Search Results (1,720)

Endocrine-disrupting chemicals (EDCs) are important environmental risk factors for urogenital malignancies, but the shared molecular mechanisms underlying their carcinogenic effects remain poorly understood. Here, we systematically investigated the common pro-tumorigenic mechanisms of 12 prevalent EDCs, including anthracene, benzo[a]pyrene (BaP), bisphenol A, clofenotane, di(2-ethylhexyl) phthalate, diazinon, dibutyl phthalate, glyphosate, malathion, perfluorooctanoic acid, polychlorinated biphenyls, and triclosan, across four urogenital cancers, including bladder cancer (BLCA), renal cell carcinoma (RCC), prostate adenocarcinoma (PRAD), and testicular germ cell tumor (TGCT). By integrating network toxicology and protein–protein interaction analysis, we identified shared hub targets linking EDC exposure to tumor progression. EGFR and CASP3 were identified as core targets in BLCA, EGFR and CASP9 in RCC, and CASP3, ESR1, and EGFR in PRAD, whereas KIT emerged as a broadly relevant target in TGCT. Molecular docking and molecular dynamics simulations supported the stable binding of EDCs to these targets. Among the predicted interactions, BaP showed strong binding affinity for CASP9 (ΔG = −9.8 kcal/mol) and was therefore selected for experimental validation. Analysis of TCGA data showed that elevated CASP9 expression was significantly associated with poorer overall survival in patients with RCC. In 786-O and ACHN cells, chronic exposure to an environmentally relevant concentration of BaP significantly increased CASP9 protein stability without altering its mRNA expression, suggesting post-transcriptional regulation. Collectively, these findings identify shared molecular targets of EDCs across urogenital cancers and provide new mechanistic insight into EDC-driven tumor progression, prioritizing potential biomarkers and therapeutic targets for environmentally related malignancies. Full article

Background: Bisphenol A (BPA) release from resin-based dental materials is a growing concern due to its potential endocrine-disrupting effects, particularly in pediatric patients. This in vitro study evaluated cumulative BPA release and elution kinetics from commonly used pediatric resin-based materials, due to the limited evidence available. Methods: Three restorative materials (Clearfil Majesty ES-2, Estelite Sigma Quick, and Stela Automix) and one orthodontic material (Transbond XT) were investigated. Eighteen disk-shaped specimens (5.5 mm in diameter and 2 mm in thickness) were prepared for each material and immersed in artificial saliva (pH 6.8) at 37 °C for 1, 7, and 28 days. BPA concentrations were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS). BPA release kinetics were evaluated during the early (1–7 days) and late (7–28 days) release phases. Results: All investigated materials released measurable BPA concentrations, with cumulative BPA release progressively increasing up to 28 days. Clearfil Majesty ES-2 and Estelite Sigma Quick exhibited the highest cumulative BPA concentrations, whereas Stela Automix showed markedly lower values. Transbond XT also demonstrated measurable BPA release. For all materials, BPA release kinetics were significantly higher during the early phase than during the late phase (p < 0.001), indicating a non-linear release behavior over time. Conclusions: BPA release from pediatric restorative and orthodontic resin-based materials is material-dependent and characterized by progressive cumulative accumulation associated with significantly higher early-phase release rates. These findings highlight the importance of assessing the safety of resin-based materials used in pediatric dentistry. Full article

