Investigación de biomarcadores de la saliva de neonatos: Sus posibles predicciones y métodos para evaluar la salud neonatal
DOI:
https://doi.org/10.33448/rsd-v14i12.50471Palabras clave:
Marcador clínico, Diagnóstico precoz, Recién nacidos, Tamizaje Neonatal.Resumen
La saliva humana es un biofluido exocrino compuesto por 99,5 % de agua y biomoléculas, reconocida como el “espejo de la salud del cuerpo". Durante años, la literatura científica ha documentado el potencial de los biomarcadores salivales en el cribado diagnóstico, la monitorización, el pronóstico y la predicción de enfermedades, destacando su estabilidad y la viabilidad de las recolecciones recurrentes, especialmente en neonatos. A pesar de este potencial, la saliva no se utiliza rutinariamente como muestra en el cribado neonatal. Así, esta investigación tiene como objetivo investigar los biomarcadores presentes en la saliva de neonatos, aplicaciones predictivas y los métodos para evaluar la salud neonatal. Mediante un enfoque cualitativo y exploratorio, se realizó una revisión de literatura integradora en las siguientes bases de datos: Catálogo de Tesis y Disertaciones de CAPES, Portal de Revistas de CAPES, PubMed y SCOPUS, con los descriptores en portugués e inglés: "Biomarkers" AND "saliva"; "biomarkers" AND "saliva" AND "neonates". Los criterios de inclusión incluyeron estudios de los últimos cinco años, disponibles en línea con acceso gratuito; estudios que utilizaron saliva como muestra; y estudios realizados con neonatos. Veintiuno estudios cumplieron los criterios de inclusión y se analizaron plenamente para identificar biomarcadores salivales. Los biomarcadores identificados se clasificaron en cuatro categorías: Expresión génica de genes específicos; Citocinas; Hormonas; y otras proteínas. La implementación clínica de estos biomarcadores está condicionada por tres desafíos principales: la necesidad de validación comparativa entre saliva y sangre, la aceptación por parte de los profesionales de la salud y la estandarización de protocolos en la comunidad médica. A pesar de estas limitaciones, las evidencias presentadas en las investigaciones sugieren que los biomarcadores salivales tienen el potencial de revolucionar el monitoreo neonatal.
Referencias
Abed, N. T., Behiry, E. G., & El-Aty, B. F. A. (2023). The Role of Salivary C-Reactive Protein in Diagnosis of Neonatal Sepsis. Journal of Neonatology, 37(1), 31–37. https://doi.org/10.1177/09732179231151757
Al Habobe, H., Haverkort, E. B., Nazmi, K., Van Splunter, A. P., Pieters, R. H. H., & Bikker, F. J. (2024). The impact of saliva collection methods on measured salivary biomarker levels. Clinica chimica acta; international journal of clinical chemistry, 552, 117628. https://doi.org/10.1016/j.cca.2023.117628
Barekatain, B., HasanGhalyaei, N., Mohammadizadeh, M., & Tavakolifard, N. (2021). Investigation of salivary C-reactive protein and interleukin-18 for the diagnosis of neonatal sepsis. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 26, 131. https://doi.org/10.4103/jrms.JRMS_1256_20
Bartolome, R., Kaneko-Tarui, T., Maron, J., & Zimmerman, E. (2020). The Utility of Speech-Language Biomarkers to Predict Oral Feeding Outcomes in the Premature Newborn. American journal of speech-language pathology, 29(2S), 1022–1029. https://doi.org/10.1044/2019_AJSLP-CSW18-19-0027
Bengnér, J., Quttineh, M., Gäddlin, P. O., Salomonsson, K., & Faresjö, M. (2021). Serum amyloid A - A prime candidate for identification of neonatal sepsis. Clinical immunology (Orlando, Fla.), 229, 108787. https://doi.org/10.1016/j.clim.2021.108787
Brasier, N., Osthoff, M., De Ieso, F., & Eckstein, J. (2021). Next-Generation Digital Biomarkers for Tuberculosis and Antibiotic Stewardship: Perspective on Novel Molecular Digital Biomarkers in Sweat, Saliva, and Exhaled Breath. Journal of medical Internet research, 23(8), e25907. https://doi.org/10.2196/25907
