{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:27Z","timestamp":1787028447900,"version":"build-2736575974"},"reference-count":81,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014434","name":"Narodowa Agencja Wymiany Akademickiej","doi-asserted-by":"publisher","award":["PPN\/BIL\/2018\/1\/00250\/U\/0001"],"award-info":[{"award-number":["PPN\/BIL\/2018\/1\/00250\/U\/0001"]}],"id":[{"id":"10.13039\/501100014434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00276\/2020"],"award-info":[{"award-number":["UIDB\/00276\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/CVT-REP\/4202\/2014"],"award-info":[{"award-number":["PTDC\/CVT-REP\/4202\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/101058\/2014"],"award-info":[{"award-number":["SFRH\/BD\/101058\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometrosis is a reproductive pathology that is responsible for mare infertility. Our recent studies have focused on the involvement of neutrophil extracellular traps enzymes, such as elastase (ELA), in the development of equine endometrosis. Noscapine (NOSC) is an alkaloid derived from poppy opium with anticough, antistroke, anticancer, and antifibrotic properties. The present work investigates the putative inhibitory in vitro effect of NOSC on collagen type I alpha 2 chain (COL1A2) mRNA and COL1 protein relative abundance induced by ELA in endometrial explants of mares in the follicular or mid-luteal phases at 24 or 48 h of treatment. The COL1A2 mRNA was evaluated by qPCR and COL1 protein relative abundance by Western blot. In equine endometrial explants, ELA increased COL 1 expression, while NOSC inhibited it at both estrous cycle phases and treatment times. These findings contribute to the future development of new endometrosis treatment approaches. Noscapine could be a drug capable of preventing collagen synthesis in mare\u2019s endometrium and facilitate the therapeutic approach.<\/jats:p>","DOI":"10.3390\/ijms22105333","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T12:58:07Z","timestamp":1621429087000},"page":"5333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-262X","authenticated-orcid":false,"given":"Ana","family":"Amaral","sequence":"first","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Fun\u00e7\u00e3o, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Fernandes","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Fun\u00e7\u00e3o, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sz\u00f3stek-Mioduchowska","sequence":"additional","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-445X","authenticated-orcid":false,"given":"Maria Rosa","family":"Rebord\u00e3o","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Fun\u00e7\u00e3o, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"},{"name":"Polytechnic of Coimbra, Coimbra Agriculture School, Bencanta, 3045-601 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-3560","authenticated-orcid":false,"given":"Dariusz Jan","family":"Skarzynski","sequence":"additional","affiliation":[{"name":"Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-6513","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Ferreira-Dias","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Fun\u00e7\u00e3o, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"ref_1","unstructured":"Morrow, D.A. (1986). Equine endometrial biopsy. Current Therapy in Theriogenology 2: Diagnosis, Treatment, and Prevention of Reproductive Diseases in Small and Large Animals, W.B. Saunders. [2nd ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.anireprosci.2008.03.019","article-title":"The Equine Endometrosis: New Insights into the Pathogenesis","volume":"111","author":"Hoffmann","year":"2009","journal-title":"Anim. Reprod. Sci."},{"key":"ref_3","first-page":"186","article-title":"The aetiology, diagnosis, and classification of chronic degenerative endometritis","volume":"Volume 125","author":"Hughes","year":"1992","journal-title":"Workshop on Equine Endometritis"},{"key":"ref_4","first-page":"463","article-title":"Endometrial biopsy of mares: Visualization of healthy and diseased structure","volume":"63","author":"Katkiewicz","year":"2007","journal-title":"Med. Weter."