Chia-Chi Wang

TIPdb: a database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan.

The unique geographic features of Taiwan are attributed to the rich indigenous and endemic plant species in Taiwan. These plants serve as resourceful bank for biologically active phytochemicals. Given that these plant-derived chemicals are prototypes of potential drugs for diseases, databases connecting the chemical structures and pharmacological activities may facilitate drug development. To enhance the utility of the data, it is desirable to develop a database of chemical compounds and corresponding activities from indigenous plants in Taiwan. A database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan was constructed. The database, TIPdb, is composed of a standardized format of published anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan. A browse function was implemented for users to browse the database in a taxonomy-based manner. Search functions can be utilized to filter records of interest by botanical name, part, chemical class, or compound name. The structured and searchable database TIPdb was constructed to serve as a comprehensive and standardized resource for anticancer, antiplatelet, and antituberculosis compounds search. The manually curated chemical structures and activities provide a great opportunity to develop quantitative structure-activity relationship models for the high-throughput screening of potential anticancer, antiplatelet, and antituberculosis drugs.

An in silico toxicogenomics approach for inferring potential diseases associated with maleic acid

Maleic acid is a multi-functional chemical widely applied in the manufacturing of polymer products including food packaging. However, the contamination of maleic acid in modified starch has raised the concerns about the effects of chronic exposure to maleic acid on human health. This study proposed a novel toxicogenomics approach for inferring functions, pathways and diseases potentially affected by maleic acid on humans by using known interactions between maleic acid and proteins. Neuronal signal transmission and cell metabolism were identified to be most influenced by maleic acid in this study. The top disease categories inferred to be associated with maleic acid were mental disorder, nervous system diseases, cardiovascular diseases, and cancers. The results from the in silico analysis showed that maleic acid could penetrate the blood-brain barrier to affect the nervous system. Several functions and pathways were further analyzed and identified to give insights into the mechanisms of maleic acid-associated diseases. The toxicogenomics approach may offer both a better understanding of the potential risks of maleic-acid exposure to humans and a direction for future toxicological investigation.

TIPdb-3D: the three-dimensional structure database of phytochemicals from Taiwan indigenous plants

The rich indigenous and endemic plants in Taiwan serve as a resourceful bank for biologically active phytochemicals. Based on our TIPdb database curating bioactive phytochemicals from Taiwan indigenous plants, this study presents a three-dimensional (3D) chemical structure database named TIPdb-3D to support the discovery of novel pharmacologically active compounds. The Merck Molecular Force Field (MMFF94) was used to generate 3D structures of phytochemicals in TIPdb. The 3D structures could facilitate the analysis of 3D quantitative structure–activity relationship, the exploration of chemical space and the identification of potential pharmacologically active compounds using protein–ligand docking. Database URL: http://cwtung.kmu.edu.tw/tipdb.

Assessment of urinary thiodiglycolic acid exposure in school-aged children in the vicinity of a petrochemical complex in central Taiwan

BACKGROUNDnSchool-aged children living in the vicinity of vinyl chloride (VCM)/polyvinyl chloride (PVC) factories may have an increased risk of exposure to hazardous air pollutants.nnnOBJECTIVESnWe aimed to evaluate the urinary thiodiglycolic acid (TDGA) level, as TDGA is a major metabolite of VCM, for students at elementary schools near a petrochemical complex in central Taiwan.nnnMETHODSnWe recruited 343 students from 5 elementary schools based on distance to the VCM/PVC factory. First-morning urine and blood samples were obtained from our subjects from October 2013 to September 2014. Urine samples were analyzed for urinary creatinine and TDGA using LC/MS-MS. Hepatitis virus infection were assessed using blood samples. We determined their vitamin consumption, resident location, parents employment, and other demographic or lifestyle characteristics using a questionnaire.nnnRESULTSnMedian urinary TDGA levels for 316 students at 5 elementary schools from the closest (<.9km) to the farthest (∼8.6km) with respect to the petrochemical complex were 147.6, 95.5, 115.5, 86.8, and 17.3μg/g creatinine, respectively. After adjusting for age, gender, hepatitis virus infection, vitamin B consumption, passive smoking, and home to source distance, we found that urinary TDGA levels for the closest students was significantly higher than those at other schools. Further, median urinary TDGA levels for students during school time were 4.1-fold higher than those during summer vacation.nnnCONCLUSIONSnAfter adjusting for confounders, urinary TDGA levels for the school-aged children decreased with increasing distances between the elementary schools and the petrochemical complex.

