Tyan Yu-Chang - Academia.edu (original) (raw)

Papers by Tyan Yu-Chang

PLOS ONE, 2016

Recent phylodynamic studies have focused on using tree topology patterns to elucidate interaction... more Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis. Analyses of the 915-nucleotide VP1 and 690-nt 3Dpol regions of 21 strains isolated in Taiwan and worldwide during 1985-2010 revealed a clear chronological trend in both the VP1 and 3Dpol phylogenetic trees: the emergence of a single dominant cluster in each outbreak. The VP1 sequences included three genotypes: GI (prototype), GIII (isolated 1985-1999), and GIV (isolated after 2000); no VP1 sequences from GII strains have been deposited in GenBank. Another five genotypes identified in the 3Dpol region had support values >0.9. Geographic and demographic transitions among CV-A24v clusters were clearly identified by Bayes algorithm. The transmission route was mapped from India to China and then to Taiwan, and each prevalent viral population declined before new clusters emerged. Notably, the VP1 and 3Dpol genes had high nucleotide sequence similarities (94.1% and 95.2%, respectively). The lack of co-circulating lineages and narrow tissue tropism affected the CV-A24v gene pool.

BioMed Research International, 2015

Hepatitis C virus (HCV) infection can cause permanent liver damage and hepatocellular carcinoma, ... more Hepatitis C virus (HCV) infection can cause permanent liver damage and hepatocellular carcinoma, and deaths related to HCV deaths have recently increased. Chronic HCV infection is often undiagnosed such that the virus remains infective and transmissible. Identifying HCV infection early is essential for limiting its spread, but distinguishing individuals who require further HCV tests is very challenging. Besides identifying high-risk populations, an optimal subset of indices for routine examination is needed to identify HCV screening candidates. Therefore, this study analyzed data from 312 randomly chosen blood donors, including 144 anti-HCV-positive donors and 168 anti-HCV-negative donors. The HCV viral load in each sample was measured by real-time polymerase chain reaction method. Receiver operating characteristic curves were used to find the optimal cell blood counts and thrombopoietin measurements for screening purposes. Correlations with values for key indices and viral load were also determined. Strong predictors of HCV infection were found by using receiver operating characteristics curves to analyze the optimal subsets among red blood cells, monocytes, platelet counts, platelet large cell ratios, and mean corpuscular hemoglobin concentrations. Sensitivity, specificity, and area under the receiver operator characteristic curve (P < 0.0001) were 75.6%, 78.5%, and 0.859, respectively.

BMC bioinformatics, Jan 21, 2015

Studies regarding coxsackievirus (CV) tend to focus on epidemic outbreaks, an imbalanced topology... more Studies regarding coxsackievirus (CV) tend to focus on epidemic outbreaks, an imbalanced topology is considered to be an indication of acute infection with partial cross-immunity. In enteroviruses, a clear understanding of the characteristics of tree topology, transmission, and its demographic dynamics in viral succession and circulation are essential for identifying prevalence trends in endemic pathogens such as coxsackievirus B2 (CV-B2). This study applied a novel Bayesian evolutionary approach to elucidate the phylodynamic characteristics of CV-B2. A dataset containing 51 VP1 sequences and a dataset containing 34 partial 3D(pol) sequencing were analyzed, where each dataset included Taiwan sequences isolated during 1988-2013. Four and five genotypes were determined based on the 846-nucleotide VP1 and 441-nucleotide 3D(pol) (6641-7087) regions, respectively, with spatiotemporally structured topologies in both trees. Some strains with tree discordance indicated the occurrence of rec...

BMC Veterinary Research, 2015

Canine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite th... more Canine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite the widespread use of vaccines, the prevalence of the CD virus (CDV) has increased at an alarming rate in recent years. In this phylodynamic study, we investigated the spatiotemporal modes of dispersal, viral demographic trends, and effectiveness of vaccines for CDV. A total of 188 full-length CDV hemagglutinin (H) gene sequences dataset were subjected to recombination analysis, including seven from modified live vaccine (MLV) strains and 12 from Taiwan specimens. After excluding the MLV strains and potential recombinant strains, alignments of 176 of 188 previous CDV strains were further used to analyze phylodynamic characteristics, and evidence of selection, and co-evolution. The CDV genotype consisted of MLV-associated genotypes such as America-1 and Rockborn-like strains, which were characterized by long terminal branches and no distinct geographical patterns among lineages. In contrast, wild-type isolates clustered into lineages with a spatiotemporal structure and short terminal branches. Co-circulation and extensive diversification were simultaneously observed. The sequence variation signature was shaped by both geographic diversity and host tropism. Codon 506 was identified as a multi-epistatic interacting in the H protein. The topological signature revealed in this study suggests different epidemic scenarios. For example, a ladder-like backbone is a hallmark of directional selection, and cladogenesis at long terminal branches indicates the emergence of a surviving lineage. The stable effective viral population of CDV indicate the effectiveness of vaccines currently used to control the virus.

