TY - JOUR AU - Kovács, Dominika AU - Bagóné Vántus, Viola AU - Vámos, Eszter AU - Kálmán, Nikoletta AU - Schicho, Rudolf AU - Gallyas, Ferenc AU - Radnai, Balázs TI - Olaparib : A Clinically Applied PARP Inhibitor Protects from Experimental Crohn's Disease and Maintains Barrier Integrity by Improving Bioenergetics through Rescuing Glycolysis in Colonic Epithelial Cells JF - OXIDATIVE MEDICINE AND CELLULAR LONGEVITY J2 - OXID MED CELL LONGEV VL - 2021 PY - 2021 PG - 17 SN - 1942-0900 DO - 10.1155/2021/7308897 UR - https://m2.mtmt.hu/api/publication/32266554 ID - 32266554 AB - Crohn's disease (CD) is an inflammatory disorder of the intestines characterized by epithelial barrier dysfunction and mucosal damage. The activity of poly(ADP-ribose) polymerase-1 (PARP-1) is deeply involved in the pathomechanism of inflammation since it leads to energy depletion and mitochondrial failure in cells. Focusing on the epithelial barrier integrity and bioenergetics of epithelial cells, we investigated whether the clinically applied PARP inhibitor olaparib might improve experimental CD. We used the oral PARP inhibitor olaparib in the 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced mouse colitis model. Inflammatory scoring, cytokine levels, colon histology, hematological analysis, and intestinal permeability were studied. Caco-2 monolayer culture was utilized as an epithelial barrier model, on which we used qPCR and light microscopy imaging, and measured impedance-based barrier integrity, FITC-dextran permeability, apoptosis, mitochondrial oxygen consumption rate, and extracellular acidification rate. Olaparib reduced the inflammation score, the concentration of IL-1β and IL-6, enhanced the level of IL-10, and decreased the intestinal permeability in TNBS-colitis. Blood cell ratios, such as lymphocyte to monocyte ratio, platelet to lymphocyte ratio, and neutrophil to lymphocyte ratio were improved. In H2O2-treated Caco-2 monolayer, olaparib decreased morphological changes, barrier permeability, and preserved barrier integrity. In oxidative stress, olaparib enhanced glycolysis (extracellular acidification rate), and it improved mitochondrial function (mitochondrial coupling efficiency, maximal respiration, and spare respiratory capacity) in epithelial cells. Olaparib, a PARP inhibitor used in human cancer therapy, improved experimental CD and protected intestinal barrier integrity by preventing its energetic collapse; therefore, it could be repurposed for the therapy of Crohn's disease. LA - English DB - MTMT ER - TY - JOUR AU - Isbera, Mostafa AU - Bognár, Balázs AU - Gallyas, Ferenc AU - Bényei, Attila Csaba AU - Jekő, József AU - Kálai, Tamás TI - Syntheses and Study of a Pyrroline Nitroxide Condensed Phospholene Oxide and a Pyrroline Nitroxide Attached Diphenylphosphine JF - MOLECULES J2 - MOLECULES VL - 26 PY - 2021 IS - 14 PG - 10 SN - 1420-3049 DO - 10.3390/molecules26144366 UR - https://m2.mtmt.hu/api/publication/32113887 ID - 32113887 N1 - Cited By :2 Export Date: 6 March 2024 CODEN: MOLEF Correspondence Address: Kálai, T.; Faculty of Pharmacy, Szigeti st. 12, Hungary; email: tamas.kalai@aok.pte.hu AB - The reaction of a diene nitroxide precursor with dichlorophenylphosphine in a McCormac procedure afforded 1,1,3,3-tetramethyl-5-phenyl-1,2,3,4,5,6-hexahydrophospholo[3,4-c]pyrrole-5-oxide-2-oxyl. Lithiation of the protected 3-iodo-pyrroline nitroxide followed by treatment with chlorodiphenylphosphine after deprotection afforded (1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)diphenylphosphine oxide, and after reduction, (1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)diphenylphosphine was realized, which was also supported by X-ray single crystal diffraction measurements. This