The prevalent endocrine disruptor bisphenol A (BPA) is associated with aging-related conditions, including metabolic disorders. It has been shown that BPA promotes bone fragility through oxidative stress-induced apoptosis and impaired osteoblast differentiation. The identification of sustainable bioactive substances that alleviate BPA-induced bone toxicity is thus of biomedical and environmental significance. Wolffia globosa (WG), the world’s smallest flowering aquatic plant, has recently gained attention as a high-protein, antioxidant-rich nutraceutical, yet its impact on BPA-induced osteoblast dysfunction has not been systematically investigated. This study presents a comprehensive assessment of WG ethanolic extract (WGE) in MC3T3-E1 pre-osteoblasts, incorporating thorough phytochemical characterization, acute high-dose and chronic low-dose BPA exposure models, and multi-faceted mechanistic analysis. LC-MS/MS profiling identified luteolin (116.17 ± 0.69 µg/g), rosmarinic acid (54.80 ± 2.12 µg/g), and apigenin (48.77 ± 0.61 µg/g) as the predominant bioactive compounds. WGE exhibited potent antioxidant capacity across DPPH and ABTS radical scavenging assays, complemented by high ORAC and FRAP values, reflecting broad-spectrum antioxidant mechanisms. Treatment with WGE (25 and 50 µg/mL) resulted in significant alleviation of BPA-induced cytotoxicity, decreased intracellular ROS levels, and inhibited apoptosis. WGE (12.5 µg/mL) also modulated autophagy-related markers (LC3-II, Beclin-1, and p62), suggesting potential autophagic participation, although flux verification was not conducted. Treatment with WGE (12.5 µg/mL) also restored BPA-suppressed osteogenesis under chronic exposure, as evidenced by enhanced alkaline phosphatase activity, and increased both mineralization and upregulation of osteogenic genes including runt-related transcription factor2 (Runx2), collagen type I alpha 1 (Colla1), alkaline phosphatase (ALP), and osteocalcin (OCN). These effects were accompanied by partial reactivation of Wnt/β-catenin signaling. This study is the first to demonstrate that WGE protects osteoblasts from BPA toxicity by concurrently strengthening antioxidant defenses, limiting apoptosis, modulating autophagy-related markers, and supporting β-catenin-mediated osteogenesis, highlighting WG as a promising sustainable nutraceutical candidate for the prevention of environmental toxin-related bone fragility. Full article

In recent years, bisphenol F (BPF) and bisphenol S (BPS) have been used in several everyday products to replace bisphenol A (BPA), since exposure to BPA has been associated with the development of several pathologies. However, recent studies have also been associating exposure to BPA substitutes with the development of various pathologies, including cardiovascular diseases, and the safety of BPA substitutes for human health has been questioned. Thus, this study aimed to investigate and compare BPA, BPF and BPS effects on arterial tone and to explore the mechanisms involved. The results suggest that BPA, BPS and BPF exert non-genomic and endothelium-independent relaxant effects on arteries and smooth muscle cells from the umbilical cord. Regarding genomic effects, the results suggest that BPA, BPF, and BPS disrupted the primary mechanisms underlying HUA relaxation by interfering with the cGMP signaling pathway and modulating the Ca²⁺ channels activity. Moreover, these results suggest that BPF alters the vasorelaxant response more than BPA and BPS. Therefore, replacing BPA with its substitutes does not appear to be beneficial for human cardiovascular health. Thus, in the future, the vascular effects of these bisphenols should be further evaluated to clarify their modes of action and future implications for maternal-fetal health. Full article

Endocrine-disrupting chemicals (EDCs) are a heterogeneous group of exogenous compounds capable of interfering with hormonal homeostasis and endocrine-regulated physiological processes. Their widespread occurrence in food, water, air, consumer products and industrial materials has raised increasing concern regarding their contribution to chronic disease burden. This review synthesizes current evidence on the exposure characteristics, molecular mechanisms, health effects, and prevention strategies related to major EDC classes, including bisphenol A and phthalates, dioxins and polychlorinated biphenyls, per- and polyfluoroalkyl substances, pesticides, and brominated flame retardants. Evidence indicates that EDCs may act through receptor-mediated signaling, altered hormone synthesis and metabolism, oxidative stress, mitochondrial dysfunction, immune modulation, and epigenetic mechanisms, with effects that may vary according to dose, timing, sex, age, and developmental susceptibility. Reported health outcomes include metabolic and cardiovascular disorders, reproductive dysfunction, hormone-dependent cancers, thyroid disruption, immune dysregulation, and adverse developmental effects. Although complete avoidance is unrealistic, exposure reduction and risk mitigation can be achieved through coordinated individual, clinical, environmental, and regulatory interventions. A life-course approach is essential to limit the health burden associated with endocrine disruption. Full article