PLOS ONE, 2015

The infectious activity of coxsackievirus B1 (CV-B1) in Taiwan was high from 2008 to 2010, follow... more The infectious activity of coxsackievirus B1 (CV-B1) in Taiwan was high from 2008 to 2010, following an alarming increase in severe neonate disease in the United States (US). To examine the relationship between CV-B1 strains isolated in Taiwan and those from other parts of the world, we performed a phylodynamic study using VP1 and partial 3Dpol (414 nt) sequences from 22 strains of CV-B1 isolated in Taiwan (1989-2010) and compared them to sequences from strains isolated worldwide. Phylogenetic trees were constructed by neighbor-joining, maximum likelihood, and Bayesian Monte Carlo Markov Chain methods. Four genotypes (GI-IV) in the VP1 region of CV-B1 and three genotypes (GA-C) in the 3Dpol region of enterovirus B were identified and had high support values. The phylogenetic analysis indicates that the GI and GIII strains in VP1 were geographically distributed in Taiwan (1993-1994) and in India (2007-2009). On the other hand, the GII and GIV strains appear to have a wider spatiotemporal distribution and ladder-like topology A stair-like phylogeny was observed in the VP1 region indicating that the phylogeny of the virus may be affected by different selection pressures in the specified regions. Further, most of the GI and GII strains in the VP1 tree were clustered together in GA in the 3D tree, while the GIV strains diverged into GB and GC. Taken together, these data provide important insights into the population dynamics of CV-B1 and indicate that incongruencies in specific gene regions may contribute to spatiotemporal patterns of epidemicity for this virus.

Biomarkers and Genomic Medicine, 2013

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. The purpose of this stud... more Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. The purpose of this study is to characterize proteins secreted from the HepG2 cells, which may relate to cell differentiation and tumor metastasis. In the proteomic analysis, the secretome was identified by nano-higheperformance liquid chromatography/electrospray ionization tandem mass spectrometry (nano-HPLC/ESIMS/MS) followed by peptide fragmentation pattern analysis. In this study, three proteins, p130Cas-associated protein (p130Cas/BCAR1), TAR DNA-binding protein 43 (TDP43/TARDBP) and translationally controlled tumor protein (TCTP/ TPT1), were identified and confirmed by Western blotting, which showed significantly Biomarkers and Genomic Medicine (2013) 5, 96e99 differential expression compared with the normal liver cells. Analyzing differential protein expressions in HepG2 cell by proteomic approaches suggests that p130Cas/BCAR1, TDP43/ TARDBP and TCTP/TPT1 as key proteins and may serve as biomarkers for HCC.

Biomarkers and Genomic Medicine, 2013

Alzheimer's disease (AD) is the most common cause of dementia in late life. The objective of util... more Alzheimer's disease (AD) is the most common cause of dementia in late life. The objective of utilizing proteomic techniques in this study was to identify protein biomarkers associated with NAP (NAPVSIPQ, amino acid sequence from 354 to 361) treated with human neuroblastoma cells SH-SY5Y. Experimental results suggested that stathmin was a protein marker for NAP-induced neuroprotective activity in neuroblastoma cells. Thus, the use of NAP is suggested as a treatment to provide additional protection in patients with AD.

RSC Adv., 2014

Technetium-99 ( 99 Tc) is a key nuclide, produced by the fission of uranium-235 ( 235 U) and plut... more Technetium-99 ( 99 Tc) is a key nuclide, produced by the fission of uranium-235 ( 235 U) and plutonium-239 ( 239 Pu), through a cascade decay process, and is one kind of target element in environmental analysis due to its long half-life (t 1/2 ¼ 2.1 Â 10 5 years). This study developed a 99 Tc analytical technique using automatic solid phase extraction (SPE) with TEVA resin and inductively coupled plasma mass spectrometry (ICP-MS). The chemical recovery of 99 Tc was 94.15 AE 3.14% and the minimum detectable activity (MDA) for cement solidified samples spiked with 99 Tc was 1.5 mBq g À1 (2.4 pg mL À1 ). In this study, standard reference material (SRM), an environmental sample was measured by this analytical method. The proposed method is more convenient than traditional radiochemical methods in terms of reducing the time required for analysis, the consumption of reagents, and radiation exposure of operators.

BioMed research international, 2014

It is becoming increasingly evident that certain phytochemicals possess cancer chemopreventive pr... more It is becoming increasingly evident that certain phytochemicals possess cancer chemopreventive properties. In this study, the antiproliferative activity of extracts from different parts of the jaboticaba (Myrciaria cauliflora) plant was evaluated for its effect on human oral carcinoma cell lines. The cytotoxicities of various plant extract concentrations were examined and the 50% maximal inhibitory concentration (IC50) was determined. Water extracts of jaboticaba seeds showed concentration-dependent antiproliferative effects. Annexin V/propidium iodide positivity with active caspase-3 induction indicated that the treated cells underwent apoptosis. Several important regulatory proteins (Bcl-2, Bcl-xL, Bid, and survivin) involved in apoptosis were also evaluated. The antioxidant activity of jaboticaba was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, and the drug concentration eliciting 50% maximum...

BioMed research international, 2014

Chitosan nanoparticle, a biocompatible material, was used as a potential drug delivery system wid... more Chitosan nanoparticle, a biocompatible material, was used as a potential drug delivery system widely. Our current investigation studies were the bioeffects of the chitosan nanoparticle uptake by liver cells. In this experiment, the characterizations of chitosan nanoparticles were measured by transmission electron microscopy and particle size analyzer. The average size of the chitosan nanoparticle was 224.6 ± 11.2 nm, and the average zeta potential was +14.08 ± 0.7 mV. Moreover, using proteomic approaches to analyze the differential protein expression patterns resulted from the chitosan nanoparticle uptaken by HepG2 and CCL-13 cells identified several proteins involved in the PI3K/AKT1/mTOR pathway. Our experimental results have demonstrated that the chitosan nanoparticle may involve in the liver cancer cell metastasis and proliferation.

