Publications by authors named "Hao-Teng Chang"

52 Publications

pLG72 induces superoxide radicals via interaction and aggregation with SOD1.

Free Radic Res 2018 Sep 21;52(9):970-976. Epub 2018 Sep 21.

d School of Medicine, China Medical University , Taichung , Taiwan.

G72 has been characterised as a susceptibility gene that can have wide-ranging effects in a number of neurodegenerative diseases, including schizophrenia and major depression. Indeed, its product, pLG72, is a potential serum biomarker for schizophrenia. Previous transcriptomic and biochemical studies have indicated that pLG72 may induce the production of mitochondrial reactive oxygen species (ROS), resulting in cell damage. Here, we investigated the mechanism of pLG72 by transfecting a human U87 glioblastoma cell line with a G72 construct. By employing ROS-specific scavengers, we discovered that superoxide radicals were specifically induced in the pLG72-expressing cells. We also found that pLG72 interacted and co-localised with superoxide dismutase 1 (SOD1), resulting in aggregation of SOD1 with a concomitant 23% or 74% reduction of total SOD activity, depending on the amount of G72 transfection plasmid. Finally, we found that transfection of U87 cells with the G72 construct caused a 29% decrease in cell proliferation. The observed loss of SOD1 function in pLG72-expressing cells may explain the elevated ROS levels and inhibition of U87 cell proliferation and has implications for understanding the onset of neurodegenerative diseases in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10715762.2018.1504293DOI Listing
September 2018

Eosinophilic biomarkers for detection of acute exacerbation of chronic obstructive pulmonary disease with or without pulmonary embolism.

Exp Ther Med 2017 Oct 2;14(4):3198-3206. Epub 2017 Aug 2.

Department of Respiratory Medicine, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang 322100, P.R. China.

Eosinophilia has been implicated in the pathophysiology of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the role of eosinophil activation in the development of AECOPD remains unclear. In the present study, the reliability of plasma levels of eosinophil activation markers, including eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPX), were measured and used as diagnostic biomarkers of AECOPD with or without pulmonary embolism (PE). A total of 47 patients with AECOPD, 30 patients with AECOPD/PE and 35 healthy adults were enrolled in the present study. Plasma levels of ECP, EDN, EPX and MBP were measured using commercial ELISA kits. The mean concentrations of plasma ECP, EDN, EPX and MBP in the patients with AECOPD was significantly 2.87-, 3.06-, 1.60- and 1.92-fold higher, respectively, compared with the control group (P<0.05). Similar results were obtained in patients with AECOPD/PE, for whom plasma levels of ECP, EDN, EPX and MBP were significantly 2.06-, 2.21-, 1.42- and 2.42-fold higher, respectively, compared with the controls (P<0.05). No significant differences were observed in the levels of these proteins between patients with AECOPD or AECOPD/PE. Among the four potential markers, ECP was determined to be the optimal marker for distinguishing patients with AECOPD or AECOPD/PE from the controls. No significant correlation was observed between marker concentrations and gender, age or disease severity. The results of the present study may have clinical applications in the diagnosis of AECOPD using these novel biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2017.4876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585757PMC
October 2017

Intelligent Informatics in Translational Medicine 2016.

Biomed Res Int 2017;2017:1572730. Epub 2017 Feb 28.

Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung, Taiwan; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2017/1572730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350342PMC
October 2018

Electrolyte disorders and aging: risk factors for delirium in patients undergoing orthopedic surgeries.

BMC Psychiatry 2016 Nov 23;16(1):418. Epub 2016 Nov 23.

Department of Orthopedics, Dongyang People's Hospital, Wenzhou Medical University, 60 Wuning West Road, 322100, Dongyang, People's Republic of China.

Background: At present, the exact mechanism of postoperative delirium has not been elucidated. The purpose of this study was to analyze the incidence of delirium in patients undergoing orthopedic surgeries and to explore possible related factors.

Methods: This is a retrospective study. We used 582 patients who had undergone orthopedic surgery between January 2011 and December 2014. The surgeries consisted of 155 cases of internal fixation for intertrochanteric fracture (IFIF), 128 cases of femoral head replacement (FHR), 169 cases of total hip arthroplasty (THA) and 130 cases of total knee arthroplasty (TKA). Among the 582 patients, 75 developed postoperative delirium (an incidence of 12.9%). The demographics of the patients, which included age, gender, operation duration and blood loss, were statistically analyzed with univariate logistic regression analysis and then multivariate logistic regression. To investigate the influences of different electrolytes disorders for postoperative delirium, the Chi-square test was used.

Results: Multivariate logistic regression analysis indicated that postoperative delirium incidence in patients aged 70-79 years and in patients aged ≥80 years was higher than that in patients aged <70 years, odds ratio (OR) values were 6.33 and 26.37, respectively. In addition, the incidence of postoperative delirium in the group of patients with electrolyte disorders was higher than that in the normal group (OR, 2.38). There were statistically significant differences between the delirium group and the non-delirium group in the incidences of the sodium and calcium disorders.

