TY - JOUR AU - Szántó, Magdolna AU - Yélamos, J AU - Bay, Péter TI - Specific and shared biological functions of PARP2 – is PARP2 really a lil’ brother of PARP1? JF - EXPERT REVIEWS IN MOLECULAR MEDICINE J2 - EXPERT REV MOL MED PY - 2024 SN - 1462-3994 UR - https://m2.mtmt.hu/api/publication/34817464 ID - 34817464 LA - English DB - MTMT ER - TY - JOUR AU - Szeőcs, Dóra AU - Vida, Beáta AU - Petővári, Gábor AU - Póliska, Szilárd AU - Janka, Eszter Anna AU - Sipos, Adrienn AU - Uray (Davis), Karen L. AU - Sebestyén, Anna AU - Krasznai, Zoárd Tibor AU - Bay, Péter TI - Cell-free ascites from ovarian cancer patients induces Warburg metabolism and cell proliferation through TGFbeta-ERK signalling JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE PY - 2024 PG - 17 SN - 2509-2715 DO - 10.1007/s11357-023-01056-1 UR - https://m2.mtmt.hu/api/publication/34483936 ID - 34483936 N1 - Funding Agency and Grant Number: University of Debrecen; NKFIH [K142141, FK128387, FK146852, TKP2021-EGA-19, TKP2021-EGA-20]; Hungarian Academy of Sciences [POST-COVID2021-33, NKM2022-30]; National Research, Development and Innovation Fund of Hungary [TKP2021-EGA-19, TKP2021-EGA-20]; HUN-REN Hungarian Research Network Funding text: Open access funding provided by University of Debrecen. Our work was supported by grants from NKFIH (K142141, FK128387, FK146852, TKP2021-EGA-19, and TKP2021-EGA-20) and the Hungarian Academy of Sciences (POST-COVID2021-33, NKM2022-30). Project no. TKP2021-EGA-19 and TKP2021-EGA-20 were implemented with support provided by the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme. AS is supported by the Bolyai fellowship of the Hungarian Academy of Sciences. This project received funding from the HUN-REN Hungarian Research Network. AB - Ascites plays a key role in supporting the metastatic potential of ovarian cancer cells. Shear stress and carry-over of cancer cells by ascites flow support carcinogenesis and metastasis formation. In addition, soluble factors may participate in the procarcinogenic effects of ascites in ovarian cancer. This study aimed to determine the biological effects of cell-free ascites on carcinogenesis in ovarian cancer cells. Cell-free ascites from ovarian cancer patients (ASC) non-selectively induced cell proliferation in multiple models of ovarian cancer and untransformed primary human dermal fibroblasts. Furthermore, ASC induced a Warburg-type rearrangement of cellular metabolism in A2780 ovarian cancer cells characterized by increases in cellular oxygen consumption and glycolytic flux; increases in glycolytic flux were dominant. ASC induced mitochondrial uncoupling and fundamentally reduced fatty acid oxidation. Ascites-elicited effects were uniform among ascites specimens. ASC-elicited transcriptomic changes in A2780 ovarian cancer cells included induction of the TGF beta-ERK/MEK pathway, which plays a key role in inducing cell proliferation and oncometabolism. ASC-induced gene expression changes, as well as the overexpression of members of the TGF beta signaling system, were associated with poor survival in ovarian cancer patients. We provided evidence that the activation of the autocrine/paracrine of TGF beta signaling system may be present in bladder urothelial carcinoma and stomach adenocarcinoma. Database analysis suggests that the TGF beta system may feed forward bladder urothelial carcinoma and stomach adenocarcinoma. Soluble components of ASC support the progression of ovarian cancer. These results suggest that reducing ascites production may play an essential role in the treatment of ovarian cancer by inhibiting the progression and reducing the severity of the disease. