目的探讨去甲基化酶脂肪质量和肥胖相关基因(fat mass and obesity associated gene,FTO)在糖尿病冠脉平滑肌收缩功能异常中的影响。方法Cre-loxP重组技术制备平滑肌特异性FTO敲除小鼠(FTO^(SMKO))。分为4组:对照组(WT)、糖尿病组(DM)、...目的探讨去甲基化酶脂肪质量和肥胖相关基因(fat mass and obesity associated gene,FTO)在糖尿病冠脉平滑肌收缩功能异常中的影响。方法Cre-loxP重组技术制备平滑肌特异性FTO敲除小鼠(FTO^(SMKO))。分为4组:对照组(WT)、糖尿病组(DM)、FTO敲除组(FTO^(SMKO))和FTOSMKO糖尿病组(FTO^(SMKO)-DM),每组各15只。糖尿病小鼠由腹腔注射链脲佐菌素(STZ)制备;其余小鼠注射等量的柠檬酸-柠檬酸钠缓冲液。通过小血管环张力测定技术,观察5-HT对4组小鼠冠脉平滑肌收缩反应的影响;采用Western blot与Dot blot技术检测小鼠血管组织FTO蛋白及n6-甲基腺嘌呤(m6A)甲基化修饰水平的变化。结果与WT组相比,DM组血糖明显升高(P<0.01),体质量明显下降(P<0.05);DM组小鼠主动脉FTO蛋白水平升高( P <0.01),m6A甲基化修饰水平降低( P <0.01)。DM组5-HT诱导收缩反应与WT组相比明显下降( P <0.01),而FTOSMKO-DM组收缩反应比DM组明显增加( P <0.01);FTO^(SMKO) -DM组非L型钙通道介导的血管平滑肌收缩反应增强,其中,1,4,5-三磷酸肌醇受体(IP3R)和咖啡因激活兰尼碱受体(RyR)介导的肌浆网钙释放诱导收缩反应均明显增加( P <0.05)。 结论 特异性敲除平滑肌 FTO 可改善糖尿病小鼠冠脉对血管收缩剂5-HT的反应性,可能与FTO介导5-HT受体信号通路异常有关。展开更多
目的:探讨山奈酚(kaempferol,KF)对胃癌细胞顺铂化疗敏感性及细胞迁移的影响及机制。方法:采用慢病毒转染构建稳定低表达肥胖相关蛋白(fat mass and obesity-associated protein,FTO)的人胃癌细胞AGS。将细胞分为对照组、山奈酚组、顺...目的:探讨山奈酚(kaempferol,KF)对胃癌细胞顺铂化疗敏感性及细胞迁移的影响及机制。方法:采用慢病毒转染构建稳定低表达肥胖相关蛋白(fat mass and obesity-associated protein,FTO)的人胃癌细胞AGS。将细胞分为对照组、山奈酚组、顺铂组、山奈酚+顺铂组、空载组、FTO低表达组、顺铂+空载组、顺铂+FTO低表达组、山奈酚+顺铂+空载组、山奈酚+顺铂+FTO低表达组。CCK-8法及平板克隆实验检测各不同处理对细胞增殖的影响;Transwell迁移实验检测不同处理对细胞迁移的影响。免疫印迹和实时荧光定量PCR检测FTO的表达。应用CB-Dock2在线工具分析山奈酚与FTO之间的分子对接情况。结果:山奈酚呈时间剂量依赖性抑制胃癌细胞的增殖能力,且显著增强胃癌细胞对顺铂的化疗敏感性,抑制胃癌细胞的迁移能力(P<0.05)。山奈酚可有效抑制胃癌细胞内FTO表达水平,低表达FTO则抑制细胞增殖和迁移能力(P<0.05)。与对照组相比,FTO的抑制消除了山奈酚对胃癌细胞顺铂化疗敏感性及迁移的影响(P<0.05)。此外,分子对接结果显示山奈酚与FTO之间有5个相互结合的活性口袋。结论:山奈酚通过抑制FTO的表达增强胃癌细胞顺铂化疗敏感性并抑制细胞迁移。展开更多
Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematic...Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematically invest-igates the mechanism by which curcumol ameliorates DR through regulation of the FTO/MAFG-AS1 epigenetic axis and reveals its therapeutic potential in tar-geting the retinal microenvironment via a nano-delivery system.Experimental results demonstrate that curcumol activates the demethylase activity of FTO,sta-bilizing the expression of the long non-coding RNA MAFG-AS1,thereby inhi-biting high glucose-induced retinal endothelial cell inflammation,migration,and vascular leakage.Single-cell transcriptomic analysis further uncovered the dual role of FTO in DR:On the one hand,it promotes pathological angiogenesis in endothelial