Dimosthenis Sarigiannis

Background: Thyroid hormone synthesis, deiodination, and redox regulation depend on iodine availability and selenium-dependent proteins. Therefore, these nutrients may alter sensitivity to thyroid disturbance brought on by metals and metalloids; nevertheless, direct human evidence has not been compiled independently from rescue experiments. Goal: To determine the mechanistic, biomarker, and study-design needs for interpretable human research, as well as to critically assess whether iodine or selenium alters metal-associated thyroid effects. Methods: Terms for metals, metalloids, iodine, selenium, and thyroid endpoints were used to search PubMed/MEDLINE until 14 July 2026. The database search was improved by selective forward citation searching, backward citation searching, and exact-title and DOI retrieval. A thyroid-specific outcome, a measurable or experimentally manipulated iodine or selenium variable, and a metal or metalloid exposure were all necessary for studies to be eligible. An author-developed framework that distinguished between formal interaction, stratification, joint-exposure modeling, contextual co-measurement, factorial nutritional-status experiments, physiologically interpretable supplementation, and pharmacological or nanoparticle rescue was used to categorize experimental evidence from humans and mammals. Results: Seven human studies and nine mammalian experimental studies made up the core evidence set. One additional human study was retained as contextual evidence. The results of the three human studies that directly assessed modification were mixed. One showed no clear interactions with iodine or selenium, one discovered an isolated strontium-by-iodine interaction, and one reported a suggestive mercury-by-iodine-supplement interaction. Most experimental trials employed high-dose, combination, parenteral, or nanoparticle rescue methods, but they more consistently demonstrated mitigation of thyroid damage by selenium-containing treatments. Conclusions: Although iodine- and selenium-dependent sensitivity is biologically feasible, there is currently little human data to support a consistent protective or detrimental modifying impact. Rather than supporting population-level prevention, experimental rescue promotes mechanistic modifiability. Repeated iodine testing, functional selenium biomarkers, metal speciation, vulnerable-window sampling, thyroid-specific outcomes, and predetermined interaction analyses are all necessary for future research.

Urban environments expose residents to multiple simultaneous stressors that often act synergistically (e.g., air pollution and extreme heat amplifying card

Red blood cells (RBCs) are sensitive biomarkers of human health, influenced by urbanization and agricultural exposures. Using scanning electron microscopy (SEM) within an exposome framework, we examined RBC morphology in residents of an industrialized area of Thessaloniki, Greece, and in a rural population primarily exposed to agricultural stressors. Blood samples and questionnaires covering demographics, lifestyle, and environmental factors were statistically analyzed. SEM revealed moderate morphological alterations without significant differences between groups. Observed features were associated with longer residence duration and suboptimal nutrition, suggesting subclinical cellular stress. Integrating these findings into exposome research may clarify cumulative industrial and agricultural impacts on RBC morphology.

Safe and Sustainable by Design (SSbD) and life‑course exposome science share a primary‑prevention goal: reducing harmful exposures by intervening early in the chemical and product life cycle. Here we propose an integrated, replacement‑first decision workflow that links life‑course exposure considerations to SSbD stage‑gates using New Approach Methodologies (NAMs). The framework combines: (i) problem formulation informed by susceptible windows and populations; (ii) AOP‑guided selection and curation of mechanistic in vitro bioactivity evidence (e.g., ToxCast/Tox21, transcriptomics); (iii) physiologically based pharmacokinetic (PBPK) modelling with quantitative in vitro‑to‑in vivo extrapolation to translate in vitro potency into internal dose anchors; and (iv) transparent multi‑criteria synthesis to support early design trade‑offs. We illustrate this approach with an endocrine‑relevant substitution scenario comparing bisphenol A (BPA) with a structurally similar alternative (BPAP) and a bio‑based monomer candidate (isosorbide). Estrogen receptor (ER) bioactivity anchors derived from curated HTS assays are contrasted with PBPK‑predicted internal concentration ranges to generate an internal margin for stage‑gate decisions. The example shows how candidates with weak or absent pathway‑relevant bioactivity can be advanced, while structurally similar alternatives with ER potency approaching predicted internal concentrations can be deprioritised or redesigned pending improved exposure controls. By explicitly mapping NAM outputs to AOP key events and life‑course windows, the workflow operationalises the 3Rs by replacing broad exploratory animal testing with targeted, human‑relevant evidence and reducing unnecessary in vivo studies through early prioritisation.

