Exploring Dysregulated Ferroptosis-Related Genes in Septic Myocardial Injury Based on Human Heart Transcriptomes: Evidence and New Insights

References

• Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ. 2016;353:i1585. PMID: 27217054. doi:10.1136/bmj.i1585
   PubMed Web of Science ®Google Scholar
• Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–810. PMID: 26903338. doi:10.1001/jama.2016.0287
   PubMed Web of Science ®Google Scholar
• Huang M, Cai S, Su J. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci. 2019;20(21). PMID: 31671729. doi:10.3390/ijms20215376
   Google Scholar
• Perner A, Gordon AC, De Backer D, et al. Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med. 2016;42(12):1958–1969. PMID: 27695884. doi:10.1007/s00134-016-4577-z
   PubMed Web of Science ®Google Scholar
• Prescott HC, Angus DC. Enhancing Recovery From Sepsis: a Review. JAMA. 2018;319(1):62–75. PMID: 29297082. doi:10.1001/jama.2017.17687
   PubMed Web of Science ®Google Scholar
• Martin L, Derwall M, Al Zoubi S, et al. The septic heart: current understanding of molecular mechanisms and clinical implications. Chest. 2019;155(2):427–437. PMID: 30171861. doi:10.1016/j.chest.2018.08.1037
   PubMed Web of Science ®Google Scholar
• Walley KR. Sepsis-induced myocardial dysfunction. Curr Opin Crit Care. 2018;24(4):292–299. PMID: 29846206. doi:10.1097/mcc.0000000000000507
   PubMed Web of Science ®Google Scholar
• Hollenberg SM, Singer M. Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol. 2021;18(6):424–434. PMID: 33473203. doi:10.1038/s41569-020-00492-2
   PubMed Web of Science ®Google Scholar
• Lin Y, Xu Y, Zhang Z. Sepsis-induced myocardial dysfunction (SIMD): the pathophysiological mechanisms and therapeutic strategies targeting mitochondria. Inflammation. 2020;43(4):1184–1200. PMID: 32333359. doi:10.1007/s10753-020-01233-w
   PubMed Web of Science ®Google Scholar
• Stanzani G, Duchen MR, Singer M. The role of mitochondria in sepsis-induced cardiomyopathy. Biochim Biophys Acta Mol Basis Dis. 2019;1865(4):759–773. PMID: 30342158. doi:10.1016/j.bbadis.2018.10.011
   PubMed Web of Science ®Google Scholar
• Pierrakos C, Velissaris D, Bisdorff M, Marshall JC, Vincent JL. Biomarkers of sepsis: time for a reappraisal. Critical Care. 2020;24(1):287. PMID: 32503670. doi:10.1186/s13054-020-02993-5
   PubMed Web of Science ®Google Scholar
• Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet. 2018;392(10141):75–87. PMID: 29937192. doi:10.1016/s0140-6736(18)30696-2
   PubMed Web of Science ®Google Scholar
• Liu Q, Wu J, Zhang X, Wu X, Zhao Y, Ren J. Iron homeostasis and disorders revisited in the sepsis. Free Radic Biol Med. 2021;165:1–13. PMID: 33486088. doi:10.1016/j.freeradbiomed.2021.01.025
   PubMed Web of Science ®Google Scholar
• Fang X, Ardehali H, Min J, Wang F. The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease. Nat Rev Cardiol. 2022:1–17. PMID: 35788564; PubMed Central PMCID: PMCPMC9252571. doi:10.1038/s41569-022-00735-4
   Google Scholar
• Brandtner A, Tymoszuk P, Nairz M, et al. Linkage of alterations in systemic iron homeostasis to patients’ outcome in sepsis: a prospective study. J Intensive Care. 2020;8:76. PMID: 33014378. doi:10.1186/s40560-020-00495-8
   PubMed Web of Science ®Google Scholar
• Akkaş İ, Ince N, Sungur MA. Serum trace element and heavy metal levels in patients with sepsis. Aging Male. 2020;23(3):222–226. PMID: 32183594. doi:10.1080/13685538.2020.1740200
