本研究旨在探讨酰基辅酶A合成酶中链家族成员3(acyl-CoA synthetase medium chains 3,ACSM3)在泛癌中的表达模式、预后意义及其与免疫浸润的关系,特别关注其在肾透明细胞癌(kidney renal clear cell carcinoma,KIRC)中的潜在机制。通过...本研究旨在探讨酰基辅酶A合成酶中链家族成员3(acyl-CoA synthetase medium chains 3,ACSM3)在泛癌中的表达模式、预后意义及其与免疫浸润的关系,特别关注其在肾透明细胞癌(kidney renal clear cell carcinoma,KIRC)中的潜在机制。通过癌症基因组图谱(the cancer genome atlas,TCGA)、基因型-组织表达(the genotype-tissue expression,GTEx)数据库和UALCAN(the university of Alabama at Birmingham cancer data analysis portal)数据库分析ACSM3在多种肿瘤中的表达情况。Cox回归分析发现,ACSM3在KIRC、急性髓性白血病、间皮瘤和皮肤黑色素瘤中的高表达与总生存期(overall survival,OS)改善相关,而在脑低级别胶质瘤中则与较差预后相关。此外,单样本基因集富集分析揭示,ACSM3表达与多种肿瘤类型中的免疫细胞浸润显著相关。功能富集分析揭示,ACSM3在KIRC中的相关基因参与了免疫反应和抗原结合等过程。基于ACSM3表达、年龄和M分期构建的列线图模型在预测KIRC患者的OS方面具有较好的临床实用性。综合分析表明,ACSM3在多种肿瘤中,特别是在KIRC中,可能通过调节免疫反应发挥关键作用,作为潜在的预后生物标志物和靶向治疗的候选靶点,具有重要的临床应用潜力。展开更多
酰基辅酶A合成酶中链家族(Acyl-CoA Synthetase Medium Chains,ACSMs)是一类可以活化C6~C10脂肪酸,并参与中链脂肪酸的合成与分解的酶,对于细胞的存活具有重要意义。肿瘤发生时,由于肿瘤细胞增长快速,需要高出正常细胞所需的更多的能量...酰基辅酶A合成酶中链家族(Acyl-CoA Synthetase Medium Chains,ACSMs)是一类可以活化C6~C10脂肪酸,并参与中链脂肪酸的合成与分解的酶,对于细胞的存活具有重要意义。肿瘤发生时,由于肿瘤细胞增长快速,需要高出正常细胞所需的更多的能量供给,除外糖酵解途径,脂肪酸供能也是肿瘤细胞获取能量的重要途径。研究中链脂肪酸合成与代谢的关键酶ACSMs,对于深入探究肿瘤的发生发展及预后等方面均具有重要意义。主要介绍近年来ACSMs家族成员与肿瘤发生发展的研究进展。展开更多
Objective This study investigates the role of miR-144-5p in doxorubicin(DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.Methods Bioinformatics anal...Objective This study investigates the role of miR-144-5p in doxorubicin(DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.Methods Bioinformatics analysis was performed using the gene expression omnibus dataset GSE136547 to identify differentially expressed miRNAs in heart failure.DOX-induced in vitro and in vivo heart failure models were used to study the effects of miR-144-5p on cardiomyocyte viability,apoptosis,and lipid peroxidation.The targeting relationship between miR-144-5p and ACSM1 was verified using dual-luciferase reporter assays.Cardiac function was assessed by echocardiography,and biochemical markers of heart failure were measured using ELISA.The GO and KEGG enrichment analyses of ACSM1 were performed via the bioinformatic tools GeneMANIA and STRING.Results miR-144-5p was significantly upregulated in DOX-treated cardiomyocytes and mouse hearts.Inhibition of miR-144-5p attenuated DOX-induced cardiomyocyte apoptosis,lipid peroxidation,and cardiac dysfunction.ACSM1 was identified as a direct target of miR-144-5p,and its expression was downregulated by DOX.Silencing ACSM1 abolished the protective effects of the miR-144-5p inhibitor on the viability,apoptosis,and lipid peroxidation of cardiomyocytes.Furthermore,miR-144-5p inhibition improved cardiac function in DOX-treated mice,as evidenced by reduced left ventricular dysfunction and decreased levels of heart failure markers(BNP,LDH,Ang II,and ALD).Conclusions Our findings demonstrate that inhibiting miR-144-5p alleviates DOX-induced heart failure by targeting ACSM1 and suppressing lipid peroxidation.The miR-144-5p/ACSM1 axis may represent a novel therapeutic target for heart failure.Future studies should focus on further elucidating the mechanisms underlying this axis and exploring its potential clinical applications.展开更多