pyrroline diphenylphosphine derivative was converted to hexadecylphosphonium salt, which is an analogue of antineoplastic agent, MITO-CP. LA - English DB - MTMT ER - TY - JOUR AU - Kanokwiroon, K. AU - Erős, Krisztián AU - Graidist, P. AU - Nakatake, A. AU - Morishita, K. TI - Microarray-predicted molecular effect of WT1 isoforms in MCF-7 breast cancer cell line JF - FEBS OPEN BIO J2 - FEBS OPEN BIO VL - 9 PY - 2019 SP - 333 EP - 333 PG - 1 SN - 2211-5463 UR - https://m2.mtmt.hu/api/publication/31997390 ID - 31997390 LA - English DB - MTMT ER - TY - JOUR AU - Bock-Marquette, Ildikó AU - Gallyas, Ferenc TI - Introduction JF - CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY J2 - CAN J PHYSIOL PHARM VL - 96 ET - 0 PY - 2018 IS - 10 SP - V EP - V SN - 0008-4212 DO - 10.1139/cjpp-2018-0484 UR - https://m2.mtmt.hu/api/publication/30356192 ID - 30356192 N1 - Editorial Special Issue: SI LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Lóránd AU - Fűr, Gabriella AU - Mátrai, Péter AU - Hegyi, Péter AU - Ivány, Emese AU - Cazacu, IM AU - Szabó, Imre AU - Habon, Tamás AU - Alizadeh, Hussain AU - Gyöngyi, Zoltán AU - Vigh, Éva AU - Erőss, Bálint Mihály AU - Erős, Adrienn AU - Ottoffy, M AU - Czakó, László AU - Rakonczay, Zoltán TI - The effect of serum triglyceride concentration on the outcome of acute pancreatitis : systematic review and meta-analysis JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 8 PY - 2018 IS - 1 PG - 14 SN - 2045-2322 DO - 10.1038/s41598-018-32337-x UR - https://m2.mtmt.hu/api/publication/3422217 ID - 3422217 N1 - * Megosztott szerzőség AB - Elevated serum triglyceride concentration (seTG, >1.7 mM or >150 mg/dL) or in other words hypertriglyceridemia (HTG) is common in the populations of developed countries. This condition is accompanied by an increased risk for various diseases, such as acute pancreatitis (AP). It has been proposed that HTG could also worsen the course of AP. Therefore, in this meta-analysis, we aimed to compare the effects of various seTGs on the severity, mortality, local and systemic complications of AP, and on intensive care unit admission. 16 eligible studies, including 11,965 patients were retrieved from PubMed and Embase. The results showed that HTG significantly elevated the odds ratio (OR = 1.72) for severe AP when compared to patients with normal seTG (<1.7 mM). Furthermore, a significantly higher occurrence of pancreatic necrosis, persistent organ failure and renal failure was observed in groups with HTG. The rates of complications and mortality for AP were significantly increased in patients with seTG >5.6 mM or >11.3 mM versus <5.6 mM or <11.3 mM, respectively. We conclude that the presence of HTG worsens the course and outcome of AP, but we found no significant difference in AP severity based on the extent of HTG. LA - English DB - MTMT ER - TY - JOUR AU - Martin, NA AU - Nawrocki, A AU - Molnár, Viktor AU - Elkjaer, ML AU - Thygesen, EK AU - Palkovits, Miklós AU - Ács, Péter AU - Sejbaek, T AU - Nielsen, HH AU - Hegedűs, Zoltán AU - Sellebjerg, F AU - Molnár, Tihamér AU - Barbosa, EGV AU - Alcaraz, N AU - Gallyas, Ferenc AU - Svenningsen, AF AU - Baumbach, J AU - Lassmann, H AU - Larsen, MR AU - Illés, Zsolt László TI - Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes JF - PLOS ONE J2 - PLOS ONE VL - 13 PY - 2018 IS - 8 PG - 26 SN - 1932-6203 DO - 10.1371/journal.pone.0202530 UR - https://m2.mtmt.hu/api/publication/3407190 ID - 3407190 AB - OBJECTIVE: Here, we applied a multi-omics approach (i) to examine molecular pathways related to de- and remyelination in multiple sclerosis (MS) lesions; and (ii) to translate these findings to the CSF proteome in order to identify molecules that are differentially