Background:N-Alkylamides(NAAs),derived from Anacyclus pyrethrum(L.)DC,have potential anti-tumor effects.To explore the molecular mechanism and chemo-preventive capacity of NAAs,we synthesized an NAA(H-10)and evaluated...Background:N-Alkylamides(NAAs),derived from Anacyclus pyrethrum(L.)DC,have potential anti-tumor effects.To explore the molecular mechanism and chemo-preventive capacity of NAAs,we synthesized an NAA(H-10)and evaluated whether it could inhibit the proliferation of B16,HepG2,HeLa,and HCT116 cancer cells in 2D culture.Methods:To evaluate the antiproliferative activity of H-10 in 2D and 3D culture of BD,HepG2,HeLa,and HCT116 cells,multicellular tumor spheroids were constructed to more accurately reflect the cell tumor environment.To visualize nuclear changes related to apoptosis,Hoechst 33258 staining and propidium iodide-Annexin V double staining were performed.Results:Compound H-10 strongly inhibited the growth of all tested cell lines.Hoechst 33258 staining and propidium iodide-Annexin V double staining revealed that H-10 did not cause morphological alterations in the nuclei and moderately induced late apoptosis only when treated at 180 mM.The strongest inhibitory effect was observed in HCT116 cells.Flow cytometry analysis indicated that treatment of HCT116 cells with compound H-10 resulted in robust cell growth arrest in G2 phase in 2D and 3D cell culture;in 3D-cultured HCT116 cells,growth arrest occurred in G1 phase.Treatment with compound H-10 also significantly suppressed angiogenesis of chick chorioallantoic membrane in vivo.Conclusion:Treatment with compound H-10 strongly affected clonogenic survival(in the long-term)and migration of HCT116 cells.Therefore,H-10,a compound of NAAs may be useful for treating cancer because of its anti-neoplastic effect and easy synthesis.展开更多
A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rot...A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rotavirus gastroenteritis(RVGE).A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV(n?3200)or placebo(n?3200)group.All the subjects received three oral doses of vaccine four weeks apart.The vaccine efficacy(VE)against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season.VE against severe RVGE,VE against RVGE hospitalization caused by serotypes contained in HRV,and VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated.All adverse events(AEs)were collected for 30 days after each dose.Serious AEs(SAEs)and intussusception cases were collected during the entire study.Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21%(95%CI:53.31-79.69).VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36%(95%CI:78.45-96.53)and 89.21%(95%CI:64.51-96.72)respectively.VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88%(95%CI:49.11-72.92),85.51%(95%CI:72.74-92.30)and 83.68%(95%CI:61.34-93.11).Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable.There was no significant difference in incidences of SAEs in HRV and placebo groups.This study shows that this hexavalent reassortant rotavirus vaccine is an effective,well-tolerated,and safe vaccine for Chinese infants.展开更多
基金This study was supported by The Natural Science Foundation of the Xinjiang Uygur Autonomous Region(201318101-5).
文摘Background:N-Alkylamides(NAAs),derived from Anacyclus pyrethrum(L.)DC,have potential anti-tumor effects.To explore the molecular mechanism and chemo-preventive capacity of NAAs,we synthesized an NAA(H-10)and evaluated whether it could inhibit the proliferation of B16,HepG2,HeLa,and HCT116 cancer cells in 2D culture.Methods:To evaluate the antiproliferative activity of H-10 in 2D and 3D culture of BD,HepG2,HeLa,and HCT116 cells,multicellular tumor spheroids were constructed to more accurately reflect the cell tumor environment.To visualize nuclear changes related to apoptosis,Hoechst 33258 staining and propidium iodide-Annexin V double staining were performed.Results:Compound H-10 strongly inhibited the growth of all tested cell lines.Hoechst 33258 staining and propidium iodide-Annexin V double staining revealed that H-10 did not cause morphological alterations in the nuclei and moderately induced late apoptosis only when treated at 180 mM.The strongest inhibitory effect was observed in HCT116 cells.Flow cytometry analysis indicated that treatment of HCT116 cells with compound H-10 resulted in robust cell growth arrest in G2 phase in 2D and 3D cell culture;in 3D-cultured HCT116 cells,growth arrest occurred in G1 phase.Treatment with compound H-10 also significantly suppressed angiogenesis of chick chorioallantoic membrane in vivo.Conclusion:Treatment with compound H-10 strongly affected clonogenic survival(in the long-term)and migration of HCT116 cells.Therefore,H-10,a compound of NAAs may be useful for treating cancer because of its anti-neoplastic effect and easy synthesis.
基金supported by National Health Commission of the People’s Republic of China (grant number:2019ZX09302059)sponsored and funded by Wuhan Institute of Biological Products Co.,Ltd.,Hubei,China
文摘A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rotavirus gastroenteritis(RVGE).A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV(n?3200)or placebo(n?3200)group.All the subjects received three oral doses of vaccine four weeks apart.The vaccine efficacy(VE)against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season.VE against severe RVGE,VE against RVGE hospitalization caused by serotypes contained in HRV,and VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated.All adverse events(AEs)were collected for 30 days after each dose.Serious AEs(SAEs)and intussusception cases were collected during the entire study.Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21%(95%CI:53.31-79.69).VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36%(95%CI:78.45-96.53)and 89.21%(95%CI:64.51-96.72)respectively.VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88%(95%CI:49.11-72.92),85.51%(95%CI:72.74-92.30)and 83.68%(95%CI:61.34-93.11).Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable.There was no significant difference in incidences of SAEs in HRV and placebo groups.This study shows that this hexavalent reassortant rotavirus vaccine is an effective,well-tolerated,and safe vaccine for Chinese infants.