Search Results (680)

Obesity is a disease characterized by excessive accumulation of adipose tissue. It is a multifactorial condition arising from complex interactions among genetic background, lifestyle-related factors (such as physical inactivity, socioeconomic and cultural determinants), and environmental factors, including dietary patterns and exposure to environmental pollutants. In this context, exposure to environmental pollutants has been considered an independent risk factor for the development of obesity. However, the evidence linking herbicide exposure and obesity is limited. Therefore, the present scoping review aimed to map the available evidence regarding the obesogenic effects of herbicides across in vitro, in vivo, and epidemiological models, evaluate their translational concordance, and identify methodological gaps in the available literature. A systematic literature search was conducted in PubMed, Web of Science, and Scopus to identify studies reporting the effect of herbicide exposure and obesity-related endpoints. The search was limited to March 2026. A total of 24 studies fully met our eligibility criteria and were classified into in vitro, in vivo, and epidemiological evidence categories. The findings revealed a substantial disconnect across the different levels of evidence. In both in vitro and in vivo studies, the concentrations and doses tested often did not reflect realistic exposure scenarios, thereby limiting the applicability of these findings to human health risk assessment. In contrast, epidemiological studies frequently relied on obesity indicators with limited sensitivity and specificity, such as body mass index (BMI). Overall, the evidence suggests limited external validity in population-based studies and the arbitrary selection of concentrations and doses in experimental models. Full article

Air pollution and temperature are important environmental risk factors for mortality, but variation in risks across causes of death, population groups, and co-exposure conditions remains incompletely characterised. This study used nationwide monthly data from Portugal for the period 2010–2022 to estimate cause-specific mortality risks associated with nitrogen dioxide (NO₂), fine particulate matter (PM_2.5), and temperature, while evaluating sex–age interaction structures and selected co-exposure patterns. Mortality from malignant tumours, circulatory diseases, and respiratory diseases was modelled using Generalised Estimating Equations to account for temporal correlation and interaction effects. Pollutant exposures were defined as concentrations exceeding the 2021 World Health Organization air quality guideline values. Associations varied by cause of death. Respiratory mortality showed the strongest environmental association, with a 1.4% increase in risk per 1 μg/m³ increase in NO₂ above the guideline value (RR 1.014, 95% CI 1.009–1.019), and the highest predicted risk was observed among males aged ≥65 years (RR 142.610, 95% CI 142.200–143.020). Circulatory mortality was also associated with NO₂ (RR 1.005, 95% CI 1.001–1.008) and showed a submultiplicative sex–age interaction (RR 0.344, 95% CI 0.343–0.344), indicating attenuation of sex differences at older ages. Malignant tumour mortality showed weaker environmental associations but a greater-than-multiplicative sex–age interaction (RR 1.117) and attenuation of the NO₂ association at higher PM_2.5 levels, although the pollutant-related findings were less robust in sensitivity analyses. These findings indicate that mortality risks are not uniform across causes of death or population groups, supporting the value of locally derived, demographically stratified estimates for environmental health assessment and targeted public health strategies. Full article

Ultrashort-chain (USC) per- and polyfluoroalkyl substances (PFAS) are increasingly detected in environmental and drinking water systems, yet information regarding their occurrence in alcoholic beverages remains limited. The analysis of USC PFAS in wine is particularly challenging because of their high polarity and the complex composition of wine matrices. This study presents a streamlined analytical method for the simultaneous determination of 42 PFAS, including C1–C13 perfluoroalkyl carboxylic and sulfonic acids, in red, white, rosé, and sparkling wines. Chromatographic separation was achieved using a polar-embedded alkyl-phase liquid chromatography column, providing enhanced retention of USC PFAS while maintaining adequate performance for longer-chain analytes. A dilute-and-shoot sample preparation approach combined with 18 isotopically labeled internal standards enabled efficient analysis with minimal sample handling. Method verification using PFAS-spiked wine samples demonstrated satisfactory accuracy (recoveries within ±30% of nominal values) and precision (%RSD < 15%) across analyte-specific calibration ranges of 1–2500 ng/L. Application to commercial wines revealed the widespread occurrence of trifluoroacetic acid (TFA), trifluoromethanesulfonic acid (TFMS), perfluoropropionic acid (PFPrA), and perfluorobutanoic acid (PFBA) across all wine categories examined. These findings demonstrate the feasibility of comprehensive PFAS monitoring in wines and highlight the importance of including USC PFAS in exposure assessments of beverages. Full article