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.theriogenology.2018.10.005","article-title":"Effect of Transforming Growth Factor -\u03921 on \u03b1-Smooth Muscle Actin and Collagen Expression in Equine Endometrial Fibroblasts","volume":"124","author":"Lukasik","year":"2019","journal-title":"Theriogenology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"154767","DOI":"10.1016\/j.cyto.2019.154767","article-title":"Effect of Proinflammatory Cytokines on Endometrial Collagen and Metallopeptidase Expression during the Course of Equine Endometrosis","volume":"123","author":"Baclawska","year":"2019","journal-title":"Cytokine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1038\/s41598-020-58109-0","article-title":"Matrix Metallopeptidase Expression and Modulation by Transforming Growth Factor-\u03921 in Equine Endometrosis","volume":"10","author":"Pacewicz","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.theriogenology.2018.02.001","article-title":"Constituents of Neutrophil Extracellular Traps Induce in Vitro Collagen Formation in Mare Endometrium","volume":"113","author":"Amaral","year":"2018","journal-title":"Theriogenology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.domaniend.2018.10.004","article-title":"Impairment of the Antifibrotic Prostaglandin E2 Pathway May Influence Neutrophil Extracellular Traps\u2013Induced Fibrosis in the Mare Endometrium","volume":"67","author":"Amaral","year":"2019","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/rda.13258","article-title":"Elastase Inhibition Affects Collagen Transcription and Prostaglandin Secretion in Mare Endometrium during the Estrous Cycle","volume":"53","author":"Amaral","year":"2018","journal-title":"Reprod. Dom. Anim."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Amaral, A., Fernandes, C., Rebord\u00e3o, M.R., Sz\u00f3stek-Mioduchowska, A., Lukasik, K., Gawronska-Kozak, B., Telo da Gama, L., Skarzynski, D.J., and Ferreira-Dias, G. (2020). The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium. Animals, 10.","DOI":"10.3390\/ani10050863"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"582211","DOI":"10.3389\/fvets.2020.582211","article-title":"The Inhibition of Cathepsin G on Endometrial Explants With Endometrosis in the Mare","volume":"7","author":"Amaral","year":"2020","journal-title":"Front. Vet. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Amaral, A., Fernandes, C., Rebord\u00e3o, M.R., Sz\u00f3stek-Mioduchowska, A., Lukasik, K., Pinto-Bravo, P., Telo da Gama, L., Jan Skarzynski, D., and Ferreira-Dias, G. (2021). Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions. Animals, 11.","DOI":"10.3390\/ani11010208"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/0093-691X(94)90173-G","article-title":"Sperm-Induced Leukocytosis in the Equine Uterus","volume":"41","author":"Kotilainen","year":"1994","journal-title":"Theriogenology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/biolreprod\/52.monograph_series1.515","article-title":"Onset and Duration of Uterine Inflammatory Response of Mares after Insemination with Fresh Semen","volume":"52","author":"Katila","year":"1995","journal-title":"Biol. Reprod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1095\/biolreprod49.3.507","article-title":"Function of Uterine and Blood-Derived Polymorphonuclear Neutrophils in Mares Susceptible and Resistant to Chronic Uterine Infection: Phagocytosis and Chemotaxis1","volume":"49","author":"Troedsson","year":"1993","journal-title":"Biol. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.cveq.2006.07.003","article-title":"Breeding-Induced Endometritis in Mares","volume":"22","author":"Troedsson","year":"2006","journal-title":"Vet. Clin. N. Am. Equine Pract."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil Extracellular Traps Kill Bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nm.4294","article-title":"An Emerging Role for Neutrophil Extracellular Traps in Noninfectious Disease","volume":"23","author":"Jorch","year":"2017","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.2042-3306.1991.tb02752.x","article-title":"The Effect of Age and Parity on the Development of Equine Chronic Endometrial Disease","volume":"23","author":"Ricketts","year":"1991","journal-title":"Equine Vet. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.theriogenology.2012.02.028","article-title":"Susceptibility to Persistent Breeding-Induced Endometritis in the Mare: Relationship to Endometrial Biopsy Score and Age, and Variations between Seasons","volume":"78","author":"Woodward","year":"2012","journal-title":"Theriogenology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"588","DOI":"10.21836\/PEM19990619","article-title":"The treatment of equine endometritis in studfarm practice","volume":"15","author":"Ricketts","year":"1999","journal-title":"PHK"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1439-0531.2009.01485.x","article-title":"Clinical and Subclinical Endometritis in the Mare: Both Threats to Fertility","volume":"44","author":"LeBlanc","year":"2009","journal-title":"Reprod. Domest. Anim."