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We applied serial analysis of gene expression (SAGE) to study differentially expressed genes in mouse brain 14 hr after the induction of focal cerebral ischemia. Analysis of >60,000 transcripts revealed 83 upregulated and 94 downregulated transcripts (more than or equal to eightfold). Reproducibility was demonstrated by performing SAGE in duplicate on the same starting material. Metallothionein-II (MT-II) was the most significantly upregulated transcript in the ischemic hemisphere. MT-I and MT-II are assumed to be induced by metals, glucocorticoids, and inflammatory signals in a coordinated manner, yet their function remains elusive. Upregulation of both MT-I and MT-II was confirmed by Northern blotting. MT-I and MT-II mRNA expression increased as early as 2 hr after 2 hr of transient ischemia, with a maximum after 16 hr. Western blotting and immunohistochemistry revealed MT-I/-II upregulation in the ischemic hemisphere, whereas double labeling demonstrated the colocalization of MT with markers for astrocytes as well as for monocytes/macrophages. MT-I- and MT-II-deficient mice developed approximately threefold larger infarcts than wild-type mice and a significantly worse neurological outcome. For the first time we make available a comprehensive data set on brain ischemic gene expression and underscore the important protective role of metallothioneins in ischemic damage of the brain. Our results demonstrate the usefulness of SAGE to screen functionally relevant genes and the power of knock-out models in linking function to expression data generated by high throughput techniques.
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http://dx.doi.org/10.1523/JNEUROSCI.22-14-05879.2002 | DOI Listing |
CNS Neurosci Ther
December 2024
The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Background: Previous research has demonstrated correlations between the complex types and functions of brain cells and the etiology of glioma. However, the causal relationship between gene expression regulation in specific brain cell types and glioma risk, along with its therapeutic implications, remains underexplored.
Methods: Utilizing brain cell type-specific cis-expression quantitative trait loci (cis-eQTLs) and glioma genome-wide association study (GWAS) datasets in conjunction with Mendelian randomization (MR) and colocalization analyses, we conducted a systematic investigation to determine whether an association exists between the gene expression of specific brain cell types and the susceptibility to glioma, including its subtypes.
Biotechnol Appl Biochem
December 2024
Department of Thoracic Surgery, Affiliated Sanming First Hospital of Fujian Medical University Sanming, Fujian, China.
Non-small cell lung cancer (NSCLC) is the most pervasive sort of lung cancer with deadly outcome. According to recent studies, a number of neoplastic disorders and ferroptosis are intimately connected. This study aims to identify the role of key ferroptosis-related gene (protein kinase AMP-activated catalytic subunit alpha 2, PRKAA2) and explore new directions for the diagnosis and treatment of NSCLC.
View Article and Find Full Text PDFJ Egypt Natl Canc Inst
December 2024
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Background: Tumor recurrence or metastasis after surgery is a significant factor influencing bladder cancer (BC) prognosis. Novel molecular biomarkers are necessary to determine each patient's specific outcome because current biomarkers have limited power for predicting prognosis. The proto-oncogene MET encodes c-MET, a tyrosine kinase receptor.
View Article and Find Full Text PDFIntroduction: Low back pain (LBP) is a significant global health burden, with variable treatment outcomes and an unclear underlying molecular mechanism. Effective prediction of treatment responses remains a challenge. In this study, we aimed to develop gene signature-based machine learning models using transcriptomic data from peripheral immune cells to predict treatment outcomes in patients with LBP.
View Article and Find Full Text PDFJ Mol Histol
December 2024
Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, Shandong Province, China.
A poorer prognosis is thought to be associated with "double expressor lymphomas," which are a subtype of diffuse large B cell lymphomas (DLBCL) that co-express MYC and BCL2. While the role of ubiquitin-specific peptidase 37 (USP37) in lung cancer, where it mediates the deubiquitination and stabilization of c-myc, has been well-documented, its involvement in DLBCL remains unexplored. The use of RT-PCR, immunohistochemistry, or WB test allowed for the detection of elevated USP37 in DLBCL tissues and cells.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!