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
Walnut dreg protein hydrolysates(WDPHs)exhibit a variety of biological activities,however,the cyclooxygenase-2(COX-2)inhibitory peptide of WDPHs remain unclear.The aim of this study was to rapidly screen for such pept...Walnut dreg protein hydrolysates(WDPHs)exhibit a variety of biological activities,however,the cyclooxygenase-2(COX-2)inhibitory peptide of WDPHs remain unclear.The aim of this study was to rapidly screen for such peptides in WDPHs through a combination of in silico and in vitro analysis.In total,1262 peptide sequences were observed by nano liquid chromatography/tandem mass spectrometry(nano LC-MS/MS)and 4 novel COX-2 inhibitory peptides(AGFP,FPGA,LFPD,and VGFP)were identified.Enzyme kinetic data indicated that AGFP,FPGA,and LFPD displayed mixed-type COX-2 inhibition,whereas VGFP was a non-competitive inhibitor.This is mainly because the peptides form hydrogen bonds and hydrophobic interactions with residues in the COX-2 active site.These results demonstrate that computer analysis combined with in vitro evaluation allows for rapid screening of COX-2 inhibitory peptides in walnut protein dregs.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
Objective： To investigate the expression of cyclooxygenase-2 （COX-2） and p16 proteins in non-Hodgkin＇s lymphomas （NHL） and their relationship with the genesis and progress of it. Methods： The expression of COX-...Objective： To investigate the expression of cyclooxygenase-2 （COX-2） and p16 proteins in non-Hodgkin＇s lymphomas （NHL） and their relationship with the genesis and progress of it. Methods： The expression of COX-2 and p16 protein were studied in the lymph nodes tissue from 60 NHL patients and 10 control patients with non-malignant diseases by flow cytometry. Results： Positive rate of COX-2 protein expression in NHL tissues （63.3%, 38/60） was higher than that in normal lymphaden tissues （0, 0/10）. The difference was significant between the two groups （P 〈 0.01）. Expression of COX-2 protein was related with the clinical stage of NHL. In stage Ⅰ ＋ Ⅱ patients, it was significantly lower （35.0% ± 54.6%） than that in stage Ⅲ ＋ Ⅳ patients （84.6% ±87.5%） （P 〈 0.01）. In different sex, age, tumor malignant degree, IPI grade, extranodal involvement and B symptoms groups, the differences of COX-2 expression were not statistically significant （P 〉 0.05）. Positive rate of p16 protein expression （41.7%, 25/60） in NHL＇ was statistically lower than that in normal lymphomas （100%, 10/10） （P 〈 0.01）. Expression of p16 protein was related to malignant degree of NHL. The positive rates of p16 protein in low malignant degree tissues （64.7%, 11/17） was higher than that in high malignant degree tissues （14.3%, 2/14） （P 〈 0.05）. Positive rates of p16 protein of NHL tissues in different sex, age, IPI grade, extranodal involvement, clinical stages and B symptoms were not statistically significant （P 〉 0.05）. The p16 protein expression in COX-2 positive patients was 47.4% （18/38）, and in negative patients it was 31.8% （7/22）. There was no statistically difference between them （P 〉 0.05）. Correlation analysis revealed there was no correlation between expression of COX-2 and p16 protein. Conclusion： Both COX-2 and p16 protein may all have relationship with the genesis and progress of NHL. The expression of COX-2 protein in NHL may be a poor prognostic indicator. COX-2 and p16 protein probably have different mechanisms in the genesis and progress of NHL. Their relationship is firstly put forward in this article and needed further studying.展开更多
背景与目的:研究表明,环氧化酶-2(cyclooxygenase-2,COX-2)及信号转导和转录活化因子(signal transducers and activators of transcription,STAT)的活化均与肿瘤的发生、发展密切相关。本研究旨在检测COX-2、p-Stat3及p-Stat5在不同食...背景与目的:研究表明,环氧化酶-2(cyclooxygenase-2,COX-2)及信号转导和转录活化因子(signal transducers and activators of transcription,STAT)的活化均与肿瘤的发生、发展密切相关。本研究旨在检测COX-2、p-Stat3及p-Stat5在不同食管病变组织中的表达,并探讨三者在食管癌组织中表达的意义。方法:采用免疫组织化学SP法检测59例食管鳞状细胞癌、24例鳞状上皮非典型增生及18例正常鳞状上皮中COX-2、p-Stat3及p-Stat5的表达,并分析其与临床病理特征的关系。结果:COX-2在食管正常鳞状上皮、非典型增生和鳞状细胞癌的免疫组化染色平均积分分别为0.83±0.46、1.85±1.24和2.10±1.77,鳞状细胞癌与非典型增生组织的COX-2表达高于正常鳞状上皮,差异有统计学意义(P<0.05);在正常鳞状上皮、非典型增生及鳞状细胞癌中,p-Stat3的平均积分分别为0、0.76±0.59、2.83±1.27,p-Stat5分别为1.98±0.78、3.92±0.41、5.02±0.34,三种组织间两两比较,p-Stat3和p-Stat5表达的差异均有统计学意义(P<0.05)。食管鳞癌中淋巴结转移者及分化较低者COX-2表达低(P<0.05),且不同浸润深度的组织中p-Stat3表达的差异有统计学意义(P<0.05)。不同临床病理特征的组织中p-Stat5表达的差异无统计学意义(P>0.05)。COX-2、p-Stat3及p-Stat5三者的表达之间呈正相关。结论:COX-2可能在食管癌变早期具有重要作用,COX-2高表达可能是食管癌变过程中的早期事件。Stat3的磷酸化与食管癌的进展相关。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 the Major Project of Science and Technology Department of Yunnan Province (202002AA100005 and 202102AE090027-2)the Project of Yunnan Province Food and Drug Homologous Resources Functional Food Innovation Team (A3032023057)+2 种基金the YEFICRC project of Yunnan provincial key programs (2019ZG009)Yunnan Province Ten Thousand Plan Industrial Technology Talents project (YNWR-CYJS-2020-010)the Yunnan Provincial Department of Science and Technology Agricultural Joint Special Project (202101BD070001-120)。
文摘Walnut dreg protein hydrolysates(WDPHs)exhibit a variety of biological activities,however,the cyclooxygenase-2(COX-2)inhibitory peptide of WDPHs remain unclear.The aim of this study was to rapidly screen for such peptides in WDPHs through a combination of in silico and in vitro analysis.In total,1262 peptide sequences were observed by nano liquid chromatography/tandem mass spectrometry(nano LC-MS/MS)and 4 novel COX-2 inhibitory peptides(AGFP,FPGA,LFPD,and VGFP)were identified.Enzyme kinetic data indicated that AGFP,FPGA,and LFPD displayed mixed-type COX-2 inhibition,whereas VGFP was a non-competitive inhibitor.This is mainly because the peptides form hydrogen bonds and hydrophobic interactions with residues in the COX-2 active site.These results demonstrate that computer analysis combined with in vitro evaluation allows for rapid screening of COX-2 inhibitory peptides in walnut protein dregs.