expressed among MS subtypes. METHODS: To relate differentially expressed genes in MS lesions to de- and remyelination, we compared transcriptome of MS lesions to transcriptome of cuprizone (CPZ)-induced de- and remyelination. Protein products of the overlapping orthologous genes were measured within the CSF by quantitative proteomics, parallel reaction monitoring (PRM). Differentially regulated proteins were correlated with molecular markers of inflammation by using MesoScale multiplex immunoassay. Expression kinetics of differentially regulated orthologous genes and proteins were examined in the CPZ model. RESULTS: In the demyelinated and remyelinated corpus callosum, we detected 1239 differentially expressed genes; 91 orthologues were also differentially expressed in MS lesions. Pathway analysis of these orthologues suggested that the TYROBP (DAP12)-TREM2 pathway, TNF-receptor 1, CYBA and the proteasome subunit PSMB9 were related to de- and remyelination. We designed 129 peptides representing 51 orthologous proteins, measured them by PRM in 97 individual CSF, and compared their levels between relapsing (n = 40) and progressive MS (n = 57). Four proteins were differentially regulated among relapsing and progressive MS: tyrosine protein kinase receptor UFO (UFO), TIMP-1, apolipoprotein C-II (APOC2), and beta-2-microglobulin (B2M). The orthologous genes/proteins in the mouse brain peaked during acute remyelination. UFO, TIMP-1 and B2M levels correlated inversely with inflammation in the CSF (IL-6, MCP-1/CCL2, TARC/CCL17). APOC2 showed positive correlation with IL-2, IL-16 and eotaxin-3/CCL26. CONCLUSIONS: Pathology-based multi-omics identified four CSF markers that were differentially expressed in MS subtypes. Upregulated TIMP-1, UFO and B2M orthologues in relapsing MS were associated with reduced inflammation and reflected reparatory processes, in contrast to the upregulated orthologue APOC2 in progressive MS that reflected changes in lipid metabolism associated with increased inflammation. LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Lóránd AU - Fűr, Gabriella AU - Mátrai, Péter AU - Hegyi, Péter AU - Ivány, Emese AU - Mihaela Cazacu, Irina AU - Szabó, Imre AU - Habon, Tamás AU - Alizadeh, Hussain AU - Gyöngyi, Zoltán AU - Vigh, Éva AU - Erőss, Bálint AU - Erős, Adrienn AU - Ottoffy, Máté AU - Czakó, László AU - Rakonczay, Zoltán TI - The effect of serum triglyceride concentration on the outcome of acute pancreatitis: Systematic review and meta-analysis JF - PANCREATOLOGY J2 - PANCREATOLOGY VL - 18 PY - 2018 IS - 4S SP - S97 EP - S98 PG - 2 SN - 1424-3903 DO - 10.1016/j.pan.2018.05.262 UR - https://m2.mtmt.hu/api/publication/3390792 ID - 3390792 LA - English DB - MTMT ER - TY - JOUR AU - Bognár, Zita AU - Fekete, Katalin AU - Bognár, Rita AU - Szabó, Aliz AU - Vass, Réka Anna AU - Sümegi, Balázs TI - Amiodarone’s major metabolite, desethylamiodarone induces apoptosis in human cervical cancer cells JF - CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY J2 - CAN J PHYSIOL PHARM VL - 96 PY - 2018 IS - 10 SP - 1004 EP - 1011 PG - 8 SN - 0008-4212 DO - 10.1139/cjpp-2018-0113 UR - https://m2.mtmt.hu/api/publication/3375670 ID - 3375670 N1 - Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary Department of Anatomy, University of Pécs Medical School, Pécs, Hungary Nuclear-Mitochondrial Interactions Research Group, Hungarian Academy of Sciences, Budapest, Hungary Szentagothai Research Center, University of Pécs, Pécs, Hungary Export Date: 13 December 2019 CODEN: CJPPA Correspondence Address: Bognar, Z.; Department of Biochemistry and Medical Chemistry, University of Pécs Medical SchoolHungary; email: zita.bognar@aok.pte.hu Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary