Empagliflozin induces apoptotic-signaling pathway in embryonic vasculature: In vivo and in silico approaches via chick’s yolk sac membrane model

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Сен. 1, 2022

The present investigation was conducted to evaluate the vascular-toxicity of empagliflozin (EMP) in embryonic vasculature. Firstly, drug as well its interaction with apoptotic regulator proteins predicted via silico approach. In next step, apoptotic-signaling pathway vasculature evaluated using a chick's YSM model. simulation confirmed EMP. There also an accurate affinity between EMP, Bax and Bcl-2 (-7.9 kcal/mol). Molecular dynamics assay revealed complex stability human body conditions. Furthermore, EMP is suggested alter more than BAX. Morphometric quantification vessels showed that activity related marked reduction vessel area, diameter mean capillary area. Based on qPCR immunohistochemistry assays, enhanced expression level BAX reduced responses YSM. We observed induction signal can cause defect vascular system following treatment. acquired data raised suspicions alteration genes are two critical pathways

Язык: Английский

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In silico study to identify novel NEK7 inhibitors from natural source by a combination strategy

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Авг. 7, 2023

Abstract Cancer remains a significant health problem and stands as one of the primary causes death worldwide. NEK7, NIMA-related protein kinase, plays crucial role in spindle assembly cell division. Dysregulation NEK7 contributes to development progression various malignancies, such colon cancer breast cancer. Therefore, inhibition shows promise potential clinical target for anticancer therapy. Nevertheless, there is dearth high-quality inhibitors. In this study, we utilized virtual screening, molecular docking, silicon-based pharmacokinetics, dynamics (MD) simulations, mechanics Poisson-Boltzmann surface area (MM/PBSA)-based binding free energy calculations comprehensively analyze effective natural inhibitors that within current framework. By employing including semi-flexible flexible docking methods, identified three products hit compounds with modes similar active control dabrafenib. ADME/T predictions indicated these molecules exhibited lower toxicity when administered orally. Additionally, through DFT calculations, determined popular compound (-)-balanol possessed high chemical activity. Finally, 100 ns simulations decomposition revealed displayed superior compared demonstrated higher affinity. Based on findings our research, conclude newly discovered may serve parent structures more potent derivatives promising biological activities. However, further experimental validation necessary part subsequent investigations.

Язык: Английский

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Therapeutic Targets and Molecular Mechanisms of Resveratrol in Amyotrophic Lateral Sclerosis: A Systematic Study of Network Pharmacology Incorporating Molecular Docking

MEDS Clinical Medicine, Год журнала: 2023, Номер 4(7)

Опубликована: Янв. 1, 2023

In order to explore the therapeutic targets and molecular mechanisms of resveratrol in amyotrophic lateral sclerosis based on network pharmacology docking techniques. this study, we obtained active compounds from TCMSP Chinese Medicine System Pharmacology database used Swiss Target Prediction platform predict potential compounds. The effective were GeneCards database, intersection was taken with resveratrol. Protein interaction networks performed using STRING further topology analysis Cytoscape 3.9.1 software. Meanwhile, gene ontology (GO) functional Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment intersecting by Metascape database; finally, validation carried out Pubchem PDB databases as well Pymol Autodocktools Resultly, forty-nine 1599 obtained. showed that could have effects through multi-targets multi-pathways. results core components bind better. Resveratrol mainly acts Pathways cancer pathway, Proteoglycans proteoglycans, Relaxin signaling Lipid atherosclerosis lipids such EGFR, PTGS2, SRC, MMP9, IGF1R so on. conclusion, study for treatment sclerosis, which provides a theoretical basis promoting development clinical application targeted drugs.

Язык: Английский

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Exploring the Potential Mechanism of Danshen in the Treatment of Concurrent Ischemic Heart Disease and Depression Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

Natural Product Communications, Год журнала: 2022, Номер 17(12)

Опубликована: Дек. 1, 2022

Objective: This study aimed to explore the potential targets and mechanism of action Danshen in treating concurrent ischemic heart disease (IHD) depression using network pharmacology, molecular docking, dynamics simulation (MDS). Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used obtain active ingredients Danshen. Candidate for IHD were obtained from Genecards DisGeNet databases. protein–protein interaction (PPI) constructed STRING Cytoscape 3.8.2 software. Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway analyses performed Metascape GlueGO package Molecular docking Autodock 1.5.6 Vina, MDS completed GROMACS 5.1.2. Results: We 65 with 131 candidate 39 intersection diseases. Luteolin, tanshinone IIA, salviolone core ingredients, AKT1, TNF, IL-6, MMP9, CASP3, IL-10, PTGS2, STAT3, PPARG, IL-4, EGFR, MAPK14, NOS3, EDN1 targets. GO KEGG enrichment revealed that mainly enriched positive regulation protein phosphorylation, blood circulation, IL-17 signaling pathway, VEGF JAK/STAT pathway. had a good affinity results protein-ligand complexes stable. Conclusions: pharmacology analyze treatment depression. Additionally, provided theoretical basis further studying pharmacological mechanisms

Язык: Английский

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Bioinformatics and systems biology approaches to identify the effects of COVID-19 on neurodegenerative diseases: A review

Medicine, Год журнала: 2022, Номер 101(49), С. e32100 - e32100

Опубликована: Дек. 9, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing disease (COVID-19), has been devastated by COVID-19 in an increasing number of countries and health care systems around the world since its announcement a global pandemic on 11 March 2020. During pandemic, emerging novel viral mutant variants have caused multiple outbreaks are prone to genetic evolution, serious damage human health. As confirmed cases spread rapidly, there is evidence that SARS-CoV-2 infection involves central nervous system (CNS) peripheral (PNS), directly or indirectly damaging neurons further leading neurodegenerative diseases (ND), but molecular mechanisms ND CVOID-19 unknown. We employed transcriptomic profiling detect several major ND: Alzheimer 's (AD), Parkinson' s (PD), sclerosis (MS) common pathways biomarkers association with COVID-19, helping understand link between COVID-19. There were 14, 30 19 differentially expressed genes (DEGs) (PD) (MS), respectively; enrichment analysis showed MAPK, IL-17, PI3K-Akt other signaling significantly expressed; hub (HGs) DEGs CRH, SST, TAC1, SLC32A1, GAD2, GAD1, VIP SYP. Analysis transcriptome data suggests co-morbid AD, PD, MS, providing new ideas therapeutic strategies for clinical prevention treatment ND.

Язык: Английский

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