Publications by authors named "Lianxian Guo"

8 Publications

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Triphenyl phosphate disturbs the lipidome and induces endoplasmic reticulum stress and apoptosis in JEG-3 cells.

Chemosphere 2021 Feb 15;275:129978. Epub 2021 Feb 15.

School of Public Health, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, Guangdong, 523-808, China. Electronic address:

Triphenyl phosphate (TPP) is a frequently used aryl organophosphate flame retardant. Epidemiological studies have shown that TPP and its metabolite diphenyl phosphate (DPP) can accumulate in the placenta, and positively correlated with abnormal birth outcomes. TPP can disturb placental hormone secretion through the peroxisome proliferator-activated receptor γ (PPARγ) pathway. However, the extent and mechanism of placental toxicity mediation by TPP remains unknown. In this study, we used JEG-3 cells to investigate the role of PPARγ-regulated lipid metabolism in TPP-mediated placental toxicity. The results of lipidomic analysis showed that TPP increased the production of triglycerides (TG), fatty acids (FAs), and phosphatidic acid (PA), but decreased the levels of phosphatidylethanol (PE), phosphatidylserine (PS), and sphingomyelin (SM). TG accumulation was accompanied by increased levels of sterol regulatory element binding transcription factor 1 (SREBP1), acetyl-coA carboxylase (ACC), and fatty acid transport protein (CD36). Although PPARγ and its target CCAAT/enhancer binding proteins (C/EBPα) was decreased, the TG content and gene expression of SREBP1, ACC, and CD36 decreased when TPP was co-exposed to the PPARγ antagonist GW9662. TPP also induced inflammatory responses, endoplasmic reticulum stress (ERS), and cell apoptosis. Expression of genes related to ERS and apoptosis were attenuated by GW9662. Together, these results show that TPP can disturb lipid metabolism and cause lipid accumulation through PPARγ, induce ERS, and cell apoptosis. Our findings reveal that the developmental toxicity of TPP through placental toxicity should not be ignored.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129978DOI Listing
February 2021

The mycobiome in murine intestine is more perturbed by food arsenic exposure than in excreted feces.

Sci Total Environ 2021 Jan 21;753:141871. Epub 2020 Aug 21.

Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China. Electronic address:

Arsenic is a global pollutant that can accumulate in rice and has been confirmed to disturb the gut microbiome. By contrast, the influence on the gut mycobiome is seldom concerned because fungi comprise a numerically small proportion of the whole gut microcommunity. To expand the detection of the mycobiome in different gut sections of mammals and investigate the influence of food arsenic on the gut mycobiome in the digestive tract, we treated mice with feeds containing different compositions of arsenic species (7.3% sodium arsenate, 72.7% sodium arsenite, 1.0% sodium monomethylarsonate, and 19.0% sodium dimethylarsinate) in rice at a total arsenic dose of 30 mg/kg. After 60 days of exposure, the feces of four different sites, the ileum, cecum, colon, and excreted feces, were collected and analyzed by internal transcribed spacer gene sequencing. Among the samples, the major fungal phyla were Ascomycota, Basidiomycota, and Zygomycota; the top 10 fungal genera were Aspergillus, Verticillium, Penicillium, Cladosporium, Alternaria, Fusarium, Ophiocordyceps, Trametes, Mucor, and Nigrospora. In control mice, along the murine digestive tract, the mycobial richness and composition were significantly changed; Aspergillus and Penicillium possessed the higher ability to be stabilized in the murine gut, and larger proportions of positive correlations were observed among the major fungi. After arsenic exposure, the fungal composition was more disturbed in the intestinal tract than in feces. Along the digestive tract, arsenic can trigger larger mycobial variations, and the sensitivities of major fungi to arsenic were changed. Thus, the murine intestinal spatial mycobiota are more perturbed than excreted fecal mycobiota after food arsenic exposure. Feces are insufficient to be selected as a representative of the gut mycobiota in arsenic exposure studies.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141871DOI Listing
January 2021

Determination of arsenicals in mouse tissues after simulated exposure to arsenic from rice for sixteen weeks and the effects on histopathological features.

Ecotoxicol Environ Saf 2020 Sep 26;200:110742. Epub 2020 May 26.

Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, China. Electronic address:

The accumulation of arsenic in rice has become a worldwide concern. In this study, dose-dependency in tissues (intestine, liver and kidney) and blood distribution of inorganic arsenicals and their methylated metabolites were investigated in male C57BL/6 mice exposed to four arsenic species (arsenite [iAs], arsenate [iAs], monomethylarsonate [MMA], and dimethylarsinate [DMA]) at four doses (control [C]: 0 μg/g, simulation [S]: 0.91 μg/g, medium [M]: 9.1 μg/g and high [H]: 30 μg/g) according to the arsenical composition in rice for 8 and 16 weeks. No adverse effects were observed, while body weight gain decreased in group H. Increases in total arsenic concentrations (C) and histopathological changes in the tissues occurred in all of the test groups. C presented a tendency of kidney > intestine > liver > blood and were time-/dose-dependent in the liver and kidney in groups M and H. In the intestine and blood, abundant iAs (23%-28% in blood and 36%-49% in intestine) was detected in groups M and H, and C decreased in group H from the 8th week to the 16th week. PMI decreased in the liver and SMI decreased in the kidney. These results indicate that the three tissues are injured through food arsenic. The intestine can also accumulate food arsenic, and the high arsenic dose will cause a deficiency in the absorbing function of the intestine. Thus, long-term exposure to arsenic-contaminated rice should be taken seriously attention.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110742DOI Listing
September 2020

Triphenyl phosphate permeates the blood brain barrier and induces neurotoxicity in mouse brain.