Polygenic risk scores (PRS) have emerged as important tools for quantifying inherited susceptibility to cancer, and are increasingly combined with environmental and lifestyle factors into composite risk scores (CRS). In this context, environmental inputs should be understood not as isolated covariates, but as components of the human exposome, encompassing cumulative, time-varying, and interacting exposures across the life course, which fundamentally shape cancer risk alongside inherited susceptibility. These approaches are often discussed as candidates for precision prevention and screening, yet their evidentiary basis spans heterogeneous study designs, outcomes, and methodological assumptions. Here, we provide an integrated review of genetic, environmental, and composite cancer risk models, explicitly distinguishing etiologic association from predictive performance and clinical translation. We synthesize evidence from large genome-wide association studies, cohort and case-control analyses, and recent CRS evaluations using both narrative assessment and structured quantitative summaries. Across cancer sites, PRS and CRS consistently stratify relative risk, with monotonic increases in odds ratios across score percentiles. However, gains in discrimination metrics such as the area under the curve or C-index are generally modest and heterogeneous, and calibration performance varies substantially across populations and settings. External validation and multi-ancestry evaluations remain limited, and methodological challenges, including overfitting, population stratification, and model transportability, are frequently under-reported. We argue that current evidence supports the use of PRS and CRS primarily as tools for risk stratification, prioritization, and risk-enriched research designs, rather than as stand-alone clinical decision systems. The most near-term translational value lies in targeted screening strategies, prevention trials, and population-level risk assessment, provided that calibration, governance, and equity considerations are explicitly addressed. We conclude by outlining key methodological and data requirements needed to advance CRS from exploratory models toward robust, population-appropriate tools in cancer prevention.

Background: Brain-derived neurotrophic factor (BDNF) is central to synaptic plasticity and neurodevelopment. Toxic metal exposure is linked to oxidative stress and neuroinflammation, yet its effects on BDNF signaling remain unclear. Objectives: To systematically synthesize evidence from human and experimental studies on the association between environmental or occupational metal exposure and BDNF alterations, and to highlight research gaps with an emphasis on hexavalent chromium (Cr(VI)). Methods: PubMed, Scopus, and ScienceDirect were searched following PRISMA guidelines. Eligible studies included human observational research and animal models reporting quantitative associations between metal exposure (biomarkers/environmental measures) and BDNF outcomes (protein or gene expression). Data were extracted on exposure assessment, BDNF measurement, and neurobehavioral outcomes. Study quality was assessed using NOS (human studies) and SciRAP (experimental studies). Results: Nineteen studies were included. Across metals such as Pb, Hg, Cd, As, Mn, and mixtures, exposure was associated with altered BDNF levels in blood or brain tissue, often alongside oxidative stress markers, inflammatory changes, and cognitive or behavioral impairment in animal models. Most human studies reported decreased circulating BDNF with higher exposure, while experimental evidence suggested context-dependent regulation across exposure windows and brain regions. Conclusions: The available evidence supports a biologically plausible link between metal exposure and BDNF dysregulation. No eligible studies evaluated BDNF in relation to Cr(VI), indicating a major research gap. Future studies should integrate neurotrophic biomarkers with exposome-oriented designs to clarify chromium-related neurotoxicity and support Adverse Outcome Pathway (AOP)-informed frameworks.

Chromium (Cr) remains a significant environmental health concern, with exposure mainly through ingestion and inhalation. Its toxicological profile is driven by oxidation state: trivalent chromium [Cr(III)] shows low bioavailability, whereas hexavalent chromium [Cr(VI)] is highly bioavailable, crosses cell membranes, and generates reactive intermediates associated with oxidative and genotoxic effects. Several studies have highlighted the assessment of chromium exposure, particularly Cr(III) and Cr(VI), across different biological matrices as a key approach for accurate exposure characterization. This review synthesizes experimental and epidemiological evidence regarding urinary chromium (uCr) as a biomarker of exposure, alongside advances in analytical techniques and the emerging exposome framework. Although widely used due to non-invasive sampling and suitability for large studies, uCr primarily reflects recent exposure (<48 h), exhibits high intra- and inter-individual variability, and lacks routine Cr(VI)/Cr(III) speciation, limiting its value for low-level environmental exposure. Unlike urinary or whole blood chromium, chromium in red blood cells (RBCs) is specific to Cr(VI) exposure, since in vitro studies reveal selective, donor-independent accumulation of hexavalent chromium in RBCs. However, the current literature is primarily concerned with sampling strategies, pre-treatment procedures, and analytical validation, with comparatively little consideration given to chromium speciation and species interconversion in biological matrices, despite their essential significance for exposure assessment and toxicological interpretation.