Research progress on role of hydrogen sulfide in liver diseases_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SONG Shuxian , ZHANG Yuqing , LI Yundong , LI Kuan , PA Chengzhou ,  GAO Hongqiang

Department of Hepatobiliary Pancreatic Surgery, The First People’s Hospital of Kunming / The Affiliated Calmette Hospital of Kunming Medical University, Kunming 650100, P. R. China;

Corresponding author：

GAO Hongqiang, Email: 13708466595@163.com

Keywords：

hydrogen sulfide; liver ischemia-reperfusion injury; liver cirrhosis; nonalcoholic fatty liver disease; hepatocellular carcinoma; liver transplantation

DOI：

10.7507/1007-9424.202409011

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To understand the current research progress on the role of hydrogen sulfide (H₂S) in liver diseases. Method The relevant literature on the role of H₂S in the liver diseases published in recent years was retrieved and reviewed. Results Current research focused primarily on exploring the mechanisms of H₂S in various liver diseases. Studies had shown that H₂S played an important role in the occurrence and development of liver diseases through mechanisms such as antioxidative stress, anti-inflammatory effects, regulation of autophagy, endoplasmic reticulum stress, angiogenesis, and cell death. Conclusions By supplementing exogenous H₂S, adjusting the gut microbiota, or inhibiting key enzymes involved in H₂S synthesis, the concentration of H₂S in the body can be modulated, providing new strategies for treating liver diseases. However, the related mechanisms are still controversial. Future research should further investigate the specific role of H₂S in different liver diseases and how to precisely control its level in the body to achieve targeted drug delivery.

Citation： SONG Shuxian, ZHANG Yuqing, LI Yundong, LI Kuan, PA Chengzhou, GAO Hongqiang. Research progress on role of hydrogen sulfide in liver diseases. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2025, 32(3): 367-373. doi: 10.7507/1007-9424.202409011 Copy

1.	Wu Z, Xia F, Wang W, et al. Worldwide burden of liver cancer across childhood and adolescence, 2000–2021: a systematic analysis of the Global Burden of Disease Study 2021. EClinicalMedicine, 2024, 75: 102765. doi: 10.1016/j.eclinm.2024.102765.
2.	Younossi ZM, Kalligeros M, Henry L. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol, 2024 Aug 19. doi: 10.3350/cmh.2024.0431. Online ahead of print.
3.	Wang R. Two’s company, three’s a crowd: can H₂S be the third endogenous gaseous transmitter?. FASEB J, 2002, 16(13): 1792-1798.
4.	Wallace JL, Wang R. Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter. Nat Rev Drug Discov, 2015, 14(5): 329-345.
5.	Munteanu C, Turnea MA, Rotariu M. Hydrogen sulfide: An emerging regulator of oxidative stress and cellular homeostasis—A comprehensive one-year review. Antioxidants (Basel), 2023, 12(9): 1737. doi: 10.3390/antiox12091737.
6.	Pandey T, Pandey V. Hydrogen sulfide (H₂S) metabolism: Unraveling cellular regulation, disease implications, and therapeutic prospects for precision medicine. Nitric Oxide, 2024, 144: 20-28.
7.	Sun HJ, Wu ZY, Nie XW, et al. Implications of hydrogen sulfide in liver pathophysiology: Mechanistic insights and therapeutic potential. J Adv Res, 2020, 27: 127-135.
8.	Nguyen TTP, Nguyen PL, Park SH, et al. Hydrogen sulfide and liver health: Insights into liver diseases. Antioxid Redox Signal, 2024, 40(1-3): 122-144.
9.	徐文静. 肝脏内源性硫化氢代谢和功能. 生命的化学, 2020, 40(8): 1289-1297.
10.	Jeitner TM, Azcona JA, Ables GP, et al. Cystine rather than cysteine is the preferred substrate for β-elimination by cystathionine γ-lyase: implications for dietary methionine restriction. Geroscience, 2024, 46(4): 3617-3634.
