Péptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión Narrativa
Digital
- Autores:
-
Piza-Figueroa, Angie Lineth
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2023
- Institución:
- Universidad de Santander
- Repositorio:
- Repositorio Universidad de Santander
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.udes.edu.co:001/10456
- Palabra clave:
- Catelicidinas
Diabetes Mellitus
Enfermedades Cardiovasculares
Neoplasias
Péptidos Antimicrobianos
Antimicrobial Peptides
Cardiovascular Diseases
Catelicidins
Diabetes Mellitus
Neoplasms
- Rights
- embargoedAccess
- License
- http://purl.org/coar/access_right/c_f1cf
| id |
RUDES2_78fd6b5f368e2329729c7ae833d6529b |
|---|---|
| oai_identifier_str |
oai:repositorio.udes.edu.co:001/10456 |
| network_acronym_str |
RUDES2 |
| network_name_str |
Repositorio Universidad de Santander |
| repository_id_str |
|
| dc.title.spa.fl_str_mv |
Péptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión Narrativa |
| dc.title.translated.none.fl_str_mv |
Antimicrobial Peptides for the Treatment of Chronic Non-Communicable Diseases: Narrative Review |
| title |
Péptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión Narrativa |
| spellingShingle |
Péptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión Narrativa Catelicidinas Diabetes Mellitus Enfermedades Cardiovasculares Neoplasias Péptidos Antimicrobianos Antimicrobial Peptides Cardiovascular Diseases Catelicidins Diabetes Mellitus Neoplasms |
| title_short |
Péptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión Narrativa |
| title_full |
Péptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión Narrativa |
| title_fullStr |
Péptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión Narrativa |
| title_full_unstemmed |
Péptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión Narrativa |
| title_sort |
Péptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión Narrativa |
| dc.creator.fl_str_mv |
Piza-Figueroa, Angie Lineth |
| dc.contributor.advisor.none.fl_str_mv |
Trejos-Suarez, Juanita |
| dc.contributor.author.none.fl_str_mv |
Piza-Figueroa, Angie Lineth |
| dc.contributor.jury.none.fl_str_mv |
Lozano-Ramírez, Claudia Pilar Montes-Rincón, Claudia Ximena |
| dc.subject.proposal.spa.fl_str_mv |
Catelicidinas Diabetes Mellitus Enfermedades Cardiovasculares Neoplasias Péptidos Antimicrobianos |
| topic |
Catelicidinas Diabetes Mellitus Enfermedades Cardiovasculares Neoplasias Péptidos Antimicrobianos Antimicrobial Peptides Cardiovascular Diseases Catelicidins Diabetes Mellitus Neoplasms |
| dc.subject.proposal.eng.fl_str_mv |
Antimicrobial Peptides Cardiovascular Diseases Catelicidins Diabetes Mellitus Neoplasms |
| description |
Digital |
| publishDate |
2023 |
| dc.date.issued.none.fl_str_mv |
2023-12-04 |
| dc.date.accessioned.none.fl_str_mv |
2024-05-29T15:59:19Z |
| dc.date.available.none.fl_str_mv |
2024-05-29T15:59:19Z 2026-04-20 |
| dc.type.none.fl_str_mv |
Trabajo de grado - Pregrado |
| dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_7a1f |
| dc.type.coarversion.none.fl_str_mv |
http://purl.org/coar/version/c_71e4c1898caa6e32 |
| dc.type.content.none.fl_str_mv |
Text |
| dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/bachelorThesis |
| dc.type.version.none.fl_str_mv |
info:eu-repo/semantics/submittedVersion |
| format |
http://purl.org/coar/resource_type/c_7a1f |
| status_str |
submittedVersion |
| dc.identifier.instname.none.fl_str_mv |
Universidad de Santander |
| dc.identifier.local.none.fl_str_mv |
T 17.23 P491p |
| dc.identifier.reponame.none.fl_str_mv |
Repositorio Digital Universidad de Santander |
| dc.identifier.repourl.none.fl_str_mv |
https://repositorio.udes.edu.co |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.udes.edu.co/handle/001/10456 |
| identifier_str_mv |
Universidad de Santander T 17.23 P491p Repositorio Digital Universidad de Santander |
| url |
https://repositorio.udes.edu.co https://repositorio.udes.edu.co/handle/001/10456 |
| dc.language.iso.none.fl_str_mv |
spa |
| language |
spa |
| dc.relation.references.none.fl_str_mv |
World Health Organization. Noncommunicable diseases [Internet]. Geneva: WHO; 2023 [citado el 18 de octubre de 2023]. Disponible en: https://www.who.int/news-room/fact- sheets/detail/noncommunicable-diseases. Serra Valdés M, Serra Ruíz M, Viera García M. Las enfermedades crónicas no transmisibles: magnitud actual y tendencias futuras. Rev Finlay. 2018;8(2):140-148. Muka T, Imo D, Jaspers L, Colpani V, Chaker L, van der Lee SJ, Mendis S, Chowdhury R, Bramer WM, Falla A, Pazoki R, Franco OH. The global impact of non-communicable diseases on healthcare spending and national income: a systematic review. Eur J Epidemiol. 2015 Apr;30(4):251-277. doi: 10.1007/s10654-014-9984-2. PMID: 25595318. Al-Hanawi MK. Socioeconomic determinants and inequalities in the prevalence of non- communicable diseases in Saudi Arabia. Int J Equity Health. 2021;20(1):174. doi: 10.1186/s12939-021-01510-6. PMID: 34321000; PMCID: PMC8320210. Wang L, Wang N, Zhang W, et al. Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther. 2022;7(1):48. doi: 10.1038/s41392-022-00904-4. PMID: 35165272; PMCID: PMC8844085. Al Musaimi O, Lombardi L, Williams DR, Albericio F. Strategies for Improving Peptide Stability and Delivery. Pharmaceuticals (Basel). 2022 Oct 19;15(10):1283. doi: 10.3390/ph15101283. PMID: 36297395; PMCID: PMC9610364. Mukherjee AG, et al. Evolving strategies and application of proteins and peptide therapeutics in cancer treatment. Biomed Pharmacother. 