Publications by authors named "Choon Nam Ong"

169 Publications

Peat-forest burning smoke in Maritime Continent: Impacts on receptor PM and implications at emission sources.

Environ Pollut 2021 Apr 2;275:116626. Epub 2021 Feb 2.

Department of Civil and Environmental Engineering, National University of Singapore, 117576, Singapore; NUS Environmental Research Institute, National University of Singapore, 117411, Singapore. Electronic address:

This study characterizes the impacts of transported peat-forest (PF) burning smoke on an urban environment and evaluates associated source burning conditions based on carbon properties of PM at the receptor site. We developed and validated a three-step classification that enables systematic and more rapid identification of PF smoke impacts on a tropical urban environment with diverse emissions and complex atmospheric processes. This approach was used to characterize over 300 daily PM data collected during 2011-2013, 2015 and 2019 in Singapore. A levoglucosan concentration of ≥0.1 μg/m criterion indicates dominant impacts of transported PF smoke on urban fine aerosols. This approach can be used in other ambient environments for practical and location-dependent applications. Organic carbon (OC) concentrations (as OC indicator) can be an alternate to levoglucosan for assessing smoke impacts on urban environments. Applying the OC concentration indicator identifies smoke impacts on ∼80% of daily samples in 2019 and shows an accuracy of 51-86% for hourly evaluation. Following the systematic identification of urban PM predominantly affected by PF smoke in 2011-2013, 2015 and 2019, we assessed the concentration ratio of char-EC/soot-EC as an indicator of smoldering- or flaming-dominated burning emissions. When under the influence of transported PF smoke, the mean concentration ratio of char-EC to soot-EC in urban PM decreased by >70% from 8.2 in 2011 to 2.3 in 2015 but increased to 3.8 in 2019 (p < 0.05). The reversed trend with a 65% increase from 2015 to 2019 shows stronger smoldering relative to flaming, indicating a higher level of soil moisture at smoke origins, possibly associated with rewetting and revegetating peatlands since 2016.
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http://dx.doi.org/10.1016/j.envpol.2021.116626DOI Listing
April 2021

Transcriptomic analysis identifies dysregulated genes and functional networks in human small airway epithelial cells exposed to ambient PM.

Ecotoxicol Environ Saf 2021 Jan 27;208:111702. Epub 2020 Nov 27.

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. Electronic address:

Cellular models exhibiting human physiological features of pseudostratified columnar epithelia, provide a more realistic approach for elucidating detailed mechanisms underlying PM-induced pulmonary toxicity. In this study, we characterized the barrier and mucociliary functions of differentiated human small airway epithelial cells (SAECs), cultured at the air-liquid interface (ALI). Due to the presence of mucociliary protection, particle internalization was reduced, with a concomitant decrease in cytotoxicity in differentiated S-ALI cells, as compared to conventional submerged SAEC cultures. After 24-hour exposure to PM surrogates, 117 up-regulated genes and 156 down-regulated genes were detected in S-ALI cells, through transcriptomic analysis using the Affymetrix Clariom™ S Human Array. Transcription-level changes in >60 signaling pathways, were revealed by functional annotation of the 273 differentially expressed genes, using the PANTHER Gene List Analysis. These pathways are involved in multiple cellular processes, that include inflammation and apoptosis. Exposure to urban PM led to complex responses in airway epithelia, including a net induction of downstream pro-inflammatory and pro-apoptotic responses. Collectively, this study highlights the importance of using the more advanced ALI model rather than the undifferentiated submerged model, to avoid over-assessment of inhaled particle toxicity in human. The results of our study also suggest that reduction of ambient PM concentrations would have a protective effect on respiratory health in humans.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111702DOI Listing
January 2021

Skin carotenoids status as a potential surrogate marker for cardiovascular disease risk determination in middle-aged and older adults.

Nutr Metab Cardiovasc Dis 2021 02 26;31(2):592-601. Epub 2020 Oct 26.

Department of Food Science & Technology, Faculty of Science, National University of Singapore, Singapore. Electronic address:

Background And Aims: Upon consumption, carotenoids, which may attenuate cardiovascular disease (CVD) risk, diffuse from the blood and accumulate in the skin. This study aimed to assess the associations between dietary, plasma, and skin carotenoids with CVD risk indicators and to examine the mediational role of plasma carotenoids in the relationship between skin carotenoids status (SCS) and CVD risk.

Methods And Results: Dietary, plasma, and skin carotenoids were assessed in a cross-sectional study from a community in Singapore (n = 103) aged 50 to 75 y. Multiple linear regression and binary logistics regression models were used to examine the associations between the carotenoids status with classical CVD risk factors and composite CVD risk indicators. After controlling for covariates, SCS and plasma carotenoids were inversely associated with systolic blood pressure (skin: P < 0.001; plasma: P < 0.05) and diastolic blood pressure (skin: P < 0.001; plasma: P < 0.005). Additionally, each increment of 1000 in SCS was associated with an odds ratio of 0.924 (P < 0.01) for metabolic syndrome diagnosis and 0.945 (P < 0.05) for moderate to high CVD risk classification. Associations between SCS and composite CVD risk indicators were null when adjusted for the corresponding plasma carotenoids, indicating complete mediation. Dietary carotenoids, however, showed no relationship with the CVD risk indicators.

Conclusion: Carotenoids bioavailability may be important for cardiovascular protection. SCS, driven by the corresponding plasma carotenoids, could be a potential noninvasive surrogate marker for CVD risk determination in middle-aged and older adults.

Clinical Trial Registration: NCT03554954, https://clinicaltrials.gov/.

Trial Registration Date: 13 June 2018.
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http://dx.doi.org/10.1016/j.numecd.2020.10.016DOI Listing
February 2021

Effect of plasma polyunsaturated fatty acid levels on leukocyte telomere lengths in the Singaporean Chinese population.

Nutr J 2020 10 30;19(1):119. Epub 2020 Oct 30.

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 12, 1E Kent Ridge Road, Singapore, 119228, Singapore.

Background: Shorter telomere length (TL) has been associated with poor health behaviors, increased risks of chronic diseases and early mortality. Excessive shortening of telomere is a marker of accelerated aging and can be influenced by oxidative stress and nutritional deficiency. Plasma n6:n3 polyunsaturated fatty acid (PUFA) ratio may impact cell aging. Increased dietary intake of marine n-3 PUFA is associated with reduced telomere attrition. However, the effect of plasma PUFA on leukocyte telomere length (LTL) and its interaction with genetic variants are not well established.