11.	Kabil O, Vitvitsky V, Xie P, et al. The quantitative significance of the transsulfuration enzymes for H₂S production in murine tissues. Antioxid Redox Signal, 2011, 15(2): 363-372.
12.	Kabil O, Banerjee R. Enzymology of H₂S biogenesis, decay and signaling. Antioxid Redox Signal, 2014, 20(5): 770-782.
13.	Hao Y, Hao Z, Zeng X, et al. Gut microbiota and metabolites of cirrhotic portal hypertension: a novel target on the therapeutic regulation. J Gastroenterol, 2024, 59(9): 788-797.
14.	Li X, Jiang K, Ruan Y, et al. Hydrogen sulfide and its donors: Keys to unlock the chains of nonalcoholic fatty liver disease. Int J Mol Sci, 2022, 23(20): 12202. doi: 10.3390/ijms232012202.
15.	Sun X, Wu S, Mao C, et al. Therapeutic potential of hydrogen sulfide in ischemia and reperfusion injury. Biomolecules, 2024, 14(7): 740. doi: 10.3390/biom14070740.
16.	Lin X, Zhou Y, Ye L, et al. A bibliometric and visualized analysis of hepatic ischemia-reperfusion injury (HIRI) from 2002 to 2021. Heliyon, 2023, 9(11): e22644. doi: 10.1016/j.heliyon.2023.e22644.
17.	Yang F, Gao H, Niu Z, et al. Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway. Braz J Med Biol Res, 2024, 57: e13229. doi: 10.1590/1414-431X2024e13229.
18.	Dugbartey GJ. Cellular and molecular mechanisms of cell damage and cell death in ischemia-reperfusion injury in organ transplantation. Mol Biol Rep, 2024, 51(1): 473. doi: 10.1007/s11033-024-09261-7.
19.	Tang SP, Mao XL, Chen YH, et al. Reactive oxygen species induce fatty liver and ischemia-reperfusion injury by promoting inflammation and cell death. Front Immunol, 2022, 13: 870239. doi: 10.3389/fimmu.2022.870239.
20.	Press AT, Ungelenk L, Medyukhina A, et al. Sodium thiosulfate refuels the hepatic antioxidant pool reducing ischemia-reperfusion-induced liver injury. Free Radic Biol Med, 2023, 204: 151-160.
21.	Zhao S, Song T, Gu Y, et al. Hydrogen sulfide alleviates liver injury through the S-sulfhydrated-kelch-like ECH-associated protein 1/nuclear erythroid 2-related factor 2/low-density lipoprotein receptor-related protein 1 pathway. Hepatology, 2021, 73(1): 282-302.
22.	Bos EM, Snijder PM, Jekel H, et al. Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia/reperfusion injury. Transpl Int, 2012, 25(8): 897-908.
23.	Ruan Z, Liang M, Deng X, et al. Exogenous hydrogen sulfide protects fatty liver against ischemia-reperfusion injury by regulating endoplasmic reticulum stress-induced autophagy in macrophage through mediating the class A scavenger receptor pathway in rats. Cell Biol Int, 2020, 44(1): 306-316.
24.	Cheng P, Wang F, Chen K, et al. Hydrogen sulfide ameliorates ischemia/reperfusion-induced hepatitis by inhibiting apoptosis and autophagy pathways. Mediators Inflamm, 2014, 2014: 935251. doi: 10.1155/2014/935251.
25.	Wu D, Wang H, Teng T, et al. Hydrogen sulfide and autophagy: A double edged sword. Pharmacol Res, 2018, 131: 120-127.
26.	Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology, 2023, 78(6): 1966-1986.
27.	Peh MT, Anwar AB, Ng DS, et al. Effect of feeding a high fat diet on hydrogen sulfide (H₂S) metabolism in the mouse. Nitric Oxide, 2014, 41: 138-145.
