HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy.

Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced the occurrence of comorbidities, including ocular manifestations. The involvement of endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation with cellular senescence or its role in initiating senescent traits. This study investigated how ER stress and dysregulated autophagy impact cellular senescence triggered by HIV-1 Tat in the MIO-M1 cell line (human Müller glial cells). Cells exposed to HIV-1 Tat exhibited increased vimentin expression combined with markers of ER stress (BiP, p-eIF2α), autophagy (LC3, Beclin-1, p62), and the senescence marker p21 compared to control cells. Western blotting and staining techniques like SA-ß-gal were employed to examine these markers. Additionally, treatments with ER stress inhibitor 4-PBA before HIV-1 Tat exposure led to a decreased expression of ER stress, senescence, and autophagy markers. Conversely, pre-treatment with the autophagy inhibitor 3-MA resulted in reduced autophagy and senescence markers but did not alter ER stress markers compared to control cells. The findings suggest a link between ER stress, dysregulated autophagy, and the initiation of a senescence phenotype in MIO-M1 cells induced by HIV-1 Tat exposure.

Differential impact of diesel exhaust particles on glutamatergic and dopaminergic neurons in Caenorhabditis elegans: A neurodegenerative perspective.

The growing body of evidence links exposure to particulate matter pollutants with an increased risk of neurodegenerative diseases. In the present study, we investigated whether diesel exhaust particles can induce neurobehavioral alterations associated with neurodegenerative effects on glutamatergic and dopaminergic neurons in Caenorhabditis elegans (C. elegans). Exposure to DEP at concentrations of 0.167 µg/cm2 and 1.67 µg/cm2 resulted in significant developmental delays and altered locomotion behaviour. These effects were accompanied by discernible alterations in the expressions of antioxidant genes sod-3 and gst-4 observed in transgenic strains. Behaviour analysis demonstrated a significant reduction in average speed (p < 0.001), altered paths, and decreased swimming activities (p < 0.01), particularly at mid and high doses. Subsequent assessment of neurodegeneration markers in glutamatergic (DA1240) and dopaminergic (BZ555) transgenic worms revealed notable glutamatergic neuron degeneration at 0.167 µg/cm2 (∼30 % moderate, ∼20 % advanced) and 1.67 µg/cm2 (∼28 % moderate, ∼24 % advanced, p < 0.0001), while dopaminergic neurons exhibited structural deformities (∼16 %) without significant degeneration in terms of blebs and breaks. Furthermore, in silico docking simulations suggest the presence of an antagonistic competitive inhibition induced by DEP in the evaluated neuro-targets, stronger for the glutamatergic transporter than for the dopaminergic receptor from the comparative binding affinity point of view. The results underscore DEP's distinctive neurodegenerative effects and suggest a link between locomotion defects and glutamatergic neurodegeneration in C. elegans, providing insights into environmental health risks assessment.

Differential DNA methylation and metabolite profiling of Atlantic killifish (Fundulus heteroclitus) from the New Bedford Harbor Superfund site.

Atlantic killifish (Fundulus heteroclitus) is a valuable model in evolutionary toxicology to study how the interactions between genetic and environmental factors serve the adaptive ability of organisms to resist chemical pollution. Killifish populations inhabiting environmental toxicant-contaminated New Bedford Harbor (NBH) show phenotypes tolerant to polychlorinated biphenyls (PCBs) and differences at the transcriptional and genomic levels. However, limited research has explored epigenetic alterations and metabolic effects in NBH killifish. To identify the involvement of epigenetic and metabolic regulation in the adaptive response of killifish, we investigated tissue- and sex-specific differences in global DNA methylation and metabolomic profiles of NBH killifish populations, compared to sensitive populations from a non-polluted site, Scorton Creek (SC). The results revealed that liver-specific global DNA hypomethylation and differential metabolites were evident in fish from NBH compared with those from SC. The sex-specific differences were not greater than the tissue-specific differences. We demonstrated liver-specific enriched metabolic pathways (e.g., amino acid metabolic pathways converged into the urea cycle and glutathione metabolism), suggesting possible crosstalk between differential metabolites and DNA hypomethylation in the livers of NBH killifish. Additional investigation of methylated gene regions is necessary to understand the functional role of DNA hypomethylation in the regulation of enzyme-encoding genes associated with metabolic processes and physiological changes in NBH populations.

In Vitro Cell Transformation Assays: A Valuable Approach for Carcinogenic Potentiality Assessment of Nanomaterials.

