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001-es BibID:	BIBFORM103624
035-os BibID:	(WoS)000923633900005 (Scopus)85142716887
Első szerző:	Cho, Yeonhee
Cím:	Neutrophil extracellular traps contribute to liver damage and increase defective low-density neutrophils in alcoholic hepatitis / Cho Yeonhee, Bukong Terence Ndonyi, Tornai David, Babuta Mrigya, Vlachos Ioannis S., Kanata Eleni, Catalano Donna, Szabo Gyongyi
Dátum:	2023
ISSN:	0168-8278
Megjegyzések:	Background & Aims In alcoholic hepatitis (AH), inflammation and neutrophil counts correlate with poor clinical outcomes. Here, we investigated how neutrophils contribute to liver damage in AH. Methods We isolated blood neutrophils from AH patients to examine neutrophils extracellular traps (NETs) and performed RNA sequencing to explore unique characteristics. Results We found a significant increase of NET production in AH. We also observed a unique low-density neutrophil (LDNs) population in AH patients and alcohol-fed mice that was not present in healthy controls. Transcriptome analysis of peripheral LDNs and high-density neutrophils (HDNs) from AH patients revealed that LDNs exhibit a functionally exhausted phenotype, while HDNs are activated. Indeed, we found that AH HDNs have increased resting reactive oxygen species (ROS) and produce higher ROS upon LPS stimulation than control HDNs, whereas AH LDNs fail to respond to LPS. We show that LDNs are generated from HDNs after alcohol-induced NET release in vitro, and this LDN subset has decreased functionality including reduced phagocytosis. Moreover, LDNs showed reduced homing capacity and clearance by macrophage efferocytosis; therefore, dysfunctional neutrophils could remain in the circulation and liver. Depletion of both HDNs and LDNs in vivo prevented alcohol-induced NET production and liver damage in mice. Granulocyte-colony stimulating factor (G-CSF) treatment also ameliorated alcohol-induced liver injury in mice. Conclusion Neutrophils contribute to liver damage through increased NET formation which increases defective LDNs in AH. Alcohol induces neutrophil phenotype changes; HDNs are activated whereas LDNs are defective. Our findings provide mechanistic insights for therapeutic interventions in AH.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal Of Hepatology. - 78 : 1 (2023), p. 28-44. -
További szerzők:	Bukong, Terence Ndonyi Tornai Dávid (1989-) (hepatológia, biomarker kutatás) Babuta, Mrigya Vlachos, Ioannis S. Kanata, Eleni Catalano, Donna Szabó Gyöngyi
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001-es BibID:	BIBFORM078868
035-os BibID:	(PMID)31464790
Első szerző:	Janka Tamás
Cím:	Deleterious effect of proton pump inhibitors on the disease course of cirrhosis / Tamas Janka, Tamas Tornai, Brigitta Borbely, David Tornai, Istvan Altorjay, Maria Papp, Zsuzsanna Vitalis
Dátum:	2020
Megjegyzések:	OBJECTIVES: Proton pump inhibitors (PPIs) are widely prescribed to patients with liver cirrhosis. We hypothesized that long-standing PPI use is associated with spontaneous bacterial peritonitis (SBP) and accelerated development of disease-specific complications and liver-related death. METHODS: A 5-year follow-up observational cohort study assessed the impact of long-standing PPI use on the clinical course of cirrhosis in a large referral patient cohort. 350 patients with cirrhosis (males: 188, females: 162, ages: 56?6 years, alcohol: 242 [69.1%], Child-Pugh stage A/B/C: 206/108/36) were assigned to two groups: regular PPI users (n=196) and non-users (n=154). Occurrence of SBP, decompensation events (development of ascites, hepatic encephalopathy and variceal bleeding), and liver-related death were assessed. RESULTS: Regular PPI use was associated with an increased cumulative probability of SBP compared to non-users [CP: 55% vs 24.8%, HR: 4.25 (95%CI: 1.42-12.67), p=0.05], but only in patients who had no previous SBP episode (n=84). A similar association was found between regular PPI use and decompensation events. The risk of the development of a first decompensation event (ascites, HE or VB) was higher in regular PPI users compared to non-users, in patients with compensated clinical stage at enrollment (HR: 2.81, 95%CI: 1.31-6.01, p=0.008, n=146). The risk of liver-related death was also significantly increased among regular PPI users (p<0.001). In multivariate Cox-regression analysis, regular PPI use (HR: 2.81, 95%CI: 1.43-5.51, p=0.003) and MELD score (HR: 1.21, 95%CI: 1.08-1.35, p<0.001) was an independent predictor of mortality. In the present follow-up cohort study, long-term PPI use was associated with the development of SBP and a progressive disease course in patients with cirrhosis that may have been caused by enhanced pathologic BT, accelerated development of BT-dependent disease-specific complications, and liver-related death.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban proton pump inhibitors bacterial translocation spontaneous bacterial peritonitis disease progression mortality
Megjelenés:	European Journal of Gastroenterology & Hepatology. - 32 : 2 (2020), p. 257-264. -
További szerzők:	Tornai Tamás István (1984-) (belgyógyász) Borbély Brigitta Tornai Dávid (1989-) (hepatológia, biomarker kutatás) Altorjay István (1954-) (belgyógyász, gasztroenterológus, onkológus) Papp Mária (1975-) (belgyógyász, gasztroenterológus) Vitális Zsuzsanna (1963-) (belgyógyász, gasztroenterológus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00048 GINOP EFOP-3.6.1-16-2016-00022 EFOP EFOP-3.6.2-16-2017-00006 EFOP BO/00232/17/5 Egyéb ÚNKP-17-4 Egyéb
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001-es BibID:	BIBFORM102210
Első szerző:	Tornai Tamás István (belgyógyász)
Cím:	Soluble CD163 (SCD163) is a marker of infection in patients with cirrhosis and acute decompensation and an independent predictor of the short-term mortality / Tornai Tamás, Tornai Dávid, Sipeki Nóra, Földi Ildikó, Dinya Tamás, Vitalis Zsuzsanna, Antal-Szalmás Péter, Tornai István, Papp Mária
Dátum:	2015
ISSN:	0168-8278
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idézhető absztrakt folyóiratcikk
Megjelenés:	Journal Of Hepatology. - 62 : Supplement 2 (2015), p. S368. -
További szerzők:	Tornai Dávid (1989-) (hepatológia, biomarker kutatás) Sipeki Nóra (1987-) (általános orvos) Földi Ildikó (1981-) (orvos) Dinya Tamás (1974-) (sebész szakorvos, onkológus szakorvos) Vitális Zsuzsanna (1963-) (belgyógyász, gasztroenterológus) Antal-Szalmás Péter (1968-) (laboratóriumi szakorvos) Tornai István (1954-) (belgyógyász, gasztroenterológus) Papp Mária (1975-) (belgyógyász, gasztroenterológus)
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