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Role of RNA m6A modification in titanium dioxide nanoparticle-induced acute pulmonary injury: An in vitro and in vivo study النص الكامل
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.
اظهر المزيد [+] اقل [-]Diet influences on growth and mercury concentrations of two salmonid species from lakes in the eastern Canadian Arctic النص الكامل
2021
Chételat, John | Shao, Yueting | Richardson, Murray C. | MacMillan, Gwyneth A. | Amyot, Marc | Drevnick, Paul E. | Gilla, Haradīpa | Köck, Günter | Muir, Derek C.G.
Diet, age, and growth rate influences on fish mercury concentrations were investigated for Arctic char (Salvelinus alpinus) and brook trout (Salvelinus fontinalis) in lakes of the eastern Canadian Arctic. We hypothesized that faster-growing fish have lower mercury concentrations because of growth dilution, a process whereby more efficient growth dilutes a fish’s mercury burden. Using datasets of 57 brook trout and 133 Arctic char, linear regression modelling showed fish age and diet indices were the dominant explanatory variables of muscle mercury concentrations for both species. Faster-growing fish (based on length-at-age) fed at a higher trophic position, and as a result, their mercury concentrations were not lower than slower-growing fish. Muscle RNA/DNA ratios were used as a physiological indicator of short-term growth rate (days to weeks). Slower growth of Arctic char, inferred from RNA/DNA ratios, was found in winter versus summer and in polar desert versus tundra lakes, but RNA/DNA ratio was (at best) a weak predictor of fish mercury concentration. Net effects of diet and age on mercury concentration were greater than any potential offset by biomass dilution in faster-growing fish. In these resource-poor Arctic lakes, faster growth was associated with feeding at a higher trophic position, likely due to greater caloric (and mercury) intake, rather than growth efficiency.
اظهر المزيد [+] اقل [-]The role of respiratory droplet physicochemistry in limiting and promoting the airborne transmission of human coronaviruses: A critical review النص الكامل
2021
Niazi, Sadegh | Groth, Robert | Spann, Kirsten | Johnson, Graham R.
Whether virulent human pathogenic coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) are effectively transmitted by aerosols remains contentious. Transmission modes of the novel coronavirus have become a hot topic of research with the importance of airborne transmission controversial due to the many factors that can influence virus transmission. Airborne transmission is an accepted potential route for the spread of some viral infections (measles, chickenpox); however, aerosol features and infectious inoculum vary from one respiratory virus to another. Infectious virus-laden aerosols can be produced by natural human respiratory activities, and their features are vital determinants for virus carriage and transmission. Physicochemical characteristics of infectious respiratory aerosols can influence the efficiency of virus transmission by droplets. This critical review identifies studies reporting instances of infected patients producing airborne human pathogenic coronaviruses, and evidence for the role of physical/chemical characteristics of human-generated droplets in altering embedded viruses’ viability. We also review studies evaluating these viruses in the air, field studies and available evidence about seasonality patterns. Ultimately the literature suggests that a proportion of virulent human coronaviruses can plausibly be transmitted via the air, even though this might vary in different conditions. Evidence exists for respirable-sized airborne droplet nuclei containing viral RNA, although this does not necessarily imply that the virus is transmittable, capable of replicating in a recipient host, or that inoculum is sufficient to initiate infection. However, evidence suggests that coronaviruses can survive in simulated droplet nuclei for a significant time (>24 h). Nevertheless, laboratory nebulized virus-laden aerosols might not accurately model the complexity of human carrier aerosols in studying airborne viral transport. In summary, there is disagreement on whether wild coronaviruses can be transmitted via an airborne path and display seasonal patterns. Further studies are therefore required to provide supporting evidence for the role of airborne transmission and assumed mechanisms underlying seasonality.