Conclusions: Aging and postoperative electrolyte disorders (hyponatremia and hypocalcemia) are risk factors for postoperative delirium in patients undergoing orthopedic surgeries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12888-016-1130-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120472PMC
November 2016

Elevated Levels of Plasma Superoxide Dismutases 1 and 2 in Patients with Coronary Artery Disease.

Biomed Res Int 2016 17;2016:3708905. Epub 2016 Oct 17.

Department of Cardiology Medicine, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China.

. To measure plasma levels of superoxide dismutases 1, 2, and 3 (SOD1, 2, 3) and determine whether SODs can function as biomarkers for coronary artery disease (CAD). . Patient groups were as follows: patients with stable angina pectoris (SAP, = 33), patients with acute coronary syndrome (ACS, = 49), and controls ( = 42). Protein quantification was done using ELISA. . The concentrations of plasma SOD1 and SOD2 were higher in CAD than in healthy controls. No difference in SOD3 levels between CAD and control groups was found. Limited correlations were found between SODs and gender, age, and severity of coronary artery stenosis. . Plasma levels of SOD1 and SOD2 were elevated in patients with CAD and might serve as surrogate biomarkers for CAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/3708905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086506PMC
March 2017

Role of IGF1R(+) MSCs in modulating neuroplasticity via CXCR4 cross-interaction.

Sci Rep 2016 09 2;6:32595. Epub 2016 Sep 2.

Center for Neuropsychiatry, China Medical University Hospital, Taichung, 40440, Taiwan.

To guide the use of human mesenchymal stem cells (MSCs) toward clinical applications, identifying pluripotent-like-markers for selecting MSCs that retain potent self-renewal-ability should be addressed. Here, an insulin-like growth factor 1 receptor (IGF1R)-expressing sub-population in human dental pulp MSCs (hDSCs), displayed multipotent properties. IGF1R expression could be maintained in hDSCs when they were cultured in 2% human cord blood serum (hUCS) in contrast to that in 10% fetal calf serum (FCS). Cytokine array showed that hUCS contained higher amount of several growth factors compared to FCS, including IGF-1 and platelet-derived growth factor (PDGF-BB). These cytokines modulates the signaling events in the hDSCs and potentially enhances engraftment upon transplantation. Specifically, a bidirectional cross-talk between IGF1R/IGF1 and CXCR4/SDF-1α signaling pathways in hDSCs, as revealed by interaction of the two receptors and synergistic activation of both signaling pathways. In rat stroke model, animals receiving IGF1R(+) hDSCs transplantation, interaction between IGF1R and CXCR4 was demonstrated to promote neuroplasticity, therefore improving neurological function through increasing glucose metabolic activity, enhancing angiogenesis and anti-inflammatiory effects. Therefore, PDGF in hUCS-culture system contributed to the maintenance of the expression of IGF1R in hDSCs. Furthermore, implantation of IGF1R(+) hDSCs exerted enhanced neuroplasticity via integrating inputs from both CXCR4 and IGF1R signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep32595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009335PMC
September 2016

Biomarker discovery using dry-lab technologies and high-throughput screening.

Authors:
Hao-Teng Chang

Biomark Med 2016 06;10(6):559-61

Graduate Institute of Basic Medical Science, China Medical University, Taichung City, Taiwan; Department of Computer Science & Information Engineering, Asia University, Taichung City, Taiwan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/bmm-2016-0111DOI Listing
June 2016

Potential diagnostic and prognostic biomarkers for cholangiocarcinoma in serum and bile.

Biomark Med 2016 06 27;10(6):613-9. Epub 2016 May 27.

Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 40402, Taiwan.

Cholangiocarcinoma (CCA) is a devastating malignancy that is difficult to treat because of its insensitivity to conventional therapies and the inability to detect early tumor formation. Novel molecular techniques have enabled the use of serum and bile markers for CCA diagnosis and prognosis. Herein, we summarize the principal characteristics of serum and bile markers of CCA. Biomarkers such as interleukin-6, matrix metalloproteinases, serotonin (5-hydroxytryptamine) and bile acids have shown promise for improving CCA diagnosis. Several markers such as CYFRA 21-1, MK-1 and C-reactive protein were recently shown to be effective for CCA prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/bmm-2015-0062DOI Listing
June 2016

Fascin-1 as a novel diagnostic marker of triple-negative breast cancer.

Cancer Med 2016 08 17;5(8):1983-8. Epub 2016 May 17.

Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China.

