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Effects of methanolic and aqueous Carica Papaya leaf extracts in transcriptional and miRNA-mediated regulation of fetal hemoglobin

dc.contributor.authorJacques, Filipa
dc.contributor.authorDelgadinho, Mariana
dc.contributor.authorGinete, Catarina
dc.contributor.authorGomes, Mário
dc.contributor.authorRibeiro, Edna
dc.contributor.authorBrito, Miguel
dc.contributor.authorGomes, Anita Q.
dc.date.accessioned2024-01-16T10:08:03Z
dc.date.available2024-01-16T10:08:03Z
dc.date.issued2023-11
dc.descriptionThis project was supported by the grant IDI&CA - IPL/2022/miRCa/ESTeSL.pt_PT
dc.description.abstractIntroduction: Hemoglobinopathies are genetic blood disorders characterized by abnormal hemoglobin that disrupts oxygen transport and leads to diverse health complications. Raising fetal hemoglobin (HbF) levels is one possible therapeutic approach. But the current main therapy based on the use of hydroxyurea (HU), faces limitations related to cost and safety, especially in underserved areas. To overcome these constraints, researchers are investigating natural alternatives like Carica papaya (CP) leaf extracts to boost HbF production with fewer side effects. Methodology: We conducted a comparative study using aqueous (AECP) and methanolic (MECP) CP leaf extracts to evaluate their impact on HbF regulation in K562 myeloid cells. Gene expression changes were assessed using RT-qPCR after 24-hour exposure to varying extract concentrations (0,05 μg/ml, 0,5μg/ml, and 5μg/ml). Results: The transcriptional analysis of hemoglobin genes (HBA, HBB, and HBG1), as well as that of its epigenetic regulators (HDAC1, HDAC2, HDAC3, DNMT1 and DNMT3b), transcription inhibitors (BCL11A and KLF1), transcription activators (MYC and HIC2) and miRNA-mediated regulators (miR-30a-3p, miR-29C-3p and miR-148b-3p), has revealed distinct expression patterns in K562 cells exposed to AECP when compared to MECP. While the expression levels of some genes were affected by one extract, other genes were affected by the other extract and some remained unaffected suggesting that the concentration and specific composition of AECP or MECP have a different impact on hemoglobin expression. Discussion: The differential effects of MECP and AECP exposure on hemoglobin-related genes expressed in K562 cells indicate that complex regulatory mechanisms underlie their action. The concentration-dependent responses observed emphasize the need for further research to comprehend their implications in hemoglobinopathies. Overall, this study highlights the potential of extracts of CP leaf as modulators of HbF gene expression in K562 cells. Further investigation into their gene modulation mechanisms is warranted.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJacques F, Delgadinho M, Ginete C, Gomes M, Ribeiro E, Brito M, Gomes AQ. Effects of methanolic and aqueous Carica Papaya leaf extracts in transcriptional and miRNA-mediated regulation of fetal hemoglobin. In: 27th Annual meeting of the Portuguese Society of Human Genetics, Instituto Superior Técnico, November 23-25, 2023. Medicine. 2025;104(4):e39478. pt_PT
dc.identifier.doi10.1097/MD.0000000000039478
dc.identifier.urihttp://hdl.handle.net/10400.21/16892
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationIPL/2022/miRCa/ESTeSLpt_PT
dc.relation.publisherversionhttps://www.spp.pt/eventos/default.asp?ida=12618&ID=136pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectCarica papayapt_PT
dc.subjectβ-hemoglobinopathiespt_PT
dc.subjectFetal hemoglobin reactivationpt_PT
dc.subjectGene expressionpt_PT
dc.subjectTranscriptional regulationpt_PT
dc.subjectmiRNA-mediated regulationpt_PT
dc.subjectIPL/2022/miRCa/ESTeSLpt_PT
dc.titleEffects of methanolic and aqueous Carica Papaya leaf extracts in transcriptional and miRNA-mediated regulation of fetal hemoglobinpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceLisboapt_PT
person.familyNameNeves Delgadinho
person.familyNameHonrado Ginete
person.familyNameRibeiro
person.familyNameBrito
person.familyNameGomes
person.givenNameMariana Isabel
person.givenNameAna Catarina
person.givenNameEdna
person.givenNameMiguel
person.givenNameAnita
person.identifierCAJ-5082-2022
person.identifier.ciencia-id231E-02E3-D9A9
person.identifier.ciencia-id8715-F62E-1E0F
person.identifier.ciencia-idC414-CDF2-D35A
person.identifier.ciencia-id231F-F341-7E93
person.identifier.ciencia-id4B10-E015-52B7
person.identifier.orcid0000-0003-0586-9154
person.identifier.orcid0000-0002-2334-782X
person.identifier.orcid0000-0003-1316-7750
person.identifier.orcid0000-0001-6394-658X
person.identifier.orcid0000-0002-3348-0448
person.identifier.ridA-7970-2016
person.identifier.ridC-3580-2014
person.identifier.scopus-author-id35224551000
person.identifier.scopus-author-id7202386033
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT
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