Background:Tryptophan metabolism is involved in esophageal carcinogenesis.However,its genetic mechanisms remain unclear.This study aimed to investigate the effect of genetic variants that encode tryptophan metabolism ...Background:Tryptophan metabolism is involved in esophageal carcinogenesis.However,its genetic mechanisms remain unclear.This study aimed to investigate the effect of genetic variants that encode tryptophan metabolism on susceptibility to esophageal cancer(EC)and elucidate the mechanisms underlying genetic variation in EC progression.Methods:Age-and sex-matched cohorts of 167 patients with EC and 236 healthy controls were enrolled in this study.The concentrations of tryptophan and its metabolites were determined by self-assembled high-performance liquid chromatography-tandem mass spectrometry.High-throughput sequencing techniques were utilized to detect candidate coding genetic variants,and dominant genetic models were used to elucidate the genotypic associations.Results:Tryptophan metabolism was significantly imbalanced in patients with EC,with elevated indolepropionic acid(IPA)levels reducing the risk of EC susceptibility.ACSM2B rs73530508(A>G)mutation was associated with higher IPA levels in vivo(P?0.0004,false discovery rate[FDR]?0.0092)and significantly reduced the risk of EC susceptibility(odds ratio[OR]:0.576,Padj?0.0161).Mediation effect analysis indicated that singlenucleotide polymorphism may inhibit carcinogenesis by reducing IPA metabolism and excretion with a mediation effect of 45.54%.Conclusions:This study identifies the potential mechanism of ACSM2B rs73530508(A>G)in esophageal carcinogenesis and its role in driving increased IPA levels,thereby suppressing the risk of development.展开更多
大型机械设备的关键铁磁构件服役工况恶劣,易形成应力集中并可能导致疲劳累积损伤、裂纹等破坏性缺陷,因此准确评价铁磁构件的应力集中程度可有效防止危险性缺陷的产生。研制了用于测量应力的交变磁场应力测量法（Alternating current s...大型机械设备的关键铁磁构件服役工况恶劣,易形成应力集中并可能导致疲劳累积损伤、裂纹等破坏性缺陷,因此准确评价铁磁构件的应力集中程度可有效防止危险性缺陷的产生。研制了用于测量应力的交变磁场应力测量法（Alternating current stress measurement,ACSM）系统,其硬件部分包括检测探头、激励模块、信号调理电路和信号采集模块等,信号采集系统基于LabVIEW软件设计。对Q235钢进行静态应力检测,通过分析检测传感器二维信号的变化特征,研究不同应力程度、激励磁场与应力方向夹角a和激励频率f对ACSM检测信号的影响。试验结果表明:随应力的增加,仅△UBx呈线性逐渐增大;激励磁场与应力方向相同时（α=0°）,△UBx最大值为160 mV,并随α角的增加逐渐变大,当α=90°时达到最大值270mV;当f≤3kHz时,检测信号△UBx随激励频率的增加呈递增趋势,而f（29）3 k Hz时,检测信号趋于稳定或减小。展开更多
2025年3月,《ACSM运动测试与运动处方指南》(以下简称“《ACSM指南》”)第12版正式出版[1]。让我感到意外的是,本次更新距离上一版仅3年多的时间。翻开书籍封面,“50”这个醒目的数字提醒:自1975年第一版问世以来,《ACSM指南》已走过了...2025年3月,《ACSM运动测试与运动处方指南》(以下简称“《ACSM指南》”)第12版正式出版[1]。让我感到意外的是,本次更新距离上一版仅3年多的时间。翻开书籍封面,“50”这个醒目的数字提醒:自1975年第一版问世以来,《ACSM指南》已走过了整整半个世纪。毫无疑问,无论是美国运动医学会(American College of Sports Medicine,ACSM),还是从第五版就开始负责出版《ACSM指南》的Wolters Kluwer出版社,都不会错过这一极具纪念意义的年份。展开更多
