Search Results (1,360)

Background: Clear cell renal cell carcinoma (ccRCC) is a prevalent urological malignancy, accounting for approximately 1.6% of all cancer-related deaths in 2022. While endocrine-disrupting chemicals (EDCs) have been implicated as risk factors for ccRCC, the toxicological profiles and immune mechanisms underlying Bisphenol A (BPA) exposure in ccRCC progression remain inadequately understood. Materials and Methods: Protein–protein interaction (PPI) analysis and visualization were performed on overlapping genes between ccRCC and BPA exposure. This was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to elucidate potential underlying mechanisms. Subsequently, 108 distinct machine learning algorithm combinations were evaluated to identify the optimal predictive model. An integrated CoxBoost and Ridge regression model was constructed to develop a prognostic signature, the performance of which was rigorously validated across two independent external datasets. Finally, molecular docking analyses were employed to investigate interactions between key genes and BPA. Results: A total of 114 overlapping targets associated with both ccRCC and BPA were identified. GO and KEGG analyses revealed enrichment in cancer-related pathways, including pathways in cancer, endocrine resistance, PD-L1 expression and PD-1 checkpoint signaling, T-cell receptor signaling, endocrine function, and immune responses. Machine learning algorithm selection identified the combined CoxBoost-Ridge approach as the optimal predictive model (achieving a training set concordance index (C-index) of 0.77). This model identified eight key genes (CHRM3, GABBR1, CCR4, KCNN4, PRKCE, CYP2C9, HPGD, FASN), which were the top-ranked by coefficient magnitude in the prognostic model. The prognostic signature demonstrated robust predictive performance in two independent external validation cohorts (C-index = 0.74 in cBioPortal; C-index = 0.81 in E-MTAB-1980). Furthermore, molecular docking analyses predicted strong binding affinities between BPA and these key targets (Vina scores all <−6.5 kcal/mol), suggesting a potential mechanism through which BPA may modulate their activity to promote renal carcinogenesis. Collectively, These findings suggested potential molecular mechanisms that may underpin BPA-induced ccRCC progression, generating hypotheses for future experimental validation. Conclusions: These findings enhance our understanding of the molecular mechanisms by which BPA induces ccRCC and highlight potential targets for therapeutic intervention, particularly in endocrine and immune-related pathways. This underscores the need for collaborative efforts to mitigate the impact of environmental toxins like BPA on public health. Full article

Breast cancer is one of the most prevalent malignancies affecting women worldwide. Among environmental risk factors, increasing attention has been given to endocrine-disrupting chemicals (EDCs), which can interfere with hormonal signaling pathways. Chronic exposure to these compounds, even at low doses, may lead to molecular changes that initiate carcinogenesis or promote tumor progression. Owing to EDCs’ resistance to degradation and ability to bioaccumulate in organisms and the environment, they pose a growing concern for human health. They can mimic or block natural hormones by binding to receptors, such as estrogen, progesterone, aryl hydrocarbon, or thyroid-stimulating receptors, disrupting hormone synthesis, secretion, and metabolism. They have shown the ability to initiate carcinogenic changes in breast tissue or accelerate cancer progression. This review focuses on the relationship between EDC exposure and breast cancer, examining both their mechanisms of action and long-term health effects. Compounds such as polychlorinated biphenyls, parabens, phenols, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylhexyl phthalate, and bisphenol A, which are frequently encountered in everyday products, are discussed in detail. By presenting European Union guidelines and exploring EDCs’ biological activity and pathways of endocrine disruption, we aimed to raise awareness of their potential risks and emphasize the need for further research. Full article

Breast milk (BM) is a unique biological fluid that represents the optimal nutritional source for infants, uniquely adapted through millions of years of evolution. BM is not only a nutritional fluid but a dynamic biological system, evolved to provide optimal growth, immune protection, and neurodevelopmental support. Its unique composition—including macronutrients, micronutrients, bioactive molecules, and stem cells—makes it essential in early life. Breastfeeding further promotes psychological well-being, secure attachment, and maternal–infant bonding. Yet, in recent decades, concern has grown over environmental contaminants in BM, including endocrine-disrupting chemicals (EDCs) and micro/nanoplastics. These pollutants have the potential to disrupt endocrine signaling, neurodevelopment, metabolic programming, and immune development, thereby undermining the natural advantages of breastfeeding. Therefore, a better understanding of the unique features of BM, while investigating the effects of these contaminants, is important for safeguarding maternal and infant health. This perspective article highlights the current knowledge on BM and indicates the need for further research. It also emphasizes the need for appropriate public health measures aimed at reducing exposure to pollutants and lowering associated risks, as well as preventive strategies to protect breast milk and breastfeeding in such a changing environment, as it is uniquely designed to promote the health of children. Full article

