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Exposure to fine particulate matter-bound polycyclic aromatic hydrocarbons, male semen quality, and reproductive hormones: The MARCHS study
2021
Chen, Qing | Wang, Furong | Yang, Huan | Wang, Xiaogang | Zhang, Aihua | Ling, Xi | Li, Lianbing | Zou, Peng | Sun, Lei | Huang, Linping | Chen, Hongqiang | Ao, Lin | Liu, Jinyi | Cao, Jia | Zhou, Niya
Exposure to outdoor fine particulate matter (PM₂.₅)-bound polycyclic aromatic hydrocarbons (PAHs) is linked to reproductive dysfunction. However, it is unclear which component of PAHs is responsible for the adverse outcomes. In the Male Reproductive Health in Chongqing College Students (MARHCS) cohort study, we measured the exposure levels of 16 PAHs by collecting air PM₂.₅ particles and assessed eight PAHs metabolites from four parent PAHs, including naphthalene, fluorene, phenanthrene, and pyrene in urine samples. We investigated compositional profiles and variation characteristics for 16 PAHs in PM₂.₅, and then assessed the association between PAHs exposure and semen routine parameters, sperm chromatin structure, and serum hormone levels in 1452 samples. The results showed that naphthalene (95% CI: −17.989, −8.101), chrysene (95% CI: −64.894, −47.575), benzo[a]anthracene (95% CI: −63.227, −45.936) and all the high molecular weight (HMW) PAHs in PM₂.₅ were negatively associated with sperm normal morphology. Most of the low molecular weight (LMW) PAHs, such as acenaphthylene, fluorene, phenanthrene, fluoranthene, pyrene, chrysene, benzo[a]anthracene, ∑LMW PAHs and ∑16 PAHs, were correlated with increased sperm motility (all corrected P < 0.05). On the other hand, sperm normal morphology was all negatively associated with urinary metabolites of ∑OH-Nap (95% CI: −5.611, −0.536), ∑OH-Phe (95% CI: −5.741, −0.957), and ∑OH-PAHs (95% CI: −5.274, −0.361). Urinary concentrations of ∑OH-PAHs were found to be negatively associated with sperm high DNA stainability (HDS) (P = 0.023), while ∑OH-Phe were negatively associated with serum testosterone level and sperm HDS (P = 0.004). Spearman correlation analysis showed that except for the urinary OH-Nap metabolites, the rest of the urinary OH-PAHs metabolites were negatively correlated with their parent PAHs in air. The results of this study suggest that various PAHs’ components may affect reproductive parameters differently. Inhalation of PAHs in air, especially HMW PAHs, may be a potential risk factor for male reproductive health.
Показать больше [+] Меньше [-]Thioredoxin-albumin fusion protein prevents urban aerosol-induced lung injury via suppressing oxidative stress-related neutrophil extracellular trap formation
2021
Tanaka, Ken-ichiro | Kubota, Maho | Shimoda, Mikako | Hayase, Tomoko | Miyaguchi, Mamika | Kobayashi, Nahoko | Ikeda, Mayumi | Ishima, Yu | Kawahara, Masahiro
The number of deaths from air pollution worldwide is estimated at 8.8 million per year, more than the number of deaths from smoking. Air pollutants, such as PM₂.₅, are known to induce respiratory and cardiovascular diseases by inducing oxidative stress. Thioredoxin (Trx) is a 12-kDa endogenous protein that exerts antioxidant activity by promoting dithiol disulfide exchange reactions. We previously synthesized human serum albumin-fused thioredoxin (HSA-Trx), which has a longer half-life in plasma compared with Trx, and demonstrated its efficacy against various diseases including respiratory diseases. Here, we examined the effect of HSA-Trx on urban aerosol-induced lung injury in mice. Urban aerosols induced lung injury and inflammatory responses in ICR mice, but intravenous administration of HSA-Trx markedly inhibited these responses. We next analyzed reactive oxygen species (ROS) production in murine lungs using an in vivo imaging system. The results show that intratracheal administration of urban aerosols induced ROS production that was inhibited by intravenously administered HSA-Trx. Finally, we found that HSA-Trx inhibited the urban aerosol-induced increase in levels of neutrophilic extracellular trap (NET) indicators (i.e., double-stranded DNA, citrullinated histone H3, and neutrophil elastase) in bronchoalveolar lavage fluid (BALF). Together, these findings suggest that HSA-Trx prevents urban aerosol-induced acute lung injury by suppressing ROS production and neutrophilic inflammation. Thus, HSA-Trx may be a potential candidate drug for preventing the onset or exacerbation of lung injury caused by air pollutants.
