Anti-TSC2 (aa 540-658) polyclonal antibody

The injury of intestinal epithelial barrier is considered as the key pathophysiological process in response to gastrointestinal infection and inflammation, and plays an important role in the initiation and development of colitis. Alpinetin has been shown to improve intestinal barrier homeostasis under colitis condition, but the mechanism is still unclear. Here, we showed that alpinetin significantly improved transepithelial electrical resistance (TEER) in TNF-alpha-stimulated Caco-2 cells, which was mainly mediated by inhibiting the apoptosis. Mechanistic studies demonstrated that alpinetin markedly increased the production of autophagosomes, along with obvious regulation of LC3B-II, beclin-1, p62, Atg7 and Atg5 expressions. In addition, it also markedly repressed the activation of mTORC1 signaling pathway, which was ascribed to TSC2 rather than p-AKT, p-ERK, p-AMPK alpha or PTEN expressions in Caco-2 and NCM460 cells. Furthermore, the enrichment of H3K9me3 at TSC2 promoter region was decreased and ubiquitin proteasome degradation of suv39h1 was increased. Additionally, alpinetin activated aryl hydrocarbon receptor (AhR) and promoted co-localization of AhR with suv39h1 in the cytoplasm. The relationship between alpinetin-regulated AhR/suv39h1/TSC2/mTORC1 signals, autophagy and apoptosis of Caco-2 and NCM460 cells was confirmed by using CH223191, siAhR, siTSC2 and chloroquine. Finally, CH223191 and leucine abolished alpinetin-mediated inhibition of intestinal epithelial cells apoptosis, improvement of intestinal epithelial barrier and amelioration of colitis.

Background: Lung cancer in never smokers (LCINS) differs etiologically and clinically from lung cancer attributed to smoking. After smoking, radon exposure is the second leading cause and the primary risk factor of lung cancer among never smokers. Exposure to radon can lead to genetic and epigenetic alterations in tumor genomes affecting genes and pathways involved in lung cancer development. The present study sought to explore genetic alterations associated with LCINS exposed to radon gas indoors. Methods: Genetic associations were assessed via a case-control study of LCINS (39 cases and 30 controls) using next generation sequencing. Associations between genetic mutations and high exposure to radon were investigated by OncoPrint and heatmap graphs. Bioinformatic analysis was conducted using various tools. According radon exposure levels, we divided subjects in two groups of cases and controls. Results: We found that ABL2 rs117218074, SMARCA4 rs2288845, PIK3R2 rs142933317, MAPK1 rs1803545, and androgen receptor (AR) rs66766400 were associated with LCINS exposed to high radon levels. Among these, Chromodomain helicase DNA-binding protein 4 (CHD4) rs74790047, TSC2 rs2121870, and AR rs66766408 were identified as common exonic mutations in both lung cancer patients and normal individuals exposed to high levels of radon indoor. Conclusion: We identified that CHD4 rs74790047, TSC2 rs2121870, and AR rs66766408 are found to be common exonic mutations in both lung cancer patients and normal individuals exposed to radon indoors. Further analysis is needed to determine whether these genes are completely responsible for LCINS exposed to residential radon.