Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progression

Autores:
León Gabriel Gómez-Archila
Martina Palomino-Schätzlein
Wildeman Zapata-Builes
Maria T. Rugeles
Elkin Galeano
Tipo de recurso:
Article of journal
Fecha de publicación:
2023
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
eng
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/57153
Acceso en línea:
https://hdl.handle.net/20.500.12494/57153
Palabra clave:
NMR
metabolomics
HIV-1
biomarkers
pathways
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/4.0/
id COOPER2_8fb3dab74b1de07c9e580facf6282517
oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/57153
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.none.fl_str_mv Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progression
title Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progression
spellingShingle Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progression
NMR
metabolomics
HIV-1
biomarkers
pathways
title_short Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progression
title_full Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progression
title_fullStr Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progression
title_full_unstemmed Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progression
title_sort Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progression
dc.creator.fl_str_mv León Gabriel Gómez-Archila
Martina Palomino-Schätzlein
Wildeman Zapata-Builes
Maria T. Rugeles
Elkin Galeano
dc.contributor.author.none.fl_str_mv León Gabriel Gómez-Archila
Martina Palomino-Schätzlein
Wildeman Zapata-Builes
Maria T. Rugeles
Elkin Galeano
dc.contributor.corporatename.none.fl_str_mv Universidad Cooperativa de Colombia
Universidad de Antioquia
dc.contributor.researchgroup.none.fl_str_mv INFETTARE
dc.subject.proposal.none.fl_str_mv NMR
metabolomics
HIV-1
biomarkers
pathways
topic NMR
metabolomics
HIV-1
biomarkers
pathways
publishDate 2023
dc.date.issued.none.fl_str_mv 2023-06-29
dc.date.accessioned.none.fl_str_mv 2024-09-27T18:24:14Z
dc.date.available.none.fl_str_mv 2024-09-27T18:24:14Z
dc.type.none.fl_str_mv Artículo de revista
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.coarversion.none.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.content.none.fl_str_mv Text
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.redcol.none.fl_str_mv http://purl.org/redcol/resource_type/ART
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_6501
status_str publishedVersion
dc.identifier.issn.none.fl_str_mv 2296-889X
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/57153
dc.identifier.doi.none.fl_str_mv 10.3389/fmolb.2023.1204273
dc.identifier.eissn.none.fl_str_mv 2296-889X
identifier_str_mv 2296-889X
10.3389/fmolb.2023.1204273
url https://hdl.handle.net/20.500.12494/57153
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.citationendpage.none.fl_str_mv 17
dc.relation.citationissue.none.fl_str_mv 1204273
dc.relation.citationstartpage.none.fl_str_mv 01
dc.relation.citationvolume.none.fl_str_mv 10
dc.relation.ispartofjournal.none.fl_str_mv Front. Mol. Biosci.
dc.relation.references.none.fl_str_mv Aguilar-Jiménez, W., Zapata, W., Caruz, A., and Rugeles, M. T. (2013). High transcript levels of vitamin D receptor are correlated with higher mRNA expression of human beta defensins and IL-10 in mucosa of HIV-1-Exposed seronegative individuals. PLoS One [Internet 8 (12), e82717. Available from. doi:10.1371/journal. pone.0082717
Aldunate, M., Tyssen, D., Johnson, A., Zakir, T., Sonza, S., Moench, T., et al. (2013). Vaginal concentrations of lactic acid potently inactivate HIV. J. Antimicrob. Chemother. [Internet] 68 (9), 2015–2025. –25. Available from. doi:10.1093/jac/dkt156
Alves, C. R. R., Ferreira, J. C., de Siqueira-Filho, M. A., Carvalho, C. R., Lancha, A. H., and Gualano, B. Creatine-induced glucose uptake in type 2 diabetes: A role for AMPK- α? Amino acids Amino Acids, [Internet]. 2012;43(4):1803–1807. doi:10.1007/s00726- 012-1246-6
Arnold, K. B., Burgener, A., Birse, K., Romas, L., Dunphy, L. J., Shahabi, K., et al. (2016). Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol. 9 (1), 194–205. doi:10.1038/mi. 2015.51
