Inhalation of toxic chemicals, including recent e-cigarettes, often cause life-threatening lung injury. Although exposure to polyhexamethylene guanidine (PHMG)-containing humidifier disinfectant (HD) has been identified as a cause of fatal lung injury, the mechanism underlying HD-associated lung injury (HDLI) is unknown. The present study evaluated global changes in gene expression in lung tissues from patients with PHMG-induced HDLI, and compared gene expression changes in PHMG-induced rat lung tissues. Significantly different expressions in lung tissues between patients with HDLI and unaffected controls were observed. Furthermore, several fibrosis-associated overlapping genes (such as MMP2 and COL1A2) shared between humans with HDLI and rats exposed to PHMG were identified. Interactome network analysis predicted different pathways between children and adults with HDLI: the TGFβ/SMAD signaling pathway was central in adults, whereas other pathways, including integrin signaling, were associated with HDLI in children. Further interactome network analysis revealed that Rap1 and CCKR signaling pathways were significantly enriched in HDLI compared with idiopathic pulmonary fibrosis as well as their recapitulation in the lung tissues of rats exposed to PHMG. Our results suggest that MMP2-mediated different mechanisms between children and adults may be associated with PHMG-induced HDLI development, and Rap1 and CCKR pathways appear to be crucial.
Integrative multi-omics approach for mechanism of humidifier disinfectant-associated lung injury.
Age, Specimen part
View SamplesDespite continual efforts to establish pre-operative prognostic model of gastric cancer by using clinical and pathological parameters, a staging system that reliably separates patients with early and advanced gastric cancer into homogeneous groups with respect to prognosis does not exist. With use of microarray and quantitative RT-PCR technologies, we exploited series of experiments in combination with complementary data analyses on tumor specimens from 161 gastric cancer patients. Various statistical analyses were applied to gene expression data to uncover subgroups of gastric cancer, to identify potential biomarkers associated with prognosis, and to construct molecular predictor of risk from identified prognostic biomarkers.Two subgroups of gastric cancer with strong association with prognosis were uncovered. The robustness of prognostic gene expression signature was validated in independent patient cohort with use of support vector machines prediction model. For easy translation of our finding to clinics, we develop scoring system based on expression of six genes that can predict the likelihood of recurrence after curative resection of tumors. In multivariate analysis, our novel risk score was an independent predictor of recurrence (P=0.004) in cohort of 96 patients, and its robustness was validated in two other independent cohorts. We identified novel prognostic subgroups of gastric cancer that are distinctive in gene expression patterns. Six-gene signature and risk score derived from them has been validated for predicting the likelihood of survival at diagnosis.
Gene expression signature-based prognostic risk score in gastric cancer.
No sample metadata fields
View SamplesUnder steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. We performed a global gene expression analysis to examine which genes are highly expressed by small intestinal eosinophils (CD11b+CD11c(int)MHCII-SiglecF+) compared with dendritic cells (CD11c+MHCII+).
Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.
Age, Specimen part
View SamplesWe found constitutive upregulation and higher degree induction of drug metabolism and disposition-related genes in a three-dimensional HepG2 culture. The upregulated genes are those believed to be regulated by different regulatory factors. The global gene expression analysis by Affymetrix GeneChip indicated that altered expressions of microtubule-related genes may change expressed levels of drug metabolism and disposition genes. Stabilization of the microtubule molecules with docetaxel, a tubulin stabilizing agent, in the two-dimensional culture showed gene expression patterns similar to those in the three-dimensional culture, indicating that culture environment affects drug metabolism functions in HepG2 cells.
Global gene expression changes including drug metabolism and disposition induced by three-dimensional culture of HepG2 cells-Involvement of microtubules.
No sample metadata fields
View SamplesBackground: Causative genes for autosomal dominantly inherited familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) have been well characterized. There is, however, another 10-15 % early onset colorectal cancer (CRC) whose genetic components are currently unknown. In this study, we used DNA chip technology to systematically search for genes differentially expressed in early onset CRC.
A susceptibility gene set for early onset colorectal cancer that integrates diverse signaling pathways: implication for tumorigenesis.
Sex, Age, Specimen part
View SamplesReconstructed mutants of yeast by inverse metabolic engineering were characterized by fermentation physiology and tools from systems biology.
Recovery of phenotypes obtained by adaptive evolution through inverse metabolic engineering.
Time
View SamplesDrosophila translationally controled tumor protein (dTCTP) is important to repair double stranded DNA breaks in cell nucleus. However, besides damaged DNA loci, dTCTP is also located in interbands region of polytene chromsomes of salivary gland tissues.
Antagonistic roles of Drosophila Tctp and Brahma in chromatin remodelling and stabilizing repeated sequences.
Specimen part
View SamplesExploring molecular details of carbon utilization trade-offs in galactose-evolved yeast
Adaptively evolved yeast mutants on galactose show trade-offs in carbon utilization on glucose.
Time
View SamplesWe generate ZNF423 knockdown and control DAOY cells with lentivirus that co-expressed the fluorescent protein mCherry. We performed whole genome RNA sequencing (RNA-seq) of three batched of cultured ZNF423 KD or control KD cells. The sequence reads were analyzed by Homer followed by edgeR. The analyzed RNA-seq results showed differential expression profile including 12 known cilia genes, and 3 of these were validated with qRT-PCR on mouse granule cell precursors. This study proved data how ZNF423 linked to cilia complexes. Overall design: RNA-seq in three batched of control and ZNF423 KD cells(generated by lentivirus delivered shRNA targeting ZNF423 sequence).
Zfp423 Regulates Sonic Hedgehog Signaling via Primary Cilium Function.
No sample metadata fields
View SamplesThe miR-16 family, which targets genes important for the G1-S transition, is a known modulator of the cell cycle, and members of this family are often deleted or down-regulated in many types of cancers. Here we report the reciprocal relationship - that of the cell cycle controlling the miR-16 family. Levels of this family increase rapidly as cells are arrested in G0. Conversely, as cells are released from G0 arrest, levels of the miR-16 family rapidly decrease. Such rapid changes are made possible by the unusual instabilities of several family members. The repression mediated by the miR-16 family is sensitive to these cell cycle changes, which suggests that the rapid up-regulation of the miR-16 family reinforces cell cycle arrest in G0. Upon cell cycle re-entry, the rapid decay of several members allows levels of the family to decrease, alleviating repression of target genes and allowing proper resumption of the cell cycle. Overall design: Small RNAs were profiled by high-throughput sequencing either during synchronous release after serum starvation or during cell-cycle arrest by contact inhibition.
MicroRNA destabilization enables dynamic regulation of the miR-16 family in response to cell-cycle changes.
Specimen part, Cell line, Subject
View Samples