A recent study published by Simon Alberti1 in Cell has revealed that DNA double-strand break(DSB)sites that prevent the disjunction of broken DNA ends are formed through poly(ADPribose)(PAR)polymerase 1(PARP1)-DNA co-...A recent study published by Simon Alberti1 in Cell has revealed that DNA double-strand break(DSB)sites that prevent the disjunction of broken DNA ends are formed through poly(ADPribose)(PAR)polymerase 1(PARP1)-DNA co-condensation.1(Fig.1).Here,a comprehensive and novel model was provided for the ordered assembly of PARP1-DNA condensates,which can rationally make clear broken DNA end synapses and how repair effectors are recruited to repair DSB.展开更多
Background The reproductive performance of chickens mainly depends on the development of follicles.Abnor-mal follicle development can lead to decreased reproductive performance and even ovarian disease among chick-ens...Background The reproductive performance of chickens mainly depends on the development of follicles.Abnor-mal follicle development can lead to decreased reproductive performance and even ovarian disease among chick-ens.Chicken is the only non-human animal with a high incidence of spontaneous ovarian cancer.In recent years,the involvement of circRNAs in follicle development and atresia regulation has been confirmed.Results In the present study,we used healthy and atretic chicken follicles for circRNA RNC-seq.The results showed differential expression of circRALGPS2.It was then confirmed that circRALGPS2 can translate into a protein,named cir-cRALGPS2-212aa,which has IRES activity.Next,we found that circRALGPS2-212aa promotes apoptosis and autophagy in chicken granulosa cells by forming a complex with PARP1 and HMGB1.Conclusions Our results revealed that circRALGPS2 can regulate chicken granulosa cell apoptosis and autophagy through the circRALGPS2-212aa/PARP1/HMGB1 axis.展开更多
In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5...In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage.Furthermore,5d induced apoptosis and caused an extended G1/S-phase in these cell lines.Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1.In vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 expression.Overall,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.展开更多
目的观察饮水铅暴露对大鼠大脑皮质、小脑、海马组织中腺苷酸二磷酸核糖聚合酶(PARP)1基因m RNA表达的影响及其与氧化应激的关系。方法 40只SD大鼠根据体重按随机区组法分为5组(对照组和4个暴露组),每组分别自由饮用去离子水、100、200...目的观察饮水铅暴露对大鼠大脑皮质、小脑、海马组织中腺苷酸二磷酸核糖聚合酶(PARP)1基因m RNA表达的影响及其与氧化应激的关系。方法 40只SD大鼠根据体重按随机区组法分为5组(对照组和4个暴露组),每组分别自由饮用去离子水、100、200、400、800 mg/L的醋酸铅溶液,连续染毒60 d后取大脑皮质、小脑和海马,RT-PCR技术检测脑组织PARP1基因m RNA的表达量,并测定脑组织铅、超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-PX)的含量。结果与对照组比较,4个铅暴露组大脑皮质、小脑和海马中PARP1 m RNA表达量显著下降,铅含量显著上升(均P<0.05);最低剂量组大脑皮质及小脑SOD、GSH-PX含量,低剂量组大脑皮质及小脑SOD、GSH-PX含量、海马SOD含量,中、高剂量组大脑皮质、小脑、海马中SOD、GSH-PX含量均显著低于对照组(均P<0.05);最低剂量组海马MDA,低剂量组小脑及海马MDA,中、高剂量组大脑皮质、小脑、海马MDA含量均显著高于对照组(均P<0.05)。随着染铅剂量的升高,各脑组织SOD、GSH-PX含量基本呈逐渐下降趋势,MDA水平基本呈逐渐升高趋势。大脑皮质、小脑、海马PARP1 m RNA表达量均与其组织铅含量及MDA含量呈显著负相关(P<0.05,P<0.01),与SOD含量呈显著正相关(P<0.05);大脑皮质及小脑PARP1 m RNA表达量与GSH-PX含量显著正相关(P<0.05,P<0.01)。结论铅可通过诱导细胞氧化应激影响PARP1基因m RNA表达。展开更多
基金supported by Chinese National Natural Science Funds(31925013,32125016,U20A20393,T2321005)special programs from the Ministry of Science and Technology of China(2021YFA1101000 and 2023YFA1800200)+1 种基金Suzhou Innovation and Entrepreneurship Leading Talent Program(ZXL2022505,ZXL2022442)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘A recent study published by Simon Alberti1 in Cell has revealed that DNA double-strand break(DSB)sites that prevent the disjunction of broken DNA ends are formed through poly(ADPribose)(PAR)polymerase 1(PARP1)-DNA co-condensation.1(Fig.1).Here,a comprehensive and novel model was provided for the ordered assembly of PARP1-DNA condensates,which can rationally make clear broken DNA end synapses and how repair effectors are recruited to repair DSB.
