Bone tissue engineering is considered one of the pivotal treatments for bone defects in patients. However, the conventional strategies for repairing irregular and complex bone defects are highly unsatisfactory, and appropriate repairing of bone defects remains a challenge. In recent years, smart scaffolds integrated with multiple functions have emerged as promising alternatives for the treatment of various bone defects. In this study, 4D printed shape memory polymer (SMP) scaffolds containing bioactive fillers (hydroxyapatite and alendronate) and collagen–dexamethasone (Col–Dex) coating were fabricated, and their microstructures, porosity, mechanical properties, and biological functions were thoroughly investigated. The SMP scaffolds manufactured in this study could be programmed into temporary shapes of small sizes and then recovered to working sizes and shapes under an alternating magnetic field to fill bone defects. In addition, the biological studies including cytotoxicity tests, osteogenesis-related gene expressions, fluorescence staining imaging, and animal experiments demonstrated the effective biological activities and osteogenic effects of the 4D printed SMP scaffolds, with potential applications in bone tissue regeneration. In other words, the prepared 4D printed scaffolds with bioactive fillers and the Col–Dex coating will provide an efficient approach for personalized bone tissue repair as well as enhanced bone tissue regeneration.
Objective. This study is aimed at screening out effective active compounds of Qizhen capsule (QZC) and exploring the underlying mechanisms against gastric cancer (GACA) by combining both bioinformatic analysis and experimental approaches. Weighted gene coexpression network analysis (WGCNA), network pharmacology, molecular docking simulation, survival analysis, and data-based differential gene and protein expression analysis were employed to predict QZC’s potential targets and explore the underlying mechanisms. Subsequently, multiple experiments, including cell viability, apoptosis, and protein expression analyses, were conducted to validate the bioinformatics-predicted therapeutic targets. The results indicated that luteolin, rutin, quercetin, and kaempferol were vital active compounds, and TP53, MAPK1, and AKT1 were key targets. Molecular docking simulation showed that the four abovementioned active compounds had high binding affinities to the three main targets. Enrichment analysis showed that vital active compounds exerted therapeutic effects on GACA through regulating the TP53 pathway, MAPK pathway, and PI3K/AKT pathway. Furthermore, data-based gene expression analysis revealed that TP53 and JUN genes were not only differentially expressed between normal and GACA tissues but also correlated with clinical stages. In parallel, in vitro experimental results suggested that QZC exerted therapeutic effects on GACA by decreasing IC50 values, downregulating AKT expression, upregulating TP53 and MAPK expression, and increasing apoptosis of SGC-7901 cells. This study highlights the potential candidate biomarkers, therapeutic targets, and basic mechanisms of QZC in treating GACA, providing a foundation for new drug development, target mining, and related animal studies in GACA.
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