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GCN5-mediated PKM2 acetylation participates in benzene-induced hematotoxicity through regulating glycolysis and inflammation via p-Stat3/IL17A axis
2022
Zhang, Wei | Guo, Xiaoli | Ren, Jing | Chen, Yujiao | Wang, Jingyu | Gao, Ai
Benzene is a common environmental carcinogen that induces leukemia. Studies suggest that metabolic disorder has a relationship with the toxicity of benzene. Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. However, the upstream and downstream regulatory mechanisms of PKM2 in benzene-induced hematotoxicity and the therapeutic effects of targeting PKM2 in vivo are unclear. This study aims to provide insights into the new mechanism of benzene-induced hematotoxicity and reveal the therapeutic significance of targeting PKM2. Herein, we demonstrated that PKM2-dependent glycolysis contributes to benzene-induced hematotoxicity by regulating inflammation reaction. Mechanistically, acetylated proteomics revealed that 1,4-benzoquinone (1,4-BQ) induced acetylation of PKM2 at position K66, and this modification contributed to the increase of PKM2 expression and can be inhibited by inhibition of acetyltransferase GCN5. Meanwhile, the elevated PKM2 was shown to prompt the activation of nuclear phosphorylated Stat3 (p-Stat3) and IL17A. Clinically, pharmacological inhibition of PKM2 alleviated the blood toxicity induced by benzene, which was mainly characterized by an increase in routine blood parameters and improvement of hematopoietic imbalance. Besides, elevated PKM2 is a promising biomarker in people occupationally exposed to benzene. Overall, we identified PKM2/p-Stat3/IL-17A axis participates in the hematotoxicity of benzene, and targeting PKM2 has certain therapeutic implications in hematologic diseases.
Afficher plus [+] Moins [-]Chronic carbon black nanoparticles exposure increases lung cancer risk by affecting the cell cycle via circulatory inflammation
2022
Zhang, Jianzhong | Li, Xin | Cheng, Wenting | Li, Yanting | Shi, Teng | Jiang, Yingying | Wang, Tao | Wang, Hongmei | Ren, Dunqiang | Zhang, Rong | Zheng, Yuxin | Tang, Jinglong
As a widely used pure elemental carbon in colloidal particles, carbon black was listed as a group 2B carcinogen by IARC in 2010. The most available mechanism information about carbon black and carcinogenesis are from in vivo or in vitro studies. However, few studies concerned the nanoparticle's real-ambient exposure causing systemic change and further affecting the target organ. Herein, we used an ex vivo biosensor assay to investigate the transcriptome change of primary bronchial epithelial cells after treatment with the plasma from workers with long-term occupational carbon black exposure history. Based on ex vivo biosensor assay and transcriptome sequencing, we found the effect of internal systemic environment on epithelial cells after carbon black exposure was an inflammatory response, which mainly activates cell cycle-related pathways. After exposure to carbon black, the internal systemic environment could activate cancer-related pathways like epithelial-mesenchymal transition, hypoxia, TNF-α signaling via NF-κB. The hub genes in the carbon black group (CDC20 and PLK1) and their correlation with the systemic environment were uncovered by constructing the protein-protein interaction network. Inflammatory cytokines, especially CRP, were strongly correlated with the expression of CDC20 and PLK1. Besides, we also find a strong correlation between CDC20 and cytokinesis-block micronucleus endpoints in peripheral blood (rho = 0.591, P < 0.001). Our results show that long-term carbon black exposure might activate cell cycle-related pathways through circulating inflammation and increase the risk of cancer, while the oxidative stress caused by diesel exhaust particles are mainly related to PAHs exposure. After exposure to carbon black, the systemic environment could activate cancer-related pathways like diesel exhaust particles, increasing the risk of lung cancer. These attempts might provide a further understanding of the indirect effect of chronic occupational inhaled carbon black exposure on pulmonary carcinogenesis.
