] PB - Szegedi Tudományegyetem PY - 2025 SP - 73 DO - 10.14232/phd.12169 UR - https://m2.mtmt.hu/api/publication/35064816 ID - 35064816 LA - English DB - MTMT ER - TY - JOUR AU - Martins, Ana AU - Judák, Fanni Orsolya AU - Farkas, Zoltán AU - Szili, Petra AU - Grézal, Gábor AU - Csörgő, Bálint AU - Czikkely, Márton Simon AU - Maharramov, Elvin AU - Daruka, Lejla AU - Spohn, Réka AU - Balogh, Dávid AU - Daraba, Andreea AU - Juhász, Szilvia AU - Vágvölgyi, Máté AU - Hunyadi, Attila AU - Cao, Yihui AU - Sun, Zhenquan AU - Li, Xuechen AU - Papp, Balázs AU - Pál, Csaba TI - Antibiotic candidates for Gram-positive bacterial infections induce multidrug resistance JF - SCIENCE TRANSLATIONAL MEDICINE J2 - SCI TRANSL MED VL - 17 PY - 2025 IS - 780 PG - 12 SN - 1946-6234 DO - 10.1126/scitranslmed.adl2103 UR - https://m2.mtmt.hu/api/publication/35680190 ID - 35680190 N1 - Synthetic and Systems Biology Unit, institute of Biochemistry, HUn-ren Biological research centre Szeged, Szeged, HU-6726, Hungary institute of pharmacognosy, Faculty of pharmacy, University of Szeged, Szeged, HU-6720, Hungary doctoral School of pharmaceutical Sciences, University of Szeged, Szeged, HU-6720, Hungary HceMM-Brc Metabolic Systems Biology lab, Szeged, HU-6726, Hungary doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, HU-6722, Hungary department of Forensic Medicine, albert-Szent-Györgyi Medical School, University of Szeged, Szeged, HU-6722, Hungary doctoral School of Biology, University of Szeged, Szeged, HU-6726, Hungary cancer Microbiome core Group, Hungarian centre of excellence for Molecular Medicine (HceMM), Szeged, HU-6728, Hungary HUn-ren-SZTe Biologically active natural products research Group, Szeged, HU-6720, Hungary department of chemistry, State Key lab of Synthetic chemistry, Hong Kong University, pokfulam road, Hong Kong, Hong Kong Export Date: 16 February 2025 Correspondence Address: Martins, A.; Synthetic and Systems Biology Unit, Hungary; email: ana.martins@brc.hu Correspondence Address: Pál, C.; Synthetic and Systems Biology Unit, Hungary; email: cpal@brc.hu Chemicals/CAS: afabicin, 1518800-35-5; daptomycin, 103060-53-3; lefamulin, 1061337-51-6, 1350636-82-6; linezolid, 165800-03-3; oritavancin, 171099-57-3, 192564-14-0; oxacillin, 1173-88-2, 66-79-5, 7240-38-2; teixobactin, 1613225-53-8; vancomycin, 1404-90-6, 1404-93-9; Anti-Bacterial Agents; Daptomycin; Depsipeptides; teixobactin Tradenames: GraphPad Prism 9, Graphpad; version 4.3.2, R Foundation Manufacturers: Graphpad; R Foundation AB - Several antibiotic candidates are in development against Gram-positive bacterial pathogens, but their long-term utility is unclear. To investigate this issue, we studied the laboratory evolution of resistance to antibiotics that have not yet reached the market. We found that, with the exception of compound SCH79797, antibiotic resistance generally readily evolves in Staphylococcus aureus . Cross-resistance was detected between such candidates and antibiotics currently in clinical use, including vancomycin, daptomycin, and the promising antibiotic candidate teixobactin. These patterns were driven by overlapping molecular mechanisms through mutations in regulatory systems. In particular, teixobactin-resistant bacteria displayed clinically relevant multidrug resistance and retained their virulence in an invertebrate infection model, raising concerns. More generally, we demonstrate that putative resistance mutations against candidate antibiotics are already present in natural bacterial populations. Therefore, antibiotic resistance in nature may evolve readily from the selection of preexisting genetic variants. Our work highlights the importance of predicting future evolution of resistance to antibiotic candidates at an early stage of drug development. LA - English DB - MTMT ER - TY - JOUR AU - Daruka, Lejla AU - Czikkely, Márton Simon AU - Szili, Petra AU - Farkas, Zoltán AU - Balogh, Dávid AU - Grézal, Gábor AU - Maharramov, Elvin AU - Vu, Thu-Hien AU - Sipos, Levente AU - Juhász, Szilvia AU - Dunai, Anett AU - Daraba, Andreea AU - Számel, Mónika AU - Sári, Tóbiás AU - Stirling, Tamás AU - Vásárhelyi, Bálint Márk AU - Ari, Eszter AU - Christodoulou, Chryso AU - Manczinger, Máté AU - Enyedi, Márton Zsolt AU - Jaksa, Gábor AU - Kovács, Károly AU - van Houte, Stineke AU - Pursey, Elizabeth AU - Pintér, Lajos AU - Haracska, Lajos AU - Kintses, Bálint AU - Papp, Balázs AU - Pál, Csaba TI - ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro JF - NATURE MICROBIOLOGY J2 - NAT MICROBIOL VL - 10 PY - 2025 IS - 2 SP - 313 EP - 331 PG - 19 