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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 PDFTherapeutic Potential of Curcumin in Diabetic Cardiomyopathy: Modulation of Pyroptosis Pathways.
Cardiovasc Drugs Ther
January 2025
Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, China.
Purpose: Cardiac inflammation is a basic pathological process of diabetic cardiomyopathy (DCM). Inflammatory response is closely related to pyroptosis, which is a recently identified programmed cell death type. Curcumin (CUR) is a polyphenol extracted from turmeric and has been reported to be crucial in alleviating pyroptosis in DCM.
View Article and Find Full Text PDFBackground: Cholinergic innervation is particularly vulnerable in many neurodegenerative diseases such as Alzheimer's diseases. Nerve growth factor (NGF) plays a major role in the maintenance and function of cholinergic neurons, and a decrease in trophic signalling by NGF-Tropomyosin receptor kinase A (TrkA) contributes to cholinergic and synaptic degeneration. E2511 is a novel small molecule TrkA biased positive allosteric modulator showing an increase in specific trophic signalling via direct binding to TrkA with a potential to recover and reinnervate damaged cholinergic neurons.
View Article and Find Full Text PDFBackground: Increasing data indicates that the pathophysiology of microtubule associated protein tau is mediated by its interactions with RNA and RNA binding proteins via stress granules (SGs) and the translational stress response. Aquinnah now reports identifying small molecule compounds that inhibit tau/TIA1 SGs in neuronal cell lines and show strong in vivo efficacy in a classic mouse model of tauopathy.
Method: Compounds identified using high content imaging screening in SH-SY5Y neuroblastoma cells, inducibly over-expressing tau::GFP and TIA1::mKate2, following exposure to stressor.
Alzheimer's Imaging Consortium.
Alzheimers Dement
December 2024
Texas A&M University Health, Bryan, TX, USA.
Background: Our studies show that the small non-coding RNA, mir20a-3p, is neuroprotective for stroke in the acute phase and also attenuates long term cognitive decline in middle-aged female rats. Cognitive decline due to vascular diseases, such as stroke, is associated with secondary neurodegeneration in cortex and limbic structures. In this study, we assessed the volume of white matter, ventricles and regional diffusion-weighted MR imaging measures to delineate pathological tissue characteristics from the postmortem brain of stroke rats.
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