@article{MTMT:33153168,
	title = {OGG1 Inhibition Reduces Acinar Cell Injury in a Mouse Model of Acute Pancreatitis},
	url = {https://m2.mtmt.hu/api/publication/33153168},
	author = {Hajnády, Zoltán and Nagy-Pénzes, Máté and Demény, Máté Ágoston and Kovács, Katalin and El-Hamoly, Tarek and Maléth, József and Hegyi, Péter and Polgár, Zsuzsanna and Hegedűs, Csaba and Virág, László},
	doi = {10.3390/biomedicines10102543},
	journal-iso = {BIOMEDICINES},
	journal = {BIOMEDICINES},
	volume = {10},
	unique-id = {33153168},
	abstract = {Acute pancreatitis (AP) is a potentially life-threatening gastrointestinal disease with a complex pathology including oxidative stress. Oxidative stress triggers oxidative DNA lesions such as formation of 7,8-dihydro-8-oxo-2′-oxoguanine (8-oxoG) and also causes DNA strand breaks. DNA breaks can activate the nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1) which contributes to AP pathology. 8-oxoG is recognized by 8-oxoG glycosylase 1 (OGG1) resulting in the removal of 8-oxoG from DNA as an initial step of base excision repair. Since OGG1 also possesses a DNA nicking activity, OGG1 activation may also trigger PARP1 activation. In the present study we investigated the role played by OGG1 in AP. We found that the OGG1 inhibitor compound TH5487 reduced edema formation, inflammatory cell migration and necrosis in a cerulein-induced AP model in mice. Moreover, TH5487 caused 8-oxoG accumulation and reduced tissue poly(ADP-ribose) levels. Consistent with the indirect PARP inhibitory effect, TH5487 shifted necrotic cell death (LDH release and Sytox green uptake) towards apoptosis (caspase activity) in isolated pancreatic acinar cells. In the in vivo AP model, TH5487 treatment suppressed the expression of various cytokine and chemokine mRNAs such as those of TNF, IL-1β, IL1ra, IL6, IL16, IL23, CSF, CCL2, CCL4, CCL12, IL10 and TREM as measured with a cytokine array and verified by RT-qPCR. As a potential mechanism underlying the transcriptional inhibitory effect of the OGG1 inhibitor we showed that while 8-oxoG accumulation in the DNA facilitates NF-κB binding to its consensus sequence, when OGG1 is inhibited, target site occupancy of NF-κB is impaired. In summary, OGG1 inhibition provides protection from tissue injury in AP and these effects are likely due to interference with the PARP1 and NF-κB activation pathways.},
	year = {2022},
	eissn = {2227-9059},
	orcid-numbers = {Demény, Máté Ágoston/0000-0003-4623-4091; Maléth, József/0000-0001-5768-3090; Hegyi, Péter/0000-0003-0399-7259}
}

@article{MTMT:32886684,
	title = {Tricetin Reduces Inflammation and Acinar Cell Injury in Cerulein-Induced Acute Pancreatitis: The Role of Oxidative Stress-Induced DNA Damage Signaling},
	url = {https://m2.mtmt.hu/api/publication/32886684},
	author = {Nagy-Pénzes, Máté and Hajnády, Zoltán and Regdon, Zsolt and Demény, Máté Ágoston and Kovács, Katalin and El-Hamoly, Tarek and Maléth, József and Hegyi, Péter and Hegedűs, Csaba and Virág, László},
	doi = {10.3390/biomedicines10061371},
	journal-iso = {BIOMEDICINES},
	journal = {BIOMEDICINES},
	volume = {10},
	unique-id = {32886684},
	year = {2022},
	eissn = {2227-9059},
	orcid-numbers = {Maléth, József/0000-0001-5768-3090; Hegyi, Péter/0000-0003-0399-7259}
}

@article{MTMT:32499339,
	title = {Beneficial effects of tricetin in cerulein induced acute pancreatitis},
	url = {https://m2.mtmt.hu/api/publication/32499339},
	author = {Nagy-Pénzes, Máté and Hajnády, Zoltán and Regdon, Zsolt and Virág, László},
	journal-iso = {FEBS OPEN BIO},
	journal = {FEBS OPEN BIO},
	volume = {11},
	unique-id = {32499339},
	issn = {2211-5463},
	year = {2021},
	eissn = {2211-5463},
	pages = {493-494}
}