Cyclo(Pro-Tyr), a marine-derived cyclic dipeptide, has demonstrated anticancer activity, but its toxicological profile remains insufficiently characterized. The present study evaluated the preliminary toxicological effects of Cyclo(Pro-Tyr) using complementary in vitro cytotoxicity, zebrafish embryo developmental toxicity, and sub-acute oral toxicity in mice models. Cytotoxicity was assessed in 3T3-L1, HEK293, and HepG2 cells following 24 h exposure to Cyclo(Pro-Tyr) at 0–250 µM. Developmental toxicity was evaluated in zebrafish embryos exposed to 0–1000 µM for up to 96 h post-fertilization. A repeated-dose oral toxicity study was conducted in male and female BALB/c mice administered Cyclo(Pro-Tyr) at 100 or 500 mg/kg/day for 30 consecutive days, followed by hematological, serum biochemical, organ-weight, and histopathological assessments. Cyclo(Pro-Tyr) produced concentration-dependent reductions in cellular viability, with pronounced effects at the upper concentrations tested. In zebrafish embryos, exposure to 750 and 1000 µM was associated with increased mortality, reduced hatchability, developmental malformations, and reduced body length. In mice, repeated oral administration did not produce mortality, overt clinical toxicity, or significant changes in body weight or relative liver and kidney weights. However, dose-dependent alterations in selected hematological and serum biochemical parameters were observed, particularly at 500 mg/kg, accompanied by mild inflammatory and degenerative changes in hepatic and renal tissues. Overall, Cyclo(Pro-Tyr) exhibited concentration-dependent cellular and developmental toxicity at higher exposure concentrations and produced mild systemic alterations following repeated oral administration at the higher tested dose. These findings provide preliminary toxicological information relevant to the further preclinical evaluation of Cyclo(Pro-Tyr) as a marine-derived bioactive compound. Full article

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by chronic inflammation, insulin resistance, and reproductive dysfunction. Although empagliflozin, a sodium-glucose cotransporter-2 inhibitor, has demonstrated anti-inflammatory and metabolic benefits, its molecular mechanisms in PCOS remain poorly understood. This study investigated the anti-inflammatory mechanisms of empagliflozin in PCOS using network pharmacology, molecular docking, and molecular dynamics simulations. Potential drug targets were identified using SwissTargetPrediction and SuperPred, while PCOS- and inflammation-related genes were obtained from GeneCards. Overlapping targets were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein–protein interaction network, and hub gene analyses. Molecular docking and 50 ns molecular dynamics simulations were performed to evaluate binding affinity and complex stability. Key inflammatory targets identified included TNF, IL6, IL1B, TLR4, STAT3, and PTGS2, with significant enrichment in cytokine-mediated signaling, TNF signaling, and NF-κB pathways. Empagliflozin showed strong binding affinities for PTGS2 (−9.0 kcal/mol) and TLR4 (−8.8 kcal/mol), while molecular dynamics simulations demonstrated stable protein–ligand complexes throughout the simulation. These findings suggest that empagliflozin may alleviate PCOS-associated inflammation by modulating the TLR4/NF-κB/PTGS2 signaling axis, supporting its potential as a repurposed therapeutic agent for PCOS and providing a foundation for future experimental validation. Full article

Pesticide contamination of food and environmental matrices represents a potential risk to human health. This study investigated the toxicological effects of commercial glyphosate and dicamba-based herbicide formulations, individually and in combination, on human intestinal epithelial Caco-2 cells. Cells were exposed to a concentration range of 0.1–10,000 mg/L for 24, 48, and 72 h to determine IC₅₀ values. Subsequent assays were conducted using concentrations based on the lowest IC₅₀ obtained and in the limits established by the Environmental Protection Agency for drinking water. After 48 h of exposure, glyphosate at the highest tested concentration, as well as co-exposure to glyphosate and dicamba, induced significant cytotoxicity, modulation of oxidative stress parameters, and alterations in antioxidant defenses, accompanied by increased rates of apoptosis and necrosis. Dicamba exposure alone also resulted in elevated apoptotic and necrotic cell populations. A reduction in N-acetyl-β-D-glucosaminidase activity was observed across most tested concentrations, suggesting impaired inflammatory response capacity. This work identified alterations in Caco-2 that impair cellular homeostasis by cytotoxicity, alterations in oxidative stress, antioxidant response, inflammation, apoptosis and necrosis. Future studies investigating inflammatory pathways, genetic damage, and assays with in vivo and in silico models are important to elucidate the mechanism of the cellular damage caused by exposure to these herbicides. Full article

