Construction of hollow polydopamine nanoparticle based drug sustainable release system and its application in bone regeneration / 国际口腔科学杂志·英文版

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.

Regulation of FN1 degradation by the p62/SQSTM1-dependent autophagy-lysosome pathway in HNSCC / 国际口腔科学杂志·英文版

Epithelial-mesenchymal transition (EMT) is involved in both physiological and pathological processes. EMT plays an essential role in the invasion, migration and metastasis of tumours. Autophagy has been shown to regulate EMT in a variety of cancers but not in head and neck squamous cell carcinoma (HNSCC). Herein, we investigated whether autophagy also regulates EMT in HNSCC. Analyses of clinical data from three public databases revealed that higher expression of fibronectin-1 (FN1) correlated with poorer prognosis and higher tumour pathological grade in HNSCC. Data from SCC-25 cells demonstrated that rapamycin and Earle's balanced salt solution (EBSS) promoted autophagy, leading to increased FN1 degradation, while 3-methyladenine (3-MA), bafilomycin A1 (Baf A1) and chloroquine (CQ) inhibited autophagy, leading to decreased FN1 degradation. On the other hand, autophagic flux was blocked in BECN1 mutant HNSCC Cal-27 cells, and rapamycin did not promote autophagy in Cal-27 cells; also in addition, FN1 degradation was inhibited. Further, we identified FN1 degradation through the lysosome-dependent degradation pathway using the proteasome inhibitor MG132. Data from immunoprecipitation assays also showed that p62/SQSTM1 participated as an autophagy adapter in the autophagy-lysosome pathway of FN1 degradation. Finally, data from immunoprecipitation assays demonstrated that the interaction between p62 and FN1 was abolished in p62 mutant MCF-7 and A2780 cell lines. These results indicate that autophagy significantly promotes the degradation of FN1. Collectively, our findings clearly suggest that FN1, as a marker of EMT, has adverse effects on HNSCC and elucidate the autophagy-lysosome degradation mechanism of FN1.

Effect of gefitinib on mucus hypersecretion in chronic obstructive pulmonary disease / 中华老年医学杂志

Objective To investigate the effect of gefitinib on mucus hypersecretion by inhibiting epidermal growth factor receptor (EGFR) activity in chronic obstructive pulmonary disease (COPD).Methods Human airway epithelail cell lines 16HBE cells were exposed to cigarette smoke extraction (CSE) to establish the COPD model.EGFR activity was inhibited by tyrosine kinase inhibitor gefitinib.The mRNA expressions of EGFR and MUC5AC were detected by real-time PCR.EGFR,p-EGFR and MUC5AC protein levels were determined by Western blot and ELISA.Results EGFR mRNA level was increased by 12.7％ in CSE and 8.6％ in gefitinib group,but had no significant differences among CSE,gefitinib group and control group (all P＞ 0.05).MUC5AC mRNA levels were enhanced by 141.7％,26.4％ in CSE group and gefitinib group respectively,and there were significant differences among CSE,gefitinib group and control group (all P＜0.05).EGFR protein levels were (600.34±64.58) μg/mg,(632.58±72.94) μg/mg,(584.57±67.39) μg/mg,in control,CSE and gefitinib groups,respectively,and there were no significant differences between groups (all P＞0.05).p-EGFR protein levels were (338.62±45.28) μg/mg,(679.43±78.23) μg/mg,(292.74±59.17) μg/mg in control,CSE and gefitinib groups,respectively.MUC5AC protein levels were(72.80±6.25)μg/mg,(187.00±±10.26)μg/mg,(92.57±8.32)μg/mg in control,CSE and gefitinib groups respectively.Compared with control group,p-EGFR and MUC5AC protein levels were increased significantly in CSE group (both P＜0.05),and had no significant differences in p EGFR and MUC5AC protein levels between control group and gefitinib group.Conclusions CSE may lead to mucus hypersecretion through activating the EGFR-mediated signaling pathways.Gefitinib may inhibit mucus hypersecretion by inhibiting EGFR tyrosine kinanse activity.EGFR may serve as a potential target for COPD.

Comparison of body artery imaging between dual-energy CT angiography and traditional 3D CT angiography / 中国医学影像技术

Objective To evaluate the effect of automatic bone and plaque removal on image quality and grading of steno-occlusive lesions in patients undergoing dual energy CT angiography (DE-CTA) of body artery. Methods DE-CTA was performed in 23 patients with suspected body vascular disease. Separate datasets were calculated for each of the two tubes and used to generate automatically bone-subtracted images (ABS) as well as additional manual bone removes after plaque subtracted images (ABPS). In addition, a weighted average dataset from both dual energy acquisitions resembling routine 3D CT acquisition was used for automatic bone remove (ABR). Residual bone in the ABR dataset was removed manually (ABR-M). Operator time for bone removal was measured, while effectiveness of bone subtraction and the time needed of ABPS and ABR-M was assessed. Compared with MPR, ABR images and stenosis grading in plaque subtracted were assessed with two radiologists. Results The imaging quality of ABR was superior to that of ABS (P<0.05). The time needed of ABPS was (7.8±4.3) min, significantly lower than that of ABR-M (11.4 min±2.5 min, P<0.05). A total of 325 steno-occlusive lesions were assessed. The sensitivity, specificity of DE-CTA and traditional 3D CTA was 95.74%, 96.19% and 92.93%, 97.87%, respectively. Conclusion The imaging quality is good after automatic bone and plaque subtraction of DE-CTA. Automatic plaque subtraction for the first time provides a true CTA imaging which is easy to interpret and reduces the need for further post-processing. The diagnosis of vascular stenosis with DE-CTA is also accurate, and the time spent in post-processing is less than that of traditional 3D angiography.

Application of energy subtract angiography of dual source CT in diagnosis of arterial diseases of the lower extremities / 中国医学影像技术

Objective To observe the value of dual source CT (DSCT) dual energy subtract method in diagnosis of lower extremity arterial occlusion. Methods Thirty-two patients with lower extremity arterial occlusive diseases underwent DSCT direct bone removal CT angiography (DE-BR-CTA) and digital subtraction angiography (DSA) within 2 weeks. Raw data were reconstructed with techniques including MIP and VR. Arterial visibility of DE-BR-CTA was analyzed by two experienced radiologists taking DSA as the standard. Results A total of 328 arterial segments were selected in 32 patients with lower extremity arterial occlusive diseases. The correlation between DSA and DE-BR-CTA was good. There was no significant difference in arterial visibility between DE-BR-CTA and DSA (P＞0.05). Compared with DSA, 12 of the segmental stenosis were overestimated and 6 were underestimated with DE-BR-CTA. When stenosis was over 10%, the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of DE-BR-CTA was 94.51%, 96.15%, 93.02%, 92.59% and 96.39%, respectively. Conclusion DSCT energy subtraction angiography is an accurate diagnostic method and non-invasive imaging technology in the assessment of lower extremity arterial occlusive diseases. It may provide precious information for pre-surgery evaluation and screening the arterial diseases of the lower extremities.