Baker, B. M., Block, B. L., Rothchild, A. C., and Walker, B. D. (2009). Elite control of HIV infection: implications for vaccine design. Expert Opin. Biol. Ther. 9 (1), 55–69. doi:10.1517/14712590802571928
Balmer, M. L.,Ma, E. H., Bantug, G. R., Grählert, J., Pfister, S., Glatter, T., et al. (2016). Memory CD8(+) T cells require increased concentrations of acetate induced by stress for optimal function. Immunity 44 (6), 1312–1324. doi:10.1016/j.immuni.2016.03.016
Barré-Sinoussi, F., Chermann, J. C., Rey, F., Nugeyre, M. T., Chamaret, S., Gruest, J., et al. (1983). Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220 (4599), 868–871. doi:10.1126/ science.6189183
Behl, C., Widmann, M., Trapp, T., and Holsboer, F. (1995). 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem. Biophys. Res. Commun. 216 (2), 473–482. doi:10.1006/bbrc.1995.2647
Bertini, I., Cacciatore, S., Jensen, B. V., Schou, J. V., Johansen, J. S., Kruhøffer,M., et al. (2012). Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer. Cancer Res. 72 (1), 356–364. Available at:. doi:10. 1158/0008-5472.CAN-11-1543
Bertran-Cobo, C., Wedderburn, C. J., Robertson, F. C., Subramoney, S., Narr, K. L., Joshi, S. H., et al. (2022), A neurometabolic pattern of elevated myo-inositol in children who are HIV-exposed and uninfected: A South African birth cohort study Front. Immunol, [Internet]. Vol. 13, 800273, doi:10.3389/fimmu.2022.800273
Bose, S., Ramesh, V., and Locasale, J. W. Acetate metabolism in physiology, cancer, and beyond. Trends Cell Biol. [Internet]. 2019;29(9):695–703. doi:10.1016/j.tcb.2019. 05.005
Brass, A. L., Dykxhoorn, D. M., Benita, Y., Yan, N., Engelman, A., Xavier, R. J., et al. (2008). Identification of host proteins required for HIV infection through a functional genomic screen. Science 319 (5865), 921–926. doi:10.1126/science.1152725
Brenchley, J. M., Price, D. A., and Douek, D. C. (2006). HIV disease: Fallout from a mucosal catastrophe? Nat. Immunol. 7 (3), 235–239. doi:10.1038/ni1316
Brennan, E., Kantharidis, P., Cooper, M. E., and Godson, C. (2021). Pro-resolving lipid mediators: Regulators of inflammation, metabolism and kidney function. Nat. Rev. Nephrol. [Internet] 17 (11), 725–739. Available from. doi:10.1038/s41581-021-00454-y
Cao, Y., Qin, L., Zhang, L., Safrit, J., and Ho, D. D. (1995). Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N. Engl. J. Med. 332 (4), 201–208. doi:10.1056/ NEJM199501263320401
Cassol, E., Misra, V., Holman, A., Kamat, A., Morgello, S., and Gabuzda, D. (2013). Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors. BMC Infect. Dis. 13, 203. doi:10.1186/1471-2334-13-203
Chang, L., Lee, P. L., Yiannoutsos, C. T., Ernst, T., Marra, C. M., Richards, T., et al. (2004). A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age. Neuroimage 23 (4), 1336–1347. doi:10.1016/j.neuroimage.2004. 07.067
Che, X., He, F., Deng, Y., Xu, S., Fan, X., Gu, P., et al. (2014). HIV-1 Tat-mediated apoptosis in human blood-retinal barrier-associated cells. PLoS One 9 (4), e95420. doi:10.1371/journal.pone.0095420
Cheng, D-C., Zhong, G-C., Su, J-X., Liu, Y-H., Li, Y., Wang, J-Y., et al. (2010). A sensitive HIV-1 envelope induced fusion assay identifies fusion enhancement of thrombin. Biochem. Biophys. Res. Commun. 391 (4), 1780–1784. doi:10.1016/j.bbrc. 2009.12.155
Cohen, R. A., Harezlak, J., Gongvatana, A., Buchthal, S., Schifitto, G., Clark, U., et al. (2010). Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes. J. Neurovirol 16 (6), 435–444. doi:10.3109/13550284.2010.520817
dc.rights.uri.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.accessrights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.creativecommons.en.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.coar.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
Attribution-NonCommercial-NoDerivatives 4.0 International
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia.
dc.publisher.place.none.fl_str_mv Externo
publisher.none.fl_str_mv Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia.
