Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and...Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress.Sinensetin(Sin)is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities.Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms.We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs)under inflammatory conditions.Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo.By molecular docking,we identified Bach1 as a strong binding target of Sin,and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays.Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter,subsequently upregulating the expression of the key antioxidant factor HO-1.Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects.Additionally,we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress.Overall,Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.展开更多
文章以达拉皮科拉《献给安娜莉贝拉的音乐札记》(Quaderno Musicale di Annalibera)为例,通过不同的分析视角与方法,对其各乐章的不同音高组织结构即12音序列内部结构及序列之间的发展逻辑的特点进行凸现与分类,试图阐明12音序列作品中...文章以达拉皮科拉《献给安娜莉贝拉的音乐札记》(Quaderno Musicale di Annalibera)为例,通过不同的分析视角与方法,对其各乐章的不同音高组织结构即12音序列内部结构及序列之间的发展逻辑的特点进行凸现与分类,试图阐明12音序列作品中除以序列内部顺序作为结构特征之外,还通过共有相同音级子集、强调微观音程与宏观路径的对称性等建构音高组织的多重结构思路。展开更多
基金supported by National Natural Science Foundation of China(82001050,82173871)Natural Science Foundation of Jiangsu Province(BK20190135)+2 种基金Fundamental Research Funds for the Central Universities(021414380503)“3456”Cultivation Program for Junior Talents of Nanjing Stomatological Hospital,Medical School of Nanjing University(0222R209)Jiangsu Provincial Medical Key Discipline Cultivation Unit(JSDW202246).
文摘Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress.Sinensetin(Sin)is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities.Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms.We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs)under inflammatory conditions.Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo.By molecular docking,we identified Bach1 as a strong binding target of Sin,and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays.Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter,subsequently upregulating the expression of the key antioxidant factor HO-1.Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects.Additionally,we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress.Overall,Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.
文摘文章以达拉皮科拉《献给安娜莉贝拉的音乐札记》(Quaderno Musicale di Annalibera)为例,通过不同的分析视角与方法,对其各乐章的不同音高组织结构即12音序列内部结构及序列之间的发展逻辑的特点进行凸现与分类,试图阐明12音序列作品中除以序列内部顺序作为结构特征之外,还通过共有相同音级子集、强调微观音程与宏观路径的对称性等建构音高组织的多重结构思路。