Brasil. (2014). Lei n. 13.002, de 20 de junho de 2014. Obriga a realização do Protocolo de Avaliação do Frênulo da Língua em Bebês. Brasília, DF: Presidência da República. Disponível em https://www.planalto.gov.br/ccivil_03/_ato2011-2014/2014/lei/l13002.htm
Brooks, S., Friedes, B. D., Northington, F., Graham, E., Tekes, A., Burton, V. J., Gerner, G., Zhu, J., Chavez-Valdez, R., Vaidya, D., & Everett, A. D. (2023). Serum brain injury biomarkers are gestationally and post-natally regulated in non-brain injured neonates. Pediatric research, 93(7), 1943–1954. https://doi.org/10.1038/s41390-021-01906-8
Brown, J. V. E., Meader, N., Cleminson, J., & McGuire, W. (2019). C-reactive protein for diagnosing late-onset infection in newborn infants. The Cochrane database of systematic reviews, 1(1), CD012126. https://doi.org/10.1002/14651858.CD012126.pub2
Castelli, B., Shapoori, S., McMahon, J., & FitzGerald, U. (2024). Measurement of immune and inflammatory biomarkers in serum and saliva in a multiple sclerosis cohort. Neuroscience Applied, 3, 104659. https://doi.org/10.1016/j.nsa.2024.104659
Ceyhan-Birsoy, O., Murry, J. B., Machini, K., Lebo, M. S., Yu, T. W., Fayer, S., Genetti, C. A., Schwartz, T. S., Agrawal, P. B., Parad, R. B., Holm, I. A., McGuire, A. L., Green, R. C., Rehm, H. L., Beggs, A. H., & BabySeq Project Team (2019). Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. American journal of human genetics, 104(1), 76–93. https://doi.org/10.1016/j.ajhg.2018.11.016
Chen, I. L., Huang, H. C., Ou-Yang, M. C., Chen, F. S., Chung, M. Y., & Chen, C. C. (2020). A novel method to detect bacterial infection in premature infants: Using a combination of inflammatory markers in blood and saliva. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, 53(6), 892–899. https://doi.org/10.1016/j.jmii.2019.11.002
Datla, S., Kitchanan, S., & Sethuraman, G. (2021). Diagnostic Reliability of Salivary C-Reactive Protein as an Alternative Noninvasive Biomarker of Neonatal Sepsis. Indian pediatrics, 58(8), 745–748.
Dias, L. R., Tomasi, Y. T., & Boing, A. F. (2024). The newborn screening tests in Brazil: regional and socioeconomic prevalence and inequalities in 2013 and 2019. Jornal de pediatria, 100(3), 296–304. https://doi.org/10.1016/j.jped.2023.11.008
Diesch, T., Filippi, C., Fritschi, N., Filippi, A., & Ritz, N. (2021). Cytokines in saliva as biomarkers of oral and systemic oncological or infectious diseases: A systematic review. Cytokine, 143, 155506. https://doi.org/10.1016/j.cyto.2021.155506
Dressendörfer, R. A., Kirschbaum, C., Rohde, W., Stahl, F., & Strasburger, C. J. (1992). Synthesis of a cortisol-biotin conjugate and evaluation as a tracer in an immunoassay for salivary cortisol measurement. The Journal of steroid biochemistry and molecular biology, 43(7), 683–692. https://doi.org/10.1016/0960-0760(92)90294-s
Ergünol, E., Şemsi, R., & Dinçel, A. S. (2024). Age and gender related changes on total antioxidant/oxidant status and electrolyte composition of saliva. Aspects of Molecular Medicine, 4, 100054. https://doi.org/10.1016/j.amolm.2024.100054
Fonseca, João José Saraiva. (2002). Metodologia da Pesquisa Científica. Universidade Estadual do Ceará.
Franco, V. L. de M., Marques, L. de O. C., Diniz, S. G. S., Assunção, V. I. de S., Nogueira, A. B. L., Bragagnolo, J. C. B., Barezani, A. F. B., & Paim, M. J. A. (2021). A técnica de elisa e a sua importância para o diagnóstico clinico / The elisa technique and its importance for clinical diagnosis. Brazilian Journal of Development, 7(9), 89877–89885. https://doi.org/10.34117/bjdv7n9-243
Gerona, R. R., & French, D. (2022). Drug testing in the era of new psychoactive substances. Advances in clinical chemistry, 111, 217–263. https://doi.org/10.1016/bs.acc.2022.08.001
GIL, A. C. (2002). Como elaborar projetos de pesquisa (4ed.) São Paulo: Atlas.