In some cases of breast cancer, diagnosis of triple-negative breast cancer (TNBC) requires further fluorescence in situ hybridization (FISH) for determining human epidermal growth factor receptor 2 (HER2) status. However, few cases undergo FISH in China, leading to difficulty regarding subsequent treatment decisions. Here, we used immunohistochemical analysis to explore expression of fascin-1, an actin-bundling protein, as a diagnostic marker of TNBC. A total of 457 cases of breast cancer were divided into four molecular subtypes, including 82 cases (17.9%) of TNBC, 81 (17.7%) of HER2-enriched, 185 (40.5%) of luminal A, and 109 (23.9%) of luminal B. Positive fascin-1 expression was seen in 144 cases (31.5%), including 77 (16.8%) strong positive cases. Rates of positive and strong positive expression of fascin-1 were significantly higher in cases of TNBC than in the other molecular subtypes. In all cases of breast cancer, the sensitivities and specificities of positive and strong positive fascin-1 expression for predicting TNBC were 87.8% and 80.8%, and 78.0% and 96.5%, respectively. In cases of hormone receptor-negative breast cancer, the sensitivities and specificities of positive and strong positive fascin-1 expression for predicting TNBC were 87.8% and 61.7%, and 78.0% and 92.6%, respectively. In 24 cases with estrogen receptor (ER)-, PR-, and HER2 2 +  equivocal status who underwent FISH, the sensitivity and specificity of strong positive fascin-1 expression for predicting TNBC were 71.4% and 90.0%. These results suggest that strong positive fascin-1 expression can be used as a diagnostic marker of TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971926PMC
August 2016

Pressure Combined with Ischemia/Reperfusion Injury Induces Deep Tissue Injury via Endoplasmic Reticulum Stress in a Rat Pressure Ulcer Model.

Int J Mol Sci 2016 Feb 25;17(3):284. Epub 2016 Feb 25.

Department of Nursing School, Wenzhou Medical University, Wenzhou 325035, China.

Pressure ulcer is a complex and significant health problem in long-term bedridden patients, and there is currently no effective treatment or efficient prevention method. Furthermore, the molecular mechanisms and pathogenesis contributing to the deep injury of pressure ulcers are unclear. The aim of the study was to explore the role of endoplasmic reticulum (ER) stress and Akt/GSK3β signaling in pressure ulcers. A model of pressure-induced deep tissue injury in adult Sprague-Dawley rats was established. Rats were treated with 2-h compression and subsequent 0.5-h release for various cycles. After recovery, the tissue in the compressed regions was collected for further analysis. The compressed muscle tissues showed clear cellular degenerative features. First, the expression levels of ER stress proteins GRP78, CHOP, and caspase-12 were generally increased compared to those in the control. Phosphorylated Akt and phosphorylated GSK3β were upregulated in the beginning of muscle compression, and immediately significantly decreased at the initiation of ischemia-reperfusion injury in compressed muscles tissue. These data show that ER stress may be involved in the underlying mechanisms of cell degeneration after pressure ulcers and that the Akt/GSK3β signal pathway may play an important role in deep tissue injury induced by pressure and ischemia/reperfusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms17030284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813148PMC
February 2016

High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells.

Sci Rep 2016 Jan 7;6:18815. Epub 2016 Jan 7.

Graduate Institute of Immunology, College of Medicine, China Medicine University, Taichung, Taiwan.

Epithelial-mesenchymal transition (EMT) is implicated in bronchial remodeling and loss of lung function in chronic inflammatory airway diseases. Previous studies showed the involvement of the high mobility group box 1 (HMGB1) protein in the pathology of chronic pulmonary inflammatory diseases. However, the role of HMGB1 in EMT of human airway epithelial cells is still unclear. In this study, we used RNA sequencing to show that HMGB1 treatment regulated EMT-related gene expression in human primary-airway epithelial cells. The top five upregulated genes were SNAI2, FGFBP1, VIM, SPARC (osteonectin), and SERPINE1, while the downregulated genes included OCLN, TJP1 (ZO-1), FZD7, CDH1 (E-cadherin), and LAMA5. We found that HMGB1 induced downregulation of E-cadherin and ZO-1, and upregulation of vimentin mRNA transcription and protein translation in a dose-dependent manner. Additionally, we observed that HMGB1 induced AKT phosphorylation, resulting in GSK3β inactivation, cytoplasmic accumulation, and nuclear translocation of β-catenin to induce EMT in human airway epithelial cells. Treatment with PI3K inhibitor (LY294006) and β-catenin shRNA reversed HMGB1-induced EMT. Moreover, HMGB1 induced expression of receptor for advanced glycation products (RAGE), but not that of Toll-like receptor (TLR) 2 or TLR4, and RAGE shRNA inhibited HMGB1-induced EMT in human airway epithelial cells. In conclusion, we found that HMGB1 induced EMT through RAGE and the PI3K/AKT/GSK3β/β-catenin signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep18815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703978PMC
January 2016

Decreased level of serum autoantibody against LG72 is a biosignature of amyotrophic lateral sclerosis.

Biomark Med 2016 ;10(1):73-9

Graduate Institute of Basic Medical Science and PhD Program for Aging, China Medical University, Taichung, Taiwan.

