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El potencial terapéutico y anti inflamatorio del Genipin en un modelo de infección corneal

dc.rights.licenseAtribución-NoComercial-SinDerivadas 4.0 Internacional
dc.contributor.advisorÁvila Castañeda, Marcel Yecid
dc.contributor.advisorKoudouna, Elena
dc.contributor.authorHuertas Bello, Marcela
dc.date.accessioned2021-02-22T17:46:55Z
dc.date.available2021-02-22T17:46:55Z
dc.date.issued2021-02-16
dc.identifier.citationMarcela Huertas-Bello, Cristian N Rodriguez, Sandra C Henao, Myriam L Navarrete, Marcel Y Avila, Elena Koudouna, “El potencial terapéutico y antiinflamatorio del Genipin en un modelo de infección corneal”
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/79278
dc.description.abstractPropósito: Investigar la efectividad de la reticulación de colágeno corneal con Genipin (GEN) para el tratamiento de la queratitis bacteriana, en un modelo de infección corneal ex vivo con córneas porcinas. Métodos: Se descontaminaron parejas de botones corneales y posteriormente se infectaron con Staphylococcus aureus (ATCC 25923) o Pseudomonas aeruginosa (ATCC 27853) según el grupo. Treinta minutos después de la inoculación bacteriana; un ojo se trató con solución salina y el ojo contralateral se trató con GEN (n = 6 pares para cada microorganismo). También se realizó un control de esterilidad con corneas no expuestas a bacterias. Después de 24 h de incubación, la mitad de cada córnea se homogenizo y la se realizaron diluciones seriadas de la suspensión resultante, posteriormente se sembraron en placas de agar para recuento de unidades formadoras de colonias (UFC) / córnea. La otra mitad de cada cornea se sometió a examen histológico. Resultados: Macroscópicamente las corneas infectadas tratadas con Solución Salina (SSN) mostraron más turbidez y ulceración corneal versus las tratadas con GEN. Histológicamente, las tinciones de H-E y Gram confirmaron una infiltración bacteriana extensa en toda la córnea. El número de UFC disminuyó significativamente en las córneas tratadas con GEN vs las tratadas con SSN (p <0,05). Las córneas de control de esterilidad no evidenciaron ninguna infección. Conclusiones: El entrecruzamiento corneal con GEN podría servir como una opción terapéutica novedosa para el tratamiento de la queratitis bacteriana. Se necesitan más estudios para esclarecer la actividad antibacteriana y el mecanismo de acción de GEN. Palabras clave: crosslinking, queratitis infecciosa, queratitis bacteriana, infección corneal por Staphylococcus aureus, infección corneal por Pseudomonas aeruginosa, Genipin, modelo de infección corneal ex vivo.
dc.description.abstractPurpose: To investigate the effectiveness of corneal collagen crosslinking with Genipin (GEN) for the treatment of bacterial keratitis, in an ex vivo corneal infection model with porcine corneas. Methods: Previously decontaminated pairs of corneal buttons were infected with Staphylococcus aureus (ATCC 25923) or Pseudomonas aeruginosa (ATCC 27853). Thirty minutes after bacterial inoculation; one eye was treated with saline solution and the contralateral eye was treated with GEN (n = 6 pairs for each microorganism). A sterility control was also carried out. After 24 h of incubation, half of each cornea was homogenized and serial dilutions of the resulting suspension were made, later they were seeded on agar plates for the count of colony forming units (CFU) / cornea. The other half of each cornea underwent histological examination. Results: Macroscopically, infected corneas treated with Saline Solution (SSN) showed more turbidity and corneal ulceration versus corneas with GEN treatment. Histologically, H&E and Gram stains confirmed extensive bacterial infiltration throughout the cornea. The number of CFUs decreased significantly in corneas treated with GEN vs those treated with SSN (p <0.05). The sterility control corneas did not show any infection. Conclusions: Corneal crosslinking with GEN could serve as a novel therapeutic option for the treatment of bacterial keratitis. More studies are needed to clarify the antibacterial activity and mechanism of action of GEN. Keywords: corneal crosslinking, infectious keratitis, bacterial keratitis, Staphylococcus aureus corneal infection, Pseudomonas aeruginosa corneal infection, Genipin, Keratitis ex vivo animal model.
