The Akt pathway plays a significant role in various diseases like Alzheimer's, Parkinson's, and Diabetes. Akt is the central protein whose phosphorylation controls many downstream pathways. Binding of small molecules to the PH domain of Akt facilitates its phosphorylation in the cytoplasm and upregulates the Akt pathway. In the current study, to identify Akt activators, ligand-based approaches like 2D QSAR, shape, and pharmacophore-based screening were used, followed by structure-based approaches such as docking, MM-GBSA, ADME prediction, and MD simulation. The top twenty-five molecules from the Asinex gold platinum database found to be active in most 2D QSAR models were used for shape and pharmacophore-based screening. Later docking was performed using the PH domain of Akt1 (PDB: 1UNQ), and 197105, 261126, 253878, 256085, and 123435 were selected based on docking score and interaction with key residues, which were druggable and formed a stable protein-ligand complex. MD simulations of 261126 and 123435 showed better stability and interactions with key residues. To further investigate the SAR of 261126 and 123435, derivatives were downloaded from PubChem, and structure-based approaches were employed. MD simulation of derivatives 12289533, 12785801, 83824832, 102479045, and 6972939 was performed, in which 83824832 and 12289533 showed interaction with key residues for a longer duration of time, proving that they may act as Akt activators.
Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
Background: Acute myocardial infarction (AMI) remains a significant cause of global mortality, exacerbated by ischemia-reperfusion (IR) injury. Myocardial cell pyroptosis has emerged as a critical pathway influencing IR injury severity.
Methods: We aimed to investigate the cardioprotective effects of aerobic exercise on IR injury by examining the modulation of IGFBP2 and its impact on GSDME-dependent myocardial cell pyroptosis.
Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis, and the main objective of this study was to reveal the specific mechanism of action of TN-CAP1-mediated macrophage-fibroblast crossinulation in the progression of PDAC, and to evaluate the function and potential therapeutic value of ITGB5 and ITGB1 recombinant proteins in this process. The expression of TN-CAP1 in tumor tissues of PDAC patients was analyzed by immunohistochemistry and compared with normal pancreatic tissues. The co-culture system of macrophages and fibroblasts was constructed using in vitro cell culture model.
Bipolar disorder (BD) is a central nervous system condition that is typified by fluctuations in mood, oscillating between depressive and manic, and/or hypomanic episodes. The objective of this study was to test the hypothesis that strength training may act as a potent protector against behavioral and neurochemical changes induced by BD. A strength training protocol was performed with adult male Wistar rats, and seven days following the conclusion of training, a single ouabain injection was administered.
The management of hair loss is vital in clinical dermatology due to its prevalence and impact on patients' quality of life. Quercetin is recognized for its diverse activities, including anti-inflammatory, anti-cancer, and immune regulation. However, its effects on human hair follicles and mechanisms remain unclear.
Decidualization of endometrial stromal cells is a prerequisite for successful embryo implantation and early pregnancy. Decidualization dysregulation results in implantation failure. In our previous study, we reported that PAI-1 is abnormally downregulated in the endometrial tissue samples of patients with recurrent implantation failure.