Aim: LG72 can increase mitochondrial ROSs and oxidative stress has been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). The serum level of LG72 or LG72-related molecules might therefore be associated with ALS. Here, we aim to determine the serum autoantibody against LG72 has potential as a biomarker for the diagnosis of ALS.

Materials: Seventy-eighty patients with ALS, 45 patients with AD, 43 patients with PD and 88 healthy adults were enrolled.

Results: The concentration of serum autoantibody against LG72 was more than fourfold lower in ALS than other control groups (p < 0.001). The AUC was 0.9627 when the cut-off value for autoantibody concentration was 0.167 μg/ml.

Conclusion: This finding suggests that the autoantibody against LG72 might serve as a surrogate biomarker for ALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/bmm.15.80DOI Listing
September 2016

A genome-wide association study on amyotrophic lateral sclerosis in the Taiwanese Han population.

Biomark Med 2016 06 18;10(6):597-611. Epub 2015 Nov 18.

Department of Neurology, Taipei City Hospital, Taipei, Taiwan.

Identification of mutations in patients with amyotrophic lateral sclerosis (ALS) in a genome-wide association study can reveal possible biomarkers of such a rapidly progressive and fatal neurodegenerative disease. It was observed that significant single nucleotide polymorphisms vary when the tested population changes from one ethnic group to another. To identify new loci associated with ALS susceptibility in the Taiwanese Han population, we performed a genome-wide association study on 94 patients with sporadic ALS and 376 matched controls. We uncovered two new susceptibility loci at 13q14.3 (rs2785946) and 11q25 (rs11224052). In addition, we analyzed the functions of all the associated genes among 54 significant single nucleotide polymorphisms using Gene Ontology annotations, and the results showed several statistically significant neural- and muscle-related Gene Ontology terms and the associated diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/bmm.15.115DOI Listing
June 2016

Evaluation of platelet distribution width in chronic obstructive pulmonary disease patients with pulmonary embolism.

Biomark Med 2016 06 16;10(6):587-96. Epub 2015 Nov 16.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310000, China.

Background: Platelets play an important role in the pathogenesis of pulmonary embolism (PE). We aimed to investigate whether there is a correlation between platelet distribution width (PDW) and chronic obstructive pulmonary disease (COPD) patients with PE.

Methods: We conducted a retrospective study using 126 COPD patients with PE and 51 COPD patients without PE. Blood biomarkers, including PDW and d-dimer, were included. Odds ratios (OR) associated with PDW and interactions with d-dimer, SpO2 were estimated for PE.

Results: PDW was higher in the COPD patients with PE group (p = 0.007). A higher PDW had a significantly increased risk of PE than a lower PDW (adjusted OR 2.724, 95% CI: 1.290-5.753).

Conclusion: PDW are elevated in COPD patients with PE and are associated with the risk of PE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/bmm.15.112DOI Listing
June 2016

Identification of pLG72-Induced Oxidative Stress Using Systemic Approaches.

Biomed Res Int 2015 11;2015:429253. Epub 2015 Oct 11.

Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Computer Science and Information Engineering, Asia University, Taichung 41354, Taiwan.

G72 is a schizophrenia-susceptible gene encoding a polypeptide with 153 amino acids. In 2002, it was originally proposed as an activator of D-amino acid oxidase (DAOA) that could enhance the activity of DAAO and subsequently reduce the neurotransmission of N-methyl-D-aspartate receptors. However, several controversial findings have been reported recently. Due to a number of inconsistent descriptions of pLG72's biofunctions, this study aims to identify the cellular effects induced by pLG72 in U87 cells using systems biology approaches. The analyses of transcriptomics and biological networks showed that pLG72 might be involved in the induction of oxidative stress. To confirm the in silico prediction, we tested and discovered that overexpression of pLG72 effectively enhanced reactive oxygen species (ROS) in U87 cells and, furthermore, this induction can be quenched by Tempol, a general ROS scavenger. Therefore, G72-transgenic mice presenting some psychiatric symptoms, along with the pLG72 level being significantly increased in the serum of patients with schizophrenia, have led us to propose that the ROS enhancement in mental diseases may be from the overexpression of pLG72 in brain cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/429253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619840PMC
August 2016

Intelligent Informatics in Translational Medicine.

Biomed Res Int 2015 6;2015:717210. Epub 2015 May 6.

Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung 20224, Taiwan ; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 20224, Taiwan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/717210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438178PMC
March 2016

The epidemiology and progression time from transient to permanent psychiatric disorders of substance-induced psychosis in Taiwan.

Addict Behav 2015 Aug 21;47:1-4. Epub 2015 Feb 21.

Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. Electronic address:

Introduction: Substance-induced psychosis (SIP), including alcohol-induced psychotic disorder (AIPD) and substance-induced psychotic disorder (SIPD), is gradually increasing in importance in clinical practice. However, few studies have investigated the epidemiology and progression time from transient to permanent psychiatric disorders for AIPD and SIPD patients.