Green, R. C., Shah, N., Genetti, C. A., Yu, T., Zettler, B., Uveges, M. K., Ceyhan-Birsoy, O., Lebo, M. S., Pereira, S., Agrawal, P. B., Parad, R. B., McGuire, A. L., Christensen, K. D., Schwartz, T. S., Rehm, H. L., Holm, I. A., Beggs, A. H., & BabySeq Project Team (2023). Actionability of unanticipated monogenic disease risks in newborn genomic screening: Findings from the BabySeq Project. American journal of human genetics, 110(7), 1034–1045. https://doi.org/10.1016/j.ajhg.2023.05.007
Golubinskaya, V., Nilsson, H., Rydbeck, H., Hellström, W., Hellgren, G., Hellström, A., Sävman, K., & Mallard, C. (2024). Cytokine and growth factor correlation networks associated with morbidities in extremely preterm infants. BMC pediatrics, 24(1), 723. https://doi.org/10.1186/s12887-024-05203-1
Gomes, L.H.F, Marques, A. B., DIAS, I.C.M., Gabeira, S.C.O., Barcelos, T.R., Guimarães, M.O., Ferreira, I.R., Guida, L.C., Lucena, S.L & Rocha, A. D. (2024). Validation of Gene Expression Patterns for Oral Feeding Readiness: Transcriptional Analysis of Set of Genes in Neonatal Salivary Samples. Genes, 15(7), 936–936. https://doi.org/10.3390/genes15070936
Gomes, L. H. F., Marques, A. B., Dias, I. C. M., Cunha, D. P., Pimenta, H. P., Guida, L. D. C., Lucena, S. L., & Rocha, A. D. (2025). FOXP2 Expression and Oral Feeding Success in Preterm Infants: Sex 2 Differences. Genes, 16(2), 190. https://doi.org/10.3390/genes16020190
Gulati, P., Singh, A. K., Yadav, A. K., Pasbola, K., Pandey, P., Sharma, R., Thakar, A., & Solanki, P. R. (2023). Nano-modified screen-printed electrode-based electrochemical immunosensors for oral cancer biomarker detection in undiluted human serum and saliva samples. Nanoscale advances, 6(2), 705–721. https://doi.org/10.1039/d3na00682d
Huang, H. B., Lin, Y. B., Chen, J. H., Zhu, M., Chen, L. J., Ye, W., Luo, L. H., & Ye, H. M. (2024). Management of refined and personalized newborn blood specimen collection. Practical laboratory medicine, 40, e00408. https://doi.org/10.1016/j.plabm.2024.e00408
Iavarone, F., Tirone, C., Fattore, S., De Tomaso, D., Menzella, N., Vento, G., Olianas, A., Manconi, B., Cabras, T., Guadalupi, G., Contini, C., Boroumand, M., Desiderio, C., Muntiu, A., Fiorita, A., Fraschini, M., Fanos, V., Faa, G., Messana, I., & Castagnola, M. (2025). Characterization of N-Terminal Acetylated α-Hemoglobin Stabilizing Protein (AHSP) by Top-Down High-Resolution Mass Spectrometry From Human Preterm Newborns Oral Fluid. Rapid communications in mass spectrometry : RCM, 39(21), e10107. https://doi.org/10.1002/rcm.10107
Janakiraman, S., Sha, R., & Mani, N. K. (2025). Recent advancements in Point-of-Care Detection of Contaminants and Biomarkers in Human Breast Milk: A comprehensive review. Sensors and Actuators Reports, 9, 100280. https://doi.org/10.1016/j.snr.2024.100280
Kataoka, H., Ohshima, H., & Ohkawa, T. (2022). Simultaneous analysis of multiple steroidal biomarkers in saliva for objective stress assessment by on-line coupling of automated in-tube solid-phase microextraction and polarity-switching LC-MS/MS. Talanta Open, 7, 100177. https://doi.org/10.1016/j.talo.2022.100177
Kim, J. S., Taitt, C. R., Ligler, F. S., & Anderson, G. P. (2010). Multiplexed magnetic microsphere immunoassays for detection of pathogens in foods. Sensing and instrumentation for food quality and safety, 4(2), 73–81. https://doi.org/10.1007/s11694-010-9097-x
Kimura, M., Ito, Y., Shimomura, M., Morishita, H., Meguro, T., Adachi, Y., Seto, S. (2017). Cytokine profile after oral food challenge in infants with food protein-induced enterocolitis syndrome. Allergol Int. Jul;66(3):452-457. https://www.sciencedirect.com/science/article/pii/S1323893016301708?via%3Dihub
Knudsen, N., Tang, S., Lauzon, S., Dhaurali, S., Snyder, N. W., & Voegtline, K. M. (2024). Meconium as an Analyte for Androgen Exposure: Analysis Through Varying Maternal-Fetal Biomarkers. Developmental psychobiology, 66(7), e22550. https://doi.org/10.1002/dev.22550
Khurshid, Z., Zafar, M., Khan, E., Mali, M., & Latif, M. (2019). Human saliva can be a diagnostic tool for Zika virus detection. Journal of infection and public health, 12(5), 601–604. https://doi.org/10.1016/j.jiph.2019.05.004
LI, G. (2019). Nano-inspired biosensors for protein assay with clinical applications. Amsterdam, Netherlands ; Cambridge, Ma: Elsevier.