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.
文摘Objective： To investigate the expression of cyclooxygenase-2 （COX-2） and p16 proteins in non-Hodgkin＇s lymphomas （NHL） and their relationship with the genesis and progress of it. Methods： The expression of COX-2 and p16 protein were studied in the lymph nodes tissue from 60 NHL patients and 10 control patients with non-malignant diseases by flow cytometry. Results： Positive rate of COX-2 protein expression in NHL tissues （63.3%, 38/60） was higher than that in normal lymphaden tissues （0, 0/10）. The difference was significant between the two groups （P 〈 0.01）. Expression of COX-2 protein was related with the clinical stage of NHL. In stage Ⅰ ＋ Ⅱ patients, it was significantly lower （35.0% ± 54.6%） than that in stage Ⅲ ＋ Ⅳ patients （84.6% ±87.5%） （P 〈 0.01）. In different sex, age, tumor malignant degree, IPI grade, extranodal involvement and B symptoms groups, the differences of COX-2 expression were not statistically significant （P 〉 0.05）. Positive rate of p16 protein expression （41.7%, 25/60） in NHL＇ was statistically lower than that in normal lymphomas （100%, 10/10） （P 〈 0.01）. Expression of p16 protein was related to malignant degree of NHL. The positive rates of p16 protein in low malignant degree tissues （64.7%, 11/17） was higher than that in high malignant degree tissues （14.3%, 2/14） （P 〈 0.05）. Positive rates of p16 protein of NHL tissues in different sex, age, IPI grade, extranodal involvement, clinical stages and B symptoms were not statistically significant （P 〉 0.05）. The p16 protein expression in COX-2 positive patients was 47.4% （18/38）, and in negative patients it was 31.8% （7/22）. There was no statistically difference between them （P 〉 0.05）. Correlation analysis revealed there was no correlation between expression of COX-2 and p16 protein. Conclusion： Both COX-2 and p16 protein may all have relationship with the genesis and progress of NHL. The expression of COX-2 protein in NHL may be a poor prognostic indicator. COX-2 and p16 protein probably have different mechanisms in the genesis and progress of NHL. Their relationship is firstly put forward in this article and needed further studying.
文摘背景与目的:研究表明,环氧化酶-2(cyclooxygenase-2,COX-2)及信号转导和转录活化因子(signal transducers and activators of transcription,STAT)的活化均与肿瘤的发生、发展密切相关。本研究旨在检测COX-2、p-Stat3及p-Stat5在不同食管病变组织中的表达,并探讨三者在食管癌组织中表达的意义。方法:采用免疫组织化学SP法检测59例食管鳞状细胞癌、24例鳞状上皮非典型增生及18例正常鳞状上皮中COX-2、p-Stat3及p-Stat5的表达,并分析其与临床病理特征的关系。结果:COX-2在食管正常鳞状上皮、非典型增生和鳞状细胞癌的免疫组化染色平均积分分别为0.83±0.46、1.85±1.24和2.10±1.77,鳞状细胞癌与非典型增生组织的COX-2表达高于正常鳞状上皮,差异有统计学意义(P<0.05);在正常鳞状上皮、非典型增生及鳞状细胞癌中,p-Stat3的平均积分分别为0、0.76±0.59、2.83±1.27,p-Stat5分别为1.98±0.78、3.92±0.41、5.02±0.34,三种组织间两两比较,p-Stat3和p-Stat5表达的差异均有统计学意义(P<0.05)。食管鳞癌中淋巴结转移者及分化较低者COX-2表达低(P<0.05),且不同浸润深度的组织中p-Stat3表达的差异有统计学意义(P<0.05)。不同临床病理特征的组织中p-Stat5表达的差异无统计学意义(P>0.05)。COX-2、p-Stat3及p-Stat5三者的表达之间呈正相关。结论:COX-2可能在食管癌变早期具有重要作用,COX-2高表达可能是食管癌变过程中的早期事件。Stat3的磷酸化与食管癌的进展相关。
