ABSTRACT
SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF) plays dual roles in the initiation and development of human malignancies. However, the biological role of SPDEF in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, the expression level of SPDEF and its correlation with the clinical parameters of patients with HNSCC were determined using TCGA-HNSC, GSE65858, and our own clinical cohorts. CCK8, colony formation, cell cycle analysis, and a xenograft tumor growth model were used to determine the molecular functions of SPDEF in HNSCC. ChIP-qPCR, dual luciferase reporter assay, and rescue experiments were conducted to explore the potential molecular mechanism of SPDEF in HNSCC. Compared with normal epithelial tissues, SPDEF was significantly downregulated in HNSCC tissues. Patients with HNSCC with low SPDEF mRNA levels exhibited poor clinical outcomes. Restoring SPDEF inhibited HNSCC cell viability and colony formation and induced G0/G1 cell cycle arrest, while silencing SPDEF promoted cell proliferation in vitro. The xenograft tumor growth model showed that tumors with SPDEF overexpression had slower growth rates, smaller volumes, and lower weights. SPDEF could directly bind to the promoter region of NR4A1 and promoted its transcription, inducing the suppression of AKT, MAPK, and NF-κB signaling pathways. Moreover, silencing NR4A1 blocked the suppressive effect of SPDEF in HNSCC cells. Here, we demonstrate that SPDEF acts as a tumor suppressor by transcriptionally activating NR4A1 in HNSCC. Our findings provide novel insights into the molecular mechanism of SPDEF in tumorigenesis and a novel potential therapeutic target for HNSCC.
Subject(s)
Humans , Carcinogenesis , Cell Proliferation , Head and Neck Neoplasms , Nuclear Receptor Subfamily 4, Group A, Member 1 , Proto-Oncogene Proteins c-ets , Squamous Cell Carcinoma of Head and Neck , Transcription FactorsABSTRACT
BACKGROUND@#Decreased heart rate variability (HRV) is a predictor of autonomic system dysfunction, and is considered as a potential mechanism of increased risk of cardiovascular disease (CVD) induced by exposure to particulate matter less than 2.5 μm in diameter (PM@*METHODS@#An updated systematic review and meta-analysis of panel studies till November 1, 2019 was conducted to evaluate the acute effect of exposure to ambient PM@*RESULTS@#A total of 33 panel studies were included in our meta-analysis, with 16 studies conducted in North America, 12 studies in Asia, and 5 studies in Europe. The pooled results showed a 10 μg/m@*CONCLUSION@#Short-term exposure to PM
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Air Pollutants/analysis , Air Pollution/analysis , Heart Rate/drug effects , Particulate Matter/analysisABSTRACT
Background:China's accelerating development and increasingly important role in global health engagement create a great demand for global health professionals including international consulting experts.This study reported the detailed development and evaluation of an international consulting training for global health workforce.Methods:Based on Kirkpatrick's model,a mixed-methods approach was used to evaluate the effectiveness of the training.Quantitative and qualitative data on participants' reaction,learning,and application of the learned knowledge and skills were collected by a training evaluation survey at the ending of training and a follow-up interview in three months after the training.Results:Thirty-six participants attended the training and 34 of them completed quantitative investigation.The training satisfaction evaluations were positive,for which participants rated the training program highly and over 90％ of them agreed with the usefulness of the training.About knowledge and skills change,participants showed improved consulting knowledge and skills from pre-to post-training (P ＜ 0.001).A total of 23 participants accepted follow-up interview,and most participants applied knowledge and skills learned from the training in their daily work or study.However,only 30.4％ of participants applied their learning in the consulting program.The largest barrier of application was the lack of consulting opportunities.In addition,almost all the participants reported that they would be glad to attend more training courses in the future.Conclusion:The international consulting training program was well-received,and was feasible to improve the consulting service competence of global health professionals.According to participants' feedback,it is essential to develop and expand consulting training in the field of global health.