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Zhang L.,Capital Medical University | Ding H.,Capital Medical University | Ding H.,Key Laboratory for Neurodegenerative Diseases of Ministry of Education | Wang D.-H.,Capital Medical University | And 12 more authors.
PLoS ONE | Year: 2013

Recent studies point to an association between the late-onset sporadic Parkinson's disease (PD) and single nucleotide polymorphisms (SNPs) rs1559085 and rs27852 in Ca2+-dependent protease calpain inhibitor calpastatin (CAST) gene. This finding is of interest since loss of CAST activity could result in over activated calpain, potentially leading to Ca2+ dysregulation and loss of substantia nigra neurons in PD. We explored the association between CAST SNPs and late-onset sporadic PD in the Han Chinese population. The study included 615 evaluable patients (363 male, 252 female) with PD and 636 neurologically healthy controls (380 male, 256 female) matched for age, gender, ethnicity, and area of residence. PD cases were identified from the PD cohort of the Chinese National Consortium on Neurodegenerative Diseases (www.chinapd.cn). A total of 24 tag-SNPs were genotyped capturing 95% of the genetic variation across the CAST gene. There was no association found between any of the polymorphisms and PD in all models tested (co-dominant, dominant-effect and recessive-effect). Similarly, none of the common haplotypes was associated with a risk for PD. Our data do not support a significant association between the CAST gene polymorphisms and late onset sporadic PD in the Han Chinese population. © 2013 Zhang et al.


Yang Z.,China Agricultural University | Wang C.,China Agricultural University | Wang T.,China Agricultural University | Bai J.,China Agricultural University | And 8 more authors.
Immunogenetics | Year: 2015

CD1, as the third family of antigen-presenting molecules, is previously only found in mammals and chickens, which suggests that the chicken and mammalian CD1 shared a common ancestral gene emerging at least 310 million years ago. Here, we describe CD1 genes in the green anole lizard and Crocodylia, demonstrating that CD1 is ubiquitous in mammals, birds, and reptiles. Although the reptilian CD1 protein structures are predicted to be similar to human CD1d and chicken CD1.1, CD1 isotypes are not found to be orthologous between mammals, birds, and reptiles according to phylogenetic analyses, suggesting an independent diversification of CD1 isotypes during the speciation of mammals, birds, and reptiles. In the green anole lizard, although the single CD1 locus and MHC I gene are located on the same chromosome, there is an approximately 10-Mb-long sequence in between, and interestingly, several genes flanking the CD1 locus belong to the MHC paralogous region on human chromosome 19. The CD1 genes in Crocodylia are located in two loci, respectively linked to the MHC region and MHC paralogous region (corresponding to the MHC paralogous region on chromosome 19). These results provide new insights for studying the origin and evolution of CD1. © 2015, Springer-Verlag Berlin Heidelberg.


PubMed | Shenyang Pharmaceutical University, Peking University, Chinese PLA 302 Hospital, Capital Medical University and 3 more.
Type: | Journal: Proteomics. Clinical applications | Year: 2016

Type 2 diabetes mellitus (T2DM) is a complex, pandemic disease contributing towards the global burden of health issues. To date, there are no simple clinical tests for the early detection of T2DM.To identify potential peptide biomarkers for such applications, 406 sera of T2DM patients (n = 206) and healthy controls (n = 200) are analyzed by using MALDI-TOF MS with a cross-sectional case-control design.Six peptides (peaks m/z 1452.9, 1692.8, 1946.0, 2115.1, 2211.0 and 4053.6) are identified as candidate biomarkers for T2DM. A diagnostic model constructed with six peptides is able to discriminate T2DM patients from healthy controls, with an accuracy of 82.20%, sensitivity of 82.50%, and specificity of 77.80% in the validation set. Peptide peaks m/z 1452.9 and 1692.8 are identified as fragments of the complement C3f, while peptide peaks m/z 1946.0, 2115.1, and 2211.0 are identified as the fragments of kininogen 1 isoform 1 precursor.This study reinforces proteomic analyses as a potential technique for defining significant clinical peptide biomarkers, providing a simple and convenient diagnostic model for T2DM in clinical examination.


Tao Y.-L.,Sun Yat Sen University | Li Y.,Sun Yat Sen University | Li Y.,Bioyong Beijing Technology Co. | Gao J.,Sun Yat Sen University | And 17 more authors.
Journal of Cellular Biochemistry | Year: 2012

Early diagnosis and treatment is known to improve prognosis for nasopharyngeal carcinoma (NPC). The study determined the specific peptide profiles by comparing the serum differences between NPC patients and healthy controls, and provided the basis for the diagnostic model and identification of specific biomarkers of NPC. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can be used to detect the molecular mass of peptides. Mass spectra of peptides were generated after extracting and purification of 40 NPC samples in the training set, 21 in the single center validation set and 99 in the multicenter validation set using weak cationic-exchanger magnetic beads. The spectra were analyzed statistically using FlexAnalysis and ClinProtbioinformatics software. The four most significant peaks were selected out to train a genetic algorithm model to diagnose NPC. The diagnostic sensitivity and specificity were 100% and 100% in the training set, 90.5% and 88.9% in the single center validation set, 91.9% and 83.3% in the multicenter validation set, and the false positive rate (FPR) and false negative rate (FNR) were obviously lower in the NPC group (FPR, 16.7%; FNR, 8.1%) than in the other cancer group (FPR, 39%; FNR, 61%), respectively. So, the diagnostic model including four peptides can be suitable for NPC but not for other cancers. FGA peptide fragments identified may serve as tumor-associated biomarkers for NPC. © 2012 Wiley Periodicals, Inc.