   PubMedGoogle Scholar
• Xl L, Gy Z. Ferroptosis in sepsis: the mechanism, the role and the therapeutic potential. Front Immunol. 2022;13:956361. PMID: 35990689. doi:10.3389/fimmu.2022.956361
   PubMedGoogle Scholar
• Stockwell BR. Ferroptosis turns 10: emerging mechanisms, physiological functions, and therapeutic applications. Cell. 2022;185(14):2401–2421. PMID: 35803244. doi:10.1016/j.cell.2022.06.003
   PubMed Web of Science ®Google Scholar
• Kong C, Ni X, Wang Y, et al. ICA69 aggravates ferroptosis causing septic cardiac dysfunction via STING trafficking. Cell Death Discov. 2022;8(1):187. PMID: 35397620. doi:10.1038/s41420-022-00957-y
   PubMedGoogle Scholar
• Xiao Z, Kong B, Fang J, et al. Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction. Bioengineered. 2021;12(2):9367–9376. PMID: 34787054. doi:10.1080/21655979.2021.2001913
   PubMed Web of Science ®Google Scholar
• Wang X, Simayi A, Fu J, Zhao X, Xu G. Resveratrol mediates the miR-149/HMGB1 axis and regulates the ferroptosis pathway to protect myocardium in endotoxemia mice. Am J Physiol Endocrinol Metab. 2022;323(1):E21–e32. PMID: 35532075. doi:10.1152/ajpendo.00227.2021
   PubMed Web of Science ®Google Scholar
• Zou HX, Qiu BQ, Lai SQ, et al. Role of ferroptosis-related genes in Stanford type a aortic dissection and identification of key genes: new insights from bioinformatic analysis. Bioengineered. 2021;12(2):9976–9990. PMID: 34652258. doi:10.1080/21655979.2021.1988840
   PubMed Web of Science ®Google Scholar
• Banchereau R, Cepika AM, Banchereau J, Pascual V. Understanding human autoimmunity and autoinflammation through transcriptomics. Annu Rev Immunol. 2017;35:337–370. PMID: 28142321. doi:10.1146/annurev-immunol-051116-052225
   PubMed Web of Science ®Google Scholar
• Ren X, Wen W, Fan X, et al. COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas. Cell. 2021;184(7):1895–913.e19. PMID: 33657410. doi:10.1016/j.cell.2021.01.053
   PubMed Web of Science ®Google Scholar
• O’Donoghue ML, Rosenson RS, Gencer B, et al. Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease. N Engl J Med. 2022. PMID: 36342163. doi:10.1056/NEJMoa2211023
   PubMedGoogle Scholar
• Wang W, Xu H, Lin H, Molnar M, Ren H. The role of the cholinergic anti-inflammatory pathway in septic cardiomyopathy. Int Immunopharmacol. 2021;90:107160. PMID: 33243604. doi:10.1016/j.intimp.2020.107160
   PubMedGoogle Scholar
• Dou J, Liu X, Yang L, Huang D, Tan X. Ferroptosis interaction with inflammatory microenvironments: mechanism, biology, and treatment. Biomed Pharmacother. 2022;155:113711. PMID: 36126457. doi:10.1016/j.biopha.2022.113711
   PubMedGoogle Scholar
• Ni S, Yuan Y, Song S, Li X. A double-edged sword with a therapeutic target: iron and ferroptosis in immune regulation. Nutr Rev. 2022. PMID: 36130411. doi:10.1093/nutrit/nuac071
   PubMedGoogle Scholar
• Zou HX, Qiu BQ, Zhang ZY, et al. Dysregulated autophagy-related genes in septic cardiomyopathy: comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation. Front Cardiovasc Med. 2022;9:923066. PMID: 35983185. doi:10.3389/fcvm.2022.923066
   PubMedGoogle Scholar
• He Y, Yuan H, Wu C, Xie Z. DISC: a highly scalable and accurate inference of gene expression and structure for single-cell transcriptomes using semi-supervised deep learning. Genome Biol. 2020;21(1):170. PMID: 32650816. doi:10.1186/s13059-020-02083-3
   PubMedGoogle Scholar
