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Role of RNA m6A modification in titanium dioxide nanoparticle-induced acute pulmonary injury: An in vitro and in vivo study Texte intégral
2022
Ruan, Fengkai | Liu, Changqian | Wang, Yi | Cao, Xisen | Tang, Zhen | Xu, Jiaying | Zeng, Jie | Yin, Hanying | Zheng, Naying | Yang, Chunyan | Zuo, Zhenghong | He, Chengyong
RNA N⁶-methyladenosine (m⁶A) modification regulates the cell stress response and homeostasis, but whether titanium dioxide nanoparticle (nTiO₂)-induced acute pulmonary injury is associated with the m⁶A epitranscriptome and the underlying mechanisms remain unclear. Here, the potential association between m⁶A modification and the bioeffects of several engineered nanoparticles (nTiO₂, nAg, nZnO, nFe₂O₃, and nCuO) were verified thorough in vitro experiments. nFe₂O₃, nZnO, and nTiO₂ exposure significantly increased the global m⁶A level in A549 cells. Our study further revealed that nTiO₂ can induce m⁶A-mediated acute pulmonary injury. Mechanistically, nTiO₂ exposure promoted methyltransferase-like 3 (METTL3)-mediated m⁶A signal activation and thus mediated the inflammatory response and IL-8 release through the degeneration of anti-Mullerian hormone (AMH) and Mucin5B (MUC5B) mRNAs in a YTH m⁶A RNA-binding protein 2 (YTHDF2)-dependent manner. Moreover, nTiO₂ exposure stabilized METTL3 protein by the lipid reactive oxygen species (ROS)-activated ERK1/2 pathway. The scavenging of ROS with ferrostatin-1 (Fer-1) alleviates the ERK1/2 activation, m⁶A upregulation, and the inflammatory response caused by nTiO₂ both in vitro and in vivo. In conclusion, our study demonstrates that m⁶A is a potential intervention target for alleviating the adverse effects of nTiO₂-induced acute pulmonary injury in vitro and in vivo, which has far-reaching implications for protecting human health and improving the sustainability of nanotechnology.
Afficher plus [+] Moins [-]Characterization of polycyclic aromatic compounds in historically contaminated soil by targeted and non-targeted chemical analysis combined with in vitro bioassay Texte intégral
2021
Titaley, Ivan A. | Lam, Monika M. | Bülow, Rebecca | Enell, Anja | Wiberg, Karin | Larsson, Maria
Characterization of polycyclic aromatic compounds in historically contaminated soil by targeted and non-targeted chemical analysis combined with in vitro bioassay Texte intégral
2021
Titaley, Ivan A. | Lam, Monika M. | Bülow, Rebecca | Enell, Anja | Wiberg, Karin | Larsson, Maria
Soil samples from a contaminated site in Sweden were analyzed to identify the presence of 78 polycyclic aromatic compounds (PACs) using gas chromatography coupled with mass spectrometry (GC-MS). The target analysis revealed large contributions not only from polycyclic aromatic hydrocarbons (PAHs), but also from alkylated- and oxygenated-PAHs (alkyl- and oxy-PAHs, respectively), and N-heterocyclics (NPACs). PAC profiles indicated primarily pyrogenic sources, although contribution of petrogenic sources was also observed in one sample as indicated by a high ratio of alkylated naphthalene compared to naphthalene. The aryl hydrocarbon receptor (AhR)-activity of the soil extracts was assessed using the H4IIe-pGudluc 1.1 cells bioassay. When compared with the calculated total AhR-activity of the PACs in the target list, 35–97% of the observed bioassay activity could be explained by 62 PACs with relative potency factors (REPs). The samples were further screened using GC coupled with Orbitrap™ high resolution MS (GC-HRMS) to investigate the presence of other PACs that could potentially contribute to the AhR-activity of the extracts. 114 unique candidate compounds were tentatively identified and divided into four groups based on their AhR-activity and environmental occurrence. Twelve substances satisfied all the criteria, and these compounds are suggested to be included in regular screening in future studies, although their identities were not confirmed by standards in this study. High unexplained bio-TEQ fractions in three of the samples may be explained by tentatively identified compounds (n = 35) with high potential of being toxic. This study demonstrates the benefit of combining targeted and non-targeted chemical analysis with bioassay analysis to assess the diversity and effects of PACs at contaminated sites. The applied prioritization strategy revealed a number of tentatively identified compounds, which likely contributed to the overall bioactivity of the soil extracts.