SN - 2058-5276 DO - 10.1038/s41564-024-01891-8 UR - https://m2.mtmt.hu/api/publication/35685373 ID - 35685373 N1 - Funding Agency and Grant Number: European Research Council; National Laboratory of Biotechnology Grant [2022-2.1.1-NL-2022-00008]; National Research Development and Innovation Office 'Elvonal' Programme KKP [126506]; National Research, Development and Innovation Office [K146323, FK-135245, RRF-2.3.1-21-2022-00015, TKP-31-8/PALY-2021]; National Research, Development and Innovation Office 'Elvonal' program KKP [KH125616]; National Laboratory for Health Security [RRF-2.3.1-21-2022-00006]; European Union [739593]; Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences [BO/352/20, bo_656_20]; New National Excellence Program of the Ministry of Human Capacities; Proof-of-Concept grant of the Eoetvoes Lorand Research Network [ELKH-PoC-2022-034]; New National Excellence Program of the Ministry for Culture and Innovation [UNKP-22-2-SZTE-220, UNKP-23-3-SZTE-272]; National Academy of Scientist Education under the sponsorship of the Hungarian Ministry of Culture and Innovation; University Research Scholarship Program Grant under the sponsorship of the Hungarian Ministry of Culture and Innovation [EKOEP-KDP-24-SZTE-13]; National Research, Development and Innovation Office, Hungary (NKFIH) [131839, FK-142312, FK-131961]; National Research, Development and Innovation Office, Hungary (NKFIH) KIM NKFIA [TKP-2021-EGA-05, 2022-2.1.1-NL-2022-00005, H2020-WIDESPREA-01-2016-2017-TeamingPhase2, 739593-HCEMM]; New National Excellence Program of the Ministry of Human Capacities Bolyai+ [UNKP-22-5-SZTE-578-Bolyai+]; Lister Institute for Preventative Medicine; [ERC-2023-ADG 101142626]; [UNKP-20-5-SZTE-654]; [UNKP-21-5-SZTE-579] Funding text: We thank A. Kobl for her help with illustrations in Extended Data Fig. 1. This work was supported by The European Research Council ERC-2023-ADG 101142626 FutureAntibiotics (C.P.); The National Laboratory of Biotechnology Grant 2022-2.1.1-NL-2022-00008 (C.P., B.K. and B.P.); National Research Development and Innovation Office 'Elvonal' Programme KKP 126506 (C.P.); National Research, Development and Innovation Office K146323 (C.P.); National Research, Development and Innovation Office 'Elvonal' program KKP KH125616 (B.P.); The National Laboratory for Health Security RRF-2.3.1-21-2022-00006 (B.P.); The European Union's Horizon 2020 research and innovation programme under grant agreement number 739593 (B.K., B.P. and M.M.); National Research, Development and Innovation Office grant FK-135245 (B.K.); Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences (BO/352/20; B.K.); New National Excellence Program of the Ministry of Human Capacities (UNKP-20-5-SZTE-654 and UNKP-21- 5-SZTE-579; B.K.); Proof-of-Concept grant of the Eoetvoes Lorand Research Network (ELKH-PoC-2022-034; B.K.); The New National Excellence Program of the Ministry for Culture and Innovation (UNKP-22-2-SZTE-220 and UNKP-23-3-SZTE-272; M.S.C.); The National Academy of Scientist Education under the sponsorship of the Hungarian Ministry of Culture and Innovation (M.S.C.); University Research Scholarship Program Grant under the sponsorship of the Hungarian Ministry of Culture and Innovation (EKOEP-KDP-24-SZTE-13; M.S.C.); The National Research, Development and Innovation Office, Hungary (NKFIH) grant PD, grant number 131839 (E.A.); The National Research, Development and Innovation Office, Hungary (NKFIH) grant FK-142312 (M.M.); The National Research, Development and Innovation Office, Hungary (NKFIH) KIM NKFIA TKP-2021-EGA-05 (S.J.); The National Research, Development and Innovation Office, Hungary (NKFIH) KIM NKFIA 2022-2.1.1-NL-2022-00005 (S.J.); H2020-WIDESPREA-01-2016-2017-TeamingPhase2, GA:739593-HCEMM (S.J.); The National Research, Development and Innovation Office, Hungary (NKFIH) grant FK-131961 (S.J.); The New National Excellence Program of the Ministry of Human Capacities Bolyai+, UNKP-22-5-SZTE-578-Bolyai+ (S.J.); The Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences bo_656_20 (S.J.); The Lister Institute for Preventative Medicine (S.v.H.); and The National Research, Development and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015 and TKP-31-8/PALY-2021; L.H.