DSpace Repository :: Browsing by Author "Duan, J."

Browsing by Author "Duan, J."

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1H NMR-based metabolomics study on repeat dose toxicity of fine particulate matter in rats after intratracheal instillation
(Elsevier, 2017-07) Zhang, Y.; Hu, H.; Shi, Y.; Yang, X.; Cao, L.; Wu, J.; Asweto, Collins O.; Feng, L.; Duan, J.; Sun, Z.
Systemic metabolic effects and toxicity mechanisms of ambient fine particulate matter (PM2.5) remain uncertain. In order to investigate the mechanisms in PM2.5 toxicity, we explored the endogenous metabolic changes and possible influenced metabolic pathways in rats after intratracheal instillation of PM2.5 by using a 1H nuclear magnetic resonance (NMR)-based metabolomics approach. Liver and kidney histopathology examinations were also performed. Chemical characterization demonstrated that PM2.5 was a complex mixture of elements. Histopathology showed cellular edema in liver and glomerulus atrophy of the PM2.5 treated rats. We systematically analyzed the metabolites changes of serum and urine in rats using 1H NMR techniques in combination with multivariate statistical analysis. Significantly reduced levels of lactate, alanine, dimethylglycine, creatine, glycine and histidine in serum, together with increased levels of citrate, arginine, hippurate, allantoin and decreased levels of allthreonine, lactate, alanine, acetate, succinate, trimethylamine, formate in urine were observed of PM2.5 treated rats. The mainly affected metabolic pathways by PM2.5 were glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, citrate cycle (TCA cycle), nitrogen metabolism and methane metabolism. Our study provided important information on assessing the toxicity of PM2.5 and demonstrated that metabolomics approach can be employed as a tool to understand the toxicity mechanism of complicated environmental pollutants.
Cellular pathways involved in silica nanoparticles induced apoptosis: A systematic review of in vitro studies.
(Elsevier, 2017-12) Asweto, Collins O.; Wu, J.; Alzain, M. A.; Hu, H.; Andrea, S.; Feng, L.; Yeng, X.; Duan, J.; Sun, Z.
Silica nanoparticles (SiNPs) have been found to pass through biological barriers and get distributed in the human body. They induce cell apoptosis via various mechanisms in body organs. To understand these mechanisms, we carried out systematic review of in vitro studies on SiNPs-induced cell apoptosis. Office of Health Assessment and Translation approach for Systematic Review and Evidence Integration was used to identify 14 studies dating from the year 2000 to current. Four studies showed an increase in DNA damage, cell cycle arrest, proapoptotic factors and decrease in antiapoptotic factors resulting to apoptosis. Eight studies showed induction of mitochondrial dysfunction, Bax upregulation, Bcl-2 downregulation, and caspase-3, -7, -9 activities increase. Increase in FADD, TNFR1 and Bid proteins was observed in one study, while the other NO production and caspase-3 activity was increased. These studies found the potency of SiNPs to induce cell apoptosis through DNA damage, mitochondrial, tumor necrosis factor, and nitric oxide related pathways.
Co-exposure to amorphous silica nanoparticles and benzo[a]pyrene at low level in human bronchial epithelial BEAS-2B cells
(SpringerLink, 2016-11) Wu, J.; Shi, Y.; Asweto, Collins O.; Lin, F.; Xiaozhe, Y.; Zhang, Y.; Duan, J.; Sun, Z.
Both ultrafine particles (UFP) and polycyclic aromatic hydrocarbons (PAHs) are widely present in the environment, thus increasing their chances of exposure to human in the daily life. However, the study on the combined toxicity of UFP and PAHs on respiratory system is still limited. In this study, we examined the potential interactive effects of silica nanoparticles (SiNPs) and benzo[a]pyrene (B[a]P) in bronchial epithelial cells (BEAS-2B). Cells were exposed to SiNPs and B[a]P alone or in combination for 24 h. Co-exposure to SiNPs and B[a]P enhanced the malondialdehyde (MDA) contents and reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities significantly, while the reactive oxygen species (ROS) generation had a slight increase in the exposed groups compared to the control but not statistically significant. Cell cycle arrest induced by the co-exposure showed a significant percentage increase in G2/M phase cells and a decrease in G0/G1 phase cells. In addition, there was a significant increase in BEAS-2B cells multinucleation as well as DNA damage. Cellular apoptosis was markedly increased even at the low-level co-exposure. Our results suggest that co-exposure to SiNPs and B[a]P exerts synergistic and additive cytotoxic and genotoxic effects.
Comprehensive gene and microRNA expression profiling on cardiovascular system in zebrafish co exposured of SiNPs and MeHg
(Elsevier, 2017-12) Hu, H.; Shi, Y.; Zhang, Y.; Wu, J.; Asweto, Collins O.; Feng, L.; Yang, X.; Duan, J.; Sun, Z.
