Multiomics Analysis of PCB126's Effect on a Mouse Chronic-Binge Alcohol Feeding Model.

BACKGROUND: Environmental pollutants, including polychlorinated biphenyls (PCBs) have been implicated in the pathogenesis of liver disease. Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in a rodent model of alcohol-associated liver disease (ALD). OBJECTIVE: To better understand how PCB126 promoted ALD in our previous model, the current study adopts multiple omics approaches to elucidate potential mechanistic hypotheses. METHODS: Briefly, male C57BL/6J mice were exposed to 0.2mg/kg polychlorinated biphenyl (PCB) 126 or corn oil vehicle prior to ethanol (EtOH) or control diet feeding in the chronic-binge alcohol feeding model. Liver tissues were collected and prepared for mRNA sequencing, phosphoproteomics, and inductively coupled plasma mass spectrometry for metals quantification. RESULTS: Principal component analysis showed that PCB126 uniquely modified the transcriptome in EtOH-fed mice. EtOH feeding alone resulted in >4,000 differentially expressed genes (DEGs), and PCB126 exposure resulted in more DEGs in the EtOH-fed group (907 DEGs) in comparison with the pair-fed group (503 DEGs). Top 20 significant gene ontology (GO) biological processes included "peptidyl tyrosine modifications," whereas top 25 significantly decreasing GO molecular functions included "metal/ion/zinc binding." Quantitative, label-free phosphoproteomics and western blot analysis revealed no major significant PCB126 effects on total phosphorylated tyrosine residues in EtOH-fed mice. Quantified hepatic essential metal levels were primarily significantly lower in EtOH-fed mice. PCB126-exposed mice had significantly lower magnesium, cobalt, and zinc levels in EtOH-fed mice. DISCUSSION: Previous work has demonstrated that PCB126 is a modifying factor in metabolic dysfunction-associated steatotic liver disease (MASLD), and our current work suggests that pollutants also modify ALD. PCB126 may, in part, be contributing to the malnutrition aspect of ALD, where metal deficiency is known to contribute and worsen prognosis. https://doi.org/10.1289/EHP14132.

Relationship between phthalates exposures and metabolic dysfunction-associated fatty liver disease in United States adults.

As a new definition for the evidence of hepatic steatosis and metabolic dysfunctions, the relationship between phthalates (PAEs) and metabolic dysfunction-associated fatty liver disease (MAFLD) remains virtually unexplored. This study included 3,137 adults from the National Health and Nutrition Examination Survey spanning 2007-2018. The diagnosis of MAFLD depended on the US Fatty Liver Index (US FLI) and evidence of metabolic dysregulation. Eleven metabolites of PAEs were included in the study. Poisson regression, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were used to assess the associations between phthalate metabolites and MAFLD. After adjusting for potential confounders, Poisson regression analysis showed that mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate were generally significant positively associated with MAFLD (P<0.05). Furthermore, the WQS index constructed for the eleven phthalates was significantly related to MAFLD (OR:1.43; 95%CI: 1.20, 1.70), MEHHP (33.30%), MEP (20.84%), MECPP (15.43%), and mono-isobutyl phthalate (11.78%) contributing the most. This study suggests that exposure to phthalates, individually or in combination, may be associated with an increased risk of MAFLD.

Assessing preconception exposure to environmental chemicals and fecundity: Strategies, challenges, and research priorities.

In 2022, approximately one out of six people globally experienced infertility at some point in their life. Environmental chemicals, particularly those with endocrine disrupting activity, may contribute to impaired fecundity and infertility. We review existing prospective cohort studies of environmental chemicals and fecundity, identify methodological challenges and biases, and outline future research priorities. Studies of preconception environmental chemical exposures and fecundity have occurred in US, Singapore, China and Denmark with recruitment as early as 1982-1986, as recent as 2015-2017 and sample sizes ranging from 99 to 936. Higher exposure to certain chemicals (e.g. heavy metals, perfluoroalkyl substances) was associated with longer time to pregnancy; yet the literature is scarce or nonexistent for many chemicals. Furthermore, prospective studies face challenges and potential biases related to recruiting participants prior to conception, measuring environmental chemicals during critical windows of exposure, and ascertaining when pregnancy occurred. Research priorities include expanding the scope of biomonitoring data collected during the preconception period, continuing to develop and validate analytic methods for self-sampled biospecimens in traditional and novel matrices, collecting data in male partners and investigating etiologic associations according to indicators of marginalization.

