Análisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, Colombia

La biodiversidad marina ha dado lugar a una extraordinaria variedad de compuestos químicos, muchos de ellos con propiedades biológicas excepcionales. Estos metabolitos secundarios, le confieren ventajas adaptativas a los organismos marinos, las cuales han sido utilizadas por su gran potencial en áre...

Full description

Autores:
Julio Berrio, Mirleth
Tipo de recurso:
Fecha de publicación:
2025
Institución:
Universidad de Córdoba
Repositorio:
Repositorio Institucional Unicórdoba
Idioma:
spa
OAI Identifier:
oai:repositorio.unicordoba.edu.co:ucordoba/9007
Acceso en línea:
https://repositorio.unicordoba.edu.co/handle/ucordoba/9007
https://repositorio.unicordoba.edu.co/
Palabra clave:
Holoturoideos
Ácidos grasos
Actividad biológica
Actividad antioxidante
Córdoba
Sea cucumbers
Fatty acids
Biological activity
Antioxidant activity
Córdoba
Rights
embargoedAccess
License
Copyright Universidad de Córdoba, 2025
id UCORDOBA2_897f216d5b7cfacf51554b00207ddb4b
oai_identifier_str oai:repositorio.unicordoba.edu.co:ucordoba/9007
network_acronym_str UCORDOBA2
network_name_str Repositorio Institucional Unicórdoba
repository_id_str
dc.title.spa.fl_str_mv Análisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, Colombia
title Análisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, Colombia
spellingShingle Análisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, Colombia
Holoturoideos
Ácidos grasos
Actividad biológica
Actividad antioxidante
Córdoba
Sea cucumbers
Fatty acids
Biological activity
Antioxidant activity
Córdoba
title_short Análisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, Colombia
title_full Análisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, Colombia
title_fullStr Análisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, Colombia
title_full_unstemmed Análisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, Colombia
title_sort Análisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, Colombia
dc.creator.fl_str_mv Julio Berrio, Mirleth
dc.contributor.advisor.none.fl_str_mv Santafé Patiño, Gilmar
Quirós-Rodríguez, Jorge A.
dc.contributor.author.none.fl_str_mv Julio Berrio, Mirleth
dc.contributor.jury.none.fl_str_mv Oviedo Zumaqué, Luis Eliécer
Valle Zapata, Hernan Alonso
dc.subject.proposal.spa.fl_str_mv Holoturoideos
Ácidos grasos
Actividad biológica
Actividad antioxidante
Córdoba
topic Holoturoideos
Ácidos grasos
Actividad biológica
Actividad antioxidante
Córdoba
Sea cucumbers
Fatty acids
Biological activity
Antioxidant activity
Córdoba
dc.subject.keywords.eng.fl_str_mv Sea cucumbers
Fatty acids
Biological activity
Antioxidant activity
Córdoba
description La biodiversidad marina ha dado lugar a una extraordinaria variedad de compuestos químicos, muchos de ellos con propiedades biológicas excepcionales. Estos metabolitos secundarios, le confieren ventajas adaptativas a los organismos marinos, las cuales han sido utilizadas por su gran potencial en áreas como la medicina, debido a sus propiedades anticancerígenas, antimicrobianas, antifúngicas y antioxidantes. En este estudio se identificaron estructuralmente 23 compuestos mediante la cromatografía de gases acoplado a espectrometría de masas de impacto electrónico. De los 23 compuestos aislados 22 correspondían a ácidos grasos saturados e insaturados y uno de naturaleza esterólica. Por otro lado, mediante la evaluación de la actividad antioxidante del extracto etanólico de la especie Holothuria grisea frente al radical catiónico ABTS+● se determinó el valor de IC50 de 235,32 μg/mL. En cuanto al ensayo antioxidante por el método del radical DPPH● se determinó un IC50 de 1604,27 μg/mL. La evaluación de la actividad antibacteriana de las dos especies de holotúridos se realizó frente a los aislados clínicos Gram positivas (Staphylococcus aureus, Enterococcus faecium) y Gram negativas (Escherichia coli, Stenotrophomonas maltophilia) por el método de microdilución. El extracto etanólico de H. grisea presentó porcentajes significativos a 2000 mg/L reduciendo el crecimiento de estos microorganismos, destacándose la mayor sensibilidad en la especie S. maltophilia con un porcentaje de reducción de crecimiento del 100% a 1250 mg/L, seguido de E. coli y E. faecium con porcentajes de reducción de 99,34% y 91,85% respectivamente. Por su parte, el extracto etanólico de H. princeps, no presentó una considerable inhibición del crecimiento en estas cepas bacterianas. Para la evaluación de la actividad antifúngica frente a las cepas del género Candida (C. albicans, C. tropicalis, C. glabrata y C. auris), a nivel general los mejores resultados de inhibición de crecimiento se mostraron a mayores concentraciones de los extractos etanólicos (desde 2500 mg/L). Se evidenció que los aislados clínicos C. tropicalis y C. glabrata, fueron las cepas fúngicas más susceptible al extracto etanólico de H. grisea, presentando una reducción de crecimiento del 100% a 2500 mg/L y para H. princeps la cepa fúngica más suceptible fue C. glabrata, la cual presentó una reducción de crecimiento de 95,7% a 5000 mg/L.
publishDate 2025
dc.date.accessioned.none.fl_str_mv 2025-02-05T17:13:39Z
dc.date.available.none.fl_str_mv 2025-02-05T17:13:39Z
2026-12-31
dc.date.issued.none.fl_str_mv 2025-02-03
dc.type.none.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.none.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.none.fl_str_mv Text
dc.type.redcol.none.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unicordoba.edu.co/handle/ucordoba/9007
dc.identifier.instname.none.fl_str_mv Universidad de Córdoba
dc.identifier.reponame.none.fl_str_mv Repositorio Universidad de Córdoba
dc.identifier.repourl.none.fl_str_mv https://repositorio.unicordoba.edu.co/
url https://repositorio.unicordoba.edu.co/handle/ucordoba/9007
https://repositorio.unicordoba.edu.co/
identifier_str_mv Universidad de Córdoba
Repositorio Universidad de Córdoba
dc.language.iso.none.fl_str_mv spa
language spa
dc.relation.references.none.fl_str_mv Ahmed, H. O., Mahdy, A., Nasser, S. A. M., El-Wakeil, K. F. Abd, Obuid-Allah, A. H., & Hassan, M. M. (2022). Biochemical composition of some Echinodermata (Holothuroidea, Echinoidea) from the Red Sea, Egypt. Brazilian Journal of Biology, 82(e246309), 1-7. doi: 10.1590/1519-6984.246309.
Alvarado, J. J., Solís-Marín, F. A., & Ahearn, C. G. (2010). Echinoderm (Echinodermata) diversity in the Pacific coast of Central America. Marine Biodiversity, 40, 45-56.
Álvarez, C., Morales, S., Rodríguez, G., Rodríguez, J., Roberto, E., Picot, C., Ceballos, A., Parra, C., Le Pape, P. (2023). The mortality attributable to Candidemia in C. auris is higher than that in other Candida species: Myth or Reality? Journal of Fungi, 9(4), 430. https://doi.org/10.3390/jof9040430
Aman, S.; Mittal, D.; Shriwastav, S.; Tuli, H.S.; Chauhan, S.; Singh, P.; Sharma, S.; Saini, R.V.; Kaur, N.; Saini, A.K. (2022). Prevalence of multidrug-resistant strains in device associated nosocomial infection and their in vitro killing by nanocomposites. Ann. Med. Surg. 2022, 78, 103687.
Ardiansyah, A., Bayu, A., Wulandari, D., & Putra, M. Y. (2022). Fatty acid from sea cucumber: Mini review. In AIP Conference Proceedings (Vol. 2641, No. 1, p. 020022). AIP Publishing LLC.
Ardiansyah, A., Nugroho, A., Rasyid, A., Putra, M.Y., (2021). Screening of antioxidant and antiacne activities in 16 sea cucumbers in Indonesia. IOP Conf. Ser. Earth Environ. Sci. 695, 012048. https://doi.org/10.1088/1755-1315/695/1/012048.
Arizza, V. y otros 5 autores (2013). Gender differences in the immune system activities of sea urchin Paracentrotus lividus. Comparative Biochemistry and Physiology, Part A: 164, 447–455.
Aties López, L., Duret Gala, Y., Tabares Tabío, M., & Fernández Pérez, S. (2017). Los enzibióticos como alternativa terapéutica contra las enfermedades bacterianas. Medisan, 21(10), 3077-3083.
Avato, P. (2020). Editorial to the Special Issue—“Natural products and drug discovery”. Molecules , 25, 1128.
Ayobami, O.; Willrich, N.; Harder, T.; Okeke, I.N.; Eckmanns, T.; Markwart, R. (2019). The incidence and prevalence of hospital-acquired (carbapenem-resistant) Acinetobacter baumannii in Europe, Eastern Mediterranean and Africa: A systematic review and meta-analysis. Emerg. Microbes Infect. 8, 1747–1759.
Baharara, J., Amini, E., Kerachian, M. A., & Soltani, M. (2014). The osteogenic differentiation stimulating activity of Sea cucumber methanolic crude extraction on rat bone marrow mesenchymal stem cells. Iranian journal of basic medical sciences, 17(8), 626.
