@article {287, title = {An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Feb 03}, pages = {1280}, abstract = {

The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases.

}, keywords = {Animals, Anti-Inflammatory Agents, Colitis, Colon, Furans, Humans, Inflammation, Ligands, Male, Mice, Mice, Inbred C57BL, Pregnane X Receptor, Zingiber officinale}, issn = {2041-1723}, doi = {10.1038/s41467-025-56624-0}, author = {Wang, Xiaojuan and Zhang, Guohui and Bian, Zhiwei and Chow, Vimanda and Grimaldi, Marina and Carivenc, Coralie and Sirounian, Savannah and Li, Hao and Sladekova, Lucia and Mott, Stefano and Luperi, Yulia and Gong, Yufeng and Costello, Cait and Li, Linhao and Jachimowicz, Matthew and Guo, Miao and Hu, Shian and Wilson, Derek and Balaguer, Patrick and Bourguet, William and Mani, Sridhar and Bonati, Laura and Peng, Hui and March, John and Wang, Hongbing and Wang, Shengpeng and Krause, Henry M and Liu, Jiabao} } @article {288, title = {Fast autoxidation of unsaturated lipid films on indoor surfaces.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Feb 12}, pages = {1557}, abstract = {

Organic films containing unsaturated lipids are widespread, yet their oxidation pathways with associated impacts on contaminant lifetimes and human exposure remain poorly explored under indoor environmental conditions. This study demonstrates that UVA radiation and radical exposure drive rapid autoxidation of thin films of methyl linolenate (ML) and canola oil (which contains polyunsaturated triglycerides), primarily producing organic hydroperoxides. For ML films this fast chemistry occurs at the same rate under entirely dark, genuine indoor conditions as it does when the films are exposed to significantly higher OH radicals in a flow reactor. Both OH and organic radicals are detected within the oxidized films, propagating fast autoxidation in dark indoor environments with minimal sensitivity to the radical initiation rate. When mixed into the films, bisphenol A is hydroxylated, illustrating potential transformation pathways for toxic organic contaminants. This study uncovers insights into lipid autoxidation processes under environmental conditions and underscores their potential health impacts.

}, keywords = {Benzhydryl Compounds, Bisphenol A Compounds, Fatty Acids, Monounsaturated, Humans, Hydrogen Peroxide, Linoleic Acids, Oxidation-Reduction, Phenols, Rapeseed Oil, Surface Properties, Ultraviolet Rays}, issn = {2041-1723}, doi = {10.1038/s41467-025-56802-0}, author = {Wang, Xinke and Fahy, William D and Xie, Linna and Peng, Hui and Abbatt, Jonathan P D} } @article {130, title = {Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish () Is Prone to Aromatic Substituent Changes.}, journal = {Environ Sci Technol}, volume = {54}, year = {2020}, month = {2020 04 07}, pages = {4421-4431}, abstract = {

Brominated azo dyes (BADs) have been identified as predominant indoor brominated pollutants in daycare dust; thus, their potential health risk to children is of concern. However, the toxicities of BADs remain elusive. In this study, the toxicokinetics of two predominant BADs, Disperse Blue 373 (DB373) and Disperse Violet 93 (DV93), and their suspect metabolite 2-bromo-4,6-dinitroaniline (BDNA) was investigated in embryos of zebrafish (). The bioconcentration factor of DV93 at 120 hpf is 6.2-fold lower than that of DB373. The nontarget analysis revealed distinct metabolism routes between DB373 and DV93 by reducing nitro groups to nitroso (DB373) or amine (DV93), despite their similar structures. NAD(P)H quinone oxidoreductase 1 (NQO1) and pyruvate dehydrogenase were predicted as the enzymes responsible for the reduction of DB373 and DV93 by correlating time courses of the metabolites and enzyme development. Further in vitro recombinant enzyme and in vivo inhibition results validated NQO1 as the enzyme specifically reducing DB373, but not DV93. Global proteome profiling revealed that the expression levels of proteins from the "apoptosis-induced DNA fragmentation" pathway were significantly upregulated by all three BADs, supporting the bioactivation of BADs to mutagenic aromatic amines. This study discovered the bioactivation of BADs via distinct eukaryotic enzymes, implying their potential health risks.

