The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resu...The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endothelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.展开更多
This research explores emerging concepts of tourism education,training,and entrepreneurship development.Nowadays,the discourses on this theme have been growing in both developed and developing countries,especially to ...This research explores emerging concepts of tourism education,training,and entrepreneurship development.Nowadays,the discourses on this theme have been growing in both developed and developing countries,especially to reduce unemployment rates through the education of young people.For this purpose,this study uses secondary data sources to analyze individual rationality and the creativity of educated young people for entrepreneurship development in the business sector.The analytical framework begins from the investigation of the tourism industry and the processes for empowering those people since tourism industry is considered as one of the agents of economic changes in developing countries,such as Nepal.However,skilled and trained manpower are required to operate well.The main theme of this study is that the aforesaid manpower can be developed with entrepreneurship skills by providing education and training in this business.This study entirely agrees that once the tourism industry is well run by removing the hurdles seen in this sector,there would be an increase in employment opportunities and a raise in the country’s revenue in addition to solving many other social problems.展开更多
Background/aims: To determine whether the 17-hydroxyprogesterone (17-OHP)/cortisol ratio as a marker of immature11-beta hydroxylase activity can predict severe systemic hypotension in preterm neonates. Methods: Serum ...Background/aims: To determine whether the 17-hydroxyprogesterone (17-OHP)/cortisol ratio as a marker of immature11-beta hydroxylase activity can predict severe systemic hypotension in preterm neonates. Methods: Serum cortisol and 17-OHP concentrations were measured in capillary blood deposited on blotter paper on day 3 post-natal age (Day 3) in infants less than 32 weeks postmenstrual age (PMA). The predictive value of 17-OHP/cortisol ratio for a first episode of systemic hypotension occurring after Day 3 (FESH) was evaluated. Results: Of 105 infants included, 14 patients (13%) presented a FESH. Neither the 17-OHP/cortisol ratio, nor the 17-OHP or cortisol concentrations were associated with the occurrence of a FESH when adjusted for potential confounding factors. 17-OHP and cortisol were inversely associated to PMA (r = ﹣0.36 and ﹣0.40, respectively). Cortisol, but not 17-OHP, was associated with the type of hospitalization unit, the respiratory support and the presence of a patent ductus arteriosus. The 17-OHP/cortisol ratio was associated with the type of hospitalization unit only. Conclusions: The 17-OHP/ cortisol ratio at Day 3 did not predict the occurrence of a first episode of systemic hypotension after Day3 inpreterm neonates.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.:81972811)the Key Research and Development Foundation of Shaanxi Province(Grant Nos.:2018SF-099,S2021SF-136,2021JM-273,and 2022JQ-848)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.:xzy012022094)the Provincial Science and Technology Rising Star(Grant No.:2021KJXX-03).
文摘The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endothelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.
文摘This research explores emerging concepts of tourism education,training,and entrepreneurship development.Nowadays,the discourses on this theme have been growing in both developed and developing countries,especially to reduce unemployment rates through the education of young people.For this purpose,this study uses secondary data sources to analyze individual rationality and the creativity of educated young people for entrepreneurship development in the business sector.The analytical framework begins from the investigation of the tourism industry and the processes for empowering those people since tourism industry is considered as one of the agents of economic changes in developing countries,such as Nepal.However,skilled and trained manpower are required to operate well.The main theme of this study is that the aforesaid manpower can be developed with entrepreneurship skills by providing education and training in this business.This study entirely agrees that once the tourism industry is well run by removing the hurdles seen in this sector,there would be an increase in employment opportunities and a raise in the country’s revenue in addition to solving many other social problems.
基金the French National Registry(Direction Generale de la Sante)with the following number:DGS 2005/0503
文摘Background/aims: To determine whether the 17-hydroxyprogesterone (17-OHP)/cortisol ratio as a marker of immature11-beta hydroxylase activity can predict severe systemic hypotension in preterm neonates. Methods: Serum cortisol and 17-OHP concentrations were measured in capillary blood deposited on blotter paper on day 3 post-natal age (Day 3) in infants less than 32 weeks postmenstrual age (PMA). The predictive value of 17-OHP/cortisol ratio for a first episode of systemic hypotension occurring after Day 3 (FESH) was evaluated. Results: Of 105 infants included, 14 patients (13%) presented a FESH. Neither the 17-OHP/cortisol ratio, nor the 17-OHP or cortisol concentrations were associated with the occurrence of a FESH when adjusted for potential confounding factors. 17-OHP and cortisol were inversely associated to PMA (r = ﹣0.36 and ﹣0.40, respectively). Cortisol, but not 17-OHP, was associated with the type of hospitalization unit, the respiratory support and the presence of a patent ductus arteriosus. The 17-OHP/cortisol ratio was associated with the type of hospitalization unit only. Conclusions: The 17-OHP/ cortisol ratio at Day 3 did not predict the occurrence of a first episode of systemic hypotension after Day3 inpreterm neonates.