Rapid communications in mass spectrometry : RCM, 2009

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is used ... more Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is used to rapidly characterize the human neutrophil peptides - HNP 1, 2, and 3 - in saliva. The saliva excreted from the parotid and sublingual/submandibular glands of 70 individuals were collected and examined using MALDI-TOF. The MALDI approach requires no sample pretreatment other than mixing the saliva-absorbing material with the matrix and drying under ambient conditions. Tissue paper was the best material for collecting the saliva samples because of its strong texture and high absorbance, and sinapinic acid was the best MALDI matrix for the analysis of the HNPs. HNPs were detected in almost all the samples collected from the parotid glands, with no obvious differences among age or gender. In contrast, the distribution of the HNPs in the samples collected from the sublingual/submandibular glands was age-dependent: no HNPs were detected for those collected from individuals younger than 30, ...

Journal of materials science. Materials in medicine, 2003

Antenna coupling microwave plasma enables a highly efficient and oxidative treatment of the outer... more Antenna coupling microwave plasma enables a highly efficient and oxidative treatment of the outermost surface of polypropylene (PP) non-woven fabric within a short time period. Subsequently, grafting copolymerization with acrylic acid (AAc) makes the plasma-treated fabric durably hydrophilic and excellent in water absorbency. With high grafting density and strong water affinity, the pAAc-grafted fabric greatly becomes feasible as an intensive absorbent and as a support to promote chitosan-immobilization through amide bonds. Experimental result demonstrated that surface analyses by FTIR-ATR have shown that R-CONH-R', amide binding were emerged between pAAc and chitosan. The XPS measurements on C(1s) 286.0 eV (C-OH), 286.5 eV (C-N) and 288.1 eV (O=C-NH) also could be found. Bioactivity assessments on the chitosan-immobilized surfaces were anticipated by activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen concentration. By means of cell counter we count...

BioMed Research International, 2014

The purpose of this study was to develop the pathway of silk fibroin (SF) biopolymer surface indu... more The purpose of this study was to develop the pathway of silk fibroin (SF) biopolymer surface induced cell membrane protein activation. Fibroblasts were used as an experimental model to evaluate the responses of cellular proteins induced by biopolymer material using a mass spectrometry-based profiling system. The surface was covered by multiwalled carbon nanotubes (CNTs) and SF to increase the surface area, enhance the adhesion of biopolymer, and promote the rate of cell proliferation. The amount of adhered fibroblasts on CNTs/SF electrodes of quartz crystal microbalance (QCM) greatly exceeded those on other surfaces. Moreover, analyzing differential protein expressions of adhered fibroblasts on the biopolymer surface by proteomic approaches indicated that CD44 may be a key protein. Through this study, utilization of mass spectrometry-based proteomics in evaluation of cell adhesion on biopolymer was proposed.

2007 7th IEEE Conference on Nanotechnology (IEEE NANO), 2007

The study presents the mass spectrometric application of carbon nanomaterials in proteomic resear... more The study presents the mass spectrometric application of carbon nanomaterials in proteomic research. We utilized two spherical carbon nanomaterials, C60 buckyball and iron-cored carbonball (Fe-C), in peptide sequence identification of a serum protein using matrix-assisted laser desorption ionization-time of flight mass spectrometer (MALDI-TOF-MS). The biological samples used in the experiments were enzymatically trypsinized bovine serum albumins (BSA) peptides instead of

Journal of Neuroradiology, 2013

Behçet's disease; Behçet's syndrome; Neuro-Behçet's syndrome; Brain SPECT scan; 99m Tc-HMPAO Summ... more Behçet's disease; Behçet's syndrome; Neuro-Behçet's syndrome; Brain SPECT scan; 99m Tc-HMPAO Summary The aim of this study was to detect brain functional deficits in patients with Behçet's disease (BD) and signs or symptoms of central nervous system (CNS) involvement at different times in their clinical history. A total of 24 patients aged 20 to 53 years (median age 39 years; 20 women, four men) with Behçet's syndrome fulfilling the diagnosis as defined by the syndrome classification were enrolled in this study. Single-photon emission computed tomography (SPECT) with 99m Technetium (Tc)-hexamethylpropyleneamine oxime (HMPAO) as the perfusion tracer was performed to detect brain lesions. The results of 99m Tc-HMPAO brain SPECT scans showed impaired perfusion in all cases with neurological complaints (24 out of 24, 100%). Temporal lobes and basal ganglia were the most common areas with such lesions. In contrast, brain MRI and CT images were normal or non-specific in all cases. In conclusion, 99m Tc-HMPAO brain SPECT imaging is a powerful and sensitive tool for disclosing brain involvement in numerous clinical situations, even including patients with subtle neurological symptoms/signs such as headaches and dizziness. It is also a useful modality for evaluating the effects of treatment and disease monitoring to prevent CNS damage.