Afficher plus [+] Moins [-]Socioeconomic vulnerability and public water arsenic concentrations across the US
2022
Nigra, Anne E. | Cazacu-De Luca, Adina | Navas-Acien, Ana
Inorganic arsenic is a known human carcinogen and is routinely detected in US community water systems (CWSs). Inequalities in CWS arsenic exist across broad sociodemographic subgroups. Our objective was to evaluate the county-level association between socioeconomic vulnerability and CWS arsenic concentrations across the US. We evaluated previously developed, population-weighted CWS arsenic concentrations (2006–2011) and three socioeconomic domains (the proportion of adults with a high school diploma, median household income, and the Centers for Disease Control and Prevention's overall socioeconomic vulnerability score) for 2,604 conterminous US counties. We used spatial lag models and evaluated the adjusted geometric mean ratio (GMR) of CWS arsenic concentrations per higher socioeconomic domain score corresponding to the interquartile range, and also evaluated flexible quadratic spline models. We also stratified by region and by United States Department of Agriculture Rural-Urban Continuum Codes to assess potential effect measure modification by region and rurality. Associations between socioeconomic vulnerability and CWS arsenic were modified by region and rurality and specific to socioeconomic domain. The fully adjusted GMR (95% CIs) of CWS arsenic per interquartile range higher proportion of adults with a high school education was 0.83 (0.71, 0.98) in the Southwest (corresponding to 17% lower arsenic with higher education), 0.82 (0.71, 0.94) in the Eastern Midwest (18% lower), and 0.65 (0.31, 1.36) in New England (35% lower). Associations between median household income and CWS arsenic were largely null. Higher overall socioeconomic vulnerability was significantly associated with lower CWS arsenic, but only in counties in the Central Midwest and those with total populations less than 20,000. Findings may reflect regional/local differences in both socioeconomic/socio-cultural context and public drinking water regulatory efforts. Across the US, individual domains of socioeconomic vulnerability (especially educational attainment) are more strongly associated with inequalities in CWS arsenic than the complex overall socioeconomic vulnerability index.
Afficher plus [+] Moins [-]Impact of benzo[a]pyrene with other pollutants induce the molecular alternation in the biological system: Existence, detection, and remediation methods
2022
Saravanakumar, Kandasamy | Sivasantosh, Sugavaneswaran | Sathiyaseelan, Anbazhagan | Sankaranarayanan, Alwarappan | Naveen, Kumar Vishven | Zhang, Xin | Jamla, Monica | Vijayasarathy, Sampathkumar | Vishnu Priya, Veeraraghavan | MubarakAli, Davoodbasha | Wang, Myeong-Hyeon
The exposure of benzo [a]pyrene (BaP) in recent times is rather unavoidable than ever before. BaP emissions are sourced majorly from anthropogenic rather than natural provenance from wildfires and volcanic eruptions. A major under-looked source is via the consumption of foods that are deep-fried, grilled, and charcoal smoked foods (meats in particular). BaP being a component of poly aromatic hydrocarbons has been classified as a Group I carcinogenic agent, which has been shown to cause both systemic and localized effects in animal models as well as in humans; has been known to cause various forms of cancer, accelerate neurological disorders, invoke DNA and cellular damage due to the generation of reactive oxygen species and involve in multi-generational phenotypic and genotypic defects. BaP's short and accumulated exposure has been shown in disrupting the fertility of gamete cells. In this review, we have discussed an in-depth and capacious run-through of the various origins of BaP, its economic distribution and its impact as well as toxicological effects on the environment and human health. It also deals with a mechanism as a single compound and its ability to synergize with other chemicals/materials, novel sensitive detection methods, and remediation approaches held in the environment.
Afficher plus [+] Moins [-]Association between urinary propylene oxide metabolite and the risk of dyslexia
2022
Liu, Qi | Wan, Yanjian | Zhu, Bing | Xie, Xinyan | Zhu, Kaiheng | Jiang, Qi | Feng, Yanan | Xiao, Pei | Xiang, Zhen | Wu, Xiaoqian | Zhang, Jiajia | Meng, Heng | Song, Ranran
Although it is a probable human carcinogen, propylene oxide is widely applied in industry and daily life. However, data on neurodevelopmental effects of propylene oxide exposure among children are extremely limited. We aimed to determine the urinary concentrations of propylene oxide metabolite among school-aged children and evaluate the potential association of propylene oxide exposure with risk of dyslexia. A total of 355 dyslexic children and 390 controls were recruited from three cities (Jining, Wuhan, and Hangzhou) in China, between 2017 and 2020. Urinary N-acetyl-S-(2-hydroxypropyl)-L-cysteine (i.e., 2-hydroxypropyl mercapturic acid; 2-HPMA) was measured as the biomarker of propylene oxide exposure. The detection frequency of 2-HPMA was 100%. After adjusting for potential confounders, the odds ratio (OR) for dyslexia per 2-fold increase in urinary 2-HPMA was 1.19 [95% confidence interval (95% CI): 1.01, 1.40, P = 0.042]. Compared with the lowest quartile of urinary 2-HPMA concentrations, children with the highest quartile of 2-HPMA had a 1.63-fold (95% CI: 1.03, 2.56, P = 0.036) significantly increased risk of dyslexia, with a dose-response relationship (P-trend = 0.047). This study provides epidemiological data on the potential association between propylene oxide exposure and the risk of dyslexia in children. Further studies are warranted to confirm the findings and reveal the underlying biological mechanisms.