文摘本研究旨在探讨酰基辅酶A合成酶中链家族成员3(acyl-CoA synthetase medium chains 3,ACSM3)在泛癌中的表达模式、预后意义及其与免疫浸润的关系,特别关注其在肾透明细胞癌(kidney renal clear cell carcinoma,KIRC)中的潜在机制。通过癌症基因组图谱(the cancer genome atlas,TCGA)、基因型-组织表达(the genotype-tissue expression,GTEx)数据库和UALCAN(the university of Alabama at Birmingham cancer data analysis portal)数据库分析ACSM3在多种肿瘤中的表达情况。Cox回归分析发现,ACSM3在KIRC、急性髓性白血病、间皮瘤和皮肤黑色素瘤中的高表达与总生存期(overall survival,OS)改善相关,而在脑低级别胶质瘤中则与较差预后相关。此外,单样本基因集富集分析揭示,ACSM3表达与多种肿瘤类型中的免疫细胞浸润显著相关。功能富集分析揭示,ACSM3在KIRC中的相关基因参与了免疫反应和抗原结合等过程。基于ACSM3表达、年龄和M分期构建的列线图模型在预测KIRC患者的OS方面具有较好的临床实用性。综合分析表明,ACSM3在多种肿瘤中,特别是在KIRC中,可能通过调节免疫反应发挥关键作用,作为潜在的预后生物标志物和靶向治疗的候选靶点,具有重要的临床应用潜力。
文摘酰基辅酶A合成酶中链家族(Acyl-CoA Synthetase Medium Chains,ACSMs)是一类可以活化C6~C10脂肪酸,并参与中链脂肪酸的合成与分解的酶,对于细胞的存活具有重要意义。肿瘤发生时,由于肿瘤细胞增长快速,需要高出正常细胞所需的更多的能量供给,除外糖酵解途径,脂肪酸供能也是肿瘤细胞获取能量的重要途径。研究中链脂肪酸合成与代谢的关键酶ACSMs,对于深入探究肿瘤的发生发展及预后等方面均具有重要意义。主要介绍近年来ACSMs家族成员与肿瘤发生发展的研究进展。
基金supported by Chongqing Science and Health Joint Medical Research Project(No.2023MSXM081)2023 Key Disciplines on Public Health Construction in Chongqing.
文摘Objective This study investigates the role of miR-144-5p in doxorubicin(DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.Methods Bioinformatics analysis was performed using the gene expression omnibus dataset GSE136547 to identify differentially expressed miRNAs in heart failure.DOX-induced in vitro and in vivo heart failure models were used to study the effects of miR-144-5p on cardiomyocyte viability,apoptosis,and lipid peroxidation.The targeting relationship between miR-144-5p and ACSM1 was verified using dual-luciferase reporter assays.Cardiac function was assessed by echocardiography,and biochemical markers of heart failure were measured using ELISA.The GO and KEGG enrichment analyses of ACSM1 were performed via the bioinformatic tools GeneMANIA and STRING.Results miR-144-5p was significantly upregulated in DOX-treated cardiomyocytes and mouse hearts.Inhibition of miR-144-5p attenuated DOX-induced cardiomyocyte apoptosis,lipid peroxidation,and cardiac dysfunction.ACSM1 was identified as a direct target of miR-144-5p,and its expression was downregulated by DOX.Silencing ACSM1 abolished the protective effects of the miR-144-5p inhibitor on the viability,apoptosis,and lipid peroxidation of cardiomyocytes.Furthermore,miR-144-5p inhibition improved cardiac function in DOX-treated mice,as evidenced by reduced left ventricular dysfunction and decreased levels of heart failure markers(BNP,LDH,Ang II,and ALD).Conclusions Our findings demonstrate that inhibiting miR-144-5p alleviates DOX-induced heart failure by targeting ACSM1 and suppressing lipid peroxidation.The miR-144-5p/ACSM1 axis may represent a novel therapeutic target for heart failure.Future studies should focus on further elucidating the mechanisms underlying this axis and exploring its potential clinical applications.