BioMed Research International, 2013

Peritoneal dialysis (PD) is an increasingly accepted modality of renal replacement therapy. It pr... more Peritoneal dialysis (PD) is an increasingly accepted modality of renal replacement therapy. It provides the advantages of having a flexible lifestyle, stable hemodynamics, and better preservation of residual renal function. To enhance our understanding of the peritoneal dialysate of diabetes mellitus (DM), peritoneal dialysate proteins were identified by two-dimensional gel electrophoresis (2DE) combined with reverse-phase nano-ultra performance liquid chromatography electrospray ionization tandem mass spectrometry (RP-nano-UPLC-ESI-MS/MS) followed by peptide fragmentation patterning. To validate the differential proteins, ELISA and Western blotting analyses were applied to detect candidate proteins that may be related to DM. We performed 2DE on the peritoneal dialysate samples, with detection of more than 300 spots. From this, 13 spots were excised, in-gel digested, and identified by RP-nano-UPLC-ESI-MS/MS. Ten of these showed significant differential expression between the DM and chronic glomerulonephritis (CGN) peritoneal dialysate samples. In this study, we conducted a comparative proteomic study on these two groups of dialysate that may provide evidence for understanding the different peritoneal protein changes. These proteins may not be new biomarkers; however, they may indicate a situation for possible drug treatment and can be the predictors of peritonitis for a validation study in the future.

International Journal of Pharmaceutics, 2009

This study investigates in vitro the drug delivery characteristics of new thermo-sensitive gels, ... more This study investigates in vitro the drug delivery characteristics of new thermo-sensitive gels, P-CS/GA gels, in which a chitosan (CS) network is crosslinked with various concentrations of glutaraldehyde (GA) that interpenetrates Poloxamer (P) gels. The results indicate that the swelling ratios of all P-CS/GA gels are markedly superior to those of non-swelling P and P-CS gels. For example, P-CS/GA (0.1 wt.%) gels have swelling ratios of 13.2 ± 1.0, which are maintained for approximately 18 h in water at 37 • C. In vitro releases of 5-FU from P-CS/GA (0.1 wt.%) gels had significantly lower initial burst release (P < 0.01) and lasted much longer than those from gels without a CS network. For example, the duration of release of 5-FU was in a significantly sustained manner for up to 52 h, which was about 10 times or longer than the period of delivery using P or P-CS gels. The release of drugs from gels with an interpenetrating CS network could be modeled by Fickian diffusion; the characteristic constant 'k' of drug-gel systems decreased as increasing GA concentrations in the P-CS/GA gels, and increasing the viscosities of the P, P-CS and P-CS/GA solutions.

Journal of Thoracic Oncology, 2015

Differential expression and secretion of alpha-actinin 4 (ACTN4) in the lung cancer cell lines CL... more Differential expression and secretion of alpha-actinin 4 (ACTN4) in the lung cancer cell lines CL1-0 and CL1-5 have been reported in previous proteomic studies. The aim of this study is to investigate the functional properties of the ACTN4 protein in non-small-cell lung cancer (NSCLC) cells and evaluate its clinical importance. We used RNA interference to knock down and overexpress ACTN4 protein to evaluate the effects of this intervention on cancer cell invasion and migration, as well as on microscopic cellular morphology. Furthermore, we examined by immunohistochemistry the expression of ACTN4 protein in tissue samples at different stages of lung cancer and compared the protein levels of ACTN4 in blood plasma samples from patients with histologically confirmed lung cancer and healthy controls. CL1-5 cell motility was significantly suppressed by the knockdown of ACTN4 protein. The morphology of CL1-5 cells changed from a predominantly mesenchymal-like shape into a globular shape in response to ACTN4 protein knockdown. A quantitative immunohistochemical assessment of lung cancer tissues revealed that ACTN4 protein level was considerably higher in cancerous tissues than in the adjacent normal ones, and the area under the receiver operating characteristic curve was 0.736 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). According to an enzyme-linked immunosorbent assay, the plasma levels of ACTN4 protein were significantly different between cancer patients and healthy controls, and the areas under the receiver operating characteristic curves were 0.828 and 0.909, respectively, for two independent cohorts (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). We demonstrate that the knockdown of ACTN4 protein inhibited cell invasion and migration. These results suggest that ACTN4 is associated with lung cancer cell motility. Thus, the level of ACTN4 in cancerous tissue and plasma is related to the presence of lung cancer.

PLoS ONE, 2014

Due to the limited information of the contribution of various antibiotic resistance mechanisms in... more Due to the limited information of the contribution of various antibiotic resistance mechanisms in clinical Burkholderia cepacia complex isolates, Antibiotic resistance mechanisms, including integron analysis, identification of quinolone resistance-determining region mutations, measurement of efflux pump activity, and sequence analysis of efflux pump regulators, were investigated in 66 clinical B. cepacia complex isolates. Species were identified via recA-RFLP and MALDI-TOF. Four genomovars were identified by recA-RFLP. B. cenocepacia (genomovar III) was the most prevalent genomovar (90.1%). Most isolates (60/66, 90.9%) were correctly identified by MALDI-TOF analysis. Clonal relatedness determined by PFGE analysis revealed 30 pulsotypes, including two major pulsotypes that comprised 22.7% and 18.2% of the isolates, respectively. Seventeen (25.8%) isolates harboured class 1 integron with various combinations of resistance genes. Among six levofloxacin-resistant isolates, five had single-base substitutions in the gyrA gene and three demonstrated efflux pump activities. Among the 42 isolates exhibiting resistance to at least one antimicrobial agent, 94.4% ceftazidime-resistant isolates (17/18) and 72.7% chloramphenicol-resistant isolates (16/22) demonstrated efflux pump activity. Quantitation of efflux pump RNA level and sequence analysis revealed that over-expression of the RND-3 efflux pump was attributable to specific mutations in the RND-3 efflux pump regulator gene. In conclusion, high-level expression of efflux pumps is prevalent in B. cepacia complex isolates. Mutations in the RND-3 efflux pump regulator gene are the major cause of efflux pump activity, resulting in the resistance to antibiotics in clinical B. cepacia complex isolates.

