BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essenti...BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.展开更多
目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性...目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性别、年龄相匹配的277例健康女性作为对照组,采用iMLDR单核苷酸多态性(SNP)分型方法检测GAS5基因rs145204276 I/D、rs55829688 C/T和rs6790 G/A位点基因型。采用logistic回归分析GAS5基因多态性与PCOS的相关性。结果:GAS5基因rs145204276 I/D位点多态性在对照组和PCOS组之间差异有统计学意义,logistic回归分析结果显示,与I/I基因型相比,I/D和D/D基因型以及显性模型I/D+D/D具有较低的PCOS发病风险[I/D vs I/I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D/D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D/D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002];与I等位基因相比,D等位基因显著降低PCOS的发病风险[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001]。rs55829688 C/T和rs6790 G/A位点多态性在对照组和PCOS组之间比较差异均无统计学意义(P>0.05)。单倍型联合分析显示D-T-A单倍型在对照组和PCOS组间的分布差异有统计学意义[OR(95%CI)=0.61(0.45,0.84),P=0.002]。结论:GAS5基因rs145204276 I/D位点多态性可能与PCOS遗传易感性相关,即携带D等位基因的个体可能具有较低的PCOS发病风险。展开更多
文摘BACKGROUND Diabetic retinopathy(DR)is a major microvascular complication of diabetes mellitus,leading to significant visual impairment and blindness among adults.Current treatment options are limited,making it essential to explore novel therapeutic strategies.Curcumol,a sesquiterpenoid derived from traditional Chinese medicine,has shown anti-inflammatory and anti-cancer properties,but its potential role in DR remains unclear.AIM To investigate the therapeutic effects of curcumol on the progression of DR and to elucidate the underlying molecular mechanisms,particularly its impact on the fat mass and obesity-associated(FTO)protein and the long non-coding RNA(lncRNA)MAF transcription factor G antisense RNA 1(MAFG-AS1).METHODS A streptozotocin-induced mouse model of DR was established,followed by treatment with curcumol.Retinal damage and inflammation were evaluated through histological analysis and molecular assays.Human retinal vascular endothelial cells were exposed to high glucose conditions to simulate diabetic environments in vitro.Cell proliferation,migration,and inflammation markers were assessed in curcumoltreated cells.LncRNA microarray analysis identified key molecules regulated by curcumol,and further experiments were conducted to confirm the involvement of FTO and MAFG-AS1 in the progression of DR.RESULTS Curcumol treatment significantly reduced blood glucose levels and alleviated retinal damage in streptozotocininduced DR mouse models.In high-glucose-treated human retinal vascular endothelial cells,curcumol inhibited cell proliferation,migration,and inflammatory responses.LncRNA microarray analysis identified MAFG-AS1 as the most upregulated lncRNA following curcumol treatment.Mechanistically,FTO demethylated MAFG-AS1,stabilizing its expression.Rescue experiments demonstrated that the protective effects of curcumol against DR were mediated through the FTO/MAFG-AS1 signaling pathway.CONCLUSION Curcumol ameliorates the progression of DR by modulating the FTO/MAFG-AS1 axis,providing a novel therapeutic pathway for the treatment of DR.These findings suggest that curcumol-based therapies could offer a promising alternative for managing this debilitating complication of diabetes.
文摘目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性别、年龄相匹配的277例健康女性作为对照组,采用iMLDR单核苷酸多态性(SNP)分型方法检测GAS5基因rs145204276 I/D、rs55829688 C/T和rs6790 G/A位点基因型。采用logistic回归分析GAS5基因多态性与PCOS的相关性。结果:GAS5基因rs145204276 I/D位点多态性在对照组和PCOS组之间差异有统计学意义,logistic回归分析结果显示,与I/I基因型相比,I/D和D/D基因型以及显性模型I/D+D/D具有较低的PCOS发病风险[I/D vs I/I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D/D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D/D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002];与I等位基因相比,D等位基因显著降低PCOS的发病风险[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001]。rs55829688 C/T和rs6790 G/A位点多态性在对照组和PCOS组之间比较差异均无统计学意义(P>0.05)。单倍型联合分析显示D-T-A单倍型在对照组和PCOS组间的分布差异有统计学意义[OR(95%CI)=0.61(0.45,0.84),P=0.002]。结论:GAS5基因rs145204276 I/D位点多态性可能与PCOS遗传易感性相关,即携带D等位基因的个体可能具有较低的PCOS发病风险。