Environmental Pollution and Risk of Childhood Cancer: A Scoping Review of Evidence from the Last Decade.

The long-term effects of environmental pollution have been of concern as several pollutants are carcinogenic, potentially inducing a variety of cancers, including childhood cancer, which is a leading cause of death around the world and, thus, is a public health issue. The present scoping review aimed to update and summarize the available literature to detect specific environmental pollutants and their association with certain types of childhood cancer. Studies published from 2013 to 2023 regarding environmental pollution and childhood cancer were retrieved from the PubMed database. A total of 174 studies were eligible for this review and were analyzed. Our search strategy brought up most of the articles that evaluated air pollution (29%) and pesticides (28%). Indoor exposure to chemicals (11%), alcohol and tobacco use during pregnancy (16%), electromagnetic fields (12%), and radon (4%) were the subjects of less research. We found a particularly high percentage of positive associations between prenatal and postnatal exposure to indoor (84%) and outdoor (79%) air pollution, as well as to pesticides (82%), and childhood cancer. Positive associations were found between leukemia and pesticides and air pollution (33% and 27%); CNS tumors and neuroblastoma and pesticides (53% and 43%); and Wilms tumor and other rare cancers were found in association with air pollution (50%). Indoor air pollution was mostly reported in studies assessing several types of cancer (26%). Further studies are needed to investigate the mechanisms underlying the potential associations between indoor/outdoor air pollution and pesticide exposure with childhood cancer risk as more preventable measures could be taken.

Environmental pollutants and exosomes: A new paradigm in environmental health and disease.

This study investigates the intricate interplay between environmental pollutants and exosomes, shedding light on a novel paradigm in environmental health and disease. Cellular stress, induced by environmental toxicants or disease, significantly impacts the production and composition of exosomes, crucial mediators of intercellular communication. The heat shock response (HSR) and unfolded protein response (UPR) pathways, activated during cellular stress, profoundly influence exosome generation, cargo sorting, and function, shaping intercellular communication and stress responses. Environmental pollutants, particularly lipophilic ones, directly interact with exosome lipid bilayers, potentially affecting membrane stability, release, and cellular uptake. The study reveals that exposure to environmental contaminants induces significant changes in exosomal proteins, miRNAs, and lipids, impacting cellular function and health. Understanding the impact of environmental pollutants on exosomal cargo holds promise for biomarkers of exposure, enabling non-invasive sample collection and real-time insights into ongoing cellular responses. This research explores the potential of exosomal biomarkers for early detection of health effects, assessing treatment efficacy, and population-wide screening. Overcoming challenges requires advanced isolation techniques, standardized protocols, and machine learning for data analysis. Integration with omics technologies enhances comprehensive molecular analysis, offering a holistic understanding of the complex regulatory network influenced by environmental pollutants. The study underscores the capability of exosomes in circulation as promising biomarkers for assessing environmental exposure and systemic health effects, contributing to advancements in environmental health research and disease prevention.

A realistic mixture of ubiquitous persistent organic pollutants affects bone and cartilage development in zebrafish by interaction with nuclear receptor signaling.

