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Modulation of PI3K/AKT signaling and DFT modeling via selected pharmaceutical compounds attenuates carrageenan-induced inflammation and oxidative stress in rats.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, 12622, Egypt.
The main goal of the current study is to estimate the in vivo anti-inflammatory/antioxidant ability of four selected pharmaceutical compounds: bisoprolol (Biso), piracetam (Pirc), clopidogrel (Clop), and cinnarizine (Cinna). Indomethacin (Indo) was used as a reference drug to perform a realistic comparison between the four compounds and the Indo in vivo through tracking PI3K/AKT signaling and computational chemistry via density functional theory (DFT) modeling to analyze the electrostatic potential across the molecule and provide insight into the regions for receptor binding of the studied compounds. To achieve the safe dose of these compounds, cytotoxicity was performed against isolated adipose tissue-derived mesenchymal stem cells (ADMSCs) using MTT assay.
View Article and Find Full Text PDFRole of NRF2 in Pathogenesis of Alzheimer's Disease.
Antioxidants (Basel)
December 2024
Department of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan.
Alzheimer's disease (AD) is a polygenic, multifactorial neurodegenerative disorder and remains the most prevalent form of dementia, globally. Despite decades of research efforts, there is still no effective cure for this debilitating condition. AD research has increasingly focused on transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) as a potential therapeutic target.
View Article and Find Full Text PDFNrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases.
Antioxidants (Basel)
December 2024
Laboratory of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.
The NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is a potential therapeutic target for central nervous system diseases. This review emphasizes the role of oxidative stress and neuroinflammation in neurodegenerative diseases, highlighting the therapeutic potential of Nrf2 activators such as dimethyl fumarate (DMF). DMF, initially administered for treating psoriasis, has demonstrated efficacy in multiple sclerosis and is metabolized to monomethyl fumarate, which may exert significant therapeutic effects.
View Article and Find Full Text PDFPolysulfur-based bulking of dynamin-related protein 1 prevents ischemic sulfide catabolism and heart failure in mice.
Nat Commun
January 2025
National Institute for Physiological Sciences, National Institutes of Natural Sciences (NINS), Okazaki, Japan.
The presence of redox-active molecules containing catenated sulfur atoms (supersulfides) in living organisms has led to a review of the concepts of redox biology and its translational strategy. Glutathione (GSH) is the body's primary detoxifier and antioxidant, and its oxidized form (GSSG) has been considered as a marker of oxidative status. However, we report that GSSG, but not reduced GSH, prevents ischemic supersulfide catabolism-associated heart failure in male mice by electrophilic modification of dynamin-related protein (Drp1).
View Article and Find Full Text PDFPatient-derived response estimates from zero-passage organoids of luminal breast cancer.
Breast Cancer Res
December 2024
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
Background: Primary luminal breast cancer cells lose their identity rapidly in standard tissue culture, which is problematic for testing hormone interventions and molecular pathways specific to the luminal subtype. Breast cancer organoids are thought to retain tumor characteristics better, but long-term viability of luminal-subtype cases is a persistent challenge. Our goal was to adapt short-term organoids of luminal breast cancer for parallel testing of genetic and pharmacologic perturbations.
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