Chlorobenzoic acids (CBAs) are a group of chlorinated persistent environmental pollutants with hard biodegradability, high water solubility, and well-documented carcinogenic and endocrine-disrupting properties. Electrocatalytic hydrodechlorination (ECH) is a highly efficient method under mild conditions without harmful by-products, but the ECH process commonly requires adding precious metal catalysts such as palladium (Pd). To address the economic constraints and more effective utilization of Pd, a palladium/manganese dioxide (Pd/MnO₂) composite catalyst was developed in this study by chemical deposition. This method utilized the excellent electrochemical activity of MnO₂ as a carrier as well as the hydrogen storage and activation capacity of Pd. The test showed the optimal Pd loading was 7.5%, and the removal percent of 2,4-dichlorobenzoic acid (2,4-DCBA), a typical CBA, reached 97.3% using 0.5 g/L of Pd/MnO₂ after 120 min of electrochemical reaction. Under these conditions, the dechlorination percent can also be as high as 89.6%. A higher current density enhanced the dechlorination efficiency but showed the lower current utilization efficiency. In practical applications, current density should be minimized on the premise of compliance with the water treatment requirement. Mechanistic studies showed that MnO₂ synergistically promoted hydrolysis dissociation and hydrogen spillover and facilitated Pd-mediated adsorption of atomic hydrogen (H*) for dehydrogenation of 2,4-DCBA. The presence of MnO₂ can effectively disperse the loaded Pd and reduce the amount of Pd via the above process. The catalyst exhibited excellent stability over multiple cycles, and the 2,4-DCBA removal could still reach more than 80% after the five cycles. This work establishes electrocatalytic strategies for effectively reducing Pd usage and maintaining high removal of typical CBAs to support CBA-related water treatment. Full article

Targeting juvenile hormone esterase (JHE) is an emerging strategy to combat the broadly resistant pest, Plutella xylostella; this study employed transcriptomics to investigate the sublethal effects of the JHE inhibitor OTFP, revealing a non-monotonic dose response characterized by stronger transcriptional changes at lower concentrations, resulting in low mortality, prolonged pupation time, and increased pupal weight. The results from the Differentially Expressed Genes (DEGs) analysis revealed that the core effect of OTFP is the persistent perturbation of the “insect hormone biosynthesis” pathway and altered expression of components of the JH/20E axis; to cope with this stress, the larvae exhibited a dual defense associated with compensatory upregulation of JH-degrading enzyme genes to attempt to restore hormone homeostasis, and the activation of a broad-spectrum detoxification network to clear the compound. More critically, the developmental delay resulting from endocrine disruption KEGG-enriched growth-related pathways (amino-acid and central-carbon metabolism; ribosome biogenesis; aminoacyl-tRNA biosynthesis), consistent with a growth-permissive milieu during prolonged feeding. This study therefore elucidates a novel integrative regulatory network that links endocrine disruption, detoxification, and compensatory growth, revealing a complex physiological trade-off strategy in this pest that sacrifices developmental tempo for survival. Full article

Paper spray ionization mass spectrometry (PSI-MS) enables rapid analysis with minimal sample preparation, yet negative-ion mode performance has been limited by poor sensitivity and unstable signals, similar to conventional electrospray ionization. In this study, we optimized negative PSI tandem MS (MS/MS) for twelve endocrine-disrupting chemicals (EDCs) and related biomarkers—including bisphenols, phthalates, parabens, and substituted phenols—used as model analytes. A systematic solvent and additive screen identified 1 mM ammonium fluoride in methanol and 0.1% ammonium hydroxide in 9:1 MeOH/carbon tetrachloride as optimal conditions, providing enhanced deprotonated-ion intensities and improved stability. Calibration curves generated under these conditions showed excellent linearity, with limits of quantitation (LOQs) in the low-ppb range. Application to cosmetic formulations demonstrated reliable paraben quantitation. In fortified hand cream, LOQs below 1 mg/kg were achieved, with recoveries of 93–110% and intra- and inter-day precision below 10% RSD. Notably, PSI-MS/MS performance was comparable to LC–MS/MS, without a separation step. These results demonstrate the feasibility of optimized negative PSI-MS as a sensitive and robust tool for paraben determination in cosmetics and highlight its potential as a versatile platform for broader EDC quantification. Full article

