Project description:Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype.
Project description:Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype. Microarray Studies. Biotinylated cRNA samples from freshly sorted brain SMCs (four Notch 3 +/- mice and five Notch 3 -/- mice) were fragmented before hybridization (15 ug each) onto mouse 430 2.0 Affymetrix chips. The chips were washed, stained by using strepavidin-phycoerytrin, and scanned the next day as described in ref. 24. For data normalization, all probe sets were scaled to a target intensity of 150. Microarray data analysis was performed by using Rosetta Resolver. All cells were from 10- to 12-week-old male mice. Gene Ontology Analyses. PANTHER software was used to define over- and underrepresented functions in the list of signature genes found by microarray analysis (25). P values were calculated by using binomial statistics.
Project description:The purpose of this project was to elucidate gene expression in the peripheral whole blood of acute ischemic stroke patients to identify a panel of genes for the diagnosis of acute ischemic stroke. Peripheral blood samples were collected in Paxgene Blood RNA tubes from stroke patients who were >18 years of age with MRI diagnosed ischemic stroke and controls who were non-stroke neurologically healthy. The results suggest a panel of genes can be used to diagnose ischemic stroke, and provide information about the biological pathways involved in the response to acute ischemic stroke in humans. Total RNA extracted from whole blood in n=39 ischemic stroke patients compared to n=24 healthy control subjects.
Project description:Background: Ischemic stroke is a disease with high rate of death and disability worldwide. This study investigated key circRNAs related to ischemic stroke. Methods: Three ischemic stroke patients and three healthy individuals were included in the current study to obtain the circRNA expression profiles by RNA sequencing. Through bioinformatic analysis, differentially expressed circRNAs (DEcircRNAs) were identified, and GO and pathway analyses for the host genes of DEcircRNAs were conducted. To further explore the functions of key circRNAs, a DEcircRNA-miRNA interaction network was constructed. Finally, the expression levels of selected circRNAs were validated with qRT-PCR. Results: A total of 736 DEcircRNAs were detected in ischemic stroke. Functional annotation of host genes of DEcircRNAs revealed several significantly enriched pathways, including Fc epsilon RI signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway. A circRNA-miRNA network, including 1544 circRNA-miRNA pairs, 456 circRNAs and 4 miRNAs, was obtained. The qRT-PCR results were largely in keeping with our RNA-seq data. Conclusion: The results of our study may help to elucidate the specific mechanism underlying ischemic stroke.
Project description:The purpose of this project was to elucidate gene expression in the peripheral whole blood of acute ischemic stroke patients to identify a panel of genes for the diagnosis of acute ischemic stroke. Peripheral blood samples were collected in Paxgene Blood RNA tubes from stroke patients who were >18 years of age with MRI diagnosed ischemic stroke and controls who were non-stroke neurologically healthy. The results suggest a panel of genes can be used to diagnose ischemic stroke, and provide information about the biological pathways involved in the response to acute ischemic stroke in humans.
Project description:Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Previous publication showed the obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. The goal of this experiment was to compare genome wide enrichment of H3K9ac histone mark profile of white blood cells of healthy controls, patients with obesity and/or stroke in order to understand the histone modifications differences behind the different phenotypes. There were 3 subjects in each group.
Project description:The high incidence, mortality, and disability rate of ischemic stroke impose huge economic burdens on patients and social health care systems.N6-methyladenosine (m6A) is one of the most extensive RNA methylation modifications in eukaryotes and participates in the pathogenesis of numerous diseases including ischemic stroke. Peripheral blood neutrophils are forerunners after ischemic brain injury and exert crucial functions.However, the underlying mechanisms of neutrophils in ischemic stroke need to be further clarified. This study aims to explore the transcriptional profiles of m6A modification in neutrophils of patients with ischemic stroke. The Arraystar Human m6A-mRNA&lncRNA Epitranscriptomic microarray analysis was performed on the peripheral blood neutrophils of 3 patients with ischemic stroke and 3 healthy controls, providing the clinical significance of m6A modification on ischemic stroke.
Project description:blood miRNA expression in ischemic stroke compared to controls miRNA expression in blood cells from patients with ischemic stroke were compared to controls with vascular risk factors
Project description:Analysis of microglial gene expression profiles after ischemic stroke. Stroke is a complicated disease caused by the interaction of multiple celltypes. Results provide new insights into the molecular mechanisms underlying microglial activation after ischemic stroke.