cells,while on the other hand,it exerts protective effects through MAFG-AS1-mediated antioxidative and anti-inflammatory functions.Moreover,this study proposes a multidimensional epigenetic regulatory network based on histone lactylation,N6-methyladenosine modification,and DNA methylation,and verifies that curcumol delays DR progression by coordinately modulating these modifications.To overcome the limitations of conventional therapies,this study innovatively designed a macrophage membrane-coated nano-delivery system,significantly enhancing the retinal targeting and bioavailability of curcumol.Finally,the study advocates a paradigm shift from passive treatment to early prevention,proposing a three-tiered intervention strategy that integrates epigenetic biomarkers with artificial intelligence-based risk assessment.These findings not only elucidate the multi-target regulatory mechanisms of curcumol but also provide a theoretical foundation for the development of precision therapies for DR based on epigenetic remodeling and microenvironmental synergistic intervention.展开更多
In the article“MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma”(Oncology Research.2024 Oct 16;32(11):1777-1789.doi:10.32604/or.2024.047704),an inadvertent error occurred during...In the article“MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma”(Oncology Research.2024 Oct 16;32(11):1777-1789.doi:10.32604/or.2024.047704),an inadvertent error occurred during the compilation of Figs.3b and 6c.This needed corrections to ensure the accuracy and integrity of the data presented.展开更多
为了探究脂肪量和肥胖相关(fat mass and obesity associated,FTO)基因多态性及其对鸡屠体性状和生长性状的影响,试验采用DNA测序检测鸡FTO基因编码区的单核苷酸多态性(SNP),并采用一般线性模型中的LSD法分析FTO基因多态性对和盈黑鸡屠...为了探究脂肪量和肥胖相关(fat mass and obesity associated,FTO)基因多态性及其对鸡屠体性状和生长性状的影响,试验采用DNA测序检测鸡FTO基因编码区的单核苷酸多态性(SNP),并采用一般线性模型中的LSD法分析FTO基因多态性对和盈黑鸡屠体性状和生长性状的影响。结果表明:在FTO基因第5外显子和第7外显子上各检测到一个SNP位点,分别为g.57337C>A和g.64757T>G突变。g.57337C>A突变形成AA、AB和BB 3种基因型,g.64757T>G突变形成TT、TG和GG 3种基因型。g.57337C>A位点对和盈黑鸡屠体重、宰前活重、头重、胸肌重、腿肌重上、肝脏重、心脏重7个屠体性状有显著或极显著影响(P<0.05或P<0.01),对8,10,16周龄体重影响显著(P<0.05)。g.64757T>G位点对和盈黑鸡宰前活重、全净膛重、半净膛重、屠体重和翅重5个屠体性状有显著影响(P<0.05),对16周龄体重影响显著(P<0.05)。说明FTO基因g.57337C>A和g.64757T>G位点可作为和盈黑鸡屠体性状和生长性状遗传改良的重要候选分子标记。展开更多
