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Sodium-glucose cotransporter protein 2 inhibition, plasma proteins, and ischemic stroke: A mediation Mendelian randomization and colocalization study.
J Stroke Cerebrovasc Dis
January 2025
Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China. Electronic address:
Article Synopsis
- The study aimed to investigate how inhibiting the sodium-glucose cotransporter protein 2 (SGLT2) affects ischemic stroke (IS) and to identify circulating proteins that mediate these effects.
- Using Mendelian randomization analyses, researchers assessed 4,907 circulating proteins and validated findings through various analyses, including sensitivity and colocalization.
- Results showed that SGLT2 inhibition significantly reduces the risk of IS and cardioembolic stroke, with potential mediators identified as tryptophanyl-transfer RNA synthetase (WARS) and matrix metalloproteinase 12 (MMP12), suggesting a new way to approach IS treatment.
Tryptophanyl-Transfer RNA Synthetase Is Involved in a Negative Feedback Loop Mitigating Interferon-γ-Induced Gene Expression.
Cells
January 2024
The Rappaport Technion Integrated Cancer Center (R-TICC) and the Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 3109601, Israel.
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes responsible for linking a transfer RNA (tRNA) with its cognate amino acid present in all the kingdoms of life. Besides their aminoacyl-tRNA synthetase activity, it was described that many of these enzymes can carry out non-canonical functions. They were shown to be involved in important biological processes such as metabolism, immunity, development, angiogenesis and tumorigenesis.
View Article and Find Full Text PDFTryptophanyl-tRNA Synthetase Sensitizes Hormone Receptor-Positive Breast Cancer to Docetaxel-Based Chemotherapy.
J Breast Cancer
December 2020
Center for Medical Innovation, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
Purpose: A relatively low response to chemotherapy has been reported for hormone receptor (HR)-positive breast cancer. In this study, we investigated the role of tryptophanyl-transfer RNA synthetase WARS) in the chemotherapeutic response of HR-positive breast cancer.
Methods: Pre-chemotherapeutic needle biopsy samples of 45 HR-positive breast cancer patients undergoing the same chemotherapeutic regimen were subjected to immunohistochemistry.
Gene expression in chronic granulomatous disease and interferon-γ receptor-deficient cells treated in vitro with interferon-γ.
J Cell Biochem
March 2019
Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts.
Interferon-γ (IFN-γ) plays an important role in innate and adaptive immunity against intracellular infections and is used clinically for the prevention and control of infections in chronic granulomatous disease (CGD) and inborn defects in the IFN-γ/interleukin (IL)-12 axis. Using transcriptome profiling (RNA-seq), we sought to identify differentially expressed genes, transcripts and exons in Epstein-Barr virus-transformed B lymphocytes (B-EBV) cells from CGD patients, IFN-γ receptor deficiency patients, and normal controls, treated in vitro with IFN-γ for 48 hours. Our results show that IFN-γ increased the expression of a diverse array of genes related to different cellular programs.
View Article and Find Full Text PDFSelective incorporation of 5-hydroxytryptophan into proteins in mammalian cells.
Proc Natl Acad Sci U S A
June 2004
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
An orthogonal tryptophanyl-transfer RNA (tRNA) synthetase (TrpRS)-mutant opal suppressor tRNA(Trp) (mutRNA(UCA)(Trp)) pair was generated for use in mammalian cells. The anticodon loop of the Bacillus subtilis tRNA(Trp) was mutated to UCA, three positions in the D arm were mutated to generate an internal promoter sequence, and the mutRNA(UCA)(Trp) gene was inserted between the 5' and 3' flanking sequences of the tRNA(Trp-1) gene from Arabidopsis to enhance its expression in mammalian cells. In vitro aminoacylation assays and in vivo opal suppression assays showed that B.
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