},{"key":"ref_25","unstructured":"Samper, J.C. (2009). Equine Breeding Management and Artificial Insemination, Saunders Elsevier. [2nd ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1071\/RD14390","article-title":"Not Just a Number: Effect of Age on Fertility, Pregnancy and Offspring Vigour in Thoroughbred Brood-Mares","volume":"27","author":"Scoggin","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_27","unstructured":"Oddsd\u00f3ttir, C. (2007). Development of Endometrial Fibrosis in the Mare: Factors Involved in Tissue Remodeling and Collagen Deposition. [Ph.D Thesis, University of Edinburgh]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.biochi.2007.10.009","article-title":"Neutrophil Elastase, Proteinase 3 and Cathepsin G: Physicochemical Properties, Activity and Physiopathological Functions","volume":"90","author":"Korkmaz","year":"2008","journal-title":"Biochimie"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"O\u2019Donoghue, A.J., Jin, Y., Knudsen, G.M., Perera, N.C., Jenne, D.E., Murphy, J.E., Craik, C.S., and Hermiston, T.W. (2013). Global Substrate Profiling of Proteases in Human Neutrophil Extracellular Traps Reveals Consensus Motif Predominantly Contributed by Elastase. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075141"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1189\/jlb.3HI1014-493R","article-title":"Neutrophil Elastase Promotes Myofibroblast Differentiation in Lung Fibrosis","volume":"98","author":"Gregory","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1701910","DOI":"10.1183\/13993003.01910-2017","article-title":"Elastase Activity on Sputum Neutrophils Correlates with Severity of Lung Disease in Cystic Fibrosis","volume":"51","author":"Dittrich","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0093-691X(89)90317-8","article-title":"Dimethyl Sulfoxide Intrauterine Therapy in the Mare: Effects upon Endometrial Histological Features and Biopsy Classification","volume":"32","author":"Ley","year":"1989","journal-title":"Theriogenology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.theriogenology.2019.11.014","article-title":"Uterine Responses and Equine Chorionic Gonadotropin Concentrations after Two Intrauterine Infusions with Kerosene Post Early Fetal Loss in Mares","volume":"147","author":"Podico","year":"2020","journal-title":"Theriogenology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.theriogenology.2020.06.010","article-title":"Assessment of the Anti-Inflammatory and Engraftment Potential of Horse Endometrial and Adipose Mesenchymal Stem Cells in an in Vivo Model of Post Breeding Induced Endometritis","volume":"155","author":"Navarrete","year":"2020","journal-title":"Theriogenology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"110100","DOI":"10.1016\/j.vetimm.2020.110100","article-title":"In Vitro Preconditioning of Equine Adipose Mesenchymal Stem Cells with Prostaglandin E2, Substance P and Their Combination Changes the Cellular Protein Secretomics and Improves Their Immunomodulatory Competence without Compromising Stemness","volume":"228","author":"Cabezas","year":"2020","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/BF00315110","article-title":"Pharmacokinetics of Oral Noscapine","volume":"39","author":"Karlsson","year":"1990","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1002\/med.21357","article-title":"The Noscapine Chronicle: A Pharmaco-Historic Biography of the Opiate Alkaloid Family and Its Clinical Applications: THE NOSCAPINE CHRONICLE","volume":"35","author":"Rida","year":"2015","journal-title":"Med. Res. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00228-003-0676-1","article-title":"A Preliminary Report on the Application of Noscapine in the Treatment of Stroke","volume":"59","author":"Mahmoudian","year":"2003","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_39","first-page":"244","article-title":"The Protective Activity of Noscapine on Renal Ischemia\u2014Reperfusion Injury in Male Wistar Rat","volume":"17","author":"Khanmoradi","year":"2014","journal-title":"Iran J. Basic Med. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zughaier, S., Karna, P., Stephens, D., and Aneja, R. (2010). Potent Anti-Inflammatory Activity of Novel Microtubule-Modulating Brominated Noscapine Analogs. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009165"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1073\/pnas.95.4.1601","article-title":"Opium Alkaloid Noscapine Is an Antitumor Agent That Arrests Metaphase and Induces Apoptosis in Dividing Cells","volume":"95","author":"Ye","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/0041-008X(61)90013-8","article-title":"Toxicity Studies on Noscapine","volume":"3","author":"Winter","year":"1961","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.3892\/ijo.2016.3476","article-title":"Apoptotic Effect of Noscapine in Breast Cancer Cell Lines","volume":"48","author":"Calaf","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1208\/s12249-020-01710-3","article-title":"A Combinational Approach Towards Treatment of Breast Cancer: An Analysis of Noscapine-Loaded Polymeric Nanoparticles and