In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers a...In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers.The fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes.Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles,with an inverse relationship observed for m6A levels and nuclear-localized FTO expression.Application of Fto small interfering RNA(si RNA)altered the expression of genes related to cell proliferation,hormone regulation,and cell chemotaxis,and affected RNA alternative splicing.Overexpression of the full-length Fto gene led to changes in m6A levels,alternative splicing of Cdk5,cell proliferation,cell cycle progression,and proportion of primordial follicles.Conversely,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle assembly.These findings suggest that FTO,localized in the nucleus but not in the cytoplasm,regulates RNA m6A demethylation and plays a role in cell proliferation,cell cycle progression,and primordial follicle assembly.These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.展开更多
文摘目的探讨去甲基化酶脂肪质量和肥胖相关基因(fat mass and obesity associated gene,FTO)在糖尿病冠脉平滑肌收缩功能异常中的影响。方法Cre-loxP重组技术制备平滑肌特异性FTO敲除小鼠(FTO^(SMKO))。分为4组:对照组(WT)、糖尿病组(DM)、FTO敲除组(FTO^(SMKO))和FTOSMKO糖尿病组(FTO^(SMKO)-DM),每组各15只。糖尿病小鼠由腹腔注射链脲佐菌素(STZ)制备;其余小鼠注射等量的柠檬酸-柠檬酸钠缓冲液。通过小血管环张力测定技术,观察5-HT对4组小鼠冠脉平滑肌收缩反应的影响;采用Western blot与Dot blot技术检测小鼠血管组织FTO蛋白及n6-甲基腺嘌呤(m6A)甲基化修饰水平的变化。结果与WT组相比,DM组血糖明显升高(P<0.01),体质量明显下降(P<0.05);DM组小鼠主动脉FTO蛋白水平升高( P <0.01),m6A甲基化修饰水平降低( P <0.01)。DM组5-HT诱导收缩反应与WT组相比明显下降( P <0.01),而FTOSMKO-DM组收缩反应比DM组明显增加( P <0.01);FTO^(SMKO) -DM组非L型钙通道介导的血管平滑肌收缩反应增强,其中,1,4,5-三磷酸肌醇受体(IP3R)和咖啡因激活兰尼碱受体(RyR)介导的肌浆网钙释放诱导收缩反应均明显增加( P <0.05)。 结论 特异性敲除平滑肌 FTO 可改善糖尿病小鼠冠脉对血管收缩剂5-HT的反应性,可能与FTO介导5-HT受体信号通路异常有关。
文摘目的:探讨山奈酚(kaempferol,KF)对胃癌细胞顺铂化疗敏感性及细胞迁移的影响及机制。方法:采用慢病毒转染构建稳定低表达肥胖相关蛋白(fat mass and obesity-associated protein,FTO)的人胃癌细胞AGS。将细胞分为对照组、山奈酚组、顺铂组、山奈酚+顺铂组、空载组、FTO低表达组、顺铂+空载组、顺铂+FTO低表达组、山奈酚+顺铂+空载组、山奈酚+顺铂+FTO低表达组。CCK-8法及平板克隆实验检测各不同处理对细胞增殖的影响;Transwell迁移实验检测不同处理对细胞迁移的影响。免疫印迹和实时荧光定量PCR检测FTO的表达。应用CB-Dock2在线工具分析山奈酚与FTO之间的分子对接情况。结果:山奈酚呈时间剂量依赖性抑制胃癌细胞的增殖能力,且显著增强胃癌细胞对顺铂的化疗敏感性,抑制胃癌细胞的迁移能力(P<0.05)。山奈酚可有效抑制胃癌细胞内FTO表达水平,低表达FTO则抑制细胞增殖和迁移能力(P<0.05)。与对照组相比,FTO的抑制消除了山奈酚对胃癌细胞顺铂化疗敏感性及迁移的影响(P<0.05)。此外,分子对接结果显示山奈酚与FTO之间有5个相互结合的活性口袋。结论:山奈酚通过抑制FTO的表达增强胃癌细胞顺铂化疗敏感性并抑制细胞迁移。
基金Supported by Quzhou Science and Technology Plan Project,No.2024K076.
