The composition of serum is extremely complex,which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to effi...The composition of serum is extremely complex,which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich lowabundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and developed a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56%using PC-based proteomic analysis,which was twice the number of proteins identified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.展开更多
基金support from the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000 and 2020YFE0205100)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-C-202002)+3 种基金the National Natural Science Foundation of China(Grant Nos.:82074098,82173914,and 82141001)the CACMS Innovation Fund(Grant Nos.:CI2021A05101 and CI2021A05104)the Fundamental Research Funds for the Central Public Welfare Research Institutes(Grant Nos.:ZZ15-YQ-065,ZZ14-YQ-058,ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-ND-010,ZZ15-ND-10,and ZZ14-FL-002)the Chinese Academy of Sciences(Grant No.:YJKYYQ20210025).
文摘The composition of serum is extremely complex,which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich lowabundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and developed a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56%using PC-based proteomic analysis,which was twice the number of proteins identified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.