Air pollution has been shown to increase cardiovascular diseases. However, little attention has been paid to the combined effects of PM and air pollutants on the cardiovascular system. To explore this, a high-throughput sequencing technology was used to determine combined effects of silica nanoparticles (SiNPs) and MeHg in zebrafish. Our study demonstrated that SiNPs and MeHg co-exposure could cause significant changes in mRNA and miRNA expression patterns in zebrafish. The differentially expressed (DE) genes in profiles 17 and 26 of STC analysis suggest that SiNPs and MeHg co-exposure had more proinflammatory and cardiovascular toxicity in zebrafish than single exposure. Major gene functions associated with cardiovascular system in the co-exposed zebrafish were discerned from the dynamic-gene-network, including stxbp1a, celf4, ahr1b and bai2. In addition, the prominently expressed pathway of cardiac muscle contraction was targeted by 3 DE miRNAs identified by the miRNA-pathway-network (dre-miR-7147, dre-miR-26a and dre-miR-375), which included 23 DE genes. This study presents a global view of the combined SiNPs and MeHg toxicity on the dynamic expression of both mRNAs and miRNAs in zebrafish, and could serve as fundamental research clues for future studies, especially on cardiovascular system toxicity.
Fine particle matters induce DNA damage and G2/M cell cycle arrest in human bronchial epithelial BEAS-2B cells
(SpringerLink, 2017-11) Wu, J.; Shi, Y.; Asweto, Collins O.; Feng, L.; Yang, X.; Zhang, Y.; Hu, H.; Duan, J.; Sun, Z.
There is compelling evidence that exposure to particulate matter (PM) is linked to lung tumorigenesis. However, there is not enough experimental evidence to support the specific mechanisms of PM2.5-induced DNA damage and cell cycle arrest in lung tumorigenesis. In this study, we investigated the toxic effects and molecular mechanisms of PM2.5 on bronchial epithelial (BEAS-2B) cells. PM2.5 exposure reduced cell viability and enhanced LDH activity. The cell growth curves of BEAS-2B cells decreased gradually with the increase in PM2.5 dosage. A significant increase in MDA content and a decrease in GSH-Px activity were observed. The generation of ROS was enhanced obviously, while apoptosis increased in BEAS-2B cells exposed to PM2.5 for 24 h. DNA damage was found to be more severe in the exposed groups compared with the control. For in-depth study, we have demonstrated that PM2.5 stimulated the activation of HER2/ErbB2 while significantly upregulating the expression of Ras/GADPH, p-BRAF/BRAF, p-MEK/MEK, p-ERK/ERK, and c-Myc/GADPH in a dose-dependent manner. In summary, we suggested that exposure to PM2.5 sustained the activation of HER2/ErbB2, which in turn promoted the activation of the Ras/Raf/MAPK pathway and the expression of the downstream target c-Myc. The overexpression of c-Myc may lead to G2/M arrest and aggravate the DNA damage and apoptosis in BEAS-2B after exposure to PM2.5.
Fine particulate matter induces vascular endothelial activation 4 via IL-6 dependent JAK1/STAT3 signaling pathway. Toxicol.
(2016-04) Hu, H.; Wu, J.; Li, Q.; Asweto, Collins O.; Lin, F.; Xiaozhe, Y.; Duan, F.; Duan, J.; Sun, Z.
Exposure to PM2.5 has been strongly linked to endothelial dysfunction. However, the underlying mechanism of PM2.5 on the vascular endothelial function is poorly understood. This study examined the toxic effect and underlying mechanism of PM2.5 on human umbilical vein endothelial cells (HUVECs). Decreased cell viability and increased LDH activity were observed in the PM2.5-treated HUVECs in a dose-dependent manner. The production of ROS, MDA, and the inhibition of SOD activity were also triggered by PM2.5 in HUVECs. In addition, PM2.5 increased the intracellular levels of proinflammatory cytokines (IL-6, TNF-a, IL-1β, IL-8 and CRP), cell adhesion molecules (ICAM-1, VCAM-1) and tissue factor (TF), resulted in endothelial activation. For an in-depth study, the protein levels of IL-6, JAK1 and STAT3 were up-regulated significantly, while the expression of JAK2 and SOCS1 were down-regulated gradually in PM2.5-treated HUVECs in a dose-dependent manner. These results show that PM2.5 triggered endothelial activation via upregulation of the IL-6 dependent JAK1/STAT3 signaling pathway. This will provide new insights into the toxic effects and mechanisms of cardiovascular diseases triggered by ambient air pollution.
Gene expression profiles and bioinformatics analysis of human umbilical vein endothelial cells exposed to PM2.5
(Elsevier, 2017-05) Hu, H.; Asweto, Collins O.; Wu, J.; Shi, Y.; Feng, L.; Yang, X.; Liang, S.; Cao, L.; Duan, J.; Sun, Z.