2023 Jul;163:114832. doi: 10.1016/j.biopha.2023.114832. Chinnadurai RK, Khan N, Meghwanshi GK, Ponne S, Althobiti M, Kumar R. Current research status of anti-cancer peptides: Mechanism of action, production, and clinical applications. Biomed Pharmacother. 2023 Aug;164:114996. doi: 10.1016/j.biopha.2023.114996. Epub 2023 Jun 11. PMID: 37311281. Bailey CJ, Flatt PR, Conlon JM. An update on peptide-based therapies for type 2 diabetes and obesity. Peptides. 2023 Mar;161:170939. doi: 10.1016/j.peptides.2023.170939. Epub 2023 Jan 3. PMID: 36608818. Neal D Shore et al. A New Sustained-release, 3-Month Leuprolide Acetate Formulation Achieves and Maintains Castrate Concentrations of Testosterone in Patients With Prostate Cancer. Clin Ther. 2019 Mar;41(3):412-425. doi: 10.1016/j.clinthera.2019.01.004. Epub 2019 Feb 8. Marso SP, Baeres FMM, Bain SC, Goldman B, Husain M, Nauck MA, Poulter NR, Pratley RE, Thomsen AB, Buse JB; LEADER Trial Investigators. Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure. J Am Coll Cardiol. 2020 Mar 17;75(10):1128-1141. doi: 10.1016/j.jacc.2019.12.063. PMID: 32164886. Zhiye Zhang et al. Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition. Immunity. 2015 Dec 15;43(6):1137-1147. doi: 10.1016/j.immuni.2015.10.018. Epub 2015 Dec 8. Chernomordik F, Cercek B, Lio WM, Mihailovic PM, Yano J, Herscovici R, Zhao X, Zhou J, Chyu KY, Shah PK, Dimayuga PC. The Role of T Cells Reactive to the Cathelicidin Antimicrobial Peptide LL-37 in Acute Coronary Syndrome and Plaque Calcification. Front Immunol. 2020 Oct 6;11:575577. doi: 10.3389/fimmu.2020.575577. PMID: 33123157; PMCID: PMC7573569. Othman Al Musaimi, Lucia Lombardi, Daryl R Williams, Fernando Albericio. Strategies for Improving Peptide Stability and Delivery. Pharmaceuticals (Basel). 2022 Oct 19;15(10):1283. doi: 10.3390/ph15101283. PMID: 36297395; PMCID: PMC9610364. Zhang QY, Yan ZB, Meng YM, Hong XY, Shao G, Ma JJ, Cheng XR, Liu J, Kang J, Fu CY. Antimicrobial peptides: mechanism of action, activity and clinical potential. Military Medical Research. 2021;8(1):47. doi: 10.1186/s40779-021-00334-7. Wang G. Human antimicrobial peptides and proteins. Pharmaceuticals (Basel). 2014 May 13;7(5):545-94. doi: 10.3390/ph7050545. PMID: 24828484; PMCID: PMC4035769. Wang G, Li X, Wang Z. APD3: the antimicrobial peptide database as a tool for research and education. Nucleic Acids Res. 2016;44(D1):D1087-1093. Tornesello AL, Borrelli A, Buonaguro L, Buonaguro FM, Tornesello ML. Antimicrobial peptides as anticancer agents: Functional properties and biological activities. Molecules [Internet]. 2020 [citado el 13 de marzo de 2023];25(12):2850. Disponible en: https://www.mdpi.com/1420-3049/25/12/2850. Mookherjee N, Anderson MA, Haagsman HP, Davidson DJ. Péptidos de defensa antimicrobianos del huésped: funciones y potencial clínico. Nat Rev Drug Discov [Internet]. 2020 [citado el 13 de marzo de 2023];19(5):311–32. Disponible en: https://www.nature.com/articles/s41573-019-0058-8. Haney, E. F., & Hancock, R. E. W. (2013). Peptide design for antimicrobial and immunomodulatory applications. Biopolymers, 100(6), 572–583. Malmsten M. Interactions of Antimicrobial Peptides with Bacterial Membranes and Membrane Components. Curr Top Med Chem. 2016;16(1):16-24. doi: 10.2174/1568026615666150703121518. PMID: 26139113. Brogden, K. A. (2005). Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nature Reviews Microbiology, 3(3), 238–250. Porto, W. F., Irazazabal, L., & Alves, E. S. F. (2018). In silico approaches to discover new antimicrobial peptides. Current Opinion in Pharmacology, 43, 1–7. Mansour, S. C., Pena, O. M., & Hancock, R. E. W. (2014). Host defense peptides: front- line immunomodulators. Trends in Immunology, 35(9), 443–450. Zhang Q, Ul Ain Q, Schulz C, Pircher J. Role of antimicrobial peptide cathelicidin in thrombosis and thromboinflammation. Front Immunol [Internet]. 2023;14. Disponible en: http://dx.doi.org/10.3389/fimmu.2023.1151926. Pircher J, Czermak T, Ehrlich A, Eberle C, Gaitzsch E, Margraf A, et al. Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation. Nat Commun [Internet]. 2018 [citado el 18 de noviembre de 2023];9(1):1–15. Disponible en: https://www.nature.com/articles/s41467-018-03925-2. Bei Y, Pan L-L, Zhou Q, Zhao C, Xie Y, Wu C, et al. Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury. BMC Med [Internet]. 2019;17(1). Disponible en: http://dx.doi.org/10.1186/s12916-019-1268-y. Klyachkin YM, Idris A, Rodell CB, Tripathi H, Ye S, Nagareddy P, et al. Cathelicidin related antimicrobial peptide (CRAMP) enhances bone marrow cell retention and attenuates cardiac dysfunction in a mouse model of myocardial infarction. Stem Cell Rev [Internet]. 2018 [citado el 18 de noviembre de 2023];14(5):702–14. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29948752/. Vukic VR, Vukic DV, Milanovic SD, Ilicic MD, Kanuric KG, Johnson MS. In silico identification of milk antihypertensive di- and tripeptides involved in angiotensin I-converting enzyme inhibitory activity. Nutr Res. 2017 Oct;46:22-30. doi: 10.1016/j.nutres.2017.07.009. Epub 2017 Jul 28. PMID: 29173648. Domínguez González KN, Cruz Guerrero AE, Márquez HG, Gómez Ruiz LC, García-Garibay M, Rodríguez Serrano GM. El efecto antihipertensivo de las leches fermentadas. Rev Argent Microbiol [Internet]. 