{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T10:02:52Z","timestamp":1784282572130,"version":"3.55.0"},"reference-count":165,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Papaverine (PPV) has long been used in obstetric practice to facilitate cervical dilatation, yet its mechanism of action remains poorly understood. This creates an apparent paradox, as experimental studies indicate that PPV suppresses several inflammatory signaling pathways traditionally considered essential for physiological cervical ripening, despite its reported clinical benefits during labor. In this narrative review, we critically integrate current knowledge of cervical ripening biology with the pharmacological actions of PPV to reconcile this discrepancy. We propose that the reported clinical effects of PPV may be explained predominantly by modulation of cervical biomechanics rather than by direct enhancement of inflammatory remodeling. In particular, smooth muscle relaxation and cyclic nucleotide-dependent signaling may reduce functional cervical resistance and facilitate cervical dilatation despite the predominantly anti-inflammatory molecular profile of PPV. Although this mechanistic framework remains hypothetical, it provides a biologically plausible explanation for the apparent discrepancy between the molecular and clinical effects of papaverine and highlights priorities for future experimental and clinical research.<\/jats:p>","DOI":"10.3390\/ijms27146344","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:00:52Z","timestamp":1784278852000},"page":"6344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Papaverine in the Molecular and Biomechanical Mechanisms of Cervical Ripening: A Narrative Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5847-3092","authenticated-orcid":false,"given":"Wojciech","family":"Flis","sequence":"first","affiliation":[{"name":"Department of Perinatology, Gynecology and Gynecologic Oncology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, \u0141ukasiewicza 1, 85-821 Bydgoszcz, Poland"},{"name":"Department of Obstetrics and Gynecology, St. Adalbert\u2019s Hospital in Gda\u0144sk, Copernicus Healthcare Entity, Jana Paw\u0142a II 50, 80-462 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-4515","authenticated-orcid":false,"given":"Mateusz","family":"Wart\u0119ga","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie-Sk\u0142odowskiej 9, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-9614","authenticated-orcid":false,"given":"Tomasz","family":"G\u00f3ra","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, John Paul II City Hospital, Rycerska 4, 35-241 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-3334","authenticated-orcid":false,"given":"Maciej W.","family":"Socha","sequence":"additional","affiliation":[{"name":"Department of Perinatology, Gynecology and Gynecologic Oncology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, \u0141ukasiewicza 1, 85-821 Bydgoszcz, Poland"},{"name":"Department of Obstetrics and Gynecology, St. Adalbert\u2019s Hospital in Gda\u0144sk, Copernicus Healthcare Entity, Jana Paw\u0142a II 50, 80-462 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1093\/humrep\/deu195","article-title":"The role of the cervix in fertility: Is it time for a reappraisal?","volume":"29","author":"Martyn","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151216","DOI":"10.1016\/j.semperi.2019.151216","article-title":"Cervical ripening: Why we do what we do","volume":"44","author":"Levine","year":"2020","journal-title":"Semin. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1080\/25785826.2020.1809951","article-title":"Harmful and beneficial effects of inflammatory response on reproduction: Sterile and pathogen-associated inflammation","volume":"44","author":"Negishi","year":"2021","journal-title":"Immunol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1146\/annurev.arplant.59.032607.092730","article-title":"Alkaloid biosynthesis: Metabolism and trafficking","volume":"59","author":"Ziegler","year":"2008","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1039\/D0NP00031K","article-title":"The scaffold-forming steps of plant alkaloid biosynthesis","volume":"38","author":"Lichman","year":"2021","journal-title":"Nat. Prod. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101388","DOI":"10.1016\/j.ajogmf.2024.101388","article-title":"Papaverine prior to catheter balloon insertion for labor induction: A randomized controlled trial","volume":"6","author":"Goldinfeld","year":"2024","journal-title":"Am. J. Obstet. Gynecol. MFM"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ashrafi, S., Alam, S., Sultana, A., Raj, A., Emon, N.U., Richi, F.T., Sharmin, T., Moon, M., Park, M.N., and Kim, B. (2023). Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application. Molecules, 28.","DOI":"10.3390\/molecules28073149"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yellon, S.M. (2019). Immunobiology of Cervix Ripening. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.03156"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/00003081-199506000-00009","article-title":"Anatomy and physiology of cervical ripening","volume":"38","author":"Leppert","year":"1995","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0070-2153(05)68004-0","article-title":"Comparative Developmental Biology of the Mammalian Uterus","volume":"68","author":"Spencer","year":"2005","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.jbiomech.2015.02.065","article-title":"The mechanical role of the cervix in pregnancy","volume":"48","author":"Myers","year":"2015","journal-title":"J. Biomech."