Bahrami Y, Zhang W, Franco C MM. (2018) Distribution of saponins in the sea cucumber Holothuria lessoni; the body wall versus the viscera, and their biological activities. Mar Drugs 16:1–30. https:// doi. org/ 10. 3390/md161 10423
Bahrami, Y.; Franco, C.M. (2016) Acetylated triterpene glycosides and their biological activity from holothuroidea reported in the past six decades. Mar. Drugs, 14, 147. https://doi.org/10.3390/md14080147
Batra, B., Sharma, D., Bose, D., Parthasarthy, V., & Sarkar, A. (2023). Implications of bioprospecting marine diversity and sustainable production of bioactive compounds. In Marine Antioxidants (pp. 27-43). Academic Press.
Benavides-Serrato, M., Borrero-Pérez, G. H., Cantera K, J. R., Cohen-Rengifo, M., & Neira, R. (2013). Echinoderms of Colombia. In Echinoderm research and diversity in Latin America (pp. 145-182). Springer, Berlin, Heidelberg.
Blunt, J. W., Copp, B. R., Keyzers, R. A., Munro, M. H., & Prinsep, M. R. (2012). Marine natural products. Natural product reports, 29(2), 144-222.
Boonsilp, S.; Homkaew, A.; Phumisantiphong, U.; Nutalai, D.; Wongsuk, T. (2021). Species distribution, antifungal susceptibility, and molecular epidemiology of Candida species causing candidemia in a tertiary care hospital in Bangkok, Thailand. J. Fungi 2021, 7, 577.
Bordbar, S., Anwar, F., Saari, N. (2011). High-value components and bioactives from sea cucumbers for functional foods A review. Marine Drugs 9:1761-1805
Borrero-Pérez G.H., M. Benavides-Serrato y C.M. Diaz-Sanchez (2012). Equinodermos del Caribe colombiano II: Echinoidea y Holothuroidea. Serie de Publicaciones Especiales de Invemar No. 30. Santa Marta, 250 p. ISBN 978-958-8448-52-7
Campos Péret, V. A., Reis, R. C. F. M., Braga, S. F. P., Benedetti, M. D., Caldas, I. S., Carvalho, D. T., Santana, L. F. de A., Johann, S., & Souza, T. B. de. (2023). New miconazole-based azoles derived from eugenol show activity against Candida spp. and Cryptococcus gattii by inhibiting the fungal ergosterol biosynthesis. European Journal of Medicinal Chemistry, 256(2023), 115436.
Carletti, A.; Cardoso, C.; Lobo-Arteaga, J.; Sales, S.; Juliao, D.; Ferreira, I.; Chainho, P.; Dionísio, M.A.; Cardoso, J., Nakayama, D. G., Sousa, E., & Pinto, E. (2020). Marine-derived compounds and prospects for their antifungal application. Molecules, 25(24), 5856.
Centers for Disease Control. Antibiotic Resistance Threats in the United States, 2019; U.S. Department of Health and Human Services, CDC: Atlanta, GA, USA, 2019.
Contreras, O. I., Angulo, A. A., & Santafé, G. G. (2022). Antibacterial Screening of Isoespintanol, an Aromatic Monoterpene Isolated from Oxandra xylopioides Diels. Molecules, 27(22). https://doi.org/10.3390/molecules27228004.
Cortés, J. A., Ruiz, J. F., Melgarejo-Moreno, L. N., & Lemos, E. V. (2020). Candidemia en Colombia. Biomédica, 40(1), 195. https://doi.org/10.7705/biomedica.4400.
Cusimano, M. G., Spinello, A., Barone, G., Schillaci, D., Cascioferro, S., Magistrato, A., Parrino, B., Arizza, V., & Vitale, M. (2019). A Synthetic derivative of antimicrobial peptide Holothuroidin 2 from Mediterranean Sea Cucumber (Holothuria tubulosa) in the control of Listeria monocytogenes. Marine drugs, 17(3), 159.
Cutress, B. M. (1996). Changes in dermal ossicles during somatic growth in Caribbean littoral sea cucumbers (Echinoidea: Holothuroidea: Aspidochirotida). Bulletin of Marine Science, 58(1), 44-116.
Darya, M., Sajjadi, M.M., Yousefzadi, M., Sourinejad, I. and Zarei, M., (2020). Antifouling and antibacterial activities of bioactive extracts from different organs of the sea cucumber Holothuria leucospilota. Helgoland Marine Research, 74(1), 4. https://doi.org/10.1186/s10152-020-0536-8.
De Oliveira, D.; Forde, B.; Kidd, T.; Harris, P.; Schembri, M.; Beatson, S.; Paterson, D.; Walker, M. (2020). Antimicrobial resistance in ESKAPE pathogens. Clin. Microbiol. Rev. 33, e00181-19.
Dellière, S., Sze Wah Wong, S., & Aimanianda, V. (2020). Soluble mediators in antifungal immunity. Current Opinion in Microbiology, 58(2020), 24–31. https://doi.org/10.1016/J.MIB.2020.05.005
Denissen, J.; Reyneke, B.; Waso-Reyneke, M.; Havenga, B.; Barnard, T.; Khan, S.; Khan, W. (2022). Prevalence of ESKAPE pathogens in the environment: Antibiotic resistance status, community-acquired infection and risk to human health. Int. J. Hyg. Environ. Health, 244, 114006.
Diaz, T. A., Reyes, E. R., González, J. C., & Carrasco, J. M. (2021). Estrés oxidativo, terapia antioxidante y cáncer. Revista Cubana de Oncología, 19(2).
Diba G, Jamili S, Ramezani FE. (2017). Evaluation of the antioxidant ac- tivity of dried (rehydrate) and fresh sea cucumber Holothuria parva. Iranian Scientific Fisheries Journal 25(4): 77–86.
Diniz-Neto, H., Silva, S. L., Cordeiro, L. V., Silva, D. F., Oliveira, R. F., AthaydeFilho, P. F., Oliveira-Filho, A. A., Guerra, F. Q. S., & Lima, E. O. (2022). Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp. Brazilian Journal of Biology, 84(2024), e255080. https://doi.org/10.1590/1519-6984.255080
Eaves, A. A., & Palmer, A. R. (2003). Widespread cloning in echinoderm larvae. Nature, 425(6954), 146-146
Ereguero MG, Cordero MA, Dalayap R, Tabugo SR. (2022). Antifungal activity of selected sea cucumber species from Tukuran, Zamboanga del Sur, Mindanao, Philippines using modified SPOTi assay. Biodiversitas 23: 6049-6055.
Esmat AY, Said MM, Soliman AA, El-Masry KS, Badiea EA. (2013). Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats. Nutrition, 29:258-67.
Esmat AY, Said MM, Soliman AA, El-Masry KS, Badiea EA. (2013). Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats. Nutrition, 29:258-67.
Gocer M, Olgunoglu, IA, Oglunoglu MP. (2018). A study on fatty acid profile and some major mineral contents of sea cucumber (Holothuria (platyperona) sanctori) from Mediterranean Sea (Turkey). Food Science and Quality Management 72: 1–5.
Gomes, E.R., Freitas, A.C., Rocha-Santos, T.A.P., Duare, A.C. (2014). Bioactive compounds derived from echinoderms. RSC Adv. 4, 29365–29382.
Guo K, Su L, Wang Y, Liu H, Lin J, Cheng P, Yin X, Liang M, Wang Q, Huang Z. (2020). Antioxidant and anti-aging effect of sea cucumber protein hydrolysate and bioinformatics characterization of its composing peptides. Food & Function 11: 5004–5016. https://doi.org/10.1039/D0FO00560F
Gutiérrez, E. B. G., Rubio, J. A. R., & Rus, T. I. (2023). Competencias de prevención y control de infecciones y bioseguridad en los programas de instrumentación quirúrgica en Colombia. Educación Médica, 24(2), 100786.
Gutiérrez, E. B. G., Rubio, J. A. R., & Rus, T. I. (2023). Competencias de prevención y control de infecciones y bioseguridad en los programas de instrumentación quirúrgica en Colombia. Educación Médica, 24(2), 100786.
Hendler, G., Miller, J. E., Pawson, D. L., & Kier, P. M. (1995). Sea stars, sea urchins, and allies: echinoderms of Florida and the Caribbean.
Hossain, A., Dave, D., & Shahidi, F. (2022). Antioxidant Potential of Sea Cucumbers and Their Beneficial Effects on Human Health. Marine Drugs, 20(8), 1–22. https://doi.org/10.3390/md20080521
Hossain, A.; Dave, D.; Shahidi, F. (2020). Northern Sea cucumber (Cucumaria frondosa): A potential candidate for functional food, nutraceutical, and pharmaceutical sector. Mar. Drugs 2020, 18, 274.
Hossain, A.; Dave, D.; Shahidi, F. (2022). Effect of high-pressure processing (HPP) on phenolics of North Atlantic sea cucumber (Cucumaria frondosa). J. Agric. Food Chem. 70, 3489–3501.
Hua, H.A.N.; Ling, L.I.; Yi, Y.H.; Wang, X.H.; Pan, M.X. (2012). Triterpene glycosides from sea cucumber Holothuria scabra with cytotoxic activity. Chin. Herb. Med. 4, 183–188.
Jenzri, M., Bouraoui, Z., Guerbej, H., Jebali, J., & Gharred, T. (2024). Seasonal variation in fatty acid profiles of Holothuria poli (Delle Chiaje, 1823) from Monastir Bay (Tunisia): implications for trophic markers and lipid nutritional quality assessment. New Zealand Journal of Marine and Freshwater Research, 1-23.