Afficher plus [+] Moins [-]Characterization of polycyclic aromatic compounds in historically contaminated soil by targeted and non-targeted chemical analysis combined with in vitro bioassay Texte intégral
2021
Titaley, Ivan A. | Lam, Monika M. | Bülow, Rebecca | Enell, Anja | Wiberg, Karin | Larsson, Maria
Soil samples from a contaminated site in Sweden were analyzed to identify the presence of 78 polycyclic aromatic compounds (PACs) using gas chromatography coupled with mass spectrometry (GC-MS). The target analysis revealed large contributions not only from polycyclic aromatic hydrocarbons (PAHs), but also from alkylated- and oxygenated-PAHs (alkyl- and oxy-PAHs, respectively), and N-heterocyclics (NPACs). PAC profiles indicated primarily pyrogenic sources, although contribution of petrogenic sources was also observed in one sample as indicated by a high ratio of alkylated naphthalene compared to naphthalene. The aryl hydrocarbon receptor (AhR)-activity of the soil extracts was assessed using the H4IIe-pGudluc 1.1 cells bioassay. When compared with the calculated total AhR-activity of the PACs in the target list, 35-97% of the observed bioassay activity could be explained by 62 PACs with relative potency factors (REPs). The samples were further screened using GC coupled with OrbitrapTM high resolution MS (GC-HRMS) to investigate the presence of other PACs that could potentially contribute to the AhR-activity of the extracts. 114 unique candidate compounds were tentatively identified and divided into four groups based on their AhR-activity and environmental occurrence. Twelve substances satisfied all the criteria, and these compounds are suggested to be included in regular screening in future studies, although their identities were not confirmed by standards in this study. High unexplained bio-TEQ fractions in three of the samples may be explained by tentatively identified compounds (n = 35) with high potential of being toxic. This study demonstrates the benefit of combining targeted and non-targeted chemical analysis with bioassay analysis to assess the diversity and effects of PACs at contaminated sites. The applied prioritization strategy revealed a number of tentatively identified compounds, which likely contributed to the overall bioactivity of the soil extracts.
Afficher plus [+] Moins [-]Pharmaceutically active compounds (PhACs) in surface sediments of the Jiaozhou Bay, north China Texte intégral
2020
Peng, Quancai | Song, Jinming | Li, Xuegang | Yuan, Huamao | Liu, Mengtan | Duan, Liqin | Zuo, Jiulong
Pharmaceutically active compounds (PhACs) have attracted increasing attention due to their large consumption volumes, high bioactivity and potential ecotoxicity. In this study, a total of 150 commonly used drugs were investigated in sediments of Jiaozhou Bay (JZB). Twenty-five target compounds were detected, of which ten were discovered for the first time in marine sediments. The range of total PhAC content was 3.62–21.4 ng/g dry weight. Ketoprofen (2.49 ng/g), oxytetracycline (1.00 ng/g) and roxithromycin (0.97 ng/g) were the preponderant PhACs. PhACs gradually decreased from east to west, and the distribution of PhACs in the sediment was controlled by the source channel, seawater dynamic process and sediment composition. The diatom, organic matter, and clay proportions in the sediments and the nutrients in the overlying water were the most important environmental factors affecting the distribution of PhACs. PhAC pollution in the sediments of the JZB exhibited an increasing trend. Coprostanol could be used as a chemical indicator of the PhAC concentration in JZB sediments. PhACs were mainly derived from direct pollution due to human fecal excretion in the eastern region. Ofloxacin, tetracycline and oxytetracycline were found to pose high or medium risks to aquatic organisms. It is necessary and urgent to improve the treatment technology of drug residues in sewage treatment plants to decrease the pollution of PhAC residues. With the continuous aging of the global population, the use of PhACs will increase rapidly, which may cause more unpredictable threats to the marine ecosystem. Therefore, the monitoring of PhACs in the marine environment needs to be strengthened, and studies on PhAC occurrence and effects must be considered a priority in global environmental research.