"Persistent organic pollutants (POPs)" have a plethora of deleterious effects on humans and the environment due to their bioaccumulative, persistent, and mimicking properties. Individually, each of these chemicals has been tested and its effects measured, however they are rather found as parts of complex mixtures of which we do not fully grasp the extent of their potential consequences. Here we studied the effects of realistic, environmentally relevant mixtures of 29 POPs on cartilage and bone development using zebrafish as a model species. We observed developmental issues in cartilage, in the form of diverse malformations such as micrognathia, reduced size of the Meckel's and other structures. Also, mineralized bone formation was disrupted, hence impacting the overall development of the larvae at later life stages. Assessment of the transcriptome revealed disruption of nuclear receptor pathways, such as androgen, vitamin D, and retinoic acid, that may explain the mechanisms of action of the compounds within the tested mixtures. In addition, clustering of the compounds using their chemical signatures revealed structural similarities with the model chemicals vitamin D and retinoic acid that can explain the effects and/or enhancing the phenotypes we witnessed. Further mechanistic studies will be required to fully understand this kind of molecular interactions and their repercussions in organisms. Our results contribute to the already existing catalogue of deleterious effects caused by exposure to POPs and help to understand the potential consequences in at risk populations.

Influence of lead-induced toxicity on the inflammatory cytokines.

Lead (Pb2+) is a hazardous heavy metal that is pervasive in the human environment as a result of anthropogenic activity, and poses serious health risks, particularly in children. Due to its innumerable unique physical and chemical properties, it has various applications; therefore, it has become a common environmental pollutant. Lead may cause oxidative stress, and accumulating evidence indicates that oxidative stress influences the pathophysiology of lead poisoning, also called plumbism. The immune system is continually exposed to various environmental pathogens and xenobiotics, including heavy metals such as lead, and appears to be one of the most vulnerable targets. After being exposed to lead, cells are subjected to oxidative stress as a result of reactive oxygen species (ROS) production. When the generation and consumption of ROS are out of equilibrium, various cell structures, particularly phospholipids are disrupted leading to lipid peroxidation. Various inflammatory signalling pathways are activated as a consequence, along with reduced disease resistance, inflammation, autoimmunity, sensitization and disruption of the cell-mediated and humoral immune systems. Lead negatively affects the metabolism of cytokines, including the interleukins IL-2, IL-1b, IL-6, IL-4, IL-8, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN), as well as the expression and functioning of inflammatory enzymes such as cyclooxygenases. However, the cause of toxicity depends on the kind of lead, dosage, route of entry, exposure period, age, host and genetic predisposition.

Exploring the impact of prenatal perfluoroalkyl and polyfluoroalkyl substances exposure on blood pressure in early childhood: A longitudinal analysis.

Previous research investigating the correlation between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and subsequent blood pressure (BP) in offspring has yielded limited and contradictory findings. This study was conducted to investigate the potential relationship between maternal PFAS levels during pregnancy and subsequent BP in early childhood. A total of 129 expectant mothers from the Shanghai Birth Cohort were included in the study. Using high-performance liquid chromatography/tandem mass spectrometry, we measured ten PFAS compounds in maternal plasma throughout the pregnancy. When the children reached the age of 4, we examined their systolic BP (SBP) and diastolic BP (DBP), along with mean arterial pressure (MAP) and pulse pressure (PP). Data interpretation employed multiple linear and logistic regression models, complemented by Bayesian kernel machine regression (BKMR).We found that the majority of PFAS concentrations remained stable during pregnancy. The linear and BKMR models indicated a positive relationship between the PFAS mixture in maternal plasma and offspring's DBP and MAP, with perfluorohexanesulphonic acid (PFHxS) having the most significant influence (PFHxS and DBP [first trimester:ß=3.03, 95%CI: (1.01,5.05); second trimester: ß=2.35, 95%CI: (0.94,3.75); third trimester: ß=2.57, 95%CI:(0.80,4.34)]; MAP [first trimester:ß=2.55, 95%CI: (0.64,4.45); second trimester: ß=2.28, 95%CI: (0.95,3.61); third trimester: ß=2.35, 95%CI:(0.68,4.01)]). Logistic regression highlighted an increased risk of prehypertension and hypertension in offspring with higher maternal PFHxS concentrations during all three trimesters [first trimester: OR=2.53, 95%CI:(1.11,5.79), second trimester: OR=2.05, 95%CI:(1.11,3.78), third trimester: OR=3.08, 95%CI:(1.40,6.79)]. A positive correlation was identified between the half-lives of PFAS and the odds ratio (OR) of prehypertension and hypertension in childhood (ß=0.139, P=0.010). In conclusion, this research found maternal plasma PFAS concentrations to be positively associated with BP in offspring, with PFHxS showing the most significant influence. This correlation remained consistent throughout pregnancy, and this effect was proportional to the half-lives of PFAS.