}, keywords = {Animals, Azo Compounds, Child, Dust, Embryo, Nonmammalian, Humans, Mutagens, Toxicokinetics, Zebrafish}, issn = {1520-5851}, doi = {10.1021/acs.est.9b07178}, author = {Han, Jiajun and Yang, Diwen and Hall, David Ross and Liu, Jiabao and Sun, Jianxian and Gu, Wen and Tang, Song and Alharbi, Hattan A and Jones, Paul D and Krause, Henry M and Peng, Hui} } @article {129, title = {Abundances and concentrations of brominated azo dyes detected in indoor dust.}, journal = {Environ Pollut}, volume = {252}, year = {2019}, month = {2019 Sep}, pages = {784-793}, abstract = {

Dust samples were collected from four indoor environments, including childcare facilities, houses, hair salons, and a research facility from the USA and were analyzed for brominated compounds using full scan liquid chromatography high-resolution mass spectrometry. A total of 240 brominated compounds were detected in these dust samples, and elemental formulas were predicted for 120 more abundant ions. In addition to commonly detected brominated flame retardants (BFRs), nitrogen-containing brominated azo dyes (BADs) were among the most frequently detected and abundant. Specifically, greater abundances of BADs were detected in indoor dusts from daycares and salons compared to houses and the research facility. Using authentic standards, a quantitative method was established for two BADs (DB373: Disperse Blue 373 and DV93: Disperse Violet 93) and 2-bromo-4,6-dinitroaniline, a commonly used precursor in azo dye production, in indoor dust. Generally, greater concentrations of DB373 (<=3850 ng/g) and DV93 (<=1190 ng/g) were observed in indoor dust from daycares highlighting children as a susceptible population to potential health risk from exposure to BADs. These data are important because, to date, targeted analysis of brominated compounds in indoor environments has focused mainly on BFRs and appears to underestimate the total amount of brominated compounds.

}, keywords = {Air Pollution, Indoor, Aniline Compounds, Azo Compounds, Child, Child Day Care Centers, Chromatography, Liquid, Dust, Flame Retardants, Halogenated Diphenyl Ethers, Humans, Hydrocarbons, Brominated, Nitrogen, Tandem Mass Spectrometry}, issn = {1873-6424}, doi = {10.1016/j.envpol.2019.05.153}, author = {Dhungana, Birendra and Peng, Hui and Kutarna, Steven and Umbuzeiro, Gisela and Shrestha, Sujan and Liu, Jing and Jones, Paul D and Subedi, Bikram and Giesy, John P and Cobb, George P} } @article {89, title = {A rapid and sensitive fluorometric method for determination of aldehyde oxidase activity.}, journal = {Toxicol Appl Pharmacol}, volume = {341}, year = {2018}, month = {2018 02 15}, pages = {30-37}, abstract = {

Previous research has characterized the important role of aldehyde oxidases (AOX) in biotransformation of N-heterocyclic therapeutic drugs and environmental contaminants in mammals. Research pertaining to AOX activity in non-mammalian vertebrates, however, is scarce, despite its biological role as a potentially important metabolic pathway for xenobiotics. One of the limiting factors of research on AOX is that available photometric methods are relatively insensitive, limited in throughput, and prone to cross-reactivity from other enzymes. Therefore, this study aimed to develop a novel and improved fluorometric AOX assay. This assay is based on the conversion of the exogenous aldehyde substrate 4-(dimethyl)amino cinnamaldehyde to its corresponding fluorescent acid by AOX, and was evaluated using partially purified hepatic cytosol from rat, human, and rainbow trout. Purification of native cytosol by heat treatment and ammonium sulfate precipitation resulted in increased specific activity of AOX. Michaelis-Menten kinetic parameters (Kand V) were comparable to values previously generated by photometric methods. Furthermore, effects of the inhibitor hydralazine on AOX activity revealed half maximal inhibitory concentrations comparable to those generated using conventional methods. Product identity was confirmed by liquid chromatography and mass spectrometry. In summary, this study successfully developed a rapid and sensitive assay for determination of AOX activity in across different vertebrate species that is 4- to 10-fold more sensitive compared to conventional absorbance-based methods. It can be applied in environmental, toxicological, and pharmacological studies relating to identification of AOX substrates, as well as the induction of AOX expression through drugs and environmental contaminants.

