Project description:BACKGROUND: Evaluation of the airway transcriptome may reveal patterns of gene expression that are associated with clinical phenotypes of asthma. To define transcriptomic endotypes of asthma (TEA) we analyzed gene expression in induced sputum that correlate with phenotypes of disease. METHODS: Gene expression was measured in sputum of subjects with asthma using Affymetrix HuGene ST 1.0 microarrays. Unsupervised clustering analysis of genes in pathways selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) identified TEA clusters. Clinical characteristics were compared and logistic regression analysis of matched blood samples defined an expression profile to determine the TEA cluster assignment in a cohort of children with asthma for validation. RESULTS: Three TEA clusters were identified. TEA cluster 1 had the most subjects with a history of intubation (P = 0.05), a lower pre-bronchodilator FEV1 (P = 0.006), a higher bronchodilator response (P = 0.03), and higher exhaled nitric oxide levels (P = 0.04), compared to the other TEA clusters. TEA cluster 2, the smallest cluster had the most subjects that were hospitalized for asthma (P = 0.04). Subjects in TEA cluster 3, the largest cluster, had normal lung function, low exhaled nitric oxide levels, and lower inhaled steroid requirements. Evaluation of TEA clusters in children confirmed that TEA clusters 1 and 2 are associated with a history of intubation (P = 5.58 x 10-06) and hospitalization (P = 0.01), respectively. CONCLUSIONS: Patterns of gene expression in the sputum and blood reveal TEA clusters that are associated with severe asthma phenotypes in children and adults. Gene expression was measured in sputum of subjects with asthma using Affymetrix HuGene ST 1.0 microarrays. Unsupervised clustering analysis of genes in pathways selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) identified TEA clusters. Clinical characteristics were compared and logistic regression analysis of matched blood samples defined an expression profile to determine the TEA cluster assignment in a cohort of children with asthma for validation.
Project description:Down syndrome is the main genetic cause of intellectual disability and is due to triplication of human chromosome 21 (HSA21). Green tea extracts containing epigallocatechin-3-gallate (green tea) improve cognition both in mouse models and individuals with Down syndrome. We here analyzed the proteome and phosphoproteome alterations in a Down syndrome mouse model, the partial trisomic Ts65Dn mice, and the effect produced by the green tea extract and environmental enrichment (EE). Trisomic hippocampi presented a dysregulated proteome, especially when looking at the phosphorylation level in cognitive-related categories (synaptic proteins, neuronal projection, neuron development, microtubule), and GTPases/kinase activity and chromatin related categories. Green tea, EE, and their phospholipids in the plasma membrane and regulates signal transduction pathways, transcription factors, DNA methylation, mitochondrial function and phosphorylation, and autophagy to exert many of its beneficial biological actions Of interest for DS, it inhibits the activity of the Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase 1A (DYRK1A), a DS candidate gene located in the 21q22.2 human chromosome region4,5. Previous work from our group showed that EGCG partially rescues the effects of overexpression of a DS candidate gene, DYRK1A, on the proteome and phosphoproteome of the hippocampus of TgDyrk1A mice6. However, the extent to which these mechanisms apply to a trisomy scenario is unknown. To get insight in these mechanisms we analyzed changes in protein abundances and phosphorylation in Ts65Dn mice, and their disomic counterparts in baseline conditions and upon three treatments known to improve cognition in Ts65Dn: i) green tea extract containing EGCG, ii) environmental enrichment (EE), and iii) their combination.
Project description:For developing the more SNPs and new high-density genetic linkage map of tea plant, two parents and their 326 progenies and 147 registered tea cultivars was sequencing by newly developed Affymetrix Axiom genotyping technology
Project description:Hawk tea (Litsea coreana var. lanuginose) is a traditional Chinese tea, widely cultivated and consumed in southwestern China. It has been widely used to treat gastrosis, hepatitis, and inflammatory diseases for hundreds of years. Modern pharmacological studies demonstrate that hawk tea has protective effects against liver fibrosis, hypercholesterolemia, hyperglycemia, and inflammatory diseases . However, the molecular mechanism of hawk tea against hypercholesterolemia remains unclear. The aims of this study were to investigate the mechanisms of hawk tea extract (HTE) to lower cholesterol. Therefore, we performed genome-wide transcriptional analysis of hawk tea extracts treated HepG2 cells. Hawk tea extracts (HTE) induced significant gene modulation on HepG2 cells.