dc.description.sponsorshipGRANT 793328 MARIE CURIE
dc.format.extent1 recurso electrónico (46 páginas)
dc.format.mimetypeapplication/pdf
dc.language.isospa
dc.relationhttps://iovs.arvojournals.org/article.aspx?articleid=2766522
dc.rightsDerechos reservados - Universidad Nacional de Colombia
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleEl potencial terapéutico y anti inflamatorio del Genipin en un modelo de infección corneal
dc.typeOtro
dc.rights.spaAcceso abierto
dc.description.projectEl potencial terapéutico y anti inflamatorio del Genipin en un modelo de infección corneal
dc.description.additionalLínea de Investigación: Ciencias Básicas en Oftalmología
dc.type.driverinfo:eu-repo/semantics/other
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.publisher.programBogotá - Medicina - Especialidad en Oftalmología
dc.description.degreelevelEspecialidades Médicas
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
dc.relation.references1. Marquart, M. E., & O'Callaghan, R. J. Infectious keratitis: secreted bacterial proteins that mediate corneal damage. J. Ophthalmol. 2013, 369094 (2013).
dc.relation.references2. Ezisi, C. N., et al. Microbial Keratitis—A Review of Epidemiology, Pathogenesis, Ocular Manifestations, and Management. Nig. J. Ophthalmol. 26, 13-23 (2018).
dc.relation.references3. Whitcher, J.P., Srinivasan. M. & Upadhyay, M.P. Corneal blindness: a global perspective. Bull World Health Organ. 79, 214-221 (2001).
dc.relation.references4.Green M, Apel A & Stapleton F. Risk factors and causative organisms in microbial keratitis. Cornea. 27, 22-27 (2008).
dc.relation.references5. Bartimote, C., Foster, J. & Watson, S. The spectrum of microbial keratitis: An updated review. Open Ophthalmol. J. 13, 100-130 (2019).
dc.relation.references6. Lakhundi, S., Siddiqui, R. & Khan, N. A. Pathogenesis of microbial keratitis. Microbial Pathogenesis 104, 97–109 (2017).
dc.relation.references7. Sagerfors, S., Ejdervik-Lindblad, B., & Söderquist, B. Infectious keratitis: isolated microbes and their antibiotic susceptibility pattern during 2004-2014 in Region Örebro County, Sweden. Acta ophthalmol, 98, 255–260 (2020).
dc.relation.references8. Khor, W. B. et al. The Asia Cornea Society Infectious Keratitis Study: A Prospective Multicenter Study of Infectious Keratitis in Asia. Am. J. Ophthalmol. 195, 161–170 (2018).
dc.relation.references9. Wynants, S., Koppen, C. & Tassignon, M.J. Spontaneous corneal perforation and endophthalmitis in Pseudomonas aeruginosa infection in a ventilated patient: a case report. Bull. Soc. belge Ophtalmol. 276, 53-56, (2000).
dc.relation.references10. Al-Mujaini, A., Al-Kharusi, N., Thakral, A., & Wali, U. K. Bacterial keratitis: perspective on epidemiology, clinico-pathogenesis, diagnosis and treatment. Sultan Qaboos Univ. Med. J. 9, 184–195 (2009).
dc.relation.references11. Gupta, N., Tandon, R., Gupta, S.K, Sreenivas, V. & Vashist P. Burden of corneal blindness in India. Indian J Community Med. 38,198-206 (2013).
dc.relation.references12. Ung, L., Bispo, P.J.M., Shanbhag, S.S., Gilmore, M.S. & Chodosh, J. The persistent dilemma of microbial keratitis: Global burden, diagnosis, and antimicrobial resistance. Surv Ophthalmol. 64, 255-271 (2019).
dc.relation.references13. Lalitha, P., et al. Trends in antibiotic resistance in bacterial keratitis isolates from South India. Br J Ophthalmol. 101, 108-113 (2017).
dc.relation.references14. Alanis, A.J. Resistance to antibiotics: are we in the post-antibiotic era? Arch Med Res. 36, 697-705 (2005).
dc.relation.references15. Cabrera-Aguas, M., Khoo, P., George, C. R. R., Lahra, M. M. & Watson, S. L. Antimicrobial resistance trends in bacterial keratitis over 5 years in Sydney, Australia. Clin. Exp. Ophthalmol. 48, 183–191 (2020).