基金funded by the 2022 Guangdong Province Clinical Drug Research Fund Project(Clinical Treatment Precision Medicine Special Project)(No:2022JZ21)the 2022 Bai Qiu En-Qiu Suo-Pharmacy Scientific Research Capacity Building Project(No:Z04JKM2021005)+3 种基金the 2022 Guangdong Science and Technology Innovation Strategic Project(“Major ProjcetstTask List”)Shan Fu Ke Letter[2022]124(No:STKJ202209072)the 2022 Special Fund for Hospital Pharmaceutical Research of Guangdong Province Hospital Association(No:YXKY202204)the 2023 Guangdong Provincial Hospital Pharmacist Youth Trust Research Fund(Qingyue Pharmacy Fund)(No:2023QNTJ14)the 2024 Guangdong Provincial Hospital Pharmaceutical Research Foundation(No:2024A05).
文摘Background:Tryptophan metabolism is involved in esophageal carcinogenesis.However,its genetic mechanisms remain unclear.This study aimed to investigate the effect of genetic variants that encode tryptophan metabolism on susceptibility to esophageal cancer(EC)and elucidate the mechanisms underlying genetic variation in EC progression.Methods:Age-and sex-matched cohorts of 167 patients with EC and 236 healthy controls were enrolled in this study.The concentrations of tryptophan and its metabolites were determined by self-assembled high-performance liquid chromatography-tandem mass spectrometry.High-throughput sequencing techniques were utilized to detect candidate coding genetic variants,and dominant genetic models were used to elucidate the genotypic associations.Results:Tryptophan metabolism was significantly imbalanced in patients with EC,with elevated indolepropionic acid(IPA)levels reducing the risk of EC susceptibility.ACSM2B rs73530508(A>G)mutation was associated with higher IPA levels in vivo(P?0.0004,false discovery rate[FDR]?0.0092)and significantly reduced the risk of EC susceptibility(odds ratio[OR]:0.576,Padj?0.0161).Mediation effect analysis indicated that singlenucleotide polymorphism may inhibit carcinogenesis by reducing IPA metabolism and excretion with a mediation effect of 45.54%.Conclusions:This study identifies the potential mechanism of ACSM2B rs73530508(A>G)in esophageal carcinogenesis and its role in driving increased IPA levels,thereby suppressing the risk of development.
文摘大型机械设备的关键铁磁构件服役工况恶劣,易形成应力集中并可能导致疲劳累积损伤、裂纹等破坏性缺陷,因此准确评价铁磁构件的应力集中程度可有效防止危险性缺陷的产生。研制了用于测量应力的交变磁场应力测量法（Alternating current stress measurement,ACSM）系统,其硬件部分包括检测探头、激励模块、信号调理电路和信号采集模块等,信号采集系统基于LabVIEW软件设计。对Q235钢进行静态应力检测,通过分析检测传感器二维信号的变化特征,研究不同应力程度、激励磁场与应力方向夹角a和激励频率f对ACSM检测信号的影响。试验结果表明:随应力的增加,仅△UBx呈线性逐渐增大;激励磁场与应力方向相同时（α=0°）,△UBx最大值为160 mV,并随α角的增加逐渐变大,当α=90°时达到最大值270mV;当f≤3kHz时,检测信号△UBx随激励频率的增加呈递增趋势,而f（29）3 k Hz时,检测信号趋于稳定或减小。
文摘2025年3月,《ACSM运动测试与运动处方指南》(以下简称“《ACSM指南》”)第12版正式出版[1]。让我感到意外的是,本次更新距离上一版仅3年多的时间。翻开书籍封面,“50”这个醒目的数字提醒:自1975年第一版问世以来,《ACSM指南》已走过了整整半个世纪。毫无疑问,无论是美国运动医学会(American College of Sports Medicine,ACSM),还是从第五版就开始负责出版《ACSM指南》的Wolters Kluwer出版社,都不会错过这一极具纪念意义的年份。