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. LA - English DB - MTMT ER - TY - THES AU - Zsikai, Bettina Ágnes TI - Bridging the gap between experimental and human sepsis: Porcine models for sepsis research with improved clinical relevance [Klinikailag releváns sertésmodell kifejlesztése a kísérletes és humán szepszis közötti eltérések áthidalására] PB - Szegedi Tudományegyetem PY - 2025 SP - 75 DO - 10.14232/phd.12367 UR - https://m2.mtmt.hu/api/publication/36134328 ID - 36134328 LA - English DB - MTMT ER - TY - THES AU - László, Ildikó TI - Effects of goal-directed fluid therapy on microcirculation during human study and animal experiment [A célzott folyadékterápia hatásai a mikrocirkulációra: állat kísérletben és klinikai vizsgálatban] PB - Szegedi Tudományegyetem PY - 2025 SP - 71 DO - 10.14232/phd.12358 UR - https://m2.mtmt.hu/api/publication/36134774 ID - 36134774 AB - Fluid resuscitation remains one of the cornerstone’s in the management of acute bleeding. According to Starling's “Three-compartment model”, four-times more crystalloids (Cryst) have the same volume-replacement (VR) effect as colloids (Coll). However, this VR ratio remains a controversial issue as it may be affected by the degradation of the endothelial glycocalyx layer (GX), a situation often found in the critically ill. On the other hand, macro- and microcirculatory effects of solutions are difficult to compare, because the endpoints of resuscitation seldom based on similar criteria. Our aims were: (1) to compare the effects of Coll and Cryst based fluid resuscitation during an experimental stroke volume index (SVI) guided haemorrhage and resuscitation animal model; (2) to investigate the effects of Cryst and Coll’s on the microcirculation during free flap surgery when management was guided by detailed haemodynamic assessment. In our animal experiment, anesthetized and mechanically ventilated pigs were randomised to receive Coll or Cryst infusion. Animals were bled until baseline SVI (Tbsl) dropped by 50% (T0), followed by resuscitation until initial SVI was reached (T4) in four steps. In our clinical trial patients undergoing maxillofacial tumour resection and free flap reconstruction were randomised into groups treated with either intra-operative Cryst or Coll solutions. In the animal experiment, hemodynamic changes and GX degradation products serum levels followed similar pattern without significant difference between the groups. Animals received significantly less resuscitation fluid in the Coll as compared to the Cryst-group. In the clinical trial there was no difference between the groups regarding patient characteristics. Both groups remained haemodynamically stable throughout, but patients in the Cryst group required approximately 1.5 times more total fluid volume than in the Coll group. There was no significant difference in the microcirculatory blood flow between the groups as indicated by laser-Doppler flowmetry. We concluded that: (1) volume-replacement ratio for solutions follows the Starling's principle when the GX is intact, and (2) when fluid management is guided by detailed haemodynamic assessment there was no difference between the effects of solutions on the microcirculation, hence it may not be the type of the fluid, but the appropriate VR caused haemodynamic stability and perfusion that is responsible for microcirculatory blood flow. LA - English DB - MTMT ER - TY - THES AU - Fejes, Roland TI - Temporal changes of the microcirculatory-mitochondrial functions in experimental rodent sepsis [A mikrokeringési és mitokondriális funkciók időbeli változásainak vizsgálata kísérletes rágcsáló szepszis modellben] PB - Szegedi Tudományegyetem PY - 2025 SP - 56 DO - 10.14232/phd.12377 UR - https://m2.mtmt.hu/api/publication/36136239 ID - 36136239 LA - English DB - MTMT ER - TY - THES AU - Fabó, Csongor TI - The role of preserved spontaneous breathing during thoracic surgery [A megtartott spontán légzés szerepe mellkassebészeti beavatkozások során] PB - Szegedi Tudományegyetem PY - 2025 SP - 68 DO - 10.14232/phd.11975 UR - https://m2.mtmt.hu/api/publication/36137015 ID - 36137015 LA - English DB - MTMT ER - TY - THES AU - Borbás, János TI - Clinical and genetic analysis of rare ion channel diseases [Ritka ioncsatorna betegségek klinikai és genetikai elemzése] PB - Szegedi Tudományegyetem PY - 2025 SP - 72 DO - 10.14232/phd.12255 UR - https://m2.mtmt.hu/api/publication/36137071 ID - 36137071 LA - English DB - MTMT ER - TY - THES AU - Barna, Tamara TI - Investigation of potential tocolytic combinations of terbutaline with magnesium sulfate and sildenafil in pregnant rat model [A terbutalin magnézium-szulfáttal és szildenafillal történő vizsgálata patkánymodellen, mint új, potenciális tokolitikus kombinációk] PB - Szegedi Tudományegyetem PY - 2025 SP - 42 DO - 10.14232/phd.12225 UR - https://m2.mtmt.hu/api/publication/36137111 ID - 36137111 LA - English DB - MTMT ER -