ABSTRACT
In this study, biomarkers and transcriptional factor motifs were identified in order to investigate the etiology and phenotypic severity of Down syndrome. GSE 1281, GSE 1611, and GSE 5390 were downloaded from the gene expression ominibus (GEO). A robust multiarray analysis (RMA) algorithm was applied to detect differentially expressed genes (DEGs). In order to screen for biological pathways and to interrogate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, the database for annotation, visualization, and integrated discovery (DAVID) was used to carry out a gene ontology (GO) function enrichment for DEGs. Finally, a transcriptional regulatory network was constructed, and a hypergeometric distribution test was applied to select for significantly enriched transcriptional factor motifs. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were each up-regulated two-fold in Down syndrome samples compared to normal samples; of these, SON and TTC3 were newly reported. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were located on human chromosome 21 (mouse chromosome 16). The DEGs were significantly enriched in macromolecular complex subunit organization and focal adhesion pathways. Eleven significantly enriched transcription factor motifs (PAX5, EGR1, XBP1, SREBP1, OLF1, MZF1, NFY, NFKAPPAB, MYCMAX, NFE2, and RP58) were identified. The DEGs and transcription factor motifs identified in our study provide biomarkers for the understanding of Down syndrome pathogenesis and progression.
Subject(s)
Animals , Humans , Mice , Rats , Amino Acid Motifs/genetics , Computational Biology/methods , Down Syndrome/genetics , Gene Regulatory Networks/genetics , Transcription Factors/analysis , Algorithms , Biomarkers/analysis , Databases, Genetic , Down Syndrome/etiology , Gene Expression , Gene Ontology , Molecular Sequence Annotation/methods , Phenotype , Protein Array Analysis/methods , Up-Regulation/geneticsABSTRACT
OBJECTIVE@#To explore the difference of expression of proteins between the serum and hippocampus after brain injury in rats.@*METHODS@#Male SD rats were used to establish brain injury model. The changes of proteins expression profile in serum and hippocampus at different time after brain injury were analyzed using weak cationic exchanger (WCX2) chips and immobilized metal affinity capture arrays-Cu (IMAC-Cu) chips by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.@*RESULTS@#A total of 436 protein peaks were detected in serum and 346 protein peaks were detected in hippocampus using WCX2 chips. A total of 229 protein peaks were detected in serum and 345 protein peaks were detected in hippocampus using IMAC-Cu chips. The same 10 protein peaks were respectively detected in serum and hippocampus using WCX2 chips. The same 13 protein peaks were respectively detected in serum and hippocampus using IMAC-Cu chips.@*CONCLUSION@#The changes of protein expression profile in serum and hippocampus are obvious after closed brain injury and show a significant difference. The different proteins detected in serum and hippocampus using the same chip could be biochemical markers for determining brain injury.
Subject(s)
Animals , Male , Rats , Blood Proteins/analysis , Brain/pathology , Disease Models, Animal , Head Injuries, Closed/metabolism , Hippocampus/metabolism , Predictive Value of Tests , Protein Array Analysis/methods , Proteins/metabolism , Proteomics , Rats, Sprague-Dawley , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
El Retardo Mental en los niños es una condición anormal del desarrollo del Sistema Nervioso, cuyo origen es usualmente multifactorial pero aun insuficientemente estudiada, lo cual repercute en la efectividad de acciones de intervención preventiva. Con el objetivo de tratar de establecer una relación entre las insuficiencias nutricionales de las madres embarazadas y la aparición de retardo mental no explicado por otras causas en sus hijos, se diseñó una investigación cualitativa con un diseño tipo descriptivo, cualitativo etnográfico por categorías, correlacional, parcialmente retrospectivo-prospectivo, desarrollado en el Centro de Recuperación Nutricional Infantil Integral Dr. Pastor Oropeza. La muestra estuvo constituida por 10 binomios madre-hijo, aplicándose una metodología de encuesta con la Encuesta Identificación de riesgos nutricionales y peligros de discapacidad prenatal a las madres y la Guía Portage de Educación Preescolar a los niños, para identificar posibles retardos en las áreas de socialización, lenguaje, motricidad, cognición y autoayuda. Los resultados fueron: se ejecutaron 918 evaluaciones a los 10 niños incluidos según los ítems sugeridos en la Guía Portage, encontrando que el 84.20 por ciento no logró superar lo explorado y de manera mas severa el área de lenguaje y cognitivo con 90 por ciento de fallas. En cuanto a las madres, se encontró que el 84 por ciento no poseían conocimientos ni practicas saludables en nutrición durante el embarazo, atribuibles no solo a las madres sino también al equipo de salud que las hubo de atender durante los controles de embarazo. La casi coincidencia de los dos porcentajes: 84.20 y 84, sugieren una posible asociación (RR=1) (OR=7), cuya fundamentación es ampliamente discutida en el texto de trabajo, analizada a la luz de las numerosas evidencias obtenidas en la bibliografía disponible.