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Identification of key antifibrotic targets FPR1, TAS2R5, and LRP2BP of valsartan in diabetic nephropathy: A transcriptomics-driven study integrating machine learning, molecular docking, and dynamics simulations.
Int J Biol Macromol
January 2025
Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China. Electronic address:
Diabetic nephropathy (DN) is a major complication of diabetes and a leading cause of renal failure. While valsartan has been shown to alleviate DN clinically, its antifibrotic mechanisms require further investigation. This study used a transcriptomics-driven approach, integrating in vitro, Machine Learning, molecular docking, dynamics simulations and RT-qCPR to identify key antifibrotic targets.
View Article and Find Full Text PDFBeyond Redox Regulation: Novel Roles of TXNIP in the Pathogenesis and Therapeutic Targeting of Kidney Disease.
Am J Pathol
January 2025
Division of Nephrology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:
Cellular stress conditions, such as oxidative and endoplasmic reticulum (ER) stresses contribute to development of various kidney diseases. Oxidative stress is prompted by reactive oxygen species (ROS) accumulation and delicately mitigated by glutathione and thioredoxin (Trx) antioxidant systems. Initially identified as a Trx-binding partner, thioredoxin interacting protein (TXNIP) is significantly upregulated and activated by oxidative and ER stresses.
View Article and Find Full Text PDFEpithelial OPA1 links mitochondrial fusion to inflammatory bowel disease.
Sci Transl Med
January 2025
Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91052 Erlangen, Germany.
Dysregulation at the intestinal epithelial barrier is a driver of inflammatory bowel disease (IBD). However, the molecular mechanisms of barrier failure are not well understood. Here, we demonstrate dysregulated mitochondrial fusion in intestinal epithelial cells (IECs) of patients with IBD and show that impaired fusion is sufficient to drive chronic intestinal inflammation.
View Article and Find Full Text PDFHorizontal and longitudinal targeted metabolomics in healthy pregnancy and gestational diabetes mellitus.
Acta Diabetol
January 2025
Department of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Objective: The objective is to investigate the differences in urinary organic acid (OA) profiles and metabolism between healthy control (HC) pregnant women and those with gestational diabetes mellitus (GDM) during the second trimester and third trimester of pregnancy.
Methods: A total of 66 HC pregnant women and 32 pregnant women with GDM were assessed for 107 hydrophilic metabolites in urine samples collected during the second and third trimester of pregnancy using tandem mass spectrometry. The urine OA profiles for each group were obtained, and metabolomic analysis and discussion were conducted.
Mitoregulin self-associates to form likely homo-oligomeric pore-like complexes.
iScience
January 2025
Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
We and others previously found that a misannotated long noncoding RNA encodes for a conserved mitochondrial transmembrane microprotein named Mitoregulin (Mtln). Beyond an established role for Mtln in lipid metabolism, Mtln has been shown to broadly influence mitochondria, boosting respiratory efficiency and Ca retention capacity, while lowering ROS, yet the underlying mechanisms remain unresolved. Prior studies have identified possible Mtln protein interaction partners; however, a lack of consensus persists, and no claims have been made about Mtln's structure.
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