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
为了明确肉质相关基因氟烷基因(Hal)、酸肉基因(RN)和脂肪肥胖相关基因(FTO)在国内外不同猪种群体间的遗传变异特性,本研究以大约克、长白、杜洛克和金华猪等猪种群体为研究对象,应用PCR-RFLP技术分别检测了Hal、RN和FTO基因的多态性,...为了明确肉质相关基因氟烷基因(Hal)、酸肉基因(RN)和脂肪肥胖相关基因(FTO)在国内外不同猪种群体间的遗传变异特性,本研究以大约克、长白、杜洛克和金华猪等猪种群体为研究对象,应用PCR-RFLP技术分别检测了Hal、RN和FTO基因的多态性,并分析了FTO基因上2个多态位点g.276G>T和c.594C>G的遗传变异情况。结果表明:(1)在杜洛克猪中发现了Hal的基因型Hal NHal n,其频率为0.166,但未发现基因型Hal n Hal n,其它猪种群体中仅检测到了基因型Hal NHal N;(2)在已检测的所有猪种群体中只检测到RN基因的rn/rn基因型,未发现rn/RN和RN/RN基因型;(3)在FTO的g.276G>T位点上,金华猪呈现单态,其它猪种群体均呈现多态。在FTO的c.594C>G位点上,4个猪种群体均呈现多态,3个外来猪种群体均以CC基因型频率较高,而金华猪则以GG基因型频率较高。研究结果提示,由于Hal基因在养猪生产中的利弊双重性,因此在某些猪种群体中仍然存在较高频率的Hal NHal n基因型。此外,结合FTO基因的生理功能和已有的研究结果,可在特定的猪群中将其作为影响猪肉质性状的候选基因。本研究发现FTO的基因型分布在我国优良地方猪种金华猪与国外3个种猪群间存在较大差异,为深入研究不同品种猪的肉质形成机理提供了基础数据。展开更多
目的:FTO(fat-mass and obesity-associated)基因是首个得以广泛验证的肥胖易感基因,FTO rs9939609位点的突变与肥胖和糖尿病等密切相关。以男大学生为例,探讨运动和饮食干预对于FTO不同基因型个体影响的差异。方法:将被试随机分为运动...目的:FTO(fat-mass and obesity-associated)基因是首个得以广泛验证的肥胖易感基因,FTO rs9939609位点的突变与肥胖和糖尿病等密切相关。以男大学生为例,探讨运动和饮食干预对于FTO不同基因型个体影响的差异。方法:将被试随机分为运动组(E组)、运动饮食控制组(E+D组)、对照组(C组),运动类型主要为有氧运动,饮食干预主要包括营养知识讲座和反馈。检测所有被试FTO rs9939609位点基因型,测试指标主要为体成分和糖尿病相关指标。结果:对于FTO rs9939609位点TT型,E组在干预后BMI和体脂百分比的下降程度显著性高于C组,E+D组BMI、体脂百分比、内脏脂肪指数和血糖的下降程度显著性高于C组;而对于FTO rs9939609位点TA型被试,E+D组BMI、腰围和体脂百分比、血糖的下降程度显著高于C组。运动饮食干预对于风险等位基因携带者腰围的干预效果更明显。结论:运动和饮食干预显著改善被试体成分和血糖等指标。运动饮食干预对于携带FTO风险等位基因的TA型被试腰围干预效果更明显。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.
文摘为了明确肉质相关基因氟烷基因(Hal)、酸肉基因(RN)和脂肪肥胖相关基因(FTO)在国内外不同猪种群体间的遗传变异特性,本研究以大约克、长白、杜洛克和金华猪等猪种群体为研究对象,应用PCR-RFLP技术分别检测了Hal、RN和FTO基因的多态性,并分析了FTO基因上2个多态位点g.276G>T和c.594C>G的遗传变异情况。结果表明:(1)在杜洛克猪中发现了Hal的基因型Hal NHal n,其频率为0.166,但未发现基因型Hal n Hal n,其它猪种群体中仅检测到了基因型Hal NHal N;(2)在已检测的所有猪种群体中只检测到RN基因的rn/rn基因型,未发现rn/RN和RN/RN基因型;(3)在FTO的g.276G>T位点上,金华猪呈现单态,其它猪种群体均呈现多态。在FTO的c.594C>G位点上,4个猪种群体均呈现多态,3个外来猪种群体均以CC基因型频率较高,而金华猪则以GG基因型频率较高。研究结果提示,由于Hal基因在养猪生产中的利弊双重性,因此在某些猪种群体中仍然存在较高频率的Hal NHal n基因型。此外,结合FTO基因的生理功能和已有的研究结果,可在特定的猪群中将其作为影响猪肉质性状的候选基因。本研究发现FTO的基因型分布在我国优良地方猪种金华猪与国外3个种猪群间存在较大差异,为深入研究不同品种猪的肉质形成机理提供了基础数据。
