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
目的观察白斑颗粒Ⅰ号方对白癜风患者Foxp3 m RNA表达的影响,阐明白斑Ⅰ号方治疗白癜风的作用机制。方法白癜风患者60例,随机分为试验组和对照组各30例,健康对照组30例,采用RT-PCR方法检测各组PBMC中Foxp3 m RNA表达变化情况。结果白癜...目的观察白斑颗粒Ⅰ号方对白癜风患者Foxp3 m RNA表达的影响,阐明白斑Ⅰ号方治疗白癜风的作用机制。方法白癜风患者60例,随机分为试验组和对照组各30例,健康对照组30例,采用RT-PCR方法检测各组PBMC中Foxp3 m RNA表达变化情况。结果白癜风患者组Foxp3 m RNA水平低于健康对照组,差异有统计学意义(P<0.05);实验组治疗3个月后Foxp3 m RNA水平高于治疗前,差异有统计学意义(P<0.05);对照组治疗3个月后Foxp3 m RNA水平高于治疗前,差异有统计学意义(P<0.05);治疗3个月后,实验组治疗前后外周血Foxp3 m RNA升高值高于对照组治疗前后外周血Foxp3 m RNA升高值,差异有统计学意义(P<0.05)。结论白斑颗粒Ⅰ号可能通过上调调节T细胞功能,使PBMC Foxp3 m RNA恢复或接近正常水平达到治疗白癜风的目的。展开更多
Background： Sequence-specific binding by transcription factors （TFs） plays a significant role in the selection and regulation of target genes. At the protein：DNA interface, amino acid side-chains construct a diver...Background： Sequence-specific binding by transcription factors （TFs） plays a significant role in the selection and regulation of target genes. At the protein：DNA interface, amino acid side-chains construct a diverse physicochemical network of specific and non-specific interactions, and seemingly subtle changes in amino acid identity at certain positions may dramatically impact TF：DNA binding. Variation of these specificity-determining residues （SDRs） is a major mechanism of functional divergence between TFs with strong structural or sequence homology. Methods： In this study, we employed a combination of high-throughput specificity profiling by SELEX and Spec-seq, structural modeling, and evolutionary analysis to probe the binding preferences of winged helix-turn-helix TFs belonging to the OmpR sub-family in Escherichia coil Results： We found that E. coli OmpR paralogs recognize tandem, variably spaced repeats composed of＂GT-A＂ or ＂GCT＂-containing half-sites. Some divergent sequence preferences observed within the ＂GT-A＂ mode correlate with amino acid similarity; conversely, ＂GCT＂-based motifs were observed for a subset of paralogs with low sequence homology. Direct specificity profiling of a subset of OmpR homologues （CpxR, RstA, and OmpR） as well as predicted ＂SDR-swap＂ variants revealed that individual SDRs may impact sequence preferences locally through direct contact with DNA bases or distally via the DNA backbone. Conclusions： Overall, our work provides evidence for a common structural code for sequence-specific wHTH：DNA interactions, and demonstrates that surprisingly modest residue changes can enable recognition of highly divergent sequence motifs. Further examination of SDR predictions will likely reveal additional mechanisms controlling the evolutionary divergence of this important class of transcriptional regulators.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.
文摘目的观察白斑颗粒Ⅰ号方对白癜风患者Foxp3 m RNA表达的影响,阐明白斑Ⅰ号方治疗白癜风的作用机制。方法白癜风患者60例,随机分为试验组和对照组各30例,健康对照组30例,采用RT-PCR方法检测各组PBMC中Foxp3 m RNA表达变化情况。结果白癜风患者组Foxp3 m RNA水平低于健康对照组,差异有统计学意义(P<0.05);实验组治疗3个月后Foxp3 m RNA水平高于治疗前,差异有统计学意义(P<0.05);对照组治疗3个月后Foxp3 m RNA水平高于治疗前,差异有统计学意义(P<0.05);治疗3个月后,实验组治疗前后外周血Foxp3 m RNA升高值高于对照组治疗前后外周血Foxp3 m RNA升高值,差异有统计学意义(P<0.05)。结论白斑颗粒Ⅰ号可能通过上调调节T细胞功能,使PBMC Foxp3 m RNA恢复或接近正常水平达到治疗白癜风的目的。
文摘Background： Sequence-specific binding by transcription factors （TFs） plays a significant role in the selection and regulation of target genes. At the protein：DNA interface, amino acid side-chains construct a diverse physicochemical network of specific and non-specific interactions, and seemingly subtle changes in amino acid identity at certain positions may dramatically impact TF：DNA binding. Variation of these specificity-determining residues （SDRs） is a major mechanism of functional divergence between TFs with strong structural or sequence homology. Methods： In this study, we employed a combination of high-throughput specificity profiling by SELEX and Spec-seq, structural modeling, and evolutionary analysis to probe the binding preferences of winged helix-turn-helix TFs belonging to the OmpR sub-family in Escherichia coil Results： We found that E. coli OmpR paralogs recognize tandem, variably spaced repeats composed of＂GT-A＂ or ＂GCT＂-containing half-sites. Some divergent sequence preferences observed within the ＂GT-A＂ mode correlate with amino acid similarity; conversely, ＂GCT＂-based motifs were observed for a subset of paralogs with low sequence homology. Direct specificity profiling of a subset of OmpR homologues （CpxR, RstA, and OmpR） as well as predicted ＂SDR-swap＂ variants revealed that individual SDRs may impact sequence preferences locally through direct contact with DNA bases or distally via the DNA backbone. Conclusions： Overall, our work provides evidence for a common structural code for sequence-specific wHTH：DNA interactions, and demonstrates that surprisingly modest residue changes can enable recognition of highly divergent sequence motifs. Further examination of SDR predictions will likely reveal additional mechanisms controlling the evolutionary divergence of this important class of transcriptional regulators.