Chemosphere 2020 Aug 16;252:126470. Epub 2020 Mar 16.

School of Public Health, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, Guangdong, 523-808, China. Electronic address:

Concerns have been raised over the neurotoxicity of triphenyl phosphate (TPP), but there have been few studies of the neurotoxic effects of TPP on mammals and the underlying mechanisms. In this study, weaned male mice (C57/BL6) were used and exposed to 0, 50, or 150 mg/kg TPP daily by oral gavage for 30 days. The blood brain barrier (BBB) permeability of TPP and its metabolite diphenyl phosphate (DPP) in the brain, and TPP induced metabolomic and transcriptomic changes of the brain were investigated. The results showed that TPP and DPP can cross the BBB of mice. Histopathological examination of the brain revealed abnormalities in the hippocampus, cortex and thalamus, and mice treated with high doses showed a potential inflammation in the thalamus and hippocampus. Untargeted metabolomic results revealed that the changed level of glutamic acid, N-acetyl CoA metabolites, and organic acid in the brain of treated mice, suggest that amino acid and lipid metabolism was interfered. RNA-seq data indicated that neuronal transcription processes and cell apoptosis pathway (forkhead box (FOXO), and mitogen-activated protein kinase (MAPK) signaling pathways) were significantly affected by TPP exposure. RT-PCR showed proinflammation cytokine tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6)) levels were increased, while antioxidant genes including nuclear factor-E2-related factor 2 (Nrf2), heme oxygenase1 (HO-1) and superoxide dismutase (SOD1) decreased. These results suggest that TPP could cause a degree of neurotoxicity by inducing neuroinflammation and neuronal apoptosis, which are related to oxidative stress. The potential implications for neurophysiology and behavioral regulation cannot be ignored.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126470DOI Listing
August 2020

Arsenic concentrations, diversity and co-occurrence patterns of bacterial and fungal communities in the feces of mice under sub-chronic arsenic exposure through food.

Environ Int 2020 05 28;138:105600. Epub 2020 Feb 28.

Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China. Electronic address:

Background: Arsenic, a global pollutant and a threshold-free primary carcinogen, can accumulate in rice. Previous studies have focused on arsenic poisoning in drinking water and the effects on gut microbes. The research on arseniasis through food, which involves the bio-transformation of arsenic, and the related changes in gut microbiome is insufficient.

Method: Mice were exposed from animal feed prepared with four arsenic species (iAs, iAs, MMA, and DMA) at a dose of 30 mg/kg according to the arsenic species proportion in rice for 30 days and 60 days. The levels of total arsenic (tAs) and arsenic species in mice feces and urine samples were determined using ICP-MS and HPLC-ICP-MS, respectively. 16S rRNA and ITS gene sequencing were conducted on microbial DNA extracted from the feces samples.

Results: At 30 days and 60 days exposure, the tAs levels excreted from urine were 0.0092 and 0.0093 mg/day, and tAs levels in feces were 0.0441 and 0.0409 mg/day, respectively. We found significant differences in arsenic species distribution in urine and feces (p < 0.05). In urine, the predominant arsenic species were iAs (23% and 14%, respectively), DMA (55% and 70%, respectively), and uAs (unknown arsenic, 14% and 10%, respectively). In feces, the proportion of major arsenic species (iAs, 26% and 21%; iAs, 16% and 15%; MMA, 14% and 14%; DMA, 19% and 19%; and uAs, 22% and 29%, respectively) were evenly distributed. Microbiological analysis (MRPP test, α- and β-diversities) showed that diversity of gut bacteria was significantly related to arsenic exposure through food, but diversity of gut fungi is less affected. Manhattan plot and LEfSe analysis showed that arsenic exposure significantly changes microbial taxa, which might be directly associated with arsenic metabolism and diseases mediated by arsenic exposure, such as Deltaproteobacteria, Polynucleobacter, Saccharomyces, Candida, Amanitaceae, and Fusarium. Network analysis was used to identify the changing hub taxa in feces along with arsenic exposure. Function predicting analysis indicated that arsenic exposure might also significantly increase differential metabolic pathways and would disturb carbohydrates, lipid, and amino acids metabolism of gut bacteria.

Conclusions: The results demonstrate that subchronic arsenic exposure via food significantly changes the gut microbiome, and the toxicity of arsenic in food, especially in staples, should be comprehensively evaluated in terms of the disturbance of microbiome, and feces might be the main pathway through which arsenic from food exposure is excreted and bio-transformed, providing a new insight into the investigation of bio-detoxification for arseniasis.
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http://dx.doi.org/10.1016/j.envint.2020.105600DOI Listing
May 2020

Internal and External Microbial Community of the Moth, the Host of .