基金This research was funded by The National Key Research and Development Program of China,grant number 2021YFD1300600China Agriculture Research System of MOF and MARA,grant number CARS-40+1 种基金Sichuan Science and Technology Program,grant number 2021YFYZ0007,2021YFYZ0031 and 2022YFYZ0005National Natural Science Foundation of China Grants,grant number 31972543.
文摘Background The reproductive performance of chickens mainly depends on the development of follicles.Abnor-mal follicle development can lead to decreased reproductive performance and even ovarian disease among chick-ens.Chicken is the only non-human animal with a high incidence of spontaneous ovarian cancer.In recent years,the involvement of circRNAs in follicle development and atresia regulation has been confirmed.Results In the present study,we used healthy and atretic chicken follicles for circRNA RNC-seq.The results showed differential expression of circRALGPS2.It was then confirmed that circRALGPS2 can translate into a protein,named cir-cRALGPS2-212aa,which has IRES activity.Next,we found that circRALGPS2-212aa promotes apoptosis and autophagy in chicken granulosa cells by forming a complex with PARP1 and HMGB1.Conclusions Our results revealed that circRALGPS2 can regulate chicken granulosa cell apoptosis and autophagy through the circRALGPS2-212aa/PARP1/HMGB1 axis.
基金This work was supported by the Clinical Research Center for Breast&Thyroid Disease Prevention in Hunan Province(No.2018SK4001)the Scientific Research Project of Hunan Provincial Health Commission(No.20201969)。
文摘In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage.Furthermore,5d induced apoptosis and caused an extended G1/S-phase in these cell lines.Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1.In vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 expression.Overall,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.
文摘目的观察饮水铅暴露对大鼠大脑皮质、小脑、海马组织中腺苷酸二磷酸核糖聚合酶(PARP)1基因m RNA表达的影响及其与氧化应激的关系。方法 40只SD大鼠根据体重按随机区组法分为5组(对照组和4个暴露组),每组分别自由饮用去离子水、100、200、400、800 mg/L的醋酸铅溶液,连续染毒60 d后取大脑皮质、小脑和海马,RT-PCR技术检测脑组织PARP1基因m RNA的表达量,并测定脑组织铅、超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-PX)的含量。结果与对照组比较,4个铅暴露组大脑皮质、小脑和海马中PARP1 m RNA表达量显著下降,铅含量显著上升(均P<0.05);最低剂量组大脑皮质及小脑SOD、GSH-PX含量,低剂量组大脑皮质及小脑SOD、GSH-PX含量、海马SOD含量,中、高剂量组大脑皮质、小脑、海马中SOD、GSH-PX含量均显著低于对照组(均P<0.05);最低剂量组海马MDA,低剂量组小脑及海马MDA,中、高剂量组大脑皮质、小脑、海马MDA含量均显著高于对照组(均P<0.05)。随着染铅剂量的升高,各脑组织SOD、GSH-PX含量基本呈逐渐下降趋势,MDA水平基本呈逐渐升高趋势。大脑皮质、小脑、海马PARP1 m RNA表达量均与其组织铅含量及MDA含量呈显著负相关(P<0.05,P<0.01),与SOD含量呈显著正相关(P<0.05);大脑皮质及小脑PARP1 m RNA表达量与GSH-PX含量显著正相关(P<0.05,P<0.01)。结论铅可通过诱导细胞氧化应激影响PARP1基因m RNA表达。