Methods: A nested coronary artery disease (CAD) case-control study comprising 711 cases and 638 controls was conducted within the Singapore Chinese Health Study (SCHS). Samples genotyped with the Illumina ZhongHua-8 array. Plasma n-3 and n-6 PUFA were quantified using mass spectrometry (MS). LTL was measured with quantitative PCR method. Linear regression was used to test the association between PUFA and LTL. The interaction between plasma PUFAs and genetic variants was assessed by introducing an additional term (PUFA×genetic variant) in the regression model. Analysis was carried out in cases and controls separately and subsequently meta-analyzed using the inverse-variance weighted method. We further assessed the association of PUFA and LTL with CAD risk by Cox Proportional-Hazards model and whether the effect of PUFA on CAD was mediated through LTL by using structural equation modeling.

Results: Higher n6:n3 ratio was significantly associated with shorter LTL (p = 0.018) and increased CAD risk (p = 0.005). These associations were mainly driven by elevated plasma total n-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (p < 0.05). There was a statistically significant interaction for an intergenic single nucleotide polymorphism (SNP) rs529143 with plasma total n-3 PUFA and DHA on LTL beyond the genome-wide threshold (p < 5 ×  10). Mediation analysis showed that PUFA and LTL affected CAD risk independently.

Conclusions: Higher plasma n6:n3 PUFA ratio, and lower EPA and DHA n-3 PUFAs were associated with shorter LTL and increased CAD risk in this Chinese population. Furthermore, genetic variants may modify the effect of PUFAs on LTL. PUFA and LTL had independent effect on CAD risk in our study population.
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http://dx.doi.org/10.1186/s12937-020-00626-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602302PMC
October 2020

Urban PM reduces angiogenic ability of endothelial cells in an alveolar-capillary co-culture lung model.

Ecotoxicol Environ Saf 2020 Oct 10;202:110932. Epub 2020 Jul 10.

Department of Anatomy, 4 Medical Drive, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore. Electronic address:

Adverse health effects arising from exposure to fine particulates have become a major concern. Angiogenesis is a vital physiological process for the growth and development of cells and structures in the human body, whereby excessive or insufficient vessel growth could contribute to pathogenesis of diseases. We therefore evaluated indirect effects of carbon black (CB) and inhalable airborne particles on the angiogenic ability of unexposed Human Umbilical Vein Endothelial Cells (HUVECs) by co-culturing HUVECs with pre-exposed Small Airway Epithelial Cells (SAECs). As endothelial cells are major components of blood vessels and potential targets of fine particles, we investigated if lung epithelial cells exposed to ambient PM surrogates could induce bystander effects on neighboring unexposed endothelial cells in an alveolar-capillary co-culture lung model. Epithelial exposure to CB at a non-toxic dose of 25 μg/mL reduced endothelial tube formation and cell adhesion in co-cultured HUVECs, and decreased expression of angiogenic genes in SAECs. Similarly, exposure of differentiated SAECs to PM surrogates reduced cell reproductive ability, adhesion and tube formation of neighboring HUVECs. This indicates epithelial exposure to CB and urban PM surrogates both compromised the angiogenic ability of endothelial cells through bystander effects, thereby potentially perturbing the ventilation-perfusion ratio and affecting lung function.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110932DOI Listing
October 2020

An Integrated Metabolomics Study of Glucosinolate Metabolism in Different Brassicaceae Genera.

Metabolites 2020 Jul 31;10(8). Epub 2020 Jul 31.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore.

Glucosinolates are a group of plant secondary metabolites that can be hydrolyzed into a variety of breakdown products such as isothiocyanates, thiocyanates, and nitriles. These breakdown products can facilitate plant defense and function as attractants to natural enemies of insect pests. As part of the diet, some of these compounds have shown cancer-preventing activities, and the levels of these metabolites in the edible parts of the plants are of interest. In this study, we systematically examined variations in glucosinolates, their precursors, and their breakdown products in 12 commonly consumed vegetables of the Brassicaceae family with gas chromatography-quadrupole time-of-flight mass spectrometer (GC-Q-TOF/MS), liquid chromatography-quadrupole time-of-flight mass spectrometer (LC-Q-TOF/MS), and liquid chromatography-triple quadrupole mass spectrometer (LC-QQQ/MS), using both untargeted and targeted approaches. The findings were integrated with data from literature to provide a comprehensive map of pathways for biosynthesis of glucosinolates and isothiocyanates. The levels of precursor glucosinolates are found to correlate well with their downstream breakdown products. Further, the types and abundances of glucosinolates among different genera are significantly different, and these data allow the classification of plants based on morphological taxonomy. Further validation on three genera, which are grown underground, in damp soil, and above ground, suggests that each genus has its specific biosynthetic pathways and that there are variations in some common glucosinolate biosynthesis pathways. Our methods and results provide a good starting point for further investigations into specific aspects of glucosinolate metabolism in the Brassica vegetables.
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http://dx.doi.org/10.3390/metabo10080313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463649PMC
July 2020

Higher maternal plasma β-cryptoxanthin concentration is associated with better cognitive and motor development in offspring at 2 years of age.

Eur J Nutr 2021 Mar 20;60(2):703-714. Epub 2020 May 20.

Singapore Institute for Clinical Sciences, Agency for Science and Technology Research, Singapore, Singapore.

Purpose: Current literature on the roles of α-, β-carotene and β-cryptoxanthin in neurocognitive function has largely focused on preventing cognitive decline in older people, and less on neuro-development in children. We examined the relations of maternal plasma carotenoids concentrations with offspring cognitive development up to age 4.5 years in the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study.

Methods: Maternal plasma α-, β-carotene and β-cryptoxanthin concentrations at delivery were determined by ultra-performance liquid chromatography. Children's cognition was assessed at ages 2 (Bayley Scales of Infant and Toddler Development) and 4.5 (Kaufman Brief Intelligence Test) years. Associations were examined in 419 mother-offspring pairs using linear regressions adjusting for key confounders.

Results: Median and interquartile range of maternal plasma concentrations (mg/L) were: α-carotene 0.052 (0.032, 0.081), β-carotene 0.189 (0.134, 0.286), and β-cryptoxanthin 0.199 (0.123, 0.304). In 2 years old children, higher maternal carotenoids [per standard deviation (SD) log-concentration] were positively associated with neurocognitive functions: β-cryptoxanthin with higher scores in cognitive [β = 0.18, (0.08, 0.28) SD], receptive language [β = 0.17 (0.07, 0.27) SD], fine motor [β = 0.16 (0.05, 0.26) SD], and gross motor [β = 0.16 (0.06, 0.27) SD] scales; β-carotene with higher cognitive score [β = 0.17 (0.05, 0.29) SD]. No significant associations were observed with neurocognitive functions at age 4.5 years.