This review explores the application of in vitro cell transformation assays (CTAs) as a screening platform to assess the carcinogenic potential of nanomaterials (NMs) resulting from continuously growing industrial production and use. The widespread application of NMs in various fields has raised concerns about their potential adverse effects, necessitating safety evaluations, particularly in long-term continuous exposure scenarios. CTAs present a realistic screening platform for known and emerging NMs by examining their resemblance to the hallmark of malignancy, including high proliferation rates, loss of contact inhibition, the gain of anchorage-independent growth, cellular invasion, dysregulation of the cell cycle, apoptosis resistance, and ability to form tumors in experimental animals. Through the deliberate transformation of cells via chronic NM exposure, researchers can investigate the tumorigenic properties of NMs and the underlying mechanisms of cancer development. This article examines NM-induced cell transformation studies, focusing on identifying existing knowledge gaps. Specifically, it explores the physicochemical properties of NMs, experimental models, assays, dose and time requirements for cell transformation, and the underlying mechanisms of malignancy. Our review aims to advance understanding in this field and identify areas for further investigation.

Prediction of zebrafish embryonic developmental toxicity by integrating omics with adverse outcome pathway.

New approach methodologies (NAMs), especially omics-based high-throughput bioassays have been developed rapidly, providing rich mechanistic information such as molecular initiation events (MIEs) and (sub)cellular key events (KEs) in adverse outcome pathways (AOPs). However, how to apply the knowledge of MIEs/KEs to predict adverse outcomes (AOs) induced by chemicals represents a new challenge for computational toxicology. Here, an integrated method named ScoreAOP was developed and evaluated to predict chemicals' developmental toxicity for zebrafish embryos by integrating four related AOPs and dose-dependent reduced zebrafish transcriptome (RZT). The rules of ScoreAOP included 1) sensitivity of responsive KEs demonstrated by point of departure of KEs (PODKE), 2) evidence reliability and 3) distance between KEs and AOs. Moreover, eleven chemicals with different modes of action (MoAs) were tested to evaluate ScoreAOP. Results showed that eight of the eleven chemicals caused developmental toxicity at tested concentration in apical tests. All the tested chemicals' developmental defects were predicted using ScoreAOP, whereas eight out of the eleven chemicals predicted by ScoreMIE which was developed to score MIEs disturbed by chemicals based on in vitro bioassays data. Finally, in terms of mechanism explanation, ScoreAOP clustered chemicals with different MoAs while ScoreMIE failed, and ScoreAOP revealed the activation of aryl hydrocarbon receptor (AhR) plays a significant role in dysfunction of cardiovascular system, resulting in zebrafish developmental defects and mortality. In conclusion, ScoreAOP represents a promising approach to apply mechanism information obtained from omics to predict AOs induced by chemicals.

A Comparative Analysis of Heavy Metal Effects on Medicinal Plants.

Popularity of herbal drugs has always been in high demand, but recently it has been increasing all over the world, especially in India, because of the lower range of adverse health effects as compared to synthetic or man-made drugs. Not only this but their cost-effectiveness and easy availability to the poor people and the masses, particularly in developing countries, are major causes for their demand. But there lies a huge problem during the process of plant collection that affects their medicinal properties to certain degrees. This is caused by heavy metal toxicity in soil in different locations of the Indian subcontinent. This was correlated with their potential to cause health damage. Exposure of humans to heavy metals includes diverse pathways from food to water to consumption and inhalation of polluted air to permanent damage to exposed skin and even by occupational exposure at workplaces. As we can understand, the main mechanisms of heavy metal toxicity include the production of free radicals to affect the host by oxidative stress, damaging biological molecules such as enzymes, proteins, lipids, and even nucleic acids and finally damaging DNA which is the fastest way to carcinogenesis and in addition, neurotoxicity. Therefore, in this paper, we have researched how the plants/herbs are affected due to heavy metal deposition in their habitat and how it can lead to serious clinical complications.

Mixture and individual effects of benzene, toluene, and formaldehyde in zebrafish (Danio rerio) development: Metabolomics, epigenetics, and behavioral approaches.