Показать больше [+] Меньше [-]Indoor heating triggers bacterial ecological links with tap water stagnation during winter: Novel insights into bacterial abundance, community metabolic activity and interactions
2021
Zhang, Haihan | Xu, Lei | Huang, Tinglin | Liu, Xiang | Miao, Yutian | Liu, Kaiwen | Qian, Xuming
The overnight stagnation of tap water in plumbing systems can lead to water quality deterioration. Meanwhile, the indoor heating can improve the indoor temperature in cold areas during winter, which may affect the quality of tap water during stagnation. However, indoor heating drives bacterial ecological links with tap water stagnation during winter are not well understood. The results indicated that the water temperature increased significantly after stagnation during indoor heating periods. Moreover, the average intact cell number and total adenosine triphosphate (ATP) concentration increased 1.53-fold and 1.35-fold after stagnation, respectively (P < 0.01). In addition, the increase in the ATP per cell number indicated that the combined effects of stagnation and indoor heating could enhance the bacterial activity. Biolog data showed that the bacterial community metabolic capacity was significantly higher in stagnant water than that of fresh water. Co-occurrence networks suggested that the bacterial metabolic profile changed after stagnation during the heating periods. DNA analysis indicated that the composition of the bacterial community changed dramatically after stagnation. The abundances of potential pathogens such as Mycobacterium sp. and Pseudomonas sp. also increased after stagnation. These results will give novel insights on comprehensive understanding the combined effects of indoor heating and overnight stagnation on the water bacterial community ecology of plumbing systems, and provide a scientific basis for tap water quality management after overnight stagnation during the indoor heating periods.
Показать больше [+] Меньше [-]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
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.
Показать больше [+] Меньше [-]Dichlorodiphenyltrichloroethane metabolites inhibit DNMT1 activity which confers methylation-specific modulation of the sex determination pathway
2021
Hu, Junjie | Yang, Yan | Lv, Xiaomei | Lao, Zhilang | Yu, Lili
Dichlorodiphenyltrichloroethane (DDT) poses a significant health risk to humans which is associated with genomic DNA hypomethylation. However, the mechanism and biological consequences remain poorly understood. In vitro assays confirmed that the DDT metabolites 2,2-bis(p-chlorophenyl)-acetic acid (DDA) and 1-chloro-2,2-bis-(p-chlorophenyl)ethylene (DDMU), but not other DDT metabolites, significantly inhibited DNA methyltransferase 1 (DNMT1) activity, leading to genomic hypomethylation in cell culture assays. DNMT1 as a target for DNA hypomethylation induced by DDT metabolites was also confirmed using cell cultures in which DNMT1 was silenced or highly expressed. DDA and DDMU can modify methylation markers in the promoter regions of sexual development-related genes, and change the expression of Sox9 and Oct4 in embryonic stem cells. Molecular docking indicated that DDA and DDMU bound to DNMT1 with high binding affinity. Molecular dynamic simulation revealed that DDA and DDMU acted as allosteric modulators that reshaped the conformation of the catalytic domain of DNMT1. These findings provide a new insight into DDT-induced abnormalities in sexual development and demonstrate that selective binding to DNMT1 by DDA and DDMU can interfere with human DNMT1 activity and regulate the expression of the Sox9 and Oct4 genes.