}, keywords = {Aldehyde Oxidase, Animals, Chromatography, Liquid, Dose-Response Relationship, Drug, Enzyme Activation, Enzyme Inhibitors, Fluorometry, Humans, Hydralazine, Mass Spectrometry, Oncorhynchus mykiss, Rats, Time Factors}, issn = {1096-0333}, doi = {10.1016/j.taap.2018.01.006}, author = {Apenova, Nancy and Peng, Hui and Hecker, Markus and Brinkmann, Markus} } @article {92, title = {Hydroxylated 2-Ethylhexyl tetrabromobenzoate isomers in house dust and their agonistic potencies with several nuclear receptors.}, journal = {Environ Pollut}, volume = {227}, year = {2017}, month = {2017 Aug}, pages = {578-586}, abstract = {

In the current study, by combining ultra-high resolution (UHR) MS spectra, MS spectra, and derivatization, three hydroxylated isomers of 2-ethylhexyl tetrabromobenzoate (OH-TBB) were identified in Firemaster 550 and BZ-54 technical products. Also, a new LC-UHRMS method, using atmospheric pressure chemical ionization (APCI), was developed for simultaneous analysis of OH-TBB, TBB, hydroxylated bis(2-ethylhexyl)-tetrabromophthalate (OH-TBPH) and TBPH in 23 samples of dust collected from houses in Saskatoon, SK, Canada. OH-TBBs were detected in 91\% of samples, with a geometric mean concentration of 0.21\ ng/g, which was slightly less than those of OH-TBPH (0.35\ ng/g). TBB was detected in 100\% of samples of dust with a geometric mean concentration of 992\ ng/g. Significant (p\ \<\ 0.001) log-linear relationships between concentrations of OH-TBBs, TBB, or OH-TBPHs and TBPH in dust support the hypothesis of a common source of these compounds. OH-TBBs were found to be strong agonists of peroxisome proliferator-activated receptor gamma (PPARγ) and weaker agonists of the estrogen receptor (ER), but no agonistic potencies was observed with the androgen receptor (AR). Occurrence of OH-TBBs in technical products and house dust, together with their relatively strong PPARγ potencies, indicated their potential risk to health of humans.

}, keywords = {Air Pollution, Indoor, Bromobenzoates, Canada, Dust, Environmental Monitoring, Flame Retardants, Halogenated Diphenyl Ethers, Humans}, issn = {1873-6424}, doi = {10.1016/j.envpol.2017.04.094}, author = {Peng, Hui and Sun, Jianxian and Saunders, David M V and Codling, Garry and Wiseman, Steve and Jones, Paul D and Giesy, John P} } @article {90, title = {Mass spectrometry methods to study protein-metabolite interactions.}, journal = {Expert Opin Drug Discov}, volume = {12}, year = {2017}, month = {2017 12}, pages = {1271-1280}, abstract = {

