Perfluorooctane sulfonate (PFOS) is associated with male reproductive disorders, but its targets and mechanisms are poorly understood. We used in vitro and in vivo models to explore the roles of Sertoli cells and the blood-testis barrier (BTB) in PFOS-induced male reproductive dysfunction. First, we used primary Sertoli cell to estimate PFOS-induced cytotoxicity, junction proteins expression, and the changes of barrier function. ICR mice were then administered PFOS (0.25–50mg/kg/day) for 4 weeks. Sperm count, ultrastructure and permeability of the Sertoli cell–based BTB, and testicular PFOS were estimated. Furthermore, the expression and localization of proteins related to junctions between Sertoli cells and mitogen-activated protein kinase (MAPK) signaling pathway were evaluated. Apparent decreases in sperm count were found. PFOS significantly increased vacuolization in Sertoli cells in seminiferous tubules and BTB ultrastructural disassembly, which subsequently increased BTB permeability and testicular PFOS levels, which was confirmed by in vitro results that PFOS decreased transepithelial electrical resistance between Sertoli cells. Additionally, PFOS decreased the expression of junction proteins in Sertoli cells, which was further confirmed by in vivo results that PFOS decreased or dislocated junction proteins (i.e., ZO-1, occludin, claudin-11, and connexin-43) and increased proteins related to the MAPK signaling pathway (i.e., Erk and p38), whereas basal ectoplasmic specialization proteins did not change. The results were confirmed by SB203580, a p38 MAPK selective inhibitor. Sertoli cells appear to be a new cellular target for PFOS. Together with disruption of BTB integrity and function, these cells play an important role in PFOS-induced male reproductive toxicity.
3 May 2014 in Journal of Experimental & Clinical Cancer Research
Gastric carcinoma (GC) is a common and lethal malignancy, and epithelial-mesenchymal transition (EMT) is believed to contribute to invasive and metastatic tumor growth. Aquaporin 3 (AQP3) is overexpressed in human GC tissues, while human epidermal growth factor (EGF) and hepatocyte growth factor, which can induce EMT, are able to up-regulate AQP3 expression, subsequently promoting GC cell migration and proliferation. The purpose of this study was to investigate the effects of AQP3 on EMT in human GC. AQP3 and EMT-related proteins were detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. AQP3 knockdown was attempted using small interfering RNAs, while EGF was used to up-regulate AQP3 expression. Western blotting, real-time quantitative polymerase chain reaction assays and immunofluorescence were used to evaluate changes in expression of AQP3 and EMT-related proteins in the SGC7901 and MGC803 human GC cell lines. AQP3 up-expression was associated with EMT-related proteins in human GC specimens, which correlated with poor prognosis for GC. AQP3 modulated GC cell proliferation, migration and invasion in vitro, and induced E-cadherin repression. AQP3 also up-regulated the expression of vimentin and fibronectin in vitro. The PI3K/AKT/SNAIL signaling pathway was likely involved in the induction of EMT by AQP3 in GC. AQP3 promotes EMT in human cases of GC, allowing us to understand the mechanisms of AQP3 in GC progression, thus providing a potential strategy for its treatment.
Team-based learning (TBL) has been adopted as a new medical pedagogical approach in China. However, there are no studies or reviews summarizing the effectiveness of TBL on medical education. This study aims to obtain an overall estimation of the effectiveness of TBL on outcomes of theoretical teaching of medical education in China. We retrieved the studies from inception through December, 2015. Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Wanfang Database, Chinese Scientific Journal Database, PubMed, EMBASE and Cochrane Database were searched. The quality of included studies was assessed by the Newcastle-Ottawa scale. Standardized mean difference (SMD) was applied for the estimation of the pooled effects. Heterogeneity assumption was detected by I2 statistics, and was further explored by meta-regression analysis. A total of 13 articles including 1545 participants eventually entered into the meta-analysis. The quality scores of these studies ranged from 6 to 10. Altogether, TBL significantly increased students’ theoretical examination scores when compared with lecture-based learning (LBL) (SMD = 2.46, 95% CI: 1.53–3.40). Additionally, TBL significantly increased students’ learning attitude (SMD = 3.23, 95% CI: 2.27–4.20), and learning skill (SMD = 2.70, 95% CI: 1.33–4.07). The meta-regression results showed that randomization, education classification and gender diversity were the factors that caused heterogeneity. TBL in theoretical teaching of medical education seems to be more effective than LBL in improving the knowledge, attitude and skill of students in China, providing evidence for the implement of TBL in medical education in China. The medical schools should implement TBL with the consideration on the practical teaching situations such as students’ education level.
The association between endocrine disrupting chemicals (EDCs) and human sperm quality is controversial due to the inconsistent literature findings, therefore, a systematic review with meta-analysis was performed. Through the literature search and selection based on inclusion criteria, a total of 9 studies (7 cross-sectional, 1 case-control and 1 pilot study) were analyzed for classic EDCs (5 studies for phthalate esters and 4 studies for organochlorines). Funnel plots revealed a symmetrical distribution with no evidence of publication bias (Begg’s test: intercept = 0.40; p = 0.692). The summary odds ratios (OR) of human sperm quality associated with the classic EDCs was 1.67 (95% CI: 1.31–2.02). After stratification by specific chemical class, consistent increases in the risk of abnormal sperm quality were found in phthalate ester group (OR = 1.52; 95% CI: 1.09–1.95) and organochlorine group (OR = 1.98; 95% CI: 1.34–2.62). Additionally, identification of official data and a comprehensive review of the mechanisms were performed and better elucidated the increased risk of these classic EDCs on abnormal sperm quality. The present systematic review and meta-analysis helps to identify the impact of classic EDCs on human sperm quality. However, it still highlights the need for additional epidemiological studies in a larger variety of geographic locations.