Показать больше [+] Меньше [-]Epigenetic silencing of TET1 mediated hydroxymethylation of base excision repair pathway during lung carcinogenesis
2021
Chen, Hong-qiang | Chen, Dong-jiao | Li, Yan | Yuan, Wen-bo | Fan, Jun | Zhang, Zhe | Han, Fei | Jiang, Xiao | Chen, J. P. (Jian-ping) | Wang, Dan-dan | Cao, Jia | Liu, Jin-yi | Liu, Wen-bin
The methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is an important regulator for the balance of DNA methylation and hydroxymethylation through various pathways. Increasing evidence has suggested that TET1 probably involved in DNA methylation and demethylation dysregulation during chemical carcinogenesis. However, the role and mechanism of TET1 during lung cancer remains unclear. In this study, we found that TET1 expression was significantly down-regulated and the methylation level was significantly up-regulated in 3-methylcholanthrene (3-MCA) induced cell malignant transformation model, rat chemical carcinogenesis model, and human lung cancer tissues. Demethylation experiment further confirmed that DNA methylation negatively regulated TET1 gene expression. TET1 overexpression inhibited cell proliferation, migration and invasion in vitro and in vivo, while knockdown of TET1 resulted in an opposite phenotype. DNA hydroxymethylation level in the promoter region of base excision repair (BER) pathway key genes XRCC1, OGG1, APEX1 significantly decreased and the degree of methylation gradually increased in malignant transformed cells. After differential expression of TET1, the level of hydroxymethylation, methylation and expression of these genes also changed significantly. Furthermore, TET1 binds to XRCC1, OGG1, and APEX1 to maintain them hydroxymethylated. Blockade of BER pathway key gene alone or in combination significantly diminished the effect of TET1. Our study demonstrated for the first time that TET1 expression is regulated by DNA methylation and TET1-mediated hydroxymethylation regulates BER pathway to inhibit the proliferation, migration and invasion during 3-MCA-induced lung carcinogenesis. These results suggested that TET1 gene can be a potential biomarker and therapy target for lung cancer.
Показать больше [+] Меньше [-]In vitro renal toxicity evaluation of copper-based metal–organic framework HKUST-1 on human embryonic kidney cells
2021
Chen, Yi-Chun | Andrew Lin, Kun-Yi | Chen, Ku-Fan | Jiang, Xin-Yu | Lin, Chia-Hua
HKUST-1 is currently studied for a very diverse range of applications. Despite its exciting potential, significant concerns remain regarding the safety of HKUST-1. Therefore, human embryonic kidney 293 (HEK293) cells were used to verify the renal toxicity of HKUST-1. In this study, HKUST-1 induced concentration-dependent cytotoxic effects in HEK293 cells. The depolarization of mitochondrial membrane potential and formation of apoptotic bodies and autophagic vesicles were observed in HKUST-1–treated HEK293 cells. Oxidative (oxidative stress and haem oxygenase-1 activation) and inflammatory responses (NF-κB and NLRP3 activation) in HEK293 cells were induced by HKUST-1 exposure. In addition, the observed reduction in NAD(P)H levels in HKUST-1–treated HEK293 cells may be attributable to PARP-1 activation following DNA single- and double-strand breaks. The HKUST-1–induced depletion of zonula occludens proteins in HEK293 cells might lead to altered renal barrier integrity. The variations of α1-antitrypsin, oxidised α1-antitrypsin and NLRP3 protein expression in HEK293 cells suggested that HKUST-1 increases the risk of chronic kidney diseases. However, most of these adverse effects were significantly induced only by high HKUST-1 concentration (100 μg/mL), which do not reflect the actual exposure. Thus, the toxic risk of HKUST-1 appears to be negligible.
Показать больше [+] Меньше [-]Diversity and predicted inter- and intra-domain interactions in the Mediterranean Plastisphere
2021
Amaral-Zettler, Linda A. | Ballerini, Tosca | Zettler, Erik R. | Asbun, Alejandro Abdala | Adame, Alvaro | Casotti, Raffaella | Dumontet, Bruno | Donnarumma, Vincenzo | Engelmann, Julia C. | Frère, Laura | Mansui, Jeremy | Philippon, Marion | Pietrelli, Loris | Sighicelli, Maria
This study investigated the biogeography, the presence and diversity of potentially harmful taxa harbored, and potential interactions between and within bacterial and eukaryotic domains of life on plastic debris in the Mediterranean. Using a combination of high-throughput DNA sequencing (HTS), Causal Network Analysis, and Scanning Electron Microscopy (SEM), we show regional differences and gradients in the Mediterranean microbial communities associated with marine litter, positive causal effects between microbes including between and within domains of life, and how these might impact the marine ecosystems surrounding them. Adjacent seas within the Mediterranean region showed a gradient in the microbial communities on plastic with non-overlapping endpoints (Adriatic and Ligurian Seas). The largest predicted inter-domain effects included positive effects of a novel red-algal Plastisphere member on its potential microbiome community. Freshwater and marine samples housed a diversity of fungi including some related to disease-causing microbes. Algal species related to those responsible for Harmful Blooms (HABs) were also observed on plastic pieces including members of genera not previously reported on Plastic Marine Debris (PMD).