Methods: We utilized the National Health Insurance Research Database (NHIRD) to investigate the incidence and prevalence of AIPD and SIPD in Taiwan and determined the timing of AIPD or SIPD followed by the development of persistent psychotic conditions.

Results: The average incidence and prevalence were 1.97 and 2.94 per 100,000 person-years for AIPD, 3.09 and 5.67 per 100,000 person-years for SIPD in Taiwan. Moreover, 10.9% to 24.3% of subjects with either AIPD or SIPD had a change in diagnosis to either schizophrenia or affective disorder, and ~50% of patients had a psychotic or affective transformation in their first year after AIPD and SIPD diagnoses. The mean progression time of psychotic or affective transformation was 1.9 to 2.7 years.

Conclusions: SIP is a predictive factor for persistent psychotic and affective transformation, and a three-year follow-up may be an optimal clinical practice to prevent psychotic or affective transformation in 60% of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addbeh.2015.02.013DOI Listing
August 2015

Identification of conserved and polymorphic STRs for personal genomes.

BMC Genomics 2014 12;15 Suppl 10:S3. Epub 2014 Dec 12.

Background: Short tandem repeats (STRs) are abundant in human genomes. Numerous STRs have been shown to be associated with genetic diseases and gene regulatory functions, and have been selected as genetic markers for evolutionary and forensic analyses. High-throughput next generation sequencers have fostered new cutting-edge computing techniques for genome-scale analyses, and cross-genome comparisons have facilitated the efficient identification of polymorphic STR markers for various applications.

Results: An automated and efficient system for detecting human polymorphic STRs at the genome scale is proposed in this study. Assembled contigs from next generation sequencing data were aligned and calibrated according to selected reference sequences. To verify identified polymorphic STRs, human genomes from the 1000 Genomes Project were employed for comprehensive analyses, and STR markers from the Combined DNA Index System (CODIS) and disease-related STR motifs were also applied as cases for evaluation. In addition, we analyzed STR variations for highly conserved homologous genes and human-unique genes. In total 477 polymorphic STRs were identified from 492 human-unique genes, among which 26 STRs were retrieved and clustered into three different groups for efficient comparison.

Conclusions: We have developed an online system that efficiently identifies polymorphic STRs and provides novel distinguishable STR biomarkers for different levels of specificity. Candidate polymorphic STRs within a personal genome could be easily retrieved and compared to the constructed STR profile through query keywords, gene names, or assembled contigs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-15-S10-S3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304208PMC
July 2015

Cross-species identification of in microsatellite biomarkers for genetic disease.

Biomedicine (Taipei) 2014 2;4:14. Epub 2014 Aug 2.

Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung, Taiwan ; Department of Computer Science and Engineering & Center of Excellence for the Oceans, National Taiwan Ocean University, No. 2, Peining Road, Keelung, 20224 Taichung, Taiwan.

Microsatellites appear widely in genomes of diverse species. Variants of repeat number of microsatellites often correlate with risks of genetic disorder or severity of diseases. Using cross-species comparison, the proposed system comprehensively verifies microsatellites of specific genes related to 16 genetic disorders. Genomic information retrieved from 14 frequently used model organisms in biomedical study was thoroughly analyzed, emphasizing conserved and diverse traits. Features of microsatellite sequences among different organisms, including appearing frequency, position, pattern and distribution, could be determined automatically for stating genetically functional conservation and evolutionary correlation. This research found that among mammals and fishes, the microsatellite sequences are conserved in the genes of epidermal growth factor receptor, ataxia telangiectasia mutated and androgen receptor corresponding to cancers, ataxia telangiectasia and hepatocellular carcinoma, respectively. Still, except fruit fly conserved CAG repeats in Huntington and Spinocerebellar ataxia type 2 genes, no microsatellites were conserved in those genes linked to neurological/neurodegenerative disorders among mammal and fish species. In comparison of mammalian species, microsatellite biomarkers identified from 17 genetic disorder-related genes revealed high repeat conservation, especially in human, gorilla and macaque. Obviously, this comparative analysis illustrates microsatellite repeats affecting genetic disorders, highly correlated to evolutionary distance of species. Chief contribution of this research lies in assisting biologists to identify disease-related microsatellite biomarkers and employ appropriate model organisms for further biomedical studies relying on microsatellite conservation information. Database http://ssrtc.cs.ntou.edu.tw is for academic use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7603/s40681-014-0014-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265011PMC
August 2014

Identification of simple sequence repeat biomarkers through cross-species comparison in a tag cloud representation.

Biomed Res Int 2014 31;2014:678971. Epub 2014 Mar 31.

Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung 20224, Taiwan.

