Periodontal ligament stem cells (PDLSCs) are important candidate seed cells for alveolar bone tissue engineering. Dasatinib is a tyrosine kinase inhibitor, and its influence on the osteogenic differentiation of mesenchymal stem cells is a controversial topic. The present study explored the effects of different concentrations of dasatinib on the proliferation and osteogenic differentiation of PDLSCs and tentatively revealed the related mechanism. The results of CCK8 showed that low concentrations of dasatinib (1 nM) did not affect proliferation, while high concentrations of dasatinib significantly inhibited the proliferative activity of PDLSCs. This could be related to the inhibiting effects of dasatinib on Erk signals. ALP staining, alizarin red staining, and western blot proved that low concentrations of dasatinib (1 nM) promoted the osteogenic differentiation of PDLSCs, while high concentrations of dasatinib inhibited it. The negative effects of dasatinib on osteogenic differentiation were reversed when EID3 was knocked down, suggesting that EID3 mediates the regulation of dasatinib on the osteo-differentiation of PDLSCs. Taken together, high concentrations of dasatinib inhibited the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals, while low concentrations of dasatinib could be a potential method to enhance the bone regeneration ability of PDLSCs.
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http://dx.doi.org/10.7150/ijms.87089 | DOI Listing |
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January 2025
Jagiellonian University, Faculty of Chemistry, Department of Chemical Physics, Gronostajowa 2 St, 30-387 Krakow, Poland.
Since their approval, tyrosine kinase inhibitors (TKIs) have been widely used in antitumor therapy for chronic myeloblastic leukemia. Despite being approved by the FDA in 2001 to treat a rare cancer called chronic myeloid leukemia (CML), imatinib and other TKIs remain subjects of research for several reasons, such as their long-term effects, resistance, or molecular mechanisms. This study uses Raman and fluorescence imaging to investigate the cytotoxic effects of two TKIs, imatinib and dasatinib, on human aortic endothelial cells (HAECs).
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January 2025
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Introduction: Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous malignancy is often associated with unfavorable prognosis. Due to its unique anatomical position and the absence of effective early inspection methods, surgical intervention alone is frequently inadequate for achieving complete remission. Therefore, the identification of reliable biomarker is crucial to enhance the accuracy of screening and treatment strategies for HNSCC.
View Article and Find Full Text PDFBiomed Chromatogr
February 2025
Department of Pharmaceutical Analysis, School of Pharmacy, Anurag University, Medchal-Malkajgiri, Hyderabad, Telangana, India.
Paxalisib is a dual PI3K/mTOR inhibitor, being used in advanced cancer treatment. In this research, we report a validated LC-MS/MS method for quantifying paxalisib from mouse dried blood spot (DBS). We validated the method in-line with the FDA guidelines.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Dipartimento di Bioscienze, Università degli Studi di Milano, Milan 20133, Italy.
The computational study of ligand binding to a target protein provides mechanistic insight into the molecular determinants of this process and can improve the success rate of drug design. All-atom molecular dynamics (MD) simulations can be used to evaluate the binding free energy, typically by thermodynamic integration, and to probe binding mechanisms, including the description of protein conformational dynamics. The advantages of MD come at a high computational cost, which limits its use.
View Article and Find Full Text PDFInt J Pharm
January 2025
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India. Electronic address:
Dasatinib (DASA), a potent second-generation multitarget kinase inhibitor marketed as Sprycel® (Tablet), is limited by poor oral bioavailability (14-24 %) and dose-related gastrointestinal side effects. A supersaturable self-nanoemulsifying drug delivery system (su-SNEDDS) designed to enhance DASA's solubility, sustain supersaturation, and improve oral bioavailability. The su-SNEDDS formulation comprises DASA, an oil, surfactant, co-surfactant, and polyvinylpyrrolidone (PVP) K30 as a precipitation inhibitor (PI).
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