Proteomics Study of Peripheral Blood Mononuclear Cells (PBMCs) in Autistic Children

Autism is one of the most common neurological developmental disorder associated with social isolation and restricted interests in children. The etiology of this disorder is still unknown. There is neither any confirmed laboratory test nor any effective therapeutic strategy to diagnose or cure it. To search for biomarkers for early detection and exploration of the disease mechanisms, here, we investigated the protein expression signatures of peripheral blood mononuclear cells (PBMCs) in autistic children compared with healthy controls by using isobaric tags for relative and absolute quantitation (iTRAQ) proteomics approach. The results showed a total of 41 proteins as differentially expressed in autistic group as compared to control. These proteins are found associated with metabolic pathways, endoplasmic reticulum (ER) stress and protein folding, endocytosis, immune and inflammatory response, plasma lipoprotein particle organization, and cell adhesion. Among these, 17 proteins (13 up-regulated and four down-regulated) are found to be linked with mitochondria. Eight proteins including three already reported proteins in our previous studies were selected to be verified. Five already reported autism associated pro-inflammatory cytokines [interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α)] were detected in plasma by enzyme-linked immunosorbent assay (ELISA) analysis. The results were consistent with proteomic results and reports from previous literature. These results proposed that PBMCs from autistic children might be activated, and ER stress, unfolded protein response (UPR), acute-phase response (APR), inflammatory response, and endocytosis may be involved in autism occurrence. These reported proteins may serve as potential biomarkers for early diagnosis of autism. More specifically, simultaneous detection of three proteins [complement C3 (C3), calreticulin (CALR), and SERPINA1] in the plasma and PBMCs could increase the authenticity of detection

Evaluation of quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging in qualitative diagnosis of hepatic masses

Abstract Background To explore the value of parameters of multiphase dynamic contrast-enhanced magnetic resonance imaging (MDCE-MRI) in the qualitative diagnosis of hepatic masses. Methods Eighty patients with hepatic masses were retrospectively analyzed. All the patients underwent MDCE-MRI at 3.0 T MR before treatment. Mean enhancement time (MET), positive enhancement integral (PEI), a maximum slope of increase (MSI), and a maximum slope of decrease (MSD) were measured. Results There were significant differences between benign and malignant hepatic masses with respect to MET, PEI, and MSI values. The PEI and MSI values between hemangiomas, hepatocellular carcinomas (HCCs), cholangiocarcinomas, and metastatic tumors had significant differences. The MSD value between metastatic tumors, HCCs, and hemangiomas were significantly different. The area under the curve (AUC) values of the receiver operator characteristic curves for MET, PEI, and MSI were 0.70, 0.72, and 0.80, respectively. The specificity of MET, PEI, and MSI were all 77%, and the sensitivities of MSI was the highest, of which was 82.40%. Logistic regression analysis showed the regression equation to be P = 1/[1 + e0.008 × 1 + 0.007 × 2–6.707], and taking the Youden index maximum points as a diagnostic point was 0.2946. Conclusion Some parameters of MDCE-MRI have significant roles in differentiating hepatic masses

Redox Proteomic Profiling of Specifically Carbonylated Proteins in the Serum of Triple Transgenic Alzheimer’s Disease Mice

Oxidative stress is a key event in the onset and progression of neurodegenerative diseases, including Alzheimer’s disease (AD). To investigate the role of oxidative stress in AD and to search for potential biomarkers in peripheral blood, serums were collected in this study from the 3-, 6-, and 12-month-old triple transgenic AD mice (3×Tg-AD mice) and the age- and sex-matched non-transgenic (non-Tg) littermates. The serum oxidized proteins were quantified by slot-blot analysis and enzyme-linked immunosorbent assay (ELISA) to investigate the total levels of serum protein carbonyl groups. Western blotting, in conjunction with two-dimensional gel electrophoresis (2D-Oxyblot), was employed to identify and quantify the specifically-carbonylated proteins in the serum of 3×Tg-AD mice. The results showed that the levels of serum protein carbonyls were increased in the three month old 3×Tg-AD mice compared with the non-Tg control mice, whereas no significant differences were observed in the six and 12 months old AD mice, suggesting that oxidative stress is an early event in AD progression. With the application of 2D-Oxyblot analysis, (immunoglobin) Ig gamma-2B chain C region (IGH-3), Ig lambda-2 chain C region (IGLC2), Ig kappa chain C region (IGKC), and Ig kappa chain V-V region HP R16.7 were identified as significantly oxidized proteins compared with the control. Among them IGH-3 and IGKC were validated via immunoprecipitation and Western blot analysis. Identification of oxidized proteins in the serums of 3×Tg-AD mice can not only reveal potential roles of those proteins in the pathogenesis of AD but also provide potential biomarkers of AD at the early stage