اظهر المزيد [+] اقل [-]Integrated transcriptomics and proteomics revealed the distinct toxicological effects of multi-metal contamination on oysters النص الكامل
2021
Li, Yunlong | Wang, Wen-Xiong
The Pearl River Estuary (PRE) is the largest estuary in southern China and under high metal stress. In the present study, we employed an integrated method of transcriptomics and proteomics to investigate the ecotoxicological effects of trace metals on the Hong Kong oyster Crassostrea hongkongensis. Three oyster populations with distinct spatial distributions of metals were sampled, including the Control (Station QA, the lowest metal levels), the High Cd (Station JZ, the highest Cd), and the High Zn–Cu–Cr–Ni (Station LFS, with the highest levels of zinc, copper, chromium, and nickel). Dominant metals in oysters were differentiated by principal component analysis (PCA), and theirgene and protein profiles were studied using RNA-seq and iTRAQ techniques. Of the 2250 proteins identified at both protein and RNA levels, 70 proteins exhibited differential expressions in response to metal stress in oysters from the two contaminated stations. There were 8 proteins altered at both stations, with the potential effects on mitochondria and endoplasmic reticulum by Ag. The genotoxicity, including impaired DNA replication and transcription, was specifically observed in the High Cd oysters with the dominating influence of Cd. The structural components (cytoskeleton and chromosome-associated proteins) were impaired by the over-accumulated Cu, Zn, Cr, and Ni at Station LFS. However, enhanced tRNA biogenesis and exosome activity might help the oysters to alleviate the toxicities resulting from their exposure to these metals. Our study provided comprehensive information on the molecular changes in oysters at both protein and RNA levels in responding to multi-levels of trace metal stress.
اظهر المزيد [+] اقل [-]Urinary metabolites of multiple volatile organic compounds among general population in Wuhan, central China: Inter-day reproducibility, seasonal difference, and their associations with oxidative stress biomarkers النص الكامل
2021
Qian, Xi | Wan, Yanjian | Wang, Aizhen | Xia, Wei | Yang, Zong | He, Zhenyu | Xu, Shunqing
General population are concurrently and extensively exposed to many volatile organic compounds (VOCs), including some Group 1 human carcinogens, such as 1,3-butadiene. However, only a few studies assessed internal exposure levels of VOCs; particularly, very limited studies have examined associations between the urinary concentrations of multiple VOC metabolites (mVOCs) and oxidative stress biomarkers (OSBs) among the general population. In this study, 21 mVOCs and three OSBs including 8-hydroxy-2′-deoxyguanosine (8-OHdG; for DNA), 8-hydroxyguanosine (8-OHG; for RNA), and 4-hydroxy nonenal mercapturic acid (HNEMA; for lipid) were measured in 406 urine samples collected from 128 healthy adults during autumn and winter of 2018 in Wuhan, central China, including repeated samples taken in 3 d from 75 volunteers. Inter-day reproducibility for most mVOCs was good to excellent; urinary concentrations of mVOCs in winter were generally higher than those in autumn. Risk assessment was conducted by calculating hazard quotients for the parent compounds, and the results suggested that acrolein, 1,3-butadiene, and cyanide should be considered as high-priority hazardous ones for management. After false-discovery adjustment, 16 of the studied mVOCs were positively associated with 8-OHdG and 8-OHG (β values ranged from 0.04 to 0.48), and four mVOCs were positively associated with HNEMA (β values ranged from 0.21 to 0.78). Weighted quantile sum regression analyses were used to assess associations of mVOC mixture and OSBs, and we found significantly positive associations between the mixture index and OSBs, among which the strongest mVOC contributors for the associations were 2-methylhippuric acid for both DNA (20%) and RNA (17%) oxidative damage, and trans,trans-muconic acid (50%) for lipid peroxidation. This study firstly reported good to excellent short-term reproducibility, seasonal difference in autumn and winter, and possible health risk in urinary concentrations of multiple mVOCs among the general population.