Conclusion: Our study provides novel data suggesting a potential role of prenatal carotenoids, particularly β-cryptoxanthin, on early offspring cognitive and motor development. Whether the prenatal influences sustain beyond early childhood requires further investigation in longer term studies.
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http://dx.doi.org/10.1007/s00394-020-02277-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116811PMC
March 2021

Chemical Modification of Biomass Okara Using Poly(acrylic acid) through Free Radical Graft Polymerization.

J Agric Food Chem 2020 Nov 18;68(46):13241-13246. Epub 2020 May 18.

Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.

Okara (Ok) or soybean residue is produced as a byproduct from the soybean milk and soybean curd industries world wide, most of which is disposed or burned as waste. It is important to explore the possibilities to convert okara to useful materials, because okara is a naturally renewable bioresource. Here, we report the chemical modification of okara by grafting poly(acrylic acid) (PAA) onto the backbones of okara in water medium and the characterization of the Ok-PAA graft copolymers. It was found that the received okara mainly contained insoluble contents in water. The insoluble okara component Ok(Ins) was suspended in water and activated with ammonium persulfate as an initiator, followed by grafting PAA through a free radical polymerization. After the graft polymerization, the product (Ok-PAA) was separated into precipitate and supernatant, which were dried to give Ok-PAA(pre) and Ok-PAA(sup), respectively. It was found that PAA was grafted on Ok backbones and co-precipitated with the insoluble Ok. In addition, Ok-PAA(sup) was found to be translucent as a result of the grafting of PAA. Further, the successful grafting of PAA onto okara backbones was proven by Fourier transform infrared, thermogravimetric analysis, and microscopic measurements. Ok-PAA(sup) dispersed in water formed nanoparticles with an average diameter of 420 nm, while Ok-PAA(pre) was clustered coarse particles in water. The rheological data including the storage modulus, loss modulus, and viscosity indicated that the Ok-PAA product was a viscoelastic gel-like material with potential for agricultural and environmental applications.
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http://dx.doi.org/10.1021/acs.jafc.0c01818DOI Listing
November 2020

Maternal Lutein and Zeaxanthin Concentrations in Relation to Offspring Visual Acuity at 3 Years of Age: The GUSTO Study.

Nutrients 2020 Jan 21;12(2). Epub 2020 Jan 21.

Singapore Institute for Clinical Sciences, Agency for Science and Technology Research, Singapore 117609, Singapore.

Lutein and zeaxanthin play important roles in visual functions, but their influence on early visual development is unclear. We related maternal lutein and zeaxanthin concentrations during pregnancy to offspring visual acuity (VA) in 471 mother-child pairs from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Maternal concentrations of plasma lutein and zeaxanthin were determined at delivery. We measured uncorrected distance of VA in 3-year old children using a LEA Symbols chart; readings were converted to the logarithm of Minimum Angle of Resolution (logMAR), with >0.3 logMAR indicating poor VA. Associations were examined using linear or Poisson regression adjusted for confounders. The median (inter-quartile range) of maternal lutein and zeaxanthin concentrations were 0.13 (0.09, 0.18) and 0.09 (0.07, 0.12) µmol/L, respectively. A total of 126 children had poor VA. The highest tertile of maternal zeaxanthin concentration was associated with 38% lower likelihood of poor VA in children (95% CI: 0.42, 0.93, -Trends = 0.02). Higher maternal lutein concentrations were associated with a lower likelihood of poor VA in children (RR 0.60 (95% CI: 0.40, 0.88) for middle tertile; RR 0.78 (95% CI: 0.51, 1.19) for highest tertile (-Quadratic = 0.02)). In conclusion, lutein and zeaxanthin status during pregnancy may influence offspring early visual development; but the results require confirmation with further studies, including more comprehensive measurements of macular functions.
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http://dx.doi.org/10.3390/nu12020274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070638PMC
January 2020

Lomatogonium Rotatum for Treatment of Acute Liver Injury in Mice: A Metabolomics Study.

Metabolites 2019 Oct 14;9(10). Epub 2019 Oct 14.

NUS Environmental Research Institute, National University of Singapore, Singapore 117411, Singapore.

Fries ex Nym (LR) is used as a traditional Mongolian medicine to treat liver and bile diseases. This study aimed to investigate the hepatoprotective effect of LR on mice with CCl-induced acute liver injury through conventional assays and metabolomics analysis. This study consisted of male mice ( = 23) in four groups (i.e., control, model, positive control, and LR). The extract of whole plant of LR was used to treat mice in the LR group. Biochemical and histological assays (i.e., serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and histological changes of liver tissue) were used to evaluate LR efficacy, and metabolomics analysis based on GC-MS and LC-MS was conducted to reveal metabolic changes. The conventional analysis and metabolomic profiles both suggested that LR treatment could protect mice against CCl-induced acute liver injury. The affected metabolic pathways included linoleic acid metabolism, α-linolenic acid metabolism, arachidonic acid metabolism, CoA biosynthesis, glycerophospholipid metabolism, the TCA cycle, and purine metabolism. This study identified eight metabolites, including phosphopantothenic acid, succinic acid, AMP, choline, glycerol 3-phosphate, linoleic acid, arachidonic acid, and DHA, as potential biomarkers for evaluating hepatoprotective effect of LR. This metabolomics study may shed light on possible mechanisms of hepatoprotective effect of LR.
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http://dx.doi.org/10.3390/metabo9100227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836280PMC
October 2019

Toxicity Study of Zinc Oxide Nanoparticles in Cell Culture and in Drosophila melanogaster.

J Vis Exp 2019 09 19(151). Epub 2019 Sep 19.

Department of Anatomy, National University of Singapore;

Zinc oxide nanoparticles (ZnO NPs) have a wide range of applications, but the number of reports on ZnO NP-associated toxicity has grown rapidly in recent years. However, studies that elucidate the underlying mechanisms for ZnO NP-induced toxicity are scanty. We determined the toxicity profiles of ZnO NPs using both in vitro and in vivo experimental models. A significant decrease in cell viability was observed in ZnO NP-exposed MRC5 lung fibroblasts, showing that ZnO NPs exert cytotoxic effects. Similarly, interestingly, gut exposed to ZnO NPs exhibited a dramatic increase in reactive oxygen species levels (ROS) in the fruit fly Drosophila. More in-depth studies are required to establish a risk assessment for the increased usage of ZnO NPs by consumers.
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http://dx.doi.org/10.3791/59510DOI Listing
September 2019

Association between serum heavy metals and prostate cancer risk - A multiple metal analysis.