@article{MTMT:32499259,
	title = {Role of OGG1 in cerulein induced acute pancreatitis},
	url = {https://m2.mtmt.hu/api/publication/32499259},
	author = {Hajnády, Zoltán and Nagy-Pénzes, Máté and Regdon, Zsolt and Virág, László},
	journal-iso = {FEBS OPEN BIO},
	journal = {FEBS OPEN BIO},
	volume = {11},
	unique-id = {32499259},
	issn = {2211-5463},
	year = {2021},
	eissn = {2211-5463},
	pages = {492-493}
}

@article{MTMT:31938546,
	title = {Poly(ADP-ribose) polymerase 1 promotes inflammation and fibrosis in a mouse model of chronic pancreatitis},
	url = {https://m2.mtmt.hu/api/publication/31938546},
	author = {El-Hamoly, T and Hajnády, Zoltán and Nagy-Pénzes, Máté and Bakondi, Edina and Regdon, Zsolt and Demény, Máté Ágoston and Kovács, Katalin and Hegedűs, Csaba and Abd, El-Rahman SS and Szabó, Éva and Maléth, József and Hegyi, Péter and Virág, László},
	doi = {10.3390/ijms22073593},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {22},
	unique-id = {31938546},
	issn = {1661-6596},
	year = {2021},
	eissn = {1422-0067},
	orcid-numbers = {Maléth, József/0000-0001-5768-3090; Hegyi, Péter/0000-0003-0399-7259}
}

@article{MTMT:31831963,
	title = {High‐content screening identifies inhibitors of oxidative stress‐induced parthanatos: cytoprotective and anti‐inflammatory effects of ciclopirox},
	url = {https://m2.mtmt.hu/api/publication/31831963},
	author = {Regdon, Zsolt and Demény, Máté Ágoston and Kovács, Katalin and Hajnády, Zoltán and Nagy-Pénzes, Máté and Bakondi, Edina and Kiss, Alexandra and Hegedűs, Csaba and Virág, László},
	doi = {10.1111/bph.15344},
	journal-iso = {BR J PHARMACOL},
	journal = {BRITISH JOURNAL OF PHARMACOLOGY},
	volume = {178},
	unique-id = {31831963},
	issn = {0007-1188},
	abstract = {Background and Purpose
		Excessive oxidative stress can induce PARP1‐mediated programmed necrotic cell death, termed parthanatos. Inhibition of parthanatos may be therapeutically beneficial in a wide array of diseases associated with tissue injury and inflammation. Our goal was to identify novel molecules inhibiting parthanatos.
		
		Experimental Approach
		A small library of 774 pharmacologically active compounds was screened in a Sytox Green uptake assay, which identified 20 hits that reduced hydrogen‐peroxide‐induced parthanatos with an efficiency comparable to the benchmark PARP inhibitor, PJ34.
		
		Key Results
		Of these hits, two compounds, antifungal ciclopirox and dopamine receptor agonist apomorphine, inhibited PAR polymer synthesis. These two compounds prevented the binding of PARP1 to oxidatively damaged DNA but did not directly interfere with the interaction between DNA and PARP1. Both compounds inhibited mitochondrial superoxide and H2O2 production and suppressed DNA breakage. Since H2O2‐induced damage is dependent on Fe2+‐catalysed hydroxyl radical production (Fenton chemistry), we determined the iron chelation activity of the two test compounds and found that ciclopirox and, to a lesser extent, apomorphine act as iron chelators. We also show that the Fe2+ chelation and indirect PARP inhibitory effects of ciclopirox translate to anti‐inflammatory actions as demonstrated in a mouse dermatitis model, where ciclopirox reduced ear swelling, inflammatory cell recruitment and poly(ADP‐ribosyl)ation.
		
