| Liver cancer is the second most common cancer in the world.On the one hand,in early stage,liver cancer is difficult to diagnose and traditional therapy is not effective in advanced stage.On the other hand,liver cancer lacks targeted therapy and has resistance to existing drugs and the number of drugs that have been marketed for the treatment of liver cancer has been counted so far which make the prognosis of liver cancer poor.Quinoline derivatives have natural anti-inflammatory and anti-tumor properties.In this study,two quinolone compounds F15 and F17 with antitumor activity were discovered.Their antitumor effects were verified,and the anti-tumor mechanism was initially explored.We found that:(1)F15 and F17 can inhibit the proliferation of HepG2 cells.(2)F15 and F17 can inhibit the migration of HepG2.(3)F15 and F17 can arrest the cell cycle of HepG2 in G2/M phase and induce apoptosis(4)F15 and F17 induces apoptosis of HepG2 through mitochondrial apoptosis pathway.(5)F15 and F17 can inhibit the transcriptional expression of the oncogenic factors c-Myc and Yap-1.(6)F15 and F17 can reduce BRD4 in protein level in HepG2 but not transcription level.(7)BRD4 is not the target of F15 and F17.(8)In liver cancer,BRD4 also influences apoptosis by regulating Bax.In conclusion,this study has found new quinolone compounds that inhibit the proliferation and migration of HepG2 cells,leading to cycle arrest and induction of mitochondrial pathway-mediated apoptosis.In addition,it was found that BRD4 can also regulate the apoptotic factor Bax in hepatocellular cell HepG2.With the accelerated pace of modern life,more and more people staying up very late,sleep deprivation has become common.People with sleep disorders are passively deprived of sleep.The appearance of ocular symptoms is one result of sleep deprivation.Dry eye brings great trouble and inconvenience to millions of people around the world.However,there are no drugs or therapies that can cure it.Research has shown that the composition and quality of tear components can reflect the health of the ocular surface.With the rapid development of proteomics,tear proteomics has gradually developed and become a good method for studying tears.We first recruited volunteers without dry eye syndrome for a 24-hour acute sleep deprivation test,observed ocular surface conditions before and after the test,measured dry eye indicators and collected tears at the same time.Then compared proteins in tears by iTRAQ quantitative proteomics.The mass spectrometry data was analyzed by bioinformatics.We found that:(1)The quantity of tears and the tear film stability in healthy people decreased after acute sleep deprivation;(2)The increase of the lipid layer of healthy people after acute sleep deprivation may be due to the compensatory regulation of the tear film.(3)After acute sleep deprivation,the immune and infla mmation-related proteins in tears have changed significantly.Acute sleep deprivation may lead to the decline of immune function and promote inflammation,which leads to dry eyes.(4)Lipid transport-related proteins also increased,explaining the observed phenomenon of lipid layer.(5)In addition,the biological clock,cancer-related pathways enriched in KEGG analysis suggesting that acute sleep deprivation very harmful.In conclusion,we found that sleep deprivation leads to dry eye,which is caused by inflammation of the ocular surface and provides a reference for the study and treatment of dry eye syndrome. |
