RESUMEN
Circulating tumor cells (CTCs) play a critical role as initiators in tumor metastasis, which unlocks an irreversible process of cancer progression. Regarding the fluid environment of intravascular CTCs, a comprehensive understanding of the impact of hemodynamic shear stress on CTCs is of profound significance but remains vague. Here, we report a microfluidic circulatory system that can emulate the CTC microenvironment to research the responses of typical liver cancer cells to varying levels of fluid shear stress (FSS). We observe that HepG2 cells surviving FSS exhibit a marked overexpression of TLR4 and TPPP3, which are shown to be associated with the colony formation, migration, and anti-apoptosis abilities of HepG2. Furthermore, overexpression of these two genes in another liver cancer cell line with normally low TLR4 and TPPP3 expression, SK-Hep-1 cells, by lentivirus-mediated transfection also confirms the critical role of TLR4 and TPPP3 in improving colony formation, migration, and survival capability under a fluid environment. Interestingly, in vivo experiments show SK-Hep-1 cells, overexpressed with these genes, have enhanced metastatic potential to the liver and lungs in mouse models via tail vein injection. Mechanistically, TLR4 and TPPP3 upregulated by FSS may increase FSS-mediated cell survival and metastasis through the p53-Bax signaling pathway. Moreover, elevated levels of these genes correlate with poorer overall survival in liver cancer patients, suggesting that our findings could offer new therapeutic strategies for early cancer diagnosis and targeted treatment development.
Asunto(s)
Células Neoplásicas Circulantes , Humanos , Línea Celular Tumoral , Microfluídica , Estrés Fisiológico , Femenino , Animales , Ratones , Movimiento Celular , Análisis de la Célula Individual , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Supervivencia Celular , Anoicis , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , PronósticoRESUMEN
Objective@#To survey mental health knowledge and its influence factors among undergraduates in Henan provenience and to provide a scientific evidence for further formulating the targeted strategies.@*Methods@#Totally 840 agriculture and forestry college students, literature and history students, science students and medical students were selected with stratified multistage random sampling from 45 colleges and universities in Henan provenience,investigation of Mental Health related knowledge by self-designed questionnaire.@*Results@#The awareness rate of mental health knowledge was 75.86%(32 806/43 248). Multivariate linear regression analysis showed that score of mental health knowledge of femal students was 1.03 of the of male students; score of medical students was 5.19,3.65,2.65 of that of students in the other majors; score of students who obtained mental health knowledge through other channels(television/movie/network/talking) was 1.42 of that of than those who obtained through formal approaches(slogans/manuals/broadcast/cathedra)(P<0.05).@*Conclusion@#The awareness rate of mental health knowledge among undergraduates in Henan provenience need to be improved, the education of male, senior students, non-medical students and the explore of diversified forms should be strengthened.