Background/Objectives: The pervasive presence of microplastics (MPs) and plastic-associated chemicals has raised concerns regarding their potential effects on the central nervous system. Polyethylene (PE), widely used in food-contact materials, can carry bisphenol A (BPA), an endocrine disruptor with oxidative and neuroactive properties. Although both MPs and BPA can cross biological barriers, their acute effects on the prefrontal cortex (PFC) remain poorly understood. The aim of the study was to evaluate the acute impact of orally administered free BPA, free MPs, and BPA adsorbed onto PE MPs (PE–BPA) on oxidative stress, inflammation, and gene expression in the PFC of Wistar rats. Animals received a single dose of BPA, PE–BPA, PE alone, or vehicle. Methods: Biochemical and transcriptional analyses were performed to evaluate the antioxidant and inflammatory responses as well as the potential changes in synaptic-related gene expression. Results: BPA-containing treatments produced selective early molecular responses. Catalase (CAT) and glutathione S-transferase (GST) activities were significantly increased in the PE–BPA group, with GST being also elevated in the BPA-alone group, whereas superoxide dismutase (SOD), myeloperoxidase (MPO), and malondialdehyde (MDA) levels did not significantly change. Transcriptional analyses revealed upregulation of the antioxidant genes Nrf2 and CAT in the PE–BPA group. Co-exposure to BPA and MPs also altered synaptic markers, including decreased brain-derived neurotrophic factor (BDNF) and Sert along with increased Nr2A expression, while inflammatory gene expression remained unaffected. Conclusions: These findings indicate that acute co-exposure to BPA and PE microplastics elicits early antioxidant activation and selective synaptic-related transcriptional changes in the PFC, suggesting that MPs may modulate BPA-associated molecular responses in the brain. Full article

Bisphenol A (BPA) is a typical endocrine disruptor that poses a significant threat to ecosystems. Therefore, it is crucial to develop an efficient and environmentally friendly degradation technology. In this study, a novel bimetallic oxide-loaded GAC (Granulated Activated Carbon) particle electrode (CuFe₂O₄@GAC) was designed and applied to a three-dimensional electro-Fenton (3D-EF) system for efficient removal of BPA. The bimetallic synergistic effect of Cu and Fe was used to promote the Fenton reaction and enhance the efficiency of hydroxyl radical ·OH generation. The results show that under conditions of 20 g/L CuFe₂O₄@GAC, pH = 3, 10 mA/cm², and an electrode spacing of 2.0 cm, a BPA removal rate of over 93% (20 mg/L) was achieved within 45 min. The prepared CuFe₂O₄@GAC exhibits good stability, maintaining an 86.2% BPA degradation rate over five cycle experiments. The catalytic mechanism and degradation pathways were further analyzed through characterization methods such as radical quenching experiments, XPS analysis, EPR, and LC-MS detection. Radical quenching experiments confirmed that ·OH radicals play a significant role in the decomposition of BPA. Based on the identification of intermediates, a possible decomposition pathway for BPA was proposed. Toxicity analysis indicated that the toxicity of most intermediates was significantly lower than that of BPA. This work provides an efficient and energy-saving strategy for BPA removal. Full article

Developing circularly polarized phosphorescence (CPP) materials integrating long-afterglow room-temperature phosphorescence (RTP) and chiral optical properties is highly attractive but challenging. Herein, we report a facile and efficient strategy to achieve enhanced CPP by doping chiral naphthyl phosphoric acid derivatives (BNP-CZ, BNP-DPA, BNP-TPA) into a thermally cured Bisphenol A Epoxy Resin (DGEBA) matrix crosslinked with 1,8-diaminooctane (DAO). The rigid crosslinked network effectively suppresses nonradiative transitions and stabilizes triplet excitons, affording a long phosphorescence lifetime of up to 973 ms and a high photoluminescence quantum yield of 26.55%. Significantly, the BNP-CZ@DAO exhibits remarkably boosted CPP signals and realizes the switch from circularly polarized fluorescence (CPF) in solution to CPP in the thermally cured resin film. Benefiting from the long afterglow and chiral optical properties, these polymers are successfully applied in multi-dimensional anticounterfeiting with high security. This work provides a universal and scalable approach for developing high-performance CPP materials. Full article