Attenuation of antigen-specific T helper 1 immunity by Neolitsea hiiranensis and its derived terpenoids

Background T cells play a pivotal role in the adaptive immunity that participates in a wide range of immune responses through a complicated cytokine network. Imbalance of T-cell responses is involved in several immune disorders. Neolitsea species, one of the biggest genera in the family Lauraceae, have been employed widely as folk medicines for a long time in Asia. Previous phytochemical investigations revealed the abundance of terpenes in the leaves of N. hiiranensis, an endemic Neolitsea in Taiwan, and demonstrated anti-inflammatory activities. However, the effect of N. hiiranensis on the functionality of immune cells, especially T cells, is still unclear. In this study, we utilize in vitro and in vivo approaches to characterize the effects of leaves of N. hiiranensis and its terpenoids on adaptive immune responses. Methods Dried leaves of N. hiiranensis were extracted three times with cold methanol to prepare crude extracts and to isolate its secondary metabolites. The ovalbumin (OVA)-sensitized BALB/c mice were administrated with N. hiiranensis extracts (5–20 mg/kg). The serum and splenocytes of treated mice were collected to evaluate the immunomodulatory effects of N. hiiranensis on the production of OVA-specific antibodies and cytokines. To further identify the N. hiiranensis-derived compounds with immunomodulatory potentials, OVA-primed splenocytes were treated with compounds isolated from N. hiiranensis by determining the cell viability, cytokine productions, and mRNA expression in the presence of OVA in vitro. Results Crude extracts of leaves of N. hiiranensis significantly inhibited IL-12, IFN-γ, and IL-2 cytokine productions as well as the serum levels of antigen-specific IgM and IgG2a in vivo. Two of fourteen selected terpenoids and one diterpenoid derived from the leaves of N. hiiranensis suppressed IFN-γ in vitro. In addition, β-caryophyllene oxide attenuated the expression of IFN-γ, T-bet, and IL-12Rβ2 in a dose-dependent manner. N. hiiranensis-derived β-caryophyllene oxide inhibited several aspects of adaptive immune responses, including T-cell differentiation, IFN-γ production, and Th1-assocaited genes. Conclusion As IFN-γ is the key cytokine secreted by T helper-1 cells and plays a pivotal role in Th1 immune responses, our results suggested that the N. hiiranensis and its terpenoids may possess potential therapeutic effects on Th1-mediated immune disorders.

Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid

Background Maleic acid is a multi-functional chemical widely used in the field of industrial chemistry for producing food additives and food contact materials. As maleic acid may contaminate food by the release from food packages or intentional addition, it raises the concern about the effects of excessive dietary exposure to maleic acid on human health. However, the influence of maleic acid on human health has not been thoroughly studied. In silico toxicogenomics approaches have found the association between maleic acid and nervous system disease in human. The aim of this study is to experimentally explore the effects of maleic acid on human neuronal cells. Methods A microarray-based transcriptome profiling was performed to offer a better understanding of the effects of maleic acid on human health. Gene expression profiles of human neuroblastoma SH-SY5Y cells exposed to three concentrations of maleic acid (10, 50, and 100 μM) for 24 h were analyzed. Genes which were differentially expressed in dose-dependent manners were identified and further analyzed with an enrichment analysis. The expression profile of selected genes related to the inferred functional changes was validated using quantitative polymerase chain reaction (qPCR). Specific fluorescence probes were applied to observe the inferred functional changes in maleic acid-treated neuronal cells. Results A total of 316 differentially expressed genes (141 upregulated and 175 downregulated) were identified in response to the treatment of maleic acid. The enrichment analysis showed that DNA binding and metal ion binding were the significant molecular functions (MFs) of the neuronal cells affected by maleic acid. Maleic acid exposure decreased the expression of genes associated with calcium and thiol levels of the cells in a dose-dependent manner. The levels of intracellular calcium and thiol levels were also affected by maleic acid dose-dependent. Discussion The exposure to maleic acid is found to decrease the cellular calcium and thiol levels in human neuronal cells at both transcriptional and functional levels. This study reported the first transcriptomic profiling of human neuronal cells treated with maleic acid. It is also the first experimental validation of chemical effects predicted by in silico toxicogenomics approaches. The proposed approach may be useful in understanding the potential effects of other poorly characterized chemicals on human health.

