ABSTRACT
Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.
ABSTRACT
Objective@#To investigate the prevalence of adolescents dietary behavior in Shanghai, and to explore emotional influence on dietary behavior.@*Methods@#A total of 7 456 students from 10 junior and 6 senior high schools in Shanghai were selected to participate in the questionnaire survey with the stratified random cluster sampling method. The survey included general information, eating behavior, PHQ-2 and GAD-7.@*Results@#During the past week, the proportion of adolescents in Shanghai reported consumption of sugar sweetened beverages, sweet desserts, frequent fried food and fast food (≥4 times/week) were 13.26%, 16.90%, 6.99 % and 13.01%, respectively. The proportion of students reported consumption of fruits, vegetables, milk and breakfast every day were 56.96%, 73.00%, 65.03% and 76.11%, respectively. There were significant differences by sex and educational stages(both P <0.05). Adolescents with depression or anxiety have a higher incidence of unhealthy eating behaviors than those without depression or anxiety( P <0.01). After adjusting for gender, school, accommodation, grades, pocket money and social class, depression and anxiety increase the risk of various unhealthy eating behaviors in adolescents( P <0.05). Compared with those without anxiety, the risks of sugar sweetened beverages consumption (≥1 time/d) among adolescents with mild and moderate to severe anxiety were 1.42 times (95% CI =1.20-1.67) and 2.51 times (95% CI =2.09-3.01), the risks of insufficient fruits consumption (<1 time/d) were 1.30 times (95% CI =1.16-1.45) and 1.28 times (95% CI =1.11-1.47), the risks of insufficient vegetable consumption (<1 time/d) were 1.35 times (95% CI =1.20-1.52) and 1.41 times(95% CI =1.21-1.65), the risks of insufficient milk consumption (<1 time/d) were 1.29 times (95% CI =1.15-1.44) and 1.20 times(95% CI =1.04-1.39), and the risks of breakfast skipping were 1.75 times (95% CI =1.54-1.99) and 2.97 times (95% CI =2.55-3.46) among adolescents with mild and moderate to severe anxiety.@*Conclusion@#The proportion of unhealthy eating behaviors among adolescents in Shanghai is still high. Early education and intervention for students eating behaviors should be carried out, and attention should be paid to the occurrence of adolescents negative emotions, so as to reduce the risk of unhealthy eating behaviors among adolescents through the promotion of mental health.
ABSTRACT
Objective To observe the effect of hypoxia on the expression of epithelial growth factor receptor (EGFR) and cell apoptosis of breast and cervical cancer xenografts in nude mouse models.Methods The nude mouse models with MCF-7 and HeLa xenografts were established.The degree of hypoxia and EGFR expression were observed by confocal microscopy.The influence of EGFR expression on cell apoptosis under hypoxia was observed by TUNEL assay.Results EGFR expression was either up-regulated or down-regulated in the MCF-7 and HeLa cells with high degree of hypoxia.Furthermore,the degree of apoptosis was reduced in tumor tissues with high EGFR expression compared with that in those with low expression of EGFR.Conclusion The hypoxia in MCF-7 and HeLa cells exerts heterogeneous effect on EGFR expression.Under hypoxic conditions,EGFR exoression is negatively correlated with cell apoptosis.