dc.relation.references16. Galvis, V, Parra, M. M, Tello, A, Castellanos, Y. A, Camacho, P. A, Villarreal, D, Salcedo, S. L.L. Antibiotic resistance profile in eye infections in a reference centre in Floridablanca, Colombia. Archivos de la Sociedad Espanola de Oftalmología.,8, (2018)
dc.relation.references17. Zhang, Q., et al. Outcomes of therapeutic keratoplasty for severe infectious keratitis in Chongqing, a 16-year experience. Infect. Drug Resist. 12, 2487–2493 (2019).
dc.relation.references18. Tew, T.B., et al. Therapeutic penetrating keratoplasty for microbial keratitis in Taiwan from 2001 to 2014. J. Formos Med. Assoc. 119, 1061-1069 (2020).
dc.relation.references19. Fasolo, A., et al. Risk factors for graft failure after penetrating keratoplasty: 5-year follow-up from the corneal transplant epidemiological study. Cornea. 30, 1328-1335 (2011).
dc.relation.references20. Tabibian, D., Richoz, O. & Hafezi, F. PACK-CXL: Corneal cross-linking for treatment of infectious keratitis. J. Ophthalmic Vis Res. 10, 77–80 (2015).
dc.relation.references21. Iseli, H.P., Thiel, M.A., Hafezi, F., Kampmeier, J. & Seiler, T. Ultraviolet A/riboflavin corneal cross-linking for infectious keratitis associated with corneal melts. Cornea. 27, 590-594 (2008).
dc.relation.references22. Garg, P., Das, S. & Roy, A. Collagen Cross-linking for Microbial Keratitis. Middle East African J. Ophthalmol. 24, 18-23 (2017).
dc.relation.references23. Shetty, R., Nagaraja, H., Jayadev, C., Shivanna, Y. & Kugar, T. Collagen crosslinking in the management of advanced non-resolving microbial keratitis. Br J Ophthalmol. 98, 1033-1035 (2014).
dc.relation.references24. Panda, A., Krishna, S.N. & Kumar. S. Photo-activated riboflavin therapy of refractory corneal ulcers. Cornea. 31, 1210-1213 (2012).
dc.relation.references25. Zloto, O., et al. Does PACK-CXL change the prognosis of resistant infectious keratitis? J. Refract. Surg. 34, 559-563 (2018).
dc.relation.references26. Spoerl, E., Wollensak, G. & Seiler, T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr. Eye Res. 29, 35–40 (2004).
dc.relation.references27. Martins, S. A. R. et al. Antimicrobial efficacy of riboflavin/UVA combination (365 nm) in vitro for bacterial and fungal isolates: A potential new treatment for infectious keratitis. Invest Ophthalmol Vis Sci. 49, 3402–3408 (2008).
dc.relation.references28. Makdoumi, K., Bäckman, A., Mortensen, J. & Crafoord, S. Evaluation of antibacterial efficacy of photo-activated riboflavin using ultraviolet light (UVA). Graefes Arch Clin Exp Ophthalmol. 248, 207-212 (2010).
dc.relation.references29. Kumar, V., et al. Riboflavin and UV‐Light Based Pathogen Reduction: Extent and Consequence of DNA Damage at the Molecular Level. Photochem Photobiol. 80, 15-21 (2004).
dc.relation.references30. Ting, D.S.J., Henein, C., Said, D. G. & Dua, H. S. The Ocular Surface Photoactivated chromophore for infectious keratitis – Corneal cross-linking (PACK-CXL): A systematic review and meta-analysis. Ocul. Surf. 17, 624–634 (2019).
dc.relation.references31. Papaioannou L, Miligkos M, Papathanassiou M. Corneal Collagen Cross-Linking for Infectious Keratitis: A Systematic Review and Meta-Analysis. Cornea. 35, 62-71 (2016).
dc.relation.references32. Davis, S.A., Bovelle, R., Han, G. & Kwagyan, J. Corneal collagen cross-linking for bacterial infectious keratitis. Cochrane Database Syst Rev. 6, CD013001 (2020).
dc.relation.references33. Makdoumi, K., Mortensen, J. & Crafoord, S. Infectious keratitis treated with corneal crosslinking. Cornea. 29, 1353-1358 (2010).
dc.relation.references34. Tabibian, D., Mazzotta, C. & Hafezi, F. PACK-CXL: Corneal cross-linking in infectious keratitis. Eye and Vis. 3, 11 (2016).