Doxorubicin","volume":"21","author":"Esnaashari","year":"2020","journal-title":"AAPS PharmSciTech"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7505","DOI":"10.1074\/jbc.M113.546812","article-title":"Antifibrotic Effects of Noscapine through Activation of Prostaglandin E2 Receptors and Protein Kinase, A.J","volume":"289","author":"Kach","year":"2014","journal-title":"Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.1021\/acs.jproteome.0c00367","article-title":"Molecular Binding Mechanism and Pharmacology Comparative Analysis of Noscapine for Repurposing against SARS-CoV-2 Protease","volume":"19","author":"Kumar","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s10020-019-0084-3","article-title":"Increased Proteinase 3 and Neutrophil Elastase Plasma Concentrations Are Associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes","volume":"25","author":"Mirea","year":"2019","journal-title":"Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1084\/jem.20160530","article-title":"Peptidylarginine Deiminase 4 Promotes Age-Related Organ Fibrosis","volume":"214","author":"Martinod","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Salazar-Gonzalez, H., Zepeda-Hernandez, A., Melo, Z., Saavedra-Mayorga, D.E., and Echavarria, R. (2019). Neutrophil Extracellular Traps in the Establishment and Progression of Renal Diseases. Medicina, 55.","DOI":"10.3390\/medicina55080431"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Tucker, S.L., Sarr, D., and Rada, B. (2021). Neutrophil Extracellular Traps Are Present in the Airways of ENaC-Overexpressing Mice with Cystic Fibrosis-like Lung Disease. BMC Immunol., 22.","DOI":"10.1186\/s12865-021-00397-w"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1210\/er.2008-0021","article-title":"Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption","volume":"30","author":"Vandenberg","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jsbmb.2011.08.007","article-title":"Endocrine Disrupting Chemicals and Disease Susceptibility","volume":"127","author":"Schug","year":"2011","journal-title":"J. Steroid. Biochem. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1289\/ehp.0900887","article-title":"A Clash of Old and New Scientific Concepts in Toxicity, with Important Implications for Public Health","volume":"117","author":"Myers","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_54","first-page":"169","article-title":"Effect of Ovarian Hormones on the Phagocytic Response of Ovariectomized Mares","volume":"32","author":"Ganjam","year":"1982","journal-title":"J. Reprod. Fertil. Suppl."},{"key":"ref_55","first-page":"327","article-title":"Factors Affecting Uterine Clearance of Inoculated Materials in Mares","volume":"35","author":"Evans","year":"1987","journal-title":"J. Reprod. Fertil. Suppl."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the Regulation of Protein Abundance from Proteomic and Transcriptomic Analyses","volume":"13","author":"Vogel","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_57","first-page":"38","article-title":"Collagen I and the Fibroblast: High Protein Expression Requires a New Paradigm of Post-Transcriptional, Feedback Regulation","volume":"3","author":"Schwarz","year":"2015","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1007\/s11064-019-02837-x","article-title":"Noscapine, a Non-Addictive Opioid and Microtubule-Inhibitor in Potential Treatment of Glioblastoma","volume":"44","author":"Altinoz","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1158\/1535-7163.MCT-06-0205","article-title":"Treatment of Hormone-Refractory Breast Cancer: Apoptosis and Regression of Human Tumors Implanted in Mice","volume":"5","author":"Aneja","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/CAD.0b013e3282ffd68d","article-title":"Noscapine Induces Apoptosis in Human Glioma Cells by an Apoptosis-Inducing Factor-Dependent Pathway","volume":"19","author":"Newcomb","year":"2008","journal-title":"Anti-Cancer Drugs"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1158\/1078-0432.CCR-04-0360","article-title":"Noscapine Crosses the Blood-Brain Barrier and Inhibits Glioblastoma Growth","volume":"10","author":"Landen","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_62","first-page":"1121","article-title":"Noscapine Inhibits Hypoxia-Mediated HIF-1\u03b1 Expression Andangiogenesis in Vitro: A Novel Function for an Old Drug","volume":"5","author":"Newcomb","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1158\/0008-5472.CAN-09-4230","article-title":"Noscapine, a Benzylisoquinoline Alkaloid, Sensitizes Leukemic Cells to Chemotherapeutic Agents and Cytokines by Modulating the NF-\u039aB Signaling Pathway","volume":"70","author":"Sung","year":"2010","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Chougule, M.B., Patel, A.R., Jackson, T., and Singh, M. (2011). Antitumor Activity of Noscapine in Combination with Doxorubicin in Triple Negative Breast Cancer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017733"},{"key":"ref_65","unstructured":"Acuff, C., and Kalman, D. (2011). Noscapine and Noscapine Analogs and Their Use in treating Infectious Diseases by Tubulin Binding Inhibition. (20110274651-A1), U.S. Patent Application, Available online: http:\/\/www.freepatentsonline.com\/20110274651.pdf."