Environ Int 2019 11 3;132:105109. Epub 2019 Sep 3.

Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore. Electronic address:

Background: Prostate cancer is one of the most prevalent cancers in men. Exposure to heavy metals and their association with prostate cancer risk has been studied extensively, but combined effects remain largely inconclusive.

Objectives: To elucidate the association between serum concentrations of heavy metals and prostate cancer risk.

Methods: Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the concentrations of a panel of 10 heavy metals (Mn, Cu, Zn, As, Se, Sb, Co, Cu, Cd and Pb) in serum samples of 141 cases and 114 controls in the Singapore Prostate Cancer Study. Linear probit regression models were used to estimate risk differences (RDs) and 95% confidence intervals (CIs) for the associations between log-centered serum metal concentrations and prostate cancer risk with adjustment for potential confounders. Bayesian kernel machine regression (BKMR) models were used to account for nonlinear, interactive, and joint metal effects.

Results: Using probit regression, four heavy metals (As, Zn, Mn, Sb) were significantly and positively associated with prostate cancer risk in the unadjusted models. Using BKMR analysis, both As and Zn had positive risk differences on prostate cancer risk when all other metals were held fixed at the 25th and 50th percentiles (RD, 25th percentile: As: 0.15, Zn: 0.19, RD, 50th percentile: As: 0.45, Zn: 0.37). In addition, the overall mixture risk difference was positive and the 95% credible intervals did not include 0 when all metals in the mixture were jointly above their 55th percentile, as compared to when all metals were below their median values.

Conclusions: In summary, we found positive associations between the serum levels of As and Zn and prostate cancer risk on the risk difference scale using BKMR models. The overall mixture effect was also associated with increased prostate cancer risk. Future studies are warranted to validate these findings in prospective studies.
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http://dx.doi.org/10.1016/j.envint.2019.105109DOI Listing
November 2019

Simultaneous Quantification of 22 Glucosinolates in 12 Vegetables by Hydrophilic Interaction Chromatography-Tandem Mass Spectrometry.

ACS Omega 2018 Nov 15;3(11):15546-15553. Epub 2018 Nov 15.

NUS Environment Research Institute, National University of Singapore, 5A Engineering Drive 1, 117411 Singapore.

Glucosinolates, which are unique to vegetables, have diverse biological activities, including antimicrobial, antioxidant, and anticancer actions. In this study, we applied hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) to the simultaneous quantification of 22 glucosinolates in 12 vegetables, including pak choi, choy sum, Chinese cabbage, cauliflower, cabbage, broccoli, Kai Lan, Brussels sprouts, rocket salad, daikon radish, red cherry radish, and watercress. Significant differences in concentration and composition of glucosinolates were observed among these vegetables. Cabbage had the highest level of total glucosinolates (μg/g dry weight: 19 551.2 ± 1317.7), whereas Kai Lan had the lowest level (7611.3 ± 868.4). Aliphatic and indole glucosinolates were the major components in the 12 vegetables ranging from 76 to 100%, except watercress (37%). On the basis of the content of glucosinolates, the 12 vegetables were well distinguishable and classified according to their morphological taxonomy. This study presents a HILIC-MS/MS approach for quantification of glucosinolates, and demonstrates the potential of glucosinolate profiles for species identification.
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http://dx.doi.org/10.1021/acsomega.8b01668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643737PMC
November 2018

A Dietary Pattern Derived from Reduced Rank Regression and Fatty Acid Biomarkers Is Associated with Lower Risk of Type 2 Diabetes and Coronary Artery Disease in Chinese Adults.

J Nutr 2019 11;149(11):2001-2010

Saw Swee Hock School of Public Health, National University of Singapore (NUS), Singapore.

Background: Combinations of circulating fatty acids may affect the risk of type 2 diabetes (T2D) and coronary artery disease (CAD). No previous studies have identified a dietary pattern predicting fatty acid profiles using reduced rank regression (RRR) and evaluated its associations with the risk of T2D and CAD.

Objective: The aim of this study was to derive a dietary pattern to explain variation in plasma fatty acid concentrations using RRR and evaluate these in relation to risk of T2D and CAD.

Methods: We derived a dietary pattern using fatty acid concentrations from 711 controls of a nested case-control study in the Singapore Chinese Health Study using RRR with 36 food and beverages as predictors and 19 fatty acid biomarkers as responses. Dietary pattern scores were then calculated for the full cohort of men and women (mean age: 56 y). We followed up 45,411 and 58,065 participants for incident T2D and CAD mortality, respectively. Multivariable Cox regression models were used to estimate HRs and 95% CIs.

Results: We identified a dietary pattern high in soy, vegetables, fruits, tea, tomato products, bread, fish, margarine and dairy, and low in rice, red meat, coffee, alcohol, sugar-sweetened beverages, and eggs. This pattern predicted higher circulating n-3 (ω-3) PUFAs (18:3n-3, 20:3n-3, 20:5n-3), odd-chain fatty acids (15:0, 17:0), 18:2n-6 and 20:1, and lower 20:4n-6 and 16:1. During a mean follow-up of 11 y and 19 y, 5207 T2D and 3016 CAD mortality events, respectively, were identified. Higher dietary pattern scores were associated with a lower risk of T2D [multivariable-adjusted HR comparing extreme quintiles, 0.86 (95% CI: 0.79, 0.95); P-trend <0.001] and CAD mortality [HR, 0.76 (95% CI: 0.68, 0.86); P-trend <0.001].

Conclusions: Dietary patterns reflecting higher circulating n-3 PUFAs, odd-chain fatty acids, and linoleic acid may be associated with lower T2D and CAD risk in Chinese adults. This trial was registered at www.clinicaltrials.gov as NCT03356340.
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http://dx.doi.org/10.1093/jn/nxz164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825830PMC
November 2019

Male-biased zebrafish sex differentiation and metabolomics profile changes caused by dydrogesterone.

Aquat Toxicol 2019 Sep 11;214:105242. Epub 2019 Jul 11.