28.	Xu W, Cui C, Cui C, et al. Hepatocellular cystathionine γ lyase/hydrogen sulfide attenuates nonalcoholic fatty liver disease by activating farnesoid X receptor. Hepatology, 2022, 76(6): 1794-1810.
29.	Li M, Xu C, Shi J, et al. Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway. Gut, 2018, 67(12): 2169-2180.
30.	Sun L, Zhang S, Yu C, et al. Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway. Am J Physiol Endocrinol Metab, 2015, 309(11): E925-E935. doi: 10.1152/ajpendo.00294.2015.
31.	Wu D, Zhong P, Wang Y, et al. Hydrogen sulfide attenuates high-fat diet-induced non-alcoholic fatty liver disease by inhibiting apoptosis and promoting autophagy via reactive oxygen species/phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway. Front Pharmacol, 2020, 11: 585860. doi: 10.3389/fphar.2020.585860.
32.	Grewal T, Buechler C. Emerging insights on the diverse roles of proprotein convertase subtilisin/kexin type 9 (PCSK9) in chronic liver diseases: Cholesterol metabolism and beyond. Int J Mol Sci, 2022, 23(3): 1070. doi: 10.3390/ijms23031070.
33.	Cui X, Yao M, Feng Y, et al. Exogenous hydrogen sulfide alleviates hepatic endoplasmic reticulum stress via SIRT1/FoxO1/PCSK9 pathway in NAFLD. FASEB J, 2023, 37(8): e23027. doi: 10.1096/fj.202201705RR.
34.	Ci L, Yang X, Gu X, et al. Cystathionine γ-lyase deficiency exacerbates CCl4-induced acute hepatitis and fibrosis in the mouse liver. Antioxid Redox Signal, 2017, 27(3): 133-149.
35.	Zhang F, Jin H, Wu L, et al. Diallyl trisulfide suppresses oxidative stress-induced activation of hepatic stellate cells through production of hydrogen sulfide. Oxid Med Cell Longev, 2017, 2017: 1406726. doi: 10.1155/2017/1406726.
36.	Damba T, Zhang M, Buist-Homan M, et al. Hydrogen sulfide stimulates activation of hepatic stellate cells through increased cellular bio-energetics. Nitric Oxide, 2019, 92: 26-33.
37.	杜少严, 尹硕, 郝文洋, 等. 硫化氢在肝脏疾病中的研究进展. 临床荟萃, 2019, 34(12): 1127-1130.
38.	Lu G, Zhang Y, Ren Y, et al. Diversity and comparison of intestinal desulfovibrio in patients with liver cirrhosis and healthy people. Microorganisms, 2023, 11(2): 276. doi: 10.3390/microorganisms11020276.
39.	郝运, 李川, 文天夫, 等. 全球及中国的肝癌流行病学特征: 基于《2022全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 781-789.
40.	Oza PP, Kashfi K. The triple crown: NO, CO, and H₂S in cancer cell biology. Pharmacol Ther, 2023, 249: 108502. doi: 10.1016/j.pharmthera.2023.108502.
41.	Lu S, Gao Y, Huang X, et al. GYY4137, a hydrogen sulfide (H₂S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway. Int J Oncol, 2014, 44(4): 1259-1267.
42.	Pan Y, Ye S, Yuan D, et al. Hydrogen sulfide (H₂S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells. Mutat Res, 2014, 763-764: 10-18.
43.	Zhou YF, Song SS, Tian MX, et al. Cystathionine β-synthase mediated PRRX2/IL-6/STAT3 inactivation suppresses Tregs infiltration and induces apoptosis to inhibit HCC carcinogenesis. J Immunother Cancer, 2021, 9(8): e003031. doi: 10.1136/jitc-2021-003031.
44.	Li M, Song X, Jin Q, et al. 3-mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma. Liver Int, 2022, 42(5): 1173-1184.