dc.relation.references35. Gokhale, N.S. Corneal endothelial damage after collagen cross-linking treatment. Cornea. 30, 1495–1498 (2011).
dc.relation.references36. Raiskup, F.M.D.P.F., Hoyer, A.M.D. & Spoerl, E.P. Permanent corneal haze after riboflavin-UVA-induced cross-linking in keratoconus. J Refract Surg.25, S824–S828 (2009).
dc.relation.references37. Wollensak, G., Spoerl, E., Wilsch, M. & Seiler T. Endothelial cell damage after riboflavin–ultraviolet-A treatment in the rabbit. J Cataract Refract Surg.29, 1786–1790 (2003).
dc.relation.references38. Moore, J.E., Schiroli, D. & Moore, C.B. Potential Effects of Corneal Cross-Linking upon the Limbus. Biomed Res Intern. 2016:5062064 (2016).
dc.relation.references39. Seiler, T. & Hafezi, F. Corneal cross-linking-induced stromal demarcation line. Cornea. 25, 1057-1059 (2006).
dc.relation.references40. Sung, H. W., Chang, W. H., Ma, C. Y. & Lee, M. H. Crosslinking of biological tissues using genipin and/or carbodiimide. J Biomed Mater Res A. 64, 427–438 (2003).
dc.relation.references41. Daniel, M., K., N. K. & Myron, S. Injectable Collagen–Genipin Gel for the Treatment of Spinal Cord Injury: In Vitro Studies. Adv Funct Mater. 21, 4788–4797 (2011).
dc.relation.references42. Yan, L. P. et al. Genipin-cross-linked collagen/chitosan biomimetic scaffolds for articular cartilage tissue engineering applications. J Biomed Mater Res A. 95, 465–475 (2010).
dc.relation.references43. Výborný, K., et al. Genipin and EDC crosslinking of extracellular matrix hydrogel derived from human umbilical cord for neural tissue repair. Sci Rep. 9, 10674 (2019).
dc.relation.references44. Song, W. et al. The comparative safety of genipin versus UVA-riboflavin crosslinking of rabbit corneas. Mol Vis. 23, 504–513 (2017).
dc.relation.references45. Song, W., et al. The Short-Term Safety Evaluation of Corneal Crosslinking Agent Genipin. Ophthalmic Res, 62, 141–149 (2019).
dc.relation.references46. Tang, Y. et al. A study of corneal structure and biomechanical properties after collagen crosslinking with genipin in rabbit corneas. Mol Vis. 25, 574–582 (2019).
dc.relation.references47. Avila, M. Y., Narvaez, M. & Castañeda, J. P. Effects of genipin corneal crosslinking in rabbit corneas. J Cataract Refract Surg. 42, 1073–1077 (2016).
dc.relation.references48. Avila, M. Y. & Navia, J. L. Effect of genipin collagen crosslinking on porcine corneas. J Cataract Refract Surg 36, 659-664 (2010).
dc.relation.references49. Avila, M. Y., Gerena, V. A., & Navia, J. L. Corneal crosslinking with genipin, comparison with UV-riboflavin in ex-vivo model. Mol Vis. 18, 1068–1073 (2012).
dc.relation.references50. Wang, Y., et al. Genipin crosslinking reduced the immunogenicity of xenogeneic decellularized porcine whole-liver matrices through regulation of immune cell proliferation and polarization. Sci Rep. 6, 24779 (2016).
dc.relation.references51. Wang, J., et al. Genipin Inhibits LPS-Induced Inflammatory Response in BV2 Microglial Cells. Neurochem Res. 42, 2769-2776 (2017).
dc.relation.references52. Nam, K.N., et al. Genipin inhibits the inflammatory response of rat brain microglial cells. Int Immunopharmacol. 10, 493-499 (2010).
dc.relation.references53. Li, Z., et al. Genipin attenuates dextran sulfate sodium-induced colitis via suppressing inflammatory and oxidative responses. Inflammopharmacology. 28, 333-339 (2020).
dc.relation.references54. Koo, H.J., et al. Antiinflammatory effects of genipin, an active principle of gardenia. Eur J Pharmacol. 495, 201-208 (2004).
dc.relation.references55. Yu, S., et al. Genipin inhibits NLRP3 and NLRC4 inflammasome activation via autophagy suppression. Sci Rep 5, 17935 (2016).