Di(2-ethylhexyl) phthalate (DEHP), a widely employed exogenous plasticizer, has become pervasive in the environment and living organisms due to its extensive use in food packaging, medical devices, and daily consumer products, and is established as a typical endocrine-disrupting chemical. Growing evidence indicates a strong association between DEHP exposure and the incidence of chronic bone disorders, including osteoporosis (OP), osteoarthritis (OA), and osteonecrosis of the femoral head (ONFH). However, the molecular mechanisms underlying its pathogenic effects across these diseases remain poorly defined. In this study, we applied an environmental network toxicology approach to integrate predicted protein targets of DEHP with known disease-associated targets of the three bone disorders using multiple databases. Through Venn analysis, protein–protein interaction (PPI) network construction, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, we identified core targets and key signaling pathways. Molecular docking and molecular dynamics (MD) simulations were further employed to validate the binding modes and stability between DEHP and the core targets, thereby elucidating common and distinct mechanisms of DEHP across these bone diseases. A total of 109 overlapping targets of DEHP and the three bone diseases were identified, among which 7 core targets—AKT1, SRC, ESR1, CASP3, MMP9, BCL2, and BCL2L1—were common to all three disorders. These are implicated in critical biological processes such as apoptosis regulation, inflammation, extracellular matrix degradation, and estrogen signaling. KEGG enrichment analysis revealed significant involvement of the PI3K-Akt, MAPK, Ras, TNF, and estrogen signaling pathways across all three diseases. Molecular docking and MD simulations confirmed stable binding of DEHP to key targets including AKT1, ESR1, and MMP9, supporting its potential to disrupt bone metabolic homeostasis via multi-target and multi-pathway mechanisms. Further analysis indicated that DEHP exerts both shared and disease-specific effects: it disrupts osteoblast/osteoclast balance in OP, amplifies inflammatory responses and matrix degradation in OA, and contributes to impaired angiogenesis and osteocyte necrosis in ONFH. This study systematically reveals how DEHP disrupts bone homeostasis through a multi-target and multi-pathway network, constructing a cross-disease osteotoxicity framework. It is the first to delineate the common and distinct molecular mechanisms of DEHP in OP, OA, and ONFH. Although these insights are derived from computational models and require further experimental validation, they provide a novel theoretical basis for combined intervention strategies targeting multiple bone diseases and for environmental health risk assessment. Full article

Background/Objectives: Organic UV filters are chemical compounds that are commonly used in sunscreen products to absorb UV radiation from the Sun. To date, the filters have been detected in aquatic environments worldwide, as well as in aquatic organisms, including fish and coral. Hydroxy-4-methoxybenzophenone (BP-3) is a common organic UV filter and it is well documented to be among the filters that are detectable worldwide in water samples and aquatic organisms. Long-term exposure in vivo studies have demonstrated that high doses of BP-3 can cause endocrine-disrupting effects in aquatic organisms. Methods: Using gonadal cell culture and quantitative RT-PCR, our study aimed to ascertain the effect of environmentally relevant doses of BP-3 (detected in aquatic systems) on the gene expression of reproductive targets, estrogen and growth hormone receptors (ERs and GHRs), in Mozambique tilapia (Oreochromis mossambicus) after an acute 24 h treatment. Results/Conclusions: Our study is the first to use an in vitro design to investigate the mechanism of the action of BP-3 on gonadal tissue in fish. Our results show that BP-3 does not induce gene regulation directly on the gonads of tilapia at doses that are comparable to what is detectable in aquatic environments after 24 h. We do verify, as seen in other teleost species, homologous regulation of ERβ in male tilapia gonadal tissue. Full article

Dietary supplements provide essential nutrients and bioactive compounds that enhance health and traditional therapies. However, the quality and composition of these supplements can vary significantly, potentially containing inconsistent levels of active ingredients or undisclosed risk substances. Due to the current extensive industrial applications, bisphenols (BPs) and alkylphenols (APs) have become environmentally ubiquitous. Substantial evidence indicates that these compounds exhibit endocrine-disrupting properties, posing potential health risks to humans. The detection of trace-level BPs and APs in dietary supplements is critical. This study developed a supramolecular solvent (SUPRAS) from a water/THF/1-hexanol system under mild conditions for analyzing 19 BPs and APs in commercial botanical dietary supplements. After optimizing SUPRAS preparation and extraction parameters, we established a SUPRAS–HPLC–MS/MS method enabling one-step extraction/cleanup within 10 min for tablets, capsules, and oral liquids, with high sensitivity and simplicity. The method scored 0.71 (out of 1) on the AGREE metric, confirming its green profile. Detectable levels of bisphenol A (178.7–452.6 μg/kg) and 4-pentylphenol (145.3 μg/kg) in marketed products highlight potential health risks from botanical dietary supplement-derived exposure. Full article

