Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025076
EGFR-tyrosine kinase inhibitor (TKI) therapy is the most effective targeted therapy for non-small cell lung cancer (NSCLC). However, drug resistance remains a significant factor in the failure of lung cancer therapy. In the present study, we utilize network pharmacology, molecular docking, in vitro and in vivo experiments to explore the targets and biological mechanisms of CP, a novel curcumin-piperlongumine hybrid molecule, in EGFR-TKI-resistant NSCLC cells. The results reveal that CP exhibits enhanced biological activity compared to its parent compounds. CP can effectively inhibit cell proliferation by arresting cell cycle in the G2/M phase and inducing apoptosis. Mechanistically, CP-induced apoptosis is partially mediated by PI3K/AKT signaling pathway. These findings highlight the potential of CP as a promising therapeutic agent for EGFR-TKI-resistant lung cancer therapy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21525
BACKGROUND: Anterior tooth intrusion is commonly used in the deep overbite cases with clear aligners. However, the intrusion efficiency varies significantly among different cases. OBJECTIVE: To analyze and compare the intrusion efficiency of the anterior teeth with clear aligners by the indirect model superimposition method based on the occlusal records. METHODS: Forty-three patients with anterior deep overbite were selected as the subjects of this study and divided into the non-extraction and extraction groups. The non-extraction group was then divided into the alignment and maxillary molar distalization subgroups. The extraction group was subdivided into the first premolar extraction and second premolar extraction subgroups. In the Geomagic 2014 software, the occlusal plane inclinations of the pre- and post-treatment models were calibrated based on the angle between the Frankfort plane and occlusal plane. The maxillary and mandibular models were superimposed by the maxillary palatine folds and occlusal records. Based on the Frankfort plane, the measurement coordinate system was established to measure the actual intrusion amount. The relative intrusion amount in the ClinCheck plan was recorded as the designed intrusion amount. Correlation and linear regression analyses were performed between the designed and actual intrusion amounts. RESULTS AND CONCLUSION: (1) The actual intrusion amount of anterior teeth in both non-extraction and extraction groups was significantly less than the designed amount (P < 0.01), indicating that overcorrection should be designed when intruding anterior teeth with clear aligners. (2) The anterior intrusion efficiency in the non-extraction group (50.69%) was significantly higher than that in the extraction group (39.73%) (P < 0.01), suggesting that more overcorrection should be designed in extraction cases. (3) The intrusion efficiency of lower anterior teeth was significantly higher than that of upper anterior teeth (P < 0.01), so more overcorrection should be designed for upper anterior teeth. (4) There was no significant difference in anterior intrusion efficiency between the maxillary molar distalization subgroup and the simple alignment subgroup (P > 0.05). (5) The anterior intrusion efficiency in the second premolar extraction subgroup was significantly higher than that in the first premolar extraction subgroup (P < 0.01), indicating that extraction of the second premolar is more favorable for vertical control of anterior teeth than extraction of the first premolar. (6) There was a linear relationship between the designed and actual intrusion amounts in all groups, and the regression equations can provide a reference for clinicians to design individualized overcorrection amounts according to different tooth positions and different treatment plans.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025076
Acquired resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs) such as osimertinib (AZD9291) remains an unresolved clinical bottleneck in non-small cell lung cancer (NSCLC), with median progression-free survival plateauing at 18.9 months. This study evaluates CP, a novel curcumin-piperlongumine hybrid molecule, against AZD9291-resistant NSCLC using network pharmacology, molecular docking, and in vitro/in vivo validation. PPI network analysis of intersecting targets identified EGFR, SRC, PIK3R, PIK3CA, KDR, MET, GRB2, PIK3CB, HSP90AA1, and ITGB1 as core nodes, with KEGG enrichment converging on the PI3K/AKT signaling axis. Molecular docking confirmed hydrogen-bond-mediated binding between CP and these targets. Western blot analysis demonstrated that CP markedly suppressed phosphorylation of EGFR, PI3K, AKT, and GSK-3β. Functionally, CP arrested the cell cycle at G2/M and induced apoptosis in drug-resistant NSCLC cells, with enhanced potency relative to parent compounds curcumin and piperlongumine. In vivo xenograft experiments corroborated growth inhibition. The data position CP as a dual-pathway inhibitor targeting both EGFR and PI3K/AKT cascades, providing a mechanistic rationale for its development as a therapeutic candidate in EGFR-TKI-resistant advanced NSCLC. The unresolved question of whether GSK-3β inhibition operates independently of EGFR-AKT signaling warrants further investigation.