dc.relation.references56. Liu, J., Yin, F., Zheng, X., Jing, J. & Hu, Y. Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway. Neurochem. Int. 51,361-369 (2007).
dc.relation.references57. Zhao, H., Wang, R., Ye, M., & Zhang, L. Genipin protects against H2O2-induced oxidative damage in retinal pigment epithelial cells by promoting Nrf2 signaling. Int J Mol Med. 43, 936-944 (2019).
dc.relation.references58. Khan, A., et al. Genipin cross-linked antimicrobial nanocomposite films and gamma irradiation to prevent the surface growth of bacteria in fresh meats. Inno Food Sci Emerg. 35, 96-102 (2016).
dc.relation.references59. Espana, E.M., Birk, D.E., Composition, structure and function of the corneal stroma, Experimental Eye Research (2020).
dc.relation.references60. Yam, G.H.F., Riau, A.K., Funderburgh, M.L., Mehta, J.S., Jhanji, V., Keratocyte biology, Experimental Eye Research (2020).
dc.relation.references61. Trattler WB, Majmudar PA, Luchs JI, Swartz TS, eds. Cornea Handbook (pp. 13-22), SLACK (2010).
dc.relation.references62. Lin, Amy, Rhee, Michelle K, Akpek, Esen K, Amescua, Guillermo, Farid, Marjan, Garcia-Ferrer, Francisco J, Varu, Divya M, Musch, David C, Dunn, Steven P, Mah, Francis S. Bacterial Keratitis Preferred Practice Pattern®. Ophthalmology, 1-55 (2019)
dc.relation.references63. Amescua, G., Arboleda, A., Nikpoor, N., Durkee, H., Relhan, N., Aguilar, M.C., Flynn, H.W., Miller, D., Parel, J.M. Rose Bengal Photodynamic Antimicrobial Therapy: A Novel Treatment for Resistant Fusarium Keratitis. Cornea. 36, 1141-1144 (2017)
dc.relation.references64. Naranjo, A., Arboleda, A., Martinez, J.D., Durkee, H., Aguilar, M.C., Relhan, N., Nikpoor, N., Galor, A., Dubovy, S.R., Leblanc, R., Flynn, H.W. Jr, Miller, D., Parel, J.M., Amescua, G. Rose Bengal Photodynamic Antimicrobial Therapy for Patients With Progressive Infectious Keratitis: A Pilot Clinical Study. Am J Ophthalmol. 208, 387-396 (2019)
dc.relation.references65. Cherfan, D., Verter, E.E., Melki, S., Gisel, T.E., Doyle, F.J. Jr, Scarcelli, G., Yun, S.H., Redmond, R.W., Kochevar, I.E. Collagen cross-linking using rose bengal and green light to increase corneal stiffness. Invest Ophthalmol Vis Sci.13, 54, 3426-33 (2013)
dc.relation.references66. Hannon, B.G., et al. Sustained scleral stiffening in rats after a single genipin treatment. J R Soc Interface. 16, 20190427 (2019).
dc.relation.references67. Levy, A. M., Fazio, M. A., & Grytz, R. Experimental myopia increases and scleral crosslinking using genipin inhibits cyclic softening in the tree shrew sclera. Ophthalmic Physiol Opt. 38, 246–256 (2018).
dc.relation.references68. Wong, F.F., Lari, D.R., Schultz, D.S. & Stewart, J.M. Whole globe inflation testing of exogenously crosslinked sclera using genipin and methylglyoxal. Exp Eye Res. 103, 17-21 (2012).
dc.relation.references69. Liu, T. X., Luo, X., Gu, Y. W., Yang, B., & Wang, Z. Correlation of discoloration and biomechanical properties in porcine sclera induced by genipin. Int. J. Ophthalmol, 7, 621–62 (2014).
dc.relation.references70. Liu, T. X., & Wang, Z. Biomechanics of sclera crosslinked using genipin in rabbit. Int. J. Ophthalmol 10, 355–360 (2017).
dc.relation.references71. Li, Z., et al. Genipin attenuates dextran sulfate sodium-induced colitis via suppressing inflammatory and oxidative responses. Inflammopharmacology. 28, 333-339 (2020).
dc.relation.references72. Del Gaudio C, Baiguera S, Boieri M, et al. Induction of angiogenesis using VEGF releasing genipin-crosslinked electrospun gelatin mats. Biomaterials. 34, 7754-7765 (2013).