SkinSensDB: a curated database for skin sensitization assays

Skin sensitization is an important toxicological endpoint for chemical hazard determination and safety assessment. Prediction of chemical skin sensitizer had traditionally relied on data from rodent models. The development of the adverse outcome pathway (AOP) and associated alternative in vitro assays have reshaped the assessment of skin sensitizers. The integration of multiple assays as key events in the AOP has been shown to have improved prediction performance. Current computational models to predict skin sensitization mainly based on in vivo assays without incorporating alternative in vitro assays. However, there are few freely available databases integrating both the in vivo and the in vitro skin sensitization assays for development of AOP-based skin sensitization prediction models. To facilitate the development of AOP-based prediction models, a skin sensitization database named SkinSensDB has been constructed by curating data from published AOP-related assays. In addition to providing datasets for developing computational models, SkinSensDB is equipped with browsing and search tools which enable the assessment of new compounds for their skin sensitization potentials based on data from structurally similar compounds. SkinSensDB is publicly available at http://cwtung.kmu.edu.tw/skinsensdb.

ChemDIS-Mixture: an online tool for analyzing potential interaction effects of chemical mixtures

The assessment of bioactivity and toxicity for mixtures remains a challenging work. Although several computational models have been developed to accelerate the evaluation of chemical-chemical interaction, a specific biological endpoint should be defined before applying the models that usually relies on clinical and experimental data. The development of computational methods is desirable for identifying potential biological endpoints of mixture interactions. To facilitate the identification of potential effects of mixture interactions, a novel online system named ChemDIS-Mixture is proposed to analyze the shared target proteins, and common enriched functions, pathways, and diseases affected by multiple chemicals. Venn diagram tools have been implemented for easy analysis and visualization of interaction targets and effects. Case studies have been provided to demonstrate the capability of ChemDIS-Mixture for identifying potential effects of mixture interactions in clinical studies. ChemDIS-Mixture provides useful functions for the identification of potential effects of coexposure to multiple chemicals. ChemDIS-Mixture is freely accessible at http://cwtung.kmu.edu.tw/chemdis/mixture.

Development of novel alternative biodiesel fuels for reducing PM emissions and PM-related genotoxicity

ABSTRACT This paper intend to investigate the effects of biodiesel fuel blends comprising of waste‐cooking oil and butanol‐diesel (B10W10–B10W40) under steady‐state conditions. Both particulate organic carbon (OC) and PM including PM2.5 and PM10 significantly decreased with the increasing percentage of biodiesel fuel blends. The fuel blend of B10W40 also demonstrated the most effective function in reducing the emissions of PM10 and PM2.5 in the volume by 59.4% and 57.7%, respectively. Moreover, the emissions of nitrogen oxides decreased with the blending of B10W10‐B10W40 (13.9–28.5%), while the brake specific fuel consumption was substantially increased (5.69–13.4%). The overall biological toxicity of PM10 generated from the fuel tested in this study was determined according to Single Cell Gel Electrophoresis assay in human alveolar basal epithelial A549 cells and micronucleus assay in CHO‐K1 cells. In addition, the volume of more than 20% waste‐cooking oil (B10W20 and B10W40) significantly reduced diesel‐induced genotoxicity in lung cells and micronucleus formation in CHO‐K1 cells. Collectively, these results indicated that biodiesel fuel blends with the butanol could be a potential alternative fuels for diesel engines because of its substantial property with a significant reduction of the PM‐related genotoxicity and the emissions of PM, particulate OC, and NOX. HighlightsDiesel/biodiesel/butanol blends investigated experimentally.Butanol blends reduced the heating value and increased the fuel consumption.Butanol (10 vol%) are potential alternative fuels for diesel engines.Diesel/biodiesel/butanol blends decrease PM10, PM2.5, and NOX emissions.Diesel/biodiesel/butanol blends decrease mutagenicity and genotoxicity.

Prediction of Proinflammatory Potentials of Engine Exhausts by Integrating Chemical and Biological Features

The increasing prevalence of immune-related diseases has raised concerns about immunotoxicity of engine exhausts. The evaluation of immunotoxicity associated with engine exhausts has relied on expensive and time-consuming experiments. In this study, a computational method named CBM was developed for predicting proinflammatory potentials of engine exhausts using chemical and biological data which are routinely analyzed for toxicity evaluation. The CBM model, based on a principal component regression algorithm, performs well with high correlation coefficient values of 0.972 and 0.849 obtained from training and independent test sets, respectively. In contrast, chemical or biological features alone showed poor correlation with the toxicity. The model indicates the importance of the utilization of both chemical and biological features for developing an effective model. The proposed method could be further developed and applied to predict bioactivities of mixtures.