اظهر المزيد [+] اقل [-]Pre-pregnancy exposure to fine particulate matter (PM2.5) increases reactive oxygen species production in oocytes and decrease litter size and weight in mice النص الكامل
2021
Guo, Yi | Cao, Zhijuan | Jiao, Xianting | Bai, Dandan | Zhang, Yalin | Hua, Jing | Liu, Wenqiang | Teng, Xiaoming
Exposure of females to fine particulate matter ≤2.5 μm in diameter (PM2.5) prior to pregnancy could produce adverse impact on fertility and enhances susceptibility of the offspring to a variety of diseases. In the current study, female C57BL/6 mice (6 weeks of age) were exposed to either concentrated PM2.5 or filtered air (average PM2.5 concentration: 115.60 ± 7.77 vs. 14.07 ± 0.38 μg/m⁻³) using a whole-body exposure device for 12 weeks. Briefly, PM2.5 exposure decreased anti-Müllerian hormone level (613.40 ± 17.36 vs 759.30 ± 21.90 pg mL⁻¹, P<0.01) and increased reactive oxygen species (ROS) level (45.39 ± 0.82 vs 24.20 ± 0.85 arbitrary unit in fluorescence assay, P<0.01) in oocytes. The exposure increased oocyte degeneration rate (21.5% vs 5.1%, respectively (P<0.01) and decreased the 2-cell formation rate (71.9% vs 86.0%, P < 0.01). Transcriptome profiling using RNA sequencing showed wide spectrum of abnormal expression of genes, particularly those involved in regulating the mitochondrial respiratory complex in oocytes and metabolic processes in blastocysts. The exposure decreased litter size (6 ± 0.37 vs 7 ± 0.26, P<0.05) and weight (1.18 ± 0.02 vs 1.27 ± 0.02 g, P<0.01). In summary, PM2.5 exposure decreased female fertility, possibly through increased ROS production in oocytes and metabolic disturbances in developing embryos. The cause-effect relationship, however, requires further investigation.
اظهر المزيد [+] اقل [-]Constant light exposure causes oocyte meiotic defects and quality deterioration in mice النص الكامل
2020
Zhang, Huiting | Yan, Ke | Sui, Lumin | Nie, Junyu | Cui, Kexin | Liu, Jiahao | Zhang, Hengye | Yang, Xiaogan | Lu, Kehuan | Liang, Xingwei
Artificial light at night (ALAN) exposes us to prolonged illumination, that adversely affects female reproduction. However, it remains to be clarified how prolonged light exposure affects oocyte meiotic maturation and quality. To this end, we exposed female mice to a constant light (CL) of 250 lux for different durations. Our findings showed that CL exposure for 7 weeks reduced the oocyte maturation rate. Meanwhile, CL exposure caused greater abnormalities in spindle assembly and chromosome alignment and a higher rate of oocyte aneuploidy than the regular light dark cycle. CL exposure also induced oxidative stress and caused mitochondrial dysfunction, which resulted in oocyte apoptosis and autophagy. Notably, our results showed that CL exposure reduced the levels of α-tubulin acetylation, DNA methylation at 5 mC, RNA methylation at m⁶A and histone methylation at H3K4me2 but increased the levels of histone methylation at H3K27me2 in oocytes. In summary, our findings demonstrate that constant bright light exposure causes oocyte meiotic defects and reduces cytoplasmic quality. These results extend the current understanding of ALAN-mediated defects in female reproduction.
اظهر المزيد [+] اقل [-]Exposure of honey bee larvae to thiamethoxam and its interaction with Nosema ceranae infection in adult honey bees النص الكامل
2020
Tesovnik, Tanja | Zorc, Minja | Ristanić, Marko | Glavinić, Uroš | Stevanović, Jevrosima | Narat, Mojca | Stanimirović, Zoran
During their lifetime honey bees (Apis mellifera) rarely experience optimal conditions. Sometimes, a simultaneous action of multiple stressors, natural and chemical, results in even greater effect than of any stressor alone. Therefore, integrative investigations of different factors affecting honey bees have to be carried out. In this study, adult honey bees exposed to thiamethoxam in larval and/or adult stage and infected with Nosema ceranae were examined. Newly emerged bees from colonies, non-treated or treated with thiamethoxam, were organized in six groups and kept in cages. Thiamethoxam treated bees were further exposed to either thiamethoxam or Nosema (groups TT and TN), or simultaneously to both (group TTN). Newly emerged bees from non-treated colonies were exposed to Nosema (group CN). From both, treated and non-treated colonies two groups were organized and further fed only with sugar solution (groups C and TC). Here, we present the expression profile of 19 genes in adult worker honey bees comprising those involved in immune, detoxification, development and apoptosis response. Results showed that gene expression patterns changed with time and depended on the treatment. In group TC at the time of emergence the majority of tested genes were downregulated, among which nine were significantly altered. The same gene pattern was observed on day six, where the only significantly upregulated gene was defensin-1. On day nine most of analyzed genes in all experimental groups showed upregulation compared to control group, where upregulation of antimicrobial peptide genes abaecin, defensin-1 and defensin-2 was significant in groups TT and TTN. On day 15 we observed a similar pattern of expression in groups TC and TT exposed to thiamethoxam only, where most of the detoxification genes were downregulated. Additionally RNA loads of Nosema and honey bee viruses were recorded. We detected a synergistic interaction of thiamethoxam and Nosema, reflected in lowest honey bee survival.