dc.relation.references73. Hong, M., Lee, S., Clayton, J., Yake, W., & Li, J. Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3. J Exp Clin Cancer Res. 39, 146 (2020).
dc.relation.references74. Wang, N., et al. Up-regulation of TIMP-1 by genipin inhibits MMP-2 activities and suppresses the metastatic potential of human hepatocellular carcinoma. PloS one, 7, e46318 (2020).
dc.relation.references75. Sandeepani K Subasinghe, Kelechi C Ogbuehi, Logan Mitchell, George J Dias, Animal model with structural similarity to human corneal collagen fibrillar arrangement. Anatomical Science International volume 286-293 (2021)
dc.relation.references76. Pinnock, A., et al. Ex vivo rabbit and human corneas as models for bacterial and fungal keratitis. Graefes Arch Clin Exp Ophthalmol. 255, 333–342 (2017).
dc.relation.references77. Tripathi N, Sapra A. Gram Staining. [Updated 2020 Aug 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562156/.
dc.relation.references78. Wiegand, I., Hilpert, K. & Hancock, R. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3, 163–175 (2008).
dc.relation.references79. Ackland, P. The accomplishments of the global initiative VISION 2020: The Right to Sight and the focus for the next 8 years of the campaign. Indian J Ophthalmol. 60, 380-386 (2012).
dc.relation.references80. 89. Veeresham, C. Natural products derived from plants as a source of drugs. J Adv Pharm Technol Res. 3, 200–201 (2012).
dc.relation.references81. Yu, H., et al. Antimicrobial activity and mechanism of action of Dracocephalum moldavica L. extracts against clinical isolates of Staphylococcus aureus. Front Microbiol. 10, 1249 (2019).
dc.relation.references82. Radji, M., Agustama, R. A., Elya, B., & Tjampakasari, C. R. Antimicrobial activity of green tea extract against isolates of methicillin-resistant Staphylococcus aureus and multi-drug resistant Pseudomonas aeruginosa. Asian Pac J Trop Biomed. 3, 663–666 (2013).
dc.relation.references83. Finberg, R.W., et al. The importance of bactericidal drugs: future directions in infectious disease. Clin Infect Dis. 39, 1314-1320 (2004).
dc.relation.references84. Manickam, B., Sreedharan, R. & Elumalai, M. 'Genipin' - the natural water soluble cross-linking agent and its importance in the modified drug delivery systems: an overview. Curr Drug Deliv. 11, 139-145 (2014).
dc.relation.references85. Yoo, J. S., Kim, Y. J., Kim, S. H., & Choi, S. H. Study on genipin: a new alternative natural crosslinking agent for fixing heterograft tissue. Korean J Thorac Cardiovasc Surg. 44, 197-207 (2011).
dc.relation.references86. Silhavy, T. J., Kahne, D., & Walker, S. The bacterial cell envelope. Cold Spring Harb Perspect Biol. 2, a000414 (2010).
dc.relation.references87. Malanovic, N., & Lohner, K. Antimicrobial Peptides Targeting Gram-Positive Bacteria. Pharmaceuticals. 9, 59 (2016).
dc.relation.references88. Malanovic, N. & Lohner K. Gram-positive bacterial cell envelopes: The impact on the activity of antimicrobial peptides. Biochim Biophys Acta. 1858, 936-946 (2016).
dc.relation.references89. Chang, C.H, et al. The Suppressive Effects of Geniposide and Genipin on Helicobacter pylori Infections In Vitro and In Vivo. J Food Sci. 82, 3021-3028 (2017).
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.subject.proposalCrosslinking
dc.subject.proposalCorneal crosslinking
dc.subject.proposalInfectious keratitis
dc.subject.proposalQueratitis infecciosa
dc.subject.proposalQueratitis bacteriana
dc.subject.proposalBacterial keratitis
dc.subject.proposalInfección corneal por Staphylococcus aureus
dc.subject.proposalStaphylococcus aureus
dc.subject.proposalPseudomonas aeruginosa
dc.subject.proposalInfección corneal por Pseudomonas aeruginosa
dc.subject.proposalGenipin
dc.subject.proposalGenipin
dc.subject.proposalKeratitis ex vivo animal model
dc.subject.proposalModelo de infección corneal ex vivo
dc.type.coarhttp://purl.org/coar/resource_type/c_1843
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
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