},{"key":"ref_12","unstructured":"Nicoll, A.E. (2001). The Physiology of Cervical Ripening and the Induction of Labour: A Potential Role for the Nitric Oxide Donor Isosorbide Mononitrate. [Master\u2019s Thesis, University of Glasgow]."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"478.e1","DOI":"10.1016\/j.ajog.2016.04.053","article-title":"A new paradigm for the role of smooth muscle cells in the human cervix","volume":"215","author":"Vink","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1210\/jc.2002-021213","article-title":"Decreased type I collagen expression in human uterine cervix during pregnancy","volume":"88","author":"Iwahashi","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/0002-9378(83)90446-5","article-title":"Ripening of the human uterine cervix related to changes in collagen, glycosaminoglycans, and collagenolytic activity","volume":"147","author":"Uldbjerg","year":"1983","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, Q., and Chi, L. (2022). The Alterations and Roles of Glycosaminoglycans in Human Diseases. Polymers, 14.","DOI":"10.3390\/polym14225014"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1210\/en.2011-1950","article-title":"Dynamic changes in cervical glycosaminoglycan composition during normal pregnancy and preterm birth","volume":"153","author":"Akgul","year":"2012","journal-title":"Endocrinology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1093\/humrep\/12.5.1080","article-title":"The role of hyaluronic acid as a mediator and regulator of cervical ripening","volume":"12","author":"Kanayama","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/glycob\/cwh137","article-title":"Regulation of hyaluronan expression during cervical ripening","volume":"15","author":"Straach","year":"2005","journal-title":"Glycobiology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1530\/REP-17-0763","article-title":"Characterization of the collagen microstructural organization of human cervical tissue","volume":"156","author":"Hao","year":"2018","journal-title":"Reproduction"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1477-7827-8-82","article-title":"Collagen concentration and biomechanical properties of samples from the lower uterine cervix in relation to age and parity in non-pregnant women","volume":"8","author":"Oxlund","year":"2010","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0003-9861(83)90501-5","article-title":"The content of elastin in the uterine cervix","volume":"222","author":"Leppert","year":"1983","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1111\/febs.15899","article-title":"Elastic fibers: Formation, function, and fate during aging and disease","volume":"289","author":"Schmelzer","year":"2022","journal-title":"FEBS J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1210\/en.2016-1930","article-title":"Steroid hormones are key modulators of tissue mechanical function via regulation of collagen and elastic fibers","volume":"158","author":"Nallasamy","year":"2017","journal-title":"Endocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1161\/01.RES.0000070112.80711.3D","article-title":"Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry","volume":"92","author":"Visse","year":"2003","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104.E1","DOI":"10.1016\/j.ajog.2008.08.032","article-title":"Term labor is associated with a core inflammatory response in human fetal membranes, myometrium, and cervix","volume":"200","author":"Bollapragada","year":"2009","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S669","DOI":"10.1016\/j.ajog.2023.02.009","article-title":"Methods for the induction of labor: Efficacy and safety","volume":"230","author":"Levine","year":"2024","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_28","first-page":"CD003097","article-title":"Hyaluronidase for cervical ripening and induction of labour","volume":"2006","author":"Kavanagh","year":"2006","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Valachov\u00e1, K., and \u0160olt\u00e9s, L. (2021). Hyaluronan as a prominent biomolecule with numerous applications in medicine. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137077"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/00003081-200609000-00015","article-title":"Cervical ripening: Biochemical, molecular, and clinical considerations","volume":"49","author":"Maul","year":"2006","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jri.2008.04.002","article-title":"Inflammatory processes in preterm and term parturition","volume":"79","author":"Christiaens","year":"2008","journal-title":"J. Reprod. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1477-7827-2-74","article-title":"Factors involved in the inflammatory events of cervical ripening in humans","volume":"2","author":"Stygar","year":"2004","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejogrb.2008.08.009","article-title":"Cervicovaginal matrix metalloproteinase-9 and cervical ripening in human term parturition","volume":"142","author":"Choi","year":"2009","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16898","DOI":"10.1073\/pnas.0702761104","article-title":"Nitric oxide regulates matrix metalloproteinase-9 activity by guanylyl-cyclase-dependent and -independent pathways","volume":"104","author":"Ridnour","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Cabral-Pacheco, G.A., Garza-Veloz, I., Castruita-De la Rosa, C., Ramirez-Acu\u00f1a, J.M., Perez-Romero, B.A., Guerrero-Rodriguez, J.F., Martinez-Avila, N., and Martinez-Fierro, M.L. (2020). The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249739"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1095\/biolreprod.102.005116","article-title":"Increased level of matrix metalloproteinases 2 and 9 in the ripening process of the human cervix","volume":"67","author":"Stygar","year":"2002","journal-title":"Biol. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R177","DOI":"10.1530\/RAF-22-0015","article-title":"Matrix metalloproteinase-induced cervical extracellular matrix remodelling in pregnancy and cervical cancer","volume":"3","author":"Amabebe","year":"2022","journal-title":"Reprod. Fertil."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1189\/jlb.1209796","article-title":"Invasion of the leukocytes into the fetal-maternal interface during pregnancy","volume":"88","author":"Guilbert","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_39","first-page":"904","article-title":"Matrix metalloproteinase-8 correlates with the cervical ripening process in humans","volume":"82","author":"Brauner","year":"2003","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ejogrb.2019.05.010","article-title":"Mast cell involvement in human cervical ripening","volume":"238","author":"Bullarbo","year":"2019","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mohd Zaki, A., Hadingham, A., Flaviani, F., Haque, Y., Mi, J.D., Finucane, D., Dalla Valle, G., Mason, A.J., Saqi, M., and Gibbons, D.L. (2022). Neutrophils Dominate the Cervical Immune Cell Population in Pregnancy and Their Transcriptome Correlates with the Microbial Vaginal Environment. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.904451"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1124\/pharmrev.121.000349","article-title":"Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology","volume":"74","author":"Thode","year":"2022","journal-title":"Pharmacol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"117357","DOI":"10.1016\/j.theriogenology.2025.02.023","article-title":"Dynamics of macrophages and inflammatory cytokine concentrations in the cervix of late pregnant cows","volume":"238","author":"Kanemaru","year":"2025","journal-title":"Theriogenology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cytogfr.2024.07.007","article-title":"Inflammatory mechanisms of preterm labor and emerging anti-inflammatory interventions","volume":"78","author":"Habelrih","year":"2024","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Ch\u00e1vez, F., Correa, D., Navarrete-Meneses, P., Cancino-Diaz, J.C., Cancino-Diaz, M.E., and Rodr\u00edguez-Mart\u00ednez, S. (2021). NF-\u03baB and Its Regulators During Pregnancy. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.679106"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/s41423-025-01358-8","article-title":"IL-1 family cytokines in inflammation and immunity","volume":"22","author":"Garlanda","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1177\/1933719113492204","article-title":"The Interplay of the Interleukin 1 System in Pregnancy and Labor","volume":"21","author":"Heng","year":"2014","journal-title":"Reprod. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0028-2243(95)02085-3","article-title":"The effect of interleukin-1 in rabbit cervical ripening","volume":"60","author":"Kanayama","year":"1995","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/cas.13467","article-title":"Downregulation of 15-hydroxyprostaglandin dehydrogenase by interleukin-1\u03b2 from activated macrophages leads to poor prognosis in pancreatic cancer","volume":"109","author":"Arima","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"102763","DOI":"10.1016\/j.autrev.2021.102763","article-title":"Interleukin 1\u03b1: A comprehensive review on the role of IL-1\u03b1 in the pathogenesis and treatment of autoimmune and inflammatory diseases","volume":"20","author":"Cavalli","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Boraschi, D. (2022). What Is IL-1 for? The Functions of Interleukin-1 Across Evolution. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.872155"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1177\/154405910708600215","article-title":"Signaling pathways regulating IL-1alpha-induced COX-2 expression","volume":"86","author":"Ogata","year":"2007","journal-title":"J. Dent. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3524759","DOI":"10.1155\/2018\/3524759","article-title":"IL-1\u03b2-Induced Matrix Metalloprotease-1 Promotes Mesenchymal Stem Cell Migration via PAR1 and G-Protein-Coupled Signaling Pathway","volume":"2018","author":"Chen","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"155828","DOI":"10.1016\/j.cyto.2022.155828","article-title":"Interleukin-8: An evolving chemokine","volume":"153","author":"Matsushima","year":"2022","journal-title":"Cytokine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0301-2115(97)02757-7","article-title":"Interleukin-8 is a mediator of the final cervical ripening in humans","volume":"74","author":"Brauner","year":"1997","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1002\/eji.202049029","article-title":"Differential Interleukin-8 thresholds for chemotaxis and netosis in human neutrophils","volume":"51","author":"Teijeira","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1365-2249.2004.02584.x","article-title":"Interleukin-8 is involved in cervical dilatation but not in prelabour cervical ripening","volume":"138","author":"Sakamoto","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/humrep\/14.2.560","article-title":"Interleukin-8 potentiates the effect of interleukin-1-induced uterine contractions","volume":"14","author":"Khatun","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_59","first-page":"945","article-title":"Interleukin-1beta and interleukin-8 concentrations in the lower uterine segment during parturition at term","volume":"91","author":"Winkler","year":"1998","journal-title":"Obstet. Gynecol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1007\/s10620-006-9436-2","article-title":"Involvement of Cyclooxygenase-2\u2013Prostaglandin E2 Pathway in Interleukin-8 Production in Gastric Cancer Cells","volume":"51","author":"Takehara","year":"2006","journal-title":"Dig. Dis. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cesta, M.C., Zippoli, M., Marsiglia, C., Gavioli, E.M., Mantelli, F., Allegretti, M., and Balk, R.A. (2022). The Role of Interleukin-8 in Lung Inflammation and Injury: Implications for the Management of COVID-19 and Hyperinflammatory Acute Respiratory Distress Syndrome. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.808797"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"h217","DOI":"10.1136\/bmj.h217","article-title":"Labour induction with prostaglandins: A systematic review and network meta-analysis","volume":"350","author":"Alfirevic","year":"2015","journal-title":"BMJ"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Young, D.C., Delaney, T., Anthony Armson, B., and Fanning, C. (2020). Oral misoprostol, low dose vaginal misoprostol, and vaginal dinoprostone for labor induction: Randomized controlled trial. PLoS ONE, 15, Correction in PLoS ONE 2024, 19, e0304233.","DOI":"10.1371\/journal.pone.0304233"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/aogs.14550","article-title":"Outpatient vs inpatient induction of labor with oral misoprostol: A retrospective study","volume":"102","author":"Amini","year":"2023","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and Inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1152\/physrev.1999.79.4.1193","article-title":"Prostanoid receptors: Structures, properties, and functions","volume":"79","author":"Narumiya","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s12079-020-00585-0","article-title":"A Review of Prostanoid Receptors: Expression, Characterization, Regulation, and Mechanism of Action","volume":"15","author":"Biringer","year":"2020","journal-title":"J. Cell Commun. Signal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00404-017-4418-5","article-title":"The role of prostaglandins E1 and E2, dinoprostone, and misoprostol in cervical ripening and the induction of labor: A mechanistic approach","volume":"296","author":"Bakker","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0952-3278(03)00113-3","article-title":"Expression of prostanoid receptors in human lower segment pregnant myometrium","volume":"69","author":"Leonhardt","year":"2003","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/molehr\/gah158","article-title":"Identification and localization of prostaglandin E2 receptors in upper and lower segment human myometrium during pregnancy","volume":"11","author":"Astle","year":"2005","journal-title":"Mol. Hum. Reprod."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1095\/biolreprod64.4.1131","article-title":"Effects of gestational age and labor on expression of prostanoid receptor genes in baboon uterus","volume":"64","author":"Smith","year":"2001","journal-title":"Biol. Reprod."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1067\/S0002-9378(03)00764-6","article-title":"Expression and regulation of the rat prostaglandin E2 receptor type 4 (EP4) in pregnant cervical tissue","volume":"189","author":"Chien","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wautier, J.L., and Wautier, M.P. (2023). Pro- and Anti-Inflammatory Prostaglandins and Cytokines in Humans: A Mini Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119647"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1172\/JCI119254","article-title":"Secretory leukocyte protease inhibitor suppresses the production of monocyte prostaglandin H synthase-2, prostaglandin E2, and matrix metalloproteinases","volume":"99","author":"Zhang","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0090-6980(93)90114-M","article-title":"Biochemical changes in human cervical connective tissue after intracervical application of prostaglandin E2","volume":"45","author":"Rath","year":"1993","journal-title":"Prostaglandins"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e307","DOI":"10.1055\/s-0038-1675351","article-title":"Clinical Insights for Cervical Ripening and Labor Induction Using Prostaglandins","volume":"8","author":"Pierce","year":"2018","journal-title":"AJP Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.2147\/OPTH.S178106","article-title":"Effect of prostaglandin analogs on matrix metalloproteinases and tissue inhibitor of metalloproteinases in eyelid muscle specimens","volume":"12","author":"Karli","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"A383","DOI":"10.1016\/j.joca.2015.02.709","article-title":"Upregulation of gene expression of matrix metalloproteinases and prostaglandin E-2 production in biomechanical or biochemical stimulation to three-dimensional tissue of human synovial cells","volume":"23","author":"Nakata","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.theriogenology.2020.04.040","article-title":"Prostaglandins effect on matrix metallopeptidases and collagen in mare