In this study, we aimed to investigate the potential hazards of volatile organic compounds (VOCs) on the development of zebrafish. To this end, zebrafish embryos were exposed in two different windows, either alone or in a mixture with VOCs (benzene, toluene, and formaldehyde) [EW1: 4 ± 2 h post-fertilization (hpf) to 24 hpf and EW2: 24 ± 2 hpf to 48 hpf]. Alterations in global DNA methylation and related gene expression, behavioral responses, and stress-related gene expression were observed. In addition to these endpoints, non-targeted NMR-based global metabolomics followed by pathway analysis showed significant changes in the metabolism of various amino acids during VOC exposure. Regardless of the analyzed endpoints, toluene was the most toxic chemical when exposed individually and possibly played the most pivotal role in the mixture treatment conditions. In conclusion, our data show that exposure to VOCs at embryonic developmental stages causes physiological perturbations and adverse outcomes at later life stages.

Differential Expression of miRNA-192 is a Potential Biomarker for HIV Associated Immune Recovery Uveitis.

PURPOSE: Notwithstanding well-established clinical features of Immune Recovery Uveitis (IRU), specific diagnostic tools to identify at-risk patients are lacking. Identification of biomarkers for IRU prediction can allow high-risk patients to benefit from specific preventive strategies, development of therapies, and elucidate immune reconstitution associated pathogenesis. METHODS: HIV+ patients were classified into four groups (A, B, C and D) with and without ocular manifestations, with follow-up over a year. Patients' ocular parameters were examined and manifestations like uveitis and IRU noted. Selected miRNAs were investigated in PBMCs by using miRNA PCR assay. Bioinformatic analysis used miRNet to predict the targets of miRNA-192-5p and miRNA-543 and KOBAS for pathways. RESULTS: Hsa-miR-192-5p and hsa-miR-543 levels were measured by qPCR using RNA isolated from PBMCs of HIVinfected patients. Hsa-miR-192-5p and hsa-miR-543 were down regulated in patients exhibiting ocular manifestations. Our results showed hsa-miR-192-5p (Group B vs D p 0.007) and hsa-miR-543 levels in PBMCs reliably distinguish between HIV patients diagnosed with IRU. Both miRNAs target multiple genes involved in inflammatory pathways as predicted by bioinformatic analysis. CONCLUSION: Decreased expression levels of miRNA-192 in patients with ocular manifestations and IRU, could facilitate identification of the status of the disease in HIV patients.

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment.

The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drugs, food, water treatment, and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity, and (epi)genotoxicity. In addition, new technologies, such as organs-on-chips and sophisticated sensors, are under development and/or adaptation. All the information generated is used to develop new in silico approaches trying to predict the potential effects of newly developed materials. The overall evaluation of nanomaterials from their production to their final disposal chain is completed using the life cycle assessment (LCA), which is becoming an important element of nanosafety considering sustainability and environmental impact. In this review, we give an overview of all these elements of nanosafety.

CRISPR approach in environmental chemical screening focusing on population variability.

A significant barrier to include population variability in risk assessment is our incomplete understanding of inter-individual variability and the differential susceptibility to environmental exposures induced adverse outcomes. By combining genome editing tools with the population diversity model, this article intended to highlight a potential strategy to identify and characterize the inter-individual variability factors, the determinant gene anchoring to a particular phenotype. The goal could be achieved by integrating the perturbed CRISPR-based unbiased functional genomics screening, genome-wide or a focused subset of genes, in a population-based in vitro model system (such as the lymphoblastoid cell lines, LCL, available from HapMap and 1000 Genomes project). Then data can be translated to genetic variability and individual (or subpopulation) susceptibility by incorporating ethnicity and corresponding genome-wide association studies (GWAS) with functional genomics screening results. This approach can provide complementary data for next-generation risk assessment, in particular, for environmental stressors. The current paper outlined the previous work conducted with a population-based in vitro model system, perturbed CRISPR-based functional toxicogenomic screening of environmental chemicals, and finally, the potential strategies to combine these two platforms with their opportunities and challenges to achieve a mechanistic understanding of population variability.

Critical window of exposure of CMIT/MIT with respect to developmental effects on zebrafish embryos: Multi-level endpoint and proteomics analysis.