• Zou HX, Qiu BQ, Lai SQ, et al. Iron metabolism and idiopathic pulmonary arterial hypertension: new insights from bioinformatic analysis. Biomed Res Int. 2021;2021:5669412. PMID: 34722766. doi:10.1155/2021/5669412
   PubMed Web of Science ®Google Scholar
• Zhou N, Bao J. FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database. 2020;2020. PMID: 32219413. doi:10.1093/database/baaa021
   Google Scholar
• Shen W, Song Z, Zhong X, et al. Sangerbox: a comprehensive, interaction-friendly clinical bioinformatics analysis platform. iMeta. 2022;1(3):e36. doi:10.1002/imt2.36
   Google Scholar
• Yu G, Wang LG, Han Y, He QY. ClusterProfiler: an R package for comparing biological themes among gene clusters. Omics. 2012;16(5):284–287. PMID: 22455463. doi:10.1089/omi.2011.0118
   PubMed Web of Science ®Google Scholar
• Zhou K, Wu G, Li Y, et al. Protective effects of indomethacin and dexamethasone in a goat model with intrauterine balloon aortic valvuloplasty. J Biomed Sci. 2012;19(1):74. doi:10.1186/1423-0127-19-74
   PubMedGoogle Scholar
• Wu B, Song H, Fan M, et al. Luteolin attenuates sepsis‑induced myocardial injury by enhancing autophagy in mice. Int J Mol Med. 2020;45(5):1477–1487. PMID: 32323750. doi:10.3892/ijmm.2020.4536
   PubMed Web of Science ®Google Scholar
• Boyd JH, Kan B, Roberts H, Wang Y, Walley KR. S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products. Circ Res. 2008;102(10):1239–1246. PMID: 18403730. doi:10.1161/circresaha.107.167544
   PubMedGoogle Scholar
• Anwar-mohamed A, Zordoky BN, Aboutabl ME, El-Kadi AO. Alteration of cardiac cytochrome P450-mediated arachidonic acid metabolism in response to lipopolysaccharide-induced acute systemic inflammation. Pharmacol Res. 2010;61(5):410–418. PMID: 20045729. doi:10.1016/j.phrs.2009.12.015
   PubMed Web of Science ®Google Scholar
• Shi G, Xing L, Wu D, et al. A rare mutation of β(1)-adrenergic receptor affects sleep/wake behaviors. Neuron. 2019;103(6):1044–55.e7. PMID: 31473062. doi:10.1016/j.neuron.2019.07.026
   PubMedGoogle Scholar
• Tucker NR, Chaffin M, Fleming SJ, et al. Transcriptional and cellular diversity of the human heart. Circulation. 2020;142(5):466–482. PMID: 32403949. doi:10.1161/circulationaha.119.045401
   PubMed Web of Science ®Google Scholar
• Miao Y, Tian L, Martin M, et al. Abstract 12937: single-cell transcriptomic analysis reveals developmentally impaired endocardial population in hypoplastic left heart syndrome. Circulation. 2020;142(Suppl_3):A12937–A. doi:10.1161/circ.142.suppl_3.12937
   Google Scholar
• Yoo M, Shin J, Kim J, et al. DSigDB: drug signatures database for gene set analysis. Bioinformatics. 2015;31(18):3069–3071. PMID: 25990557. doi:10.1093/bioinformatics/btv313
   PubMed Web of Science ®Google Scholar
• Chen EY, Tan CM, Kou Y, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform. 2013;14:128. PMID: 23586463. doi:10.1186/1471-2105-14-128
   PubMed Web of Science ®Google Scholar
• Kim S, Chen J, Cheng T, et al. PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res. 2021;49(D1):D1388–d95. PMID: 33151290. doi:10.1093/nar/gkaa971
   PubMed Web of Science ®Google Scholar
• Burley SK, Bhikadiya C, Bi C, et al. RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences. Nucleic Acids Res. 2020;49(D1):D437–D51. doi:10.1093/nar/gkaa1038
   Google Scholar
• Jumper J, Evans R, Pritzel A, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583–589. PMID: 34265844. doi:10.1038/s41586-021-03819-2
