It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD+’s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Post-operative eNAD+ levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD+ biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD+ in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD+ treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD+ was upregulated in PHLF, and rate-limiting enzymes of NAD+ biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD+ administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies.
An analysis on liver disease patients suggests that extracellular Nicotinamide adenine dinucleotide (eNAD + ) correlates with liver fibrosis and post-hepatectomy liver failure, with NAD+ administration improving survival and liver regeneration in mice and hepatocyte viability in vitro.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details






1 Augustenburger Platz 1, Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Surgery - Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany (GRID:grid.7468.d) (ISNI:0000 0001 2248 7639)
2 Charitéplatz 1, Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany (GRID:grid.7468.d) (ISNI:0000 0001 2248 7639)
3 Department of Pathology, University of Health Sciences, Prof. Dr. Cemil Taşçıoğlu City Hospital, Istanbul, Turkey (GRID:grid.506076.2) (ISNI:0000 0004 1797 5496)
4 Augustenburger Platz 1, Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Surgery - Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany (GRID:grid.7468.d) (ISNI:0000 0001 2248 7639); Charitéplatz 1, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Academy, Clinician Scientist Program, Berlin, Germany (GRID:grid.484013.a)
5 Augustenburger Platz 1, Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Hepatology and Gastroenterology - Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662)
6 Carl-Neuberg-Straße 1, Hannover Medical School, Department of General, Visceral and Transplant Surgery, Hannover, Germany (GRID:grid.10423.34) (ISNI:0000 0000 9529 9877)
7 Augustenburger Platz 1, Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Surgery - Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany (GRID:grid.7468.d) (ISNI:0000 0001 2248 7639); Charitéplatz 1, Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany (GRID:grid.7468.d) (ISNI:0000 0001 2248 7639)