School of Public Health, National University of Singapore, 117547, Singapore. Electronic address:

Some progestins, including the widely used dydrogesterone (DDG), have been shown to cause male-biased sex ratio in teleost. However, there is a gap to fully understand the mechanisms of the sex differentiation disturbance by progestins, particularly from the metabolic aspect. We thus aimed to examine the sex changes by exposing zebrafish embryos to 4.4 (L), 44 (M) and 440 (H) ng/L DDG for up to 140 days, and investigated metabolomic profile changes during the critical period of sex differentiation at fry stage (35 dpf). DDG increased the percentage of male zebrafish in a dose-dependent manner, with 98% male fish in the high concentration group. In zebrafish fry, DDG increased the levels of some free fatty acids, monoglycerides, acylcarnitines, organic acids, free amino acids, while decreased lysophospholipids, uric acid and bile acids. DDG exposure also decreased the nucleoside monophosphates and UDP-sugars while increased nucleosides and their bases. These metabolite changes, namely increase in n-3 PUFAs (polyunsaturated fatty acids), myo-inositol, taurine, palmitoleic acid, oleic acid, lactic acid, fumaric acid, and uracil, and decrease in uric acid and bile acids, might account for the male-biased sex ratio in zebrafish. It appears that many of these metabolites could inhibit several pathways that regulate zebrafish gonad differentiation, including NF-κB/COX-2 and Wnt/β-catenin pathways, and activate p53 pathway. Thus we proposed a hypothesis that DDG might induce oocytes apoptosis through the above pathways and finally lead to female-to-male sex reversal. The results from this study suggest that DDG at environmentally relevant concentrations could affect zebrafish metabolomic profiles and finally disturb fish sex differentiation.
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http://dx.doi.org/10.1016/j.aquatox.2019.105242DOI Listing
September 2019

Targeted metabolomics reveals differential biological effects of nanoplastics and nanoZnO in human lung cells.

Nanotoxicology 2019 10 24;13(8):1117-1132. Epub 2019 Jul 24.

Saw Swee Hock School of Public Health, National University of Singapore , Singapore , Singapore.

Engineered nanomaterials are of public health concern. Recently, there has been an increasing attention on the toxicity of nanoplastics and nanoZnO because of their increasing utilization and presence in the environment. However, knowledge of their toxicological behavior and metabolic interactions with the cellular machinery that determine their potential health effects are extremely limited. In this study, the cellular uptake, cytotoxic effects, and metabolic responses of bronchus epithelial (BEAS-2B) cells exposed to nanopolystyrene (nanoPS) and a widely used metallic nanoparticle, nanoZnO, were investigated using a tandem mass spectrometry-based metabolomics approach. The results revealed that even with low cytotoxicity, these nanoparticles (NPs) affected cell metabolism. NanoPS exposure showed autophagic- and endoplasmic reticulum (ER) stress-related metabolic changes such as increased in amino acids and tricarboxylic acid cycle (TCA) intermediate metabolites, a process known to play a critical role in regulating cell resistance to cytotoxic effects. Both metabolomics profiling and ER-stress pathway, together with quantitative real-time RT-polymerase chain reaction (qRT-PCR) analyses, demonstrated that autophagy was reciprocally regulated to couple metabolic and transcriptional reprograming. In contrast, nanoZnO-induced ROS-mediated cell death was associated with mitochondrial dysfunction and interference in regulating energy metabolism. Collectively, these two types of NPs were observed to cause perturbations albeit differential in cellular metabolism associated with their cytotoxic effects. Our findings provided an in depth understanding of metabolic changes influenced by two different types of NPs, with contrasting molecular mechanisms for the adverse effects observed.
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http://dx.doi.org/10.1080/17435390.2019.1640913DOI Listing
October 2019

Dydrogesterone exposure induces zebrafish ovulation but leads to oocytes over-ripening: An integrated histological and metabolomics study.

Environ Int 2019 07 9;128:390-398. Epub 2019 May 9.

School of Public Health, National University of Singapore, 117547, Singapore. Electronic address:

Dydrogesterone (DDG) is a synthetic progestin widely used in numerous gynecological diseases. DDG has been shown to disturb fish reproduction, however, the mechanism is still unclear. Here we studied the histological changes and differences of metabolome between exposed and control fish gonads after exposure of zebrafish (Danio rerio) embryos to 2.8, 27.6, and 289.8 ng/L DDG until sexual maturity for a total of 140 days. Dydrogesterone exposure led to male-biased zebrafish sex ratios. Histological examination revealed that DDG induced postovulatory follicles and atretic follicles in the ovary of the female fish. Postovulatory follicles indicated the occurrence of ovulation. DDG also increased spermatids and spermatozoa in the male fish testis, suggesting promotion of spermatogenesis. Ovarian metabolome showed that DDG increased the concentrations of free amino acids, urea, putrescine, free fatty acids, acylcarnitines, lysophospholipids, and other metabolites catabolized from phospholipids. Most of these metabolites are biodegradation products of proteins and lipids, suggesting the existence of ovulated oocytes over-ripening. Further, DDG upregulated arachidonic acid (AA) and its 5‑lipoxygenase (5-LOX) metabolites 5‑oxo‑6,8,11,14‑eicosatetraenoic acid (5-oxo-ETE) in the ovary, which could lead to suppression of AA cyclooxygenase (COX) metabolite prostaglandin F2α (PGF2α). It is believed that AA induced oocyte maturation, while 5-oxo-ETE and related metabolites in purinergic signaling promoted ovulation. Whereas, the suppression of PGF2α production might block spawning and damaged follicular tissue digestion, which explained the oocytes over-ripening and atretic follicles in the treated ovary. Overall, our results suggested that DDG exposure induced zebrafish oocyte maturation and ovulation but led to oocytes over-ripening via the AA metabolic pathway and purinergic signaling.
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http://dx.doi.org/10.1016/j.envint.2019.04.059DOI Listing
July 2019

Employing multi-omics to elucidate the hormetic response against oxidative stress exerted by nC on Daphnia pulex.

Environ Pollut 2019 Aug 30;251:22-29. Epub 2019 Apr 30.

NUS Environmental Research Institute, National University of Singapore, Singapore, 117597, Singapore.