45.	Wang SS, Chen YH, Chen N, et al. Hydrogen sulfide promotes autophagy of hepatocellular carcinoma cells through the PI3K/Akt/mTOR signaling pathway. Cell Death Dis, 2017, 8(3): e2688. doi: 10.1038/cddis.2017.18.
46.	Wu D, Li M, Tian W, et al. Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Sci Rep, 2017, 7(1): 5134. doi: 10.1038/s41598-017-05457-z.
47.	Yu M, Yu H, Wang H, et al. Tumor-associated macrophages activated in the tumor environment of hepatocellular carcinoma: Characterization and treatment (Review). Int J Oncol, 2024, 65(4): 100. doi: 10.3892/ijo.2024.5688.
48.	He Z, Zhu Y, Ma H, et al. Hydrogen sulfide regulates macrophage polarization and necroptosis to accelerate diabetic skin wound healing. Int Immunopharmacol, 2024, 132: 111990. doi: 10.1016/j.intimp.2024.111990.
49.	Ito T, Naini BV, Markovic D, et al. Ischemia-reperfusion injury and its relationship with early allograft dysfunction in liver transplant patients. Am J Transplant, 2021, 21(2): 614-625.
50.	Guo Z, Zhao Q, Jia Z, et al. A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease. J Hepatol, 2023, 79(2): 394-402.
51.	Wang S, Lin X, Tang Y, et al. Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts. Clin Mol Hepatol, 2024, 30(3): 421-435.
52.	McLean ST, Holkup S, Tchir A, et al. UW supplementation with AP39 improves liver viability following static cold storage. Res Sq, 2024 Jun 11: rs. 3. rs-4487319. doi: 10.21203/rs.3.rs-4487319/v1.
53.	Zhang MY, Dugbartey GJ, Juriasingani S, et al. Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation. Biomed Pharmacother, 2022, 145: 112435. doi: 10.1016/j.biopha.2021.112435.
54.	Balaban CL, Rodríguez JV, Tiribelli C, et al. The effect of a hydrogen sulfide releasing molecule (Na₂S) on the cold storage of livers from cardiac dead donor rats. A study in an ex vivo model. Cryobiology, 2015, 71(1): 24-32.
55.	Dugbartey GJ, Juriasingani S, Zhang MY, et al. H₂S donor molecules against cold ischemia-reperfusion injury in preclinical models of solid organ transplantation. Pharmacol Res, 2021, 172: 105842. doi: 10.1016/j.phrs.2021.105842.
56.	Zapolski T, Kornecki W, Jaroszyński A. The influence of balneotherapy using salty sulfide-hydrogen sulfide water on selected markers of the cardiovascular system: A prospective study. J Clin Med, 2024, 13(12): 3526. doi: 10.3390/jcm13123526.
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1. Wu Z, Xia F, Wang W, et al. Worldwide burden of liver cancer across childhood and adolescence, 2000–2021: a systematic analysis of the Global Burden of Disease Study 2021. EClinicalMedicine, 2024, 75: 102765. doi: 10.1016/j.eclinm.2024.102765.
2. Younossi ZM, Kalligeros M, Henry L. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol, 2024 Aug 19. doi: 10.3350/cmh.2024.0431. Online ahead of print.
3. Wang R. Two’s company, three’s a crowd: can H₂S be the third endogenous gaseous transmitter?. FASEB J, 2002, 16(13): 1792-1798.
4. Wallace JL, Wang R. Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter. Nat Rev Drug Discov, 2015, 14(5): 329-345.
5. Munteanu C, Turnea MA, Rotariu M. Hydrogen sulfide: An emerging regulator of oxidative stress and cellular homeostasis—A comprehensive one-year review. Antioxidants (Basel), 2023, 12(9): 1737. doi: 10.3390/antiox12091737.