Simple sequence repeats (SSRs) are not only applied as genetic markers in evolutionary studies but they also play an important role in gene regulatory activities. Efficient identification of conserved and exclusive SSRs through cross-species comparison is helpful for understanding the evolutionary mechanisms and associations between specific gene groups and SSR motifs. In this paper, we developed an online cross-species comparative system and integrated it with a tag cloud visualization technique for identifying potential SSR biomarkers within fourteen frequently used model species. Ultraconserved or exclusive SSRs among cross-species orthologous genes could be effectively retrieved and displayed through a friendly interface design. Four different types of testing cases were applied to demonstrate and verify the retrieved SSR biomarker candidates. Through statistical analysis and enhanced tag cloud representation on defined functional related genes and cross-species clusters, the proposed system can correctly represent the patterns, loci, colors, and sizes of identified SSRs in accordance with gene functions, pattern qualities, and conserved characteristics among species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/678971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988901PMC
December 2014

An eye-tracking assistive device improves the quality of life for ALS patients and reduces the caregivers' burden.

J Mot Behav 2014 14;46(4):233-8. Epub 2014 Apr 14.

a School of Medicine , National Yang Ming University , Taipei , Taiwan.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. In some cases, patients with ALS retain a normal level of consciousness but disease progression eventually results in generalized paralysis, which first impedes and then prevents oral communication. This communication obstacle can generate a great deal of stress for the patient, family, and caregiver. Here the authors ask whether the use of an eye-tracking assistive device can improve quality of life for ALS patients and relieves burden of their primary caregivers. Subjects were divided into two groups depending on whether they used (n = 10) or did not use (n = 10) an eye-tracking assistive device. The authors assessed patients' quality of life and severity of depression using the ALS Specific Quality of Life Instrument-Revised and the Taiwanese Depression Questionnaire, respectively. The Caregiver Burden Scale was used to assess the burden on caregivers. Our study shows that the eye-tracking assistive device significantly improved patients' quality of life, as compared with patients in the nonuser group (p <.01). The assistive device also reduced the burden on caregivers (p <.05). This is likely a result of the improvement of patient's autonomy and more effective communication between patient and caregiver.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00222895.2014.891970DOI Listing
January 2015

Predicting protein-ligand interactions based on chemical preference features with its application to new D-amino acid oxidase inhibitor discovery.

Curr Pharm Des 2014 ;20(32):5202-11

State Key Laboratory of Microbial Metabolism and College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

In silico prediction of the new drug-target interactions from existing databases is of important value for the drug discovery process. Currently, the amount of protein targets that have been identified experimentally is still very small compared with the entire human proteins. In order to predict protein-ligand interactions in an accurate manner, we have developed a support vector machine (SVM) model based on the chemical-protein interactions from STITCH. New features from ligand chemical space and interaction networks have been selected and encoded as the feature vectors for SVM analysis. Both the 5-fold cross validation and independent test show high predictive accuracy that outperforms the state-of-the-art method based on ligand similarity. Moreover, 91 distinct pairs of features have been selected to rebuild a simplifier model, which still maintains the same performance as that based on all 332 features. Then, this refined model is used to search for the potential D-amino acid oxidase inhibitors from STITCH database and the predicted results are finally validated by our wet experiments. Out of 10 candidates obtained, seven D-amino acid oxidase inhibitors have been verified, in which four are newly found in the present study, and one may have a new application in therapy of psychiatric disorders other than being an antineoplastic agent. Clearly, our model is capable of predicting potential new drugs or targets on a large scale with high efficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612820666140306104823DOI Listing
March 2016

The C-terminal region of G72 increases D-amino acid oxidase activity.

Int J Mol Sci 2013 Dec 20;15(1):29-43. Epub 2013 Dec 20.

Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan.

The schizophrenia-related protein G72 plays a unique role in the regulation of D-amino acid oxidase (DAO) in great apes. Several psychiatric diseases, including schizophrenia and bipolar disorder, are linked to overexpression of DAO and G72. Whether G72 plays a positive or negative regulatory role in DAO activity, however, has been controversial. Exploring the molecular basis of the relationship between G72 and DAO is thus important to understand how G72 regulates DAO activity. We performed yeast two-hybrid experiments and determined enzymatic activity to identify potential sites in G72 involved in binding DAO. Our results demonstrate that residues 123-153 and 138-153 in the long isoform of G72 bind to DAO and enhance its activity by 22% and 32%, respectively. A docking exercise indicated that these G72 peptides can interact with loops in DAO that abut the entrance of the tunnel that substrate and cofactor must traverse to reach the active site. We propose that a unique gating mechanism underlies the ability of G72 to increase the activity of DAO. Because upregulation of DAO activity decreases d-serine levels, which may lead to psychiatric abnormalities, our results suggest a molecular mechanism involving interaction between DAO and the C-terminal region of G72 that can regulate N-methyl-d-aspartate receptor-mediated neurotransmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms15010029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907796PMC
December 2013

Basic amino acid residues of human eosinophil derived neurotoxin essential for glycosaminoglycan binding.

Int J Mol Sci 2013 Sep 16;14(9):19067-85. Epub 2013 Sep 16.

Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 300, Taiwan.