2014 [citado el 19 de noviembre de 2023];46(1):58–65. Disponible en: https://www.elsevier.es/es-revista-revista-argentina-microbiologia-372-articulo-el-efecto- antihipertensivo-leches-fermentadas-S0325754114700501. González P, Lozano P, Ros G, Solano F. Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections. Int J Mol Sci. 2023 May 27;24(11):9352. doi: 10.3390/ijms24119352. PMID: 37298303; PMCID: PMC10253853. Jia L, Li J, Zhang M, Liu H, Ren Z, Dong XL, Pan X, Qiu J, Pan LL, Sun J, et al. Cathelicidin- related antimicrobial peptide protects against enteric pathogen-accelerated type 1 diabetes in mice. Theranostics. 2022;12(10):4771-4791. doi: 10.7150/thno.61433. PMID: 35547774; PMCID: PMC9065195. Pound LD, Patrick C, Eberhard CE, Mottawea W, Wang G-S, Abujamel T, et al. Cathelicidin Antimicrobial Peptide: A Novel Regulator of Islet Function, Islet Regeneration, and Selected Gut Bacteria. Diabetes (2015) 64:4135–47. doi: 10.2337/db15-0788. Sun J, Furio L, Mecheri R, van der Does AM, Lundeberg E, Saveanu L, et al. Pancreatic β- Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed Under the Influence of the Gut Microbiota. Immunity (2015) 43:304–17. doi: 10.1016/j.immuni.2015.07.013. Aloul KM, Nielsen JE, Defensor EB, Lin JS, Fortkort JA, Shamloo M, et al. Upregulating human cathelicidin antimicrobial peptide LL-37 expression may prevent severe COVID-19 inflammatory responses and reduce microthrombosis. Front Immunol [Internet]. 2022 [citado el 18 de noviembre de 2023];13:880961. Disponible en: https://www.frontiersin.org/articles/10.3389/fimmu.2022.880961/full. Soltaninejad, H.; Zare-Zardini, H.; Ordooei, M.; Ghelmani, Y.; Ghadiri-Anari, A.; Mojahedi, S.; Hamidieh, A.A. Antimicrobial Peptides from Amphibian Innate Immune System as Potent Antidiabetic Agents: A Literature Review and Bioinformatics Analysis. J. Diabetes Res. 2021, 2021, e2894722. Zainab, A.J.A.A.; Ashish, N.; Ragnath, V. Salivary Levels of Antimicrobial Peptides in Chronic Periodontitis Patients with Type 2 Diabetes. J. Int. Acad. Periodontol. 2019, 21, 36– 44. Miani M, Le Naour J, Waeckel-Enée E, Verma SC, Straube M, Emond P, Ryffel B, van Endert P, Sokol H, Diana J. Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes. Cell Metab. 2018;28(2):238-252.e8. doi: 10.1016/j.cmet.2018.06.012. PMID: 30017352. Ramadhan AH, Nawas T, Zhang X, Pembe WM, Xia W, Xu Y. Purification and Identification of a Novel Antidiabetic Peptide from Chinese Giant Salamander (Andrias Davidianus) Protein Hydrolysate against α-Amylase and α-Glucosidase. Int J Food Prop. 2017;20(Suppl):S3360- S3372. Musale V, Moffett RC, Owolabi B, Conlon JM, Flatt PR, Abdel-Wahab YHA. Mechanisms of Action of the Antidiabetic Peptide [S4K]CPF-AM1 in Db/Db Mice. J Mol Endocrinol. 2021;66:115-128. Luo J, Zhang H. Bioactive peptides from food for the treatment of diabetes: recent progress and future perspectives. Curr Opin Food Sci. 2023;32:100786. Debarun P, Kumari B, Palla R, Moyna K, Durba P. Anti-cancer drug molecules targeting cancer cell cycle and proliferation. In: Control of Cell Cycle & Cell Proliferation. Elsevier; 2023. p. 343-395. Norouzi P, Mirmohammadi M, Houshdar Tehrani MH. Anticancer peptides mechanisms, simple and complex. Chem Biol Interact. 2022 Dec 1;368:110194. doi: 10.1016/j.cbi.2022.110194. Epub 2022 Oct 1. PMID: 36195187. Jafari A, Babajani A, Sarrami Forooshani R, Yazdani M, Rezaei-Tavirani M. Clinical applications, y efectos anticancerígenos de péptidos antimicrobianos: desde el laboratorio hasta la cabecera del paciente. Front Oncol. 2022;12. Disponible en: http://dx.doi.org/10.3389/fonc.2022.819563 Costa F, Teixeira C, Gomes P, Martins MCL. Aplicación clínica de AMP. En: Advances in Experimental Medicine and Biology. Singapur: Springer Singapur; 2019. p. 281-298. Binaymotlagh R, Hajareh Haghighi F, Aboutalebi F, Mirahmadi-Zare SZ, Hadadzadeh H, Nasr-Esfahani M-H. Quimioterapia selectiva e imágenes de células de cáncer de colon y mama mediante un nanocompuesto de Fe3O4–AuNCs recubierto con polietilenglicol- dimetacrilato modificado con aptámero MUC-1. New J Chem. 2019;43(1):238-248. Disponible en: https://pubs.rsc.org/en/content/articlelanding/2019/nj/c8nj04236e Papachristodoulou A, Signorell RD, Werner B, Brambilla D, Luciani P, Cavusoglu M, et al. Sensibilización a la quimioterapia de glioblastoma mediante la entrega mediada por ultrasonidos enfocados de liposomas terapéuticos. J Control Release. 2019;295:130-139. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30537486/ Jiang Y, Chen Y, Song Z, Tan Z, Cheng J. Avances recientes en el diseño de péptidos antimicrobianos y polipéptidos para su traducción clínica. Adv Drug Deliv Rev. 2021;170:261- 280. Disponible en: https://www.sciencedirect.com/science/article/pii/S0169409X20302957 Botelho Sampaio de Oliveira K, Lopes Leite M, Albuquerque Cunha V, Brito da Cunha N, Luiz Franco O. Desafíos y avances en el desarrollo de péptidos antimicrobianos. Drug Discov Today. 2023;28(8):103629. Disponible en: https://www.sciencedirect.com/science/article/pii/S1359644623001459 Rodríguez Guerra JA. Evaluación de la actividad anticancerígena In Vitro de péptidos sintéticos derivados de Lactoferricina Bovina en líneas celulares de cáncer de mama. 2019. Insuasty Cepeda DS. Implementación y optimización de la síntesis de péptidos diméricos derivados de la secuencia LfcinB (20-30) con potencial actividad anticancerígena contra el cáncer de mama. 2023. Guerra JR, Cárdenas AB, Ochoa-Zarzosa A, Meza JL, Umaña Pérez A, Fierro-Medina R, et al. El péptido tetramérico LfcinB (20–25)4 derivado de la lactoferricina bovina induce apoptosis en la línea celular de cáncer de mama MCF-7. RSC Adv. 2019;9(36):20497-20504. Disponible en: http://dx.doi.org/10.1039/c9ra04145a Niemirowicz K, Prokop I, Wilczewska A, Wnorowska U, Piktel E, Wątek M, et al. Nanopartículas magnéticas mejoran la actividad anticancerígena del péptido catelicidina LL- 37 contra células de cáncer de colon. Int J Nanomedicine. 2015 Jun;10:3843. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461127/ Arpornsuwan T, Sriwai W, Jaresitthikunchai J, Phaonakrop N, Sritanaudomchai H, Roytrakul S. Actividades anticancerígenas de péptidos antimicrobianos BmKn2 contra células de cáncer oral y de colon. Int J Pept Res Ther. 2014;20(4):501-509. doi: 10.1007/s10989-014- 9417-9 |
