OBJECTIVE:To primarily explore the effect and mechanism of Wenshen Yangxue decoction(温肾养血方)in promoting follicular development in elderly female mice.METHODS:Fifty Institute of Cancer Research mice were randomly ...OBJECTIVE:To primarily explore the effect and mechanism of Wenshen Yangxue decoction(温肾养血方)in promoting follicular development in elderly female mice.METHODS:Fifty Institute of Cancer Research mice were randomly divided into blank,controlled ovarian hyperstimulation(COH),low-dose Wenshen Yangxue decoction,medium-dose Wenshen Yangxue decoction,and high-dose Wenshen Yangxue decoction groups,with 10 mice in each group.The number of ovulations,number of fertilizations,mitochondrial adenosine triphosphate(ATP)level,and mitochondrial DNA(mt DNA)of oocytes in each group were compared.Reverse transcriptionpolymerase chain reaction and Western blotting were used to detect the m RNA and protein expression levels of silent information regulator 3(Sirt3)and forkhead transcription factor O13a(FOXO3a).RESULTS:Wenshen Yangxue decoction significantly increased the number of ovulations in mice(P<0.05)and promoted the formation of fertilized eggs.The ATP level and mt DNA copy number of mice oocytes in the highdose groups were significantly higher than those in the COH group(P<0.05).Wenshen Yangxue decoction significantly increased the m RNA and protein levels of Sirt3 and FOXO3a in mouse oocytes.CONCLUSION:Wenshen Yangxue decoction promoted the development of follicles in elderly female mice,increased the number of ovulations and improved fertility.Its mechanism may be related to increased mitochondrial energy metabolism and regulation of the Sirt3/FOXO3a pathway.展开更多
Cryptococcus neoformans and its sister species Cryptococcus deuterogattii are important human fungal pathogens.Despite their phylogenetically close relationship,these two Cryptococcus pathogens are greatly different i...Cryptococcus neoformans and its sister species Cryptococcus deuterogattii are important human fungal pathogens.Despite their phylogenetically close relationship,these two Cryptococcus pathogens are greatly different in their clinical characteristics.However,the determinants underlying the regulatory differences of their pathogenicity remain largely unknown.Here,we show that the forkhead transcription factor Hcm1 promotes infection in C.neoformans but not in C.deuterogattii.Monitoring in vitro and in vivo fitness outcomes of multiple clinical isolates from the two pathogens indicates that Hcm1 mediates pathogenicity in C.neoformans through its key involvement in oxidative stress defense.By comparison,Hcm1 is not critical for antioxidation in C.deuterogattii.Furthermore,we identified SRX1,which encodes the antioxidant sulfiredoxin,as a conserved target of Hcm1 in two Cryptococcus pathogens.Like HCM1,SRX1 had a greater role in antioxidation in C.neoformans than in C.deuterogattii.Significantly,overexpression of SRX1 can largely rescue the defective pathogenicity caused by the absence of Hcm1 in C.neoformans.Conversely,Srx1 is dispensable for virulence in C.deuterogattii.Overall,our findings demonstrate that the difference in the contribution of the antioxidant sulfiredoxin to oxidative stress defense underlies the Hcm1-mediated regulatory differences of pathogenicity in two closely related pathogens.展开更多
基金Supported by Grants from the Beijing Natural Science Foundation:Study on the Effect of Wenshen Yangxue Recipe on Improving the Quality of Oocytes in Aged Female Mice based on Sirt3/FoxO3a Pathway(No.7192068)National Natural Science Foundation of China:Research on the Pathogenesis of Methyl Group Deletion Caused by One Novel Mutation of BRCA2 Gene in Patients from Families at Risk of Hereditary Ovarian Cancer and Breast Cancer(No.8972444)
文摘OBJECTIVE:To primarily explore the effect and mechanism of Wenshen Yangxue decoction(温肾养血方)in promoting follicular development in elderly female mice.METHODS:Fifty Institute of Cancer Research mice were randomly divided into blank,controlled ovarian hyperstimulation(COH),low-dose Wenshen Yangxue decoction,medium-dose Wenshen Yangxue decoction,and high-dose Wenshen Yangxue decoction groups,with 10 mice in each group.The number of ovulations,number of fertilizations,mitochondrial adenosine triphosphate(ATP)level,and mitochondrial DNA(mt DNA)of oocytes in each group were compared.Reverse transcriptionpolymerase chain reaction and Western blotting were used to detect the m RNA and protein expression levels of silent information regulator 3(Sirt3)and forkhead transcription factor O13a(FOXO3a).RESULTS:Wenshen Yangxue decoction significantly increased the number of ovulations in mice(P<0.05)and promoted the formation of fertilized eggs.The ATP level and mt DNA copy number of mice oocytes in the highdose groups were significantly higher than those in the COH group(P<0.05).Wenshen Yangxue decoction significantly increased the m RNA and protein levels of Sirt3 and FOXO3a in mouse oocytes.CONCLUSION:Wenshen Yangxue decoction promoted the development of follicles in elderly female mice,increased the number of ovulations and improved fertility.Its mechanism may be related to increased mitochondrial energy metabolism and regulation of the Sirt3/FOXO3a pathway.
基金supported by the National Key Research and Development Program of China(2021YFC2300400)[Linqi Wang],2021YFC230000[Linqi Wang],2021YFA0911300[Xiao Liu],2021YFC2100600[Xiuyun Tian]:Major Infections Diseases Such as AIDS and Viral Hepatitis Prevention and Control Technology Major Projects(2018ZX10101003[Ying Yang])and CAS Interdisciplinary Innovation Team(Linqi Wang).
文摘Cryptococcus neoformans and its sister species Cryptococcus deuterogattii are important human fungal pathogens.Despite their phylogenetically close relationship,these two Cryptococcus pathogens are greatly different in their clinical characteristics.However,the determinants underlying the regulatory differences of their pathogenicity remain largely unknown.Here,we show that the forkhead transcription factor Hcm1 promotes infection in C.neoformans but not in C.deuterogattii.Monitoring in vitro and in vivo fitness outcomes of multiple clinical isolates from the two pathogens indicates that Hcm1 mediates pathogenicity in C.neoformans through its key involvement in oxidative stress defense.By comparison,Hcm1 is not critical for antioxidation in C.deuterogattii.Furthermore,we identified SRX1,which encodes the antioxidant sulfiredoxin,as a conserved target of Hcm1 in two Cryptococcus pathogens.Like HCM1,SRX1 had a greater role in antioxidation in C.neoformans than in C.deuterogattii.Significantly,overexpression of SRX1 can largely rescue the defective pathogenicity caused by the absence of Hcm1 in C.neoformans.Conversely,Srx1 is dispensable for virulence in C.deuterogattii.Overall,our findings demonstrate that the difference in the contribution of the antioxidant sulfiredoxin to oxidative stress defense underlies the Hcm1-mediated regulatory differences of pathogenicity in two closely related pathogens.