INTRODUCTION: To ​​​​understand and manipulate biochemical processes and signaling pathways, the knowledge of endogenous protein-metabolite interactions would be extremely helpful. Recent developments in precision mass spectrometry, high-throughput proteomics and sensitive metabolomic profiling are beginning to converge on a possible solution, heralding a new era of global metabolome-proteome {\textquoteright}interactome{\textquoteright} studies that promise to change biomedical research and drug discovery. Areas covered: Here, we review innovative mass spectrometry-based methods and recent pioneering studies aimed at elucidating the physical associations of small molecule ligands with cellular proteins. The technologies covered belong to two main categories: tag-based and tag-free methods. We emphasize the latter in this review, and outline promising experimental workflows and key data analysis considerations involved. Expert opinion: Recent ground-breaking advances in chemical-proteomics technology and allied computational methods now make the global detection of protein-ligand engagement an increasingly attractive research problem. Despite ongoing challenges, rapid progress in the field is expected these coming next few years, leading to a refreshed systems biology research paradigm and much needed new opportunities for improving sparse drug discovery pipelines.

}, keywords = {Biomedical Research, Drug Discovery, High-Throughput Screening Assays, Humans, Ligands, Mass Spectrometry, Metabolome, Metabolomics, Proteins, Proteome, Proteomics, Systems Biology}, issn = {1746-045X}, doi = {10.1080/17460441.2017.1378178}, author = {Guo, Hongbo and Peng, Hui and Emili, Andrew} } @article {102, title = {Ubiquitous Occurrence of Fluorotelomer Alcohols in Eco-Friendly Paper-Made Food-Contact Materials and Their Implication for Human Exposure.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 Jan 19}, pages = {942-50}, abstract = {

The occurrence of fluorotelomer alcohols (FTOHs) was investigated in 94 food-contact materials (FCMs). We detected 6:2 FTOH (\<0.60-1110 ng/g), 8:2 FTOH (\<0.40-8490 ng/g), and 10:2 FTOH (\<0.02-9350 ng/g) in most FCM samples, and four longer-chain C14-20 FTOHs were, for the first time, identified in FCMs with relatively high concentrations (\<0.02-8450 ng/g for 12:2 FTOH, \<0.02-1640 ng/g for 14:2 FTOH, \<0.02-372 ng/g for 16:2 FTOH, and \<0.02-130 ng/g for 18:2 FTOH). There were three typical profiles of FTOHs that were dominated by 6:2 FTOH (95.6 {\textpm} 8.1\% in 9 FCMs), 8:2 FTOH (50.9 {\textpm} 20.8\% in 22 FCMs), and 10:2 FTOH (44.5 {\textpm} 20.9\% in 30 FCMs), indicating the congener-specific usage of FTOHs for different commercial purposes. All nine detectable FCMs produced in the United States were dominated by 6:2 FTOH, which was significantly different from those produced in China. The median concentration of total FTOHs in eco-friendly paper tableware was 2990 ng/g, which was lower than in popcorn bags (18 200 ng/g) but much higher than other FCMs (\<0.55-38.7 ng/g). FTOHs could migrate from paper bowls, with migration efficiencies of 0.004-0.24\% into water, 0.004-0.24\% into 10\% ethanol, 0.009-2.79\% into 30\% ethanol, 0.06-13.0\% into 50\% ethanol (v/v) simulants, and 0.04-2.28\% into oil. Migration efficiencies decreased with increasing carbon chain lengths of FTOHs.

}, keywords = {Alcohols, Biodegradation, Environmental, Fluorocarbons, Food Contamination, Food Packaging, Humans, Paper}, issn = {1520-5851}, doi = {10.1021/acs.est.5b03806}, author = {Yuan, Guanxiang and Peng, Hui and Huang, Chong and Hu, Jianying} } @article {106, title = {Levels of Phthalate Metabolites in Urine of Pregnant Women and Risk of Clinical Pregnancy Loss.}, journal = {Environ Sci Technol}, volume = {49}, year = {2015}, month = {2015 Sep 01}, pages = {10651-7}, abstract = {