Karapanagiotidis, I.T.; Gkalogianni, E.Z.; Apostologamvrou, C.; Voulgaris, K.; Varkoulis, A.; Vafidis, D. (2024). Proximate Compositions and Fatty Acid Profiles of Raw and Processed Holothuria polii and Holothuria tubulosa from the Aegean Sea. Sustainability , 16, 6048. https://doi.org/10.3390/su16146048
Kareh M., Nahas R., Al Aaraj L., Al-Ghadban S., Deen N., Saliba N., El-Sabban M., Talhouk R. (2018) Anti-proliferative and anti-inflammatory activities of the sea cucumber Holothuria polii aqueous extract. SAGE Open Medicine 6:1-14.
Künili, İ. E., & Çolakoğlu, F. A. (2018). Antioxidant and antimicrobial activity of sea cucumber (Holothuria tubulosa, Gmelin 1791) extracts. Canakkale Onsekiz Mart University Journal of Marine Sciences and Fisheries, 1(2), 66-71.
Lewandowska, A.M., et al., (2014). Temperature effects on phytoplankton diversity—The zooplankton link. J. Sea Res. v. 85, 359–364.
Maier, M. S. (2007). Metabolitos secundarios bioactivos de organismo marinos pertenecientes al phylum Echinodermata.
Malve, H., (2016). Exploring the ocean for new drug developments: Marine pharmacology. Journal of Pharmacy and Bioallied Sciences, 8(2), pp. 83–91. https://doi.org/10.4103/0975-7406.171700.
Mashjoor S, Yousefzadi M. Holothurians antifungal and antibacterial activity to human pathogens in the Persian Gulf. Journal De Mycologie Médicale (2016), http://dx.doi.org/10.1016/j.mycmed.2016.08.008
Méndez N, Angulo A, Contreras O. (2016). Actividad antibacteriana in vitro de Curcuma longa (Zingiberaceae) frente a bacterias nosocomiales en Montería, Colombia. Rev Biol Trop. 64(3):1201-1208.
Misgiati, W. I., Murniasih, T., Novriyanti, E., Tarman, K., Safithri, M., Setyaningsih, I., Cahyati, D., Pratama, B. P., & Wirawati, I. (2024). The anticancer and antioxidant potential of local sea cucumber Holothuria edulis, an ecology balancer of Labuan Bajo marine ecosystem. Case Studies in Chemical and Environmental Engineering, 9, 100625. doi: 10.1016/j.cscee.2024.100625.
Miyashita, K. (2014). Marine antioxidants. Antioxidants and Functional Components in Aquatic Foods, 219–235. https://doi.org/10.1002/9781118855102.ch8.
Mohamed, M. E., Saber, S. A., El-Kafrawy, S. B., Alabdein Nassar, M. Z., & El-Naggar, H. A. (2024). Biotechnological Activities of Holothuria papillifera Mortensen, 1938 Inhabiting the Suez Gulf (Northern Red Sea), Egypt. Egyptian Journal of Aquatic Biology & Fisheries, 28(4).
Müller, C., Obermeier, M., & Berg, G. (2016). Bioprospecting plant-associated microbiomes. Journal of Biotechnology, 235, 171-180.
Nazemi M., Motallebi A., Abbasi E., Khaledi M. & Zare M. (2022). Antibacterial, antifungal, and cytotoxic activity of the fraction contains squalene in the acetone extract of a sea cucumber, Stichopus hermanni. Iranian Journal of Fisheries Sciences, 21(6), pp. 1495-1507. DOI: 10.22092/ijfs.2023.128416.
Nugroho, A., Harahap, I.A., Ardiansyah, A., Bayu, A., Rasyid, A., Murniasih, T., Setyastuti, A., Putra, M.Y., (2021). Antioxidant and antibacterial activities in 21 species of Indonesian sea cucumbers. J. Food Sci. Technol. 59, 239–248. https://doi.org/ 10.1007/s13197-021-05007-6.
Oh, G-W, Ko, S-C, Lee, DH, Heo, S-J, and Jung, W-K (2017) Biological activities and biomedical potential of sea cucumber (Stichopus japonicus): a review. Fisheries and Aquatic Sciences 20: e28. https://doi.org/10.1186/ s41240-017-007.
Pamungkas, S. Y., & Haryono, F. E. D. (2023). Bioprospecting of sea cucumber (Holothuria sp.) as industries and functional foods for human health. International Journal of Science and Research Archive, 10(2), 669-690. https://doi.org/10.30574/ijsra.2023.10.2.0994
Parrish, C.C. (2009). Essential fatty acids in aquatic food webs. In Lipids in Aquatic Ecosystems; Arts, M.T., Brett, M.T., Kainz, M.J., Eds.; Springer: New York, NY, USA; pp. 309–326.
Pastrana, O. J., Santafé, G. G., & Torres, O. L. (2016). Perfil de ácidos grasos y evaluación de las actividades antioxidante y antifúngica del Holotureo Isostichopus badionotus. Información tecnológica, 27(3), 03-10.
Pastrana, O., Santafé, G., & Sánchez, E. (2019). Perfil lipídico y ensayos de las actividades antioxidante, insecticida y antialimentaria de la esponja marina Iotrochota birotulata (Iotrochotidae: Demospongiae). Revista de Biología Tropical, 67(1), 213–223. https://doi.org/10.15517/rbt.v67i1.32357
Pawson, D. L., Pawson, D. J., & King, R. A. (2010). A taxonomic guide to the Echinodermata of the South Atlantic Bight, USA: 1. Sea cucumbers (Echinodermata: Holothuroidea). Zootaxa, 2449(1), 1-48.
Pérez-Ruzafa, A., Alvarado, J. J., Solís-Marín, F. A., Hernández, J. C., Morata, A., Marcos, C., ... & Williams, S. M. (2013). Latin America echinoderm biodiversity and biogeography: Patterns and affinities. Echinoderm research and diversity in Latin America, 511-542
Pham-Huy, L., He, H., & Pham-Huy, C. (2008). Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci, 2, 89–96. Recuperado de https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614697/.
Pires, M., & García, Y. (2024). Biochemical and ecological components of Holothuria (Halodeima) grisea, Selenka 1867 (Echinodermata: Holothuroidea). Regional Studies in Marine Science, 73, 103460.
Piri-Gharaghie, T., Ghajari, G., Hassanpoor, M., Jegargoshe-Shirin, N., Soosanirad, M., Khayati, S., ... & Mirzaei, A. (2023). Investigation of antibacterial and anticancer effects of novel niosomal formulated Persian Gulf Sea cucumber extracts. Heliyon, 9(3).
Purcell SW, Hair CA, Mills DJ (2012) Sea cucumber culture, farming and sea ranching in the tropics: Progress, problem and opportunities. Aquaculture 368–369: 68–81. https://doi.org/10.1016/j.aquacul- ture.2012.08.053
Putra, Y., Soffa, F. B., Firdaus, M., Pangestuti, R., & Siahaan, E. A. (2022). Determination of fatty acid profiles and bioactive properties of body wall and viscera of Holothuria atra collected from Lombok Island, Indonesia. In IOP Conference Series: Earth and Environmental Science (Vol. 1119, No. 1, p. 012052). IOP Publishing.
Quiroz Lobo, Y., Santafé Patiño, G., & Quirós-Rodríguez, J. A. (2021). Caracterización de los ácidos grasos y actividad antimicrobiana del extracto en metanol de Holothuria princeps (Holothuriida: Holothuriidae). Revista de Biología Tropical , 69(1), 36-44.
Rahman, M. A., Chowdhury, S. H., Hasan, M. J., Rahman, M. H., Yeasmin, S. M., Farjana, N., ... & Parvez, M. S. (2020). Status, prospects and market potentials of the sea cucumber fisheries with special reference on their proper utilization and trade. Annual Research & Review in Biology, 35(7), 84-101.
Rasyid A, Yasman Y, Putra MY (2021) Current prospects of nutraceutical and pharmaceutical use of sea cucumbers. Pharmacia 68(3): 561–572. https://doi.org/10.3897/pharmacia.68.e69140
Rosenthal, V. D., Yin, R., Lu, Y., Rodrigues, C., Myatra, S. N., Kharbanda, M., ... & Jin, Z. (2023). The impact of healthcare-associated infections on mortality in ICU: a prospective study in Asia, Africa, Eastern Europe, Latin America, and the Middle East. American journal of infection control, 51(6), 675-682.
Santafé, G. G., Guzmán, M. S., & Torres, O. L. (2014). Triterpenos Holostáticos con Actividad Antifúngica obtenidos del pepino de mar Holothuria floridana: Recolectado en la Bahía de Cispatá, Córdoba-Colombia. Información tecnológica, 25(2), 87-92
Santoyo, G.; Orozco-Mosqueda & M. Govindappa, M. C.; Govindappa, M. (2012). Mechanisms Biocontrol and Plant Growth-Promoting Activity in Soil Bacterial Species of Bacillus and Pseudomonas: A Review: Biocontrol Science and Technology: Vol 22, No 8. Biocontrol Science and Technology. pp 855–872.
