YAP1 protects against PM2.5-induced lung toxicity by suppressing pyroptosis and ferroptosis.

Pollution from fine particulate matter (PM2.5) has become a major threat to public health and has been related to lung toxicity. One of the key regulators of the Hippo signaling system, Yes-associated protein 1 (YAP1), is speculated to play a role in ferroptosis development. Here, we focused on investigating the function of YAP1 in pyroptosis and ferroptosis, aiming to explore its therapeutic potential in PM2.5-induced lung toxicity. PM2.5-induced lung toxicity was induced in Wild-type WT and conditional YAP1-knockout mice, and lung epithelial cells were stimulatd by PM2.5 in vitro. We used western blot, transmission electron microscopy, and fluorescence microscopy to investigate pyroptosis- and ferroptosis-related characteristics. We found that PM2.5 leads to lung toxicity using mechanisms involving pyroptosis and ferroptosis. YAP1 knockdown impeded pyroptosis, ferroptosis, and PM2.5-induced lung damage, as shown by increased histopathology, higher levels of proinflammatory cytokines, GSDMD protein, lipid peroxidation, and iron accumulation, as well as increased NLRP3 inflammasome activation and decreased SLC7A11 expression. YAP1 silencing consistently promoted NLRP3 inflammasome activation and reduced SLC7A11 levels, aggravating PM2.5-induced cellular damage. In contrast, YAP1-overexpressing cells inhibited NLRP3 inflammasome activation and increased SLC7A11 levels, preventing pyroptosis and ferroptosis. Overall, our data suggest that YAP1 ameliorates PM2.5-induced lung injury by inhibiting NLRP3-mediated pyroptosis and SL7A11-dependent ferroptosis.

Prediabetes is associated with a higher serum neurofilament light chain level in adolescents.

Objective: Serum neurofilament light chain (sNfL) level, which is a biomarker indicative of neuroaxonal damage and cognitive impairment, has been reported in several neurological diseases. There has been a lack of studies on the association between sNfL levels and prediabetes in adolescents. This study investigated whether sNfL levels were higher in adolescents with prediabetes undergoing elective orthopedic surgery. Methods: The sNfL level was measured in 149 adolescents aged from 12 to 18 years who underwent elective orthopedic surgery at the Hunan Children's Hospital (18 with and 131 without prediabetes). We evaluated the association between prediabetes and sNfL level after adjusting for age, sex, and triglycerides using a multivariable linear regression model. Results: The prevalence of prediabetes in adolescents was 12.08%. Univariate logistic regression analysis showed that prediabetes was related to sNfL. In multivariate logistic regression analysis, the association between prediabetes with sNfL levels remained significant after adjustment for age, sex, and triglyceride. The relationship between the two was further visualized by a smoothed curve. Conclusions: Prediabetes is associated with a higher sNfL. Further large-scale and prospective studies are needed to verify the clinical application of sNfL as a monitoring biomarker for adolescent prediabetes in adolescents and to evaluate the performance of sNfL in predicting the incidence of neuropathy and cognitive dysfunction in adolescents with prediabetes.

Correlations between plasma endothelin-1 levels and breakthrough pain in patients with cancer.

Endothelin-1 (ET-1) may be involved in driving pain in patients with advanced cancer. However, a few studies focus on the role of ET-1 in breakthrough pain (BP). The aim of this pivotal study was to explore the correlation between the plasma (ET-1) level and BP intensity. A total of 40 patients were enrolled in the study, and they were divided into two groups: BP group and non-BP group. Moreover, 20 healthy adults were used as the normal control group. Pain intensity was measured using visual analog scale (VAS) scores of 1-10. Plasma ET-1 levels were detected by an ET radioimmunoassay kit. Subsequently, the correlation of ET-1 level with the VAS score and cancer types was analyzed by Pearson's correlation coefficient. The plasma ET-1 level in the BP group (35.31±8.02 pg/mL) was higher than that in the non-BP group (29.51±6.78 pg/mL) and the normal control group (24.77±10.10 pg/mL, P<0.05). In addition, the VAS score in the BP group (7.45±0.82) was higher than that in the non-BP group (2.80±1.23, P<0.05). The plasma ET-1 level was positively correlated with the VAS score of the BP group (Pearson's r=0.42). There was no significant correlation between the plasma ET-1 level and VAS score of the non-BP group (Pearson's r=-0.22) or/and cancer types (P>0.05). The elevated plasma ET-1 levels were positively related to BP, and targeting ET-1 may provide a novel pain-reducing therapeutic treatment in BP.