Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isol...Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.展开更多
解整合素金属蛋白酶家族由膜锚定型和分泌型蛋白构成,分别是解整合素金属蛋白酶(a disintegrin and metalloproteinase, ADAMs)和具有血小板反应蛋基序的解整合素金属蛋白酶(a disintegrin-like and metalloproteinase with thrombospon...解整合素金属蛋白酶家族由膜锚定型和分泌型蛋白构成,分别是解整合素金属蛋白酶(a disintegrin and metalloproteinase, ADAMs)和具有血小板反应蛋基序的解整合素金属蛋白酶(a disintegrin-like and metalloproteinase with thrombospondin motifs, ADAMTS)。ADAMs和ADAMTS在多种肿瘤的发生、发展中发挥重要作用。在胃癌中,ADAMs和ADAMTS家族成员的异常表达与肿瘤的增殖、侵袭及转移密切相关,靶向ADAMs和ADAMTS的药物研发有望成为胃癌的有效的治疗手段。本文通过概述ADAMs和ADAMTS在胃癌中的研究进展,为其作为胃癌潜在治疗靶点提供理论依据。展开更多
【目的】针对现有桥梁施工线形预测方法的不足,提出一种基于自适应矩估计(adaptive moment estimation,Adam)优化反向传播(back propagation,BP)神经网络的连续刚构桥线形预测方法。【方法】以小乌江大桥为研究对象,通过正交试验确定了...【目的】针对现有桥梁施工线形预测方法的不足,提出一种基于自适应矩估计(adaptive moment estimation,Adam)优化反向传播(back propagation,BP)神经网络的连续刚构桥线形预测方法。【方法】以小乌江大桥为研究对象,通过正交试验确定了桥梁施工线形的敏感参数为混凝土容重、混凝土弹性模量、张拉控制应力和温度。以均方根误差、平均绝对误差、决定系数和运算耗时为评价指标,在初始学习率相同的条件下,对梯度下降、梯度下降最小化、均方根传播和Adam四种优化算法的性能进行对比。【结果】基于Adam优化算法的BP神经网络收敛时的运算耗时为0.518 s,相较于其他三种优化算法,Adam优化算法下BP神经网络具有更快的收敛速度和更高的拟合精度。【结论】所提方法可较准确地预测连续刚构桥施工过程的线形。展开更多
基金supported by the National Science and Technology Council(NSTC 113-2320-B-039-049-MY3 and NSTC 114-2314-B-039-051-MY3)China Medical University(CMU113-ASIA-05,CMU-114-ASIA-01).
文摘Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.
文摘解整合素金属蛋白酶家族由膜锚定型和分泌型蛋白构成,分别是解整合素金属蛋白酶(a disintegrin and metalloproteinase, ADAMs)和具有血小板反应蛋基序的解整合素金属蛋白酶(a disintegrin-like and metalloproteinase with thrombospondin motifs, ADAMTS)。ADAMs和ADAMTS在多种肿瘤的发生、发展中发挥重要作用。在胃癌中,ADAMs和ADAMTS家族成员的异常表达与肿瘤的增殖、侵袭及转移密切相关,靶向ADAMs和ADAMTS的药物研发有望成为胃癌的有效的治疗手段。本文通过概述ADAMs和ADAMTS在胃癌中的研究进展,为其作为胃癌潜在治疗靶点提供理论依据。
文摘【目的】针对现有桥梁施工线形预测方法的不足,提出一种基于自适应矩估计(adaptive moment estimation,Adam)优化反向传播(back propagation,BP)神经网络的连续刚构桥线形预测方法。【方法】以小乌江大桥为研究对象,通过正交试验确定了桥梁施工线形的敏感参数为混凝土容重、混凝土弹性模量、张拉控制应力和温度。以均方根误差、平均绝对误差、决定系数和运算耗时为评价指标,在初始学习率相同的条件下,对梯度下降、梯度下降最小化、均方根传播和Adam四种优化算法的性能进行对比。【结果】基于Adam优化算法的BP神经网络收敛时的运算耗时为0.518 s,相较于其他三种优化算法,Adam优化算法下BP神经网络具有更快的收敛速度和更高的拟合精度。【结论】所提方法可较准确地预测连续刚构桥施工过程的线形。
