The therapeutic potential of extracellular vesicles (EVs) in bone regeneration is noteworthy; however, their clinical application is impeded by low yield and limited efficacy. This study investigated the effect of low-intensity pulsed ultrasound (LIPUS) on the therapeutic efficacy of EVs derived from periodontal ligament stem cells (PDLSCs) and preliminarily explored its mechanism. PDLSCs were cultured with osteogenic media and stimulated with or without LIPUS, and then EVs and LIPUS-stimulated EVs (L-EVs) were isolated separately.
View Article and Find Full Text PDFBackground: There is a documented risk of emotional and behavioral disorders in children with leukemia. Assessing the factors contributing to their behavioral disorders is particularly important from a prevention perspective.
Objective: The aim of this study was to study the influencing factors of internalizing and externalizing behaviors in children with leukemia from the perspective of adult family members.
Metformin has shown outstanding anti-inflammatory and osteogenic abilities. Mesenchymal stem cell-derived extracellular vesicles (EVs) reveal promising therapeutic potency by carrying various biomolecules. This study explored the effects of metformin on the therapeutic potential of EVs derived from human periodontal ligament stem cells (PDLSCs) for periodontitis.
View Article and Find Full Text PDFHerein, we described the rational drug design and synthesis of a series of 5-amino-4-fluoro-1-benzo[]imidazole-6-carboxamide derivatives that inhibit MEK and RAF kinases. The detailed screening cascades revealed that was a preferred compound, which might act like a "clamp" to stabilize the MEK/RAF complex, thereby effectively inhibiting MEK1, BRAF, and BRAF with IC values of 28, 3, and 3 nM, respectively. possessed an excellent selectivity over other 312 human-related kinases at 1 μM.
View Article and Find Full Text PDFComb Chem High Throughput Screen
July 2024
ATM plays an important role in DNA damage response and is considered a potential target in cancer therapies. In this study, a goal-directed molecular generation approach based on ligand similarity and target specificity was applied to sample active molecules, and they were screened virtually to identify the theoretical lead compound , which was later shown to inhibit ATM adequately. However, there is a main concern about its poor metabolic stability .
View Article and Find Full Text PDFSelectively targeting the cannabinoid receptor CB2 is an attractive therapeutic strategy for the treatment of inflammatory pain without psychiatric side effects mediated by the cannabinoid receptor CB1. Herein, we report the discovery of 4-(1,2,4-oxadiazol-5-yl)azepan-2-one derivatives as a new class of CB2 agonists. Systematic structure-activity relationship investigations resulted in the identification of the most potent compound .
View Article and Find Full Text PDFCancer immunotherapy, including the inhibition of immune checkpoints, improves the tumor immune microenvironment and is an effective tool for cancer therapy. More effective and alternative inhibitory targets are critical for successful immune checkpoint blockade therapy. The interaction of the immunomodulatory ligand B7 family with corresponding receptors induces or inhibits T cell responses by sending co-stimulatory and co-inhibitory signals respectively.
View Article and Find Full Text PDFSichuan Da Xue Xue Bao Yi Xue Ban
November 2022
With the rapid development of modern biomedical technology industry, background and knowledge of a single discipline will not be adequate to meet the needs of research and development of cutting-edge technology. The cultivation of innovative research talents with interdisciplinary background at the undergraduate level poses great challenges for higher education institutions. National-level research institutes, including state key laboratories and national clinical research centers, for example, have an enormous supply of technological human resources and resources for research and teaching, which is of critical importance for the training of innovative talents at the undergraduate level.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
December 2021
Objective: To explore the effects of Eriodictyol to the growth, apoptosis and oxidative stress of Burkitt lymphoma (BL) cells and phosphorylation of protein kinase B (AKT) in children.
Methods: The effects of Eriodictyol (0, 1.25, 2.