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e02795","DOI":"10.1016\/j.heliyon.2019.e02795","article-title":"Computational Approach to Study the Synthesis of Noscapine and Potential of Stereoisomers against NsP3 Protease of CHIKV","volume":"5","author":"Singh","year":"2019","journal-title":"Heliyon"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"15466","DOI":"10.1074\/jbc.M113.464461","article-title":"Control of Myofibroblast Differentiation by Microtubule Dynamics through a Regulated Localization of MDia2","volume":"288","author":"Sandbo","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3389\/fphar.2017.00326","article-title":"Targeting Hypoxia Inducible Factors-1\u03b1 as a Novel Therapy in Fibrosis","volume":"8","author":"Xiong","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.4049\/jimmunol.0903900","article-title":"NLRC5 Limits the Activation of Inflammatory Pathways","volume":"185","author":"Benko","year":"2010","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Canisso, I.F., Segabinazzi, L.G.T.M., and Fedorka, C.E. (2020). Persistent Breeding-Induced Endometritis in Mares\u2014A Multifaceted Challenge: From Clinical Aspects to Immunopathogenesis and Pathobiology. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041432"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1530\/REP-12-0452","article-title":"Endometrial Inflammatory Markers of the Early Immune Response in Mares Susceptible or Resistant to Persistent Breeding-Induced Endometritis","volume":"145","author":"Woodward","year":"2013","journal-title":"Reproduction"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.domaniend.2006.03.007","article-title":"Endometrial Nitric Oxide Production and Nitric Oxide Synthases in the Equine Endometrium: Relationship with Microvascular Density during the Estrous Cycle","volume":"32","author":"Mateus","year":"2007","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.theriogenology.2007.05.050","article-title":"Relationships between Uterine Culture, Cytology and Pregnancy Rates in a Thoroughbred Practice","volume":"68","author":"Riddle","year":"2007","journal-title":"Theriogenology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1600-0897.2007.00548.x","article-title":"Endometrial Explant Culture for Characterizing Equine Endometritis","volume":"59","author":"Nash","year":"2008","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_75","first-page":"79","article-title":"Impairment of the Interleukin System in Equine Endometrium during the Course of Endometrosis","volume":"89","author":"Lukasik","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.bbrc.2012.04.079","article-title":"Noscapine Induces Mitochondria-Mediated Apoptosis in Human Colon Cancer Cells in Vivo and in Vitro","volume":"421","author":"Yang","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/molehr\/gaq095","article-title":"Critical Evaluation of Human Endometrial Explants as an Ex Vivo Model System: A Molecular Approach","volume":"17","author":"Schafer","year":"2011","journal-title":"Mol. Hum. Reprod."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2144\/04371RR03","article-title":"Validation of Housekeeping Genes for Normalizing RNA Expression in Real-Time PCR","volume":"37","author":"Dheda","year":"2004","journal-title":"BioTechniques"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1089\/cmb.2005.12.1047","article-title":"Comprehensive Algorithm for Quantitative Real-Time Polymerase Chain Reaction","volume":"12","author":"Zhao","year":"2005","journal-title":"J. Comput. Biol."},{"key":"ref_80","unstructured":"(2021, May 06). UniProtKB\u2014F6RTI8 (F6RTI8_HORSE). Available online: https:\/\/www.uniprot.org\/uniprot\/F6RTI8."},{"key":"ref_81","first-page":"50948","article-title":"V3 Stain-Free Workflow for a Practical, Convenient, and Reliable Total Protein Loading Control in Western Blotting","volume":"82","author":"Posch","year":"2013","journal-title":"JoVE"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5333\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:03:52Z","timestamp":1760162632000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,19]]},"references-count":81,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22105333"],"URL":"https:\/\/doi.org\/10.3390\/ijms22105333","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,19]]}}}