Department of Anatomy, University of Pécs Medical School, Pécs, Hungary Nuclear-Mitochondrial Interactions Research Group, Hungarian Academy of Sciences, Budapest, Hungary Szentagothai Research Center, University of Pécs, Pécs, Hungary Export Date: 20 February 2020 CODEN: CJPPA Correspondence Address: Bognar, Z.; Department of Biochemistry and Medical Chemistry, University of Pécs Medical SchoolHungary; email: zita.bognar@aok.pte.hu Funding Agency and Grant Number: Ministry of Human Capacities [OTKA K-104220, OTKA NN-109841, GINOP-2.3.3-15-2016-00025, GINOP-2.3.2-15-2016-00048, GINOP-2.3.2-15-2016-00049, EFOP-3.6.1-16-2016-00004, UNKP-17-4-I-PTE-209] Funding text: This work was supported by Hungarian grants OTKA K-104220, OTKA NN-109841, GINOP-2.3.3-15-2016-00025, GINOP-2.3.2-15-2016-00048, GINOP-2.3.2-15-2016-00049, EFOP-3.6.1-16-2016-00004, and UNKP-17-4-I-PTE-209 New National Excellence Program of the Ministry of Human Capacities. Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary Department of Anatomy, University of Pécs Medical School, Pécs, Hungary Nuclear-Mitochondrial Interactions Research Group, Hungarian Academy of Sciences, Budapest, Hungary Szentagothai Research Center, University of Pécs, Pécs, Hungary Cited By :2 Export Date: 21 January 2021 CODEN: CJPPA Correspondence Address: Bognar, Z.; Department of Biochemistry and Medical Chemistry, Hungary; email: zita.bognar@aok.pte.hu AB - Previously, we found that desethylamiodarone (DEA) may have therapeutic potentiality in bladder cancer. In this study, we determined its effects on human cervical cancer cells (HeLa). Cell viability was evaluated by Muse Cell Count & Viability Assay; cell apoptosis was detected by Muse Annexin V & Dead Cell Assay. Cell cycle was flow cytometrically determined by Muse Cell Cycle Kit and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33342 staining. The changes in the expression levels of apoptosis-related proteins in the HeLa cells were assessed by immunoblot. Our results showed that DEA significantly inhibited the proliferation and viability of HeLa cells and induced apoptosis in vitro in dose-dependent and also in cell cycle-dependent manner because DEA induced G0/G1 phase arrest in the HeLa cell line. We found that DEA treatment downregulated the expression of phospho-Akt and phospho-Bad. In addition, DEA could downregulate expression of Bcl-2, upregulate Bax, and induce cytochrome c release. Our results indicate that DEA might have significance as an anti-tumor agent against human cervical cancer. LA - English DB - MTMT ER - TY - JOUR AU - Martin, NA AU - Molnár, Viktor AU - Szilágyi, Tamás Gábor AU - Elkjaer, ML AU - Nawrocki, A AU - Okarmus, J AU - Wlodarczyk, A AU - Thygesen, EK AU - Palkovits, Miklós AU - Gallyas, Ferenc AU - Larsen, MR AU - Lassmann, H AU - Benedikz, E AU - Owens, T AU - Svenningsen, AF AU - Illés, Zsolt László TI - Experimental demyelination and axonal loss are reduced in MicroRNA-146a deficient mice JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 9 PY - 2018 PG - 14 SN - 1664-3224 DO - 10.3389/fimmu.2018.00490 UR - https://m2.mtmt.hu/api/publication/3352238 ID - 3352238 LA - English DB - MTMT ER - TY - JOUR AU - Pákai, Eszter AU - Tékus, Valéria AU - Zsiboras, C AU - Rumbus, Zoltán AU - Pótóné Oláh, Emőke AU - Kéringer, Patrik AU - Khidhir, N AU - Mátics, Róbert AU - Deres, László AU - Takács-Ördög, Katalin AU - Szentes, Nikolett AU - Pohóczky, Krisztina AU - Kemény, Ágnes AU - Hegyi, Péter AU - Pintér, Erika AU - Garami, András TI - The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 9 PY - 2018 PG - 15 SN - 1664-3224 DO - 10.3389/fimmu.2018.00166 UR - https://m2.mtmt.hu/api/publication/3338655 ID - 3338655 LA - English DB - MTMT ER -