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001-es BibID:	BIBFORM115266
035-os BibID:	(cikkazonosító)e0296
Első szerző:	Tornai Dávid (hepatológia, biomarker kutatás)
Cím:	A novel score of IL-13 and age predicts 90-day mortality in severe alcohol-associated hepatitis : a multicenter plasma biomarker analysis / David Tornai, Mack Mitchell, Craig J. McClain, Srinivasan Dasarathy, Arthur McCullough, Svetlana Radaeva, Aimee Kroll-Desrosiers, JungAe Lee, Bruce Barton, Gyongyi Szabo
Dátum:	2023
ISSN:	2471-254X
Megjegyzések:	Background: Severe alcoholic hepatitis (AH) has a high short-term mortality rate. The Model for End-Stage Liver Disease (MELD) assesses disease severity and mortality, however, it is not specific for AH. We screened plasma samples from severe AH patients for biomarkers of multiple pathological processes and identified predictors of short-term mortality. Methods: Plasma was collected at baseline from 85 severe AH patients (MELD?20, MDF?32) enrolled in the DASH clinical trial (investigating IL-1receptor antagonist+pentoxifylline+zinc vs. methylprednisolone+placebo). Samples were analyzed for 43 biomarkers and the markers' association with 28 and 90-day mortality was assessed. Results: Thirty-one (36.5%) patients died during the 90-day follow-up with similar ratios in the treatment groups. Eight biomarkers showed association with mortality. Interleukin-6, IL-22, IFN-?2, sTNF-R1, lipocalin-2 and ?-fetoprotein levels were associated with 28-day, while IL-6, IL-13 and endotoxin levels with 90-day mortality. In multivariable Cox regression, encephalopathy, lipocalin-2 and ?-fetoprotein levels were independent predictors of 28-day mortality and IL-6, IL-13, INR levels and age were independent predictors of 90-day mortality. The combination of IL-13 and age had superior performance predicting 90-day mortality compared to MELD in the total cohort and the individual treatment groups. Conclusions: We identified predictors of short-term mortality in a cohort exclusively involving severe AH patients. We created a composite score of IL-13 and age that predicts 90-day mortality regardless of treatment type with a performance superior to MELD in severe AH.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk anakinra interleukin short-term mortality composite score prognosis
Megjelenés:	Hepatology Communications. - 7 : 12 (2023), p. 1-13. -
További szerzők:	Mitchell, Mack McClain, Craig Dasarathy, Srinivasan McCullough, Arthur Radaeva, Svetlana Kroll-Desrosiers, Aimee Lee, JungAe Barton, Bruce Szabó Gyöngyi
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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001-es BibID:	BIBFORM082948
Első szerző:	Tornai Dávid (hepatológia, biomarker kutatás)
Cím:	Inhibition of Triggering Receptor Expressed on Myeloid Cells 1 Ameliorates Inflammation and Macrophage and Neutrophil Activation in Alcoholic Liver Disease in Mice / David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo
Dátum:	2019
ISSN:	2471-254X
Megjegyzések:	Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA/E31-HDL. As revealed in vitro, macrophages endocytosed these rationally designed complexes through scavenger receptors. A 5-week alcohol feeding with the Lieber-DeCarli diet in mice resulted in increased serum alanine aminotransferase (ALT), liver steatosis, and increased proinflammatory cytokines in the liver. TREM-1 messenger RNA (mRNA) expression was significantly increased in alcohol-fed mice, and TREM-1 inhibitors significantly reduced this increase. TREM-1 inhibition significantly attenuated alcohol-induced spleen tyrosine kinase (SYK) activation, an early event in both TLR4 and TREM-1 signaling. The TREM-1 inhibitors significantly inhibited macrophage (epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 [F4/80], clusters of differentiation [CD]68) and neutrophil (lymphocyte antigen 6 complex, locus G [Ly6G] and myeloperoxidase [MPO]) markers and proinflammatory cytokines (monocyte chemoattractant protein 1 [MCP-1], tumor necrosis factor ? [TNF-?], interleukin-1? [IL-1?], macrophage inflammatory protein 1? [MIP-1?]) at the mRNA level compared to the HDL vehicle. Administration of TREM-1 inhibitors ameliorated liver steatosis and early fibrosis markers (?-smooth muscle actin [?SMA] and procollagen1? [Pro-Col1?]) at the mRNA level in alcohol-fed mice. However, the HDL vehicle also reduced serum ALT and some cytokine protein levels in alcohol-fed mice, indicating HDL-related effects. Conclusion: HDL-delivered novel TREM-1 peptide inhibitors ameliorate early phases of inflammation and neutrophil and macrophage recruitment and activation in the liver and attenuate hepatocyte damage and liver steatosis. TREM-1 inhibition represents a promising therapeutic approach for further investigations in ALD.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Hepatology Communications. - 3 : 1 (2019), p. 99-115. -
További szerzők:	Furi István Shen, Zu T. Sigalov, Alexander B. Coban, Sahin Szabó Gyöngyi
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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