文摘Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematically invest-igates the mechanism by which curcumol ameliorates DR through regulation of the FTO/MAFG-AS1 epigenetic axis and reveals its therapeutic potential in tar-geting the retinal microenvironment via a nano-delivery system.Experimental results demonstrate that curcumol activates the demethylase activity of FTO,sta-bilizing the expression of the long non-coding RNA MAFG-AS1,thereby inhi-biting high glucose-induced retinal endothelial cell inflammation,migration,and vascular leakage.Single-cell transcriptomic analysis further uncovered the dual role of FTO in DR:On the one hand,it promotes pathological angiogenesis in endothelial cells,while on the other hand,it exerts protective effects through MAFG-AS1-mediated antioxidative and anti-inflammatory functions.Moreover,this study proposes a multidimensional epigenetic regulatory network based on histone lactylation,N6-methyladenosine modification,and DNA methylation,and verifies that curcumol delays DR progression by coordinately modulating these modifications.To overcome the limitations of conventional therapies,this study innovatively designed a macrophage membrane-coated nano-delivery system,significantly enhancing the retinal targeting and bioavailability of curcumol.Finally,the study advocates a paradigm shift from passive treatment to early prevention,proposing a three-tiered intervention strategy that integrates epigenetic biomarkers with artificial intelligence-based risk assessment.These findings not only elucidate the multi-target regulatory mechanisms of curcumol but also provide a theoretical foundation for the development of precision therapies for DR based on epigenetic remodeling and microenvironmental synergistic intervention.
文摘In the article“MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma”(Oncology Research.2024 Oct 16;32(11):1777-1789.doi:10.32604/or.2024.047704),an inadvertent error occurred during the compilation of Figs.3b and 6c.This needed corrections to ensure the accuracy and integrity of the data presented.
文摘为了探究脂肪量和肥胖相关(fat mass and obesity associated,FTO)基因多态性及其对鸡屠体性状和生长性状的影响,试验采用DNA测序检测鸡FTO基因编码区的单核苷酸多态性(SNP),并采用一般线性模型中的LSD法分析FTO基因多态性对和盈黑鸡屠体性状和生长性状的影响。结果表明:在FTO基因第5外显子和第7外显子上各检测到一个SNP位点,分别为g.57337C>A和g.64757T>G突变。g.57337C>A突变形成AA、AB和BB 3种基因型,g.64757T>G突变形成TT、TG和GG 3种基因型。g.57337C>A位点对和盈黑鸡屠体重、宰前活重、头重、胸肌重、腿肌重上、肝脏重、心脏重7个屠体性状有显著或极显著影响(P<0.05或P<0.01),对8,10,16周龄体重影响显著(P<0.05)。g.64757T>G位点对和盈黑鸡宰前活重、全净膛重、半净膛重、屠体重和翅重5个屠体性状有显著影响(P<0.05),对16周龄体重影响显著(P<0.05)。说明FTO基因g.57337C>A和g.64757T>G位点可作为和盈黑鸡屠体性状和生长性状遗传改良的重要候选分子标记。
基金supported by the Natural Science Foundation of Shandong Province,China (ZR2017MC033)National Key Research and Development Program of China (2023YFD1300504)Taishan Scholar Construction Foundation of Shandong Province,China (ts20190946)。
文摘In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers.The fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes.Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles,with an inverse relationship observed for m6A levels and nuclear-localized FTO expression.Application of Fto small interfering RNA(si RNA)altered the expression of genes related to cell proliferation,hormone regulation,and cell chemotaxis,and affected RNA alternative splicing.Overexpression of the full-length Fto gene led to changes in m6A levels,alternative splicing of Cdk5,cell proliferation,cell cycle progression,and proportion of primordial follicles.Conversely,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle assembly.These findings suggest that FTO,localized in the nucleus but not in the cytoplasm,regulates RNA m6A demethylation and plays a role in cell proliferation,cell cycle progression,and primordial follicle assembly.These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.
