RESUMEN
Alternative splicing of precursor messenger RNA (pre-mRNA), including linear splicing and back splicing, produces multiple isoforms that lead to diverse cell fates in response to stimuli including ultraviolet radiation (UVR). Although UVR-induced linear gene splicing has been extensively studied in skin cells, the UVR-induced gene back-splicing events that lead to the production of circular RNAs (circRNAs) have not been thoroughly investigated. The present study used circRNA transcriptome sequencing to screen the differentially expressed circRNAs in human keratinocytes (HaCaT) after UVA irradiation. A total of 312 differentially expressed circRNAs were found in HaCaT cells post-UVR. Among the UVA-induced differentially expressed circRNAs, circUBE2I-a novel circRNA formed by exons 2-6 of the UBE2I gene-was the most significantly upregulated circRNA. RT-qPCR assay further confirmed the increase of circUBE2I level in HaCaT cells after UVA irradiation or H2 O2 treatment. RNase R digestion experiment revealed the stability of circUBE2I. Overexpression of circUBE2I in keratinocytes induced ferroptosis after UVA or H2 O2 , preventable by the ferroptosis inhibitor ferrostatin-1. Our study provides new insights into the role of circular RNAs in UVA-induced skin cell damage and suggests that circUBE2I could be a therapeutic target in UVR-aroused ferroptosis in skin cells.
RESUMEN
Tetracaine hydrochloride (TTC) is a long-lasting local anesthetic commonly used for topical anesthesia. Inappropriate dosage or allergic reactions to TTC can lead to local anesthetic toxicity. TTC exerts cytotoxic effects on certain cell types by inducing apoptosis and necrosis; however, the effects of TTC on macrophages are currently unclear. In the present study, the RAW 264.7 and BV2 cell lines, and murine peritoneal macrophages, were used to evaluate the cytotoxicity of TTC. The present study demonstrated that TTC caused a decrease in cell viability according to a Cell Counting Kit-8 assay, increased lactate dehydrogenase and IL-1ß secretion according to ELISA, and induced morphological changes characteristic of pyroptosis according to western blotting. Moreover, TTC-induced macrophage pyroptosis was mediated by gasdermin (GSDM)D, and the cleavage of GSDMD was modulated by both caspase-1 and caspase-11. These results were experimentally validated using caspase-1 and caspase-11 inhibitors. Furthermore, it was observed that TTC and lipopolysaccharide (LPS) exerted similar effects on macrophages. However, the mechanism of induction of pyroptosis by TTC was different from that of LPS. The present study demonstrated that TTC alone could induce macrophage pyroptosis mediated by canonical and non-canonical inflammatory caspases. Therapies targeting pyroptosis may potentially provide a promising future strategy for the prevention and treatment of local anesthetic toxicity induced by TTC.
RESUMEN
Background: Persistently increased workload and stress occurred in health professionals (HPs) during the past 3 years as the COVID-19 pandemic continued. The current study seeks to explore the prevalence of and correlators of HPs' burnout during different stages of the pandemic. Methods: Three repeated online studies were conducted in different stages of the COVID-19 pandemic: wave 1: after the first peak of the pandemic, wave 2: the early period of the zero-COVID policy, and wave 3: the second peak of the pandemic in China. Two dimensions of burnout, emotional exhaustion (EE) and declined personal accomplishment (DPA), were assessed using Human Services Survey for Medical Personnel (MBI-HSMP), a 9-item Patient Health Questionnaire (PHQ-9), and a 7-item Generalized Anxiety Disorder (GAD-7) to assess mental health conditions. An unconditional logistic regression model was employed to discern the correlators. Results: There was an overall prevalence of depression (34.9%), anxiety (22.5%), EE (44.6%), and DPA (36.5%) in the participants; the highest prevalence of EE and DPA was discovered in the first wave (47.4% and 36.5%, respectively), then the second wave (44.9% and 34.0%), and the third wave had the lowest prevalence of 42.3% and 32.2%. Depressive symptoms and anxiety were persistently correlated with a higher prevalence risk of both EE and DPA. Workplace violence led to a higher prevalence risk of EE (wave 1: OR = 1.37, 95% CI: 1.16-1.63), and women (wave 1: OR = 1.19, 95% CI: 1.00-1.42; wave 3: OR =1.20, 95% CI:1.01-1.44) and those living in a central area (wave 2: OR = 1.66, 95% CI: 1.20-2.31) or west area (wave 2: OR = 1.54, 95% CI: 1.26-1.87) also had a higher prevalence risk of EE. In contrast, those over 50 years of age (wave 1: OR = 0.61, 95% CI: 0.39-0.96; wave 3: OR = 0.60, 95% CI: 0.38-0.95) and who provided care to patients with COVID-19 (wave 2: OR = 0.73, 95% CI: 0.57-0.92) had a lower risk of EE. Working in the psychiatry section (wave 1: OR = 1.38, 95% CI: 1.01-1.89) and being minorities (wave 2: OR = 1.28, 95% CI: 1.04-1.58) had a higher risk of DPA, while those over 50 years of age had a lower risk of DPA (wave 3: OR = 0.56, 95% CI: 0.36-0.88). Conclusion: This three-wave cross-sectional study revealed that the prevalence of burnout among health professionals was at a high level persistently during the different stages of the pandemic. The results suggest that functional impairment prevention resources and programs may be inadequate and, as such, continuous monitoring of these variables could provide evidence for developing optimal strategies for saving human resources in the coming post-pandemic era.
