Search Results (2,308)

Chronic exposure to benzo[a]pyrene (BaP), a Group 1 IARC carcinogen, is a major driver of lung carcinogenesis; however, how sustained subcytotoxic exposure reprograms bronchial epithelium toward preneoplastic states remains poorly defined. Here, we subjected BEAS-2B human bronchial epithelial cells to 12 weeks of continuous BaP at environmentally relevant concentrations (0.1 and 1.0 µM) and interrogated the resulting phenotypes using an integrated multi-scale framework encompassing functional toxicology, RT-qPCR, RNA-seq, phospho-kinase/NF-κB arrays, and organotypic air–liquid interface (ALI) cultures. Cells maintained metabolic competence throughout, evidenced by sustained CYP1A1 and CYP1B1 induction at both acute (4 h) and chronic (12-week) timepoints, while accumulating genotoxic stress as demonstrated by dose-dependent nuclear γ-H2AX foci formation and ATM phosphorylation (Ser1981). RNA-seq revealed a dose-dependent transcriptional shift: 0.1 µM BaP yielded 119 differentially expressed genes (DEGs; |log2FC| ≥ 1, FDR < 0.05), whereas 1.0 µM generated 255 DEGs. Downregulated transcripts were enriched for extracellular matrix and cell-adhesion programs (COL14A1, ADAMTS2, CSMD3, CADM3), while upregulated genes encompassed inflammatory, calcium-signaling, and vesicle-trafficking modules (NFATC4, CSF2RA, SYT1, PCLO). Phospho-kinase/NF-κB arrays confirmed a p53/NF-κB signaling nexus, with concurrent activation of MAPK/ERK (Thr202/Tyr204) and PI3K/Akt (Ser473) pathways. Despite persistent genotoxic stress, cells did not acquire anchorage-independent growth and remained non-tumorigenic in vivo. Critically, ALI organotypic cultures derived from BaP-exposed cells exhibited histological dysplasia, nuclear pleomorphism, and disrupted apical-basal polarity. These findings mechanistically link chronic BaP exposure to an initiation-like preneoplastic state and establish a validated 2D/3D multi-omics platform for PAH-driven lung carcinogenesis research. Full article

This study investigates the key performance-related fuel properties of emulsifier–diesel solutions and ethanol-in-diesel microemulsions. This work begins with the in situ polymerization of long alkyl chain-substituted glycidyl methacrylate (R-GMA) in diesel and the optional presence of a second methacrylate monomer. The resulting diesel-soluble oligomer functions as a nonionic emulsifier. Controlled amounts of ethanol are subsequently incorporated into the emulsifier–diesel solution to form a stable microemulsion, referred to as E-Diesel. This study examines how the structure of the emulsifier influences key fuel properties, including (i) ethanol–diesel miscibility, (ii) gross calorific value, (iii) Ramsbottom carbon residue (% of fuel), (iv) entrapped polycyclic aromatic hydrocarbons (PAHs), and (v) fuel lubricity. Both the hydrophilic–hydrophobic balance and the structure of the emulsifier side chains are found to significantly affect these properties. Compared with neat diesel, oligomeric emulsifiers enable the substantial dispersion of ethanol in diesel (up to 18 wt.%). The resulting fuel exhibits a gross calorific value exceeding the theoretical sum of diesel and ethanol at the same composition (a synergistic effect) and achieves an enhancement in lubricity up to 49.5% relative to neat diesel at a 5% emulsifier loading. Although the presence of emulsifiers leads to an increase in the carbon residue by up to 54.7% compared to neat diesel during controlled pyrolysis, it simultaneously reduces the PAH content in the exhaust. Overall, this study establishes fundamental correlations among microemulsion stability, combustion synergy, carbon residue formulation, and fuel lubricity, which are governed by the structure of the emulsifier. Full article

