Decoding the exposome: Data science methodologies and implications in Exposome-Wide association studies (ExWASs)

Exposome, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 17, 2024

Abstract This paper explores the exposome concept and its role in elucidating interplay between environmental exposures human health. We introduce two key concepts critical for exposomics research. Firstly, we discuss joint impact of genetics environment on phenotypes, emphasizing variance attributable to shared non-shared factors, underscoring complexity quantifying exposome's influence health outcomes. Secondly, importance advanced data-driven methods large cohort studies exposomic measurements. Here, exposome-wide association study (ExWAS), an approach designed systematic discovery relationships phenotypes various exposures, identifying significant associations while controlling multiple comparisons. advocate standardized use term “exposome-wide study, ExWAS,” facilitate clear communication literature retrieval this field. The aims guide future researchers understanding evaluating studies. Our discussion extends emerging topics, such as FAIR Data Principles, biobanked healthcare datasets, functional exposome, outlining directions abstract provides a succinct overview our comprehensive complex dynamics implications

Language: Английский

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Bisphenol F and bisphenol S induce metabolic perturbations in human ovarian granulosa cells

Arabian Journal of Chemistry, Journal Year: 2024, Volume and Issue: 17(9), P. 105904 - 105904

Published: July 9, 2024

Owing to its capacity damage the endocrine system, bisphenol A (BPA) is being substituted in common consumer products by chemically related compounds, including F (BPF) and S (BPS). Although BPF BPS body fluids are comparable concentration frequency BPA, toxicity of these analogs female reproduction remains largely unknown. Using a nontargeted metabolomics technique, this study aimed examine effect exposure on metabolism human ovarian granulosa (KGN) cells. Analysis differentially expressed metabolites (DEMs) identified 991 609 DEMs KGN cells exposed BPS, respectively, at three various concentrations (0.1, 1, 10 µM), with having greater interfering than BPS. Specifically, low (0.1 µM) both bisphenols more greatly affected cellular higher concentrations. Metabolic pathway enrichment analysis using KEGG database revealed that mechanisms which induced were different: significantly altered purine metabolism, autophagy-related pathways, ferroptosis, whereas mainly interfered one-carbon (vitamin B6, riboflavin, folate). These results demonstrated differences cell dysfunction.

Language: Английский

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Perfluoroalkyl Substances (PFAS) Affect Inflammation in Lung Cells and Tissues

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8539 - 8539

Published: May 10, 2023

Adverse lung outcomes from exposure to per-and polyfluoroalkyl substances (PFAS) are known; however, the mechanism of action is poorly understood. To explore this, human bronchial epithelial cells were grown and exposed varied concentrations short-chain (perfluorobutanoic acid, perflurobutane sulfonic acid GenX) or long-chain (PFOA perfluorooctane (PFOS)) PFAS, alone in a mixture identify cytotoxic concentrations. Non-cytotoxic PFAS this experiment selected assess NLRP3 inflammasome activation priming. We found that PFOA PFOS primed activated compared with vehicle control. Atomic force microscopy showed but not significantly altered membrane properties cells. RNA sequencing was performed on lungs mice had consumed drinking water for 14 weeks. Wild type (WT), PPARα knock-out (KO) humanized (KI) PFOA. multiple inflammation- immune-related genes affected. Taken together, our study demonstrated could alter biology significant manner may contribute asthma/airway hyper-responsiveness.

Language: Английский

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Associations between serum per- and polyfluoroalkyl substances and thyroid hormones in Chinese adults: A nationally representative cross-sectional study

Environment International, Journal Year: 2024, Volume and Issue: 184, P. 108459 - 108459

Published: Jan. 29, 2024

Disruption of thyroid homeostasis has been indicated in human studies on the effects per- and polyfluoroalkyl substances (PFASs). However, limited research exists this topic within general Chinese population. Based a substantial representative sample adult population, our study provides insight into how PFASs specifically affect homeostasis. The included 10 853 participants, aged 18 years above, sampled from nationally data provided by China National Human Biomonitoring (CNHBM). Weighted multiple linear regression restricted cubic spline (RCS) models were used to explore associations between eight individual PFAS concentrations total thyroxine (T4), triiodothyronine (T3), T4/T3 ratio. Bayesian kernel machine (BKMR) quantile-based g-computation (qgcomp) employed joint independent Both mixtures exhibited significant inverse association with serum T3 T4 levels, displayed positive Perfluoroundecanoic acid (PFUnDA) [-0.07 (95 % confidence interval (CI): -0.08, -0.05)] largest change level. PFUnDA also higher weight compared other compounds qgcomp models. Additionally, critical exposure threshold for each was identified based nonlinear dose-response associations; beyond these thresholds, decreases levels plateaued. Specifically, perfluoroheptane sulfonic (PFHpS) 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an initial decline hormone observed, followed slight increase when surpassed 0.7 ng/mL 2.5 ng/mL, respectively. Sex-specific more pronounced females, observed predominantly younger age groups. These insights contribute understanding impact health emphasize need further environmental management measures address complexities.

