Estrogen receptor alpha mediates 17ß-estradiol, up-regulates autophagy and alleviates hydrogen peroxide-induced vascular senescence.

Atherosclerosis threatens human health by developing cardiovascular diseases, the deadliest disease world widely. The major mechanism contributing to the formation of atherosclerosis is mainly due to vascular endothelial cell (VECs) senescence. We have shown that 17ß-estradiol (17ß-E2) may protect VECs from senescence by upregulating autophagy. However, little is known about how 17ß-E2 activates the autophagy pathway to alleviate cellular senescence. Therefore, the aim of this study is to determine the role of estrogen receptor (ER) α and ß in the effects of 17ß-E2 on vascular autophagy and aging through in vitro and in vivo models. Hydrogen peroxide (H2O2) was used to establish Human Umbilical Vein Endothelial Cells (HUVECs) senescence. Autophagy activity was measured through immunofluorescence and immunohistochemistry staining of light chain 3 (LC3) expression. Inhibition of ER activity was established using shRNA gene silencing and ER antagonist. Compared with ER-ß knockdown, we found that knockdown of ER-α resulted in a significant increase in the extent of HUVEC senescence and senescence-associated secretory phenotype (SASP) secretion. ER-α-specific shRNA was found to reduce 17ß-E2-induced autophagy, promote HUVEC senescence, disrupt the morphology of HUVECs, and increase the expression of Rb dephosphorylation and SASP. These in vitro findings were found consistent with the in vivo results. In conclusion, our data suggest that 17ß-E2 activates the activity of ER-α and then increases the formation of autophagosomes (LC3 high expression) and decreases the fusion of lysosomes with autophagic vesicles (P62 low expression), which in turn serves to decrease the secretion of SASP caused by H2O2 and consequently inhibit H2O2-induced senescence in HUVEC cells.

Cone-beam computed tomography study of the incidence and characteristics of the second mesiobuccal canal in maxillary permanent molars.

Objective: This study aimed to review the characteristics of the second mesiobuccal canal (MB2) in the maxillary first and second permanent molars of 500 patients to analyze the incidence of MB2 and its connection with gender, age, tooth position, and mesiobuccal (MB) root length. The study also aimed to investigate the distribution of the root canal orifice on the pulp chamber floor to obtain an imaging reference for clinical practices related to maxillary molars in Fujian, China. Methods: In accordance with the enrollment criteria, cone-beam computed tomography images of the maxillofacial area were collected from 500 patients, including 1,000 maxillary first molars and 1,000 maxillary second molars. The patients were grouped according to gender and tooth position. The incidence of MB2 was observed, and the MB root length and distribution angle of the mesiobuccal-palatal-distobuccal root canal orifices were measured for statistical analysis. Results: The overall incidence of MB2 in maxillary first and second molars was 51.1% and 32.9%, respectively. The incidence of MB2 in maxillary molars was 50% in male patients and 35.45% in female patients, with a significant difference (p < 0.05). The incidence of MB2 in maxillary molars was significantly higher in subjects aged below 50 (especially in male patients) than those aged 50 and above. The MB root length of maxillary first and second molars with MB2 was longer than that without MB2, and the difference was statistically significant. An association was identified between the incidences of MB2 in contralateral molars of the same type and in ipsilateral adjacent molars. When MB2 occurred in the MB root of maxillary molars, the root canals were mostly classified as type IV, followed by type II. The angle formed by the MB-P-DB orifices on the pulp chamber floor in the maxillary first and second molars was (25.23 ± 5.20) and (20.17 ± 10.88)°respectively. Conclusion: The incidence of MB2 in maxillary molars is high in Fujian, China. The occurrence of MB2 is affected by gender, age, and length of MB root, and it occurs symmetrically in adjacent molars and in contralateral molars of the same type. In addition, the distribution law of the main root canal orifice at the pulp chamber floor is conducive to locating MB2, thereby guiding clinical operations.