This study evaluated hormetic effect of oxidative stress exerted by fullerene crystals (nC) on Daphnia pulex, employing transcriptomics and metabolomics. D. pulex were exposed to various concentrations of nC for 21 days. Hormetic effect of oxidative stress was most evident after 7 days, with markedly increased L-Glutathione (GSH) concentration and Superoxide Dismutase (SOD) activity at low doses of nC exposure, and oppositely at high doses. The transcriptomics and metabolomics were used to elucidate the molecular mechanism underlying the hormesis in oxidative stress. There were significant alterations in major pathways involving oxidative stress and energy metabolism in D. pulex. Some important intermediates and the expression of their regulatory genes coincided with each other with first up-regulated and then down-regulated with the concentration increased, consistent with the hormesis description. The nC interfered the TCA cycle of D. pulex. The synthesis of L-cysteine and glutamate was directly affected, and further disturbed the synthesis of GSH. This work is of great significance to provide the molecular-level evidence into the hormetic effect in oxidative stress of D. pulex exposed to nC.
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http://dx.doi.org/10.1016/j.envpol.2019.04.097DOI Listing
August 2019

Impacts of peat-forest smoke on urban PM in the Maritime Continent during 2012-2015: Carbonaceous profiles and indicators.

Environ Pollut 2019 May 20;248:496-505. Epub 2019 Feb 20.

NUS Environmental Research Institute, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore; Department of Civil and Environmental Engineering, National University of Singapore, 1 Engineering Drive 2, 117576, Singapore. Electronic address:

This study characterizes impacts of peat-forest (PF) smoke on an urban environment through carbonaceous profiles of >260 daily PM samples collected during 2012, 2013 and 2015. Organic carbon (OC) and elemental carbon (EC) comprising eight carbonaceous fractions are examined for four sample groups - non-smoke-dominant (NSD), smoke-dominant (SD), episodic PM samples at the urban receptor, and near-source samples collected close to PF burning sites. PF smoke introduced much larger amounts of OC than EC, with OC accounting for up to 94% of total carbon (TC), or increasing by up to 20 times in receptor PM. SD PM at the receptor site and near-source samples have OC3 and EC1 as the dominant fractions. Both sample classes also exhibit char-EC >1.4 times of soot-EC, characterizing smoldering-dominant PF smoke, unlike episodic PM at the receptor site featuring large amounts of pyrolyzed organic carbon (POC) and soot-EC. Relative to the mean NSD PM at the receptor, increasing strength of transboundary PF smoke enriches OC3 and OC4 fractions, on average, by factors of >3 for SD samples, and >14 for episodic samples. A peat-forest smoke (PFS) indicator, representing the concentration ratio of (OC2+OC3+POC) to soot-EC, shows a temporal trend satisfactorily correlating with an organic marker (levoglucosan) of biomass burning. The PFS indicator systematically differentiates influences of PF smoke from source to urban receptor sites, with a progressive mean of 3.6, 13.4 and 20.1 for NSD, SD and episodic samples respectively at the receptor site, and 54.7 for the near-source PM. A PFS indicator of ≥5.0 is proposed to determine dominant influence of transboundary PF smoke on receptor urban PM in the equatorial Asia with ∼90% confidence. Assessing >2900 hourly OCEC data in 2017-2018 supports the applicability of the PFS indicator to evaluate hourly impacts of PF smoke on receptor urban PM in the Maritime Continent.
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http://dx.doi.org/10.1016/j.envpol.2019.02.049DOI Listing
May 2019

Metabolic signatures of four major histological types of lung cancer cells.

Metabolomics 2018 08 31;14(9):118. Epub 2018 Aug 31.

Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, #11-01, Tahir Foundation Building, Singapore, 117549, Singapore.

Introduction: Histologically lung cancer is classified into four major types: adenocarcinoma (Ad), squamous cell carcinoma (SqCC), large cell carcinoma (LCC), and small cell lung cancer (SCLC). Presently, our understanding of cellular metabolism among them is still not clear.

Objectives: The goal of this study was to assess the cellular metabolic profiles across these four types of lung cancer using an untargeted metabolomics approach.

Methods: Six lung cancer cell lines, viz., Ad (A549 and HCC827), SqCC (NCl-H226 and NCl-H520), LCC (NCl-H460), and SCLC (NCl-H526), were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry, with normal human small airway epithelial cells (SAEC) as the control group. The principal component analysis (PCA) was performed to identify the metabolic signatures that had characteristic alterations in each histological type. Further, a metabolite set enrichment analysis was performed for pathway analysis.

Results: Compared to the SAEC, 31, 27, 34, 34, 32, and 39 differential metabolites mainly in relation to nucleotides, amino acid, and fatty acid metabolism were identified in A549, HCC827, NCl-H226, NCl-H520, NCl-H460, and NCl-H526 cells, respectively. The metabolic signatures allowed the six cancerous cell lines to be clearly separated in a PCA score plot.

Conclusion: The metabolic signatures are unique to each histological type, and appeared to be related to their cell-of-origin and mutation status. The changes are useful for assessing the metabolic characteristics of lung cancer, and offer potential for the establishment of novel diagnostic tools for different origin and oncogenic mutation of lung cancer.
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http://dx.doi.org/10.1007/s11306-018-1417-xDOI Listing
August 2018

Reproducibility of Dietary Biomarkers in a Multiethnic Asian Population.

Mol Nutr Food Res 2019 04 7;63(8):e1801104. Epub 2019 Mar 7.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549.

Scope: Dietary biomarkers allow for study of diet and disease risk relationships, but a key requirement is that these biomarkers are reproducible and reflect long-term diet. This study assesses reproducibility of selected dietary biomarkers in a multi-ethnic Asian population, and quantifies diet-disease relationship attenuation arising from use of a single biomarker measurement.

Methods And Results: Intra-class correlation coefficients (ICC) are used to evaluate the reproducibility of urinary isoflavone and enterolignan, total plasma fatty acid (FA), and serum carotenoid concentrations measured 4 months apart in adult Singapore residents (ethnic Chinese, n 59; Malay, n 46; Indian, n 56). Total carotenoid ICC is 0.75 (95% confidence interval (CI) 0.68, 0.81), ranging from 0.63 to 0.84 for individual carotenoids. FA ICC (median) is 0.74 (inter-quartile range 0.70-0.78). Total isoflavone ICC (95% CI) is 0.21 (0.06-0.35). Total enterolignan ICC is 0.42 (0.28, 0.54). Attenuation factors associated with a single time point measure ranged from 0.74 to 0.94 for carotenoids and FAs, and 0.42 to 0.70 for isoflavones and enterolignans.

Conclusions: In a multi-ethnic Asian population, single measures of most serum carotenoids and plasma FAs likely represent habitual diet, whereas reproducibility of urinary isoflavones and enterolignans is moderate, possibly due to rapid excretion.
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http://dx.doi.org/10.1002/mnfr.201801104DOI Listing
April 2019

Serum Amino Acids in Association with Prevalent and Incident Type 2 Diabetes in A Chinese Population.