Afficher plus [+] Moins [-]Replacing the greater evil: Can legalizing decentralized waste burning in improved devices reduce waste burning emissions for improved air quality?
2022
Chaudhary, Pooja | Singh, Raj | Shabin, Muhammed | Sharma, Anita | Bhatt, Sachin | Sinha, Vinayak | Sinha, Baerbel
Open waste burning emissions constitute a significant source of air pollution affecting human health in India. In regions where cleaner fuels have displaced solid biofuel usage, open waste burning is rapidly becoming one of the largest sources of airborne human class-I-carcinogens and particulate matter. As the establishment of waste management infrastructure in rural India is likely to take years, we explore whether health-relevant emissions can be reduced by legalizing the burning of dry non-biodegradable waste in improved devices. We measure the emission factors of 76 VOCs, CH₄, CO, and CO₂ from different types of waste burned in two different improved devices, a burn basket and a local water heater. Based on our experiments, we create four “what-if” intervention scenarios to assess the improvement of air quality due to the emission reductions that can be accomplished by four management strategies. We find that substituting the traditional, more polluting water heating fuels with dry plastic waste across rural India can reduce primary emissions (e.g., −29 Ggy⁻¹ for benzene) and ozone formation potential (−2960 Ggy⁻¹) from open waste burning. When dry waste is used in lieu of more polluting fuels, and its burning serves a purpose, the net class-I-carcinogen benzene emissions, would be halved compared to the present. The change in emissions for the class-I carcinogen 1,3-butadiene would become net negative. This happens because the emissions avoided when part of the solid biofuel currently used in rural India is replaced by plastic waste (4.1 (1.2–4.1) Ggy⁻¹) exceed the waste burning emissions of this compound (3 (1.2–3.7) Ggy⁻¹) by so much, that residential sector emission reductions offset all waste burning emissions including those of landfill fires. Our study demonstrates that India's air quality can be improved by permitting and promoting the use of dry packaging waste in lieu of traditional biofuels and by promoting improved burning devices.
Afficher plus [+] Moins [-]BDE-209 and TCDD enhance metastatic characteristics of melanoma cells after chronic exposure
2022
Silva Filho, Benisio Ferreira | Filipak Neto, Francisco | Marchi, Micheli de | Moggio, Erick Laurent | Rossi, Izadora Volpato | Sabatke, Bruna | Ramirez, Marcel Ivan | Lucena, Miguel Clodomiro dos Santos | Todeschini, Adriane Regina | Oliveira Ribeiro, Ciro Alberto de
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and BDE-209 (decabromodiphenyl ether) are persistent organic pollutants (POPs) produced by industrial activities and associated with several diseases. TCDD is a known human carcinogen, but few studies investigated about the effects of exposure to both compounds, i.e., whether BDE-209 and TCDD can render tumor cells more aggressive and metastatic. In the current study we investigated if the exposure of B16–F1 and B16–F10 melanoma murine cells to environmental relevant concentrations of TCDD and BDE-209 at 24 h and 15-day exposure modulates the expression of genes related to metastasis, making the cells more aggressive. Both pollutants did not affect cell viability but lead to increase of cell proliferation, including the upregulation of vimentin, MMP2, MMP9, MMP14 and PGK1 gene expression and downregulation of E-cadherin, TIMP2, TIMP3 and RECK, strongly suggesting changes in cell phenotypes defined as epithelial to mesenchymal transition (EMT) in BDE-209 and TCDD-exposed cells. Foremost, increased expression of metalloproteinases and decreased expression of their inhibitors made B16–F1 cells similar the more aggressive B16–F10 cell line. Also, the higher secretion of extracellular vesicles by cells after acute exposure to BDE-209 could be related with the phenotype changes. These results are a strong indication of the potential of BDE-209 and TCDD to modulate cell phenotype, leading to a more aggressive profile.
Afficher plus [+] Moins [-]Impact of Water Regimes on Minimizing the Accumulation of Arsenic in Rice (Oryza sativa L.)
2022
Shehzad, Muhammad Tahir | Ṣābir, Muḥammad | Saifullah, | Siddique, Abu Bakkar | Rahman, Mohammad Mahmudur | Naidu, R.