endometrial fibroblasts","volume":"153","author":"Baclawska","year":"2020","journal-title":"Theriogenology"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Hog, P., Kuntschar, S., Rappl, P., Huard, A., Weigert, A., Br\u00fcne, B., and Schmid, T. (2023). Prostaglandin E2 Boosts the Hyaluronan-Mediated Increase in Inflammatory Response to Lipopolysaccharide by Enhancing Lyve1 Expression. Biology, 12.","DOI":"10.3390\/biology12111441"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2303259","DOI":"10.1002\/advs.202303259","article-title":"Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications","volume":"10","author":"Andrabi","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1067\/mob.2003.161","article-title":"Nitric oxide metabolites in cervical fluid during pregnancy: Further evidence for the role of cervical nitric oxide in cervical ripening","volume":"188","author":"Nuutila","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/07853890701716802","article-title":"Nitric oxide in the human uterine cervix: Endogenous ripening factor","volume":"40","year":"2008","journal-title":"Ann. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1093\/humrep\/12.10.2093","article-title":"Cervical ripening in guinea-pigs after a local application of nitric oxide","volume":"12","author":"Chwalisz","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_85","first-page":"CD006901","article-title":"Nitric oxide donors for cervical ripening and induction of labour","volume":"12","author":"Ghosh","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1080\/14767058.2017.1326898","article-title":"Is nitric oxide an essential mediator in cervical inflammation and preterm birth?","volume":"31","author":"Nold","year":"2018","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Kim, M.E., and Lee, J.S. (2025). Advances in the Regulation of Inflammatory Mediators in Nitric Oxide Synthase: Implications for Disease Modulation and Therapeutic Approaches. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031204"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2174\/1568010054526359","article-title":"Nitric oxide production and signaling in inflammation","volume":"4","author":"Korhonen","year":"2005","journal-title":"Curr. Drug Targets Inflamm. Allergy"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1124\/mi.6.4.6","article-title":"COX-2 in inflammation and resolution","volume":"6","author":"Rajakariar","year":"2006","journal-title":"Mol. Interv."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e0003","DOI":"10.5041\/RMMJ.10426","article-title":"Different Chemical Structures and Physiological\/Pathological Roles of Cyclooxygenases","volume":"12","author":"Faki","year":"2021","journal-title":"Rambam Maimonides Med. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.bbamcr.2013.12.006","article-title":"Nitric oxide-matrix metalloproteinase-9 interactions: Biological and pharmacological significance: NO and MMP-9 interactions","volume":"1843","author":"Medina","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Chen, H., Cui, Q., and Yang, W. (2025). NF-\u03baB Activation Is Essential for Cervical Cell Proliferation and Malignant Transformation. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062493"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.mce.2014.11.008","article-title":"Oxytocin activates NF-\u03baB-mediated inflammatory pathways in human gestational tissues","volume":"403","author":"Kim","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1093\/molehr\/gal113","article-title":"Involvement of nuclear factor-kB activation through RhoA\/Rho-kinase pathway in LPS-induced IL-8 production in human cervical stromal cells","volume":"13","author":"Shimizu","year":"2007","journal-title":"Mol. Hum. Reprod."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Mussbacher, M., Derler, M., Bas\u00edlio, J., and Schmid, J.A. (2023). NF-\u03baB in monocytes and macrophages\u2014An inflammatory master regulator in multitalented immune cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1134661"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Liu, D., Zhong, Z., and Karin, M. (2022). NF-\u03baB: A Double-Edged Sword Controlling Inflammation. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061250"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1080\/15384101.2024.2325802","article-title":"Sustained activation of NF-\u03baB through constitutively active IKK\u03b2 leads to senescence bypass in murine dermal fibroblasts","volume":"23","author":"Harada","year":"2024","journal-title":"Cell Cycle"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"352371","DOI":"10.1155\/2014\/352371","article-title":"Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses","volume":"2014","author":"Yang","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ganguly, P., Macleod, T., Wong, C., Harland, M., and McGonagle, D. (2023). Revisiting p38 Mitogen-Activated Protein Kinases (MAPK) in Inflammatory Arthritis: A Narrative of the Emergence of MAPK-Activated Protein Kinase Inhibitors (MK2i). Pharmaceuticals, 16.","DOI":"10.3390\/ph16091286"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.bbamcr.2007.03.010","article-title":"p38 MAP-Kinases pathway regulation, function and role in human diseases","volume":"1773","author":"Cuenda","year":"2007","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1477-7827-5-3","article-title":"Plasma membrane receptor mediated MAPK signaling pathways are activated in human uterine cervix at