Atmospheric particulate matter (PM) is a heterogeneous carrier of toxic metals whose environmental fate and biological effects depend on particle size, source-related composition, chemical form, solubility, and bioaccessibility. Lead (Pb), cadmium (Cd), and nickel (Ni) are of particular concern because atmospheric transport and deposition connect air pollution with persistent contamination of soils, vegetation, waters, sediments, food, and feed, followed by human and animal exposure. This review integrates evidence across a source-to-effect continuum encompassing emission, atmospheric transport, deposition, post-depositional redistribution, food-chain transfer, bioaccessibility, toxicokinetics, molecular toxicity, biomonitoring, remediation, and predictive assessment. Total PM mass and total metal concentration do not adequately represent biologically effective exposure, which is additionally determined by respiratory deposition, gastrointestinal release, dissolution kinetics, absorption, tissue distribution, intracellular retention, and interactions with co-associated constituents. Pb, Cd, and Ni share downstream effects including oxidative imbalance, inflammation, mitochondrial dysfunction, DNA damage, impaired genome maintenance, epigenetic remodeling, and cytogenetic abnormalities, but differ in environmental mobility, persistence, target-organ distribution, and molecular mechanisms. Effective risk assessment therefore requires coordinated multi-matrix monitoring, distinction between total and biologically accessible fractions, pathway-specific remediation, and appropriately validated predictive models. An integrated One Health framework can improve identification of priority matrices, exposure pathways, and risk-reduction measures. Full article

Pesticides represent a significant threat to aquatic ecosystems due to their persistence and widespread use in agricultural areas, altering environments and exerting adverse effects on non-target organisms. Tebuthiuron is a phenylurea herbicide extensively used as an agrochemical to control pests and weeds in various crops, which often leads to contamination of aquatic environments. Despite its high water solubility and relatively long half-life in soil, studies on Tebuthiuron toxicity in fishes at environmental concentrations are limited. This study aimed to unravel the toxicity mechanisms of Tebuthiuron using the zebrafish model. Zebrafish embryos were exposed to Tebuthiuron (one concentration of either 0.1, 10, 1000 and 5000 µg/L) for 5 days and assessed for hatchability, heart rate, locomotor activity, oxygen reactive species, apoptosis and gene expression. There was no change in frequency of hatch, heart rate, or apoptosis. However, behavioral changes were noted, with hyperactivity in zebrafish larvae during the first light (at 10 µg/L), second light (at 10 and 1000 µg/L) and third dark (10 µg/L) periods of the Visual Motor Response assay. Biochemically, a significant depletion of basal ROS levels was observed at 1000 µg/L. At the molecular level, downregulation of oxidative stress-related genes (cat, sod1, and sod2) in larval fish was noted with exposure to 10 and 5000 µg/L Tebuthiuron, suggesting a depletion of antioxidant enzymes. In addition, some neurotoxicity-related genes were downregulated, such as acetylcholinesterase (ache), while some genes were upregulated, like microtubule-associated protein tau b (maptb) and synapsin 2 alpha (syn2a), with 5000 µg/L Tebuthiuron exposure. In conclusion, Tebuthiuron induces sublethal toxicity characterized by irregular, concentration-specific disruptions to photomotor behavior, basal ROS levels, and transcriptional markers of oxidative stress and synaptic function, even in the absence of acute morphological defects. Future research should prioritize functional assays targeting mitochondrial bioenergetics and antioxidant enzyme activities, alongside evaluations of later developmental stages, to fully elucidate the long-term ecological risks of phenylurea herbicides to non-target aquatic species. Full article