Arsenic (As) is very common pollutant of the environment categorized as class-I human carcinogen. Rice crop is inherently efficient at accumulating As that is also triggered by conventional cropping methods (flooded conditions). A pot experiment was conducted with the objectives to (i) determine the accumulation of As in rice grains and shoots and As species in rice grains, (ii) determine the effect of As concentrations on physiological and agronomic characteristics of the rice crop, and (iii) assess the changes in fractions of As within the soil under different water regimes. Water regimes included flooding, intermittent, intermittent + aerobic, and aerobic irrigation. Grain As concentration from flood-irrigated rice was significantly (P ≤ 0.05) reduced in rice grown in 10 and 50 mg kg⁻¹ As-contaminated soil with less applied irrigation. Water management techniques have influenced As speciation in rice grains. As the irrigation techniques were shifted from flooding to intermittent, intermittent + aerobic, and aerobic irrigation, a significant decrease in concentration of inorganic species (11.98–76.81% at 10 mg kg⁻¹ and 66.04–93.61% at 50 mg kg⁻¹) was observed. Aerobic irrigation has effectively reduced the concentration of arsenic in rice grain as compared to other irrigation techniques in both the As-contaminated soils. This study indicated that irrigation management techniques other than flood irrigation have significantly affected the As (total and speciation) concentration within the rice grains and non-significantly affecting crop yield and this must be considered if regulations are based on inorganic As percentage of total As concentration.
Afficher plus [+] Moins [-]Evaluation of formaldehyde exposure among gross dissection after modified embalming solution and health assessment
2022
Soonklang, Nantawan | Saowakon, Naruwan
Mainly embalming fixative contains formaldehyde which is classified as a carcinogen. People who work with cadavers have been at higher risk of cancer after formaldehyde exposure. We have formulated a less-formalin fixative (contained 3.6% formaldehyde,23.8% ethanol, 15% glycerin, and 0.2% phenol in the water) for preserving cadavers. Therefore, the objective of the present study was to evaluate the level of atmospheric formaldehyde indoors and the breathing exposure of medical students during dissection classes. We also analyzed the pulmonary parameters and effects of formaldehyde. The levels of atmospheric formaldehyde indoors and personal breathing exposure were sampled during anatomy dissection classes (musculoskeletal system, respiratory system, and abdominopelvic organ system) using sorbent tubes with air sampling pumps. Samples were then analyzed using Gas Chromatography with Flame Ionization Detector (GC-FID). The mean level of formaldehyde indoor air among the three classes was 0.518 ± 0.156 ppm whereas the formaldehyde level in the personal breathing zone was 0.956±0.408 ppm, which exceeded the recommended exposure standards of international agencies, including NIOSH agency and PEL of Thailand legislation. The laboratory had high humidity, high room temperature, and poor air ventilation. There was a significant difference in FVC, FEV1, and PEF (p < 0.05) between the sexes of students. Comparison pulmonary parameters between students and instructors showed that all parameters of the pulmonary function test had no significant differences. General fatigue and burnings of eyes and nose associated with strong odor were the most common symptoms reported during the dissection classes. The modified embalming fixative was used less formalin with ethanol-glycerin mixture, and it was suitable for the study of medical students, with few side effects of respiratory problems. However, the modified exhaust ventilation with local table-exhaust ventilation and heating-ventilation-air conditioning system performance were urgent issues for reducing levels of formaldehyde indoor air in the dissection room.
Afficher plus [+] Moins [-]Investigation and probabilistic health risk assessment of pesticide residues in cucumber, tomato, and okra fruits from Khuzestan, Iran
2022
Khoshnam, Farzaneh | Ziaee, Masumeh | Daei, Mina | Mahdavi, Vahideh | Mousavi Khaneghah, Amin
In this study, 30 pesticide residues in 45 fresh-eating cucumber, tomato, and okra fruit samples collected from the Khuzestan province as the main agricultural products in Iran using the QuEChERS extraction method were analyzed. In addition, noncarcinogen and carcinogen health risk assessments were evaluated. Results indicated that 93% of cucumber samples had at least one pesticide, of course, less than the maximum residue limit (MRL). All tomato and okra fruit samples were contaminated by diazinon. All pesticides detected in tomato samples were below national MRL except for thiamethoxam in four samples. In okra fruit samples, all detected diazinon and malathion, but only tebuconazole fungicide exceeded MRL. In addition, the hazard index (HI) was 0.23 and 1.06 in cucumber samples, 0.33 and 1.51 in tomato samples, and 5.5E-03 and 0.025 in okra fruit samples in adults and children, respectively. The use of cucumber and tomato may have notable risks in the short term in children group age. Ranking based on total CR was 1.2E-05 in tomato, 7.7E-06 for cucumber, and in okra 9.1E-11 because of the difenoconazole residue. However, significant carcinogenic risk threatens cucumber and tomato consumers.
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