Burnout is increasingly recognized as both a psychosocial and a chronobiological disorder characterized by endocrine dysregulation and circadian disruption. It arises from chronic occupational stress and manifests through psychological, physical, and physiological symptoms. Although psychosocial determinants are well established, the biological and chronobiological mechanisms, particularly those involving cortisol and melatonin, remain less explored. This systematic review synthesizes current evidence on hormonal and circadian dysregulation in burnout and complements it with exploratory observational data from healthcare professionals. Peer-reviewed studies evaluating endocrine or circadian biomarkers in individuals with burnout were systematically reviewed. In addition, an exploratory observational analysis was carried out among 195 Romanian clinicians using an adapted Maslach Burnout Inventory. Morning salivary cortisol was measured once at 9 a.m. in a small subsample (n = 26) to provide preliminary physiological data. Because only a single time point was obtained, these values were interpreted as indicative of stress-related activation rather than circadian rhythm. Thirty-seven studies met the inclusion criteria. Across the literature, burnout was associated with altered HPA-axis activity, blunted diurnal cortisol variation, and irregular melatonin secretion related to shift work and disrupted sleep–wake cycles. Complementary exploratory data from our Romanian cohort indicated strong correlations between burnout severity, physical symptoms, and higher morning cortisol values among shift-working clinicians. These findings are preliminary and not representative of full circadian profiles. Burnout should be considered both a psychosocial and a systemic disorder influenced by endocrine and circadian dysregulation. Recognizing alterations in cortisol and melatonin as objective indicators may facilitate earlier detection and inform chronobiological interventions such as optimized scheduling, light exposure management, or melatonin therapy. The observational data presented here is preliminary and intended to generate hypotheses; future research should employ repeated cortisol sampling under controlled Zeitgeber conditions to confirm circadian associations. Full article

Endocrine-disrupting chemicals (EDCs) are widespread contaminants that interfere with hormonal signaling and compromise reproductive success in aquatic organisms. Vitellogenin (VTG) is one of the most widely established biomarkers of estrogenic exposure, especially in males and juveniles. However, evidence from multi-omics studies indicates that VTG induction occurs within broader transcriptional and regulatory networks, involving genes such as cyp19a1 (aromatase), cyp1a (cytochrome P4501A), and other stress-responsive genes, underscoring the complexity of endocrine disruption. This review focuses on nuclear receptor isoforms, including estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and androgen receptor (AR) variants. We examine the diversification of vtg gene repertoires across teleost genomes and epigenetic mechanisms, such as DNA methylation and microRNAs, that modulate sex-dependent sensitivity. In addition, we discuss integrative approaches that combine VTG with transcriptomic, epigenetic, and histological endpoints. Within the Adverse Outcome Pathway (AOP) and weight-of-evidence (WoE) frameworks, these strategies provide mechanistic links between receptor activation and reproductive impairment. Finally, we outline future directions, focusing on the development of sex-specific biomarker panels, the integration of omics-based data with machine learning, and advances in ecogenomics. Embedding molecular responses into ecological and regulatory contexts will help bridge mechanistic insights with environmental relevance and support sustainability goals such as SDG 14 (Life Below Water). Full article

This study integrates network toxicology with molecular docking technology to systematically elucidate the key molecular mechanisms and signaling pathways by which bisphenol A (BPA) induces obesity. By cross-referencing multiple databases—including the Comparative Toxicogenomics Database (CTD), SwissTarget prediction platform, and PharmMapper—potential BPA target genes were identified, yielding a total of 1326 candidate targets. Obesity-related genes were collected from GeneCards and OMIM databases, yielding 4570 disease-associated targets. Among these, 653 overlapping genes were identified as potential mediators linking BPA exposure to obesity. Protein interaction networks were constructed using STRING and Cytoscape, and the MCC algorithm identified five core hub genes: STAT3, MYC, TP53, IL6, and mTOR. Validation using random datasets demonstrated significant upregulation of these genes in the obesity group (p < 0.05), highlighting their potential central role in BPA-induced obesity effects. Functional enrichment analysis via GO and KEGG pathways indicated that BPA may promote obesity by interfering with endocrine signaling, activating lipid metabolism, and stimulating atherosclerosis pathways. Molecular docking analysis using CB-Dock2 confirmed strong binding affinity between BPA and core targets, providing structural evidence for their potential interactions. This study elucidates the potential biological mechanism by which BPA exacerbates obesity through endocrine disruption and metabolic reprogramming, employing a multidimensional approach encompassing cross-target analysis, pathway enrichment, and molecular interactions. It provides an innovative systems toxicology framework and empirical basis for assessing metabolic health risks induced by environmental pollutants. Full article