Eastern Croatia includes settlements with historically elevated arsenic (As) concentrations in drinking water. Of 488 recruited adults, nine were excluded solely because no questionnaire was available; the exclusion was independent of measured arsenic concentrations, and the harmonised analytical cohort therefore comprised 479 adults from eight settlements. Total As concentrations in drinking water, hair, serum, and urine were measured in samples collected in June 2015 by inductively coupled plasma mass spectrometry. Kidney cancer data (ICD-10 C64) for 2000–2018 were obtained from the Croatian National Cancer Registry and analysed ecologically. MDCK1 cells were exposed to As₂O₃ at 10–200 µg/L for 48, 72, and 96 h, and acetylcholinesterase (AChE) activity was measured in human erythrocytes. Čepin had the highest median As concentrations in drinking water (191.75 µg/L) and urine (68.14 µg/L). Across all eight settlements, drinking-water As was strongly associated with urinary As (slope = 0.537; 95% CI, 0.352–0.722; R² = 0.894; p < 0.001). However, in a sensitivity analysis excluding Čepin and using the seven non-Čepin settlement means reported, the association weakened (r = 0.740; R² = 0.548; slope = 1.246; 95% CI, −0.054 to 2.547; p = 0.057), indicating substantial influence of the Čepin hotspot. Associations with hair As (R² = 0.294; p = 0.165) and serum As (R² = 0.239; p = 0.219) were not statistically significant. In a multivariable Gamma generalized linear model, residence in Čepin was associated with higher expected urinary As than residence in Vladislavci (adjusted mean ratio, 2.90; 95% CI, 1.90–4.42; p < 0.001), while female sex was associated with a lower expected concentration (adjusted mean ratio, 0.80; 95% CI, 0.66–0.97; p = 0.024). No statistically significant effect of As₂O₃ on MDCK1 viability or erythrocyte AChE activity was observed. The findings support urinary total As as a biomarker of recent environmental exposure, but do not establish causal associations with kidney toxicity or kidney cancer. Full article

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. Full article

Microplastics (MPs) and nanoplastics (NPs) have emerged as pervasive environmental contaminants with increasing evidence of human exposure and biological accumulation. Recent studies have confirmed their presence in multiple human reproductive tissues and fluids, including semen, testicular tissue, ovarian follicular fluid, cervicovaginal secretions, placenta, and breast milk, raising concerns regarding their potential implications for reproductive health. Beyond their widespread distribution, MPs have been shown in experimental studies to interact with cellular and molecular processes, including oxidative stress, inflammatory responses, mitochondrial dysfunction, and DNA damage, which are pathways commonly implicated in carcinogenesis. This review provides a comprehensive and critical synthesis of current evidence linking microplastic exposure to reproductive cancers, including prostate, testicular, ovarian, endometrial, cervical, and vaginal malignancies. Available mechanistic studies suggest that MPs may influence cancer-related biological processes through dysregulation of programmed cell death, genotoxicity, endocrine disruption, and modulation of signaling pathways such as PI3K/AKT and MAPK. Experimental findings also indicate that MPs may alter the tumor microenvironment and affect cellular behaviors associated with proliferation, migration, and invasion. However, the majority of current evidence is derived from in vitro studies, animal models, and indirect mechanistic observations, while direct epidemiological evidence in humans remain limited. Furthermore, methodological heterogeneity in microplastic detection and characterization complicates comparisons across studies and hinders causal inference. Overall, current evidence supports the biological plausibility of an association between microplastic exposure and reproductive cancer-related processes, while highlighting the need for standardized methodologies and well-designed longitudinal human studies to clarify potential health risks. Full article

Chemical pollution from industrial, agricultural, and urban activities represents a major threat to freshwater ecosystems and aquatic organisms. This study evaluated hepatic biomarker responses in Oreochromis niloticus (Nile tilapia) maintained under chronic environmental exposure to water from the Iguaçu River, one of the most polluted urban rivers in Brazil. Juvenile fish were kept in cages at three sites along the river, and hepatic biomarkers were assessed after 15 and 22 months of environmental exposure. Fish showed severe histopathological liver lesions, activation of antioxidant defenses, and oxidative stress responses accompanied by increased DNA damage. Immunological responses, particularly melanomacrophage proliferation and granuloma formation, were also observed across the monitored exposure scenarios. Alterations in plasma biochemical parameters, including AST, ALT, LDH, albumin, and globulin, were consistent with changes in hepatic function. Overall, the integrated biomarker responses revealed distinct patterns of biological alteration among the monitored exposure scenarios and were consistent with chronic exposure to complex environmental contaminant mixtures. These findings are consistent with alterations in liver integrity in fish maintained under long-term environmental exposure in the Iguaçu River. The study highlights the sensitivity of Nile tilapia as a bioindicator species for aquatic biomonitoring and provides valuable information to support environmental monitoring, risk assessment, and conservation strategies for the Iguaçu River Basin. Full article

