RESUMEN
Equine endometritis is one of the main causes of subfertility in the mare. Unraveling the molecular mechanisms involved in this condition and pinpointing proteins with biomarker potential could be crucial in both diagnosing and treating this condition. This study aimed to identify the endometritis-induced changes in the endometrial proteome in mares and to elucidate potential biological processes in which these proteins may be involved. Secondly, biomarkers related to bacterial endometritis (BE) in mares were identified. Uterine lavage fluid samples were collected from 28 mares (14 healthy: negative cytology and culture, and no clinical signs and 14 mares with endometritis: positive cytology and culture, in addition to clinical signs). Proteomic analysis was performed with a UHPLC-MS/MS system and bioinformatic analysis was carried out using Qlucore Omics Explorer. Gene Ontology enrichment and pathway analysis (PANTHER and KEGG) of the uterine proteome were performed to identify active biological pathways in enriched proteins from each group. Quantitative analysis revealed 38 proteins differentially abundant in endometritis mares when compared to healthy mares (fold changes >4.25, and q-value = 0.002). The proteins upregulated in the secretome of mares with BE were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium. A total of 24 biomarkers for BE were identified using the biomarker workbench algorithm. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B involvement in neutrophil extracellular trap (NET) formation, complement C3a, or gelsolin and profilin, two actin-binding proteins which are essential for dynamic remodeling of the actin cytoskeleton during cell migration. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and myeloperoxidase (MPO)) and two uncharacterized proteins with a high homology with cathelicidin families. Findings in this study provide the first evidence that innate immune cells in the equine endometrium undergo reprogramming of metabolic pathways similar to the Warburg effect during activation. In addition, biomarkers of BE in uterine fluid of mares including the new proteins identified, as well as other antimicrobial peptides already known, offer future lines of research for alternative treatments to antibiotics.
Asunto(s)
Biomarcadores , Endometritis , Endometrio , Enfermedades de los Caballos , Proteoma , Femenino , Animales , Caballos , Enfermedades de los Caballos/metabolismo , Enfermedades de los Caballos/microbiología , Endometritis/veterinaria , Endometritis/metabolismo , Endometritis/microbiología , Biomarcadores/metabolismo , Endometrio/metabolismo , Endometrio/microbiología , Útero/metabolismo , Útero/microbiología , Infecciones Bacterianas/veterinaria , Infecciones Bacterianas/metabolismoAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Inducción de Remisión , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Este estudio busca explicar el contraste entre la preocupación pública por la extensión del consumo, la producción y el tráfico de substancias ilícitas en la población y las dificultades para establecer programas de prevención en los lugares de trabajo. Se corrobora en una muestra de grandes empresas de la Región Metropolitana el escaso desarrollo de programas de salud preventiva en general, la casi total ausencia de actividades relacionadas con alcohol y otras drogas y los obstáculos para investigar el tema. Se vincula este problema con la cultura organizacional, que define el consumo y el abuso de substancias al margen de la gestión de la empresa, restringiéndolo al ámbito de la conducta privada de los individuos y privilegiando actividades de control y tratamiento. Se postula una concertación no consciente, asentada en representaciones sociales, entre ejecutivos, trabajadores y profesionales de salud para mantener este problema alejado de un enfoque colectivo y preventivo. Se sugiere la conveniencia de enfrentar el problema a través de un enfoque organizacional, que permita aprovechar el mantenido esfuerzo e interés de muchos profesionales y ejecutivos al interior de las empresas de las áreas de bienestar, salud, prevención y recursos humanos, sin incurrir en gastos adicionales