{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:09:55Z","timestamp":1787044195383,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006541","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["MITIC"],"award-info":[{"award-number":["MITIC"]}],"id":[{"id":"10.13039\/501100006541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Pregnancy comprises a period in a woman\u2019s life in which the circulatory system is subjected to hemodynamical and biochemical changes. During this period, while restructuring blood vessels and exchanging maternal-fetal products there is an increased risk of developing chronic venous disease (CVD), which may have an echo in life after childbirth for both mother and child. Previously, we investigated that pregnancy-associated CVD involves changes in placental architecture at angiogenesis, lymphangiogenesis and villi morphology compared with healthy controls (HC) with no history of CVD. We aimed to more deeply investigate the oxidative stress response in placenta from women with CVD versus HC through several markers (NRF2, KEAP1, CUL3, GSK-3\u03b2). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). A total of 62 participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expressions of NRF2, KEAP1, CUL3, GSK-3\u03b2 were analyzed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. Nrf2 gene and protein expression was significantly greater in placental villi of women with CVD, while Keap1, CUL-3 and GSK-3\u03b2 gene and protein expressions were significantly lower. Our results defined an aberrant gene and protein expression of Nrf2 and some of their main regulators Keap1, CUL-3 and GSK-3 \u03b2 in the placenta of women with CVD, which could be an indicator of an oxidative environment observed in this tissue.<\/jats:p>","DOI":"10.3390\/antiox11112277","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T03:35:23Z","timestamp":1668742523000},"page":"2277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Irregular Expression of Cellular Stress Response Markers in the Placenta of Women with Chronic Venous Disease"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6016-7855","authenticated-orcid":false,"given":"Cielo","family":"Garc\u00eda-Montero","sequence":"first","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Fraile-Martinez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Rodriguez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Service of Pediatric, Hospital Universitario Principe de Asturias, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9983-2955","authenticated-orcid":false,"given":"Rosa M.","family":"Funes Mo\u00f1ux","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Service of Pediatric, Hospital Universitario Principe de Asturias, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose V.","family":"Saz","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Biotechnology, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coral","family":"Bravo","sequence":"additional","affiliation":[{"name":"Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Department of Obstetrics and Gynecology, University Hospital Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-2668","authenticated-orcid":false,"given":"Juan A.","family":"De Leon-Luis","sequence":"additional","affiliation":[{"name":"Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Department of Obstetrics and Gynecology, University Hospital Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Ruiz-Minaya","sequence":"additional","affiliation":[{"name":"Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Department of Obstetrics and Gynecology, University Hospital Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-9003","authenticated-orcid":false,"given":"Leonel","family":"Pekarek","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8389-258X","authenticated-orcid":false,"given":"Miguel A.","family":"Saez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Pathological Anatomy Service, Central University Hospital of Defence\u2014UAH Madrid, 28801 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8986-2584","authenticated-orcid":false,"given":"Alberto","family":"Garc\u00eda-Lledo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Cardiology Service, University Hospital Pr\u00edncipe de Asturias, 28806 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1309-7510","authenticated-orcid":false,"given":"Melchor","family":"Alvarez-Mon","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Pr\u00edncipe de Asturias, CIBEREHD, 28806 Alcala de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-2476","authenticated-orcid":false,"given":"Julia","family":"Bujan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0904-6198","authenticated-orcid":false,"given":"Natalio","family":"Garc\u00eda-Honduvilla","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2588-1708","authenticated-orcid":false,"given":"Miguel A.","family":"Ortega","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcala de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5830\/CVJA-2016-021","article-title":"Physiological changes in pregnancy","volume":"27","author":"Tolppanen","year":"2016","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4037\/aacnacc2018911","article-title":"Physiologic and hemodynamic changes during pregnancy","volume":"29","author":"Troiano","year":"2018","journal-title":"AACN Adv. Crit. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s00392-019-01441-x","article-title":"Role of pregnancy hormones and hormonal interaction on the maternal cardiovascular system: A literature review","volume":"108","author":"Kodogo","year":"2019","journal-title":"Clin. Res. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.bpobgyn.2013.08.001","article-title":"Alterations in physiology and anatomy during pregnancy","volume":"27","author":"Tan","year":"2013","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_5","first-page":"160","article-title":"Prevention and treatment of venous disorders during pregnancy and the postpartum period\u2014Servier\u2014PhlebolymphologyServier\u2014Phlebolymphology","volume":"4","author":"Djordje","year":"2017","journal-title":"Phlebolymphology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jvsv.2017.08.001","article-title":"The hemodynamic effects of pregnancy on the lower extremity venous system","volume":"6","author":"Taylor","year":"2018","journal-title":"J. Vasc. Surg. Venous Lymphat. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s12325-019-0885-3","article-title":"How Does Chronic Venous Disease Progress from the First Symptoms to the Advanced Stages? A Review","volume":"36","author":"Labropoulos","year":"2019","journal-title":"Adv. Ther."},{"key":"ref_8","first-page":"138","article-title":"Chronic venous disease during pregnancy\u2014Servier\u2014PhlebolymphologyServier\u2014Phlebolymphology","volume":"21","author":"Boivin","year":"2014","journal-title":"Phlebolymphology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Fraile-Mart\u00ednez, O., Garc\u00eda-Montero, C., \u00c1lvarez-Mon, M.A., Chaowen, C., Ruiz-Grande, F., Pekarek, L., Monserrat, J., As\u00fansolo, A., and Garc\u00eda-Honduvilla, N. (2021). Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management. J. Clin. Med., 10.","DOI":"10.3390\/jcm10153239"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jvs.2007.09.028","article-title":"Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension","volume":"47","author":"Bergan","year":"2008","journal-title":"J. Vasc. Surg."},{"key":"ref_11","first-page":"212","article-title":"Pathophysiology of chronic venous disease","volume":"33","author":"Raffetto","year":"2014","journal-title":"Int. Angiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1161\/CIRCULATIONAHA.113.006898","article-title":"Chronic venous insufficiency","volume":"130","author":"Eberhardt","year":"2014","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jvsv.2019.12.075","article-title":"The 2020 update of the CEAP classification system and reporting standards","volume":"8","author":"Lurie","year":"2020","journal-title":"J. Vasc. Surg. Venous Lymphat. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1097\/SLA.0000000000004631","article-title":"Global Epidemiology of Chronic Venous Disease: A Systematic Review With Pooled Prevalence Analysis","volume":"274","author":"Salim","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"(2019). Davies AH The Seriousness of Chronic Venous Disease: A Review of Real-World Evidence\u2014PubMed. Adv. Ther., 36, 5\u201312.","DOI":"10.1007\/s12325-019-0881-7"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.humpath.2018.03.022","article-title":"Placentas from women with pregnancy-associated venous insufficiency show villi damage with evidence of hypoxic cellular stress","volume":"77","author":"Ortega","year":"2018","journal-title":"Hum. Pathol."},{"key":"ref_17","first-page":"567","article-title":"Remodelling of collagen fibres in the placentas of women with venous insufficiency during pregnancy","volume":"33","author":"Ortega","year":"2018","journal-title":"Histol. Histopathol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Saez, M.A., Fraile-Mart\u00ednez, O., As\u00fansolo, \u00c1., Pekarek, L., Bravo, C., Coca, S., Sainz, F., \u00c1lvarez-Mon, M., and Buj\u00e1n, J. (2020). Increased angiogenesis and lymphangiogenesis in the placental villi of women with chronic venous disease during pregnancy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072487"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., G\u00f3mez-Lahoz, A.M., S\u00e1nchez-Trujillo, L., Fraile-Martinez, O., Garc\u00eda-Montero, C., Guijarro, L.G., Bravo, C., De Leon-Luis, J.A., Saz, J.V., and Bujan, J. (2022). Chronic Venous Disease during Pregnancy Causes a Systematic Increase in Maternal and Fetal Proinflammatory Markers. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23168976"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X., and Wen, T. (2020). NRF2, a Transcription Factor for Stress Response and Beyond. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134777"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of Nrf2 in Oxidative Stress and Toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., S\u00e1nchez-Trujillo, L., Bravo, C., Fraile-Martinez, O., Garc\u00eda-Montero, C., Saez, M.A., Alvarez-Mon, M.A., Sainz, F., Alvarez-Mon, M., and Bujan, J. (2021). Newborns of Mothers with Venous Disease during Pregnancy Show Increased Levels of Lipid Peroxidation and Markers of Oxidative Stress and Hypoxia in the Umbilical Cord. Antioxidants, 10.","DOI":"10.3390\/antiox10060980"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4157","DOI":"10.1111\/jcmm.15077","article-title":"Pregnancy-associated venous insufficiency course with placental and systemic oxidative stress","volume":"24","author":"Ortega","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1042\/BJ20090471","article-title":"Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1","volume":"422","author":"Eggler","year":"2009","journal-title":"Biochem. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8477","DOI":"10.1128\/MCB.24.19.8477-8486.2004","article-title":"The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: Oxidative stress sensing by a Cul3-Keap1 ligase","volume":"24","author":"Cullinan","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9237263","DOI":"10.1155\/2017\/9237263","article-title":"The Role of Nrf2 in Cardiovascular Function and Disease","volume":"2017","author":"Satta","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e13496","DOI":"10.1111\/aji.13496","article-title":"The role of nuclear factor erythroid 2-related factor 2 (NRF2) in normal and pathological pregnancy: A systematic review","volume":"86","author":"Tantengco","year":"2021","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nprot.2006.83","article-title":"The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: Twenty-something years on","volume":"1","author":"Chomczynski","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ye, J., Coulouris, G., Zaretskaya, I., Cutcutache, I., Rozen, S., and Madden, T.L. (2012). Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-134"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.2144\/04372ST03","article-title":"AutoDimer: A screening tool for primer-dimer and hairpin structures","volume":"37","author":"Vallone","year":"2004","journal-title":"Biotechniques"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.5713\/ajas.20.0238","article-title":"TATA box binding protein and ribosomal protein 4 are suitable reference genes for normalization during quantitative polymerase chain reaction study in bovine mesenchymal stem cells","volume":"33","author":"Jang","year":"2020","journal-title":"Asian-Australas. J. Anim. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"577096","DOI":"10.3389\/fmed.2021.577096","article-title":"Association Between Lower Extremity Venous Insufficiency and Intrapartum Fetal Compromise: A Nationwide Cross-Sectional Study","volume":"8","author":"Chaowen","year":"2021","journal-title":"Front. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Fraile-Mart\u00ednez, O., Garc\u00eda-Montero, C., S\u00e1ez, M.A., \u00c1lvarez-Mon, M.A., Torres-Carranza, D., \u00c1lvarez-Mon, M., Bujan, J., Garc\u00eda-Honduvilla, N., and Bravo, C. (2022). The Pivotal Role of the Placenta in Normal and Pathological Pregnancies: A Focus on Preeclampsia, Fetal Growth Restriction, and Maternal Chronic Venous Disease. Cells, 11.","DOI":"10.3390\/cells11030568"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1742-4933-10-15","article-title":"Stress responses, vitagenes and hormesis as critical determinants in aging and longevity: Mitochondria as a \u201cchi\u201d","volume":"10","author":"Cornelius","year":"2013","journal-title":"Immun. Ageing"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1146\/annurev-pharmtox-010818-021856","article-title":"Modulating NRF2 in disease: Timing is everything","volume":"59","author":"Dodson","year":"2019","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1089\/ars.2017.7342","article-title":"Transcriptional Regulation by Nrf2","volume":"29","author":"Tonelli","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Saha, S., Buttari, B., Panieri, E., Profumo, E., and Saso, L. (2020). An overview of Nrf2 signaling pathway and its role in inflammation. Molecules, 25.","DOI":"10.3390\/molecules25225474"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1042\/CS20150436","article-title":"Nrf2 in health and disease: Current and future clinical implications","volume":"129","author":"Clarner","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/1753495X16648495","article-title":"Oxidative stress in pregnancy and reproduction","volume":"9","author":"Duhig","year":"2016","journal-title":"Obstet. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3109\/10641963.2015.1081226","article-title":"Increased oxidative stress from early pregnancy in women who develop preeclampsia","volume":"38","author":"Dsouza","year":"2016","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"295","DOI":"10.2217\/bmm-2016-0250","article-title":"Biomarkers of oxidative stress in pregnancy complications","volume":"11","author":"Cuffe","year":"2017","journal-title":"Biomark. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"582748","DOI":"10.1155\/2012\/582748","article-title":"Impact of Oxidative Stress in Fetal Programming","volume":"2012","author":"Thompson","year":"2012","journal-title":"J. Pregnancy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"eaam5711","DOI":"10.1126\/scisignal.aam5711","article-title":"Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model and improves maternal and fetal outcomes","volume":"10","author":"Nezu","year":"2017","journal-title":"Sci. Signal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"165354","DOI":"10.1016\/j.bbadis.2018.12.005","article-title":"Oxidative stress: Normal pregnancy versus preeclampsia","volume":"1866","author":"Chiarello","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5164576","DOI":"10.1155\/2019\/5164576","article-title":"Patients with incompetent valves in chronic venous