6. Pandey T, Pandey V. Hydrogen sulfide (H₂S) metabolism: Unraveling cellular regulation, disease implications, and therapeutic prospects for precision medicine. Nitric Oxide, 2024, 144: 20-28.
7. Sun HJ, Wu ZY, Nie XW, et al. Implications of hydrogen sulfide in liver pathophysiology: Mechanistic insights and therapeutic potential. J Adv Res, 2020, 27: 127-135.
8. Nguyen TTP, Nguyen PL, Park SH, et al. Hydrogen sulfide and liver health: Insights into liver diseases. Antioxid Redox Signal, 2024, 40(1-3): 122-144.
9. 徐文静. 肝脏内源性硫化氢代谢和功能. 生命的化学, 2020, 40(8): 1289-1297.
10. Jeitner TM, Azcona JA, Ables GP, et al. Cystine rather than cysteine is the preferred substrate for β-elimination by cystathionine γ-lyase: implications for dietary methionine restriction. Geroscience, 2024, 46(4): 3617-3634.
11. Kabil O, Vitvitsky V, Xie P, et al. The quantitative significance of the transsulfuration enzymes for H₂S production in murine tissues. Antioxid Redox Signal, 2011, 15(2): 363-372.
12. Kabil O, Banerjee R. Enzymology of H₂S biogenesis, decay and signaling. Antioxid Redox Signal, 2014, 20(5): 770-782.
13. Hao Y, Hao Z, Zeng X, et al. Gut microbiota and metabolites of cirrhotic portal hypertension: a novel target on the therapeutic regulation. J Gastroenterol, 2024, 59(9): 788-797.
14. Li X, Jiang K, Ruan Y, et al. Hydrogen sulfide and its donors: Keys to unlock the chains of nonalcoholic fatty liver disease. Int J Mol Sci, 2022, 23(20): 12202. doi: 10.3390/ijms232012202.
15. Sun X, Wu S, Mao C, et al. Therapeutic potential of hydrogen sulfide in ischemia and reperfusion injury. Biomolecules, 2024, 14(7): 740. doi: 10.3390/biom14070740.
16. Lin X, Zhou Y, Ye L, et al. A bibliometric and visualized analysis of hepatic ischemia-reperfusion injury (HIRI) from 2002 to 2021. Heliyon, 2023, 9(11): e22644. doi: 10.1016/j.heliyon.2023.e22644.
17. Yang F, Gao H, Niu Z, et al. Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway. Braz J Med Biol Res, 2024, 57: e13229. doi: 10.1590/1414-431X2024e13229.
18. Dugbartey GJ. Cellular and molecular mechanisms of cell damage and cell death in ischemia-reperfusion injury in organ transplantation. Mol Biol Rep, 2024, 51(1): 473. doi: 10.1007/s11033-024-09261-7.
19. Tang SP, Mao XL, Chen YH, et al. Reactive oxygen species induce fatty liver and ischemia-reperfusion injury by promoting inflammation and cell death. Front Immunol, 2022, 13: 870239. doi: 10.3389/fimmu.2022.870239.
20. Press AT, Ungelenk L, Medyukhina A, et al. Sodium thiosulfate refuels the hepatic antioxidant pool reducing ischemia-reperfusion-induced liver injury. Free Radic Biol Med, 2023, 204: 151-160.
21. Zhao S, Song T, Gu Y, et al. Hydrogen sulfide alleviates liver injury through the S-sulfhydrated-kelch-like ECH-associated protein 1/nuclear erythroid 2-related factor 2/low-density lipoprotein receptor-related protein 1 pathway. Hepatology, 2021, 73(1): 282-302.
22. Bos EM, Snijder PM, Jekel H, et al. Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia/reperfusion injury. Transpl Int, 2012, 25(8): 897-908.