Human eosinophil derived neurotoxin (EDN), a granule protein secreted by activated eosinophils, is a biomarker for asthma in children. EDN belongs to the human RNase A superfamily possessing both ribonucleolytic and antiviral activities. EDN interacts with heparin oligosaccharides and heparin sulfate proteoglycans on bronchial epithelial Beas-2B cells. In this study, we demonstrate that the binding of EDN to cells requires cell surface glycosaminoglycans (GAGs), and the binding strength between EDN and GAGs depends on the sulfation levels of GAGs. Furthermore, in silico computer modeling and in vitro binding assays suggest critical roles for the following basic amino acids located within heparin binding regions (HBRs) of EDN 34QRRCKN39 (HBR1), 65NKTRKN70 (HBR2), and 113NRDQRRD119 (HBR3) and in particular Arg35, Arg36, and Arg38 within HBR1, and Arg114 and Arg117 within HBR3. Our data suggest that sulfated GAGs play a major role in EDN binding, which in turn may be related to the cellular effects of EDN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms140919067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794821PMC
September 2013

Inhibition of high-mobility group box 1 in lung reduced airway inflammation and remodeling in a mouse model of chronic asthma.

Biochem Pharmacol 2013 Oct 12;86(7):940-9. Epub 2013 Aug 12.

Department of Microbiology and Immunology, School of Medicine, China Medicine University, Taichung, Taiwan; Graduate Institute of Immunology, College of Medicine, China Medicine University, Taichung, Taiwan; Graduate Institute of Basic Medical Science, College of Medicine, China Medicine University, Taichung, Taiwan. Electronic address:

The role of high-mobility group box 1 (HMGB1) in chronic allergic asthma is currently unclear. Both airway neutrophilia and eosinophilia and increase in HMGB1 expression in the lungs in our murine model of chronic asthma. Inhibition of HMGB1 expression in lung in ovalbumin (OVA)-immunized mice decreased induced airway inflammation, mucus formation, and collagen deposition in lung tissues. Analysis of the numbers of CD4(+) T helper (Th) cells in the mediastinal lymph nodes and lungs revealed that Th17 showed greater increases than Th2 cells and Th1 cells in OVA-immunized mice; further, the numbers of Th1, Th2, and Th17 cells decreased in anti-HMGB1 antibody (Ab)-treated mice. In OVA-immunized mice, TLR-2 and TLR-4 expression, but not RAGE expression, was activated in the lungs and attenuated after anti-HMGB1 Ab treatment. The results showed that increase in HMGB1 release and expression in the lungs could be an important pathological mechanism underlying chronic allergic asthma and HMGB1 might a potential therapeutic target for chronic allergic asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcp.2013.08.003DOI Listing
October 2013

Elevated serum autoantibody against high mobility group box 1 as a potent surrogate biomarker for amyotrophic lateral sclerosis.

Neurobiol Dis 2013 Oct 29;58:13-8. Epub 2013 Apr 29.

Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.

Amyotrophic lateral sclerosis (ALS) is a complicate and progressive onset devastating neurodegenerative disease. Its pathogenic mechanisms remain unclear and there is no specific test for diagnosis. For years, researchers have been vigorously searching for biomarkers associated with ALS to assist clinical diagnosis and monitor disease progression. Some specific inflammatory processes in the central nervous system have been reported to participate in the pathogenesis of ALS. As high mobility group box 1 (HMGB1) is elevated in spinal cord tissues of patients with ALS, we hypothesized, therefore, that serum autoantibody against HMGB1 (HMGB1 autoAb) might represent an effective biomarker for ALS. Patients with ALS, Alzheimer's disease, Parkinson's disease, and healthy age-matched control subjects were recruited for this study. ALS group consisted of 61 subjects, the other groups each consisted of forty subjects. We generated a polyclonal antibody against HMGB1 and developed an ELISA-based methodology for screening serum samples of these subjects. All samples were coded for masked comparison. For statistic analyses, two-tailed Student's t-test, ANOVA, Bonferroni multiple comparison test, Spearman correlation, and receiver operating characteristic curve were applied. We discovered that the level of HMGB1 autoAb significantly increased in patients with ALS as compared with that of patients with Alzheimer's disease, Parkinson's disease, and healthy control subjects. The differences between all groups were robust even at the early stages of ALS progression. More importantly, higher HMGB1 autoAb level was found in more severe disease status with significant correlation. Our study demonstrates that serum HMGB1 autoAb may serve as a biomarker for the diagnosis of ALS and can be used to monitor disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nbd.2013.04.013DOI Listing
October 2013

Eosinophil-derived neurotoxin is elevated in patients with amyotrophic lateral sclerosis.

Mediators Inflamm 2013 20;2013:421389. Epub 2013 Feb 20.

Graduate Institute of Molecular Systems Biomedicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.