PLOS ONE, 2016

Recent phylodynamic studies have focused on using tree topology patterns to elucidate interaction... more Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis. Analyses of the 915-nucleotide VP1 and 690-nt 3Dpol regions of 21 strains isolated in Taiwan and worldwide during 1985-2010 revealed a clear chronological trend in both the VP1 and 3Dpol phylogenetic trees: the emergence of a single dominant cluster in each outbreak. The VP1 sequences included three genotypes: GI (prototype), GIII (isolated 1985-1999), and GIV (isolated after 2000); no VP1 sequences from GII strains have been deposited in GenBank. Another five genotypes identified in the 3Dpol region had support values &gt;0.9. Geographic and demographic transitions among CV-A24v clusters were clearly identified by Bayes algorithm. The transmission route was mapped from India to China and then to Taiwan, and each prevalent viral population declined before new clusters emerged. Notably, the VP1 and 3Dpol genes had high nucleotide sequence similarities (94.1% and 95.2%, respectively). The lack of co-circulating lineages and narrow tissue tropism affected the CV-A24v gene pool.

BioMed Research International, 2015

Hepatitis C virus (HCV) infection can cause permanent liver damage and hepatocellular carcinoma, ... more Hepatitis C virus (HCV) infection can cause permanent liver damage and hepatocellular carcinoma, and deaths related to HCV deaths have recently increased. Chronic HCV infection is often undiagnosed such that the virus remains infective and transmissible. Identifying HCV infection early is essential for limiting its spread, but distinguishing individuals who require further HCV tests is very challenging. Besides identifying high-risk populations, an optimal subset of indices for routine examination is needed to identify HCV screening candidates. Therefore, this study analyzed data from 312 randomly chosen blood donors, including 144 anti-HCV-positive donors and 168 anti-HCV-negative donors. The HCV viral load in each sample was measured by real-time polymerase chain reaction method. Receiver operating characteristic curves were used to find the optimal cell blood counts and thrombopoietin measurements for screening purposes. Correlations with values for key indices and viral load were also determined. Strong predictors of HCV infection were found by using receiver operating characteristics curves to analyze the optimal subsets among red blood cells, monocytes, platelet counts, platelet large cell ratios, and mean corpuscular hemoglobin concentrations. Sensitivity, specificity, and area under the receiver operator characteristic curve (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) were 75.6%, 78.5%, and 0.859, respectively.

BMC bioinformatics, Jan 21, 2015

Studies regarding coxsackievirus (CV) tend to focus on epidemic outbreaks, an imbalanced topology... more Studies regarding coxsackievirus (CV) tend to focus on epidemic outbreaks, an imbalanced topology is considered to be an indication of acute infection with partial cross-immunity. In enteroviruses, a clear understanding of the characteristics of tree topology, transmission, and its demographic dynamics in viral succession and circulation are essential for identifying prevalence trends in endemic pathogens such as coxsackievirus B2 (CV-B2). This study applied a novel Bayesian evolutionary approach to elucidate the phylodynamic characteristics of CV-B2. A dataset containing 51 VP1 sequences and a dataset containing 34 partial 3D(pol) sequencing were analyzed, where each dataset included Taiwan sequences isolated during 1988-2013. Four and five genotypes were determined based on the 846-nucleotide VP1 and 441-nucleotide 3D(pol) (6641-7087) regions, respectively, with spatiotemporally structured topologies in both trees. Some strains with tree discordance indicated the occurrence of rec...

BMC Veterinary Research, 2015

Canine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite th... more Canine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite the widespread use of vaccines, the prevalence of the CD virus (CDV) has increased at an alarming rate in recent years. In this phylodynamic study, we investigated the spatiotemporal modes of dispersal, viral demographic trends, and effectiveness of vaccines for CDV. A total of 188 full-length CDV hemagglutinin (H) gene sequences dataset were subjected to recombination analysis, including seven from modified live vaccine (MLV) strains and 12 from Taiwan specimens. After excluding the MLV strains and potential recombinant strains, alignments of 176 of 188 previous CDV strains were further used to analyze phylodynamic characteristics, and evidence of selection, and co-evolution. The CDV genotype consisted of MLV-associated genotypes such as America-1 and Rockborn-like strains, which were characterized by long terminal branches and no distinct geographical patterns among lineages. In contrast, wild-type isolates clustered into lineages with a spatiotemporal structure and short terminal branches. Co-circulation and extensive diversification were simultaneously observed. The sequence variation signature was shaped by both geographic diversity and host tropism. Codon 506 was identified as a multi-epistatic interacting in the H protein. The topological signature revealed in this study suggests different epidemic scenarios. For example, a ladder-like backbone is a hallmark of directional selection, and cladogenesis at long terminal branches indicates the emergence of a surviving lineage. The stable effective viral population of CDV indicate the effectiveness of vaccines currently used to control the virus.