Language: Английский

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Next Generation Risk Assessment of Hair Dye HC Yellow No. 13: Ensuring Protection From Liver Steatogenic Effects

Regulatory Toxicology and Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 105794 - 105794

Published: Feb. 1, 2025

This study employs animal-free Next Generation Risk Assessment (NGRA) principles to evaluate the safety of repeated dermal exposure 2.5% (w/w) HC Yellow No. 13 (HCY13) hair dye. As multiple in silico tools consistently flagged hepatotoxic potential, likely due HCY13's trifluoromethyl group, which is known interfere with hepatic lipid metabolism, liver steatosis was chosen as primary mode action for evaluation. AOP-guided vitro tests were conducted, exposing human stem cell-derived cells varying HCY13 concentrations over 72 hours. The expression 11 metabolism-related marker genes (AHR, PPARA, LXRA, APOB, ACOX1, CPT1A, FASN, SCD1, DGAT2, CD36, and PPARG) triglyceride accumulation, a phenotypic hallmark steatosis, measured. PROAST software used calculate Points Departure (PoDNAM) each biomarker. Using GastroPlus 9.9, physiologically-based pharmacokinetic (PBPK) models estimated internal (Cmax liver) HCY13, ranging from 4 20 pM. All PoDNAM values significantly exceeded predicted Cmax liver, indicating that at unlikely induce under assumed conditions. research demonstrates utility NGRA, integrating AOP-based assays computational protect health support regulatory decision-making without animal testing.

Language: Английский

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Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort

Environmental Science & Technology, Journal Year: 2023, Volume and Issue: 57(43), P. 16206 - 16218

Published: Oct. 19, 2023

Prenatal exposure to single chemicals belonging the per- and polyfluoroalkyl substances (PFAS) family is associated with biological perturbations in mother, fetus, placenta, plus adverse health outcomes. Despite our knowledge that humans are exposed multiple PFAS, potential joint effects of PFAS on metabolome remain largely unknown. Here, we leveraged high-resolution metabolomics identify metabolites metabolic pathways perturbed by a mixture during pregnancy. Targeted assessment perfluorooctanoic acid (PFOA), perfluorononanoic (PFNA), perfluorooctanesulfonic (PFOS), perfluorohexanesulfonic (PFHxS), along untargeted profiling, were conducted nonfasting serum samples collected from pregnant African Americans at 6–17 weeks gestation. We estimated overall effect partial using quantile g-computation single-chemical linear regression. All models adjusted for maternal age, education, parity, early pregnancy body mass index, substance use, gestational sample collection. Our analytic included 268 participants was socioeconomically diverse, majority receiving public insurance (78%). observed 13.3% detected features (n = 1705, p < 0.05), which more than any chemicals. There consistent association indicative systemic inflammation oxidative stress (e.g., glutathione, histidine, leukotriene, linoleic acid, prostaglandins, vitamins A, C, D, E metabolism) across all metabolome-wide studies. Twenty-six validated against authenticated compounds (p 0.05). Based weights, PFNA contributed most γ-aminobutyric (GABA), tyrosine, uracil. In one first studies its kind, demonstrate feasibility utility methods designed mixtures conjunction assess human metabolome. identified pronounced Taken together, findings illustrate integrating environmental analyses high-throughput elucidate molecular mechanisms underlying health.

Language: Английский

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Changing the structure of PFOA and PFOS: a chemical industry strategy or a solution to avoid thyroid-disrupting effects?

Journal of Endocrinological Investigation, Journal Year: 2024, Volume and Issue: 47(8), P. 1863 - 1879

Published: March 24, 2024

Abstract Background The family of perfluoroalkyl and polyfluoroalkyl substances (PFAS) raised concern for their proven bioaccumulation persistence in the environment animals as well hazardous health effects. As a result, new congeners PFAS have rapidly replaced so-called “old long-chain PFAS” (mainly PFOA PFOS), currently out-of-law banned by most countries. These compounds derive from original structure PFAS”, cutting or making little conformational changes to structure, thus obtaining molecules with similar industrial applications. were designed obtain "safer" compounds. Indeed, old-long-chain reported exert thyroid disruptive effects vitro, vivo humans. However, shreds evidence accumulated so far indicate that “restyling” old leads production compounds, not only functionally previous ones but also potentially free adverse bioaccumulation. Studies aimed at characterizing new-PFAS on function some these showed Purpose present review is providing an overview recent data regarding novel alternatives function. Results conclusions An extensive current legislation obtained vitro studies evaluating exposure PFOS alternatives, mixture will be provided.

Language: Английский

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Per- and polyfluoroalkyl substances (PFAS): Trends in mass spectrometric analysis for human biomonitoring and exposure patterns from recent global cohort studies

Environment International, Journal Year: 2024, Volume and Issue: 194, P. 109117 - 109117

Published: Nov. 7, 2024

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants that have been shown to contribute human exposure, thereby raising a range of health concerns. In this context, biomonitoring is essential for linking exposure levels PFAS with their potential risks. Mass spectrometry-based analytical techniques extensively adopted the evaluation across various cohorts. However, challenges arising from use biological samples (e.g., plasma, serum, urine, etc.) necessitate ongoing research refinement methodologies. This review provides an overview current trends in mass approaches PFAS, including sample collection preparation, instrumental techniques. We also explore strategies overcome obtaining PFAS-free blank matrices address risk background contamination. Moreover, examines differing patterns regions by analyzing recent international cohort studies, specifically those conducted US China over past five years. Accordingly, several key gaps studies need be addressed moving forward highlighted.

Language: Английский

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Discussion. Has the human population become a sentinel for the adverse effects of PFAS contamination on wildlife health and endangered species?

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 901, P. 165939 - 165939

Published: Sept. 26, 2023

Language: Английский

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Applications of mixture methods in epidemiological studies investigating the health impact of persistent organic pollutants exposures: a scoping review

Journal of Exposure Science & Environmental Epidemiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Language: Английский

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