Pollutants to pathogens: The role of heavy metals in modulating TGF-ß signaling and lung cancer risk.

Lung cancer is a malignant tumor that develops in the lungs due to the uncontrolled growth of aberrant cells. Heavy metals, such as arsenic, cadmium, mercury, and lead, are metallic elements characterized by their high atomic weights and densities. Anthropogenic activities, such as industrial operations and pollution, have the potential to discharge heavy metals into the environment, hence presenting hazards to ecosystems and human well-being. The TGF-ß signalling pathways have a crucial function in controlling several cellular processes, with the ability to both prevent and promote tumor growth. TGF-ß regulates cellular responses by interacting in both canonical and non-canonical signalling pathways. Research employing both in vitro and in vivo models has shown that heavy metals may trigger TGF-ß signalling via complex molecular pathways. Experiments conducted in a controlled laboratory environment show that heavy metals like cadmium and arsenic may directly bind to TGF-ß receptors, leading to alterations in their structure that enable the receptor to be phosphorylated. Activation of this route sets in motion subsequent signalling cascades, most notably the canonical Smad pathway. The development of lung cancer has been linked to heavy metals, which are ubiquitous environmental pollutants. To grasp the underlying processes, it is necessary to comprehend their molecular effect on TGF-ß pathways. With a particular emphasis on its consequences for lung cancer, this abstract delves into the complex connection between exposure to heavy metals and the stimulation of TGF-ß signalling.

Prenatal PFAS exposure, gut microbiota dysbiosis, and neurobehavioral development in childhood.

Studies on the role of the gut microbiota in the associations between per- and polyfluoroalkyl substance (PFAS) exposure and adverse neurodevelopment are limited. Umbilical cord serum and faeces samples were collected from children, and the Strengths and Difficulties Questionnaire (SDQ) was conducted. Generalized linear models, linear mixed-effects models, multivariate analysis by linear models and microbiome regression-based kernel association tests were used to evaluate the associations among PFAS exposure, the gut microbiota, and neurobehavioural development. Perfluorohexane sulfonic acid (PFHxS) exposure was associated with increased scores for conduct problems and externalizing problems, as well as altered gut microbiota alpha and beta diversity. PFHxS concentrations were associated with higher relative abundances of Enterococcus spp. but lower relative abundances of several short-chain fatty acid-producing genera (e.g., Ruminococcus gauvreauii group spp.). PFHxS exposure was also associated with increased oxidative phosphorylation. Alpha and beta diversity were found significantly associated with conduct problems and externalizing problems. Ruminococcus gauvreauii group spp. abundance was positively correlated with prosocial behavior scores. Increased alpha diversity played a mediating role in the associations of PFHxS exposure with conduct problems. Our results suggest that the gut microbiota might play an important role in PFAS neurotoxicity, which may have implications for PFAS control.

Stima dei decessi attribuibili all'inquinamento da NO2, PM10 e PM2,5 nella Città di Milano nel 2019.