Metabolites 2019 Jan 14;9(1). Epub 2019 Jan 14.

Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

We aimed to simultaneously examine the associations of both essential and non-essential amino acids with both prevalent and incident type 2 diabetes in a Chinese population. A case-control study was nested within the Singapore Chinese Health Study. Participants included 144 cases with prevalent and 160 cases with incident type 2 diabetes and 304 controls. Cases and controls were individually matched on age, sex, and date of blood collection. Baseline serum levels of 9 essential and 10 non-essential amino acids were measured using liquid chromatography tandem mass spectrometry. We identified that five essential (isoleucine, leucine, lysine, phenylalanine, and valine) and five non-essential (alanine, glutamic acid, glutamine, glycine, and tyrosine) amino acids were associated with the prevalence of type 2 diabetes; four essential (isoleucine, leucine, tryptophan, and valine) and two non-essential (glutamine and tyrosine) amino acids were associated with the incidence of type 2 diabetes. Of these, valine and tyrosine independently led to a significant improvement in risk prediction of incident type 2 diabetes. This study demonstrates that both essential and non-essential amino acids were associated with the risk for prevalent and incident type 2 diabetes, and the findings could aid in diabetes risk assessment in this Chinese population.
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http://dx.doi.org/10.3390/metabo9010014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359471PMC
January 2019

Use of an integrated metabolomics platform for mechanistic investigations of three commonly used algaecides on cyanobacterium, Microcystis aeruginosa.

J Hazard Mater 2019 04 19;367:120-127. Epub 2018 Dec 19.

NUS Environmental Research Institute, National University of Singapore, 117411, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, 117549, Singapore. Electronic address:

Algal blooms are a global environmental and public health problem. Copper Sulfate (CuSO), Hydrogen Peroxide (HO) and Sodium Carbonate Peroxide (SCP) are commonly used algaecides for algal bloom control. However, their efficacy and mechanisms of interaction with algae have not been well studied. This study aimed to compare their capability, and concurrently elucidate the metabolic responses of a common cyanobacterium, Microcystis aeruginosa. Algal responses were measured by cell density, chlorophyll a, toxin release and an integrated GC- and LC- Mass Spectrometry-Time of Flight metabolomics platform. CuSO was observed to kill the algae cells rapidly at relative low concentration, compared with the other two algaecides. However, it led to severe secondary contamination, with substantial release of various microcystins. Metabolomics data showed that a total of 32 metabolites were significantly changed compared with the controls. Most of the metabolites identified in CuSO treated algae were significantly reduced, whereas metabolites in algae treated with HO and SCP were found to increase, and were of similar types. Although most of the metabolites identified for the three algaecides are associated to oxidative stress, the pathways affected appear to be different.
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http://dx.doi.org/10.1016/j.jhazmat.2018.12.069DOI Listing
April 2019

Characterization of Plant Volatiles Reveals Distinct Metabolic Profiles and Pathways among 12 Brassicaceae Vegetables.

Metabolites 2018 Dec 14;8(4). Epub 2018 Dec 14.

NUS Environment Research Institute, National University of Singapore, Singapore 117411, Singapore.

Plants emit characteristic organic volatile compounds (VOCs) with diverse biological/ecological functions. However, the links between plant species/varieties and their phytochemical emission profiles remain elusive. Here, we developed a direct headspace solid-phase microextraction (HS-SPME) technique and combined with non-targeted gas chromatography‒high-resolution mass spectrometry (GC-HRMS) platform to investigate the VOCs profiles of 12 common Brassicaceae vegetables (watercress, rocket, Brussels sprouts, broccoli, kai lan, choy sum, pak choi, cabbage, Chinese cabbage, cauliflower, radish and cherry radish). The direct HS-SPME sampling approach enabled reproducible capture of the rapid-emitting VOCs upon plant tissue disruption. The results revealed extensive variation in VOCs profiles among the 12 Brassicaceae vegetables. Furthermore, principal component analysis (PCA) showed that the VOC profiles could clearly distinguish the 12 Brassicaceae vegetables, and that these profiles well reflected the classical morphological classification. After multivariate statistical analysis, 44 VOCs with significant differences among the Brassicaceae vegetables were identified. Pathway analysis showed that three secondary metabolism pathways, including the fatty acid pathway, methylerythritol phosphate (MEP) pathway and glucosinolate (GLS) pathway, behave distinctively in these vegetables. These three pathways are responsible for the generation and emission of green leaf volatiles (GLVs), terpenes and isothiocyanates (ITCs), respectively. Correlation analysis further showed that volatile metabolites formed via the common pathway had significantly positive correlations, whereas metabolites from different pathways had either non-significant or significantly negative correlations. Genetic influences on these metabolites across various vegetable types were also evaluated. These findings extend our phytochemical knowledge of the 12 edible Brassicaceae vegetables and provide useful information on their secondary metabolism.
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http://dx.doi.org/10.3390/metabo8040094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316591PMC
December 2018

Metabolites change of Scenedesmus obliquus exerted by AgNPs.

J Environ Sci (China) 2019 Feb 25;76:310-318. Epub 2018 May 25.

School of Municipal and Environmental Engineering, Lanzhou Jiaotong University, Lanzhou 730070, China.

With increasing emission of silver nanoparticles (AgNPs) into the environment, it is important to understand the effects of ambient concentration of AgNPs. The biological effects of AgNPs on Scenedesmus obliquus, a ubiquitous freshwater microalgae, was evaluated. AgNPs exerted a minor inhibitory effect at low doses. Non-targeted metabolomic studies were conducted to understand and analyze the effect of AgNPs on algal cells from a molecular perspective. During the 48 hr of exposure to AgNPs, 30 metabolites were identified, of which nine had significant changes compared to the control group. These include d-galactose, sucrose, and d-fructose. These carbohydrates are involved in the synthesis and repair of cell walls. Glycine, an important constituent amino acid of glutathione, increased with AgNP exposure concentration increasing, likely to counteract an increased intracellular oxidative stress. These results provide a new understanding of the toxicity effects and mechanism of AgNPs. These metabolites could be useful biomarkers for future research, employed in the early detection of environmental risk from AgNPs.
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http://dx.doi.org/10.1016/j.jes.2018.05.017DOI Listing
February 2019

The use of as a model organism to study immune-nanotoxicity.