Sarhadizadeh N, Afkhami M, Ehsanpour M. (2014). Evaluation bioactivity of a sea cucumber, Stichopus hermanni from Persian Gulf. European Journal Experimental Biology 4(1): 234–258
Shi, S., Feng, W., Hu, S., Liang, S., An, N., & Mao, Y. (2016). Bioactive compounds of sea cucumbers and their therapeutic effects. Chinese Journal of Oceanology and Limnology, 34(3), 549-558.
Telahigue K, Ghali R, Nouiri E, Labidi A, Hajji T. (2020). Antibacterial activities and bioactive compounds of the ethyl acetate extract of the sea cucumber Holothuria forskali from Tunisian coasts. Journal of the Marine Biological Association of the United Kingdom, pp. 1–9. https://doi.org/10.1017/S002531542000001
Thawabteh, A.M.; Swaileh, Z.; Ammar, M.; Jaghama,W.; Yousef, M.; Karaman, R.; A. Bufo, S.; Scrano, L. (2023). Antifungal and Antibacterial Activities of Isolated Marine Compounds. Toxins. 15, 93. https://doi.org/10.3390/ toxins15020093
Verea, L. P., Ferrer, A. F., Reyes, Y. O., Miranda, Y. P., & Méndez, A. R. (2019). Infecciones nosocomiales y resistencia antimicrobiana. Revista Cubana de Medicina Intensiva y Emergencias, 18(1), 1-17. Recuperado: https://www.medigraphic.com/pdfs/revcubmedinteme/cie-2019/cie121b.
Wang, F., Cao, Y., Guo, Y., Zhu, Z., & Zhang, C. (2021). Evaluation of antioxidant and antibacterial activities of lipid extracts from Eustigmatos cf. polyphem (Eustigmatophyceae) and preliminary identification of bioactive compound. Algal Research, 59. https://doi.org/10.1016/j.algal.2021.102446
Wargasetia, T. L., Ratnawati, H., Widodo, N., & Widyananda, M. H. (2023). Antioxidant and anti-inflammatory activity of sea cucumber (Holothuria scabra) active compounds against KEAP1 and iNOS protein. Bioinformatics and Biology Insights, 17, 11779322221149613.
Yuan, H., Ma, Q., Ye, L., & Piao, G. (2016). The Traditional Medicine and Modern Medicine from Natural Products. Molecules, 21(5), 559. https://doi.org/10.3390/molecules21050559
Zhao, Y., Wang, Y., Zhang, X., Liu, H., Wang, G., & Liu, H. (2012). Effects of potential probiotic Bacillus subtilis T13 on growth, immunity and disease resistance against Vibrio splendidus infection in juvenile sea cucumber Apostichopus japonicus. Fish & Shellfish Immunology, 32(5), 750-755.
Zhukova, N.V. (2023). Fatty Acids of Echinoderms: Diversity, Current Applications and Future Opportunities. Mar. Drugs, 21, 21. https://doi.org/10.3390/md21010021
Zmemlia N, Bejaoui S, Khemiri I, Bouriga N, Louiz I, El-Bok S, Ben-Attia M, Souli A. (2020). Biochemical composition and antioxidant potential of the edible Mediterranean sea cucumber Holothuria tubulosa. Grasas Aceites 71 (3), e364. https://doi.org/10.3989/gya.0452191.
dc.rights.none.fl_str_mv Copyright Universidad de Córdoba, 2025
dc.rights.uri.none.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.license.none.fl_str_mv Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
dc.rights.accessrights.none.fl_str_mv info:eu-repo/semantics/embargoedAccess
dc.rights.coar.none.fl_str_mv http://purl.org/coar/access_right/c_f1cf
rights_invalid_str_mv Copyright Universidad de Córdoba, 2025
https://creativecommons.org/licenses/by-nc-nd/4.0/
Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
http://purl.org/coar/access_right/c_f1cf
eu_rights_str_mv embargoedAccess
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidad de Córdoba
dc.publisher.faculty.none.fl_str_mv Facultad de Ciencias Básicas
dc.publisher.place.none.fl_str_mv Montería, Córdoba, Colombia
dc.publisher.program.none.fl_str_mv Maestría en Ciencias Químicas
publisher.none.fl_str_mv Universidad de Córdoba
institution Universidad de Córdoba
bitstream.url.fl_str_mv https://repositorio.unicordoba.edu.co/bitstreams/1e9e4e66-9512-4943-a0fd-55100f2919b9/download
https://repositorio.unicordoba.edu.co/bitstreams/7d188002-64ca-4248-ac61-751c316cfaee/download
https://repositorio.unicordoba.edu.co/bitstreams/99fd3231-0e5a-4e17-a89a-5bc1e949a50b/download
https://repositorio.unicordoba.edu.co/bitstreams/77fa783b-a612-4195-831e-d98c502e3a6e/download
https://repositorio.unicordoba.edu.co/bitstreams/6eb2b8d0-fe06-4687-9bc5-c853b995ca2e/download
https://repositorio.unicordoba.edu.co/bitstreams/ccde8482-1db6-4100-a762-30afe7e9dc61/download
https://repositorio.unicordoba.edu.co/bitstreams/c63ca385-9965-4091-bd23-6f9ef5394fbd/download
bitstream.checksum.fl_str_mv eb019a0a08a7eaea71b2fed4d427be72
718c6cbbfd3357c1ad4345957009858c
73a5432e0b76442b22b026844140d683
f999bf978a9d85544b107b3f58f8aaed
1c1bce5b0a14fb5c81fb15dc475ef0ce
20548bb490252a71f706ed13870e0744
884fe31803f921b49fad2cba28f61669
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Universidad de Córdoba
repository.mail.fl_str_mv bdigital@metabiblioteca.com
_version_ 1839636188291399680
spelling Santafé Patiño, Gilmar80ca173d-544e-4b89-adc4-c08cc8c350b7600Quirós-Rodríguez, Jorge A.ebba5734-522e-4d6b-b400-3cc24b8bb851600Julio Berrio, Mirlethcd33245d-aa0a-403c-abe7-dcd4dc077729600Oviedo Zumaqué, Luis Eliécer16244141-aa15-45d4-a620-56014ced68f7600Valle Zapata, Hernan Alonso744348e2-deca-4ed4-9b02-05a6766f4f346002025-02-05T17:13:39Z2026-12-312025-02-05T17:13:39Z2025-02-03https://repositorio.unicordoba.edu.co/handle/ucordoba/9007Universidad de CórdobaRepositorio Universidad de Córdobahttps://repositorio.unicordoba.edu.co/La biodiversidad marina ha dado lugar a una extraordinaria variedad de compuestos químicos, muchos de ellos con propiedades biológicas excepcionales. Estos metabolitos secundarios, le confieren ventajas adaptativas a los organismos marinos, las cuales han sido utilizadas por su gran potencial en áreas como la medicina, debido a sus propiedades anticancerígenas, antimicrobianas, antifúngicas y antioxidantes. En este estudio se identificaron estructuralmente 23 compuestos mediante la cromatografía de gases acoplado a espectrometría de masas de impacto electrónico. De los 23 compuestos aislados 22 correspondían a ácidos grasos saturados e insaturados y uno de naturaleza esterólica. Por otro lado, mediante la evaluación de la actividad antioxidante del extracto etanólico de la especie Holothuria grisea frente al radical catiónico ABTS+● se determinó el valor de IC50 de 235,32 μg/mL. En cuanto al ensayo antioxidante por el método del radical DPPH● se determinó un IC50 de 1604,27 μg/mL. La evaluación de la actividad antibacteriana de las dos especies de holotúridos se realizó frente a los aislados clínicos Gram positivas (Staphylococcus aureus, Enterococcus faecium) y Gram negativas (Escherichia coli, Stenotrophomonas maltophilia) por el método de microdilución. El extracto etanólico de H. grisea presentó porcentajes significativos a 2000 mg/L reduciendo el crecimiento de estos microorganismos, destacándose la mayor sensibilidad en la especie S. maltophilia con un porcentaje de reducción de crecimiento del 100% a 1250 mg/L, seguido de E. coli y E. faecium con porcentajes de reducción de 99,34% y 91,85% respectivamente. Por su parte, el extracto etanólico de H. princeps, no presentó una considerable inhibición del crecimiento en estas cepas bacterianas. Para la evaluación de la actividad antifúngica frente a las cepas del género Candida (C. albicans, C. tropicalis, C. glabrata y C. auris), a nivel general los mejores resultados de inhibición de crecimiento se mostraron a mayores concentraciones de los extractos etanólicos (desde 2500 mg/L). Se evidenció que los aislados clínicos C. tropicalis y C. glabrata, fueron las cepas fúngicas más susceptible al extracto etanólico de H. grisea, presentando una reducción de crecimiento del 100% a 2500 mg/L y para H. princeps la cepa fúngica más suceptible fue C. glabrata, la cual presentó una reducción de crecimiento de 95,7% a 5000 mg/L.Marine biodiversity has led to an extraordinary variety of chemical compounds, many of them with exceptional biological properties. These secondary metabolites confer adaptive advantages to marine organisms, which have been used for their great potential in areas such as medicine, due to their anticancer, antimicrobial, antifungal and antioxidant properties. In this study, 23 compounds were structurally identified by gas chromatography coupled to electron impact mass spectrometry. Of the 23 compounds isolated, 22 corresponded to saturated and unsaturated