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Emese AU - Fagyas, Miklós AU - Nagy, Béla AU - Siket, Ivetta Mányiné AU - Szőke, Blanka AU - Mártha, Lilla AU - Mahdi, Mohamed AU - Erdősi, Gábor AU - Pólik, Zsófia AU - Kappelmayer, János AU - Papp, Zoltán AU - Borbély, Attila AU - Szabó, Tamás AU - Balla, József AU - Balla, György AU - Bácsi, Attila AU - Szekanecz, Zoltán AU - Bay, Péter AU - Tóth, Attila TI - Distinct subsets of anti-pulmonary autoantibodies correlate with disease severity and survival in severe COVID-19 patients JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE VL - 46 PY - 2024 IS - 2 SP - 1561 EP - 1574 PG - 14 SN - 2509-2715 DO - 10.1007/s11357-023-00887-2 UR - https://m2.mtmt.hu/api/publication/34148390 ID - 34148390 AB - Autoantibodies targeting the lung tissue were identified in severe COVID-19 patients in this retrospective study. Fifty-three percent of 104 patients developed anti-pulmonary antibodies, the majority of which were IgM class, suggesting that they developed upon infection with SARS-CoV-2. Anti-pulmonary antibodies correlated with worse pulmonary function and a higher risk of multiorgan failure that was further aggravated if 3 or more autoantibody clones were simultaneously present (multi-producers). Multi-producer patients were older than the patients with less or no autoantibodies. One of the identified autoantibodies (targeting a pulmonary protein of ~ 50 kDa) associated with worse clinical outcomes, including mortality. In summary, severe COVID-19 is associated with the development of lung-specific autoantibodies, which may worsen the clinical outcome. Tissue proteome-wide tests, such as the ones applied here, can be used to detect autoimmunity in the post-COVID state to identify the cause of symptoms and to reveal a new target for treatment. LA - English DB - MTMT ER - TY - PAT AU - Bay, Péter AU - Bokor, Éva AU - Somsák, László AU - Kacsir, István AU - Buglyó, Péter AU - Sipos, Adrienn AU - Kardos, Gábor AU - Toth, Zoltan AU - Kis, Gyorgy Attila TI - Half-sandwich transition metal complexes and uses thereof PY - 2023 PG - 188 UR - https://m2.mtmt.hu/api/publication/34449504 ID - 34449504 N1 - A 2021-ben benyújtott és 2022-ben megjelent HU2100326 magyar szabadalom alapján benyújtva 2022-ben. AB - The invention relates to half-sandwich transition metal complexes with general formula (I), (wherein in Me is a transition metal ion selected from the group consisting of Ru, Os, Rh, Ir, Pd and Pt, preferably selected from Ru, Os, Rh, Ir, X is a halogen selected from the group consisting of Cl, Br and I, preferably Cl,Ar is a capping mol. having a Cs or C6 aromatic ring substituted with one or more, preferably one to five or one to six straight or branched chain C1-C6 alkyl, preferably C1-C3 alkyl, resp.); and uses thereof, in particular in neo-plastic diseas or as antifungal agent. LA - English DB - MTMT ER - TY - JOUR AU - Ujlaki, Gyula AU - Kovács, Tünde AU - Vida, András AU - Kókai, Endre AU - Rauch, Boglárka AU - Schwarcz, Szandra AU - Mikó, Edit AU - Janka, Eszter AU - Sipos, Adrienn AU - Hegedűs, Csaba AU - Uray (Davis), Karen L. AU - Nagy, Péter AU - Bay, Péter TI - Identification of Bacterial Metabolites Modulating Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 15 SN - 1420-3049 DO - 10.3390/molecules28155898 UR - https://m2.mtmt.hu/api/publication/34089348 ID - 34089348 AB - Breast cancer patients are characterized by the oncobiotic transformation of multiple microbiome communities, including the gut microbiome. Oncobiotic transformation of the gut microbiome impairs the production of antineoplastic bacterial metabolites. The goal of this study was to identify bacterial metabolites with antineoplastic properties. We constructed a 30-member bacterial metabolite library and screened the library compounds for effects on cell proliferation and epithelial-mesenchymal transition. The metabolites were applied to 4T1 murine breast cancer cells in concentrations corresponding to the reference serum concentrations. However, yric acid, glycolic acid, d-mannitol, 