Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Extracellular NAD + response to post-hepatectomy liver failure: bridging preclinical and clinical findings.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-
    • الموضوع:
      NAD*/metabolism ; Hepatectomy* ; Liver Failure*/etiology ; Liver Failure*/metabolism ; Liver Failure*/pathology ; Liver Failure*/surgery; Animals ; Humans ; Mice ; Male ; Hepatocytes/metabolism ; Middle Aged ; Female ; Mice, Inbred C57BL ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/surgery ; Disease Models, Animal ; Aged
    • نبذة مختصرة :
      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.
      (© 2024. The Author(s).)
    • References:
      Surg Endosc. 2020 Jan;34(1):349-360. (PMID: 30989374)
      J Biol Chem. 2004 Dec 3;279(49):50754-63. (PMID: 15381699)
      Nat Commun. 2019 Sep 20;10(1):4291. (PMID: 31541116)
      J Clin Endocrinol Metab. 2016 Jan;101(1):275-83. (PMID: 26574954)
      Cell. 2016 Apr 21;165(3):535-50. (PMID: 27104977)
      Rejuvenation Res. 2016 Mar 16;19(5):406-415. (PMID: 26725653)
      Surg Endosc. 2022 Aug;36(8):5854-5862. (PMID: 35641702)
      Eur J Med Res. 2021 Jan 9;26(1):6. (PMID: 33422147)
      Signal Transduct Target Ther. 2020 Oct 7;5(1):227. (PMID: 33028824)
      Br J Pharmacol. 2016 Aug;173(15):2352-68. (PMID: 27174364)
      Cancers (Basel). 2022 Jan 12;14(2):. (PMID: 35053523)
      Nat Cancer. 2022 Apr;3(4):386-401. (PMID: 35484418)
      Cell Metab. 2015 Jul 7;22(1):31-53. (PMID: 26118927)
      JAMA Netw Open. 2019 Jan 4;2(1):e187142. (PMID: 30657533)
      J Hepatol. 2019 Nov;71(5):920-929. (PMID: 31203152)
      Front Immunol. 2021 Aug 04;12:704779. (PMID: 34421911)
      Clin Gastroenterol Hepatol. 2023 Jul;21(8):1978-1991. (PMID: 37121527)
      Langenbecks Arch Surg. 2021 Aug;406(5):1499-1509. (PMID: 34075473)
      HPB (Oxford). 2016 Nov;18(11):915-921. (PMID: 27600437)
      Perioper Med (Lond). 2022 Oct 7;11(1):51. (PMID: 36203213)
      EXCLI J. 2016 Dec 15;15:817-828. (PMID: 28337112)
      Dig Surg. 2012;29(1):6-17. (PMID: 22441614)
      PLoS Biol. 2010 Jun 29;8(6):e1000412. (PMID: 20613859)
      Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2876-81. (PMID: 25730862)
      Purinergic Signal. 2007 Mar;3(1-2):71-81. (PMID: 18404420)
      Life (Basel). 2021 May 31;11(6):. (PMID: 34073099)
      J Physiol. 2022 Mar;600(5):1135-1154. (PMID: 33932956)
      Sci Rep. 2015 Jun 08;5:10775. (PMID: 26053859)
      J Hepatol. 2022 Dec;77(6):1598-1606. (PMID: 36208844)
      Comput Struct Biotechnol J. 2013 May 27;4:e201301012. (PMID: 24688693)
      J Biol Chem. 2008 Dec 12;283(50):34833-43. (PMID: 18945671)
      Cells. 2019 Aug 13;8(8):. (PMID: 31412683)
      Diagn Pathol. 2014 Nov 29;9:221. (PMID: 25432701)
      Dig Surg. 2012;29(1):79-85. (PMID: 22441624)
      HPB (Oxford). 2013 May;15(5):327-36. (PMID: 23323939)
      Cell Metab. 2007 Nov;6(5):363-75. (PMID: 17983582)
      J Clin Epidemiol. 2008 Apr;61(4):344-9. (PMID: 18313558)
      Hepatology. 2016 Apr;63(4):1190-204. (PMID: 26404765)
      FEBS Lett. 2003 Jun 5;544(1-3):74-8. (PMID: 12782293)
      Asian J Surg. 2018 Nov;41(6):551-561. (PMID: 29454570)
      Cell Death Dis. 2020 Jan 27;11(1):70. (PMID: 31988281)
      Nutrients. 2021 Dec 27;14(1):. (PMID: 35010977)
      J Hepatol. 2013 Oct;59(4):731-7. (PMID: 23712050)
      Sci Rep. 2018 Oct 31;8(1):16110. (PMID: 30382125)
      Curr Protoc Mouse Biol. 2013 Oct 18;3(3):141-170. (PMID: 24416636)
      Cell Metab. 2018 May 01;27(5):1067-1080.e5. (PMID: 29685734)
      Hepatol Commun. 2020 May 31;4(8):1183-1192. (PMID: 32766477)
      Sci Transl Med. 2020 Dec 2;12(572):. (PMID: 33268509)
      J Nutr Sci Vitaminol (Tokyo). 2018;64(2):90-98. (PMID: 29710037)
      Nat Metab. 2020 Jan;2(1):9-31. (PMID: 32694684)
      Hepatobiliary Surg Nutr. 2014 Oct;3(5):238-46. (PMID: 25392835)
      Patient Saf Surg. 2008 Apr 25;2:8. (PMID: 18439273)
      Langenbecks Arch Surg. 2021 Aug;406(5):1295-1305. (PMID: 32839889)
      Surgery. 2011 May;149(5):713-24. (PMID: 21236455)
      Cell Mol Life Sci. 2021 Apr;78(7):3317-3331. (PMID: 33755743)
      Front Med (Lausanne). 2024 Jan 08;10:1278641. (PMID: 38259852)
      Sci Rep. 2023 Feb 11;13(1):2464. (PMID: 36774401)
      Pathol Res Pract. 2019 Nov;215(11):152662. (PMID: 31575452)
      CMAJ. 2005 Feb 1;172(3):367-79. (PMID: 15684121)
      Ann Surg. 2009 Jul;250(1):119-25. (PMID: 19561474)
      Eur J Immunol. 2002 Nov;32(11):3225-34. (PMID: 12555668)
      PLoS One. 2012;7(7):e42357. (PMID: 22848760)
      Eur J Surg Oncol. 2021 Feb;47(2):216-224. (PMID: 32943278)
    • Grant Information:
      EKFS, 2020_EKTP29 Else Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)
    • الرقم المعرف:
      0U46U6E8UK (NAD)
    • الموضوع:
      Date Created: 20240814 Date Completed: 20240814 Latest Revision: 20241220
    • الموضوع:
      20241220
    • الرقم المعرف:
      PMC11324947
    • الرقم المعرف:
      10.1038/s42003-024-06661-0
    • الرقم المعرف:
      39143151