BACKGROUND: there is growing evidence that exposure to environmental pollutants affects health, including mortality, chronic diseases, and acute diseases. The World Health Organisation has recently revised downwards the safety thresholds for exposure to environmental pollutants. The City of Milan (CoM) has particularly high levels of pollution; this is due both to the presence of various emission sources and to climatic and orographic conditions. OBJECTIVES: to describe the health effects of exposure to pollutants, measured by deaths due to environmental exposure to NO2, PM10, and PM2.5 in 2019. DESIGN: observational study. Using a pollutant concentration estimation model, annual mean values of NO2, PM10, and PM2.5 were estimated for the CoM in 2019. The number of deaths attributable to each exposure was estimated using risk functions available in the literature; the values recommended by the new World Health Organisation guidelines were used as counterfactual exposure limits. SETTING AND PARTICIPANTS: the population assisted by the Agency for Health Protection of Milan and resident in the CoM on 01.01.2019, aged 30 years or older. The place of residence was georeferenced and the population was followed up until 31.12.2019. Deaths and their causes were obtained from the Causes of Death Registry. MAIN OUTCOME MEASURES: deaths attributable to exposure from non-accidental causes, cardiovascular diseases, respiratory diseases, and lung cancer were estimated. RESULTS: in 2019, the estimated annual average level of NO2 was 36.6 µg/m3, that of PM10 was 24.9 µg/m3, and that of PM2.5 was 22.4 µg/m3, with levels varying across the city area. Concerning exposure to NO2, in 2019 10% of deaths for natural causes were estimated to be attributable to annual mean levels of NO2 above 10 µg/m3. As regard PM2.5, 13% of deaths for natural causes and 18% of deaths from lung cancer were attributable to an annual mean level above 5 µg/m3. The impact of exposure to particulate matter on mortality does not seem to be the same in all the areas of the CoM. CONCLUSIONS: the health impact of exposure to airborne particulate matter in the CoM population is high. It is important that citizens, policy-makers, and stakeholders address this issue, because of its impact on both health and healthcare costs.

Photoreactivity of polycyclic aromatic hydrocarbons (PAHs) and their mechanisms of phototoxicity against human immortalized keratinocytes (HaCaT).

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic compounds in the environment. They are produced by many anthropogenic sources of different origins and are known for their toxicity, carcinogenicity, and mutagenicity. Sixteen PAHs have been identified as Priority Pollutants by the US EPA, which are often associated with particulate matter, facilitating their dispersion through air and water. When human skin is exposed to PAHs, it might occur simultaneously with solar radiation, potentially leading to phototoxic effects. Phototoxic mechanisms involve the generation of singlet oxygen and reactive oxygen species, DNA damage under specific light wavelengths, and the formation of charge transfer complexes. Despite predictions of phototoxic properties for some PAHs, there remains a paucity of experimental data. This study examined the photoreactive and phototoxic properties of the 16 PAHs enlisted in the Priority Pollutants list. Examined PAHs efficiently photogenerated singlet oxygen and superoxide anion in simple solutions. Furthermore, singlet oxygen phosphorescence was detected in PAH-loaded HaCaT cells. Phototoxicity against human keratinocytes was evaluated using various assays. At 5 nM concentration, examined PAHs significantly reduced viability and mitochondrial membrane potential of HaCaT cells following the exposure to solar simulated light. Analyzed compounds induced a substantial peroxidation of cellular proteins after light treatment. The results revealed that a majority of the examined PAHs exhibited substantial reactive oxygen species photoproduction under UVA and violet-blue light, with their phototoxicity corresponding to their photoreactive properties. These findings improve our comprehension of the interactions between PAHs and human skin cells under environmental conditions, particularly when exposed to solar radiation.

Toxicity of urban stormwater on Chlorella pyrenoidosa: Implications for reuse safety.