Nanotoxicology 2019 05 19;13(4):429-446. Epub 2018 Nov 19.

a Department of Anatomy Yong Loo Lin School of Medicine , National University of Singapore , Singapore , Singapore.

Nanomaterials (NMs) are widely used in consumer and industrial products, as well as in the field of nanomedicine. Despite their wide array of applications, NMs are regarded as foreign entities by the body and thus induce various immune reactions. In mammals, NMs trigger differential recognition by immune cells such as macrophages, causing perturbation of the immune system. Studies on the pattern recognition of NMs have revealed that the Toll-like receptor signaling pathway plays an essential role in NM-induced innate immunity. However, effects caused by physicochemical properties of NMs on immune response and how NMs are recognized by immune cells are not fully understood. Furthermore, the complexity of the mammalian immune system and interspecies variation are still being debated, and the discordant results warrant the need to address these issues. has gained popularity as a model to study nanotoxicity. innate immunity has extensively been studied, providing insights into our understanding of key signaling cascades involved, and importantly it has conserved immune-related genes and mechanogenetic pathways that represents a useful basis for studying its biological response at molecular level to environmental contaminants such as NMs. Moreover, various genetic tools and reagents enable to elucidate the molecular mechanisms underlying the internalization of NMs by immune cells. Furthermore, numerous forward and reverse genetic approaches can be employed to dissect complex biological processes, such as identifying signal transduction pathways and their core components involved in NM-induced immune responses. This review presents an overview of innate immunity, as well as summarizes the impact of NM exposure on immune response in . We also highlight the recent advancement of suitable methodologies and tools regarding the use of as a model for studying the immune-related toxicity of NMs, taking into account the limitations associated with studying NM-induced toxicity in the mammalian system.
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http://dx.doi.org/10.1080/17435390.2018.1546413DOI Listing
May 2019

Occurrence and distribution of pesticides in precipitation as revealed by targeted screening through GC-MS/MS.

Chemosphere 2018 Nov 26;211:210-217. Epub 2018 Jul 26.

NUS Environmental Research Institute, National University of Singapore, Singapore, 117411, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, 117549, Singapore. Electronic address:

Facing the tough challenge of precise measurement of ever-increasing numbers of organic contaminants in the environment, there is an urgent need for more reliable and cost-effective methodologies. In this study, we developed and validated a screening method for analysis of over 450 pesticides in precipitation using gas chromatography with tandem mass spectrometry (GC-MS/MS) in multiple reaction monitoring (MRM) mode. Solid phase extraction (SPE) was applied to extract target analytes from precipitation. Using this targeted approach, we managed to detect 123 pesticides with maximum retention time shifts below 0.1 min (except for DEET) in 101 precipitation samples collected between October 2015 and March 2017 in Singapore. This is probably the first study to report the measurements of a wide range of pesticides in precipitation. A spectrum of insecticides, herbicides, fungicides and their synergists were detected and among them DEET, malathion and carbaryl were the most frequently detected pesticides (detection frequency: 100%, 96% & 67%). The Spearman correlations suggest that some pesticides of different subgroups had significant correlations. It is believed that these finding could shed light on the understanding of the contribution of precipitation to environmental contaminants in water cycle.
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http://dx.doi.org/10.1016/j.chemosphere.2018.07.151DOI Listing
November 2018

Metabolite changes behind faster growth and less reproduction of Daphnia similis exposed to low-dose silver nanoparticles.

Ecotoxicol Environ Saf 2018 Nov 26;163:266-273. Epub 2018 Jul 26.

School of Environmental Science & Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

With increasing presence of silver nanoparticles (AgNPs) into the environment, the chronic and low-dose effects of AgNPs are of vital concern. This study evaluated chronic physiological effects of AgNPs on Daphnia similis, which were exposed to two ambient encountered concentrations (0.02 and 1 ppb) of AgNPs for 21 days. It was observed that the low-dose AgNPs stimulated a significant increase in average length/dry mass, but inhibited reproduction compared to control specimens. Non-targeted metabolomics based on liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-QTOFMS-MS) and gas chromatograph-quadrupole time of flight mass spectrometry (GC-QTOF-MS) were utilized to elucidate the underlying molecular mechanisms of these responses. Forty one metabolites were identified, including 18 significantly-changed metabolites, suggesting up regulation in protein digestion and absorption (amino acids, such as isoleucine, tryptophan, lysine, leucine, valine, aspartic acid, threonine, tyrosine) and down regulation of lipid related metabolism (fatty acids, such as arachidonic acid, stearidonic acid, linoelaidic acid and eicosapentaenoic acid) were key events in these responses. The increase in these amino acid contents explains the accelerated growth of D. similis from the metabolic pathway of aminoacyl-tRNA biosynthesis. Down regulation of fatty acid contents corresponds to the observed drop in the reproduction rate considering the fatty acid biological enzymatic reaction pathways. Significant changes in metabolites provided a renewed mechanistic understanding of low concentration chronic toxicity of AgNP toxicity on D. similis.
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http://dx.doi.org/10.1016/j.ecoenv.2018.07.080DOI Listing
November 2018

Detection of Lung Cancer: Concomitant Volatile Organic Compounds and Metabolomic Profiling of Six Cancer Cell Lines of Different Histological Origins.

ACS Omega 2018 May 10;3(5):5131-5140. Epub 2018 May 10.

NUSNNI-Nanocore, National University of Singapore, 5A Engineering Drive 1, 117411, Singapore.

In recent years, there has been an extensive search for a non-invasive screening technique for early detection of lung cancer. Volatile organic compound (VOC) analysis in exhaled breath is one such promising technique. This approach is based on the fact that tumor growth is accompanied by unique oncogenesis, leading to detectable changes in VOC emitting profile. Here, we conducted a comprehensive profiling of VOCs and metabolites from six different lung cancer cell lines and one normal lung cell line using mass spectrometry. The concomitant VOCs and metabolite profiling allowed significant discrimination between lung cancer and normal cell, nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC), as well as between different subtypes of NSCLC. It was found that a combination of benzaldehyde, 2-ethylhexanol, and 2,4-decadien-1-ol could serve as potential volatile biomarkers for lung cancer. A detailed correlation between nonvolatile metabolites and VOCs can demonstrate possible biochemical pathways for VOC production by the cancer cells, thus enabling further optimization of VOCs as biomarkers. These findings could eventually lead to noninvasive early detection of lung cancer and differential diagnosis of lung cancer subtypes, thus revolutionizing lung cancer treatment.
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http://dx.doi.org/10.1021/acsomega.7b02035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044508PMC
May 2018