Lin, G. C., Küng, E., Smajlhodzic, M., Domazet, S., Friedl, H. P., Angerer, J., Wisgrill, L., Berger, A., Bingle, L., Peham, J. R., & Neuhaus, W. (2021). Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis. Pharmaceutics, 13(2), 256. https://doi.org/10.3390/pharmaceutics13020256
Madera Anaya, M. V., & Suárez Causado, A. (2017). Evaluation of two RNA extraction methods in children’s saliva. Revista Odontológica Mexicana, 21(4), e237–e243. https://doi.org/10.1016/j.rodmex.2018.01.014
Marin J. L. (2016). The Neonatal Salivary Transcriptome. Cold Spring Harbor perspectives in medicine, 6(3), a026369. https://doi.org/10.1101/cshperspect.a026369
McCarty, D., Silver, R., Quinn, L., Dusing, S., & O'Shea, T. M. (2024). Infant massage as a stress management technique for parents of hospitalized extremely preterm infants. Infant mental health journal, 45(1), 11–21. https://doi.org/10.1002/imhj.22095
Medeiros, P.D.S., & Da Silva, M.R.B. (2022). Conhecimento dos pais acerca da triagem neonatal. Revista Multidisciplinar do Sertão, v. 4, n. 3, p. 286-295. Disponível em https://www.revistamultisertao.com.br/index.php/revista/article/view/440/279
Metwali, W. A., Elmashad, A. M., Hazzaa, S. M. E., Al-Beltagi, M., & Hamza, M. B. (2024). Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia. World journal of clinical pediatrics, 13(1), 88645. https://doi.org/10.5409/wjcp.v13.i1.0000
Mohd Amin, A. T., Zaki, R. A., Friedmacher, F., & Sharif, S. P. (2021). C-reactive protein/albumin ratio is a prognostic indicator for predicting surgical intervention and mortality in neonates with necrotizing enterocolitis. Pediatric surgery international, 37(7), 881–886. https://doi.org/10.1007/s00383-021-04879-1
Moo-Young, Murray (Ed) (2011). Comprehensive biotechnology. (Vol. 6, 2.ed). Saint Louis, Mo.: Newnes.