   PubMed Web of Science ®Google Scholar
• Li N, Wang W, Zhou H, et al. Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury. Free Radic Biol Med. 2020;160:303–318. PMID: 32846217. doi:10.1016/j.freeradbiomed.2020.08.009
   PubMed Web of Science ®Google Scholar
• Miotto G, Rossetto M, Di Paolo ML, et al. Insight into the mechanism of ferroptosis inhibition by ferrostatin-1. Redox Biol. 2020;28:101328. PMID: 31574461. doi:10.1016/j.redox.2019.101328
   PubMed Web of Science ®Google Scholar
• Rosenzweig R, Kumar V, Gupta S, et al. Estrogen receptor-β agonists modulate t-lymphocyte activation and ameliorate left ventricular remodeling during chronic heart failure. Circ Heart Fail. 2022;15(7):e008997. PMID: 35730443. doi:10.1161/circheartfailure.121.008997
   PubMedGoogle Scholar
• Kumar V, Prabhu SD, Bansal SS. CD4(+) T-lymphocytes exhibit biphasic kinetics post-myocardial infarction. Front Cardiovasc Med. 2022;9:992653. PMID: 36093172. doi:10.3389/fcvm.2022.992653
   PubMedGoogle Scholar
• Liu YC, Yu MM, Shou ST, Chai YF. Sepsis-induced cardiomyopathy: mechanisms and treatments. Front Immunol. 2017;8:1021. PMID: 28970829. doi:10.3389/fimmu.2017.01021
   PubMed Web of Science ®Google Scholar
• Xu S, Min J, Wang F. Ferroptosis: an emerging player in immune cells (News&Views). Sci Bull. 2021;2021:2731–2744.
   Google Scholar
• Wang P, Lu YQ. Ferroptosis: a critical moderator in the life cycle of immune cells. Front Immunol. 2022;13:877634. PMID: 35619718. doi:10.3389/fimmu.2022.877634
   PubMedGoogle Scholar
• Cao G, Zeng Y, Zhao Y, et al. H2S regulation of ferroptosis attenuates sepsis‑induced cardiomyopathy. Mol Med Rep. 2022;26(5). PMID: 36102305. doi:10.3892/mmr.2022.12851
   Google Scholar
• Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 2021;22(4):266–282. PMID: 33495651. doi:10.1038/s41580-020-00324-8
   PubMed Web of Science ®Google Scholar
• Ajoolabady A, Aslkhodapasandhokmabad H, Libby P, et al. Ferritinophagy and ferroptosis in the management of metabolic diseases. Trends Endocrinol Metab. 2021;32(7):444–462. PMID: 34006412. doi:10.1016/j.tem.2021.04.010
   PubMed Web of Science ®Google Scholar
• Qin X, Zhang J, Wang B, et al. Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells. Autophagy. 2021;17(12):4266–4285. PMID: 33843441. doi:10.1080/15548627.2021.1911016
   PubMed Web of Science ®Google Scholar
• Zhang Z, Guo M, Li Y, et al. RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells. Autophagy. 2020;16(8):1482–1505. PMID: 31679460. doi:10.1080/15548627.2019.1687985
   PubMed Web of Science ®Google Scholar
• Zhang X, Du L, Qiao Y, et al. Ferroptosis is governed by differential regulation of transcription in liver cancer. Redox Biol. 2019;24:101211. PMID: 31108460. doi:10.1016/j.redox.2019.101211
   PubMed Web of Science ®Google Scholar
• Yang WS, Stockwell BR. Ferroptosis: death by Lipid Peroxidation. Trends Cell Biol. 2016;26(3):165–176. PMID: 26653790. doi:10.1016/j.tcb.2015.10.014
   PubMed Web of Science ®Google Scholar
• Park MW, Cha HW, Kim J, et al. NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer’s diseases. Redox Biol. 2021;41:101947. PMID: 33774476. doi:10.1016/j.redox.2021.101947
   PubMed Web of Science ®Google Scholar
• Liu N, Liang Y, Wei T, et al. The role of ferroptosis mediated by NRF2/ERK-regulated ferritinophagy in CdTe QDs-induced inflammation in macrophage. J Hazard Mater. 2022;436:129043. PMID: 35525219. doi:10.1016/j.jhazmat.2022.129043