Afficher plus [+] Moins [-]Formation of perfluorocarboxylic acids from 6:2 fluorotelomer sulfonate (6:2 FTS) in landfill leachate: Role of microbial communities Texte intégral
2020
Hamid, Hanna | Li, Loretta Y. | Grace, John R.
Fluorotelomer compounds in landfill leachate can undergo biotransformation under aerobic conditions and act as a secondary source of perfluorocarboxylic acids (PFCAs) to the environment. Very little is known about the role of various microbial communities towards fluorotelomer compounds biotransformation. Using an inoculum prepared from the sediment of a leachate collection ditch, 6:2 fluorotelomer sulfonate (6:2 FTS) biotransformation experiments were carried out. Specific substrates (i.e., glucose, ammonia) and ammonia-oxidizing inhibitor (allylthiourea) were used to produce two experimental runs with heterotrophic (HET) growth only and heterotrophic with ammonia-oxidizing and nitrite- oxidizing bacteria (HET + AOB + NOB). After 10 days, ∼20% of the spiked 6:2 FTS removal was observed in HET + AOB + NOB, compared to ∼7% under HET condition. Higher 6:2 FTS removal in HET + AOB + NOB likely resulted from ammonia monooxygenase enzyme that catalyzes the first step of ammonia oxidation. The HET + AOB + NOB condition also showed higher PFCA (C4–C6) formation (∼2% of initially spiked 6:2 FTS), possibly due to higher overall bioactivity. Microbial community analysis through 16s rRNA sequencing confirmed that Proteobacteria and Bacteroidetes were the most abundant phyla (>75% relative abundance) under all experimental conditions. High abundance of Actinobacteria (>17%) was observed under the HET + AOB + NOB condition on day 7. Since Actinobacteria can synthesize a wide range of enzymes including monooxygenases, they likely play an important role in 6:2 FTS biotransformation and PFCA production.
Afficher plus [+] Moins [-]Bisphenol S induced epigenetic and transcriptional changes in human breast cancer cell line MCF-7 Texte intégral
2019
Huang, Wei | Zhao, Chao | Zhong, Huan | Zhang, Shoudong | Xia, Yiji | Cai, Zongwei
In recent years, concerns about using Bisphenol A (BPA) in daily consume products and its effects in many chronic human diseases have prompted the removal of BPA. However, the widely used BPA alternatives, including Bisphenol S (BPS), have a high structural similarity with BPA, suggesting that they may have similar biological effects towards human beings. Indeed, BPS was also found to have endocrine-disrupting effects. Epigenetic mechanism was reported to be involved in BPA-induced biological effects in both in vitro and in vivo models. However, there is no assessment on whether BPS could cause epigenetic changes. In this work, we investigated the possible epigenetic effects of BPS that might induce in human breast cancer cell line MCF-7. We found that BPS could change DNA methylation level of transposons. Besides, methylation status in promoter of breast cancer related genes CDH1, SFN, TNFRSF10C were also changed, which implied that BPS might play a role in the development of breast cancer. Gene expression profiling showed that some genes related to breast cancer progression were upregulated, including THBS4, PPARGC1A, CREB5, COL5A3. Gene ontology (GO) analysis of the differentially expressed genes revealed the significantly changes in PI3K-Akt signaling pathway and extracellular matrix, which were related to the proliferation, migration and invasion of breast cancer cells. These results illustrated that BPS exposure might play roles in the progression of breast cancer.
Afficher plus [+] Moins [-]Contaminants in bald eagles of the upper Midwestern U.S.: A framework for prioritizing future research based on in-vitro bioassays Texte intégral
2019
Elliott, Sarah M. | Route, William T. | DeCicco, Laura A. | VanderMeulen, David D. | Corsi, Steven R. | Blackwell, Brett R.