Toxicological studies have shown that phthalate esters (PAEs), a class of widely used and environmentally prevalent chemicals, can increase the abortion rate in animals, but epidemiological evidence is scarce. This study aimed to explore the relationship between the urinary concentration of phthalate metabolites and the risk of clinical pregnancy loss. A total of 132 women who underwent clinical pregnancy loss (cases) and 172 healthy pregnant women (controls) were recruited from Beijing, China. Eight phthalate metabolites in urine were determined by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono(2-ethlyhexyl) phthalate (MEHP), were detected in at least 95\% of the urine samples, with the highest median concentration of 51.0 μg/g of creatinine for MnBP of all participants. The differences in urinary concentrations of phthalate metabolites between cases and controls were evaluated using the Mann-Whitney U test. The concentrations of MEP (median of 18.7 μg/g of creatinine), MiBP (23.3 μg/g of creatinine), and MnBP (58.2 μg/g of creatinine) detected in the cases were significantly higher than those (15.7 μg/g of creatinine for MEP, 19.4 μg/g of creatinine for MiBP, and 43.9 μg/g of creatinine for MnBP) in the controls (p \< 0.05). Increasing risks of clinical pregnancy loss were observed from the first to fourth quartiles of the MEP, MiBP, and MnBP concentrations (p \< 0.05 for trend). We concluded that exposure to MEP, MiBP, and MnBP was associated with an increased risk of clinical pregnancy loss.

}, keywords = {Adult, Beijing, Case-Control Studies, Embryo Loss, Environmental Monitoring, Esters, Female, Humans, Metabolome, Middle Aged, Odds Ratio, Phthalic Acids, Pregnancy, Risk Factors, Young Adult}, issn = {1520-5851}, doi = {10.1021/acs.est.5b02617}, author = {Mu, Di and Gao, Fumei and Fan, Zhanlan and Shen, Huan and Peng, Hui and Hu, Jianying} } @article {113, title = {High-density lipoprotein of patients with type 2 diabetes mellitus upregulates cyclooxgenase-2 expression and prostacyclin I-2 release in endothelial cells: relationship with HDL-associated sphingosine-1-phosphate.}, journal = {Cardiovasc Diabetol}, volume = {12}, year = {2013}, month = {2013 Jan 30}, pages = {27}, abstract = {

BACKGROUND: Dysfunctional high-density lipoprotein (HDL) may have pro-inflammatory effects on the endothelial cells,which causes atherosclerosis in type 2 diabetes mellitus (T2DM). HDL is a major carrier of sphingosine-1-phosphate (S1P) in plasma while S1P exhibits multiple biological activities. However, potential role of HDL and S1P in T2DM remains unexplored. We hypothesized that diabetic HDL with higher contents of S1P exerts beneficial effects on the vascular system.

METHODS: Subjects with T2DM with or without proved large arteries atherosclerosis and normal controls (n=15 for each group) were recruited in the present study. HDL was isolated from the subjects by ultracentrifugation. The levels of HDL-associated S1P were determined by UPLC-MS/MS. The protective function of diabetic HDL and S1P was evaluated by measuring cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release by human umbilical vein endothelial cells (HUVECs) using western blot and enzyme-linked immunosorbent assay (ELISA), respectively.

RESULTS: The S1P levels in isolated HDL were significantly increased in T2DM subjects compared with controls (235.6 {\textpm} 13.4 vs 195.0 {\textpm} 6.4 ng/mg, P\< 0.05). The diabetic HDL exerted greater protective effects on inducing COX-2 expression and PGI-2 release by HUVECs than those of control HDL (p \< 0.05, p \< 0.01, respectively). Pertussis toxin, a common inhibitor of G-couple protein receptors, and VPC 23019, an antagonist of S1P receptor 1 and 3 significantly attenuated HDL-induced COX-2 expression and PGI-2 release.

CONCLUSIONS: Diabetic HDL carries higher level of S1P compared with normal HDL, which has the potential to contribute to protective effects on endothelial cells by inducing COX-2 expression and PGI-2 release. These findings provide a new insight of S1P function in T2DM patients, possibly leading to a new therapeutic target.