23. Ruan Z, Liang M, Deng X, et al. Exogenous hydrogen sulfide protects fatty liver against ischemia-reperfusion injury by regulating endoplasmic reticulum stress-induced autophagy in macrophage through mediating the class A scavenger receptor pathway in rats. Cell Biol Int, 2020, 44(1): 306-316.
24. Cheng P, Wang F, Chen K, et al. Hydrogen sulfide ameliorates ischemia/reperfusion-induced hepatitis by inhibiting apoptosis and autophagy pathways. Mediators Inflamm, 2014, 2014: 935251. doi: 10.1155/2014/935251.
25. Wu D, Wang H, Teng T, et al. Hydrogen sulfide and autophagy: A double edged sword. Pharmacol Res, 2018, 131: 120-127.
26. Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology, 2023, 78(6): 1966-1986.
27. Peh MT, Anwar AB, Ng DS, et al. Effect of feeding a high fat diet on hydrogen sulfide (H₂S) metabolism in the mouse. Nitric Oxide, 2014, 41: 138-145.
28. Xu W, Cui C, Cui C, et al. Hepatocellular cystathionine γ lyase/hydrogen sulfide attenuates nonalcoholic fatty liver disease by activating farnesoid X receptor. Hepatology, 2022, 76(6): 1794-1810.
29. Li M, Xu C, Shi J, et al. Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway. Gut, 2018, 67(12): 2169-2180.
30. Sun L, Zhang S, Yu C, et al. Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway. Am J Physiol Endocrinol Metab, 2015, 309(11): E925-E935. doi: 10.1152/ajpendo.00294.2015.
31. Wu D, Zhong P, Wang Y, et al. Hydrogen sulfide attenuates high-fat diet-induced non-alcoholic fatty liver disease by inhibiting apoptosis and promoting autophagy via reactive oxygen species/phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway. Front Pharmacol, 2020, 11: 585860. doi: 10.3389/fphar.2020.585860.
32. Grewal T, Buechler C. Emerging insights on the diverse roles of proprotein convertase subtilisin/kexin type 9 (PCSK9) in chronic liver diseases: Cholesterol metabolism and beyond. Int J Mol Sci, 2022, 23(3): 1070. doi: 10.3390/ijms23031070.
33. Cui X, Yao M, Feng Y, et al. Exogenous hydrogen sulfide alleviates hepatic endoplasmic reticulum stress via SIRT1/FoxO1/PCSK9 pathway in NAFLD. FASEB J, 2023, 37(8): e23027. doi: 10.1096/fj.202201705RR.
34. Ci L, Yang X, Gu X, et al. Cystathionine γ-lyase deficiency exacerbates CCl4-induced acute hepatitis and fibrosis in the mouse liver. Antioxid Redox Signal, 2017, 27(3): 133-149.
35. Zhang F, Jin H, Wu L, et al. Diallyl trisulfide suppresses oxidative stress-induced activation of hepatic stellate cells through production of hydrogen sulfide. Oxid Med Cell Longev, 2017, 2017: 1406726. doi: 10.1155/2017/1406726.
36. Damba T, Zhang M, Buist-Homan M, et al. Hydrogen sulfide stimulates activation of hepatic stellate cells through increased cellular bio-energetics. Nitric Oxide, 2019, 92: 26-33.
37. 杜少严, 尹硕, 郝文洋, 等. 硫化氢在肝脏疾病中的研究进展. 临床荟萃, 2019, 34(12): 1127-1130.
38. Lu G, Zhang Y, Ren Y, et al. Diversity and comparison of intestinal desulfovibrio in patients with liver cirrhosis and healthy people. Microorganisms, 2023, 11(2): 276. doi: 10.3390/microorganisms11020276.
39. 郝运, 李川, 文天夫, 等. 全球及中国的肝癌流行病学特征: 基于《2022全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 781-789.
40. Oza PP, Kashfi K. The triple crown: NO, CO, and H₂S in cancer cell biology. Pharmacol Ther, 2023, 249: 108502. doi: 10.1016/j.pharmthera.2023.108502.
