肺癌是全球男性常见癌症,大部分肺癌患者在确诊时已属晚期。对于肺癌晚期患者来说,放疗、化疗的不良反应较大,患者无法耐受;靶向药物普遍存在耐药现象;免疫治疗受程序性死亡配体-1(programmed cell death protein 1,PD-L1)的表达限制;...肺癌是全球男性常见癌症,大部分肺癌患者在确诊时已属晚期。对于肺癌晚期患者来说,放疗、化疗的不良反应较大,患者无法耐受;靶向药物普遍存在耐药现象;免疫治疗受程序性死亡配体-1(programmed cell death protein 1,PD-L1)的表达限制;抗血管治疗的出现为晚期肺癌患者提供了更多的选择。目前,多种药物联合治疗肺癌的手段日渐成熟,抗血管药物联合化疗药物或靶向药物都取得了显著的疗效。在肺癌肿瘤生长过程中,环氧化酶-2(cyclooxygenase-2,COX-2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)相互促进使肿瘤血管新生,所以,选择性COX-2抑制剂联合抗血管药物是否具有协同抗肿瘤作用,其抗肿瘤机制如何,本文将针对以上问题展开论述。展开更多
Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of ext...Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for RA.The production of NO and inflammatory cytokines were measured by ELISA kit.Quantitative Real-time PCR(qRT-PCR)was utilized to measure the mRNA levels.COX-2/PGE2 signaling pathway-associated proteins were determined by western blot.Results:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating RA.The in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 FPPs.The 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and XFZ.Conclusion:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.展开更多
Selective inhibition of cyclooxygenase-2 (COX-2) might avoid the side effects of current available nonsteroidal antiinflammatory drugs while retaining their therapeutic efficacy. A novel variable selection and modelin...Selective inhibition of cyclooxygenase-2 (COX-2) might avoid the side effects of current available nonsteroidal antiinflammatory drugs while retaining their therapeutic efficacy. A novel variable selection and modeling method based on prediction is developed to construct the quantitative structure-activity relationships (QSAR) between the molecular electronegativity distance vector (MEDV) based on 13 atomic types and the biological activities of a set of selective cyclooxygenase-2 inhibitory molecules,3,4-diarylcycloxazolones (DAA) plus indomethacin,naproxen,and celecoxib. Using multiple linear regression,a 5-variable linear model is developed with the calibrated correlation coefficient of 0.9271 and root mean square error of 0.17 in modeling stage and the validated correlation coefficient of 0.9030 and root mean square error of 0.20 in leave-one-out validation step,respectively. To further test the predictive ability of the model,20 DAA compounds are picked up to construct a training set which is used to build a QSAR model and then the model is employed to predict the biological activities of the balance compounds. The predicted correlation coefficient and root mean square error are 0.9332 and 0.19, respectively.展开更多
文摘肺癌是全球男性常见癌症,大部分肺癌患者在确诊时已属晚期。对于肺癌晚期患者来说,放疗、化疗的不良反应较大,患者无法耐受;靶向药物普遍存在耐药现象;免疫治疗受程序性死亡配体-1(programmed cell death protein 1,PD-L1)的表达限制;抗血管治疗的出现为晚期肺癌患者提供了更多的选择。目前,多种药物联合治疗肺癌的手段日渐成熟,抗血管药物联合化疗药物或靶向药物都取得了显著的疗效。在肺癌肿瘤生长过程中,环氧化酶-2(cyclooxygenase-2,COX-2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)相互促进使肿瘤血管新生,所以,选择性COX-2抑制剂联合抗血管药物是否具有协同抗肿瘤作用,其抗肿瘤机制如何,本文将针对以上问题展开论述。
基金supported by Sichuan Province Science and Technology Support Program(NO.2020JDJQ0063,NO.2020YFS0566 and NO.2021JDKY0037,A-2021N-Z-5).
文摘Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for RA.The production of NO and inflammatory cytokines were measured by ELISA kit.Quantitative Real-time PCR(qRT-PCR)was utilized to measure the mRNA levels.COX-2/PGE2 signaling pathway-associated proteins were determined by western blot.Results:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating RA.The in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 FPPs.The 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and XFZ.Conclusion:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.
基金ProjectsupportedbytheNationalHighTechnologyResearchandDevelopmentProgramofChina (No .2 0 0 1AA64 60 10 4)andtheNa tionalNaturalScienceFoundationofChina (No .2 0 1770 0 8)
文摘Selective inhibition of cyclooxygenase-2 (COX-2) might avoid the side effects of current available nonsteroidal antiinflammatory drugs while retaining their therapeutic efficacy. A novel variable selection and modeling method based on prediction is developed to construct the quantitative structure-activity relationships (QSAR) between the molecular electronegativity distance vector (MEDV) based on 13 atomic types and the biological activities of a set of selective cyclooxygenase-2 inhibitory molecules,3,4-diarylcycloxazolones (DAA) plus indomethacin,naproxen,and celecoxib. Using multiple linear regression,a 5-variable linear model is developed with the calibrated correlation coefficient of 0.9271 and root mean square error of 0.17 in modeling stage and the validated correlation coefficient of 0.9030 and root mean square error of 0.20 in leave-one-out validation step,respectively. To further test the predictive ability of the model,20 DAA compounds are picked up to construct a training set which is used to build a QSAR model and then the model is employed to predict the biological activities of the balance compounds. The predicted correlation coefficient and root mean square error are 0.9332 and 0.19, respectively.