Urban stormwater is an alternative water source used to mitigate water resource shortages, and ensuring the safety of stormwater reuse is essential. An in-depth understanding of both individual pollutant concentrations/loads in stormwater and holistic stormwater quality can be used to comprehensively evaluate how safely stormwater can be reused. The toxicity test takes all pollutants present in water samples into account, and the results reflect the integrated effect of these pollutants. In this study, the influence of urban stormwater sourced from different land uses on microalgae (Chlorella pyrenoidosa) and the possible toxicity mechanisms were investigated. The results showed that urban stormwater, particularly residential road stormwater, significantly inhibited microalgal growth. The chlorophyll contents of microalgae exposed to residential road stormwater were relatively lower, while the corresponding values were relatively higher for microalgae exposed to grassland road stormwater. Additionally, the antioxidant-related metabolism of microalgae could be dysregulated due to exposure to urban stormwater. A possible toxicity mechanism is that urban stormwater influences metabolic pathways related to chlorophyll synthesis and further hinders photosynthesis and hence microalgal growth. To resist oxidative stress and maintain regular microalgal cell activities, the ribosome metabolism pathway was upregulated. The research results contribute to elucidating the toxicity effects of urban stormwater and hence provide useful insight for ensuring the safety of stormwater reuse. It is also worth noting that the study outcomes can only represent the influence of land use on stormwater toxicity, while the impacts of other factors (particularly rainfall-runoff characteristics) have not been considered. Therefore, the consideration of all influential factors of stormwater is strongly recommended to generate more robust results in the future and provide more effective guidance for real practices related to stormwater reuse safety.

Combined effect of polystyrene nanoplastic and di-n-butyl phthalate on testicular health of male Swiss albino mice: analysis of sperm-related parameters and potential toxic effects.

Plastics, especially polystyrene nanoplastic particles (PSNPs), are known for their durability and absorption properties, allowing them to interact with environmental pollutants such as di-n-butyl phthalate (DBP). Previous research has highlighted the potential of these particles as carriers for various pollutants, emphasizing the need to understand their environmental impact comprehensively. This study focuses on the subchronic exposure of male Swiss albino mice to PSNP and DBP, aiming to investigate their reproductive toxicity between these pollutants in mammalian models. The primary objective of this study is to examine the reproductive toxicity resulting from simultaneous exposure to PSNP and DBP in male Swiss albino mice. The study aims to analyze sperm parameters, measure antioxidant enzyme activity, and conduct histopathological and morphometric examinations of the testis. By investigating the individual and combined effects of PSNP and DBP, the study seeks to gain insights into their impact on the reproductive profile of male mice, emphasizing potential synergistic interactions between these environmental pollutants. Male Swiss albino mice were subjected to subchronic exposure (60 days) of PSNP (0.2 mg/m, 50 nm size) and DBP (900 mg/kg bw), both individually and in combination. Various parameters, including sperm parameters, antioxidant enzyme activity, histopathological changes, and morphometric characteristics of the testis, were evaluated. The Johnsen scoring system and histomorphometric parameters were employed for a comprehensive assessment of spermatogenesis and testicular structure. The study revealed non-lethal effects within the tested doses of PSNP and DBP alone and in combination, showing reductions in body weight gain and testis weight compared to the control. Individual exposures and the combination group exhibited adverse effects on sperm parameters, with the combination exposure demonstrating more severe outcomes. Structural abnormalities, including vascular congestion, Leydig cell hyperplasia, and the extensive congestion in tunica albuginea along with both ST and Leydig cell damage, were observed in the testis, underscoring the reproductive toxicity potential of PSNP and DBP. The Johnsen scoring system and histomorphometric parameters confirmed these findings, providing interconnected results aligning with observed structural abnormalities. The study concludes that simultaneous exposure to PSNP and DBP induces reproductive toxicity in male Swiss albino mice. The combination of these environmental pollutants leads to more severe disruptions in sperm parameters, testicular structure, and antioxidant defense mechanisms compared to individual exposures. The findings emphasize the importance of understanding the interactive mechanisms between different environmental pollutants and their collective impact on male reproductive health. The use of the Johnsen scoring system and histomorphometric parameters provides a comprehensive evaluation of spermatogenesis and testicular structure, contributing valuable insights to the field of environmental toxicology.

Prenatal exposure to poly/perfluoroalkyl substances and risk for congenital heart disease in offspring.

