Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Objective: To discuss the correlation between the extraction timing of mesiodens and the orthodontic treatment duration of its eruption-related complications in children to provide a reference for the clinic. Methods : The mesiodentes of 187 children were classified as eruption type (typeⅠ), dental crown impacted type (type Ⅱ), interdental impacted type (type Ⅲ), and dental root impacted type (type Ⅳ). According to the timing of extraction, mesiodentes in typeⅠ, type Ⅲ, and type Ⅳ were divided into Groups A: before the eruption of the adjacent central incisor and B: after the eruption of the adjacent central incisor. Mesiodentes in type Ⅱ were divided into Group A: before the eruption of the contralateral central incisor and B: after the eruption of the contralateral central incisor. Eruption-related complications and orthodontic treatment durations caused by mesiodens were statistically analyzed. Results : There were 106 cases of displacement, 28 cases of failed eruption, 27 cases of tooth rotation, and 26 cases of individual cross-bite among the eruption-related complications caused by mesiodens. The mean orthodontic treatment cycle in Group A of type Ⅰ (7.07 ± 2.45 month), Group A of type Ⅱ (6.57 ± 1.12 month), and Group A of type Ⅲ (6.95 ± 2.52 month) were lower than that in Group B of type Ⅰ (9.67 ± 3.04 month), Group B of type Ⅱ (10.25 ± 1.29 month), and Group B of type Ⅲ (9.33 ± 3.26 month), and the differences were statistically significant (P<0.01). Meanwhile, there was no significant difference in the mean orthodontic treatment duration between Groups A (6.00 ± 0.94 month) and B (6.33 ± 0.80 month) of type Ⅳ (P>0.05). Conclusion In most cases, the mesiodens are removed before the eruption of the adjacent central incisor, which can reduce the duration of orthodontic treatment for eruption-related complications in children.

OBJECTIVETo observe the protective effect of acupuncture preconditioning at "Jiaji" (EX-B 2) on acute myocardial ischemia-reperfusion injury (MIRI) in the rats and explore the mechanism.

METHODSFifty Wistar rats were randomly divided into a control group, a model group, a Jiaji group, a Neiguan group and a Quchi group, 10 rats in each one. In the Jiaji group, the Neiguan group and the Quchi group, electroacupuncture was given for preconditioning at "Jiaji" T4~T5 (EX-B 2), "Neiguan" (PC 6) and "Quchi" (LI 11) for 7 days before modeling. In the control group and the model group, the regular feeding was given, without any acupuncture. At the end of acupuncture, except the control group, ligating the left anterior descending coronary artery (LAD) was adopted to duplicate MIRI models in the rest groups. Electrocardio-gram (ECG) was monitored and ST-segment shift was analyzed. HE staining method was adopted to observe the morphology of cardiac tissue in the rats of the groups. The transmission electron microscope was used to observe myocardial cell ultrastructure. WST-1 method was used to determine the activity of serum superoxide dismutase (SOD), TBA method was used to determine the content of serum malondialehyde (MDA) and the real-time fluorescent quantitative PCR method to determine the expressions of Nrf 2 in ischemic myocardial tissue and downstream HO-1 gene.

RESULTSCompared with the control group, after LAD ligation, ST-segment was elevated and depressed in ECG apparently after reperfusion in the rest groups (all<0.05). The ST-segment elevation in the Jiaji group and the Neiguan group was less than that in the model group (both<0.05). Compared with the model group, SOD activity was increased apparently in the Jiaji group and the Neiguan group (both<0.05), and MDA content was reduced apparently (both<0.05). The effects in the Jiaji group were better than those in the Neiguan group (both<0.05). Pathologically, "Jiajia" (EX-B 2) and "Neiguan" (PC 6) all improved the morphology of cardiac tissue and cell ultrastructure. The effects in the Jiaji group were much more significant and the improvements in the Quchi group were not apparent. Compared with the control group, the expressions of Nrf 2 and HO-1 gene in myocardial tissue were down-regulated in the model group (both<0.05). Those were up-regulated apparently in the Jiaji group and the Neiguan group as compared with the model group (<0.05,<0.01). The up-regulation times of the expressions of Nrf 2 and HO-1 gene in the Jiajia group were the highest in comparison.

CONCLUSIONSAcupuncture preconditioning at "Jiaji" (EX-B 2) has the protective effect on cardiac ischemia and reperfusion damage, which is probably relevant with the up-regulation of Nrf 2-ARE pathway expression, the activation of endogenous anti-oxidative pathway, the improvement of oxygen free radical scavenging capacity and the alleviation of lipid peroxide damage.