Systemic toxicity, particularly, developmental defects of humidifier disinfectant chemicals that have caused lung injuries in Korean children, remains to be elucidated. This study evaluated the mechanisms of the adverse effects of 5-chloro-2-methyl-4-isothiazoline-3-one/2methyl-4-isothiazolin-3-one (CMIT/MIT), one of the main biocides of the Korean tragedy, and identify the most susceptible developmental stage when exposed in early life. To this end, the study was designed to analyze several endpoints (morphology, heart rate, behavior, global DNA methylation, gene expressions of DNA methyl-transferases (dnmts) and protein profiling) in exposed zebrafish (Danio rerio) embryos at various developmental stages. The results showed that CMIT/MIT exposure causes bent tail, pericardial edema, altered heart rates, global DNA hypermethylation and significant alterations in the locomotion behavior. Consistent with the morphological and physiological endpoints, proteomics profiling with bioinformatics analysis suggested that the suppression of cardiac muscle contractions and energy metabolism (oxidative phosphorylation) were possible pivotal underlying mechanisms of the CMIT/MIT mediated adverse effects. Briefly, multi-level endpoint analysis indicated the most susceptible window of exposure to be ≤ 6 hpf followed by ≤ 48 hpf for CMIT/MIT. These results could potentially be translated to a risk assessment of the developmental exposure effects to the humidifier disinfectants.

Endoplasmic reticulum stress mediated apoptosis via JNK in MWCNT-exposed in vitro systems: size, surface functionalization and cell type specificity.

The aim of the present study was to evaluate the underlying mechanism of multi-walled carbon nanotubes (MWCNT) induced cellular response and their potential cross-talk, specifically, between endoplasmic reticulum (ER) stress, MAPK activation and apoptosis and how these nano-bio interactions depend on the physico-chemical properties of MWCNT. For this purpose, human bronchial epithelial (Beas2B) and human hepatoma (HepG2) cell lines, were exposed to five kinds of MWCNTs which differ in functionalization and aspect ratios. Tissue-specific sensitivity was evident for calcium homeostasis, ER-stress response, MAPK activation and apoptosis, which further depended on surface functionalization as well as aspect ratios of MWCNT. By applying specific pharmaceutical inhibitors, relevant biomarkers gene and proteins expressions, we found that possibly MWCNT induce activation of IRE1α-XPB1 pathway-mediated ER-stress response, which in turn trigger apoptosis through JNK activation in both type of cells but with variable intensity. The information presented here would have relevance in better understanding of MWCNT toxicity and their safer applications.

Development of the transcriptome for a sediment ecotoxicological model species, Chironomus dilutus.

Chironomus dilutus is a prominent model species in conventional sediment toxicity testing and sediment contamination diagnosis. However, lack of genomic data significantly limited its application in identifying toxicological mode of action (MOA) and molecular biomarkers of toxicants. Here the transcriptome of C. dilutus in full life span and both sexes (1st, 2nd, 3rd and 4th instar larvae, pupae, and adults) were developed and temporal gene expression across adjacent life stages were investigated to understand the regulation of development. Furthermore, transcriptional response of Midges (the 4th instar larvae) exposed to chemicals of different MOAs (CdCl2, nonylphenol and triclosan) were profiled based on the reference transcriptome. Consequently, a complete transcriptome of 31132 unigenes with N50 of 3117bp, covering 98.8% of the arthropod single-copy orthologs were assembled. While 364 genes were differentially expressed among adjacent larval stages, 7142 and 2127 of transcripts were significantly changed for the transition of larvae-pupae and pupae-adults, respectively. Finally, chemical-specific gene expression profile were identified in the midges, showed its potential in classifying distinct contaminants. Overall, the comprehensive transcriptome of C. dilutus developed here could not only facilitate the mechanistic understanding of environmental toxicants during critical life stage of aquatic insects, but also provide molecular diagnostic tools in sediment ecotoxicology.

Developmental trajectory of Caenorhabditis elegans nervous system governs its structural organization.

A central problem of neuroscience involves uncovering the principles governing the organization of nervous systems which ensure robustness in brain development. The nematode Caenorhabditis elegans provides us with a model organism for studying this question. In this paper, we focus on the invariant connection structure and spatial arrangement of the neurons comprising the somatic neuronal network of this organism to understand the key developmental constraints underlying its design. We observe that neurons with certain shared characteristics-such as, neural process lengths, birth time cohort, lineage and bilateral symmetry-exhibit a preference for connecting to each other. Recognizing the existence of such homophily and their relative degree of importance in determining connection probability within neurons (for example, in synapses, symmetric pairing is the most dominant factor followed by birth time cohort, process length and lineage) helps in connecting specific neuronal attributes to the topological organization of the network. Further, the functional identities of neurons appear to dictate the temporal hierarchy of their appearance during the course of development. Providing crucial insights into principles that may be common across many organisms, our study shows how the trajectory in the developmental landscape constrains the structural organization of a nervous system.