| 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 |
| dc.rights.license.none.fl_str_mv |
Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0) |
| dc.rights.uri.none.fl_str_mv |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
embargoedAccess |
| rights_invalid_str_mv |
http://purl.org/coar/access_right/c_f1cf Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.format.extent.none.fl_str_mv |
16 p |
| dc.format.mimetype.none.fl_str_mv |
application/pdf application/msword |
| dc.publisher.none.fl_str_mv |
Universidad de Santander |
| dc.publisher.branch.none.fl_str_mv |
Bucaramanga |
| dc.publisher.faculty.none.fl_str_mv |
Facultad de Ciencias Médicas y de la Salud |
| dc.publisher.place.none.fl_str_mv |
Bucaramanga, Colombia |
| dc.publisher.program.none.fl_str_mv |
Bacteriología y Laboratorio Clínico |
| publisher.none.fl_str_mv |
Universidad de Santander |
| institution |
Universidad de Santander |
| bitstream.url.fl_str_mv |
https://repositorio.udes.edu.co/bitstreams/de4d8332-9cab-49fd-85eb-d05270ae6175/download https://repositorio.udes.edu.co/bitstreams/06d1499d-5165-4521-bb47-e1106da4e064/download https://repositorio.udes.edu.co/bitstreams/2f8b2e4f-8053-4e83-a0f4-322733899b19/download https://repositorio.udes.edu.co/bitstreams/0178e763-aab3-4cd6-843e-24a69be8ca79/download https://repositorio.udes.edu.co/bitstreams/6fe44b5f-0876-4405-a432-d91927d75d30/download https://repositorio.udes.edu.co/bitstreams/7b6decf4-ec1c-4aaa-af1c-baab43666290/download https://repositorio.udes.edu.co/bitstreams/f1c5ccde-2a5b-4cb8-9835-e747f979c989/download https://repositorio.udes.edu.co/bitstreams/afb63745-3601-4c0f-a66a-d978f48ae97d/download https://repositorio.udes.edu.co/bitstreams/7feaadb7-65ca-4153-b5da-2b1d2f4c2862/download https://repositorio.udes.edu.co/bitstreams/99ff14a5-c941-4c60-8f7a-b39f4b04c300/download https://repositorio.udes.edu.co/bitstreams/055b62e1-421f-4897-b0cb-97d6a5990246/download https://repositorio.udes.edu.co/bitstreams/b3bf04b2-5ef8-439b-b584-8669bc191919/download https://repositorio.udes.edu.co/bitstreams/cedfd7a0-cc2a-41b3-99db-3707633c894e/download https://repositorio.udes.edu.co/bitstreams/41851921-f63f-4225-a1b6-07371ae070cb/download https://repositorio.udes.edu.co/bitstreams/d73a50e5-199e-4a9c-83bb-ed281ddfe4e1/download https://repositorio.udes.edu.co/bitstreams/e9dc2abc-47cf-45ad-b5ba-161afd953d87/download https://repositorio.udes.edu.co/bitstreams/4f32506e-7b86-4c8a-891c-426adb0beeb6/download https://repositorio.udes.edu.co/bitstreams/dcca543f-adbd-4321-a2ff-510fc3121064/download https://repositorio.udes.edu.co/bitstreams/7a0dac73-d6fb-4466-a1e7-988e7ec4f681/download https://repositorio.udes.edu.co/bitstreams/47490564-3dde-417d-8c70-92205c2d54d0/download https://repositorio.udes.edu.co/bitstreams/5cb13088-9741-4f8f-96fc-b28e4d394f5a/download |
| bitstream.checksum.fl_str_mv |
e1c06d85ae7b8b032bef47e42e4c08f9 56e20113ee5d7d07aa8630b7d8979155 7f8f52654589009839a2751b15ebb6b4 b1a364d9caaa0a58c9c265ad16fc38b5 9f77671cd364eeb69735e59e3f1c1120 597e37dbfebc703d86b84b3a0c2d042f a68cd0e37c2105323845e56349da7b84 6a7aeb19d113be77c53b01475598d956 14cfc3c08502d6101c1c65a4db6e2633 ba03987a9265e66c256fbb579eee1569 80221bfdda72bc6d4f1ec08cf58d3a50 f0ab9c9cea9fd7861c7cfb8ff502e81a e194e213ae76beab3fdaca94c13a35ee eda81c1be09ae42c9147bf4551e12446 75a29c23711fa2b02526b4d2aea81ace 9eb1ac5f6eecd7015a5571be66166286 1dae08e4a6e5c3dccf30342cad6a6406 d6ee58062d2e61651d6f2578710314ef cb0bcc5208a9d5e740c74f5116e1bfe8 8e4188f9a40ec35c6cfea4a3c79296af 73a5432e0b76442b22b026844140d683 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositorio Universidad de Santander |
| repository.mail.fl_str_mv |
soporte@metabiblioteca.com |
| _version_ |
1808490857946415104 |
| spelling |
Trejos-Suarez, Juanitacae66b4c-06c0-459a-bff0-bbc186d27d86600Piza-Figueroa, Angie Linethc07b314d-9ef8-40fc-935c-c99837e582f7-1Lozano-Ramírez, Claudia Pilar8c019761-8c55-4159-8fd2-fe702f21a1b2600Montes-Rincón, Claudia Ximena613e6686-3fb7-459a-9832-3313252c036b-12024-05-29T15:59:19Z2026-04-202024-05-29T15:59:19Z2023-12-04DigitalIntroducción. Los péptidos antimicrobianos, reconocidos por su capacidad defensiva en diversos organismos, emergen como candidatos prometedores para enfrentar la creciente prevalencia de Enfermedades crónicas no transmisibles (ECNT) a nivel global, como la diabetes, enfermedades cardiovasculares y cáncer. Metodología. Se utilizó un enfoque de revisión narrativa, realizando una búsqueda sistemática en bases de datos académicas con palabras clave específicas. La selección de las fuentes se basó en criterios rigurosos para garantizar la relevancia y validez científica. El análisis crítico y la síntesis de la literatura proporcionaron una comprensión coherente sobre el tema. Resultados. Los