PLOS ONE, 2015

The infectious activity of coxsackievirus B1 (CV-B1) in Taiwan was high from 2008 to 2010, follow... more The infectious activity of coxsackievirus B1 (CV-B1) in Taiwan was high from 2008 to 2010, following an alarming increase in severe neonate disease in the United States (US). To examine the relationship between CV-B1 strains isolated in Taiwan and those from other parts of the world, we performed a phylodynamic study using VP1 and partial 3Dpol (414 nt) sequences from 22 strains of CV-B1 isolated in Taiwan (1989-2010) and compared them to sequences from strains isolated worldwide. Phylogenetic trees were constructed by neighbor-joining, maximum likelihood, and Bayesian Monte Carlo Markov Chain methods. Four genotypes (GI-IV) in the VP1 region of CV-B1 and three genotypes (GA-C) in the 3Dpol region of enterovirus B were identified and had high support values. The phylogenetic analysis indicates that the GI and GIII strains in VP1 were geographically distributed in Taiwan (1993-1994) and in India (2007-2009). On the other hand, the GII and GIV strains appear to have a wider spatiotemporal distribution and ladder-like topology A stair-like phylogeny was observed in the VP1 region indicating that the phylogeny of the virus may be affected by different selection pressures in the specified regions. Further, most of the GI and GII strains in the VP1 tree were clustered together in GA in the 3D tree, while the GIV strains diverged into GB and GC. Taken together, these data provide important insights into the population dynamics of CV-B1 and indicate that incongruencies in specific gene regions may contribute to spatiotemporal patterns of epidemicity for this virus.

Biomarkers and Genomic Medicine, 2013

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. The purpose of this stud... more Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. The purpose of this study is to characterize proteins secreted from the HepG2 cells, which may relate to cell differentiation and tumor metastasis. In the proteomic analysis, the secretome was identified by nano-higheperformance liquid chromatography/electrospray ionization tandem mass spectrometry (nano-HPLC/ESIMS/MS) followed by peptide fragmentation pattern analysis. In this study, three proteins, p130Cas-associated protein (p130Cas/BCAR1), TAR DNA-binding protein 43 (TDP43/TARDBP) and translationally controlled tumor protein (TCTP/ TPT1), were identified and confirmed by Western blotting, which showed significantly Biomarkers and Genomic Medicine (2013) 5, 96e99 differential expression compared with the normal liver cells. Analyzing differential protein expressions in HepG2 cell by proteomic approaches suggests that p130Cas/BCAR1, TDP43/ TARDBP and TCTP/TPT1 as key proteins and may serve as biomarkers for HCC.

Biomarkers and Genomic Medicine, 2013

Alzheimer's disease (AD) is the most common cause of dementia in late life. The objective of util... more Alzheimer's disease (AD) is the most common cause of dementia in late life. The objective of utilizing proteomic techniques in this study was to identify protein biomarkers associated with NAP (NAPVSIPQ, amino acid sequence from 354 to 361) treated with human neuroblastoma cells SH-SY5Y. Experimental results suggested that stathmin was a protein marker for NAP-induced neuroprotective activity in neuroblastoma cells. Thus, the use of NAP is suggested as a treatment to provide additional protection in patients with AD.

RSC Adv., 2014

Technetium-99 ( 99 Tc) is a key nuclide, produced by the fission of uranium-235 ( 235 U) and plut... more Technetium-99 ( 99 Tc) is a key nuclide, produced by the fission of uranium-235 ( 235 U) and plutonium-239 ( 239 Pu), through a cascade decay process, and is one kind of target element in environmental analysis due to its long half-life (t 1/2 ¼ 2.1 Â 10 5 years). This study developed a 99 Tc analytical technique using automatic solid phase extraction (SPE) with TEVA resin and inductively coupled plasma mass spectrometry (ICP-MS). The chemical recovery of 99 Tc was 94.15 AE 3.14% and the minimum detectable activity (MDA) for cement solidified samples spiked with 99 Tc was 1.5 mBq g À1 (2.4 pg mL À1 ). In this study, standard reference material (SRM), an environmental sample was measured by this analytical method. The proposed method is more convenient than traditional radiochemical methods in terms of reducing the time required for analysis, the consumption of reagents, and radiation exposure of operators.

BioMed research international, 2014

It is becoming increasingly evident that certain phytochemicals possess cancer chemopreventive pr... more It is becoming increasingly evident that certain phytochemicals possess cancer chemopreventive properties. In this study, the antiproliferative activity of extracts from different parts of the jaboticaba (Myrciaria cauliflora) plant was evaluated for its effect on human oral carcinoma cell lines. The cytotoxicities of various plant extract concentrations were examined and the 50% maximal inhibitory concentration (IC50) was determined. Water extracts of jaboticaba seeds showed concentration-dependent antiproliferative effects. Annexin V/propidium iodide positivity with active caspase-3 induction indicated that the treated cells underwent apoptosis. Several important regulatory proteins (Bcl-2, Bcl-xL, Bid, and survivin) involved in apoptosis were also evaluated. The antioxidant activity of jaboticaba was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, and the drug concentration eliciting 50% maximum...

BioMed research international, 2014

Chitosan nanoparticle, a biocompatible material, was used as a potential drug delivery system wid... more Chitosan nanoparticle, a biocompatible material, was used as a potential drug delivery system widely. Our current investigation studies were the bioeffects of the chitosan nanoparticle uptake by liver cells. In this experiment, the characterizations of chitosan nanoparticles were measured by transmission electron microscopy and particle size analyzer. The average size of the chitosan nanoparticle was 224.6 ± 11.2 nm, and the average zeta potential was +14.08 ± 0.7 mV. Moreover, using proteomic approaches to analyze the differential protein expression patterns resulted from the chitosan nanoparticle uptaken by HepG2 and CCL-13 cells identified several proteins involved in the PI3K/AKT1/mTOR pathway. Our experimental results have demonstrated that the chitosan nanoparticle may involve in the liver cancer cell metastasis and proliferation.

