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
Drought and salt stresses are major abiotic factors that severely affect the growth,development,and yield formation of Brassica napus.Human derived FTO gene(Fat mass and obesity-associated),is a member of the Alk B fa...Drought and salt stresses are major abiotic factors that severely affect the growth,development,and yield formation of Brassica napus.Human derived FTO gene(Fat mass and obesity-associated),is a member of the Alk B family,encoding a m RNA demethylase that is dependent onα-ketoglutarate.Although previous studies have demonstrated that exogenous overexpression of FTO gene can increase plant biomass,its impact on plant stress resistance is still unclear.In this study,we cloned the FTO gene and conducted an analysis of its biological functions for drought and salt resistance for Brassicaceae plants.By overexpressing the FTO gene in Arabidopsis thaliana,the inhibitory effect of salt and drought stress on the root length growth of transgenic lines was significantly lower than that of the control.Moreover,the overexpression of FTO markedly enhanced the tolerance of Arabidopsis to drought and salt stress.It also led to a decrease in malondialdehyde(MDA)content,an increase in proline content,and a boost in superoxide dismutase(SOD)activity.Meanwhile,when the FTO gene was heterologously expressed in B.napus,the transgenic plants were less affected by stress.In comparison to control plants,they exhibited significantly lower MDA levels and markedly higher proline content and SOD activity.Furthermore,staining results with Trypan blue and nitroblue tetrazolium(NBT)staining indicate that the FTO gene can alleviate the damage to plants under stress and inhibit the accumulation of O_(2)^(-).Comprehensively,the results indicate that overexpression of the FTO gene can improve the drought and salt tolerance in transgenic plants,providing valuable references for further exploring the FTO-mediated stress resistance mechanisms.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funded by Biological Breeding-National Science and Technology Major Project(2022ZD04008)Major Science and Technology Project of Hubei Province(2023BBA004)+1 种基金Jiujiang Municipal Key Research and Development Program(2025_001556)the China Agriculture Research System under the Ministry of Agriculture and Rural Affairs and the Chinese Academy of Agricultural Sciences,as well as the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2021-OCRI)。
文摘Drought and salt stresses are major abiotic factors that severely affect the growth,development,and yield formation of Brassica napus.Human derived FTO gene(Fat mass and obesity-associated),is a member of the Alk B family,encoding a m RNA demethylase that is dependent onα-ketoglutarate.Although previous studies have demonstrated that exogenous overexpression of FTO gene can increase plant biomass,its impact on plant stress resistance is still unclear.In this study,we cloned the FTO gene and conducted an analysis of its biological functions for drought and salt resistance for Brassicaceae plants.By overexpressing the FTO gene in Arabidopsis thaliana,the inhibitory effect of salt and drought stress on the root length growth of transgenic lines was significantly lower than that of the control.Moreover,the overexpression of FTO markedly enhanced the tolerance of Arabidopsis to drought and salt stress.It also led to a decrease in malondialdehyde(MDA)content,an increase in proline content,and a boost in superoxide dismutase(SOD)activity.Meanwhile,when the FTO gene was heterologously expressed in B.napus,the transgenic plants were less affected by stress.In comparison to control plants,they exhibited significantly lower MDA levels and markedly higher proline content and SOD activity.Furthermore,staining results with Trypan blue and nitroblue tetrazolium(NBT)staining indicate that the FTO gene can alleviate the damage to plants under stress and inhibit the accumulation of O_(2)^(-).Comprehensively,the results indicate that overexpression of the FTO gene can improve the drought and salt tolerance in transgenic plants,providing valuable references for further exploring the FTO-mediated stress resistance mechanisms.
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。