Cross-sectional and longitudinal associations between global DNA (hydroxy) methylation and exposure biomarkers of the Hebei Spirit oil spill cohort in Taean, Korea.

The Hebei Spirit oil spill (HSOS) occurred on the west coast of South Korea (Taean county) on December 7, 2007, and studies revealed that exposure to the oil spill was associated with various adverse health issues in the inhabiting population. However, no studies evaluated the association between crude-oil exposure and epigenetic changes. This study aimed to investigate the HSOS exposure-associated longitudinal and cross-sectional variations in global DNA methylation (5-mc) and/or hydroxymethylation (5-hmc) and expression profiles of related genes in Taean cohort participants from 2009 (AH-baseline) and 2014 (AH-follow-up) relative to the reference group (AL). We measured global DNA 5-mc and 5-hmc levels and related gene expression levels in whole blood. We identified significant associations between HSOS exposure and AH-baseline-5-mc, AH-baseline-5-hmc, and AH-follow-up-5-hmc. HSOS exposure was associated with lower %5-mc content and higher %5-hmc content in the same individuals from both the cross-sectional and longitudinal studies. In addition, we found a strong correlation between 5-mc and DNMT3B expression, and between 5-hmc and TET1 expression. Our findings suggested that epigenetic changes are important biomarkers for HSOS exposure and that 5-hmc is likely to be more sensitive for environmental epidemiological studies.

Activation of the nucleotide excision repair pathway by crude oil exposure: A translational study from model organisms to the Hebei Spirit Oil Spill Cohort.

In order to gain insight into the human health implications of the Hebei Spirit Oil Spill (HSOS), the mechanism of toxicity of the Iranian heavy crude (IHC), the main oil component in the HSOS was investigated in Caenorhabditis elegans and zebrafish. The identified mechanism was translated to humans using blood samples from Taean residents, who experienced HSOS with different levels of exposure to the spill. C. elegans TF RNAi screening with IHC oil revealed the nucleotide excision repair (NER) pathway as being significantly involved by oil exposure. To identify the main toxicity contributors within the chemical mixture of the crude oil, further studies were conducted on C. elegans by exposure to C3-naphthalene, an alkylated polycyclic aromatic hydrocarbon (PAH), which constitutes one of the major components of IHC oil. Increased expression of NER pathway genes was observed following exposure to the IHC oil, C3-naphthalene enriched fraction and C3-naphthalene. As the NER pathway is conserved in fish and humans, the same experiment was conducted in zebrafish, and the data were similar to what was seen in C. elegans. Increased expression of NER pathway genes was observed in human samples from the high exposure group, which suggests the involvement of the NER pathway in IHC oil exposure. Overall, the study suggests that IHC oil may cause bulk damage to DNA and activation of the NER system and Alkylated PAHs are the major contributor to DNA damage. Our study provides an innovative approach for studying translational toxicity testing from model organisms to human health.

Genetic, epigenetic, and developmental toxicity of Chironomus riparius raised in metal-contaminated field sediments: A multi-generational study with arsenic as a second challenge.

Ecotoxicity tests conducted under well-controlled lab conditions often do not reflect the real environmental conditions. To this end, we designed an ecotoxicity test using an aquatic midge, Chironomus riparius, raised in metal-contaminated field sediments (MCFS), which reflect the real environmental conditions, for five consecutive generations (F0-F4) followed by a toxic response to arsenic exposure (as a second challenge). The toxic responses (i.e. DNA damage, DNA methylation, stress response gene expression, and mortality) were compared to those organisms reared in lab sediments (LS). Under the MCFS condition, increased adult emergence was observed for the second and third generations (F1 and F2), while a decreased tendency was evident thereafter (F3 and F4) compared to that of F0. When comparing C. riparius raised in MCFS or LS exposed to arsenic, increased sensitivity (declined survival) was observed in the larvae from F2. However, that tendency was not present in F4 of the MCFS midges, indicating a possible physiological adaptation. Increased DNA damage was observed in the MCFS-exposed organisms (F0, F2, and F4) compared to the those exposed to LS, particularly at F0. Arsenic exposure induced hypermethylation at F0 and, in contrast, hypomethylation at the later generations (F2, F4) in the MCFS-exposed organisms. Global DNA methylation results were supported by the expression of genes involved in enzymatic methylation. Moreover, alterations in oxidative stress related to gene expression showed that significant oxidative stress and perturbation of glutathione reserves occurred under the MCFS and the subsequent arsenic exposure conditions. Overall, our results suggest that multigenerational rearing under MCFS conditions resulted in physiological adaptation of C. riparius to metal exposure, specifically at later generations, which in turn modulated its response to arsenic stress through possible genetic and epigenetic mechanisms.