fatty acids and one of a sterol nature. On the other hand, by evaluating the antioxidant activity of the ethanolic extract of the species Holothuria grisea against the cationic radical ABTS+●, the IC50 value of 235.32 μg/mL was determined. Regarding the antioxidant assay by the DPPH● radical method, an IC50 of 1604.27 μg/mL was determined. The evaluation of the antibacterial activity of the two species of sea cucumbers was carried out against the Gram-positive (Staphylococcus aureus, Enterococcus faecium) and Gram-negative (Escherichia coli, Stenotrophomonas maltophilia) clinical isolates by the microdilution method. The ethanolic extract of H. grisea presented significant percentages at 2000 mg/L, reducing the growth of these microorganisms, with the greatest sensitivity being highlighted in the S. maltophilia species with a growth reduction percentage of 100% at 1250 mg/L, followed by E. coli and E. faecium with reduction percentages of 99.34% and 91.85%, respectively. On the other hand, the ethanolic extract of H. princeps did not present a considerable inhibition of growth in these bacterial strains. For the evaluation of antifungal activity against strains of the genus Candida (C. albicans, C. tropicalis, C. glabrata and C. auris), in general the best results of growth inhibition were shown Marine biodiversity has led to an extraordinary variety of chemical compounds, many of them with exceptional biological properties. These secondary metabolites confer adaptive advantages to marine organisms, which have been used for their great potential in areas such as medicine, due to their anticancer, antimicrobial, antifungal and antioxidant properties. In this study, 23 compounds were structurally identified by gas chromatography coupled to electron impact mass spectrometry. Of the 23 compounds isolated, 22 corresponded to saturated and unsaturated fatty acids and one of a sterol nature. On the other hand, by evaluating the antioxidant activity of the ethanolic extract of the species Holothuria grisea against the cationic radical ABTS+●, the IC50 value of 235.32 μg/mL was determined. Regarding the antioxidant assay by the DPPH● radical method, an IC50 of 1604.27 μg/mL was determined. The evaluation of the antibacterial activity of the two species of sea cucumbers was carried out against the Gram-positive (Staphylococcus aureus, Enterococcus faecium) and Gram-negative (Escherichia coli, Stenotrophomonas maltophilia) clinical isolates by the microdilution method. The ethanolic extract of H. grisea presented significant percentages at 2000 mg/L, reducing the growth of these microorganisms, with the greatest sensitivity being highlighted in the S. maltophilia species with a growth reduction percentage of 100% at 1250 mg/L, followed by E. coli and E. faecium with reduction percentages of 99.34% and 91.85%, respectively. On the other hand, the ethanolic extract of H. princeps did not present a considerable inhibition of growth in these bacterial strains. For the evaluation of antifungal activity against strains of the genus Candida (C. albicans, C. tropicalis, C. glabrata and C. auris), in general the best results of growth inhibition were shown Marine biodiversity has led to an extraordinary variety of chemical compounds, many of them with exceptional biological properties. These secondary metabolites confer adaptive advantages to marine organisms, which have been used for their great potential in areas such as medicine, due to their anticancer, antimicrobial, antifungal and antioxidant properties. In this study, 23 compounds were structurally identified by gas chromatography coupled to electron impact mass spectrometry. Of the 23 compounds isolated, 22 corresponded to saturated and unsaturated fatty acids and one of a sterol nature. On the other hand, by evaluating the antioxidant activity of the ethanolic extract of the species Holothuria grisea against the cationic radical ABTS+●, the IC50 value of 235.32 μg/mL was determined. Regarding the antioxidant assay by the DPPH● radical method, an IC50 of 1604.27 μg/mL was determined. The evaluation of the antibacterial activity of the two species of sea cucumbers was carried out against the Gram-positive (Staphylococcus aureus, Enterococcus faecium) and Gram-negative (Escherichia coli, Stenotrophomonas maltophilia) clinical isolates by the microdilution method. The ethanolic extract of H. grisea presented significant percentages at 2000 mg/L, reducing the growth of these microorganisms, with the greatest sensitivity being highlighted in the S. maltophilia species with a growth reduction percentage of 100% at 1250 mg/L, followed by E. coli and E. faecium with reduction percentages of 99.34% and 91.85%, respectively. On the other hand, the ethanolic extract of H. princeps did not present a considerable inhibition of growth in these bacterial strains. For the evaluation of antifungal activity against strains of the genus Candida (C. albicans, C. tropicalis, C. glabrata and C. auris), in general the best results of growth inhibition were shown at higher concentrations of the ethanolic extracts (from 2500 mg/L). It was evidenced that the clinical isolates C. tropicalis and C. glabrata were the most susceptible fungal strains to the ethanolic extract of H. grisea, presenting a 100% reduction in growth at 2500 mg/L, and for H. princeps the most susceptible fungal strain was C. glabrata, which presented a 95.7% reduction in growth at 5000 mg/L.INTRODUCCIÓN ..............................................151. OBJETIVOS ...................................................191.1 OBJETIVO GENERAL ...........................................191.2 OBJETIVOS ESPECÍFICOS ................................192. MARCO TEÓRICO ............................................202.1 MARCO REFERENCIAL ........................................212.2 PHYLUM ECHINODERMATA ...............242.3 CLASE Holothuroidea ............................252.3.1 Descripción general y taxonomía de la especie de Holothuria grisea. .........272.3.2 Descripción general y taxonomía de la especie de Holothuria princeps. .........282.4 ENFERMEDADES CAUSADAS POR MICROORGANISMOS Y EFECTOS DEL PROCESO DE OXIDACIÓN ..........302.4.1 Estrés oxidativo ...................................302.4.2 Enfermedades causadas por microorganismos ..............................312.4.3 Infecciones Asociadas a la Atención en Salud (IAAS) de microorganismos patógenos .......................... 323. MATERIALES Y MÉTODOS ...............343.1 RECOLECCIÓN DEL MATERIAL BIOLÓGICO ..............343.2 PREPARACIÓN DEL MATERIAL BIOLÓGICO ................343.3 ESTUDIO QUÍMICO DE H. grisea MEDIANTE EL USO DE TÉCNICAS CROMATOGRÁFICAS COMO CROMATOGRAFÍA EN COLUMNA (CC), CROMATOGRAFÍA EN CAPA DELGADA (CCD) y CGAR-EM ......353.3.1 FRACCIONAMIENTO CROMATOGRÁFICO DE H. grisea ........................353.3.2 DERIVATIZACIÓN DE ÁCIDOS GRASOS ...........................................353.3.3 IDENTIFICACIÓN QUÍMICA DE LOS METABOLITOS SECUNDARIOS MAYORITARIOS AISLADOS DE H. grisea, MEDIANTE CGAR-EM .............363.4 EVALUACIÓN DE LA ACTIVIDAD ANTIOXIDANTE FRENTE A LOS RADICALES ABTS+•, DPPH• DEL EXTRACTO ETANÓLICO DE LA ESPECIE H. grisea ...............363.4.1 Protocolo del ensayo ABTS+• ............................373.4.2 Protocolo del ensayo DPPH• ..............................393.5 ACTIVIDAD ANTIBACTERIANA Y ANTIFÚNGICA DE LOS EXTRACTOS ETANÓLICOS DE LAS ESPECIES Holothuria princeps Y Holothuria grisea SOBRE LOS AISLADOS CLÍNICOS INTRAHOSPITALARIOS .....403.5.1 Evaluación de la actividad antibacteriana ............403.5.1.1 Pruebas de susceptibilidad antibacteriana ..................413.5.2 Evaluación de la actividad antifúngica ............................433.5.2.1 Pruebas de susceptibilidad antifúngica ..............................433.6 ANÁLISIS ESTADÍSTICO ...............................444. RESULTADOS Y ANÁLISIS DE RESULTADOS .......................464.1 IDENTIFICACIÓN QUÍMICA DE LOS METABOLITOS SECUNDARIOS MAYORITARIOS AISLADOS DE H. grisea, MEDIANTE CGAR-EM. ................................................................464.1.1 Compuestos aislados de H. grisea ................................464.1.1.1 Compuesto HG4 de H. grisea ...........................484.1.1.2 Compuesto HG11 de H. grisea .........................504.1.1.3 Compuesto HG14 de H. grisea .............................524.1.1.4 Compuesto HG19 de H. grisea .................................554.2 EVALUACIÓN DE LA ACTIVIDAD ANTIOXIDANTE FRENTE A LOS RADICALES ABTS+• y DPPH• DEL EXTRACTO ETANÓLICO DE LA ESPECIE H. grisea. ..........644.2.1 Evaluación de la actividad antioxidante frente al radical ABTS+• del extracto etanólico de la especie H. grisea. ...................................654.2.2 Evaluación de la actividad antioxidante frente al radical DPPH• del extracto etanólico de la especie H. grisea. ...................................674.3 EVALUACIÓN DE LA ACTIVIDAD ANTIMICROBIANA DE LOS EXTRACTOS ETANÓLICOS DE LAS ESPECIES Holothuria princeps y Holothuria grisea SOBRE LOS AISLADOS CLÍNICOS INTRAHOSPITALARIOS. .................................................................724.3.1 Ensayo de la actividad antibacteriana de las especies Holothuria princeps y Holothuria grisea sobre los aislados clínicos intrahospitalarios .............................724.3.2 Ensayo de la actividad antifúngica de las especies Holothuria grisea y Holothuria princeps sobre los aislados clínicos intrahospitalarios ...................795. CONCLUSIONES ............................................876. BIBLIOGRAFIA ......................................897. ANEXOS ......................................................... 102MaestríaMagíster en Ciencias QuímicasTrabajos de Investigación y/o Extensiónapplication/pdfspaUniversidad de CórdobaFacultad de Ciencias BásicasMontería, Córdoba, ColombiaMaestría en Ciencias QuímicasCopyright Universidad de Córdoba, 2025https://creativecommons.org/licenses/by-nc-nd/4.0/Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)info:eu-repo/semantics/embargoedAccesshttp://purl.org/coar/access_right/c_f1cfAnálisis químico y evaluación de la actividad biológica de extractos orgánicos de holothuria spp. frente a patógenos intrahospitalarios en Montería, ColombiaTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAhmed, H. O., Mahdy, A., Nasser, S. A. M., El-Wakeil, K. F. Abd, Obuid-Allah, A. H., & Hassan, M. M. (2022). Biochemical composition of some Echinodermata (Holothuroidea, Echinoidea) from the Red Sea, Egypt. Brazilian Journal of Biology, 82(e246309), 1-7. doi: 10.1590/1519-6984.246309.Alvarado, J. J., Solís-Marín, F. A., & Ahearn, C. G. (2010). Echinoderm (Echinodermata) diversity in the Pacific coast of Central America. Marine Biodiversity, 40, 45-56.Álvarez, C., Morales, S., Rodríguez, G., Rodríguez, J., Roberto, E., Picot, C., Ceballos, A., Parra, C., Le Pape, P. (2023). The mortality attributable to Candidemia in C. auris is higher than that in other Candida species: Myth or Reality? Journal of Fungi, 9(4), 430. https://doi.org/10.3390/jof9040430Aman, S.; Mittal, D.; Shriwastav, S.; Tuli, H.S.; Chauhan, S.; Singh, P.; Sharma, S.; Saini, R.V.; Kaur, N.; Saini, A.K. (2022). Prevalence of multidrug-resistant strains in device associated nosocomial infection and their in vitro killing by nanocomposites. Ann. Med. Surg. 2022, 78, 103687.Ardiansyah, A., Bayu, A., Wulandari, D., & Putra, M. Y. (2022). Fatty acid from sea cucumber: Mini review. In AIP Conference Proceedings (Vol. 2641, No. 1, p. 020022). AIP Publishing LLC.Ardiansyah, A., Nugroho, A., Rasyid, A., Putra, M.Y., (2021). Screening of antioxidant and antiacne activities in 16 sea cucumbers in Indonesia. IOP Conf. Ser. Earth Environ. Sci. 695, 012048. https://doi.org/10.1088/1755-1315/695/1/012048.Arizza, V. y otros 5 autores (2013). Gender differences in the immune system activities of sea urchin Paracentrotus lividus. Comparative Biochemistry and Physiology, Part A: 164, 447–455.Aties López, L., Duret Gala, Y., Tabares Tabío, M., & Fernández Pérez, S. (2017). Los enzibióticos como alternativa terapéutica contra las enfermedades bacterianas. Medisan, 21(10), 3077-3083.Avato, P. (2020). Editorial to the Special Issue—“Natural products and drug discovery”. Molecules , 25, 1128.Ayobami, O.; Willrich, N.; Harder, T.; Okeke, I.N.; Eckmanns, T.; Markwart, R. (2019). The incidence and prevalence of hospital-acquired (carbapenem-resistant) Acinetobacter baumannii in Europe, Eastern Mediterranean and Africa: A systematic review and meta-analysis. Emerg. Microbes Infect. 8, 1747–1759.Baharara, J., Amini, E., Kerachian, M. A., & Soltani, M. (2014). The osteogenic differentiation stimulating activity of Sea cucumber methanolic crude extraction on rat bone marrow mesenchymal stem cells. Iranian journal of basic medical sciences, 17(8), 626.Bahrami Y, Zhang W, Franco C MM. (2018) Distribution of saponins in the sea cucumber Holothuria lessoni; the body wall versus the viscera, and their biological activities. Mar Drugs 16:1–30. https:// doi. org/ 10. 3390/md161 10423Bahrami, Y.; Franco, C.M. (2016) Acetylated triterpene glycosides and their biological activity from holothuroidea reported in the past six decades. Mar. Drugs, 14, 147. https://doi.org/10.3390/md14080147Batra, B., Sharma, D., Bose, D., Parthasarthy, V., & Sarkar, A. (2023). Implications of bioprospecting marine diversity and sustainable production of bioactive compounds. In Marine Antioxidants (pp. 27-43). Academic Press.Benavides-Serrato, M., Borrero-Pérez, G. H., Cantera K, J. R., Cohen-Rengifo, M., & Neira, R. (2013). Echinoderms of Colombia. In Echinoderm research and diversity in Latin America (pp. 145-182). Springer, Berlin, Heidelberg.Blunt, J. W., Copp, B. R., Keyzers, R. A., Munro, M. H., & Prinsep, M. R. (2012). Marine natural products. Natural product reports, 29(2), 144-222.Boonsilp, S.; Homkaew, A.; Phumisantiphong, U.; Nutalai, D.; Wongsuk, T. (2021). Species distribution, antifungal susceptibility, and molecular epidemiology of Candida species causing candidemia in a tertiary care hospital in Bangkok, Thailand. J. Fungi 2021, 7, 577.Bordbar, S., Anwar, F., Saari, N. (2011). High-value components and bioactives from sea cucumbers for functional foods A review. Marine Drugs 9:1761-1805Borrero-Pérez G.H., M. Benavides-Serrato y C.M. Diaz-Sanchez (2012). Equinodermos del Caribe colombiano II: Echinoidea y Holothuroidea. Serie de Publicaciones Especiales de Invemar No. 30. Santa Marta, 250 p. ISBN 978-958-8448-52-7Campos Péret, V. A., Reis, R. C. F. M., Braga, S. F. P., Benedetti, M. D., Caldas, I. S., Carvalho, D. T., Santana, L. F. de A., Johann, S., & Souza, T. B. de. (2023). New miconazole-based azoles derived from eugenol show activity against Candida spp. and Cryptococcus gattii by inhibiting the fungal ergosterol biosynthesis. European Journal of Medicinal Chemistry, 256(2023), 115436.Carletti, A.; Cardoso, C.; Lobo-Arteaga, J.; Sales, S.; Juliao, D.; Ferreira, I.; Chainho, P.; Dionísio, M.A.; Cardoso, J., Nakayama, D. G., Sousa, E., & Pinto, E. (2020). Marine-derived compounds and prospects for their antifungal application. Molecules, 25(24), 5856.Centers for Disease Control. Antibiotic Resistance Threats in the United States, 2019; U.S. Department of Health and Human Services, CDC: Atlanta, GA, USA, 2019.Contreras, O. I., Angulo, A. A., & Santafé, G. G. (2022). Antibacterial Screening of Isoespintanol, an Aromatic Monoterpene Isolated from Oxandra xylopioides Diels. Molecules, 27(22). https://doi.org/10.3390/molecules27228004.Cortés, J. A., Ruiz, J. F., Melgarejo-Moreno, L. N., & Lemos, E. V. (2020). Candidemia en Colombia. Biomédica, 40(1), 195. https://doi.org/10.7705/biomedica.4400.Cusimano, M. G., Spinello, A., Barone, G., Schillaci, D., Cascioferro, S., Magistrato, A., Parrino, B., Arizza, V., & Vitale, M. (2019). A Synthetic derivative of antimicrobial peptide Holothuroidin 2 from Mediterranean Sea Cucumber (Holothuria tubulosa) in the control of Listeria monocytogenes. Marine drugs, 17(3), 159.Cutress, B. M. (1996). Changes in dermal ossicles during somatic growth in Caribbean littoral sea cucumbers (Echinoidea: Holothuroidea: Aspidochirotida). Bulletin of Marine Science, 58(1), 44-116.Darya, M., Sajjadi, M.M., Yousefzadi, M., Sourinejad, I. and Zarei, M., (2020). Antifouling and antibacterial activities of bioactive extracts from different organs of the sea cucumber Holothuria leucospilota. Helgoland Marine Research, 74(1), 4. https://doi.org/10.1186/s10152-020-0536-8.De Oliveira, D.; Forde, B.; Kidd, T.; Harris, P.; Schembri, M.; Beatson, S.; Paterson, D.; Walker, M. (2020). Antimicrobial resistance in ESKAPE pathogens. Clin. Microbiol. Rev. 33, e00181-19.Dellière, S., Sze Wah Wong, S., & Aimanianda, V. (2020). Soluble mediators in antifungal immunity. Current Opinion in Microbiology, 58(2020), 24–31. https://doi.org/10.1016/J.MIB.2020.05.005Denissen, J.; Reyneke, B.; Waso-Reyneke, M.; Havenga, B.; Barnard, T.; Khan, S.; Khan, W. (2022). Prevalence of ESKAPE pathogens in the environment: Antibiotic resistance status, community-acquired infection and risk to human health. Int. J. Hyg. Environ. Health, 244, 114006.Diaz, T. A., Reyes, E. R., González, J. C., & Carrasco, J. M. (2021). Estrés oxidativo, terapia antioxidante y cáncer. Revista Cubana de Oncología, 19(2).Diba G, Jamili S, Ramezani FE. (2017). Evaluation of the antioxidant ac- tivity of dried (rehydrate) and fresh sea cucumber Holothuria parva. Iranian Scientific Fisheries Journal 25(4): 77–86.Diniz-Neto, H., Silva, S. L., Cordeiro, L. V., Silva, D. F., Oliveira, R. F., AthaydeFilho, P. F., Oliveira-Filho, A. A., Guerra, F. Q. S., & Lima, E. O. (2022). Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp. Brazilian Journal of Biology, 84(2024), e255080. https://doi.org/10.1590/1519-6984.255080Eaves, A. A., & Palmer, A. R. (2003). Widespread cloning in echinoderm larvae. Nature, 425(6954), 146-146Ereguero MG, Cordero MA, Dalayap R, Tabugo SR. (2022). Antifungal activity of selected sea cucumber species from Tukuran, Zamboanga del Sur, Mindanao, Philippines using modified SPOTi assay. Biodiversitas 23: 6049-6055.Esmat AY, Said MM, Soliman AA, El-Masry KS, Badiea EA. (2013). Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats. Nutrition, 29:258-67.Esmat AY, Said MM, Soliman AA, El-Masry KS, Badiea EA. (2013). Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats. Nutrition, 29:258-67.Gocer M, Olgunoglu, IA, Oglunoglu MP. (2018). A study on fatty acid profile and some major mineral contents of sea cucumber (Holothuria (platyperona) sanctori) from Mediterranean Sea (Turkey). Food Science and Quality Management 72: 1–5.Gomes, E.R., Freitas, A.C., Rocha-Santos, T.A.P., Duare, A.C. (2014). Bioactive compounds derived from echinoderms. RSC Adv. 4, 29365–29382.Guo K, Su L, Wang Y, Liu H, Lin J, Cheng P, Yin X, Liang M, Wang Q, Huang Z. (2020). Antioxidant and anti-aging effect of sea cucumber protein hydrolysate and bioinformatics characterization of its composing peptides. Food & Function 11: 5004–5016. https://doi.org/10.1039/D0FO00560FGutiérrez, E. B. G., Rubio, J. A. R., & Rus, T. I. (2023). Competencias de prevención y control de infecciones y bioseguridad en los programas de instrumentación quirúrgica en Colombia. Educación Médica, 24(2), 100786.Gutiérrez, E. B. G., Rubio, J. A. R., & Rus, T. I. (2023). Competencias de prevención y control de infecciones y bioseguridad en los programas de instrumentación quirúrgica en Colombia. Educación Médica, 24(2), 100786.Hendler, G., Miller, J. E., Pawson, D. L., & Kier, P. M. (1995). Sea stars, sea urchins, and allies: echinoderms of Florida and the Caribbean.Hossain, A., Dave, D., & Shahidi, F. (2022). Antioxidant Potential of Sea Cucumbers and Their Beneficial Effects on Human Health. Marine Drugs, 20(8), 1–22. https://doi.org/10.3390/md20080521Hossain, A.; Dave, D.; Shahidi, F. (2020). Northern Sea cucumber (Cucumaria frondosa): A potential candidate for functional food, nutraceutical, and pharmaceutical sector. Mar. Drugs 2020, 18, 274.Hossain, A.; Dave, D.; Shahidi, F. (2022). Effect of high-pressure processing (HPP) on phenolics of North Atlantic sea cucumber (Cucumaria frondosa). J. Agric. Food Chem. 70, 3489–3501.Hua, H.A.N.; Ling, L.I.; Yi, Y.H.; Wang, X.H.; Pan, M.X. (2012). Triterpene glycosides from sea cucumber Holothuria scabra with cytotoxic activity. Chin. Herb. Med. 4, 183–188.Jenzri, M., Bouraoui, Z., Guerbej, H., Jebali, J., & Gharred, T. (2024). Seasonal variation in fatty acid profiles of Holothuria poli (Delle Chiaje, 1823) from Monastir Bay (Tunisia): implications for trophic markers and lipid nutritional quality assessment. New Zealand Journal of Marine and Freshwater Research, 1-23.Karapanagiotidis, I.T.; Gkalogianni, E.Z.; Apostologamvrou, C.; Voulgaris, K.; Varkoulis, A.; Vafidis, D. (2024). Proximate Compositions and Fatty Acid Profiles of Raw and Processed Holothuria polii and Holothuria tubulosa from the Aegean Sea. Sustainability , 16, 6048. https://doi.org/10.3390/su16146048Kareh M., Nahas R., Al Aaraj L., Al-Ghadban S., Deen N., Saliba N., El-Sabban M., Talhouk R. (2018) Anti-proliferative and anti-inflammatory activities of the sea cucumber Holothuria polii aqueous extract. SAGE Open Medicine 6:1-14.Künili, İ. E., & Çolakoğlu, F. A. (2018). Antioxidant and antimicrobial activity of sea cucumber (Holothuria tubulosa, Gmelin 1791) extracts. Canakkale Onsekiz Mart University Journal of Marine Sciences and Fisheries, 1(2), 66-71.Lewandowska, A.M., et al., (2014). Temperature effects on phytoplankton diversity—The zooplankton link. J. Sea Res. v. 85, 359–364.Maier, M. S. (2007). Metabolitos secundarios bioactivos de organismo marinos pertenecientes al phylum Echinodermata.Malve, H., (2016). Exploring the ocean for new drug developments: Marine pharmacology. Journal of Pharmacy and Bioallied Sciences, 8(2), pp. 83–91. https://doi.org/10.4103/0975-7406.171700.Mashjoor S, Yousefzadi M. Holothurians antifungal and antibacterial activity to human pathogens in the Persian Gulf. Journal De Mycologie Médicale (2016), http://dx.doi.org/10.1016/j.mycmed.2016.08.008Méndez N, Angulo A, Contreras O. (2016). Actividad antibacteriana in vitro de Curcuma longa (Zingiberaceae) frente a bacterias nosocomiales en Montería, Colombia. Rev Biol Trop. 64(3):1201-1208.Misgiati, W. I., Murniasih, T., Novriyanti, E., Tarman, K., Safithri, M., Setyaningsih, I., Cahyati, D., Pratama, B. P., & Wirawati, I. (2024). The anticancer and antioxidant potential of local sea cucumber Holothuria edulis, an ecology balancer of Labuan Bajo marine ecosystem. Case Studies in Chemical and Environmental Engineering, 9, 100625. doi: 10.1016/j.cscee.2024.100625.Miyashita, K. (2014). Marine antioxidants. Antioxidants and Functional Components in Aquatic Foods, 219–235. https://doi.org/10.1002/9781118855102.ch8.Mohamed, M. E., Saber, S. A., El-Kafrawy, S. B., Alabdein Nassar, M. Z., & El-Naggar, H. A. (2024). Biotechnological Activities of Holothuria papillifera Mortensen, 1938 Inhabiting the Suez Gulf (Northern Red Sea), Egypt. Egyptian Journal of Aquatic Biology & Fisheries, 28(4).Müller, C., Obermeier, M., & Berg, G. (2016). Bioprospecting plant-associated microbiomes. Journal of Biotechnology, 235, 171-180.Nazemi M., Motallebi A., Abbasi E., Khaledi M. & Zare M. (2022). Antibacterial, antifungal, and cytotoxic activity of the fraction contains squalene in the acetone extract of a sea cucumber, Stichopus hermanni. Iranian Journal of Fisheries Sciences, 21(6), pp. 1495-1507. DOI: 10.22092/ijfs.2023.128416.Nugroho, A., Harahap, I.A., Ardiansyah, A., Bayu, A., Rasyid, A., Murniasih, T., Setyastuti, A., Putra, M.Y., (2021). Antioxidant and antibacterial activities in 21 species of Indonesian sea cucumbers. J. Food Sci. Technol. 