Rapid communications in mass spectrometry : RCM, 2009

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is used ... more Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is used to rapidly characterize the human neutrophil peptides - HNP 1, 2, and 3 - in saliva. The saliva excreted from the parotid and sublingual/submandibular glands of 70 individuals were collected and examined using MALDI-TOF. The MALDI approach requires no sample pretreatment other than mixing the saliva-absorbing material with the matrix and drying under ambient conditions. Tissue paper was the best material for collecting the saliva samples because of its strong texture and high absorbance, and sinapinic acid was the best MALDI matrix for the analysis of the HNPs. HNPs were detected in almost all the samples collected from the parotid glands, with no obvious differences among age or gender. In contrast, the distribution of the HNPs in the samples collected from the sublingual/submandibular glands was age-dependent: no HNPs were detected for those collected from individuals younger than 30, ...

Journal of materials science. Materials in medicine, 2003

Antenna coupling microwave plasma enables a highly efficient and oxidative treatment of the outer... more Antenna coupling microwave plasma enables a highly efficient and oxidative treatment of the outermost surface of polypropylene (PP) non-woven fabric within a short time period. Subsequently, grafting copolymerization with acrylic acid (AAc) makes the plasma-treated fabric durably hydrophilic and excellent in water absorbency. With high grafting density and strong water affinity, the pAAc-grafted fabric greatly becomes feasible as an intensive absorbent and as a support to promote chitosan-immobilization through amide bonds. Experimental result demonstrated that surface analyses by FTIR-ATR have shown that R-CONH-R', amide binding were emerged between pAAc and chitosan. The XPS measurements on C(1s) 286.0 eV (C-OH), 286.5 eV (C-N) and 288.1 eV (O=C-NH) also could be found. Bioactivity assessments on the chitosan-immobilized surfaces were anticipated by activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen concentration. By means of cell counter we count...

BioMed Research International, 2014

The purpose of this study was to develop the pathway of silk fibroin (SF) biopolymer surface indu... more The purpose of this study was to develop the pathway of silk fibroin (SF) biopolymer surface induced cell membrane protein activation. Fibroblasts were used as an experimental model to evaluate the responses of cellular proteins induced by biopolymer material using a mass spectrometry-based profiling system. The surface was covered by multiwalled carbon nanotubes (CNTs) and SF to increase the surface area, enhance the adhesion of biopolymer, and promote the rate of cell proliferation. The amount of adhered fibroblasts on CNTs/SF electrodes of quartz crystal microbalance (QCM) greatly exceeded those on other surfaces. Moreover, analyzing differential protein expressions of adhered fibroblasts on the biopolymer surface by proteomic approaches indicated that CD44 may be a key protein. Through this study, utilization of mass spectrometry-based proteomics in evaluation of cell adhesion on biopolymer was proposed.

2007 7th IEEE Conference on Nanotechnology (IEEE NANO), 2007

The study presents the mass spectrometric application of carbon nanomaterials in proteomic resear... more The study presents the mass spectrometric application of carbon nanomaterials in proteomic research. We utilized two spherical carbon nanomaterials, C60 buckyball and iron-cored carbonball (Fe-C), in peptide sequence identification of a serum protein using matrix-assisted laser desorption ionization-time of flight mass spectrometer (MALDI-TOF-MS). The biological samples used in the experiments were enzymatically trypsinized bovine serum albumins (BSA) peptides instead of

Journal of Neuroradiology, 2013

Behçet's disease; Behçet's syndrome; Neuro-Behçet's syndrome; Brain SPECT scan; 99m Tc-HMPAO Summ... more Behçet's disease; Behçet's syndrome; Neuro-Behçet's syndrome; Brain SPECT scan; 99m Tc-HMPAO Summary The aim of this study was to detect brain functional deficits in patients with Behçet's disease (BD) and signs or symptoms of central nervous system (CNS) involvement at different times in their clinical history. A total of 24 patients aged 20 to 53 years (median age 39 years; 20 women, four men) with Behçet's syndrome fulfilling the diagnosis as defined by the syndrome classification were enrolled in this study. Single-photon emission computed tomography (SPECT) with 99m Technetium (Tc)-hexamethylpropyleneamine oxime (HMPAO) as the perfusion tracer was performed to detect brain lesions. The results of 99m Tc-HMPAO brain SPECT scans showed impaired perfusion in all cases with neurological complaints (24 out of 24, 100%). Temporal lobes and basal ganglia were the most common areas with such lesions. In contrast, brain MRI and CT images were normal or non-specific in all cases. In conclusion, 99m Tc-HMPAO brain SPECT imaging is a powerful and sensitive tool for disclosing brain involvement in numerous clinical situations, even including patients with subtle neurological symptoms/signs such as headaches and dizziness. It is also a useful modality for evaluating the effects of treatment and disease monitoring to prevent CNS damage.