اظهر المزيد [+] اقل [-]Urinary bisphenol analogues concentrations and biomarkers of oxidative DNA and RNA damage in Chinese school children in East China: A repeated measures study النص الكامل
2019
Zhou, Ying | Yao, Yuan | Shao, Yijun | Qu, Weidong | Chen, Yue | Jiang, Qingwu
The associations between bisphenol analogues (BPs) exposure and oxidative damage was explored in this 3-year longitudinal study of 275 school children in East China. Nine BPs in first morning urine samples were measured to assess BPs exposure, and 8-hydroxydeoxyguanosine (8-OHdG) and 8-oxo-7,8-dihydroguanosine (8-OHG) were measured as biomarkers of oxidative DNA and RNA damage. Linear mixed model (LMM) was used for repeated measures analysis. School children were mainly exposed to BPA, BPS, BPF, and BPAF (detection frequencies: 97.9%, 42.2%, 13.3%, and 12.8%) with median concentrations of 1.55, 0.355, 0.236 and 0.238 μg g⁻¹Cᵣₑ, respectively. An interquartile range (IQR) increase in urinary BPA was significantly associated with 12.9% (95% CI: 6.1%, 19.6%) increase in 8-OHdG and 19.4% (95% CI: 11.7%, 27.1%) increase in 8-OHG, and for total of BPs (the sum of BPA, BPS, BPF, and BPAF), they were 17.4% (95% CI: 8.9%, 26.0%) for 8-OHdG and 25.9% (95% CI: 16.1%, 35.7%) for 8-OHG, respectively. BPS was positively associated with 8-OHG, but not with 8-OHdG. The study found positive associations of urinary levels of BPA and total BPs with 8-OHdG and 8-OHG and indicated that BPs exposure might cause oxidative RNA damage.
اظهر المزيد [+] اقل [-]Transcriptomic analysis of short-term 17α-ethynylestradiol exposure in two Californian sentinel fish species sardine (Sardinops sagax) and mackerel (Scomber japonicus) النص الكامل
2019
Renaud, Ludivine | Agarwal, Nisha | Richards, Dylan J. | Falcinelli, Silvia | Hazard, E Starr | Carnevali, Oliana | Hyde, John | Hardiman, Gary
Endocrine disrupting chemicals (EDCs) are substances which disrupt normal functioning of the endocrine system by interfering with hormone regulated physiological pathways. Aquatic environments provide the ultimate reservoir for many EDCs as they enter rivers and the ocean via effluent discharges and accumulate in sediments. One EDC widely dispersed in municipal wastewater effluent discharges is 17α-ethynylestradiol (EE2), which is one of the most widely prescribed medicines. EE2 is a bio-active estrogen employed in the majority of oral contraceptive pill formulations. As evidence of the health risks posed by EDCs mount, there is an urgent need to improve diagnostic tools for monitoring the effects of pollutants. As the cost of high throughput sequencing (HTS) diminishes, transcriptional profiling of an organism in response to EDC perturbation presents a cost-effective way of screening a wide range of endocrine responses. Coastal pelagic filter feeding fish species analyzed using HTS provide an excellent tool for EDC risk assessment in the marine environment. Unfortunately, there are limited genome sequence data and annotation for many of these species including Pacific sardine (Sardinops sagax) and chub mackerel (Scomber japonicus), which limits the utility of molecular tools such as HTS to interrogate the effects of endocrine disruption. In this study, we carried out RNA sequencing (RNAseq) of liver RNA harvested from wild sardine and mackerel exposed for 5 h under laboratory conditions to a concentration of 12.5 pM EE2 in the tank water. We developed an analytical framework for transcriptomic analyses of species with limited genomic information. EE2 exposure altered expression patterns of key genes involved in important metabolic and physiological processes. The systems approach presented here provides a powerful tool for obtaining a comprehensive picture of endocrine disruption in aquatic organisms.
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