Cardiovascular system is demonstrated the main target of PM2.5 and the objective of this study was to explore the toxic effect and molecular mechanisms caused by PM2.5 in primary human umbilical vein endothelial cells (HUVECs) using microarray and bioinformatics analysis. The results showed that 591 genes were differentially expressed triggered by PM2.5, of which 174 genes were down-regulated, while 417 genes were up-regulated. Gene ontology analysis revealed that PM2.5 caused significant changes in gene expression patterns, including response to stimuli, immune response, and cellular processes. Pathway analysis and Signal-net analysis suggested that endocytosis, chemokine signaling pathway, RNA transport, protein processing in endoplasmic reticulum (ER) and autophagy regulation were the most critical pathways in PM2.5-induced toxicity in HUVECs. Moreover, gene expression confirmation of LIF, BCL2L1, CSF3, HMOX1, RPS6, PFKFB, CAPN1, HSPBP1, MOGS, PREB, TUBB2A, GABARAP by qRT-PCR indicated that endocytosis might be involved in the cellular uptake of PM2.5 by forming phagosomes, and subsequently inflammation, hypoxia and ER stress was occurred, which finally activated autophagy after PM2.5 exposure in HUVECs. In summary, our data can serve as fundamental research clues for further studies of PM2.5-induced toxicity in HUVECs.
Gene profiles to characterize the combined toxicity induced by low level co-exposure of silica nanoparticles and benzo[a]pyrene using whole genome microarrays in zebrafish embryos.
(Elsevier, 2018-07) Asweto, Collins O.; Hu, H; Liang, S.; Wang, L.; Liu, M.; Yang, H.; Duan, J.; Sun, Z.
Several studies have suggested that air pollutants combine exposure have greater adverse effects. However, limited studies were available on the combined toxicity of silica nanoparticles (SiNPs) and benzo[a]pyrene (B[a]P). The study was to evaluate the toxic effect and mechanisms of low-dose exposure of SiNPs, B[a]P and co-exposure in zebrafish embryos. In this study, zebrafish embryos received intravenous microinjection of SiNPs and B[a]P, and then was used to select differentially expressed genes by microarray analysis. Multiple bioinformatics analyses and STC analysis were done to identify key genes, pathways and biological processes and the expression trend of genes in each group. 1) 3065 differentially expressed genes were identified in zebrafish embryos. 2) These differentially expressed genes were involved in multiple biological processes and cellular processes such as immunity, response to stimuli, cell proliferation, adhesion, signaling transduction, and embryonic development. 3) Dynamic Gene Network analysis was used to identify a subgroup of 26 core genes that involved in multiple biological processes and cellular processes. 4) Pathway analysis and Signal-net analysis indicated that the MAPK signaling pathway, calcium signaling pathway, p53 signaling pathway, PI3k/Akt signaling pathway, and several pathways associated with immune response were the most prominent significant pathways induced by co-exposure of SiNPs and B[a]P in zebrafish embryos. Our study demonstrated that the molecular actions of co-treated with SiNPs and B[a]P on the immune system, inflammatory process and cardiovascular development had more severe toxicity than single exposure
Genome-wide transcriptional analysis of cardiovascular-related genes and pathways induced by PM2. 5 in human myocardial cells.
(2017-04) Feng, L.; Yang, X.; Asweto, Collins O.; Wu, J.; Zhang, Y.; Hu, H.; Shi, Y.; Duan, J.; Sun, Z.
Air pollution has been a major environment-related health threat. Most of the studies on PM2.5 toxicity have verified on the cardiovascular system and endothelial cells. However, researches on PM2.5-induced myocardial-related toxicity are limited. This study aims to fully understand the toxic effects of PM2.5 on human myocardial cell (AC16) and explore its molecular mechanism based on microarray analysis and bioinformatics analysis. Microarray data analysis manifested that PM2.5-induced toxicity affected expression of 472 genes compared with the control group, including 166 upregulated genes and 306 downregulated genes in human myocardial (AC16) cells. GO analysis showed that cellular processes such as immune response, cell maturation, embryonic heart tube morphogenesis, cellular response to electrical stimulus, skeletal muscle tissue regeneration, and negative regulation of signal transduction were upregulated, while regulation of transcription (DNA-dependent), rhythmic process, protein destabilization apoptotic process, and innate immune response were downregulated. The pathway analysis indicates that cell signaling pathways such as cytokine-cytokine receptor interaction, NF-κB signaling pathway, chemokine signaling pathway, endocrine and other factor-regulated calcium reabsorption, HTLV-I infection, and cell adhesion molecules (CAMs) were upregulated, while the TGF-β signaling pathway was downregulated. In addition, Signal-net showed that the TUBA4A, ADRBK2, BRIX1, SMC4, EIF5B, PRMT1, ATG4B, and NDC80 genes were significantly decreased, while the expression of the KRT6B gene was markedly increased compared with the control group. All the genes were verified by qRT-PCR. This study had provided new bioinformatics evidences in PM2.5-induced myocardial tissue toxicity which is necessary for further cardiovascular system toxicity studies.

Browsing by Author "Duan, J."

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