parturition","volume":"5","author":"Wang","year":"2007","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.2353\/ajpath.2007.061035","article-title":"Nuclear factor-kappa B, p38, and stress-activated protein kinase mitogen-activated protein kinase signaling pathways regulate proinflammatory cytokines and apoptosis in human placental explants in response to oxidative stress: Effects of antioxidant vitamins","volume":"170","author":"Jauniaux","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1080\/14728222.2016.1216980","article-title":"p38 Mitogen activated protein kinase (MAPK): A new therapeutic target for reducing the risk of adverse pregnancy outcomes","volume":"20","author":"Menon","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Cho, W., and Choe, J. (2020). Prostaglandin E2 stimulates COX-2 expression via mitogen-activated protein kinase p38 but not ERK in human follicular dendritic cell-like cells. BMC Immunol., 21.","DOI":"10.1186\/s12865-020-00347-y"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"84608","DOI":"10.18632\/oncotarget.12358","article-title":"Heparan sulfate hexasaccharide selectively inhibits cancer stem cells self-renewal by activating p38 MAP kinase","volume":"7","author":"Patel","year":"2016","journal-title":"Oncotarget"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Christianson, H.C., van Kuppevelt, T.H., and Belting, M. (2012). ScFv Anti-Heparan Sulfate Antibodies Unexpectedly Activate Endothelial and Cancer Cells through p38 MAPK: Implications for Antibody-Based Targeting of Heparan Sulfate Proteoglycans in Cancer. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049092"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Blevins, H.M., Xu, Y., Biby, S., and Zhang, S. (2022). The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.879021"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4236\/ojmip.2013.34020","article-title":"Expression and localization of prostaglandin receptors and stromal factors in human cervix\u2014Variations in pregnant and non-pregnant states","volume":"3","author":"Blesson","year":"2013","journal-title":"Open J. Mol. Integr. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/s41590-023-01526-w","article-title":"Molecular mechanisms of gasdermin D pore-forming activity","volume":"24","author":"Devant","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41467-021-27692-9","article-title":"Gasdermin D pores are dynamically regulated by local phosphoinositide circuitry","volume":"13","author":"Schnur","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Fang, X., Wang, Y., Zhang, Y., Li, Y., Kwak-kim, J., and Wu, L. (2021). NLRP3 Inflammasome and Its Critical Role in Gynecological Disorders and Obstetrical Complications. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.555826"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.4049\/jimmunol.1900901","article-title":"Inflammasomes: Their Role in Normal and Complicated Pregnancies","volume":"203","author":"Motomura","year":"2019","journal-title":"J. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1080\/14767050802212109","article-title":"Evidence of the Involvement of Caspase-1 under Physiologic and Pathologic Cellular Stress during Human Pregnancy: A Link Between the Inflammasome and Parturition","volume":"21","author":"Gotsch","year":"2008","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"115393","DOI":"10.1016\/j.biopha.2023.115393","article-title":"Role of the NLRP3 inflammasome in gynecological disease","volume":"166","author":"Zheng","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e158238","DOI":"10.1172\/jci.insight.158238","article-title":"Fetal and maternal NLRP3 signaling is required for preterm labor and birth","volume":"7","author":"Motomura","year":"2022","journal-title":"JCI Insight"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e12648","DOI":"10.1111\/aji.12648","article-title":"Inflammasome assembly in the chorioamniotic membranes during spontaneous labor at term","volume":"77","author":"Romero","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_119","first-page":"4399","article-title":"Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury","volume":"18","author":"Li","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10565-024-09893-2","article-title":"HMGB1 as an extracellular pro-inflammatory cytokine: Implications for drug-induced organic damage","volume":"40","author":"Yuan","year":"2024","journal-title":"Cell Biol. Toxicol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Ren, Y., Zhu, D., Han, X., Zhang, Q., Chen, B., Zhou, P., Wei, Z., Zhang, Z., Cao, Y., and Zou, H. (2023). HMGB1: A double-edged sword and therapeutic target in the female reproductive system. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1238785"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.2119\/molmed.2015.00087","article-title":"High Mobility Group Box Protein 1 (HMGB1): The Prototypical Endogenous Danger Molecule","volume":"21","author":"Yang","year":"2014","journal-title":"Mol. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s12276-026-01640-3","article-title":"The redox-sensitive protein HMGB1: Intracellular and extracellular roles","volume":"58","author":"Kwak","year":"2026","journal-title":"Exp. Mol. Med."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Yang, H., Wang, H., and Andersson, U. (2020). Targeting Inflammation Driven by HMGB1. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00484"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s12276-022-00736-w","article-title":"The mechanism of HMGB1 secretion and release","volume":"54","author":"Chen","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1097\/AOG.0000000000003470","article-title":"Exploring Inflammatory Mediators in Fetal and Maternal Compartments During Human Parturition","volume":"134","author":"Menon","year":"2019","journal-title":"Obstet. Gynecol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.cyto.2016.02.013","article-title":"High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth, and the source may be the damaged fetal membranes","volume":"81","author":"Baumbusch","year":"2016","journal-title":"Cytokine"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41420-021-00729-0","article-title":"LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger hepatocyte pyroptosis by activating the NLRP3 inflammasome","volume":"7","author":"Wang","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Yang, L., Li, X., Zhu, X., Ge, F., and Wang, Y. (2025). Involvement of role of HMGB1-NLRP3 pathway in systemic disorders. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1600596"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1084\/jem.20120189","article-title":"Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release","volume":"209","author":"Venereau","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"117146","DOI":"10.1016\/j.lfs.2019.117146","article-title":"HMGB1 upregulates NF-kB by inhibiting IKB-\u03b1 and associates with diabetic retinopathy","volume":"241","author":"Liang","year":"2020","journal-title":"Life Sci."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Cross, K., Vetter, S.W., Alam, Y., Hasan, M.Z., Nath, A.D., and Leclerc, E. (2024). Role of the Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Inflammatory Responses. Biomolecules, 14.","DOI":"10.3390\/biom14121550"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2174\/1871527313666140806144831","article-title":"Receptor for AGEs (RAGE) as mediator of NF-kB pathway activation in neuroinflammation and oxidative stress","volume":"13","author":"Cuevas","year":"2014","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Bredeson, S., Papaconstantinou, J., Deford, J.H., Kechichian, T., Syed, T.A., Saade, G.R., and Menon, R. (2014). HMGB1 Promotes a p38MAPK Associated Non-Infectious Inflammatory Response Pathway in Human Fetal Membranes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113799"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.7314\/APJCP.2012.13.4.1365","article-title":"HMGB1 promotes the synthesis of pro-IL-1\u03b2 and pro-IL-18 by activation of p38 MAPK and NF-\u03baB through receptors for advanced glycation end-products in macrophages","volume":"13","author":"He","year":"2012","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1095\/biolreprod.116.144139","article-title":"HMGB1 induces an inflammatory response in the chorioamniotic membranes that is partially mediated by the inflammasome","volume":"95","author":"Plazyo","year":"2016","journal-title":"Biol. Reprod."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Padron, J.G., Saito Reis, C.A., Ng, P.K., Norman Ing, N.D., Baker, H., Davis, K., Kurashima, C., and Kendal-Wright, C.E. (2024). Stretch Causes cffDNA and HMGB1-Mediated Inflammation and Cellular Stress in Human Fetal Membranes. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105161"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2041769","DOI":"10.1155\/2022\/2041769","article-title":"Papaver Plants: Current Insights on Phytochemical and Nutritional Composition Along with Biotechnological Applications","volume":"2022","author":"Butnariu","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.phytochem.2010.04.022","article-title":"The biosynthesis of papaverine proceeds via (S)-reticuline","volume":"71","author":"Han","year":"2010","journal-title":"Phytochemistry"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-313X.2009.03937.x","article-title":"Functional characterization of a novel benzylisoquinoline O-methyltransferase suggests its involvement in papaverine biosynthesis in opium poppy (Papaver somniferum L)","volume":"60","author":"Pienkny","year":"2009","journal-title":"Plant J."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1080\/13543784.2017.1364360","article-title":"Investigational phosphodiesterase inhibitors in phase I and phase II clinical trials for Alzheimer\u2019s disease","volume":"26","author":"Prickaerts","year":"2017","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.coph.2011.10.003","article-title":"Phosphodiesterase function and endocrine cells: Links to human disease and roles in tumor development and treatment","volume":"11","author":"Levy","year":"2011","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Aslam, M., and Ladilov, Y. (2022). Emerging Role of cAMP\/AMPK Signaling. Cells, 11.","DOI":"10.3390\/cells11020308"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Gomes, D.A., Joubert, A.M., and Visagie, M.H. (2021). In vitro effects of papaverine on cell proliferation, reactive oxygen species, and cell cycle progression in cancer cells. Molecules, 26.","DOI":"10.3390\/molecules26216388"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1385\/NCC:2:2:124","article-title":"Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage","volume":"2","author":"Liu","year":"2005","journal-title":"Neurocritical Care"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cellsig.2017.07.018","article-title":"Therapeutic potentials of natural compounds acting on cyclic nucleotide phosphodiesterase families","volume":"39","author":"Abusnina","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1540\/jsmr.36.83","article-title":"Mechanism of relaxant response to papaverine on the smooth muscle of non-pregnant rat uterus","volume":"36","author":"Shimizu","year":"2000","journal-title":"J. Smooth Muscle Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1179\/016164107X191021","article-title":"The effect of papaverine on ion channels in rat basilar smooth muscle cells","volume":"29","author":"Han","year":"2007","journal-title":"Neurol. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.vph.2015.11.041","article-title":"The vasodilator papaverine stimulates L-type Ca2+ current in rat tail artery myocytes via a PKA-dependent mechanism","volume":"76","author":"Fusi","year":"2016","journal-title":"Vasc. Pharmacol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s12031-019-01289-w","article-title":"Cascade Signals of Papaverine Inhibiting LPS-Induced Retinal Microglial Activation","volume":"68","author":"Zhou","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1002\/ddr.21961","article-title":"Papaverine, a promising therapeutic agent for the treatment of COVID-19 patients with underlying cardiovascular diseases (CVDs)","volume":"83","author":"Valipour","year":"2022","journal-title":"Drug Dev. Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e70319","DOI":"10.1002\/jmv.70319","article-title":"Papaverine Targets STAT Signaling: A Dual-Action Therapy Option Against SARS-CoV-2","volume":"97","author":"Reus","year":"2025","journal-title":"J. Med. Virol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1248\/cpb.59.388","article-title":"Inhibitory effects of herbal alkaloids on the tumor necrosis factor-\u03b1 and nitric oxide production in lipopolysaccharide-stimulated RAW264 macrophages","volume":"59","author":"Yamazaki","year":"2011","journal-title":"Chem. Pharm. Bull."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1007\/s00018-011-0757-8","article-title":"Cyclic AMP: A selective modulator of NF-\u03baB action","volume":"68","author":"Gerlo","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"577476","DOI":"10.1016\/j.jneuroim.2021.577476","article-title":"Papaverine provides neuroprotection by suppressing neuroinflammation and apoptosis in the traumatic brain injury via RAGE-NF-\u03baB pathway","volume":"352","author":"Saglam","year":"2021","journal-title":"J. Neuroimmunol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Dasiran, M.F., Akba\u015f, A., Akba\u015f, B., Bora, E.S., Aygun, H., and Erbas, O. (2026). Papaverine Mitigates Acute Kidney Injury in Feces-Induced Polymicrobial Sepsis Through Regulation of the HMGB1\u2013RAGE Axis. Medicina, 62.","DOI":"10.3390\/medicina62040621"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s12974-019-1649-3","article-title":"The phosphodiesterase 10 inhibitor papaverine exerts anti-inflammatory and neuroprotective effects via the PKA signaling pathway in neuroinflammation and Parkinson\u2019s disease mouse models","volume":"16","author":"Lee","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"851","DOI":"10.2147\/DDDT.S97380","article-title":"Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-\u03baB signaling pathway","volume":"10","author":"Dang","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.bbrc.2019.01.136","article-title":"Papaverine identified as an inhibitor of high mobility group box 1\/receptor for advanced glycation end-products interaction suppresses high mobility group box 1-mediated inflammatory responses","volume":"511","author":"Tamada","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"295","DOI":"10.4062\/biomolther.2021.039","article-title":"Papaverine Exerts Neuroprotective Effect by Inhibiting NLRP3 Inflammasome Activation in an MPTP-Induced Microglial Priming Mouse Model Challenged with LPS","volume":"29","author":"Leem","year":"2021","journal-title":"Biomol. Ther."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cell.2014.11.047","article-title":"Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome","volume":"160","author":"Yan","year":"2015","journal-title":"Cell"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nature11588","article-title":"The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP","volume":"492","author":"Lee","year":"2012","journal-title":"Nature"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"101995","DOI":"10.1016\/j.ajogmf.2026.101995","article-title":"Oxytocin Alone Versus Oxytocin Plus Papaverine for Labor Induction in Primiparous Women After Catheter Ripening: A Randomized Controlled Trial","volume":"8","author":"Ganem","year":"2026","journal-title":"Am. J. Obstet. Gynecol. MFM"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/nm958","article-title":"Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure","volume":"9","author":"Tang","year":"2003","journal-title":"Nat. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1085\/jgp.200910365","article-title":"Nitric oxide induces airway smooth muscle cell relaxation by decreasing the frequency of agonist-induced Ca2+ oscillations","volume":"135","author":"Bai","year":"2010","journal-title":"J. Gen. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6344\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:03:29Z","timestamp":1784279009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":165,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146344"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146344","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}