		Conclusion and Implications
		Our findings indicate that the antimycotic drug, ciclopirox, acts as an iron chelator and thus targets an early event in hydrogen‐peroxide‐induced parthanatos. Ciclopirox has the potential to be repurposed as a cytoprotective and anti‐inflammatory agent.},
	keywords = {Inflammation; CYTOPROTECTION; Cell Death; PARP1; Regulated necrosis; Oxidative stress},
	year = {2021},
	eissn = {1476-5381},
	pages = {1095-1113}
}

@article{MTMT:30791594,
	title = {Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis},
	url = {https://m2.mtmt.hu/api/publication/30791594},
	author = {Bakondi, Edina and Singh, Salam Bhopen and Hajnády, Zoltán and Nagy-Pénzes, Máté and Regdon, Zsolt and Kovács, Katalin and Hegedűs, Csaba and Madácsy, Tamara and Maléth, József and Hegyi, Péter and Demény, Máté Ágoston and Nagy, Tibor and Kéki, Sándor and Szabó, Éva and Virág, László},
	doi = {10.3390/ijms20174308},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {20},
	unique-id = {30791594},
	issn = {1661-6596},
	abstract = {Activated macrophages upregulate inducible nitric oxide synthase (iNOS) leading to the profuse production of nitric oxide (NO) and, eventually, tissue damage. Using macrophage NO production as a biochemical marker of inflammation, we tested different parts (flower, leaf, and stem) of the medicinal plant, Spilanthes acmella. We found that extracts prepared from all three parts, especially the flowers, suppressed NO production in RAW macrophages in response to interferon-γ and lipopolysaccharide. Follow up experiments with selected bioactive molecules from the plant (α-amyrin, β-caryophylline, scopoletin, vanillic acid, trans-ferulic acid, and spilanthol) indicated that the N-alkamide, spilanthol, is responsible for the NO-suppressive effects and provides protection from NO-dependent cell death. Spilanthol reduced the expression of iNOS mRNA and protein and, as a possible underlying mechanism, inhibited the activation of several transcription factors (NFκB, ATF4, FOXO1, IRF1, ETS, and AP1) and sensitized cells to downregulation of Smad (TF array experiments). The iNOS inhibitory effect translated into an anti-inflammatory effect, as demonstrated in a phorbol 12-myristate 13-acetate-induced dermatitis and, to a smaller extent, in cerulein-induced pancreatitis. In summary, we demonstrate that spilanthol inhibits iNOS expression, NO production and suppresses inflammatory TFs. These events likely contribute to the observed anti-inflammatory actions of spilanthol in dermatitis and pancreatitis.},
	keywords = {MACROPHAGE; pancreatitis; dermatitis; nitric oxide; inducible nitric oxide synthase; NFκB; Foxo1; IRF; spilanthol},
	year = {2019},
	eissn = {1422-0067},
	orcid-numbers = {Madácsy, Tamara/0000-0001-5598-9723; Maléth, József/0000-0001-5768-3090; Hegyi, Péter/0000-0003-0399-7259; Nagy, Tibor/0000-0001-8568-914X}
}

@article{MTMT:33570198,
	title = {Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases},
	url = {https://m2.mtmt.hu/api/publication/33570198},
	author = {Fellows, Rachel and Denizot, Jeremy and Stellato, Claudia and Cuomo, Alessandro and Jain, Payal and Stoyanova, Elena and Balazsi, Szabina and Hajnády, Zoltán and Liebert, Anke and Kazakevych, Juri and Blackburn, Hector and Correa, Renan Oliveira and Fachi, Jose Luis and Sato, Fabio Takeo and Ribeiro, Willian R. and Ferreira, Caroline Marcantonio and Peree, Helene and Spagnuolo, Mariangela and Mattiuz, Raphael and Matolcsi, Csaba and Guedes, Joana and Clark, Jonathan and Veldhoen, Marc and Bonaldi, Tiziana and Ramirez Vinolo, Marco Aurelio and Varga-Weisz, Patrick},
	doi = {10.1038/s41467-017-02651-5},
	journal-iso = {NAT COMMUN},
	journal = {NATURE COMMUNICATIONS},
	volume = {9},
	unique-id = {33570198},
	issn = {2041-1723},
	abstract = {The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs.},
	year = {2018},
	eissn = {2041-1723},
	orcid-numbers = {Denizot, Jeremy/0000-0003-0078-8996; Stellato, Claudia/0000-0003-1513-3263; Cuomo, Alessandro/0000-0002-9778-7190; Liebert, Anke/0000-0002-5849-6147; Sato, Fabio Takeo/0000-0002-9863-4364; Peree, Helene/0000-0002-0751-6195; Mattiuz, Raphael/0000-0002-3292-1635; Veldhoen, Marc/0000-0002-1478-9562; Bonaldi, Tiziana/0000-0003-3556-1265; Varga-Weisz, Patrick/0000-0001-7409-8686}
}