insufficiency show increased systematic lipid peroxidation and cellular oxidative stress markers","volume":"2019","author":"Ortega","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1167\/iovs.07-1099","article-title":"Essential roles of the PI3 kinase\/Akt pathway in regulating Nrf2-dependent antioxidant functions in the RPE","volume":"49","author":"Wang","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.7150\/ijms.58992","article-title":"Abnormal proinflammatory and stressor environmental with increased the regulatory cellular IGF-1\/PAPP-A\/STC and Wnt-1\/\u03b2-Catenin canonical pathway in placenta of women with Chronic venous Disease during Pregnancy","volume":"18","author":"Ortega","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.freeradbiomed.2015.05.017","article-title":"Crosstalk between Nrf2 and Notch signaling","volume":"88","author":"Wakabayashi","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"447","DOI":"10.7150\/ijms.4593","article-title":"Notch Signaling Pathway and Human Placenta","volume":"9","author":"Zhao","year":"2012","journal-title":"Int. J. Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1128\/MCB.00389-16","article-title":"Absolute Amounts and Status of the Nrf2-Keap1-Cul3 Complex within Cells","volume":"36","author":"Iso","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.freeradbiomed.2013.02.008","article-title":"Regulation of Nrf2\u2014An update","volume":"66","author":"Niture","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1080\/15384047.2018.1564562","article-title":"The functional roles of exosomes-derived long non-coding RNA in human cancer","volume":"20","author":"Chen","year":"2019","journal-title":"Cancer Biol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Piergentili, R., Zaami, S., Cavaliere, A.F., Signore, F., Scambia, G., Mattei, A., Marinelli, E., Gulia, C., and Perelli, F. (2021). Non-Coding RNAs as Prognostic Markers for Endometrial Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063151"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"293271","DOI":"10.1155\/2015\/293271","article-title":"Oxidative stress in placenta: Health and diseases","volume":"2015","author":"Wu","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Cavaliere, A.F., Perelli, F., Zaami, S., Piergentili, R., Mattei, A., Vizzielli, G., Scambia, G., Straface, G., Restaino, S., and Signore, F. (2021). Towards Personalized Medicine: Non-Coding RNAs and Endometrial Cancer. Healthcare, 9.","DOI":"10.3390\/healthcare9080965"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mundal, S.B., Rakner, J.J., Silva, G.B., Gierman, L.M., Austdal, M., Basnet, P., Elschot, M., Bakke, S.S., Ostrop, J., and Thomsen, L.C.V. (2022). Divergent Regulation of Decidual Oxidative-Stress Response by NRF2 and KEAP1 in Preeclampsia with and without Fetal Growth Restriction. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23041966"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"654254","DOI":"10.3389\/fcvm.2021.654254","article-title":"Downregulation of Cullin 3 Ligase Signaling Pathways Contributes to Hypertension in Preeclampsia","volume":"8","author":"Zhang","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1530\/REP-15-0126","article-title":"New insights into the function of Cullin 3 in trophoblast invasion and migration","volume":"150","author":"Zhang","year":"2015","journal-title":"Reproduction"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101638","DOI":"10.1016\/j.isci.2020.101638","article-title":"Downregulation of Keap1 Confers Features of a Fasted Metabolic State","volume":"23","author":"Knatko","year":"2020","journal-title":"iScience"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.7150\/ijms.49236","article-title":"Lipidomic profiling of chorionic villi in the placentas of women with chronic venous disease","volume":"17","author":"Ortega","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1080\/14767058.2018.1531843","article-title":"Glycogen synthase kinase (GSK) 3 in Pregnancy and Parturition: A Systematic Review of Literature","volume":"33","author":"Lavu","year":"2020","journal-title":"J. Matern. Fetal. Neonatal Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1093\/biolre\/ioz119","article-title":"Oxidative stress-induced downregulation of glycogen synthase kinase 3 beta in fetal membranes promotes cellular senescence","volume":"101","author":"Lavu","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jbior.2017.06.003","article-title":"GSK3 and its interactions with the PI3K\/AKT\/mTOR signalling network","volume":"65","author":"Hermida","year":"2017","journal-title":"Adv. Biol. Regul."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1128\/MCB.00015-07","article-title":"Glycogen synthase kinase 3 phosphorylates hypoxia-inducible factor 1alpha and mediates its destabilization in a VHL-independent manner","volume":"27","author":"Michiels","year":"2007","journal-title":"Mol. Cell. Biol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/11\/2277\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:25Z","timestamp":1760145625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/11\/2277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,17]]},"references-count":64,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["antiox11112277"],"URL":"https:\/\/doi.org\/10.3390\/antiox11112277","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,17]]}}}