   PubMed Web of Science ®Google Scholar
• Yi J, Zhu J, Wu J, Thompson CB, Jiang X. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci U S A. 2020;117(49):31189–31197. PMID: 33229547. doi:10.1073/pnas.2017152117
   PubMed Web of Science ®Google Scholar
• Xing G, Meng L, Cao S, et al. PPARα alleviates iron overload-induced ferroptosis in mouse liver. EMBO Rep. 2022;23(8):e52280. PMID: 35703725. doi:10.15252/embr.202052280
   PubMed Web of Science ®Google Scholar
• Xu M, Tao J, Yang Y, et al. Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis. Cell Death Dis. 2020;11(2):86. PMID: 32015337. doi:10.1038/s41419-020-2299-1
   PubMed Web of Science ®Google Scholar
• Li Y, Cao Y, Xiao J, et al. Inhibitor of apoptosis-stimulating protein of p53 inhibits ferroptosis and alleviates intestinal ischemia/reperfusion-induced acute lung injury. Cell Death Differ. 2020;27(9):2635–2650. PMID: 32203170. doi:10.1038/s41418-020-0528-x
   PubMed Web of Science ®Google Scholar
• Yuan S, Wei C, Liu G, et al. Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1α/SLC7A11 pathway. Cell Prolif. 2022;55(1):e13158. PMID: 34811833. doi:10.1111/cpr.13158
   PubMed Web of Science ®Google Scholar
• Zhou B, Liu J, Kang R, Klionsky DJ, Kroemer G, Tang D. Ferroptosis is a type of autophagy-dependent cell death. Semin Cancer Biol. 2020;66:89–100. PMID: 30880243. doi:10.1016/j.semcancer.2019.03.002
   PubMed Web of Science ®Google Scholar
• Ma H, Wang X, Ha T, et al. MicroRNA-125b prevents cardiac dysfunction in polymicrobial sepsis by targeting TRAF6-mediated nuclear factor κB Activation and p53-mediated apoptotic signaling. J Infect Dis. 2016;214(11):1773–1783. PMID: 27683819. doi:10.1093/infdis/jiw449
   PubMed Web of Science ®Google Scholar
• Yu Y, Ou-Yang WX, Zhang H, et al. MiR-125b enhances autophagic flux to improve septic cardiomyopathy via targeting STAT3/HMGB1. Exp Cell Res. 2021;409(2):112842. PMID: 34563514. doi:10.1016/j.yexcr.2021.112842
   PubMedGoogle Scholar
• Zhao H, Zhang M, Zhou F, et al. Cinnamaldehyde ameliorates LPS-induced cardiac dysfunction via TLR4-NOX4 pathway: the regulation of autophagy and ROS production. J Mol Cell Cardiol. 2016;101:11–24. PMID: 27838370. doi:10.1016/j.yjmcc.2016.10.017
   PubMed Web of Science ®Google Scholar
• Xia C, Dong R, Chen C, Wang H, Wang DW. Cardiomyocyte specific expression of Acyl-coA thioesterase 1 attenuates sepsis induced cardiac dysfunction and mortality. Biochem Biophys Res Commun. 2015;468(4):533–540. PMID: 26518651. doi:10.1016/j.bbrc.2015.10.078
   PubMedGoogle Scholar
• Yao Y, Sun F, Lei M. miR-25 inhibits sepsis-induced cardiomyocyte apoptosis by targetting PTEN. Biosci Rep. 2018;38(2). PMID: 29440462. doi:10.1042/bsr20171511
   Google Scholar
• Ehrman RR, Sullivan AN, Favot MJ, et al. Pathophysiology, echocardiographic evaluation, biomarker findings, and prognostic implications of septic cardiomyopathy: a review of the literature. Critical Care. 2018;22(1):112. PMID: 29724231. doi:10.1186/s13054-018-2043-8
   PubMedGoogle Scholar
• Lv X, Wang H. Pathophysiology of sepsis-induced myocardial dysfunction. Mil Med Res. 2016;3:30. PMID: 27708836. doi:10.1186/s40779-016-0099-9
   PubMed Web of Science ®Google Scholar
• Pinto AR, Paolicelli R, Salimova E, et al. An abundant tissue macrophage population in the adult murine heart with a distinct alternatively-activated macrophage profile. PLoS One. 2012;7(5):e36814. PMID: 22590615. doi:10.1371/journal.pone.0036814