}, keywords = {Adult, Aged, Cells, Cultured, Cyclooxygenase 2, Diabetes Mellitus, Type 2, Endothelial Cells, Epoprostenol, Female, Gene Expression Regulation, Enzymologic, Human Umbilical Vein Endothelial Cells, Humans, Lipoproteins, HDL, Lysophospholipids, Male, Middle Aged, Sphingosine, Up-Regulation}, issn = {1475-2840}, doi = {10.1186/1475-2840-12-27}, author = {Tong, Xunliang and Peng, Hui and Liu, Donghui and Ji, Liang and Niu, Chenguang and Ren, Jun and Pan, Bing and Hu, Jianying and Zheng, Lemin and Huang, Yining} } @article {117, title = {Occurrence and source apportionment of sulfonamides and their metabolites in Liaodong Bay and the adjacent Liao River basin, North China.}, journal = {Environ Toxicol Chem}, volume = {30}, year = {2011}, month = {2011 Jun}, pages = {1252-60}, abstract = {

The presence of antibiotics in the environment is of great concern because of their potential for resistance selection among pathogens. In the present study we investigated the occurrence of 19 sulfonamides, five N-acetylated sulfonamide metabolites, and trimethoprim in the Liao River basin and adjacent Liaodong Bay, China, as well as 10 human/agricultural source samples. Within the 35 river samples, 12 sulfonamides, four acetylated sulfonamides, and trimethoprim were detected, with the dominant being sulfamethoxazole (66.6 ng/L), N-acetylsulfamethoxazole (63.1 ng/L), trimethoprim (29.0 ng/L), sulfadiazine (14.0 ng/L), and sulfamonomethoxine (8.4 ng/L); within the 36 marine samples, 10 chemicals were detected, with the main contributions from sulfamethoxazole (25.2 ng/L) and N-acetylsulfamethoxazole (28.6 ng/L). Sulfamethoxazole (25.9\%), N-acetylsulfamethoxazole (46.6\%), trimethoprim (22.9\%), and sulfapyridine (1.4\%) were the main chemicals from human sources, while sulfamonomethoxine, sulfamethazine, sulfaquinoxaline, sulfaguanidine, sulfadiazine, sulfanilamide, and sulfamethoxypyridazine were dominant in the animal husbandry sources, specifically, swine and poultry farms, and sulfamethoxazole (91\%) was dominant in the mariculture source. A principal component analysis with multiple linear regression was performed to evaluate the source apportionment of total sulfonamides in Liaodong Bay. It was found that animal husbandry contributed 15.2\% of total sulfonamides, while human sources contributed 28.5\%, and combined human and mariculture sources contributed 56.3\%. In addition, the mariculture contribution was 24.1\% of total sulfonamides into the sea based on mass flux estimation. The present study is the first report that the environmental levels of sulfonamide metabolites were comparable to the corresponding parents; therefore, we should pay attention to their environmental occurrence. Source apportionment showed human discharge (60.7\%) significantly contributed to these antibiotics in Liaodong Bay, which provides important information for environmental management.

}, keywords = {Agriculture, Anti-Bacterial Agents, Aquaculture, China, Environmental Monitoring, Humans, Linear Models, Principal Component Analysis, Rivers, Seawater, Spectrometry, Mass, Electrospray Ionization, Sulfamethazine, Sulfamethoxazole, Sulfamethoxypyridazine, Sulfamonomethoxine, Sulfapyridine, Sulfaquinoxaline, Sulfonamides, Tandem Mass Spectrometry, Trimethoprim, Water Pollutants, Chemical, Water Pollution, Chemical}, issn = {1552-8618}, doi = {10.1002/etc.508}, author = {Jia, Ai and Hu, Jianying and Wu, Xiaoqin and Peng, Hui and Wu, Shimin and Dong, Zhaomin} }