Background And Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons in the brainstem, motor cortex, and spinal cord. Oxidative stress and neuroinflammation have been implicated in the pathophysiology of ALS. Members of the family of damage-associated molecular patterns, including reactive oxygen species, high-mobility group box 1, and eosinophil-derived neurotoxin (EDN), may participate in pathological conditions. In this study, we aim to discover new biomarker for detecting ALS.

Materials And Methods: We examined 44 patients with ALS, 41 patients with Alzheimer's disease, 41 patients with Parkinson's disease, and 44 healthy controls. The concentration of serum EDN was measured using an enzyme-linked immunosorbent assay.

Results: EDN levels were significantly increased 2.17-fold in the serum of patients with ALS as compared with healthy controls (P < 0.05). No correlation between the levels of serum EDN and various clinical parameters of ALS was found. Moreover, the levels of serum EDN in patients with Parkinson's disease and Alzheimer's disease and healthy controls were similar.

Conclusion: A higher level of serum EDN was found specifically in patients with ALS, indicating that EDN may participate in the pathophysiology of ALS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2013/421389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590756PMC
August 2013

Protein-ligand binding region prediction (PLB-SAVE) based on geometric features and CUDA acceleration.

BMC Bioinformatics 2013 8;14 Suppl 4:S4. Epub 2013 Mar 8.

Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung, Taiwan, ROC.

Background: Protein-ligand interactions are key processes in triggering and controlling biological functions within cells. Prediction of protein binding regions on the protein surface assists in understanding the mechanisms and principles of molecular recognition. In silico geometrical shape analysis plays a primary step in analyzing the spatial characteristics of protein binding regions and facilitates applications of bioinformatics in drug discovery and design. Here, we describe the novel software, PLB-SAVE, which uses parallel processing technology and is ideally suited to extract the geometrical construct of solid angles from surface atoms. Representative clusters and corresponding anchors were identified from all surface elements and were assigned according to the ranking of their solid angles. In addition, cavity depth indicators were obtained by proportional transformation of solid angles and cavity volumes were calculated by scanning multiple directional vectors within each selected cavity. Both depth and volume characteristics were combined with various weighting coefficients to rank predicted potential binding regions.

Results: Two test datasets from LigASite, each containing 388 bound and unbound structures, were used to predict binding regions using PLB-SAVE and two well-known prediction systems, SiteHound and MetaPocket2.0 (MPK2). PLB-SAVE outperformed the other programs with accuracy rates of 94.3% for unbound proteins and 95.5% for bound proteins via a tenfold cross-validation process. Additionally, because the parallel processing architecture was designed to enhance the computational efficiency, we obtained an average of 160-fold increase in computational time.

Conclusions: In silico binding region prediction is considered the initial stage in structure-based drug design. To improve the efficacy of biological experiments for drug development, we developed PLB-SAVE, which uses only geometrical features of proteins and achieves a good overall performance for protein-ligand binding region prediction. Based on the same approach and rationale, this method can also be applied to predict carbohydrate-antibody interactions for further design and development of carbohydrate-based vaccines. PLB-SAVE is available at http://save.cs.ntou.edu.tw.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2105-14-S4-S4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599089PMC
July 2013

Prediction of conformational epitopes with the use of a knowledge-based energy function and geometrically related neighboring residue characteristics.

BMC Bioinformatics 2013 8;14 Suppl 4:S3. Epub 2013 Mar 8.

Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung, Taiwan, ROC.

Background: A conformational epitope (CE) in an antigentic protein is composed of amino acid residues that are spatially near each other on the antigen's surface but are separated in sequence; CEs bind their complementary paratopes in B-cell receptors and/or antibodies. CE predication is used during vaccine design and in immuno-biological experiments. Here, we develop a novel system, CE-KEG, which predicts CEs based on knowledge-based energy and geometrical neighboring residue contents. The workflow applied grid-based mathematical morphological algorithms to efficiently detect the surface atoms of the antigens. After extracting surface residues, we ranked CE candidate residues first according to their local average energy distributions. Then, the frequencies at which geometrically related neighboring residue combinations in the potential CEs occurred were incorporated into our workflow, and the weighted combinations of the average energies and neighboring residue frequencies were used to assess the sensitivity, accuracy, and efficiency of our prediction workflow.

Results: We prepared a database containing 247 antigen structures and a second database containing the 163 non-redundant antigen structures in the first database to test our workflow. Our predictive workflow performed better than did algorithms found in the literature in terms of accuracy and efficiency. For the non-redundant dataset tested, our workflow achieved an average of 47.8% sensitivity, 84.3% specificity, and 80.7% accuracy according to a 10-fold cross-validation mechanism, and the performance was evaluated under providing top three predicted CE candidates for each antigen.

Conclusions: Our method combines an energy profile for surface residues with the frequency that each geometrically related amino acid residue pair occurs to identify possible CEs in antigens. This combination of these features facilitates improved identification for immuno-biological studies and synthetic vaccine design. CE-KEG is available at http://cekeg.cs.ntou.edu.tw.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2105-14-S4-S3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599093PMC
July 2013