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Role of RNA m6A modification in titanium dioxide nanoparticle-induced acute pulmonary injury: An in vitro and in vivo study
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 [-]Specific polycyclic aromatic hydrocarbons identified as ecological risk factors in the Lagos lagoon, Nigeria
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 [-]Contaminants in bald eagles of the upper Midwestern U.S.: A framework for prioritizing future research based on in-vitro bioassays
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 [-]Environmental risk assessment of triclosan and ibuprofen in marine sediments using individual and sub-individual endpoints
2018
Pusceddu, F.H. | Choueri, R.B. | Pereira, C.D.S. | Cortez, F.S. | Santos, D.R.A. | Moreno, B.B. | Santos, A.R. | Rogero, J.R. | César, A.
The guidelines for the Environmental Risk Assessment (ERA) of pharmaceuticals and personal care products (PPCP) recommend the use of standard ecotoxicity assays and the assessment of endpoints at the individual level to evaluate potential effects of PPCP on biota. However, effects at the sub-individual level can also affect the ecological fitness of marine organisms chronically exposed to PPCP. The aim of the current study was to evaluate the environmental risk of two PPCP in marine sediments: triclosan (TCS) and ibuprofen (IBU), using sub-individual and developmental endpoints. The environmental levels of TCS and IBU were quantified in marine sediments from the vicinities of the Santos submarine sewage outfall (Santos Bay, São Paulo, Brazil) at 15.14 and 49.0 ng g⁻¹, respectively. A battery (n = 3) of chronic bioassays (embryo-larval development) with a sea urchin (Lytechinus variegatus) and a bivalve (Perna perna) were performed using two exposure conditions: sediment-water interface and elutriates. Moreover, physiological stress through the Neutral Red Retention Time Assay (NRRT) was assessed in the estuarine bivalve Mytella charruana exposed to TCS and IBU spiked sediments. These compounds affected the development of L. variegatus and P. perna (75 ng g⁻¹ for TCS and 15 ng g⁻¹ for IBU), and caused a significant decrease in M. charruana lysosomal membrane stability at environmentally relevant concentrations (0.08 ng g⁻¹ for TCS and 0.15 ng g⁻¹ for IBU). Chemical and ecotoxicological data were integrated and the risk quotient estimated for TCS and IBU were higher than 1.0, indicating a high environmental risk of these compounds in sediments. These are the first data of sediment risk assessment of pharmaceuticals and personal care products of Latin America. In addition, the results suggest that the ERA based only on individual-level and standard toxicity tests may overlook other biological effects that can affect the health of marine organisms exposed to PPCP.
Afficher plus [+] Moins [-]From Muller to mechanism: How LNT became the default model for cancer risk assessment
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 [-]Biological responses of two marine organisms of ecological relevance to on-going ocean acidification and global warming
2018
Gomiero, A. | Bellerby, R.G.J. | Manca Zeichen, M. | Babbini, L. | Viarengo, A.
Recently, there has been a growing concern that climate change may rapidly and extensively alter global ecosystems with unknown consequences for terrestrial and aquatic life. While considerable emphasis has been placed on terrestrial ecology consequences, aquatic environments have received relatively little attention. Limited knowledge is available on the biological effects of increments of seawater temperature and pH decrements on key ecological species, i.e., primary producers and/or organisms representative of the basis of the trophic web. In the present study, we addressed the biological effects of global warming and ocean acidification on two model organisms, the microbenthic marine ciliate Euplotes crassus and the green alga Dunaliella tertiocleta using a suite of high level ecological endpoint tests and sub-lethal stress measures. Organisms were exposed to combinations of pH and temperature (TR1: 7.9[pH], 25.5 °C and TR2: 7.8[pH], 27,0 °C) simulating two possible environmental scenarios predicted to occur in the habitats of the selected species before the end of this century. The outcomes of the present study showed that the tested scenarios did not induce a significant increment of mortality on protozoa. Under the most severe exposure conditions, sub-lethal stress indices show that pH homeostatic mechanisms have energetic costs that divert energy from essential cellular processes and functions. The marine protozoan exhibited significant impairment of the lysosomal compartment and early signs of oxidative stress under these conditions. Similarly, significant impairment of photosynthetic efficiency and an increment in lipid peroxidation were observed in the autotroph model organism held under the most extreme exposure condition tested.