péptidos antimicrobianos (AMP), fundamentales en el sistema inmunitario innato, exhiben una diversa estructura y mecanismo de acción, principalmente alterando membranas de microorganismos. En enfermedades cardiovasculares, específicamente las catelicidinas como LL-37, son significativas en la aterosclerosis y tromboinflamación. En diabetes, los AMP han mostrado potencial en la regulación del microbioma y la función pancreática. En cáncer, presentan efectos citotóxicos sobre diversas líneas celulares, abriendo caminos para terapias más eficaces. Conclusión. Los AMP se perfilan como una estrategia terapéutica prometedora para las ECNT, sobresaliendo por su especificidad y reducidos efectos secundarios. Sin embargo, se requiere investigación adicional para optimizar su uso clínico, abordando desafíos como la biodisponibilidad, estabilidad y minimización de efectos adversos.Introduction. Antimicrobial peptides, known for their defensive capacity in various organisms, emerge as promising candidates to address the increasing prevalence of Non- Communicable Chronic Diseases (NCCD) globally, such as diabetes, cardiovascular diseases, and cancer. Methodology. A narrative review approach was utilized, conducting a systematic search in academic databases with specific keywords. The selection of sources was based on rigorous criteria to ensure their relevance and scientific validity. Critical analysis and synthesis of the literature provided a coherent understanding of the topic. Results. Antimicrobial peptides (AMP), fundamental in the innate immune system, exhibit a diverse structure and mechanism of action, primarily by altering the membranes of microorganisms. In cardiovascular diseases, specifically catelicidins like LL-37, they play a significant role in atherosclerosis and thromboinflammation. In diabetes, AMP have shown potential in regulating the microbiome and pancreatic function. In cancer, they exhibit cytotoxic effects on various cell lines, paving the way for more effective therapies. Conclusion. AMP are emerging as a promising therapeutic strategy for NCCD, standing out for their specificity and reduced side effects. However, further research is required to optimize their clinical use, addressing challenges such as bioavailability, stability, and minimizing adverse effects.PregradoBacteriólogo(a) y Laboratorista Clínico16 papplication/pdfapplication/mswordUniversidad de SantanderT 17.23 P491pRepositorio Digital Universidad de Santanderhttps://repositorio.udes.edu.cohttps://repositorio.udes.edu.co/handle/001/10456spaUniversidad de SantanderBucaramangaFacultad de Ciencias Médicas y de la SaludBucaramanga, ColombiaBacteriología y Laboratorio ClínicoWorld Health Organization. Noncommunicable diseases [Internet]. Geneva: WHO; 2023 [citado el 18 de octubre de 2023]. Disponible en: https://www.who.int/news-room/fact- sheets/detail/noncommunicable-diseases.Serra Valdés M, Serra Ruíz M, Viera García M. Las enfermedades crónicas no transmisibles: magnitud actual y tendencias futuras. Rev Finlay. 2018;8(2):140-148.Muka T, Imo D, Jaspers L, Colpani V, Chaker L, van der Lee SJ, Mendis S, Chowdhury R, Bramer WM, Falla A, Pazoki R, Franco OH. The global impact of non-communicable diseases on healthcare spending and national income: a systematic review. Eur J Epidemiol. 2015 Apr;30(4):251-277. doi: 10.1007/s10654-014-9984-2. PMID: 25595318.Al-Hanawi MK. Socioeconomic determinants and inequalities in the prevalence of non- communicable diseases in Saudi Arabia. Int J Equity Health. 2021;20(1):174. doi: 10.1186/s12939-021-01510-6. PMID: 34321000; PMCID: PMC8320210.Wang L, Wang N, Zhang W, et al. Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther. 2022;7(1):48. doi: 10.1038/s41392-022-00904-4. PMID: 35165272; PMCID: PMC8844085.Al Musaimi O, Lombardi L, Williams DR, Albericio F. Strategies for Improving Peptide Stability and Delivery. Pharmaceuticals (Basel). 2022 Oct 19;15(10):1283. doi: 10.3390/ph15101283. PMID: 36297395; PMCID: PMC9610364.Mukherjee AG, et al. Evolving strategies and application of proteins and peptide therapeutics in cancer treatment. Biomed Pharmacother. 2023 Jul;163:114832. doi: 10.1016/j.biopha.2023.114832.Chinnadurai RK, Khan N, Meghwanshi GK, Ponne S, Althobiti M, Kumar R. Current research status of anti-cancer peptides: Mechanism of action, production, and clinical applications. Biomed Pharmacother. 2023 Aug;164:114996. doi: 10.1016/j.biopha.2023.114996. Epub 2023 Jun 11. PMID: 37311281.Bailey CJ, Flatt PR, Conlon JM. An update on peptide-based therapies for type 2 diabetes and obesity. Peptides. 2023 Mar;161:170939. doi: 10.1016/j.peptides.2023.170939. Epub 2023 Jan 3. PMID: 36608818.Neal D Shore et al. A New Sustained-release, 3-Month Leuprolide Acetate Formulation Achieves and Maintains Castrate Concentrations of Testosterone in Patients With Prostate Cancer. Clin Ther. 2019 Mar;41(3):412-425. doi: 10.1016/j.clinthera.2019.01.004. Epub 2019 Feb 8.Marso SP, Baeres FMM, Bain SC, Goldman B, Husain M, Nauck MA, Poulter NR, Pratley RE, Thomsen AB, Buse JB; LEADER Trial Investigators. Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure. J Am Coll Cardiol. 2020 Mar 17;75(10):1128-1141. doi: 10.1016/j.jacc.2019.12.063. PMID: 32164886.Zhiye Zhang et al. Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition. Immunity. 