Congenital heart disease (CHD) is the most prevalent congenital malformation worldwide, and the association between per- and polyfluoroalkyl substances (PFASs) exposure and CHD in population has only received limited study. Therefore, we conducted a multicenter case-control study to explore the associations between prenatal exposure to individual PFASs, and also a PFAS mixture, and CHD risk, including 185 CHDs and 247 controls in China from 2016 to 2021. Thirteen PFASs in maternal plasma were quantified using liquid chromatography-tandem mass spectrometry. Logistic regression and two multipollutant models (Bayesian kernel machine regression [BKMR] and quantile g-computation [qgcomp]) were used to assess the potential associations between any individual PFAS, and also a PFAS mixture, and CHD risk. After adjusting for potential confounders, logistic regression indicated significant associations between elevated levels of perfluorononanoic acid (odds ratio [OR]= 1.30, 95% confidence intervals [CI]: 1.07-1.58), perfluorodecanoic acid (OR=2.07, 95%CI: 1.32-3.26), and perfluoroundecanoic acid (OR=2.86, 95%CI:1.45-5.65) and CHD risk. The BKMR model and qgcomp approach identified that a significant positive association between the PFAS mixture and risk for CHD. These findings provide essential evidence that there is indeed a health crisis associated with PFASs and that it is linked to CHD.

Neurotoxic effects of heavy metal pollutants in the environment: Focusing on epigenetic mechanisms.

The pollution of heavy metals (HMs) in the environment is a significant global environmental issue, characterized by its extensive distribution, severe contamination, and profound ecological impacts. Excessive exposure to heavy metal pollutants can damage the nervous system. However, the mechanisms underlying the neurotoxicity of most heavy metals are not completely understood. Epigenetics is defined as a heritable change in gene function that can influence gene and subsequent protein expression levels without altering the DNA sequence. Growing evidence indicates that heavy metals can induce neurotoxic effects by triggering epigenetic changes and disrupting the epigenome. Compared with genetic changes, epigenetic alterations are more easily reversible. Epigenetic reprogramming techniques, drugs, and certain nutrients targeting specific epigenetic mechanisms involved in gene expression regulation are emerging as potential preventive or therapeutic tools for diseases. Therefore, this review provides a comprehensive overview of epigenetic modifications encompassing DNA/RNA methylation, histone modifications, and non-coding RNAs in the nervous system, elucidating their association with various heavy metal exposures. These primarily include manganese (Mn), mercury (Hg), lead (Pb), cobalt (Co), cadmium (Cd), nickel (Ni), sliver (Ag), toxic metalloids arsenic (As), and etc. The potential epigenetic mechanisms in the etiology, precision prevention, and target therapy of various neurodevelopmental disorders or different neurodegenerative diseases are emphasized. In addition, the current gaps in research and future areas of study are discussed. From a perspective on epigenetics, this review offers novel insights for prevention and treatment of neurotoxicity induced by heavy metal pollutants.

Ionic and nanoparticulate silver alleviate the toxicity of inorganic mercury in marine microalga Chaetoceros muelleri.