Multi-generational impacts of organic contaminated stream water on Daphnia magna: A combined proteomics, epigenetics and ecotoxicity approach.

The present study aimed to elucidate the mechanisms of organismal sensitivity and/or physiological adaptation in the contaminated water environment. Multigenerational cultures (F0, F1, F2) of Daphnia magna in collected stream water (OCSW), contaminated with high fecal coliform, altered the reproductive scenario (changes in first brood size timing, clutch numbers, clutch size etc.), compromised fitness (increase hemoglobin, alteration in behavior), and affected global DNA methylation (hypermethylation) without affecting survival. Using proteomics approach, we found 288 proteins in F0 and 139 proteins in F2 that were significantly differentially upregulated after OCSW exposure. The individual protein expressions, biological processes and molecular functions were mainly related to metabolic processes, development and reproduction, transport (protein/lipid/oxygen), antioxidant activity, increased globin and S-adenosylmethionine synthase protein level etc., which was further found to be connected to phenotype-dependent endpoints. The proteomics pathway analysis evoked proteasome, chaperone family proteins, neuronal disease pathways (such as, Parkinson's disease) and apoptosis signaling pathways in OCSW-F0, which might be the cause of behavioral and developmental alterations in OCSW-F0. Finally, chronic multigenerational exposure to OCSW exhibited slow physiological adaptation in most of the measured effects, including proteomics analysis, from the F0 to F2 generations. The common upregulated proteins in both generations (F0 & F2), such as, globin, vitellinogen, lipid transport proteins etc., were possibly play the pivotal role in the organism's physiological adaptation. Taken together, our results, obtained with a multilevel approach, provide new insight of the molecular mechanism in fecal coliform-induced phenotypic plasticity in Daphnia magna.

Epigenetic profiling to environmental stressors in model and non-model organisms: Ecotoxicology perspective.

Epigenetics, potentially heritable changes in genome function that occur without alterations to DNA sequence, is an important but understudied component of ecotoxicology studies. A wide spectrum of environmental challenge, such as temperature, stress, diet, toxic chemicals, are known to impact on epigenetic regulatory mechanisms. Although the role of epigenetic factors in certain biological processes, such as tumourigenesis, has been heavily investigated, in ecotoxicology field, epigenetics still have attracted little attention. In ecotoxicology, potential role of epigenetics in multi- and transgenerational phenomenon to environmental stressors needs to be unrevealed. Natural variation in the epigenetic profiles of species in responses to environmental stressors, nature of dose-response relationships for epigenetic effects, and how to incorporate this information into ecological risk assessment should also require attentions. In this review, we presented the available information on epigenetics in ecotoxicological context. For this, we have conducted a systemic review on epigenetic profiling in response to environmental stressors, mostly chemical exposure, in model organisms, as well as, in ecotoxicologically relevant wildlife species.

Immune and xenobiotic response crosstalk to chemical exposure by PA01 infection in the nematode Caenorhabditis elegans.

Most organisms simultaneously face various chemical and biological stresses in the environment. Herein, we investigated how pathogen infection modifies an organism's response to chemical exposure. To explore this phenomenon, we conducted a toxicity study combined with pathogen infection by using the nematode Caenorhabditis elegans, the pathogen Pseudomonas aeruginosa, and various environmental chemicals. C. elegans preinfected with PA01, when subsequently exposed to chemicals, became sensitized to the toxicity of nonylphenol (NP) and cadmium (Cd), whereas they became tolerant to the toxicity of silver nanoparticles (AgNPs); this led us to conduct a mechanistic study focusing on AgNP exposure. A gene expression profiling study revealed that most of the immune response genes activated by PA01 infection remained activated after subsequent exposure to AgNPs, thereby suggesting that the acquired tolerance of C. elegans to AgNP exposure may be due to boosted immunity resulting from PA01 preinfection. Further, a functional genetic analysis revealed that the immune response pathway (i.e., PMK-1/p38 MAPK) was involved in defense against AgNP exposure in PA01-preinfected C. elegans, thus suggesting immune and stress response crosstalk to xenobiotic exposure. This study will aid in the elucidation of how pathogen infection impacts the way the defense system responds to subsequent xenobiotic exposure.