2015 Dec 15;43(6):1137-1147. doi: 10.1016/j.immuni.2015.10.018. Epub 2015 Dec 8.Chernomordik F, Cercek B, Lio WM, Mihailovic PM, Yano J, Herscovici R, Zhao X, Zhou J, Chyu KY, Shah PK, Dimayuga PC. The Role of T Cells Reactive to the Cathelicidin Antimicrobial Peptide LL-37 in Acute Coronary Syndrome and Plaque Calcification. Front Immunol. 2020 Oct 6;11:575577. doi: 10.3389/fimmu.2020.575577. PMID: 33123157; PMCID: PMC7573569.Othman Al Musaimi, Lucia Lombardi, Daryl R Williams, Fernando Albericio. Strategies for Improving Peptide Stability and Delivery. Pharmaceuticals (Basel). 2022 Oct 19;15(10):1283. doi: 10.3390/ph15101283. PMID: 36297395; PMCID: PMC9610364.Zhang QY, Yan ZB, Meng YM, Hong XY, Shao G, Ma JJ, Cheng XR, Liu J, Kang J, Fu CY. Antimicrobial peptides: mechanism of action, activity and clinical potential. Military Medical Research. 2021;8(1):47. doi: 10.1186/s40779-021-00334-7.Wang G. Human antimicrobial peptides and proteins. Pharmaceuticals (Basel). 2014 May 13;7(5):545-94. doi: 10.3390/ph7050545. PMID: 24828484; PMCID: PMC4035769.Wang G, Li X, Wang Z. APD3: the antimicrobial peptide database as a tool for research and education. Nucleic Acids Res. 2016;44(D1):D1087-1093.Tornesello AL, Borrelli A, Buonaguro L, Buonaguro FM, Tornesello ML. Antimicrobial peptides as anticancer agents: Functional properties and biological activities. Molecules [Internet]. 2020 [citado el 13 de marzo de 2023];25(12):2850. Disponible en: https://www.mdpi.com/1420-3049/25/12/2850.Mookherjee N, Anderson MA, Haagsman HP, Davidson DJ. Péptidos de defensa antimicrobianos del huésped: funciones y potencial clínico. Nat Rev Drug Discov [Internet]. 2020 [citado el 13 de marzo de 2023];19(5):311–32. Disponible en: https://www.nature.com/articles/s41573-019-0058-8.Haney, E. F., & Hancock, R. E. W. (2013). Peptide design for antimicrobial and immunomodulatory applications. Biopolymers, 100(6), 572–583.Malmsten M. Interactions of Antimicrobial Peptides with Bacterial Membranes and Membrane Components. Curr Top Med Chem. 2016;16(1):16-24. doi: 10.2174/1568026615666150703121518. PMID: 26139113.Brogden, K. A. (2005). Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nature Reviews Microbiology, 3(3), 238–250.Porto, W. F., Irazazabal, L., & Alves, E. S. F. (2018). In silico approaches to discover new antimicrobial peptides. Current Opinion in Pharmacology, 43, 1–7.Mansour, S. C., Pena, O. M., & Hancock, R. E. W. (2014). Host defense peptides: front- line immunomodulators. Trends in Immunology, 35(9), 443–450.Zhang Q, Ul Ain Q, Schulz C, Pircher J. Role of antimicrobial peptide cathelicidin in thrombosis and thromboinflammation. Front Immunol [Internet]. 2023;14. Disponible en: http://dx.doi.org/10.3389/fimmu.2023.1151926.Pircher J, Czermak T, Ehrlich A, Eberle C, Gaitzsch E, Margraf A, et al. Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation. Nat Commun [Internet]. 2018 [citado el 18 de noviembre de 2023];9(1):1–15. Disponible en: https://www.nature.com/articles/s41467-018-03925-2.Bei Y, Pan L-L, Zhou Q, Zhao C, Xie Y, Wu C, et al. Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury. BMC Med [Internet]. 2019;17(1). Disponible en: http://dx.doi.org/10.1186/s12916-019-1268-y.Klyachkin YM, Idris A, Rodell CB, Tripathi H, Ye S, Nagareddy P, et al. Cathelicidin related antimicrobial peptide (CRAMP) enhances bone marrow cell retention and attenuates cardiac dysfunction in a mouse model of myocardial infarction. Stem Cell Rev [Internet]. 2018 [citado el 18 de noviembre de 2023];14(5):702–14. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29948752/.Vukic VR, Vukic DV, Milanovic SD, Ilicic MD, Kanuric KG, Johnson MS. In silico identification of milk antihypertensive di- and tripeptides involved in angiotensin I-converting enzyme inhibitory activity. Nutr Res. 2017 Oct;46:22-30. doi: 10.1016/j.nutres.2017.07.009. Epub 2017 Jul 28. PMID: 29173648.Domínguez González KN, Cruz Guerrero AE, Márquez HG, Gómez Ruiz LC, García-Garibay M, Rodríguez Serrano GM. El efecto antihipertensivo de las leches fermentadas. Rev Argent Microbiol [Internet]. 2014 [citado el 19 de noviembre de 2023];46(1):58–65. Disponible en: https://www.elsevier.es/es-revista-revista-argentina-microbiologia-372-articulo-el-efecto- antihipertensivo-leches-fermentadas-S0325754114700501.González P, Lozano P, Ros G, Solano F. Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections. Int J Mol Sci. 2023 May 27;24(11):9352. doi: 10.3390/ijms24119352. PMID: 37298303; PMCID: PMC10253853.Jia L, Li J, Zhang M, Liu H, Ren Z, Dong XL, Pan X, Qiu J, Pan LL, Sun J, et al. Cathelicidin- related antimicrobial peptide protects against enteric pathogen-accelerated type 1 diabetes in mice. Theranostics. 2022;12(10):4771-4791. doi: 10.7150/thno.61433. PMID: 35547774; PMCID: PMC9065195.Pound LD, Patrick C, Eberhard CE, Mottawea W, Wang G-S, Abujamel T, et al. Cathelicidin Antimicrobial Peptide: A Novel Regulator of Islet Function, Islet Regeneration, and Selected Gut Bacteria. Diabetes (2015) 64:4135–47. doi: 10.2337/db15-0788.Sun J, Furio L, Mecheri R, van der Does AM, Lundeberg E, Saveanu L, et al. Pancreatic β- Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed Under the Influence of the Gut Microbiota. Immunity (2015) 43:304–17. doi: 10.1016/j.immuni.2015.07.013.Aloul KM, Nielsen JE, Defensor EB, Lin JS, Fortkort JA, Shamloo M, et al. Upregulating human cathelicidin antimicrobial peptide LL-37 expression may prevent severe COVID-19 inflammatory responses and reduce microthrombosis. Front Immunol [Internet]. 