Mulder, K. E., van Oostrom, E. C., Verheul, M. C., Hendriksen, P. A., Thijssen, S., Diks, M. A., Kraneveld, A. D., Garssen, J., & Verster, J. C. (2023). The relationship between immune fitness and saliva biomarkers of systemic inflammation. Brain, behavior, & immunity - health, 31, 100660. https://doi.org/10.1016/j.bbih.2023.100660
Naseem, R., Howe, N., Williams, C. J., Pretorius, S., & Green, K. (2024). What diagnostic tests are available for respiratory infections or pulmonary exacerbations in cystic fibrosis: A scoping literature review. Respiratory investigation, 62(5), 817–831. https://doi.org/10.1016/j.resinv.2024.07.005
Niehues, T., von Hardenberg, S., & Velleuer, E. (2024). Rapid identification of primary atopic disorders (PAD) by a clinical landmark-guided, upfront use of genomic sequencing. Allergologie select, 8, 304–323. https://doi.org/10.5414/ALX02520E
Omran, A., Ali, Y., Abdalla, M. O., El-Sharkawy, S., Rezk, A. R., & Khashana, A. (2021). Salivary Interleukin-6 and C-Reactive Protein/Mean Platelet Volume Ratio in the Diagnosis of Late-Onset Neonatal Pneumonia. Journal of immunology research, 2021, 8495889. https://doi.org/10.1155/2021/8495889
Omran, A., Sobh, H., Abdalla, M. O., El-Sharkawy, S., Rezk, A. R., & Khashana, A. (2021). Salivary and Serum Interleukin-10, C-Reactive Protein, Mean Platelet Volume, and CRP/MPV Ratio in the Diagnosis of Late-Onset Neonatal Sepsis in Full-Term Neonates. Journal of immunology research, 2021, 4884537. https://doi.org/10.1155/2021/4884537
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., Chou, R., Glanville, J., Grimshaw, J. M., Hróbjartsson, A., Lalu, M. M., Li, T., Loder, E. W., Mayo-Wilson, E., McDonald, S., McGuinness, L. A., … Moher, D. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ (Clinical research ed.), 372, n71. https://doi.org/10.1136/bmj.n71
Pang, R., Mujuni, B. M., Martinello, K. A., Webb, E. L., Nalwoga, A., Ssekyewa, J., Musoke, M., Kurinczuk, J. J., Sewegaba, M., Cowan, F. M., Cose, S., Nakakeeto, M., Elliott, A. M., Sebire, N. J., Klein, N., Robertson, N. J., & Tann, C. J. (2021). Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes. Pediatric Research, 92(1), 180–189. https://doi.org/10.1038/s41390-021-01438-1
Pereira, A. S. et al. (2018). Metodologia da pesquisa científica. [ebook gratuito]. Santa Maria: Editora da UFSM.
Pourkaviani, S., Zhang, X., Spear, E. A., D'Agostino, M., Satty, R. E., Liu, S. H., & Stroustrup, A. (2020). Clinical validation of the Neonatal Infant Stressor Scale with preterm infant salivary cortisol. Pediatric research, 87(7), 1237–1243. https://doi.org/10.1038/s41390-019-0713-0
Ren, Z., Mo, W., Yang, L., Wang, J., Zhang, Q., Zhong, Z., Wei, W., Liu, Z., Wu, Z., Yao, Y., & Yang, J. (2022). Cord blood antimicrobial peptide LL37 levels in preterm neonates and association with preterm complications. The Italian Journal of Pediatrics/Italian Journal of Pediatrics, 48(1), 111–111. https://doi.org/10.1186/s13052-022-01295-6
Rocha, V. A. D., Cruz-Machado, S. D. S., Silva, I. A., Fernandes, P. A. C. M., Markus, R. P., & Bueno, M. (2024). Identification of Inflammatory Mediators in Saliva Samples From Hospitalized Newborns: Potential Biomarkers?. Clinical nursing research, 33(4), 207–219. https://doi.org/10.1177/10547738241238249
Rodriguez, N., Vining, M., & Bloch-Salisbury, E. (2020). Salivary cortisol levels as a biomarker for severity of withdrawal in opioid-exposed newborns. Pediatric research, 87(6), 1033–1038. https://doi.org/10.1038/s41390-019-0601-7
Siddaiah, R., Emery, L., Stephens, H., Donnelly, A., Erkinger, J., Wisecup, K., Hicks, S. D., Kawasawa, Y. I., Oji-Mmuo, C., Amatya, S., & Silveyra, P. (2022). Early Salivary miRNA Expression in Extreme Low Gestational Age Newborns. Life (Basel, Switzerland), 12(4), 506. https://doi.org/10.3390/life12040506
Solaz-García, A., Lara-Cantón, I., Peña-Bautista, C., Cháfer-Pericás, C., Cañada-Martínez, A. J., Pinilla-González, A., Vento, M., & Sáenz-González, P. (2021). Non-invasive monitoring of saliva can be used to identify oxidative stress biomarkers in preterm and term newborn infants. Acta paediatrica (Oslo, Norway : 1992), 110(12), 3255–3260. https://doi.org/10.1111/apa.16073
Snyder, H. (2019). Literature review as a research methodology: An overview and guidelines. Journal of Business Research. 104, 333-9. Doi: https://doi.org/10.1016/j.jbusres.2019.07.039
Swetha, P., Balijapalli, U., & Feng, S.-P. (2022). Wireless accessing of salivary biomarkers based wearable electrochemical sensors: A mini-review. Electrochemistry Communications, 140, 107314. https://doi.org/10.1016/j.elecom.2022.107314
Su, T. Y., Chen, I. L., Yeh, T. F., Yu, H. R., Hsu, Y. L., Hung, C. H., & Huang, H. C. (2021). Salivary cytokine - A non-invasive predictor for bronchopulmonary dysplasia in premature neonates. Cytokine, 148, 155616. https://doi.org/10.1016/j.cyto.2021.155616
Tang, Z., Jiang, M., Ou-Yang, Z., Wu, H., Dong, S., & Hei, M. (2019). High mobility group box 1 protein (HMGB1) as biomarker in hypoxia-induced persistent pulmonary hypertension of the newborn: a clinical and in vivo pilot study. International journal of medical sciences, 16(8), 1123–1131. https://doi.org/10.7150/ijms.34344
Testosterone Estosterone Enzyme Immunoassay Kit: Expanded Range. (2018). State College, PA: Salimetrics.
