Microarray detection of E2F pathway activation and other targets in multiple sclerosis peripheral blood mononuclear cells.
ABSTRACT We performed microarray analysis of peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients and detected a profile of immune cell activation, autoantigen upregulation, and enhanced E2F pathway transcription. Accordingly, E2f1-deficient mice manifested only mild disability upon induction of experimental autoimmune encephalomyelitis (EAE). Furthermore, PBMCs from Avonex-treated patients had lower expression of E2F targets. The profile was enriched in genes known to harbor MS-associated polymorphisms, or localized to MS susceptibility chromosomal regions. Our study shows that PBMC microarrays reflect MS pathobiology that can be validated in the EAE model.
- SourceAvailable from: Bartolomé Bejarano Herruzo[Show abstract] [Hide abstract]
ABSTRACT: Though multiple sclerosis (MS) is an autoimmune disease of the central nervous system, the etiopathogenesis is not clear, since genetic susceptibility and environmental factors are thought to be involved. Some studies emphasize the role of microRNAs (miRNAs) in its pathogenesis. Their clinical course is extremely heterogeneous and different subtypes with considerable individual variation have been described. However, no biomarkers that reliably correlate with or predict disease activity have been found. The aim of this second part is to review and discuss data mining techniques in the context of MS.Revista Española de Esclerosis Múltiple. 09/2013; V(27):10-18.
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ABSTRACT: It is currently accepted that the perturbation of complex intracellular networks, rather than the dysregulation of a single gene, is the basis for phenotypical diversity. High-throughput gene expression data allow to investigate changes in gene expression profiles among different conditions. Recently, many efforts have been made to individuate which biological pathways are perturbed, given a list of differentially expressed genes (DEGs). In order to understand these mechanisms, it is necessary to unveil the variation of genes in relation to each other, considering the different phenotypes. In this paper, we illustrate a pipeline, based on Structural Equation Modeling (SEM) that allowed to investigate pathway modules, considering not only deregulated genes but also the connections between the perturbed ones.BMC Bioinformatics 05/2014; 15(1):132. · 3.02 Impact Factor
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ABSTRACT: Background The result of primary open-angle glaucoma is the loss of retinal ganglion cells. Transient receptor potential cation channel 6 is a pressure-related channel that may function in the survival of retinal ganglion cells. The purpose of this study was to evaluate the expression levels of the transient receptor potential cation channel 6 gene in patients with primary open-angle glaucoma. DesignRandomization study at Zhongshan Ophthalmic Center in China. Participants80 primary open-angle glaucoma patients and 75 cataract patients recruited from Zhongshan Ophthalmic Center. Methods Total RNA was extracted from the leukocytes of the peripheral blood collected. The levels of transient receptor potential cation channel 6–messenger RNA were determined by real-time polymerase chain reaction. Related factors including age, intraocular pressure, optic cup-to-disc ratio and visual field defect were analysed accordingly. Main Outcome MeasuresClinical examination and the messenger RNA level. ResultsThe expression level of the transient receptor potential cation channel 6 gene in the leukocytes of primary open-angle glaucoma patients was two times higher when compared with control cataract patients. The gene expression level was also correlated with intraocular pressure and cup-to-disc ratio. Treatment with different anti-glaucoma drugs did not affect the gene expression. Conclusions Increasing expression levels of the transient receptor potential cation channel 6 gene in the blood accompanies chronic elevation of intraocular pressure in primary open-angle glaucoma and may serve as a genetic biomarker for primary open-angle glaucoma.Clinical and Experimental Ophthalmology 11/2013; 41(8). · 1.96 Impact Factor