Bisphenol F (BPF), a widespread environmental contaminant and a major substitute for the restricted bisphenol A (BPA), has raised increasing concerns regarding its potential male reproductive health risks, yet its underlying mechanisms remain poorly understood. This study investigates the mechanisms underlying BPF-induced testicular damage, focusing on the interplay among gut microbiota (GM) dysbiosis, histidine metabolism disruption, and ferroptosis. Using a mouse model exposed to BPF (50, 100, and 200 mg/kg/day) for 28 days, we observed significant testicular pathology, including seminiferous tubule atrophy, vacuolation, and blood-testis barrier (BTB) impairment. Metagenomic and metabolomic analyses revealed GM dysbiosis and suppressed intestinal histidine metabolism, accompanied by decreased abundance of beneficial taxa (e.g., Bacteroides, Ligilactobacillus) and increased potential pathobionts (e.g., Akkermansia, Mucispirillum). BPF exposure was associated with reduced testicular histidine levels and decreased expression of the histidine transporter-related marker LAT1, suggesting impaired histidine availability and a possible alteration in LAT1/CD98-mediated transport; however, direct inhibition of LAT1/CD98 transport activity was not experimentally demonstrated. BPF exposure was accompanied by ferroptosis-related alterations in the testes, including mitochondrial damage, iron accumulation, lipid peroxidation, and downregulation of the xCT-GSH-GPX4 antioxidant axis. In vitro experiments using mouse Sertoli cells (mSCs) confirmed BPF-induced ferroptosis, which was mitigated by the exogenous histidine supplementation. Histidine administration in vivo ameliorated testicular damage, restored BTB integrity, and reversed ferroptotic markers. Our findings support a working model in which a GM–histidine–testis axis may contribute to BPF-induced reproductive toxicity, while further functional studies are required to establish direct causality and transporter-level mechanisms. Full article

Ubiquitous environmental endocrine-disrupting chemicals (EDCs), including bisphenols, phthalates, and heavy metals, pose a severe and persistent threat to mammalian reproductive health worldwide. Oxidative stress acts as the pivotal mediator which drives epigenetic dysregulation in germ cells upon EDC exposure, including aberrant DNA methylation, abnormal histone post-translational modifications and dysregulated non-coding RNA networks. EDC-induced oxidative stress damages endogenous antioxidant defense systems and inactivates key epigenetic regulators, forming a self-reinforcing cycle of redox imbalance and epigenetic dysregulation, which ultimately leads to impaired gametogenesis, reduced fertility, and transgenerational reproductive abnormalities. This review summarizes current evidence indicating that multiple antioxidants, including melatonin, vitamin C, resveratrol, and epigallocatechin gallate, alleviate EDC-induced reproductive toxicity by targeting epigenetic dysregulation. Their protective effects encompass scavenging excessive reactive oxygen species, activating endogenous antioxidant signaling cascades, restoring activity of epigenetic enzymes, and rectifying aberrant histone modification profiles, contributing to the maintenance of epigenetic homeostasis in germ cells. This review clarifies the intrinsic mechanistic link among EDC exposure, oxidative stress, epigenetic dysregulation and reproductive toxicity, which provides a theoretical basis for formulating reproductive health protection strategies against EDC exposure and guides the exploration of clinical epigenetic biomarkers. Full article

Phenol (Ph), bisphenol A (BPA), and cresol isomers (o-, m-, p-C) are pollutants widely detected in industrial effluents and resistant to conventional treatment. This study investigated the catalytic potential of manganese peroxidase (MnP), derived from Phanerochaete chrysosporium and expressed in corn, for the removal, via oxidative oligomerization and precipitation, of these compounds from water. Batch experiments were conducted under controlled pH, hydrogen peroxide concentration, and enzyme activity to achieve ≥95% substrate conversion. The optimized MnP system nearly achieved this under stepwise hydrogen peroxide addition. Kinetic analyses revealed short half-lives for initial degradation phases, with BPA and p-C showing near-instantaneous transformation. Mass spectrometry confirmed the formation of soluble and insoluble oligomers (to hexamers for BPA, octamers for p-C, dodecamers for the rest), confirming radical-mediated polymerization pathways. These findings highlight MnP as a robust and eco-friendly biocatalyst for efficient treatment of phenolic pollutants, offering significant potential for integration into advanced wastewater treatment systems. Full article