Microorganisms 2019 Oct 31;7(11). Epub 2019 Oct 31.

Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.

is a widely known medicinal entomogenous fungus, which parasitizes the soil-borne larva of Thitarodes (Hepialidae, Lepidoptera) distributed in the Qinghai-Tibetan Plateau and its adjacent areas. Previous research has involved artificial cultivation of Chinese cordyceps (the fungus-caterpillar complex), but it is difficult to achieve large-scale cultivation because the coupling relation between the crucial microbes and their hosts is not quite clear. To clarify the influence of the internal microbial community on the occurrence of Chinese cordyceps, in this study, the unfertilized eggs of Thitarodes of different sampling sites were chosen to analyze the bacterial and fungal communities via 16S rRNA and ITS sequencing for the first time. The results showed that for bacteria, 348 genera (dominant genera include Wolbachia, Spiroplasma, Carnobacterium, Sphingobium, and Acinetobacter) belonging to 26 phyla (dominant phyla include Proteobacteria, Firmicutes, Tenericutes, Actinobacteria, Acidobacteria, and Bacteroidetes), 58 classes, 84 orders, and 120 families were identified from 1294 operational taxonomic units (OTUs). The dominant bacterial genus (Spiroplasma) may be an important bacterial factor promoting the occurrence of Chinese cordyceps. For fungi, 289 genera, mainly including , , and , were identified, and they belonged to 5 phyla (Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota, and Zygomycota), 26 classes, 82 orders, and 165 families. Eight bacterial OTUs and 12 fungal OTUs were shared among all of the detected samples and were considered as core species. Among them, Wolbachia, Spiroplasma, , , and may play important roles in helping the host larva to digest foods, adapt to extreme environments, or resist pathogens. On the other hand, the external (soil) microbial community was synchronously and comparatively analyzed. Comparative analysis revealed that external microbial factors might play a more significant role in the occurrence of Chinese cordyceps, owing to the significant differences revealed by α-diversity and β-diversity analyses among different groups. In summary, the results of this study may contribute to the large-scale cultivation of Chinese cordyceps.
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http://dx.doi.org/10.3390/microorganisms7110517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920881PMC
October 2019

A molecular dynamics study of the complete binding process of meropenem to New Delhi metallo-β-lactamase 1.

Phys Chem Chem Phys 2018 Feb;20(9):6409-6420

Department of Microbiology and Immunology of Guangdong Medical University, No. 2 West Wenming Road, Zhanjiang City, Guangdong Province 524023, China.

The mechanism of substrate hydrolysis of New Delhi metallo-β-lactamase 1 (NDM-1) has been reported, but the process in which NDM-1 captures and transports the substrate into its active center remains unknown. In this study, we investigated the process of the substrate entry into the NDM-1 activity center through long unguided molecular dynamics simulations using meropenem as the substrate. A total of 550 individual simulations were performed, each of which for 200 ns, and 110 of them showed enzyme-substrate binding events. The results reveal three categories of relatively persistent and noteworthy enzyme-substrate binding configurations, which we call configurations A, B, and C. We performed binding free energy calculations of the enzyme-substrate complexes of different configurations using the molecular mechanics Poisson-Boltzmann surface area method. The role of each residue of the active site in binding the substrate was investigated using energy decomposition analysis. The simulated trajectories provide a continuous atomic-level view of the entire binding process, revealing potentially valuable regions where the enzyme and the substrate interact persistently and five possible pathways of the substrate entering into the active center, which were validated using well-tempered metadynamics. These findings provide important insights into the binding mechanism of meropenem to NDM-1, which may provide new prospects for the design of novel metallo-β-lactamase inhibitors and enzyme-resistant antibiotics.
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http://dx.doi.org/10.1039/c7cp07459jDOI Listing
February 2018

A graphene tip coupled with liquid chromatography tandem mass spectrometry for the determination of four synthetic adulterants in slimming supplements.

Food Chem 2017 Jun 28;224:329-334. Epub 2016 Dec 28.

Institute of Seafood, Zhejiang Gongshang University, Hangzhou, China. Electronic address:

Slimming supplements were popularly sold online driven by the increasement of obesity and the development of social networking platform. However, events of drug abuse in slimming supplements were also frequently reported. In this study, a graphene tip solid-phase extraction (Gtip SPE) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established for determining fenfluramine, phenolphthalein, bumetanide, and sibutramine in slimming supplements. It was validated in terms of linearity (0.9985-0.9995), LOD (1.8ngmL), LOQ (5.6ngmL), intra-day precision (<5.1%), inter-day precision (<7.3%), and recovery (82.9-95.2%). Sibutramine is the most commonly used drug, which was detected in Bihais, Galong, and Aolist, with content 12.4, 3.6, 20.3mgg, respectively. Phenolphthalein was also found with content lower than 5.2mgg. The successful application of Gtip SPE and UPLC-MS/MS method indicated its advantage in analyzing low level of contaminates resulted from violation of regulation.
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http://dx.doi.org/10.1016/j.foodchem.2016.12.091DOI Listing
June 2017