Показать больше [+] Меньше [-]Adaptation mechanisms of arsenic metabolism genes and their host microorganisms in soils with different arsenic contamination levels around abandoned gold tailings
2021
Li, Xianhong | Liu, Xiaoxia | Cao, Neng | Fang, Songjun | Yu, Caihong
Soil around the gold tailing due to the smelting process of wastewater and solid waste can lead to metal (loids) contamination, especially arsenic (As). Soil microorganisms have gradually evolved adaptive mechanisms in the process of long-term adaptation to As contamination. However, comprehensive investigations on As metabolism genes and their host microbial communities in soil profiles with different levels under long-term As contamination are lacking. There are selected three typical soil profiles (0–100 cm) with different metal (loids) contamination levels (L-low, M-moderate and H-high) around tailings in this research. It uses a Metagenomic approach to explore the adaptation mechanisms of arsenic metabolism genes and arsenic metabolism gene host microorganisms in both horizontal and vertical dimensions. The results showed that four categories of As metabolism genes were prevalent in soil profiles at different As contamination, with As reduction genes being the most abundant, followed by As oxidation genes, then respiration genes and methylation genes. The As metabolism genes arsBCR, aioE, arsPH, arrAB increased with the increase of metal (loid) contaminants concentration. Longitudinal arsA, arrA, aioA, arsM and acr3 increased in abundance in deep soil. Actinobacteria, Proteobacteria, Acidobacteria, and Chloroflexi were the dominant phylum of As metabolism gene host microorganisms. Different concentrations of metal (loid) contamination significantly affected the distribution of host As metabolism genes. Random forest prediction identified As as the most critical driver of As metabolism genes and their host microorganisms. Overall, this study provides a reference for a comprehensive investigation of the detoxification mechanisms of As metabolism microorganisms in soil profiles with different As contamination conditions, and is important for the development of As metabolism gene host microbial strains and engineering applications of microbial technologies to manage As contamination.
Показать больше [+] Меньше [-]Curcumin suppresses cell growth and attenuates fluoride-mediated Caspase-3 activation in ameloblast-like LS8 cells
2021
The trace element fluoride can be beneficial for oral health by preventing dental caries. However, fluoride is also known as an environmental pollutant. Fluoride pollution can lead to fluoride over-ingestion and can cause health issues, including dental fluorosis. Curcumin attenuated fluoride-induced toxicity in animal models, however the molecular mechanisms of how curcumin affects fluoride toxicity remain to be elucidated. We hypothesized that curcumin attenuates fluoride toxicity through modulation of Ac-p53. Here we investigated how curcumin affects the p53-p21 pathway in fluoride toxicity.LS8 cells were treated with NaF with/without curcumin. Curcumin significantly increased phosphorylation of Akt [Thr308] and attenuated fluoride-mediated caspase-3 cleavage and DNA damage marker γH2AX expression. Curcumin-mediated attenuation of caspase-3 activation was reversed by Akt inhibitor LY294002 (LY). However, LY did not alter curcumin-mediated γH2AX suppression. These results suggest that curcumin inhibited fluoride-mediated apoptosis via Akt activation, but DNA damage was suppressed by other pathways. Curcumin did not suppress/alter fluoride-mediated Ac-p53. However, curcumin itself significantly increased Ac-p53 and upregulated p21 protein levels to suppress cell proliferation in a dose-dependent manner. Curcumin suppressed fluoride-induced phosphorylation of p21 and increased p21 levels within the nuclear fraction. However, curcumin did not reverse fluoride-mediated cell growth inhibition. These results suggest that curcumin-induced Ac-p53 and p21 led to cell cycle arrest, while curcumin attenuated fluoride-mediated apoptosis via activation of Akt and suppressed fluoride-mediated DNA damage.By inhibiting DNA damage and apoptosis, curcumin may potentially alleviate health issues caused by fluoride pollution. Further studies are required to better understand the mechanism of curcumin-induced biological effects on fluoride toxicity.
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