Several organic contaminants (OCs) have been detected in bald eagle (Haliaeetus leucocephalus) nestling (eaglet) plasma in the upper Midwestern United States. Despite frequent and relatively high concentrations of OCs in eaglets, little is understood about potential biological effects associated with exposure. We screened an existing database of OC concentrations in eaglet plasma collected from the Midwestern United States against bioactivity information from the ToxCast database. ToxCast bioactivity information consists of concentrations expected to elicit responses across a range of biological space (e.g. cellular, developmental, etc.) obtained from a series of high throughput assays. We calculated exposure—activity ratios (EAR) by calculating the ratio of plasma concentrations to concentrations available in ToxCast. Bioactivity data were not available for all detected OCs. Therefore, our analysis provides estimates of potential bioactivity for 19 of the detected OCs in eaglet plasma. Perfluorooctanesulfonic acid (PFOS) EAR values were consistently the highest among all study areas. Maximum EAR values were ≥1 for PFOS, perfluorononanoic acid, and bisphenol A in 99.7, 0.53 and 0.26% of samples, indicating that some plasma concentrations were greater than what may be expected to elicit biological responses. About 125 gene targets, indicative of specific biological pathways, were identified as potentially being affected. Inhibition of several CYP genes, involved in xenobiotic metabolism, were most consistently identified. Other identified biological responses have potential implications for motor coordination, cardiac functions, behavior, and blood circulation. However, it is unclear what these results mean for bald eagles, given that ToxCast data are generated using mammalian-based endpoints. Despite uncertainties and limitations, this method of screening environmental data can be useful for informing future monitoring or research focused on understanding the occurrence and effects of OCs in bald eagles and other similarly-positioned trophic species.
Afficher plus [+] Moins [-]Specific polycyclic aromatic hydrocarbons identified as ecological risk factors in the Lagos lagoon, Nigeria Texte intégral
2019
Sogbanmu, Temitope O. | Osibona, Adesola O. | Otitoloju, Adebayo A.
The ecological risk assessment (ERA) of polycyclic aromatic hydrocarbons (PAHs) is imperative due to their ubiquity and biological effects in aquatic organisms. We evaluated the seasonal levels and ERA of 16 priority PAHs in surface water, sediment and fish from four (4) anthropogenic-impacted zones of the Lagos lagoon, Nigeria. PAHs were analysed using GC-FID and standard guidelines were utilized for the ERA. Also, we developed a sediment to water-PAHs ratio and ranking of PAHs for the ERA. The dominant fish species were Sarotherodon melanotheron (Black-Jawed Tilapia), Gerres melanopterus (Gerres), Liza falcipinnis (Sicklefin Mullet) and Pseudotolithus elongatus (Bobo Croaker) at Ilaje, Iddo, Atlas cove and Apapa zones respectively. The range of sum PAHs was 195–1006 μg L⁻¹, 302–1290 μg kg⁻¹ and 8.80–26.1 μg kg⁻¹ in surface water, sediment and fish species respectively. Naphthalene was dominant in the surface water and sediment samples while 3-ring to 4-ring PAHs were predominant in fish species across the zones and seasons. The sediment to water-PAHs ratio was greater than 1 for sum PAHs and significantly higher (p < 0.05) in the wet season for specific PAHs across the zones and seasons. On the basis of the sediment PAHs level, Apapa zone was highly polluted with frequent biological effects while the other zones were moderately polluted with occasional biological effects across the zones and seasons. Fish species from all zones were minimally contaminated in both seasons except S. melanotheron which was not contaminated. The specific PAHs identified as ecological risk factors in the lagoon and ranking based on 50–75% recurrence in the ERA were; naphthalene, acenaphthene > acenaphthylene, fluorene, pyrene and benzo[a]anthracene. We recommend that the specific PAHs identified should form the basis for the establishment of environmental quality standards for individual PAHs in coastal waters based on the UN sustainable development goal 14 (life below water).
Afficher plus [+] Moins [-]From Muller to mechanism: How LNT became the default model for cancer risk assessment Texte intégral
2018
Calabrese, Edward J.