Afficher plus [+] Moins [-]Endocrine disruption and differential gene expression in sentinel fish on St. Lawrence Island, Alaska: Health implications for indigenous residents
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
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.
Afficher plus [+] Moins [-]Trophic transfer and effects of DDT in male hornyhead turbot (Pleuronichthys verticalis) from Palos Verdes Superfund site, CA (USA) and comparisons to field monitoring
2016
Crago, Jordan | Xu, Elvis Genbo | Kupsco, Allison | Jia, Fang | Mehinto, Alvine C. | Lao, Wenjian | Maruya, Keith A. | Gan, Jay | Schlenk, Daniel
High concentrations of DDT and metabolites (ΣDDT) have been detected in sediment and the demersal flatfish hornyhead turbot (Pleuronichtys verticalis) collected from Palos Verdes (PV), California, USA, a site contaminated with over 100 metric tons of DDT throughout 1960s–70s. This study was conducted to assess the transfer of ΣDDT from PV-sediment into polychaetes (Neanthes arenaceodentata) and hornyhead turbot, and to investigate if the responses in turbots from two different laboratory exposures mimic those in turbots caught in PV (PV-turbot). Turbot fed PV-sediment-contaminated polychaete for 7 days had liver concentrations of ΣDDT similar to PV-turbot. After 28 days, ΣDDT also accumulated in livers of turbot gavaged with a ΣDDT mixture. In vitro cell bioassays indicated significant increases of 17β-estradiol equivalents (EEQ) in turbot bile extracts as compared to the control in the 7-day study. These responses corresponded to those measured in PV-fish. Glucocorticoid receptor (GR), anti-androgen receptor (anti-AR), estrogen receptor (ER) or aryl hydrocarbon receptor (AhR) activities were also observed in extracts of PV-sediment, and PV-sediment-exposed worm. Anti-AR, AhR and GR activities were significantly higher in PV-sediment than reference sediment (San Diego, SD). Higher transcripts of hepatic VTG, ERα and ERβ were found in PV-turbot than SD-turbot, but were unaltered in fish exposed to sediment-contaminated worms for the 7-day study. In contrast, liver extracts from the 28-day treatment of ΣDDT showed lower EEQ but similar hepatic VTG and ERβ transcripts relative to those of PV-turbot. These data indicated that trophic transfer of sediment-associated DDT in 7-day exposures corresponded to field measurements of DDT residues and in vitro ER bioactivities, but failed to mimic in vivo biological effects observed in field fish. In contrast, treatment with ΣDDT alone for 28 days mimicked in vivo biological effects of DDTs in PV fish, but did not correspond to liver concentrations or in vitro bioactivities.
Afficher plus [+] Moins [-]Effects of riverine suspended particulate matter on the post-dredging increase in internal phosphorus loading across the sediment-water interface
2016
Liu, Cheng | Shao, Shiguang | Shen, Qiushi | Fan, Chengxin | Zhang, Lei | Zhou, Qi-Lin
Dredging is frequently used in the river mouths of eutrophic lakes to reduce internal phosphorus (P) loading from the sediment. However, the accumulation of P-adsorbed suspended particulate matter (SPM) from the inflowing rivers negatively affects the post-dredging sediment-water interface and ultimately increases internal P loading. Here, a 360-d experiment was carried out to investigate the influence of riverine SPM on the efficacy of dredging in reducing internal P loading. SPM was added to dredged and undredged sediments collected from the confluence area of Lake Chaohu. Several parameters related to internal P loading, including oxygen profile, soluble reactive P, and ferrous iron across the sediment-water interface, organic matter, alkaline phosphatase activity, and P fractions, were measured throughout the experimental period. The results showed that the P content (especially mobile P) in the sediment increased to the pre-dredging level with the accumulation of SPM in the dredged sediment. In addition, the P flux across the sediment-water interface increased with the accumulation of SPM. Several characteristics of SPM, including high organic matter content, mobile P, high activity of alkaline phosphatase, and high biological activity, were considered correlated with the post-dredging increase in internal P loading. Overall, this study showed that the heavily contaminated riverine SPM regulates the long-term efficacy of dredging as a nutrient management option in the confluence area. Management is needed to avoid or reduce this phenomenon during dredging projects of this nature.
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