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1.
Sci Rep ; 11(1): 9452, 2021 05 04.
Article in English | MEDLINE | ID: mdl-33947873

ABSTRACT

The diagnostic peripheral biomarkers are still lacking for the bipolar II disorder (BD-II). We used isobaric tags for relative and absolute quantification technology to identify five upregulated candidate proteins [matrix metallopeptidase 9 (MMP9), phenylalanyl-tRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin type 9 (PCSK9)] for the diagnosis of BD-II. We analysed the differences in the plasma levels of these candidate proteins between BD-II patients and controls (BD-II, n = 185; Controls, n = 186) using ELISA. To establish a diagnostic model for the prediction of BD-II, the participants were divided randomly into a training group (BD-II, n = 149; Controls, n = 150) and a testing group (BD-II, n = 36; Controls, n = 36). Significant increases were found in all five protein levels between BD-II and controls in the training group. Logistic regression was analysed to form the composite probability score of the five proteins in the training group. Receiver-operating characteristic curve analysis revealed the diagnostic validity of the probability score [area under curve (AUC) = 0.89, P < 0.001]. The composite probability score of the testing group also showed good diagnostic validity (AUC = 0.86, P < 0.001). We propose that plasma levels of PRDX2, CA-1, FARSB, MMP9, and PCSK9 may be associated with BD-II as potential biomarkers.


Subject(s)
Biomarkers/blood , Bipolar Disorder/blood , Blood Proteins/metabolism , Adult , Area Under Curve , Female , Humans , Logistic Models , Male , Probability , Proprotein Convertase 9/blood , ROC Curve
2.
Sci Rep ; 10(1): 15645, 2020 09 24.
Article in English | MEDLINE | ID: mdl-32973234

ABSTRACT

Kawasaki disease (KD) usually affects the children younger than 5 years of age and subsequently causes coronary artery lesions (CALs) without timely identification and treatment. Developing a robust and fast prediction method may facilitate the timely diagnosis of KD, significantly reducing the risk of CALs in KD patients. The levels of inflammatory serum proteins dramatically vary during the onsets of many immune diseases, including in KD. However, our understanding of their pathogenic roles in KD is behind satisfaction. The purpose of this study was to evaluate candidate diagnostic serum proteins and the potential mechanism in KD using iTRAQ gel-free proteomics. We enrolled subjects and conducted iTRAQ gel-free proteomics to globally screen serum proteins followed by specific validation with ELISA. Further in vitro leukocyte trans-endothelial model was also applied to investigate the pathogenesis roles of inflammatory serum proteins. We identified six KD protein biomarkers, including Protein S100-A8 (S100A8), Protein S100-A9 (S100A9), Protein S100-A12 (S100A12), Peroxiredoxin-2 (PRDX2), Neutrophil defensin 1 (DEFA1) and Alpha-1-acid glycoprotein 1 (ORM1). They enabled us to develop a high-performance KD prediction model with an auROC value of 0.94, facilitating the timely identification of KD. Further assays concluded that recombinant S100A12 protein treatment activated neutrophil surface adhesion molecules responsible for adhesion to endothelial cells. Therefore, S100A12 promoted both freshly clinically isolated neutrophils and neutrophil-like cells to infiltrate through the endothelial layer in vitro. Finally, the antibody against S100A12 may attenuate the infiltration promoted by S100A12. Our result demonstrated that evaluating S100A8, S100A9, S100A12, PRDX2, DEFA1 and ORM1 levels may be a good diagnostic tool of KD. Further in vitro study implied that S100A12 could be a potential therapeutic target for KD.


Subject(s)
Blood Proteins/metabolism , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/immunology , Neutrophil Infiltration , Biomarkers/blood , DNA Methylation , Female , Humans , Infant , Male , Mucocutaneous Lymph Node Syndrome/genetics , Mucocutaneous Lymph Node Syndrome/therapy , S100A12 Protein/blood , S100A12 Protein/immunology
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