2,3-butanediol, and trans-ferulic acid exerted cytostatic effects, and 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, and vanillic acid exerted hyperproliferative effects. Furthermore, 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 2,3-butanediol, and hydrocinnamic acid inhibited epithelial-to-mesenchymal (EMT) transition. We identified redox sets among the metabolites (d-mannitol—d-mannose, 1-butanol—butyric acid, ethylene glycol—glycolic acid—oxalic acid), wherein only one partner within the set (d-mannitol, butyric acid, glycolic acid) possessed bioactivity in our system, suggesting that changes to the local redox potential may affect the bacterial secretome. Of the nine bioactive metabolites, 2,3-butanediol was the only compound with both cytostatic and anti-EMT properties. LA - English DB - MTMT ER - TY - JOUR AU - Antal, Dóra AU - Pór, Ágnes AU - Kovács, Ilona AU - Dull, Katalin AU - Póliska, Szilárd AU - Ujlaki, Gyula AU - Demény, Máté Ágoston AU - Szöllősi, Attila AU - Kiss, Borbála AU - Szegedi, Andrea AU - Bay, Péter AU - Szántó, Magdolna TI - PARP2 promotes inflammation in psoriasis by modulating estradiol biosynthesis in keratinocytes JF - JOURNAL OF MOLECULAR MEDICINE-JMM J2 - J MOL MED-JMM VL - 101 PY - 2023 SP - 987 EP - 999 PG - 13 SN - 0946-2716 DO - 10.1007/s00109-023-02338-z UR - https://m2.mtmt.hu/api/publication/34034279 ID - 34034279 LA - English DB - MTMT ER - TY - CHAP AU - Antal, Dóra AU - Pór, Ágnes AU - Kovács, Ilona AU - Dull, Katalin AU - Póliska, Szilárd AU - Ujlaki, Gyula AU - Demény, Máté Ágoston AU - Szöllősi, A. G. AU - Kiss, B. AU - Szegedi, Andrea AU - Bay, Péter AU - Szántó, Magdolna TI - PARP2 promotes inflammation in psoriasis by modulating estradiol biosynthesis in keratinocytes . T2 - FEBS Advanced Lecture Course: PARP 2023: Research on the family of poly(ADP-ribose) polymerases; Book of Abstracts PB - Ruder Boskovic Institue CY - Hvar SN - 9789537941468 PY - 2023 SP - 60 UR - https://m2.mtmt.hu/api/publication/33998388 ID - 33998388 LA - English DB - MTMT ER - TY - JOUR AU - Jankó, Laura AU - Tóth, Emese AU - Laczik, Miklós AU - Rauch, Boglárka AU - Janka, Eszter AU - Bálint, Bálint László AU - Bay, Péter TI - PARP2 poly(ADP-ribosyl)ates nuclear factor erythroid 2-related factor 2 (NRF2) affecting NRF2 subcellular localization JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 13 SN - 2045-2322 DO - 10.1038/s41598-023-35076-w UR - https://m2.mtmt.hu/api/publication/33870536 ID - 33870536 AB - PARP2 is a member of the PARP enzyme family. Although, PARP2 plays role in DNA repair, it has regulatory roles in mitochondrial and lipid metabolism, it has pivotal role in bringing about the adverse effects of pharmacological PARP inhibitors. Previously, we showed that the ablation of PARP2 induces oxidative stress and, consequently, mitochondrial fragmentation. In attempt to identify the source of the reactive species we assessed the possible role of a central regulator of cellular antioxidant defense, nuclear factor erythroid 2-related factor 2 (NRF2). The silencing of PARP2 did not alter either the mRNA or the protein expression of NRF2, but changed its subcellular localization, decreasing the proportion of nuclear, active fraction of NRF2. Pharmacological inhibition of PARP2 partially restored the normal localization pattern of NRF2 and in line with that, we showed that NRF2 is PARylated that is absent in the cells in which PARP2 was silenced. Apparently, the PARylation of NRF2 by PARP2 has pivotal role in regulating the subcellular (nuclear) localization of NRF2. The silencing of PARP2 rearranged the expression of genes encoding proteins with antioxidant function, among these a subset of NRF2-dependent genes. LA - English DB - MTMT ER - TY - JOUR AU - Schwarcz, Szandra AU - Kovács, Patrik Bence AU - Kovács, Tünde AU - Ujlaki, Gyula AU - Nyerges, P. AU - Uray (Davis), Karen L. AU - Bay, Péter AU - Mikó, Edit TI - The pro- and antineoplastic effects of deoxycholic acid in pancreatic adenocarcinoma cell models JF - MOLECULAR BIOLOGY REPORTS J2 - MOL BIOL REP VL - 50 PY - 2023 IS - 6 SP - 5273 EP - 5282 PG - 10 SN - 0301-4851 DO - 10.1007/s11033-023-08453-x UR - https://m2.mtmt.hu/api/publication/33764771 ID - 33764771 LA - English DB - MTMT ER - TY - JOUR AU - Kacsir, István AU - Sipos, Adrienn AU - Major, Evelin AU - Bajusz, Nikolett AU - Bényei, Attila Csaba AU - Buglyó, Péter AU - Somsák, László AU - Kardos, Gábor AU - Bay, Péter AU - Bokor, Éva TI - Half-Sandwich Type Platinum-Group Metal Complexes of C-Glucosaminyl Azines: Synthesis and Antineoplastic and Antimicrobial Activities JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 7 PG - 50 SN - 1420-3049 DO - 10.3390/molecules28073058 UR - https://m2.mtmt.hu/api/publication/33734265 ID - 33734265 N1 - Funding details: NKM2022-30, POST-COVID2021-33 Funding details: Magyar Tudományos Akadémia, MTA Funding details: Debreceni Egyetem, DE, TKP2020-IKA-04, TKP2021-EGA-19, TKP2021-EGA-20 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, FK125067, K142141 Funding text 1: Our work was supported by the National Research, Development and Innovation Office of Hungary (grants K142141 and FK125067), by the University of Debrecen, by the Thematic Excellence Programme (TKP2020-IKA-04, TKP2021-EGA-19, TKP2021-EGA-20) of the Ministry for Innovation and Technology in Hungary and by the Momentum fellowship and POST-COVID2021-33 and NKM2022-30 grants of the Hungarian Academy of Sciences. AB - While platinum-based compounds such as cisplatin form the backbone of chemotherapy, the use of these compounds is limited by resistance and toxicity, driving the development of novel complexes with cytostatic properties. In this study, we synthesized a set of half-sandwich complexes of platinum-group metal ions (Ru(II), Os(II), Ir(III) and Rh(III)) with an N,N-bidentate ligand comprising a C-glucosaminyl group and a heterocycle, such as pyridine, pyridazine, pyrimidine, pyrazine or quinoline. The sugar-containing ligands themselves are unknown compounds and were obtained by nucleophilic additions of lithiated heterocycles to O-perbenzylated 2-nitro-glucal. Reduction of the adducts and, where necessary, subsequent protecting group manipulations furnished the above C-glucosaminyl heterocycles in their O-perbenzylated, O-perbenzoylated and O-unprotected forms. The derived complexes were tested on A2780 ovarian cancer cells. Pyridine, pyrazine and pyridazine-containing complexes proved to be cytostatic and cytotoxic on A2780 cells, while pyrimidine and quinoline derivatives were inactive. The best complexes contained pyridine as the heterocycle. The metal ion with polyhapto arene/arenyl moiety also impacted on the biological activity of the complexes. Ruthenium complexes with p-cymene and iridium complexes with Cp* had the best performance in ovarian cancer cells, followed by osmium complexes with p-cymene and rhodium complexes with Cp*. Finally, the chemical nature of the protective groups on the hydroxyl groups of the carbohydrate moiety were also key determinants of bioactivity; in particular, O-benzyl groups were superior to O-benzoyl groups. The IC50 values of the complexes were in the low micromolar range, and, importantly, the complexes were less active against primary, untransformed human dermal fibroblasts; however, the anticipated therapeutic window is narrow. The bioactive complexes exerted cytostasis on a set of carcinomas such as cell models of glioblastoma, as well as breast and pancreatic cancers. Furthermore, the same complexes exhibited bacteriostatic properties against multiresistant Gram-positive Staphylococcus aureus and Enterococcus clinical isolates in the low micromolar range. LA - English DB - MTMT ER -