dc.source.none.fl_str_mv https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1204273/full
institution Universidad Cooperativa de Colombia
bitstream.url.fl_str_mv https://repository.ucc.edu.co/bitstreams/9a81274a-8e92-446e-9954-5324124e490c/download
https://repository.ucc.edu.co/bitstreams/1bcd9a96-50af-4d86-a789-1bbab409327e/download
https://repository.ucc.edu.co/bitstreams/100a1306-318e-4194-a171-e44f8d143474/download
https://repository.ucc.edu.co/bitstreams/242d6272-f626-48bc-9dfd-dc0a63702393/download
https://repository.ucc.edu.co/bitstreams/65313914-1d0b-4bb8-920b-743b8a6291f1/download
bitstream.checksum.fl_str_mv 4460e5956bc1d1639be9ae6146a50347
3bce4f7ab09dfc588f126e1e36e98a45
9c712c43c0bb606f88d1ad07ddab867b
e0075f7685a20ebdde9c449e9621cd2f
3b5bbf5f9f88fff8fbd52c202c07846a
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad Cooperativa de Colombia
repository.mail.fl_str_mv bdigital@metabiblioteca.com
_version_ 1814246525193158656
spelling León Gabriel Gómez-ArchilaMartina Palomino-SchätzleinWildeman Zapata-BuilesMaria T. RugelesElkin GaleanoUniversidad Cooperativa de ColombiaUniversidad de AntioquiaINFETTARE2024-09-27T18:24:14Z2024-09-27T18:24:14Z2023-06-292296-889Xhttps://hdl.handle.net/20.500.12494/5715310.3389/fmolb.2023.12042732296-889Xapplication/pdfengGrupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia.Externohttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://purl.org/coar/access_right/c_abf2https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1204273/fullPlasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/ progressionArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersion1712042730110Front. Mol. Biosci.Aguilar-Jiménez, W., Zapata, W., Caruz, A., and Rugeles, M. T. (2013). High transcript levels of vitamin D receptor are correlated with higher mRNA expression of human beta defensins and IL-10 in mucosa of HIV-1-Exposed seronegative individuals. PLoS One [Internet 8 (12), e82717. Available from. doi:10.1371/journal. pone.0082717Aldunate, M., Tyssen, D., Johnson, A., Zakir, T., Sonza, S., Moench, T., et al. (2013). Vaginal concentrations of lactic acid potently inactivate HIV. J. Antimicrob. Chemother. [Internet] 68 (9), 2015–2025. –25. Available from. doi:10.1093/jac/dkt156Alves, C. R. R., Ferreira, J. C., de Siqueira-Filho, M. A., Carvalho, C. R., Lancha, A. H., and Gualano, B. Creatine-induced glucose uptake in type 2 diabetes: A role for AMPK- α? Amino acids Amino Acids, [Internet]. 2012;43(4):1803–1807. doi:10.1007/s00726- 012-1246-6Arnold, K. B., Burgener, A., Birse, K., Romas, L., Dunphy, L. J., Shahabi, K., et al. (2016). Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol. 9 (1), 194–205. doi:10.1038/mi. 2015.51Baker, B. M., Block, B. L., Rothchild, A. C., and Walker, B. D. (2009). Elite control of HIV infection: implications for vaccine design. Expert Opin. Biol. Ther. 9 (1), 55–69. doi:10.1517/14712590802571928Balmer, M. L.,Ma, E. H., Bantug, G. R., Grählert, J., Pfister, S., Glatter, T., et al. (2016). Memory CD8(+) T cells require increased concentrations of acetate induced by stress for optimal function. Immunity 44 (6), 1312–1324. doi:10.1016/j.immuni.2016.03.016Barré-Sinoussi, F., Chermann, J. C., Rey, F., Nugeyre, M. T., Chamaret, S., Gruest, J., et al. (1983). Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220 (4599), 868–871. doi:10.1126/ science.6189183Behl, C., Widmann, M., Trapp, T., and Holsboer, F. (1995). 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem. Biophys. Res. Commun. 216 (2), 473–482. doi:10.1006/bbrc.1995.2647Bertini, I., Cacciatore, S., Jensen, B. V., Schou, J. V., Johansen, J. S., Kruhøffer,M., et al. (2012). Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer. Cancer Res. 72 (1), 356–364. Available at:. doi:10. 