This paper provides an overview of thin-layer chromatography (TLC) and high-performance thin-layer chromatography (HPTLC) methods for analyzing plant materials and herbal formulations, as described in scientific publications from January 2022 to July 2025. It describes the use of TLC in the qualitative and quantitative examination of plant materials and pharmaceutical preparations containing herbs, including profiling plant materials using TLC and applying it to HPTLC plates. It also describes other modern methods that improve component separations, such as applying TLC to profile plant formulations and detect adulterations and contaminants in them. Additionally, it discusses TLC coupled with other methods, such as principal component analysis (PCA), hierarchical cluster analysis (HCA), orthogonal partial least squares discriminant analysis (OPLS-DA), mass spectrometry (MS), nuclear magnetic resonance (NMR), surface-enhanced Raman spectroscopy (SERS), and image analysis (IA). The quantitative determination of biologically active compounds in herbs and herbal formulations is presented based on methods that combine TLC with densitometry. The paper also discusses TLC with effect-oriented analysis, including the detection of antimicrobial, antioxidant, enzyme-inhibiting, endocrine-disrupting, genotoxic, and cytotoxic substances. The advantages, disadvantages, and prospects of analyzing plant material using the TLC technique are indicated. TLC/HPTLC has great prospects for use by regulatory authorities due to the low cost of analysis and high throughput. Full article

Environmental pollution, driven by industrialization, urbanization, and agricultural practices, has intensified global ecological degradation. Among the most concerning pollutants is PFOS, a synthetic compound known for its chemical stability, environmental persistence, and bioaccumulative potential. Widely utilised in industrial and consumer products, PFOS infiltrates ecosystems and food chains, posing substantial risks to human and animal health. Upon exposure, PFOS disrupts lipid metabolism, damages cellular membranes, and alters signaling pathways through partial metabolism by cytochrome P450 enzymes. Accumulating evidence links PFOS to oxidative stress, mitochondrial dysfunction, endocrine disruption, neurotoxicity, and immunotoxicity. Critically, PFOS contributes to the development and progression of prostate, breast, and ovarian cancers via mechanisms such as hormonal interference, chronic inflammation, and epigenetic modifications. Epidemiological studies further associate elevated PFOS serum levels with increased cancer risk, particularly in occupationally and environmentally exposed populations. This review brings together the latest knowledge on PFOS emissions, mechanistic toxicity, and cancer-causing potential, highlighting the urgent need for focused research and improved regulatory measures to safeguard public health. Full article

Maternal tobacco smoke exposure is associated with impaired fetal growth and long-term disease risk (DOHaD, Developmental Origins of Health and Disease). Whether placental steroid hormones are independently altered remains a matter of debate. We quantified six placental steroids (estradiol, estriol, estrone, progesterone, testosterone, and pregnanediol) using HPLC–Corona CAD in 70 deliveries (C = 30; PS = 20; AS = 20). Distributional differences were assessed with Kruskal–Wallis and pairwise Mann–Whitney tests with Benjamini–Hochberg (BH) control. Adjusted associations used log-linear OLS with HC3 robust SE: Model A (gestational age, maternal BMI, newborn sex) and Model B (Model A + birth weight), reported as percent change vs. controls, computed as (exp(β) − 1) × 100 with 95% CI. Secondary analyses tested (i) multiclass logistic classification of C/PS/AS from the steroid panel (5-fold stratified CV) and (ii) prediction of birth weight (OLS and 2-component PLS). All six steroids differed by group (BH-adjusted p ranging from 9.18 × 10⁻¹² to 6.66 × 10⁻⁸). In Model A, AS vs. C showed lower estrogens/progestins (estradiol, −46.2%; estriol, −24.7%; estrone, −25.9%; progesterone, −28.2%; pregnanediol, −31.4%) and higher testosterone (+40.8%); these effects persisted in Model B after adjusting for birth weight. The panel classified C/PS/AS with 0.900 cross-validated accuracy (weighted OvR AUC 0.994). Hormones poorly predicted birth weight (PLS CV R² = −0.777). Maternal active and passive smoking is associated with a coherent and independent disruption of placental steroidogenesis. A targeted placental steroid panel offers biologically meaningful early markers relevant to DOHaD. Full article