Pressure ulcers (PUs), also known as pressure injuries, are chronic wounds that represent potential lifelong complications. Pressure ulcers of a deep category (III and IV) are often indicated for surgical treatment - debridement and surgical reconstruction. Sharp surgical debridement is widely used in the debridement of PUs; however, the Versajet® hydrosurgery system is becoming an increasingly popular tool for tangential excision in surgery due to its numerous advantages. This work focused on the expression of selected genes, especially those associated with oxidative stress, in PUs debrided by two approaches - sharp surgical debridement and debridement using Versajet® hydrosurgery system. Expression of following genes was evaluated: NFE2L2, ACTA2, NFKB1, VEGFA, MKI67, HMOX1, HMOX2, HIF1A, and SOD2. ACTB and PSMB were used as housekeeping genes. So far, five patients have been enrolled in the study. Preliminary results suggest no significant difference in gene expression with different pressure ulcer treatment approaches except NFE2L2, despite the macroscopic differences. However, the results revealed correlations between the expression of some genes, namely HIF1A and SOD2, VEGFA and SOD2 and VEGFA and HIF1A. These results may indicate a connection between hypoxia, oxidative stress, pressure ulcer healing processes and angiogenesis.

Department of Physiology Faculty of Medicine Masaryk University Brno Czech Republic Department of Burns and Plastic Surgery University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Zobrazit více v PubMed

Haesler E European Pressure Ulcer Advisory Panel (EPUAP); National Pressure Injury Advisory Panel (NPIAP); Pan Pacific Pressure Injury Alliance (PPPIA) Prev Treat Press Ulcers Injuries Clin Pract Guidel Int Guidel. 2019

Grey JE, Harding KG, Enoch S. Pressure ulcers. BMJ. 2006;332:472–475. doi: 10.1136/bmj.332.7539.472. PubMed DOI PMC

Slomka N, Gefen A. Relationship between strain levels and permeability of the plasma membrane in statically stretched myoblasts. Ann Biomed Eng. 2012;40:606–618. doi: 10.1007/s10439-011-0423-1. PubMed DOI

Shoham N, Gefen A. Deformations, mechanical strains and stresses across the different hierarchical scales in weight-bearing soft tissues. J Tissue Viability. 2012;21:39–46. doi: 10.1016/j.jtv.2012.03.001. PubMed DOI

Zhang X, Zhu N, Li Z, Xie X, Liu T, Ouyang G. The global burden of decubitus ulcers from 1990 to 2019. Sci Rep. 2021;11:21750. doi: 10.1038/s41598-021-01188-4. PubMed DOI PMC

Búřilová P, Pokorná A, Benešová K, Mužík J, Klugar M, Krupová L, Dolanová D, et al. A ten-year follow-up of the prevalence of pressure injuries in the Czech Republic: Analysis of the National Registry. Int Wound J. 2022;19:1870–1877. doi: 10.1111/iwj.13793. PubMed DOI PMC

Pokorná A, Dolanová D, Benešová K, Búřilová P, Mužík J, Jarkovský J, Krupová L, et al. How the COVID-19 pandemic influences the prevalence of pressure injuries in the Czech Republic: A nationwide analysis of a health registry in 2020. J Tissue Viability. 2022;31:424–430. doi: 10.1016/j.jtv.2022.06.003. PubMed DOI PMC

Riordan J, Voegeli D. Prevention and treatment of pressure ulcers. Br J Nurs. 2009;18:S20,S22,S24–S27. doi: 10.12968/bjon.2009.18.Sup7.45132. PubMed DOI

Anghel EL, DeFazio MV, Barker JC, Janis JE, Attinger CE. Current concepts in debridement: science and strategies. Plast Reconstr Surg. 2016;138(3 Suppl):82S–93S. doi: 10.1097/PRS.0000000000002651. PubMed DOI

Strohal R, Dissemond J, Jordan O’Brien J, Piaggesi A, Rimdeika R, Young T, Apelqvist J. EWMA Document: Debridement: An updated overview and clarification of the principle role of debridement. J Wound Care. 2013;22:5. doi: 10.12968/jowc.2013.22.Sup1.S1. PubMed DOI

Klein MB, Hunter S, Heimbach DM, Engrav LH, Honari S, Gallery E, Kiriluk D-M, Gibran NS. The Versajet water dissector: a new tool for tangential excision. J Burn Care Rehabil. 2005;26:483–487. doi: 10.1097/01.bcr.0000185398.13095.c5. PubMed DOI

Shimada K, Ojima Y, Ida Y, Matsumura H. Efficacy of Versajet hydrosurgery system in chronic wounds: A systematic review. Int Wound J. 2021;18:269–278. doi: 10.1111/iwj.13528. PubMed DOI PMC

Auf Dem Keller U, Kümin A, Braun S, Werner S. Reactive oxygen species and their detoxification in healing skin wounds. J Investig Dermatol Symp Proc. 2006;11:106–111. doi: 10.1038/sj.jidsymp.5650001. PubMed DOI

Růžička J, Dejmek J, Bolek L, Beneš J, Kuncová J. Hyperbaric oxygen influences chronic wound healing - a cellular level review. Physiol Res. 2021;70(Suppl 3):S261–S273. doi: 10.33549/physiolres.934822. PubMed DOI PMC

R D. C. Team. A language and environment for statistical computing. Httpwww R-Proj.Org. 2009

Wickham H, Chang W, Wickham MH. Package “ggplot2”, Create Elegant Data Vis. Using Gramm. Graph. Version. 2016;2(1):1–189.

Wei T, Simko V. R package ‘corrplot’: Visualization of a Correlation Matrix. 2021. [Online] Available: https://github.com/taiyun/corrplot.