Tilahun, D., Yimer, M. A., & Zamanuel, T. G. (2022). High Magnitude of Neonatal Anemia Among Sick Newborns Admitted to University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. Journal of blood medicine, 13, 293–302. https://doi.org/10.2147/JBM.S361675
Toldra, F., WU, J. (2021). Biologically Active Peptides (Vol 1.). United Kingdom: Elsevier.
Tosson, A. M. S., Koptan, D., Abdel Aal, R., & Abd Elhady, M. (2021). Evaluation of serum and salivary C-reactive protein for diagnosis of late-onset neonatal sepsis: A single center cross-sectional study. Jornal de pediatria, 97(6), 623–628. https://doi.org/10.1016/j.jped.2021.01.004
Triagem neonatal biológica: manual técnico. (2016). Brasil, Brasília: Ministério da Saúde, Secretaria de Atenção à Saúde, Departamento de Atenção Especializada e Temática.
Vasan, R.S., Sawyer, B.D., (2018). Encyclopedia of cardiovascular research and medicine (Vol. 4, ed 1st.). Amsterdam, Netherlands: Elsevier
Yen, E., Kaneko-Tarui, T., & Maron, J. L. (2021). Technical Considerations and Protocol Optimization for Neonatal Salivary Biomarker Discovery and Analysis. Frontiers in pediatrics, 8, 618553. https://doi.org/10.3389/fped.2020.618553
Zamora-Obando, H. R., Godoy, A. T., Amaral, A. G., Mesquita, A. de S., Simões, B. E. S., Reis, H. O., Rocha, I., Dallaqua, M., Baptistão, M., Fernandes, M. C. V., Lima, M. F., & Simionato, A. V. C.. (2022). Biomarcadores moleculares de doenças humana: conceitos fundamentais, modelos de estudo e aplicações clínicas. Química Nova, 45(9), 1098–1113. https://doi.org/10.21577/0100-4042.20170905
Zhu, X., Mao, Z., Zheng, P., Wang, L., Zhang, F., Zi, G., Liu, H., Zhang, H., Liu, W., & Zhou, L. (2025). The role and research progress of epigenetic modifications in obstructive sleep apnoea-hypopnea syndrome and related complications. Respiratory medicine, 242, 108099. https://doi.org/10.1016/j.rmed.2025.108099
Descargas
Publicado
Número
Sección
Licencia
Derechos de autor 2025 Jamile Kisner Lacerda da Silva, Matheus Dellaméa Baldissera, Juliana Fleck, Diulie Valente de Souza, Raquel Tusi Tamiosso
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
Los autores que publican en esta revista concuerdan con los siguientes términos:
1) Los autores mantienen los derechos de autor y conceden a la revista el derecho de primera publicación, con el trabajo simultáneamente licenciado bajo la Licencia Creative Commons Attribution que permite el compartir el trabajo con reconocimiento de la autoría y publicación inicial en esta revista.
2) Los autores tienen autorización para asumir contratos adicionales por separado, para distribución no exclusiva de la versión del trabajo publicada en esta revista (por ejemplo, publicar en repositorio institucional o como capítulo de libro), con reconocimiento de autoría y publicación inicial en esta revista.
3) Los autores tienen permiso y son estimulados a publicar y distribuir su trabajo en línea (por ejemplo, en repositorios institucionales o en su página personal) a cualquier punto antes o durante el proceso editorial, ya que esto puede generar cambios productivos, así como aumentar el impacto y la cita del trabajo publicado.