59, 239–248. https://doi.org/ 10.1007/s13197-021-05007-6.Oh, G-W, Ko, S-C, Lee, DH, Heo, S-J, and Jung, W-K (2017) Biological activities and biomedical potential of sea cucumber (Stichopus japonicus): a review. Fisheries and Aquatic Sciences 20: e28. https://doi.org/10.1186/ s41240-017-007.Pamungkas, S. Y., & Haryono, F. E. D. (2023). Bioprospecting of sea cucumber (Holothuria sp.) as industries and functional foods for human health. International Journal of Science and Research Archive, 10(2), 669-690. https://doi.org/10.30574/ijsra.2023.10.2.0994Parrish, C.C. (2009). Essential fatty acids in aquatic food webs. In Lipids in Aquatic Ecosystems; Arts, M.T., Brett, M.T., Kainz, M.J., Eds.; Springer: New York, NY, USA; pp. 309–326.Pastrana, O. J., Santafé, G. G., & Torres, O. L. (2016). Perfil de ácidos grasos y evaluación de las actividades antioxidante y antifúngica del Holotureo Isostichopus badionotus. Información tecnológica, 27(3), 03-10.Pastrana, O., Santafé, G., & Sánchez, E. (2019). Perfil lipídico y ensayos de las actividades antioxidante, insecticida y antialimentaria de la esponja marina Iotrochota birotulata (Iotrochotidae: Demospongiae). Revista de Biología Tropical, 67(1), 213–223. https://doi.org/10.15517/rbt.v67i1.32357Pawson, D. L., Pawson, D. J., & King, R. A. (2010). A taxonomic guide to the Echinodermata of the South Atlantic Bight, USA: 1. Sea cucumbers (Echinodermata: Holothuroidea). Zootaxa, 2449(1), 1-48.Pérez-Ruzafa, A., Alvarado, J. J., Solís-Marín, F. A., Hernández, J. C., Morata, A., Marcos, C., ... & Williams, S. M. (2013). Latin America echinoderm biodiversity and biogeography: Patterns and affinities. Echinoderm research and diversity in Latin America, 511-542Pham-Huy, L., He, H., & Pham-Huy, C. (2008). Free Radicals, Antioxidants in Disease and Health. Int J Biomed Sci, 2, 89–96. Recuperado de https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614697/.Pires, M., & García, Y. (2024). Biochemical and ecological components of Holothuria (Halodeima) grisea, Selenka 1867 (Echinodermata: Holothuroidea). Regional Studies in Marine Science, 73, 103460.Piri-Gharaghie, T., Ghajari, G., Hassanpoor, M., Jegargoshe-Shirin, N., Soosanirad, M., Khayati, S., ... & Mirzaei, A. (2023). Investigation of antibacterial and anticancer effects of novel niosomal formulated Persian Gulf Sea cucumber extracts. Heliyon, 9(3).Purcell SW, Hair CA, Mills DJ (2012) Sea cucumber culture, farming and sea ranching in the tropics: Progress, problem and opportunities. Aquaculture 368–369: 68–81. https://doi.org/10.1016/j.aquacul- ture.2012.08.053Putra, Y., Soffa, F. B., Firdaus, M., Pangestuti, R., & Siahaan, E. A. (2022). Determination of fatty acid profiles and bioactive properties of body wall and viscera of Holothuria atra collected from Lombok Island, Indonesia. In IOP Conference Series: Earth and Environmental Science (Vol. 1119, No. 1, p. 012052). IOP Publishing.Quiroz Lobo, Y., Santafé Patiño, G., & Quirós-Rodríguez, J. A. (2021). Caracterización de los ácidos grasos y actividad antimicrobiana del extracto en metanol de Holothuria princeps (Holothuriida: Holothuriidae). Revista de Biología Tropical , 69(1), 36-44.Rahman, M. A., Chowdhury, S. H., Hasan, M. J., Rahman, M. H., Yeasmin, S. M., Farjana, N., ... & Parvez, M. S. (2020). Status, prospects and market potentials of the sea cucumber fisheries with special reference on their proper utilization and trade. Annual Research & Review in Biology, 35(7), 84-101.Rasyid A, Yasman Y, Putra MY (2021) Current prospects of nutraceutical and pharmaceutical use of sea cucumbers. Pharmacia 68(3): 561–572. https://doi.org/10.3897/pharmacia.68.e69140Rosenthal, V. D., Yin, R., Lu, Y., Rodrigues, C., Myatra, S. N., Kharbanda, M., ... & Jin, Z. (2023). The impact of healthcare-associated infections on mortality in ICU: a prospective study in Asia, Africa, Eastern Europe, Latin America, and the Middle East. American journal of infection control, 51(6), 675-682.Santafé, G. G., Guzmán, M. S., & Torres, O. L. (2014). Triterpenos Holostáticos con Actividad Antifúngica obtenidos del pepino de mar Holothuria floridana: Recolectado en la Bahía de Cispatá, Córdoba-Colombia. Información tecnológica, 25(2), 87-92Santoyo, G.; Orozco-Mosqueda & M. Govindappa, M. C.; Govindappa, M. (2012). Mechanisms Biocontrol and Plant Growth-Promoting Activity in Soil Bacterial Species of Bacillus and Pseudomonas: A Review: Biocontrol Science and Technology: Vol 22, No 8. Biocontrol Science and Technology. pp 855–872.Sarhadizadeh N, Afkhami M, Ehsanpour M. (2014). Evaluation bioactivity of a sea cucumber, Stichopus hermanni from Persian Gulf. European Journal Experimental Biology 4(1): 234–258Shi, S., Feng, W., Hu, S., Liang, S., An, N., & Mao, Y. (2016). Bioactive compounds of sea cucumbers and their therapeutic effects. Chinese Journal of Oceanology and Limnology, 34(3), 549-558.Telahigue K, Ghali R, Nouiri E, Labidi A, Hajji T. (2020). Antibacterial activities and bioactive compounds of the ethyl acetate extract of the sea cucumber Holothuria forskali from Tunisian coasts. Journal of the Marine Biological Association of the United Kingdom, pp. 1–9. https://doi.org/10.1017/S002531542000001Thawabteh, A.M.; Swaileh, Z.; Ammar, M.; Jaghama,W.; Yousef, M.; Karaman, R.; A. Bufo, S.; Scrano, L. (2023). Antifungal and Antibacterial Activities of Isolated Marine Compounds. Toxins. 15, 93. https://doi.org/10.3390/ toxins15020093Verea, L. P., Ferrer, A. F., Reyes, Y. O., Miranda, Y. P., & Méndez, A. R. (2019). Infecciones nosocomiales y resistencia antimicrobiana. Revista Cubana de Medicina Intensiva y Emergencias, 18(1), 1-17. Recuperado: https://www.medigraphic.com/pdfs/revcubmedinteme/cie-2019/cie121b.Wang, F., Cao, Y., Guo, Y., Zhu, Z., & Zhang, C. (2021). Evaluation of antioxidant and antibacterial activities of lipid extracts from Eustigmatos cf. polyphem (Eustigmatophyceae) and preliminary identification of bioactive compound. Algal Research, 59. https://doi.org/10.1016/j.algal.2021.102446Wargasetia, T. L., Ratnawati, H., Widodo, N., & Widyananda, M. H. (2023). Antioxidant and anti-inflammatory activity of sea cucumber (Holothuria scabra) active compounds against KEAP1 and iNOS protein. Bioinformatics and Biology Insights, 17, 11779322221149613.Yuan, H., Ma, Q., Ye, L., & Piao, G. (2016). The Traditional Medicine and Modern Medicine from Natural Products. Molecules, 21(5), 559. https://doi.org/10.3390/molecules21050559Zhao, Y., Wang, Y., Zhang, X., Liu, H., Wang, G., & Liu, H. (2012). Effects of potential probiotic Bacillus subtilis T13 on growth, immunity and disease resistance against Vibrio splendidus infection in juvenile sea cucumber Apostichopus japonicus. Fish & Shellfish Immunology, 32(5), 750-755.Zhukova, N.V. (2023). Fatty Acids of Echinoderms: Diversity, Current Applications and Future Opportunities. Mar. Drugs, 21, 21. https://doi.org/10.3390/md21010021Zmemlia N, Bejaoui S, Khemiri I, Bouriga N, Louiz I, El-Bok S, Ben-Attia M, Souli A. (2020). Biochemical composition and antioxidant potential of the edible Mediterranean sea cucumber Holothuria tubulosa. Grasas Aceites 71 (3), e364. https://doi.org/10.3989/gya.0452191.HoloturoideosÁcidos grasosActividad biológicaActividad antioxidanteCórdobaSea cucumbersFatty acidsBiological activityAntioxidant activityCórdobaPublicationORIGINALmirlethjulioberrio.pdfmirlethjulioberrio.pdfapplication/pdf2110913https://repositorio.unicordoba.edu.co/bitstreams/1e9e4e66-9512-4943-a0fd-55100f2919b9/downloadeb019a0a08a7eaea71b2fed4d427be72MD51FORMATO DE AUTORIZACIÓN-.pdfFORMATO DE AUTORIZACIÓN-.pdfapplication/pdf1290802https://repositorio.unicordoba.edu.co/bitstreams/7d188002-64ca-4248-ac61-751c316cfaee/download718c6cbbfd3357c1ad4345957009858cMD53LICENSElicense.txtlicense.txttext/plain; charset=utf-815543https://repositorio.unicordoba.edu.co/bitstreams/99fd3231-0e5a-4e17-a89a-5bc1e949a50b/download73a5432e0b76442b22b026844140d683MD52TEXTmirlethjulioberrio.pdf.txtmirlethjulioberrio.pdf.txtExtracted texttext/plain101862https://repositorio.unicordoba.edu.co/bitstreams/77fa783b-a612-4195-831e-d98c502e3a6e/downloadf999bf978a9d85544b107b3f58f8aaedMD54FORMATO DE AUTORIZACIÓN-.pdf.txtFORMATO DE AUTORIZACIÓN-.pdf.txtExtracted texttext/plain158https://repositorio.unicordoba.edu.co/bitstreams/6eb2b8d0-fe06-4687-9bc5-c853b995ca2e/download1c1bce5b0a14fb5c81fb15dc475ef0ceMD56THUMBNAILmirlethjulioberrio.pdf.jpgmirlethjulioberrio.pdf.jpgGenerated Thumbnailimage/jpeg7375https://repositorio.unicordoba.edu.co/bitstreams/ccde8482-1db6-4100-a762-30afe7e9dc61/download20548bb490252a71f706ed13870e0744MD55FORMATO DE AUTORIZACIÓN-.pdf.jpgFORMATO DE AUTORIZACIÓN-.pdf.jpgGenerated Thumbnailimage/jpeg13426https://repositorio.unicordoba.edu.co/bitstreams/c63ca385-9965-4091-bd23-6f9ef5394fbd/download884fe31803f921b49fad2cba28f61669MD57ucordoba/9007oai:repositorio.unicordoba.edu.co:ucordoba/90072025-02-06 03:01:29.634https://creativecommons.org/licenses/by-nc-nd/4.0/Copyright Universidad de Córdoba, 2025embargohttps://repositorio.unicordoba.edu.coRepositorio Universidad de Córdobabdigital@metabiblioteca.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