Wickham H, Averick M, Brian J, Chang W, D’Agostino McGowan L, Francois R, Grolemund G, et al. Welcome to the Tidyverse. J Open Source Softw. 2019;4:11686. doi: 10.21105/joss.01686. DOI

Kassambara A. rstatix: Pipe-Friendly Framework for Basic Statistical Test’. Feb 01, 2023. [Accessed: May 09, 2023]. [Online]. Available: https://cran.r-project.org/web/packages/rstatix/index.html.

Shao D, Gao Z, Zhao Y, Fan M, Zhao X, Wei Q, Pan M, Ma B. Sulforaphane Suppresses H2O2-Induced Oxidative Stress and Apoptosis via the Activation of AMPK/NFE2L2 Signaling Pathway in Goat Mammary Epithelial Cells. Int J Mol Sci. 2023;24:1070. doi: 10.3390/ijms24021070. PubMed DOI PMC

Li R, Fang H, Shen J, Jin Y, Zhao Y, Wang R, Fu Y, et al. Curcumin alleviates LPS-induced oxidative stress, inflammation and apoptosis in bovine mammary epithelial cells via the NFE2L2 signaling pathway. Toxins. 2021;13:208. doi: 10.3390/toxins13030208. PubMed DOI PMC

Passero FC, Jr, Ravi D, McDonald JT, Beheshti A, David KA, Evens AM. Combinatorial ixazomib and belinostat therapy induces NFE2L2-dependent apoptosis in Hodgkin and T-cell lymphoma. Br J Haematol. 2020;188:295–308. doi: 10.1111/bjh.16160. PubMed DOI

Chen X, Yu L, Zhou J, Ren J, Wang S, Tan Y, Ding Y. Inhibition of p62 and/or NFE2L2 induced autophagy impaires esophageal squamous cell cancer metastasis by reversing EMT. Gene. 2023;858:147194. doi: 10.1016/j.gene.2023.147194. PubMed DOI

Bai Z, Liu W, He D, Wang Y, Yi W, Luo C, Shen J, Hu Z. Protective effects of autophagy and NFE2L2 on reactive oxygen species-induced pyroptosis of human nucleus pulposus cells. Aging (Albany NY) 2020;12:7534–7548. doi: 10.18632/aging.103109. PubMed DOI PMC

Van Huizen AV, Kinsey LJ, Greene JM, Beane WS. Wound Repair and Regeneration. Wiley; NJ USA: 2021. Reactive Oxygen Species Signaling: A Therapeutic Target For Wound Healing And Regeneration; pp. A14–A14.

Krizanova O, Penesova A, Sokol J, Hokynkova A, Samadian A, Babula P. Signaling pathways in cutaneous wound healing. Front Physiol. 2022;13:1030851. doi: 10.3389/fphys.2022.1030851. PubMed DOI PMC

Hokynková A, Babula P, Pokorná A, Nováková M, Nártová L, Šín P. Oxidative stress in wound healing - current knowledge. Czech Slovak Neurol Neurosurg. 2019;82(Suppl 1):S37–S39. doi: 10.14735/amcsnn2019S37. DOI

Tombulturk FK, Soydas T, Sarac EY, Tuncdemir M, Coskunpinar E, Polat E, Sirekbasan S, Kanigur-Sultuybek G. Regulation of MMP 2 and MMP 9 expressions modulated by AP-1 (c-jun) in wound healing: improving role of Lucilia sericata in diabetic rats. Acta Diabetol. 2019;56:177–186. doi: 10.1007/s00592-018-1237-5. PubMed DOI

Yang L, Zheng Z, Zhou Q, Bai X, Fan L, Yang C, Su L, Hu D. miR-155 promotes cutaneous wound healing through enhanced keratinocytes migration by MMP-2. J Mol Histol. 2017;48:147–155. doi: 10.1007/s10735-017-9713-8. PubMed DOI

Caley MP, Martins VLC, O’Toole EA. Metalloproteinases and wound healing. Adv Wound Care (New Rochelle) 2015;4:225–234. doi: 10.1089/wound.2014.0581. PubMed DOI PMC

Rouhollahi E, Moghadamtousi SZ, Hajiaghaalipour F, Zahedifard M, Tayeby F, Awang K, Abdulla MA, Mohamed Z. Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity. Drug Des Devel Ther. 2015;9:5805–5813. doi: 10.2147/DDDT.S88196. PubMed DOI PMC

Braun S, Hanselmann C, Gassmann MG, auf dem Keller U, Born-Berclaz C, Chan K, Kann YW, Werner S. Nrf2 transcription factor, a novel target of keratinocyte growth factor action which regulates gene expression and inflammation in the healing skin wound. Mol Cell Biol. 2002;22:5492–5505. doi: 10.1128/MCB.22.15.5492-5505.2002. PubMed DOI PMC

Liu Y, Yang X, Liu Y, Jiang T, Ren S, Chen J, Xiong H, Yuan M, et al. NRF2 signalling pathway: new insights and progress in the field of wound healing. J Cell Mol Med. 2021;25:5857–5868. doi: 10.1111/jcmm.16597. PubMed DOI PMC

Ong HT, Dilley RJ. Novel non-angiogenic role for mesenchymal stem cell-derived vascular endothelial growth factor on keratinocytes during wound healing. Cytokine Growth Factor Rev. 2018;44:69–79. doi: 10.1016/j.cytogfr.2018.11.002. PubMed DOI

Muñoz-Sánchez J, Chánez-Cárdenas ME. A review on hemeoxygenase-2: focus on cellular protection and oxygen response. Oxid Med Cell Longev. 2014;2014:604981. doi: 10.1155/2014/604981. PubMed DOI PMC