In the process of cancer EMT, some subgroups of cancer cells simultaneously exhibit both mesenchymal and epithelial characteristics, a phenomenon termed partial EMT (pEMT). pEMT is a plastic state in which cells coexpress epithelial and mesenchymal markers. In squamous cell carcinoma (SCC), pEMT is regulated, and the phenotype is maintained via the HIPPO pathway, NOTCH pathway and TGF-β pathways and by microRNAs, lncRNAs and the cancer microenvironment (CME); thus, SCC exhibits aggressive tumorigenic properties and high stemness, which leads collective migration and therapy resistance.
View Article and Find Full Text PDFTYK2 mediates signaling of IL-23, IL-12, and Type I IFN-driven responses that are critical in immune-mediated diseases. Herein, we report the design, synthesis, and structure-activity relationships (SARs) of 3-(4-(2-((1-indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1-pyrazol-1-yl)propanenitrile derivatives as selective TYK2 inhibitors. Among them, compound exhibited acceptable TYK2 inhibition with an IC value of 9 nM, showed satisfactory selectivity characteristics over the other three homologous JAK kinases, and performed good functional potency in the JAK/STAT signaling pathway on lymphocyte lines and human whole blood.
View Article and Find Full Text PDFThe development of biomimetic bone graft materials for periodontal tissue engineering is a field of topical interest. In this study, we designed a dual-functionalized apatite nanocomposite, which could integrate multiple molecular cues for manipulating the fate of periodontal ligament stem cells (PDLSCs). Briefly, inspired by mussels, a biomimetic nanohydroxyapatite was fabricated using a polydopamine structure as a template (named as tHA) and then surface-modified with bone-forming peptide-1 (BFP-1) and vascular endothelial growth factor-mimicking peptide (QK) via a single step of catechol chemistry.
View Article and Find Full Text PDFIn this study, we described a series of -(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine derivatives as selective JAK2 (Janus kinase 2) inhibitors. Systematic exploration of the structure-activity relationship though cyclization modification based on previously reported compound led to the discovery of the superior derivative . Compound showed excellent potency on JAK2 kinase, SET-2, and Ba/F3 cells (high expression of JAK2 mutation) with IC values of 3, 11.
View Article and Find Full Text PDFHerein, we describe the design, synthesis, and structure-activity relationships of a series of unique 4-(1-pyrazol-4-yl)-pyrimidin-2-amine derivatives that selectively inhibit Janus kinase 2 (JAK2) and FLT3 kinases. These screening cascades revealed that was a preferred compound, with IC values of 0.7 and 4 nM for JAK2 and FLT3, respectively.
View Article and Find Full Text PDFPeriodontitis is a chronic infectious disease involving periodontal tissues. Periodontal ligament cells (PDLCs) play an important role in the regeneration of periodontal tissue. However, senescent PDLCs have an impeded regenerative potential.
View Article and Find Full Text PDFLow intensity pulsed ultrasound (LIPUS) promotes bone fracture healing in clinical therapy. Transcription factor Forkhead box O1 (FOXO1) is crucial for bone differentiation. But whether FOXO1 is involved in LIPUS-promoted bone differentiation is largely unknown.
View Article and Find Full Text PDFPolydopamine-templated hydroxyapatite (tHA) is a type of nano-biomaterial that can promote osteogenesis in bone tissue engineering. However, high concentrations of tHA stimulate production of reactive oxygen species (ROS), resulting in cell injury and apoptosis. Metformin has been demonstrated to activate the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which induces autophagy and decreases ROS production to prevent apoptosis.
View Article and Find Full Text PDFA series of pyrrolo[2,3- d]pyrimidine derivatives were prepared and optimized for cytotoxic activities against FLT3-ITD mutant cancer cells. Among them, compound 9u possessed nanomolar FLT3 inhibitory activities and subnanomolar inhibitory activities against MV4-11 and Molm-13 cells. It also showed excellent inhibitory activities in FLT3-ITD-D835V and FLT3-ITD-F691L cells which were resistant to quizartinib.
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