1158/0008-5472.CAN-11-1543Bertran-Cobo, C., Wedderburn, C. J., Robertson, F. C., Subramoney, S., Narr, K. L., Joshi, S. H., et al. (2022), A neurometabolic pattern of elevated myo-inositol in children who are HIV-exposed and uninfected: A South African birth cohort study Front. Immunol, [Internet]. Vol. 13, 800273, doi:10.3389/fimmu.2022.800273Bose, S., Ramesh, V., and Locasale, J. W. Acetate metabolism in physiology, cancer, and beyond. Trends Cell Biol. [Internet]. 2019;29(9):695–703. doi:10.1016/j.tcb.2019. 05.005Brass, A. L., Dykxhoorn, D. M., Benita, Y., Yan, N., Engelman, A., Xavier, R. J., et al. (2008). Identification of host proteins required for HIV infection through a functional genomic screen. Science 319 (5865), 921–926. doi:10.1126/science.1152725Brenchley, J. M., Price, D. A., and Douek, D. C. (2006). HIV disease: Fallout from a mucosal catastrophe? Nat. Immunol. 7 (3), 235–239. doi:10.1038/ni1316Brennan, E., Kantharidis, P., Cooper, M. E., and Godson, C. (2021). Pro-resolving lipid mediators: Regulators of inflammation, metabolism and kidney function. Nat. Rev. Nephrol. [Internet] 17 (11), 725–739. Available from. doi:10.1038/s41581-021-00454-yCao, Y., Qin, L., Zhang, L., Safrit, J., and Ho, D. D. (1995). Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N. Engl. J. Med. 332 (4), 201–208. doi:10.1056/ NEJM199501263320401Cassol, E., Misra, V., Holman, A., Kamat, A., Morgello, S., and Gabuzda, D. (2013). Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors. BMC Infect. Dis. 13, 203. doi:10.1186/1471-2334-13-203Chang, L., Lee, P. L., Yiannoutsos, C. T., Ernst, T., Marra, C. M., Richards, T., et al. (2004). A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age. Neuroimage 23 (4), 1336–1347. doi:10.1016/j.neuroimage.2004. 07.067Che, X., He, F., Deng, Y., Xu, S., Fan, X., Gu, P., et al. (2014). HIV-1 Tat-mediated apoptosis in human blood-retinal barrier-associated cells. PLoS One 9 (4), e95420. doi:10.1371/journal.pone.0095420Cheng, D-C., Zhong, G-C., Su, J-X., Liu, Y-H., Li, Y., Wang, J-Y., et al. (2010). A sensitive HIV-1 envelope induced fusion assay identifies fusion enhancement of thrombin. Biochem. Biophys. Res. Commun. 391 (4), 1780–1784. doi:10.1016/j.bbrc. 2009.12.155Cohen, R. A., Harezlak, J., Gongvatana, A., Buchthal, S., Schifitto, G., Clark, U., et al. (2010). Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes. J. Neurovirol 16 (6), 435–444. doi:10.3109/13550284.2010.520817NMRmetabolomicsHIV-1biomarkerspathwaysPublicationCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805https://repository.ucc.edu.co/bitstreams/9a81274a-8e92-446e-9954-5324124e490c/download4460e5956bc1d1639be9ae6146a50347MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-84334https://repository.ucc.edu.co/bitstreams/1bcd9a96-50af-4d86-a789-1bbab409327e/download3bce4f7ab09dfc588f126e1e36e98a45MD52ORIGINALPlasma metabolomics HESN UCC_UdeA 2023.pdfPlasma metabolomics HESN UCC_UdeA 2023.pdfapplication/pdf3731440https://repository.ucc.edu.co/bitstreams/100a1306-318e-4194-a171-e44f8d143474/download9c712c43c0bb606f88d1ad07ddab867bMD53TEXTPlasma metabolomics HESN UCC_UdeA 2023.pdf.txtPlasma metabolomics HESN UCC_UdeA 2023.pdf.txtExtracted texttext/plain98487https://repository.ucc.edu.co/bitstreams/242d6272-f626-48bc-9dfd-dc0a63702393/downloade0075f7685a20ebdde9c449e9621cd2fMD54THUMBNAILPlasma metabolomics HESN UCC_UdeA 2023.pdf.jpgPlasma metabolomics HESN UCC_UdeA 2023.pdf.jpgGenerated Thumbnailimage/jpeg12645https://repository.ucc.edu.co/bitstreams/65313914-1d0b-4bb8-920b-743b8a6291f1/download3b5bbf5f9f88fff8fbd52c202c07846aMD5520.500.12494/57153oai:repository.ucc.edu.co:20.500.12494/571532024-09-30 03:00:36.577http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalopen.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.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

Publicaciones similares