This paper summarizes the historical and scientific foundations of the Linear No-Threshold (LNT) cancer risk assessment model. The story of cancer risk assessment is an extraordinary one as it was based on an initial incorrect gene mutation interpretation of Muller, the application of this incorrect assumption in the derivation of the LNT single-hit model, and a series of actions by leading radiation geneticists during the 1946–1956 period, including a National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics Panel (Anonymous, 1956), to sustain the LNT belief via a series of deliberate obfuscations, deceptions and misrepresentations that provided the basis of modern cancer risk assessment policy and practices. The reaffirming of the LNT model by a subsequent and highly influential NAS Biological Effects of Ionizing Radiation (BEIR) I Committee (NAS/NRC, 1972) using mouse data has now been found to be inappropriate based on the discovery of a significant documented error in the historical control group that led to incorrect estimations of risk in the low dose zone. Correction of this error by the original scientists and the application of the adjusted/corrected data back to the BEIR I (NAS/NRC, 1972) report indicates that the data would have supported a threshold rather than the LNT model. Thus, cancer risk assessment has a poorly appreciated, complex and seriously flawed history that has undermined policies and practices of regulatory agencies in the U.S. and worldwide to the present time.
Afficher plus [+] Moins [-]Endocrine disruption and differential gene expression in sentinel fish on St. Lawrence Island, Alaska: Health implications for indigenous residents Texte intégral
2018
von Hippel, Frank A. | Miller, Pamela K. | Carpenter, David O. | Dillon, Danielle | Smayda, Lauren | Katsiadaki, Ioanna | Titus, Tom A. | Batzel, Peter | Postlethwait, John H. | Buck, C Loren
People living a subsistence lifestyle in the Arctic are highly exposed to persistent organic pollutants, including polychlorinated biphenyls (PCBs). Formerly Used Defense (FUD) sites are point sources of PCB pollution; the Arctic contains thousands of FUD sites, many co-located with indigenous villages. We investigated PCB profiles and biological effects in freshwater fish (Alaska blackfish [Dallia pectoralis] and ninespine stickleback [Pungitius pungitius]) living upstream and downstream of the Northeast Cape FUD site on St. Lawrence Island in the Bering Sea. Despite extensive site remediation, fish remained contaminated with PCBs. Vitellogenin concentrations in males indicated exposure to estrogenic contaminants, and some fish were hypothyroid. Downstream fish showed altered DNA methylation in gonads and altered gene expression related to DNA replication, response to DNA damage, and cell signaling. This study demonstrates that, even after site remediation, contaminants from Cold War FUD sites in remote regions of the Arctic remain a potential health threat to local residents – in this case, Yupik people who had no influence over site selection and use by the United States military.
Afficher plus [+] Moins [-]Community response to construction noise in three central cities of Zhejiang province, China Texte intégral
2017
Liu, Yong | Xia, Bo | Cui, Caiyun | Skitmore, R. M. (Ronald Martin)
As a common source of environmental noise in China and many developing countries worldwide, construction work provokes many complaints and deterioration in acoustic climate quality. This paper describes research to obtain an improved understanding of people's community response to, and evaluation of, construction noise in three central cities of Zhejiang province, China. This involved carrying out a social survey using standard questionnaires developed by the International Commission on Biological Effects of Noise (ICBEN). A dose-response relationship model is established using a quadratic polynomial regression analysis based on construction noise exposure measurements from 40 construction sites in Hangzhou, Ningbo and Wenzhou.The results of the study indicate that the majority of people have a negative attitude to construction noise; the noise ranges between 60 dB and 80 dB (compared with 50 dB–70 dB traffic noise in Tianjin), with the percentage of highly annoyed people affected increasing from 15%-20% to 30%–40% over the range. There also different levels of annoyance depending on the time of day, and the location and activities of those affected. Other cultural differences are also apparent both between Ningbo/Wenzhou and the more urbane citizens of Hangzhou, and the Chinese people and their more noise-tolerant EU and Vietnam counterparts.The findings of this study provide a new perspective for the study of construction noise that can help local governments have an improved understanding of how residents react to construction noise for the purpose of selecting construction noise-mitigation projects and introducing construction noise-control regulations.
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