41. Lu S, Gao Y, Huang X, et al. GYY4137, a hydrogen sulfide (H₂S) donor, shows potent anti-hepatocellular carcinoma activity through blocking the STAT3 pathway. Int J Oncol, 2014, 44(4): 1259-1267.
42. Pan Y, Ye S, Yuan D, et al. Hydrogen sulfide (H₂S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells. Mutat Res, 2014, 763-764: 10-18.
43. Zhou YF, Song SS, Tian MX, et al. Cystathionine β-synthase mediated PRRX2/IL-6/STAT3 inactivation suppresses Tregs infiltration and induces apoptosis to inhibit HCC carcinogenesis. J Immunother Cancer, 2021, 9(8): e003031. doi: 10.1136/jitc-2021-003031.
44. Li M, Song X, Jin Q, et al. 3-mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma. Liver Int, 2022, 42(5): 1173-1184.
45. Wang SS, Chen YH, Chen N, et al. Hydrogen sulfide promotes autophagy of hepatocellular carcinoma cells through the PI3K/Akt/mTOR signaling pathway. Cell Death Dis, 2017, 8(3): e2688. doi: 10.1038/cddis.2017.18.
46. Wu D, Li M, Tian W, et al. Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Sci Rep, 2017, 7(1): 5134. doi: 10.1038/s41598-017-05457-z.
47. Yu M, Yu H, Wang H, et al. Tumor-associated macrophages activated in the tumor environment of hepatocellular carcinoma: Characterization and treatment (Review). Int J Oncol, 2024, 65(4): 100. doi: 10.3892/ijo.2024.5688.
48. He Z, Zhu Y, Ma H, et al. Hydrogen sulfide regulates macrophage polarization and necroptosis to accelerate diabetic skin wound healing. Int Immunopharmacol, 2024, 132: 111990. doi: 10.1016/j.intimp.2024.111990.
49. Ito T, Naini BV, Markovic D, et al. Ischemia-reperfusion injury and its relationship with early allograft dysfunction in liver transplant patients. Am J Transplant, 2021, 21(2): 614-625.
50. Guo Z, Zhao Q, Jia Z, et al. A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease. J Hepatol, 2023, 79(2): 394-402.
51. Wang S, Lin X, Tang Y, et al. Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts. Clin Mol Hepatol, 2024, 30(3): 421-435.
52. McLean ST, Holkup S, Tchir A, et al. UW supplementation with AP39 improves liver viability following static cold storage. Res Sq, 2024 Jun 11: rs. 3. rs-4487319. doi: 10.21203/rs.3.rs-4487319/v1.
53. Zhang MY, Dugbartey GJ, Juriasingani S, et al. Sodium thiosulfate-supplemented UW solution protects renal grafts against prolonged cold ischemia-reperfusion injury in a murine model of syngeneic kidney transplantation. Biomed Pharmacother, 2022, 145: 112435. doi: 10.1016/j.biopha.2021.112435.
54. Balaban CL, Rodríguez JV, Tiribelli C, et al. The effect of a hydrogen sulfide releasing molecule (Na₂S) on the cold storage of livers from cardiac dead donor rats. A study in an ex vivo model. Cryobiology, 2015, 71(1): 24-32.
55. Dugbartey GJ, Juriasingani S, Zhang MY, et al. H₂S donor molecules against cold ischemia-reperfusion injury in preclinical models of solid organ transplantation. Pharmacol Res, 2021, 172: 105842. doi: 10.1016/j.phrs.2021.105842.
56. Zapolski T, Kornecki W, Jaroszyński A. The influence of balneotherapy using salty sulfide-hydrogen sulfide water on selected markers of the cardiovascular system: A prospective study. J Clin Med, 2024, 13(12): 3526. doi: 10.3390/jcm13123526.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress on role of hydrogen sulfide in liver diseases

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