Toxicological effects of silver nanoparticles (SNPs) in different organisms have been studied; however, interactions of SNPs with other environmental pollutants such as mercury are poorly understood. Herein, bioassay tests were performed according to ΟECD 201 guideline to assess the toxic effects induced by mercury ions (mercury chloride, MCl) on the marine microalga Chaetoceros muelleri in the presence of SNPs or silver ions (silver nitrate, SN). Acute toxicity tests displayed that the presence of SNPs or SN (0.01 mg L-1) significantly reduced the toxicity of MCl (0.001, 0.01, 0.1, 1, 10, and 100 mg L-1) and increased the IC50 of MCl from 0.072 ± 0.014 to 0.381 ± 0.029 and 0.676 ± 0.034 mg L-1, respectively. In the presence of SN or SNPs, the mercury-reducing effect on algal population growth significantly decreased. Considering the increase of IC50, the mercury toxicity decreased approximately 5.44 and 9.66 times in the presence of SNPs or SN, respectively. The chlorophyll a and c contents decreased at all exposures; however, the decrease by MCl-SNPs and MCl-SN was significantly less than MCl except at 1 mg L-1. The lowering effect of MCl-SN on chlorophyll contents was less than MCl and MCl-SNPs. MCl exposure induced significant raises in total protein content (TPC) at concentrations < 0.01mg  L-1, with a maximum of ~ 70.83% attained at 100 mg L-1. The effects of MCl-SNPs and MCl-SN on TPC were significantly less than MCl. Total lipid content (TLC) at all MCl concentrations was higher than the control, while at coexposure to MCl-SN, TLC did not change until 0.01 mg L-1 compared with the control. The effects of MCl-SN and MCL-SNPs on TPC and TLC were in line with toxicity results, and were significantly less than those of MCl individually, confirming their antagonistic effects on MCl. The morphological changes of algal cells and mercury content of the cell wall at MCl-SN and MCl-SNPs were mitigated compared with MCl exposure. These findings highlight the mitigatory impacts of silver species on mercury toxicity, emphasizing the need for better realizing the mixture toxicity effects of pollutants in the water ecosystem.

Could the gut microbiota be capable of making individuals more or less susceptible to environmental toxicants?

Environmental toxicants are chemical substances capable to impair environmental quality and exert adverse effects on humans and other animals. The main routes of exposure to these pollutants are through the respiratory tract, skin, and oral ingestion. When ingested orally, they will encounter trillions of microorganisms that live in a community - the gut microbiota (GM). While pollutants can disrupt the GM balance, GM plays an essential role in the metabolism and bioavailability of these chemical compounds. Under physiological conditions, strategies used by the GM for metabolism and/or excretion of xenobiotics include reductive and hydrolytic transformations, lyase and functional group transfer reactions, and enzyme-mediated functional transformations. Simultaneously, the host performs metabolic processes based mainly on conjugation, oxidation, and hydrolysis reactions. Thus, due to the broad variety of bacterial enzymes present in GM, the repertoire of microbial transformations of chemicals is considered a key component of the machinery involved in the metabolism of pollutants in humans and other mammals. Among pollutants, metals deserve special attention once contamination by metals is a worldwide problem, and their adverse effects can be observed even at very low concentrations due to their toxic properties. In this review, bidirectional interaction between lead, arsenic, cadmium, and mercury and the host organism and its GM will be discussed given the most recent literature, presenting an analysis of the ability of GM to alter the host organism's susceptibility to the toxic effects of heavy metals, as well as evaluating the extent to which interventions targeting the microbiota could be potential initiatives to mitigate the adverse effects resulting from poisoning by heavy metals. This study is the first to highlight the overlap between some of the bacteria found to be altered by metal exposure and the bacteria that also aid the host organism in the metabolism of these metals. This could be a key factor to determine the beneficial species able to minimize the toxicity of metals in future therapeutic approaches.

Innovative overview of the occurrence, aging characteristics, and ecological toxicity of microplastics in environmental media.

Microplastics (MPs), pollutants detected at high frequency in the environment, can be served as carriers of many kinds of pollutants and have typical characteristics of environmental persistence and bioaccumulation. The potential risks of MPs ecological environment and health have been widely concerned by scholars and engineering practitioners. Previous reviews mostly focused on the pollution characteristics and ecological toxicity of MPs, but there were few reviews on MPs analysis methods, aging mechanisms and removal strategies. To address this issue, this review first summarizes the contamination characteristics of MPs in different environmental media, and then focuses on analyzing the detection methods and analyzing the aging mechanisms of MPs, which include physical aging and chemical aging. Further, the ecotoxicity of MPs to different organisms and the associated enhanced removal strategies are outlined. Finally, some unresolved research questions related to MPs are prospected. This review focuses on the ageing and ecotoxic behaviour of MPs and provides some theoretical references for the potential environmental risks of MPs and their deep control.