Objective · To investigate the histone methyltransferase capability of DOT1L-long form and its role in breast cancer metastasis.Methods · The existence of DOT1L-long form was confirmed by PCR, and the mRNA level of DOT1L was tested by real-time PCR. In HEK293T cells in which DOT1L canonical and DOT1L-long were overexpressed respectively, Western blotting was used to test the expression level of DOT1L and the histone methyltransferase capability. In the MCF10A cell line with inducible expression of DOT1L-long, real-time PCR was used to detect the mRNA level of epithelial-mesenchymal transition (EMT) marker, and transwell assay was used to detect the migration of breast cancer cells in which the expression level of DOT1L is low or high. Results · PCR demonstrated the existence of DOT1L-long form, and real-time PCR showed it widely exists in HCT116, T98G, MCF10A cells, etc. Western blotting showed the expression of DOT1L-long form and its H3K79 methyltransferase activity. In MCF10A cells in which overexpressed canonical DOT1L and DOT1L-long, mRNA levels of N-cadherin and fibronectine increased. Transwell showed canonical DOT1L and DOT1L-long both substantially increased the migration of breast cancer cells. Conclusion · The existence of DOT1L-long was confirmed and investigated, which is 202 amino acids longer than the canonical DOT1L, and is coded by a new exon, located between exon 27 and 28. Further, the DOT1L-long has H3K79 methyltransferase activity, and is able to promote breast cancer metastasis.

The effect of realgar nanoparticles (NPs) on endogenous small molecules in rat kidney was analyzed by mass spectrometry-based metabolomics.The relationship between the changes of metabolites and the nephrotoxicity of realgar NPs was also discussed to provide a basis for the further toxicity study and the clinical application of realgar NPs.SD rats were randomly divided into seven groups,including control group,three doses (40,200,1 000 mg/kg) of relegar and realgar NPs groups,respectly.After 28 days of continuous intragastric administration,all rats were sacrificed and their serum and kidney samples were collected.The toxic effect of realgar NPs on kidney tissues were examined by biochemical analysis and histopathologic examination,which revealed a dosedependent nephrotoxicity induced by realgar NPs.The LC-MS and GC-MS analysis were performed for the subsequent metabolomics study.A series of 32 metabolites were found to be altered significandy in the kindey of realgar NPs treated rats,and might serve as potential nephrotoxicity biomarkers.The results of metabolic pathway analysis indicated that the nephrotoxicity of realgar NPs might be associated with the disorders of the amino acids and phosphatidic acid metabolism.

Objective To determine the relationship between air pollutants [SO
Acne Vulgaris ; Air Pollution/adverse effects* ; China/epidemiology* ; Environmental Pollutants ; Female ; Gases ; Humans ; Male ; Outpatients