2022 [citado el 18 de noviembre de 2023];13:880961. Disponible en: https://www.frontiersin.org/articles/10.3389/fimmu.2022.880961/full.Soltaninejad, H.; Zare-Zardini, H.; Ordooei, M.; Ghelmani, Y.; Ghadiri-Anari, A.; Mojahedi, S.; Hamidieh, A.A. Antimicrobial Peptides from Amphibian Innate Immune System as Potent Antidiabetic Agents: A Literature Review and Bioinformatics Analysis. J. Diabetes Res. 2021, 2021, e2894722.Zainab, A.J.A.A.; Ashish, N.; Ragnath, V. Salivary Levels of Antimicrobial Peptides in Chronic Periodontitis Patients with Type 2 Diabetes. J. Int. Acad. Periodontol. 2019, 21, 36– 44.Miani M, Le Naour J, Waeckel-Enée E, Verma SC, Straube M, Emond P, Ryffel B, van Endert P, Sokol H, Diana J. Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes. Cell Metab. 2018;28(2):238-252.e8. doi: 10.1016/j.cmet.2018.06.012. PMID: 30017352.Ramadhan AH, Nawas T, Zhang X, Pembe WM, Xia W, Xu Y. Purification and Identification of a Novel Antidiabetic Peptide from Chinese Giant Salamander (Andrias Davidianus) Protein Hydrolysate against α-Amylase and α-Glucosidase. Int J Food Prop. 2017;20(Suppl):S3360- S3372.Musale V, Moffett RC, Owolabi B, Conlon JM, Flatt PR, Abdel-Wahab YHA. Mechanisms of Action of the Antidiabetic Peptide [S4K]CPF-AM1 in Db/Db Mice. J Mol Endocrinol. 2021;66:115-128.Luo J, Zhang H. Bioactive peptides from food for the treatment of diabetes: recent progress and future perspectives. Curr Opin Food Sci. 2023;32:100786.Debarun P, Kumari B, Palla R, Moyna K, Durba P. Anti-cancer drug molecules targeting cancer cell cycle and proliferation. In: Control of Cell Cycle & Cell Proliferation. Elsevier; 2023. p. 343-395.Norouzi P, Mirmohammadi M, Houshdar Tehrani MH. Anticancer peptides mechanisms, simple and complex. Chem Biol Interact. 2022 Dec 1;368:110194. doi: 10.1016/j.cbi.2022.110194. Epub 2022 Oct 1. PMID: 36195187.Jafari A, Babajani A, Sarrami Forooshani R, Yazdani M, Rezaei-Tavirani M. Clinical applications, y efectos anticancerígenos de péptidos antimicrobianos: desde el laboratorio hasta la cabecera del paciente. Front Oncol. 2022;12. Disponible en: http://dx.doi.org/10.3389/fonc.2022.819563Costa F, Teixeira C, Gomes P, Martins MCL. Aplicación clínica de AMP. En: Advances in Experimental Medicine and Biology. Singapur: Springer Singapur; 2019. p. 281-298.Binaymotlagh R, Hajareh Haghighi F, Aboutalebi F, Mirahmadi-Zare SZ, Hadadzadeh H, Nasr-Esfahani M-H. Quimioterapia selectiva e imágenes de células de cáncer de colon y mama mediante un nanocompuesto de Fe3O4–AuNCs recubierto con polietilenglicol- dimetacrilato modificado con aptámero MUC-1. New J Chem. 2019;43(1):238-248. Disponible en: https://pubs.rsc.org/en/content/articlelanding/2019/nj/c8nj04236ePapachristodoulou A, Signorell RD, Werner B, Brambilla D, Luciani P, Cavusoglu M, et al. Sensibilización a la quimioterapia de glioblastoma mediante la entrega mediada por ultrasonidos enfocados de liposomas terapéuticos. J Control Release. 2019;295:130-139. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30537486/Jiang Y, Chen Y, Song Z, Tan Z, Cheng J. Avances recientes en el diseño de péptidos antimicrobianos y polipéptidos para su traducción clínica. Adv Drug Deliv Rev. 2021;170:261- 280. Disponible en: https://www.sciencedirect.com/science/article/pii/S0169409X20302957Botelho Sampaio de Oliveira K, Lopes Leite M, Albuquerque Cunha V, Brito da Cunha N, Luiz Franco O. Desafíos y avances en el desarrollo de péptidos antimicrobianos. Drug Discov Today. 2023;28(8):103629. Disponible en: https://www.sciencedirect.com/science/article/pii/S1359644623001459Rodríguez Guerra JA. Evaluación de la actividad anticancerígena In Vitro de péptidos sintéticos derivados de Lactoferricina Bovina en líneas celulares de cáncer de mama. 2019.Insuasty Cepeda DS. Implementación y optimización de la síntesis de péptidos diméricos derivados de la secuencia LfcinB (20-30) con potencial actividad anticancerígena contra el cáncer de mama. 2023.Guerra JR, Cárdenas AB, Ochoa-Zarzosa A, Meza JL, Umaña Pérez A, Fierro-Medina R, et al. El péptido tetramérico LfcinB (20–25)4 derivado de la lactoferricina bovina induce apoptosis en la línea celular de cáncer de mama MCF-7. RSC Adv. 2019;9(36):20497-20504. Disponible en: http://dx.doi.org/10.1039/c9ra04145aNiemirowicz K, Prokop I, Wilczewska A, Wnorowska U, Piktel E, Wątek M, et al. Nanopartículas magnéticas mejoran la actividad anticancerígena del péptido catelicidina LL- 37 contra células de cáncer de colon. Int J Nanomedicine. 2015 Jun;10:3843. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461127/Arpornsuwan T, Sriwai W, Jaresitthikunchai J, Phaonakrop N, Sritanaudomchai H, Roytrakul S. Actividades anticancerígenas de péptidos antimicrobianos BmKn2 contra células de cáncer oral y de colon. Int J Pept Res Ther. 2014;20(4):501-509. doi: 10.1007/s10989-014- 9417-9Derechos Reservados - Universidad de Santander, 2023. Al consultar y hacer uso de este recurso, está aceptando las condiciones de uso establecidas por los autores.info:eu-repo/semantics/embargoedAccesshttp://purl.org/coar/access_right/c_f1cfAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)https://creativecommons.org/licenses/by-nc-nd/4.0/CatelicidinasDiabetes MellitusEnfermedades CardiovascularesNeoplasiasPéptidos AntimicrobianosAntimicrobial PeptidesCardiovascular DiseasesCatelicidinsDiabetes MellitusNeoplasmsPéptidos Antimicrobianos Para el Tratamiento de Enfermedades Crónicas no Transmisibles: Revisión NarrativaAntimicrobial Peptides for the Treatment of Chronic Non-Communicable Diseases: Narrative ReviewTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/version/c_71e4c1898caa6e32Textinfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/submittedVersionTodas las AudienciasPublicationTEXTActa_de_Sustentación.pdf.txtActa_de_Sustentación.pdf.txtExtracted texttext/plain2https://repositorio.udes.edu.co/bitstreams/de4d8332-9cab-49fd-85eb-d05270ae6175/downloade1c06d85ae7b8b032bef47e42e4c08f9MD513Cesion_de_Derechos.pdf.txtCesion_de_Derechos.pdf.txtExtracted texttext/plain4337https://repositorio.udes.edu.co/bitstreams/06d1499d-5165-4521-bb47-e1106da4e064/download56e20113ee5d7d07aa8630b7d8979155MD515Péptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.docx.txtPéptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.docx.txtExtracted texttext/plain43448https://repositorio.udes.edu.co/bitstreams/2f8b2e4f-8053-4e83-a0f4-322733899b19/download7f8f52654589009839a2751b15ebb6b4MD517Péptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.pdf.txtPéptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.pdf.txtExtracted texttext/plain46235https://repositorio.udes.edu.co/bitstreams/0178e763-aab3-4cd6-843e-24a69be8ca79/downloadb1a364d9caaa0a58c9c265ad16fc38b5MD518Certificado_de_Similitud_de_Texto.pdf.txtCertificado_de_Similitud_de_Texto.pdf.txtExtracted texttext/plain9671https://repositorio.udes.edu.co/bitstreams/6fe44b5f-0876-4405-a432-d91927d75d30/download9f77671cd364eeb69735e59e3f1c1120MD520Carta_de_presentación_Revista_Bionatura.pdf.txtCarta_de_presentación_Revista_Bionatura.pdf.txtExtracted texttext/plain3113https://repositorio.udes.edu.co/bitstreams/7b6decf4-ec1c-4aaa-af1c-baab43666290/download597e37dbfebc703d86b84b3a0c2d042fMD522Label.pdf.txtLabel.pdf.txtExtracted texttext/plain738https://repositorio.udes.edu.co/bitstreams/f1c5ccde-2a5b-4cb8-9835-e747f979c989/downloada68cd0e37c2105323845e56349da7b84MD524THUMBNAILActa_de_Sustentación.pdf.jpgActa_de_Sustentación.pdf.jpgGenerated Thumbnailimage/jpeg10704https://repositorio.udes.edu.co/bitstreams/afb63745-3601-4c0f-a66a-d978f48ae97d/download6a7aeb19d113be77c53b01475598d956MD514Cesion_de_Derechos.pdf.jpgCesion_de_Derechos.pdf.jpgGenerated Thumbnailimage/jpeg14532https://repositorio.udes.edu.co/bitstreams/7feaadb7-65ca-4153-b5da-2b1d2f4c2862/download14cfc3c08502d6101c1c65a4db6e2633MD516Péptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.pdf.jpgPéptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.pdf.jpgGenerated Thumbnailimage/jpeg12534https://repositorio.udes.edu.co/bitstreams/99ff14a5-c941-4c60-8f7a-b39f4b04c300/downloadba03987a9265e66c256fbb579eee1569MD519Certificado_de_Similitud_de_Texto.pdf.jpgCertificado_de_Similitud_de_Texto.pdf.jpgGenerated Thumbnailimage/jpeg9059https://repositorio.udes.edu.co/bitstreams/055b62e1-421f-4897-b0cb-97d6a5990246/download80221bfdda72bc6d4f1ec08cf58d3a50MD521Carta_de_presentación_Revista_Bionatura.pdf.jpgCarta_de_presentación_Revista_Bionatura.pdf.jpgGenerated Thumbnailimage/jpeg13093https://repositorio.udes.edu.co/bitstreams/b3bf04b2-5ef8-439b-b584-8669bc191919/downloadf0ab9c9cea9fd7861c7cfb8ff502e81aMD523Label.pdf.jpgLabel.pdf.jpgGenerated Thumbnailimage/jpeg10317https://repositorio.udes.edu.co/bitstreams/cedfd7a0-cc2a-41b3-99db-3707633c894e/downloade194e213ae76beab3fdaca94c13a35eeMD525ORIGINALActa_de_Sustentación.pdfActa_de_Sustentación.pdfapplication/pdf971310https://repositorio.udes.edu.co/bitstreams/41851921-f63f-4225-a1b6-07371ae070cb/downloadeda81c1be09ae42c9147bf4551e12446MD55Cesion_de_Derechos.pdfCesion_de_Derechos.pdfapplication/pdf346067https://repositorio.udes.edu.co/bitstreams/d73a50e5-199e-4a9c-83bb-ed281ddfe4e1/download75a29c23711fa2b02526b4d2aea81aceMD56Péptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.docxPéptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.docxapplication/vnd.openxmlformats-officedocument.wordprocessingml.document66677https://repositorio.udes.edu.co/bitstreams/e9dc2abc-47cf-45ad-b5ba-161afd953d87/download9eb1ac5f6eecd7015a5571be66166286MD58Péptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.pdfPéptidos_Antimicrobianos_Para_el_Tratamiento_de_Enfermedades_Crónicas_no_Transmisibles.pdfapplication/pdf237836https://repositorio.udes.edu.co/bitstreams/4f32506e-7b86-4c8a-891c-426adb0beeb6/download1dae08e4a6e5c3dccf30342cad6a6406MD59Certificado_de_Similitud_de_Texto.pdfCertificado_de_Similitud_de_Texto.pdfapplication/pdf139941https://repositorio.udes.edu.co/bitstreams/dcca543f-adbd-4321-a2ff-510fc3121064/downloadd6ee58062d2e61651d6f2578710314efMD510Carta_de_presentación_Revista_Bionatura.pdfCarta_de_presentación_Revista_Bionatura.pdfapplication/pdf45903https://repositorio.udes.edu.co/bitstreams/7a0dac73-d6fb-4466-a1e7-988e7ec4f681/downloadcb0bcc5208a9d5e740c74f5116e1bfe8MD511Label.pdfLabel.pdfapplication/pdf3221341https://repositorio.udes.edu.co/bitstreams/47490564-3dde-417d-8c70-92205c2d54d0/download8e4188f9a40ec35c6cfea4a3c79296afMD512LICENSElicense.txtlicense.txttext/plain; charset=utf-815543https://repositorio.udes.edu.co/bitstreams/5cb13088-9741-4f8f-96fc-b28e4d394f5a/download73a5432e0b76442b22b026844140d683MD54001/10456oai:repositorio.udes.edu.co:001/104562024-05-30 03:01:12.027https://creativecommons.org/licenses/by-nc-nd/4.0/Derechos Reservados - Universidad de Santander, 2023. Al consultar y hacer uso de este recurso, está aceptando las condiciones de uso establecidas por los autores.https://repositorio.udes.edu.coRepositorio Universidad de Santandersoporte@metabiblioteca.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 |