Plastic pollution has become an increasingly severe global environmental issue, highlighting the urgent need for efficient and sustainable biodegradation strategies. In this study, an enriched gut microbial consortium, NE-01 derived from Tenebrio molitor, exhibited significant degradation activity toward polystyrene (PS), polyethylene (PE), and polyethylene terephthalate (PET). Metagenomic sequencing revealed that Pseudomonas and Proteobacteria were the dominant taxa, maintaining high community diversity and providing a microbial foundation for the degradation of plastics and other complex organic compounds. Functional annotation and metabolic pathway analysis indicated that xenobiotic biodegradation and metabolism occupied a large proportion of the metabolic network, suggesting the consortium’s potential for degrading exogenous pollutants. Several key genes associated with the degradation of aromatic and halogenated compounds, such as benzoate, toluene, styrene, and bisphenol A, were identified. Metabolic reconstruction further suggested possible degradation pathways for PS, PE, PET, and the plasticizer di(2-ethylhexyl) phthalate (DEHP). This study preliminarily demonstrated that the T. molitor gut-derived microbial consortium harbors multiple plastic-degrading genes and provides a theoretical basis for developing green, microbe-based strategies for plastic degradation. Full article

Here, we present a general statistical-mechanical model able to reconstruct the temperature dependence of the thermodynamic properties of non-covalent host–guest inclusion complexes using a set of molecular dynamics simulations along an isobar. Our approach, applied to $\beta$-cyclodextrin in interaction with E- and Z-dimethomorph as well as a bisphenol A derivative, provides a robust description of the in silico data, able to well reproduce the host–guest binding thermodynamics at every temperature. Full article

Emerging evidence links environmental exposures and circadian dysregulation to autism spectrum disorder (ASD), yet whether circadian phase modulates vulnerability to developmental toxicants remains unclear. Here, we investigated whether embryonic bisphenol A (BPA) exposure induces circadian phase-dependent ASD-related behavioral alterations via disruption of nr1d1 rhythmicity in zebrafish. In control larvae, nr1d1 exhibited significant circadian oscillation, whereas BPA exposure reduced expression levels and dampened oscillation amplitude. Two-way ANOVA revealed significant treatment × phase interactions in nr1d1 expression. Pharmacological activation of Nr1d1 partially restored rhythmic expression. Behavioral assessments conducted at defined circadian phases demonstrated a significant treatment × phase interaction in social preference. BPA-exposed larvae exhibited reduced social preference selectively at circadian time 15 (CT15), corresponding to the trough phase of nr1d1 expression, whereas no differences were observed at circadian time 3 (CT3). In contrast, tactile hyper-responsiveness showed a significant treatment effect but no phase interaction. BPA exposure also induced phase-dependent alterations in ASD-related genes, including α-nrxn2a and β-nrxn3a, with significant treatment × phase interactions. At the molecular level, BPA increased reactive oxygen species, impaired antioxidant defense, enhanced neuroinflammatory responses, and disrupted excitatory–inhibitory balance. Several of these endpoints exhibited phase-dependent modulation and were partially attenuated by Nr1d1 activation. These findings indicate that circadian phase modulates embryonic susceptibility to BPA-induced ASD-related behavioral and molecular alterations. Disruption of nr1d1 rhythmicity may contribute to time-of-day-specific neurodevelopmental vulnerability following environmental exposure. Full article

This work introduces a textile-based platform for biocatalysis by integrating a copper-based hybrid domain onto aminated/amidine-functionalized acrylic textile (TAC–Cu), producing a functional bio-textile capable of high-performance enzyme immobilization. The textile substrate was chemically modified with ethylenediamine to generate amine/amidine-type functional groups, enabling in situ formation of copper-based hybrid structures through either a conventional solvothermal approach or a plant-mediated route employing Costus speciosus extract. The green-synthesized TAC–Cu composite exhibited superior structural uniformity, improved porosity, and enhanced surface chemistry, resulting in a higher horseradish peroxidase (HRP) immobilization yield (92%) compared with the chemically synthesized analogue. The resulting HRP-functionalized bio-textile demonstrated markedly improved catalytic behavior, including a reaction rate constant nearly twice that of the free enzyme, and strong operational robustness. As a technical textile engineered for environmental applications, the composite achieved 90% bisphenol A (BPA) removal within 90 min and retained substantial enzymatic activity even at 80 °C, whereas free HRP was almost fully deactivated. Overall, this study highlights the potential of eco-engineered TAC–Cu materials as a new class of functional and sustainable bio-textiles, combining enzyme stabilization, high catalytic efficiency, and suitability for wastewater treatment and other technical textile applications. Full article