Microplastics and nanoplastics (MNPs) have emerged as widespread environmental contaminants, with increasing evidence suggesting that chronic exposure may adversely affect human health. Experimental and emerging human studies indicate that MNPs can interact with multiple biological systems and trigger a range of mechanisms, including oxidative stress, mitochondrial dysfunction, cellular injury, barrier disruption, and immune and inflammatory responses. These effects may involve direct interactions with tissues and cells as well as indirect pathways, including alterations in gut microbial and intestinal homeostasis. In turn, persistent inflammatory and metabolic disturbances may contribute to tissue dysfunction and the development or progression of chronic diseases. This narrative review summarizes current evidence on the biological effects of MNP exposure, focusing on the mechanisms linking environmental exposure to chronic inflammation and disease. We discuss their potential involvement in cardiovascular, liver, kidney, respiratory, and neurological diseases, while highlighting the emerging role of the gut microbiota and intestinal barrier as potential modulators of these effects. Given the limitations of current human evidence and the heterogeneity of experimental models, we also discuss major knowledge gaps and the need for further mechanistic and epidemiological studies to clarify the clinical relevance of chronic MNPs exposure. Full article

Antiretroviral therapy (ART) is essential for controlling human immunodeficiency virus (HIV) infection, requiring strict daily adherence for lifelong viral suppression. However, this continuous oral dosing results in persistent exposure of the gastrointestinal tract (GIT), raising the need to investigate the effects of TC-ART (Tri-combinationL: Abacavir, Dolutegravir, Lamivudine–ART) on epithelial integrity, barrier recovery mechanisms, and surface barrier architecture. TC-ART exposure (125 µM to 4000 µM) showed marked alterations in transepithelial resistance, permeability, and wound-healing abilities even at sub-cytotoxic doses. The dose exposure range at the mid-dose level showed the highest transcriptional activity, characterized by a downregulation of junctional genes [claudins (CLDNs), desmogleins (DSGs), and junctional plakoglobin (JUP)] and signaling mediators [the signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 1 and 3 (MAPK1/3), and catenin beta 1 (CTNNB1)], along with reduced IL-9 expression that is linked to mucin loss. These transcriptional changes were consistent with structural findings, including partial transepithelial electrical resistance (TEER) recovery followed by a decline, delayed wound closure, and waning of the apical mucin layer in a dose-dependent manner. However, several cytokines, like IL-2 and IL-6, showed increased secretion despite lower transcriptional levels, suggesting alternative regulatory control during early stress responses. Together, these results support that TC-ART exposure alters epithelial responses in a way that may transition from early adaptation to signs of impaired recovery, leading to a gradual decline in mucosal barrier function. Such concentration- and time-dependent epithelial stress may contribute to gastrointestinal disturbances observed in treated HIV populations, emphasizing the need for incorporating intestinal epithelial health endpoints in drug safety evaluations. Full article

Bisphenol A (BPA) is a non-persistent industrial chemical widely used in the production of polycarbonate plastics and epoxy resins. Due to its mass production and versatility, BPA is ubiquitous in environmental matrices, leading to human exposure through ingestion, dermal contact, and inhalation. As a known endocrine-disrupting chemical (EDC) with estrogenic activity, BPA exposure has been associated with reproductive, metabolic, immune, oncogenic, and developmental effects. Mechanistically, BPA is reported to exert its toxic effects via multiple pathways, including alterations in epigenetic microRNA (miRNA) expression. miRNAs are endogenous non-coding RNA molecules that regulate gene expression by targeting mRNAs, thereby influencing a wide range of cellular and metabolic pathways involved in development and disease. Importantly, this review consolidates evidence suggesting that the biological effects of BPA may, in part, be mediated through miRNA-driven epigenetic modifications, affecting numerous downstream proteins and signaling pathways. Altered miRNA expression induced by BPA exposure is implicated in diverse health outcomes, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental abnormalities. Notably, BPA exposure predominantly results in the upregulation of specific miRNAs, such as miR-21 and miR-146a, although tissue-specific and sex-dependent variations are evident. In this review, we provide a comprehensive overview of human, in vivo, and in vitro studies investigating BPA-induced miRNA dysregulation and its associated biological effects. Full article