BioMed Research International, 2013

Peritoneal dialysis (PD) is an increasingly accepted modality of renal replacement therapy. It pr... more Peritoneal dialysis (PD) is an increasingly accepted modality of renal replacement therapy. It provides the advantages of having a flexible lifestyle, stable hemodynamics, and better preservation of residual renal function. To enhance our understanding of the peritoneal dialysate of diabetes mellitus (DM), peritoneal dialysate proteins were identified by two-dimensional gel electrophoresis (2DE) combined with reverse-phase nano-ultra performance liquid chromatography electrospray ionization tandem mass spectrometry (RP-nano-UPLC-ESI-MS/MS) followed by peptide fragmentation patterning. To validate the differential proteins, ELISA and Western blotting analyses were applied to detect candidate proteins that may be related to DM. We performed 2DE on the peritoneal dialysate samples, with detection of more than 300 spots. From this, 13 spots were excised, in-gel digested, and identified by RP-nano-UPLC-ESI-MS/MS. Ten of these showed significant differential expression between the DM and chronic glomerulonephritis (CGN) peritoneal dialysate samples. In this study, we conducted a comparative proteomic study on these two groups of dialysate that may provide evidence for understanding the different peritoneal protein changes. These proteins may not be new biomarkers; however, they may indicate a situation for possible drug treatment and can be the predictors of peritonitis for a validation study in the future.

International Journal of Pharmaceutics, 2009

This study investigates in vitro the drug delivery characteristics of new thermo-sensitive gels, ... more This study investigates in vitro the drug delivery characteristics of new thermo-sensitive gels, P-CS/GA gels, in which a chitosan (CS) network is crosslinked with various concentrations of glutaraldehyde (GA) that interpenetrates Poloxamer (P) gels. The results indicate that the swelling ratios of all P-CS/GA gels are markedly superior to those of non-swelling P and P-CS gels. For example, P-CS/GA (0.1 wt.%) gels have swelling ratios of 13.2 ± 1.0, which are maintained for approximately 18 h in water at 37 • C. In vitro releases of 5-FU from P-CS/GA (0.1 wt.%) gels had significantly lower initial burst release (P < 0.01) and lasted much longer than those from gels without a CS network. For example, the duration of release of 5-FU was in a significantly sustained manner for up to 52 h, which was about 10 times or longer than the period of delivery using P or P-CS gels. The release of drugs from gels with an interpenetrating CS network could be modeled by Fickian diffusion; the characteristic constant 'k' of drug-gel systems decreased as increasing GA concentrations in the P-CS/GA gels, and increasing the viscosities of the P, P-CS and P-CS/GA solutions.

Journal of Thoracic Oncology, 2015

Differential expression and secretion of alpha-actinin 4 (ACTN4) in the lung cancer cell lines CL... more Differential expression and secretion of alpha-actinin 4 (ACTN4) in the lung cancer cell lines CL1-0 and CL1-5 have been reported in previous proteomic studies. The aim of this study is to investigate the functional properties of the ACTN4 protein in non-small-cell lung cancer (NSCLC) cells and evaluate its clinical importance. We used RNA interference to knock down and overexpress ACTN4 protein to evaluate the effects of this intervention on cancer cell invasion and migration, as well as on microscopic cellular morphology. Furthermore, we examined by immunohistochemistry the expression of ACTN4 protein in tissue samples at different stages of lung cancer and compared the protein levels of ACTN4 in blood plasma samples from patients with histologically confirmed lung cancer and healthy controls. CL1-5 cell motility was significantly suppressed by the knockdown of ACTN4 protein. The morphology of CL1-5 cells changed from a predominantly mesenchymal-like shape into a globular shape in response to ACTN4 protein knockdown. A quantitative immunohistochemical assessment of lung cancer tissues revealed that ACTN4 protein level was considerably higher in cancerous tissues than in the adjacent normal ones, and the area under the receiver operating characteristic curve was 0.736 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). According to an enzyme-linked immunosorbent assay, the plasma levels of ACTN4 protein were significantly different between cancer patients and healthy controls, and the areas under the receiver operating characteristic curves were 0.828 and 0.909, respectively, for two independent cohorts (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). We demonstrate that the knockdown of ACTN4 protein inhibited cell invasion and migration. These results suggest that ACTN4 is associated with lung cancer cell motility. Thus, the level of ACTN4 in cancerous tissue and plasma is related to the presence of lung cancer.

PLoS ONE, 2014

Due to the limited information of the contribution of various antibiotic resistance mechanisms in... more Due to the limited information of the contribution of various antibiotic resistance mechanisms in clinical Burkholderia cepacia complex isolates, Antibiotic resistance mechanisms, including integron analysis, identification of quinolone resistance-determining region mutations, measurement of efflux pump activity, and sequence analysis of efflux pump regulators, were investigated in 66 clinical B. cepacia complex isolates. Species were identified via recA-RFLP and MALDI-TOF. Four genomovars were identified by recA-RFLP. B. cenocepacia (genomovar III) was the most prevalent genomovar (90.1%). Most isolates (60/66, 90.9%) were correctly identified by MALDI-TOF analysis. Clonal relatedness determined by PFGE analysis revealed 30 pulsotypes, including two major pulsotypes that comprised 22.7% and 18.2% of the isolates, respectively. Seventeen (25.8%) isolates harboured class 1 integron with various combinations of resistance genes. Among six levofloxacin-resistant isolates, five had single-base substitutions in the gyrA gene and three demonstrated efflux pump activities. Among the 42 isolates exhibiting resistance to at least one antimicrobial agent, 94.4% ceftazidime-resistant isolates (17/18) and 72.7% chloramphenicol-resistant isolates (16/22) demonstrated efflux pump activity. Quantitation of efflux pump RNA level and sequence analysis revealed that over-expression of the RND-3 efflux pump was attributable to specific mutations in the RND-3 efflux pump regulator gene. In conclusion, high-level expression of efflux pumps is prevalent in B. cepacia complex isolates. Mutations in the RND-3 efflux pump regulator gene are the major cause of efflux pump activity, resulting in the resistance to antibiotics in clinical B. cepacia complex isolates.