Zhu D.,Fudan University | Wang J.,Chinese Institute of Basic Medical Sciences | Ren L.,Fudan University | Li Y.,Chinese Institute of Basic Medical Sciences | And 8 more authors.
Journal of Cellular Biochemistry | Year: 2013

No ideal serum biomarker currently exists for the early diagnosis of colorectal cancer (CRC). Magnetic bead-based fractionation coupled with MALDI-TOF MS was used to screen serum samples from CRC patients, healthy controls, and other cancer patients. A diagnostic model with five proteomic features (m/z 1778.97, 1866.16, 1934.65, 2022.46, and 4588.53) was generated using Fisher algorithm with best performance. The Fisher-based model could discriminate CRC patients from the controls with 100% (46/46) sensitivity and 100% (35/35) specificity in the training set, 95.6% (43/45) sensitivity and 83.3% (35/42) specificity in the test set. We further validated the model with 94.4% (254/269) sensitivity and 75.5% (83/110) specificity in the external independent group. In other cancers group, the Fisher-based model classified 25 of 46 samples (54.3%) as positive and the other 21 as negative. With FT-ICR-MS, the proteomic features of m/z 1778.97, 1866.16, 1934.65, and 2022.46, of which intensities decreased significantly in CRC, were identified as fragments of complement C3f. Therefore, the Fisher-based model containing five proteomic features was able to effectively differentiate CRC patients from healthy controls and other cancers with a high sensitivity and specificity, and may be CRC-specific. Serum complement C3f, which was significantly decreased in CRC group, may be relevant to the incidence of CRC. © 2012 Wiley Periodicals, Inc.


Zhu D.,Fudan University | Zhong Y.,Fudan University | Wu H.,Fudan University | Ye L.,Fudan University | And 7 more authors.
Journal of Surgical Research | Year: 2013

Background: There are currently no accurate predictive markers of metachronous liver metastasis (MLM) from colorectal cancer. Methods: Magnetic bead-based fractionation coupled with mass spectrometry analysis was used to compare serum samples from 64 patients with MLM and 64 without recurrence or metastasis for at least 3 y after radical colorectal surgery (NM). A total of 40 MLM and 40 NM serum samples were randomly selected to build a decision tree, and the remainder were tested as blinded samples. Selected peptides were identified. Results: The patients in the two groups were matched for gender, age, tumor location, TNM staging, and histologic differentiation grade. Preoperative serum carcinoembryonic antigen retained no independent power to predict MLM. The decision tree model with eight proteomic features (m/z 3315, 6637, 1207, 1466, 4167, 4210, 2660, and 4186) correctly classified 33 of 40 NM sera (82.5%) and 32 of 40 MLM sera (80%) in the training set and 19 of 24 NM sera (79.2%) and 17 of 24 MLM sera (70.8%) in the test set. The peptides were identified as fragments of alpha-fetoprotein, complement C4-A, fibrinogen alpha, eukaryotic peptide chain release factor GTP-binding subunit ERF3B, and angiotensinogen. Conclusions: In patients matched for gender, age, tumor location, TNM staging, and histologic differentiation grade, preoperative carcinoembryonic antigen retained no independent power to predict MLM. The decision tree model of eight proteomic features demonstrated promising value for predicting MLM in patients who underwent radical resection of colorectal cancer. © 2013 Elsevier Inc. All rights reserved.


Wang Y.,Chongqing Medical University | Wang Y.,Chongqing Key Laboratory of Neurobiology | Chen J.,Chongqing Key Laboratory of Neurobiology | Chen J.,Chongqing Medical University | And 18 more authors.
Psychiatry Research | Year: 2014

Major depressive disorder (MDD) is a debilitating psychiatric illness with no available objective laboratory-based diagnostic test. In this study, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based peptidomics was applied to identify potential urinary diagnostic biomarkers for MDD. A training set of 42 first-episode drug-naive MDD patients and 28 age- and gender-matched healthy controls (HC) was used to develop a peptide diagnostic pattern. Then, the diagnostic efficacy of this pattern was assessed in an independent blinded test set consisting of 24 MDD patients and 13 age- and gender-matched HC. A combination of five potential biomarkers was identified, yielding a sensitivity of 91.7% and specificity of 84.6% in the test set. Moreover, the protein precursors of four of the five peptides were identified by tandem mass spectrometric analysis: serum albumin, apolipoprotein A-I, protein AMBP, and basement membrane-specific heparan sulfate proteoglycan core protein. Taken together, the peptide pattern may be valuable for establishing an objective laboratory-based diagnostic test for MDD. © 2014 Elsevier Ireland Ltd.

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