   PubMed Web of Science ®Google Scholar
• Nicolás-ávila JA, Pena-Couso L, Muñoz-Cánoves P, Hidalgo A. Macrophages, metabolism and heterophagy in the heart. Circ Res. 2022;130(3):418–431. PMID: 35113662. doi:10.1161/circresaha.121.319812
   PubMedGoogle Scholar
• Wang L, Li Y, Wang X, et al. GDF3 protects mice against sepsis-induced cardiac dysfunction and mortality by suppression of macrophage pro-inflammatory phenotype. Cells. 2020;9(1). PMID: 31947892. doi:10.3390/cells9010120
   Google Scholar
• Zhang J, Wang M, Ye J, et al. The Anti-inflammatory mediator resolvin e1 protects mice against lipopolysaccharide-induced heart injury. Front Pharmacol. 2020;11:203. PMID: 32256344. doi:10.3389/fphar.2020.00203
   PubMed Web of Science ®Google Scholar
• Guo L, Shen S, Rowley JW, et al. Platelet MHC class I mediates CD8+ T-cell suppression during sepsis. Blood. 2021;138(5):401–416. PMID: 33895821. doi:10.1182/blood.2020008958
   PubMed Web of Science ®Google Scholar
• Guo L, Meng M, Wei Y, et al. Protective Effects of Live Combined B. subtilis and E. faecium in polymicrobial sepsis through modulating activation and transformation of macrophages and mast cells. Front Pharmacol. 2018;9:1506. PMID: 30719003. doi:10.3389/fphar.2018.01506
   PubMedGoogle Scholar
• Ver Elst KM, Spapen HD, Nguyen DN, Garbar C, Huyghens LP, Gorus FK. Cardiac troponins I and T are biological markers of left ventricular dysfunction in septic shock. Clin Chem. 2000;46(5):650–657. PMID: 10794747. doi:10.1093/clinchem/46.5.650
   PubMed Web of Science ®Google Scholar
• Nedeva C. Inflammation and cell death of the innate and adaptive immune system during sepsis. Biomolecules. 2021;11(7). PMID: 34356636. doi:10.3390/biom11071011
   PubMedGoogle Scholar
• Sun K, Li YY, Jin J. A double-edged sword of immuno-microenvironment in cardiac homeostasis and injury repair. Curr Signal Transduct Ther. 2021;6(1):79. PMID: 33612829. doi:10.1038/s41392-020-00455-6
   Google Scholar
• van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17(7):407–420. PMID: 28436424. doi:10.1038/nri.2017.36
   PubMed Web of Science ®Google Scholar
• Bai T, Hu X, Zheng Y, Wang S, Kong J, Cai L. Resveratrol protects against lipopolysaccharide-induced cardiac dysfunction by enhancing SERCA2a activity through promoting the phospholamban oligomerization. Am J Physiol Heart Circ Physiol. 2016;311(4):H1051–h62. PMID: 27591219. doi:10.1152/ajpheart.00296.2016
   PubMedGoogle Scholar
• Hao E, Lang F, Chen Y, et al. Resveratrol alleviates endotoxin-induced myocardial toxicity via the Nrf2 transcription factor. PLoS One. 2013;8(7):e69452. PMID: 23894482. doi:10.1371/journal.pone.0069452
   PubMed Web of Science ®Google Scholar
• Shang X, Lin K, Yu R, et al. Resveratrol protects the myocardium in sepsis by activating the phosphatidylinositol 3-kinases (PI3K)/AKT/mammalian target of rapamycin (mtor) pathway and inhibiting the nuclear factor-κB (NF-κB) signaling pathway. Med Sci Monit. 2019;25:9290–9298. PMID: 31806860. doi:10.12659/msm.918369
   PubMed Web of Science ®Google Scholar
• Sebai H, Sani M, Aouani E, Ghanem-Boughanmi N. Cardioprotective effect of resveratrol on lipopolysaccharide-induced oxidative stress in rat. Drug Chem Toxicol. 2011;34(2):146–150. PMID: 21314464. doi:10.3109/01480545.2010.494666
   PubMed Web of Science ®Google Scholar