Right ventricular pressure overloading [RVPO] with secondary maladaptive RV remodeling and progressive myocardial dysfunction in patients with pulmonary hypertension associated with left-sided heart diseases [PH-LHDs] and in those with pulmonary arterial hypertension [PAH] still remains one of the most complex challenges in cardio-pulmonary medicine. Despite the advances in the optimization of diagnostic tools and the expansion of treatment options, there is still a great need for further research to gain a better understanding of the major pathophysiological mechanisms involved in both the RV responses to PO and to find new possibilities to stop the progression of the alterations inside the pulmonary arterial circulation [PAC]. This article summarizes current knowledge about the particularities of the RV structural and functional responses to abnormal PO and also provides an overview of the benefits and limitations of the currently available tools for clinical evaluations of the RV adaptability to high afterload. A major focus of this review relates to the possibilities for obtaining evidence about the existence of a still remaining adaptability to a normal afterload in an over-burdened RV, in case of abolition of the pathological PO and, in this regard, to also evaluate the clinical usefulness of the RV adaptability estimation for certain critical therapeutic decisions. Among the most important conclusions of this updated overview are: 1. Whereas single parameters are insufficiently reliable for the evaluation of RV dysfunction and for predictions of its prognostic relevance across the whole spectrum of RVPO, properly selected and integrated multiparametric approaches had meanwhile unequivocally proved that they can usually become sufficiently reliable. 2. Multiparametric approaches can substantially improve the prediction of a preserved RV responsiveness to the abolition of its steady PO by reversal of RV maladaptive remodeling and by the normalization of RV pump function. Such a prediction, which can be decisive for therapeutic decision-making especially in candidates for ventricular assist device [LVAD] implantation or thoracic organ transplantation, can have a crucial impact on patient survival. 3. The complex and temporally highly variable interactions between certain structural and functional changes in both the PAC and in the hemodynamic overloaded right-sided heart, as well as between the two ventricles, can often hamper the interpretation of certain changes in the measured parameters and even relevantly alter their reliability. Additionally, the progressive aggravation of a secondary tricuspid regurgitation [TR] has a particularly high negative (often also misleading) impact on the diagnostic and prognostic relevance of RVPO evaluations. Full article

Bioturbating animals move around large amounts of sediment, changing its physicochemical properties and biogeochemical processes. The present study assessed the role of the ghost shrimp Lepidophthalmus louisianensis, a major coastal bioturbator in the Northern Gulf of Mexico, in the fate of crude oil after the 2010 Deepwater Horizon blowout. Experiments were conducted in greenhouse mesocosms, with or without ghost shrimp and with or without added oil, reflecting mild surface or subsurface oiling in a beach environment. To evaluate the hydrocarbon-degradation potential of the sediment microbial community, a respirometric radiotracer assay was conducted with ¹⁴C naphthalene as a model polycyclic aromatic hydrocarbon (PAH) compound. Oil augmentation led to a substantial increase in the PAH degradation potential of mesocosm sediments, which was further enhanced by the presence of the bioturbator. However, bioturbation alone, without previous oil exposure, did not enhance naphthalene degradation. 16S rRNA gene analyses showed that there were no significant changes in the microbial community composition associated with either bioturbation, oil augmentation, or both. This study demonstrated bioturbation- and oil-exposure-related enhancement in hydrocarbon degradation in mildly oiled sediment, and indicated that this may be due to an increased expression of PAH degrading activities in the preexisting community of hydrocarbon-degrading bacteria rather than resulting from a shift in the microbial community composition. Full article

The occurrence and spatial distribution of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), fragrances, UV filters and photoinitiators were investigated in surface sediments of Nerbioi-Ibaizabal estuary between 2005 and 2013, in 2020. Samples were extracted by focused ultrasound solid–liquid extraction technique and analyzed by gas chromatography coupled with mass spectrometry. Total PAHs, PCBs, OCPs, musks, UV filters and photoinitiators concentrations ranged between not detected (n.d.) and 43000 ng g⁻¹, n.d. and 2500 ng g⁻¹, n.d. and 820 ng g⁻¹, n.d. and 880 ng g⁻¹, n.d. and 91 ng g⁻¹ and from nd to 120 ng g⁻¹, respectively. Hexachlorocyclohexanes (HCHs) were ubiquitous in the estuary, suggesting that these compounds, although banned, leach from landfills. The PCB concentrations showed a decreasing trend. Ecological risk assessments based on sediment quality guidelines (SQGs) and risk quotient (RQ) suggested semi-volatile organic compounds could represent a potential ecological risk in the Nerbioi-Ibaizabal estuary. Full article

Polyelectrolyte microcapsules (PMCs) fabricated by layer-by-layer assembly require predictable shell stability for applications in drug delivery, biosensing, and environmental remediation. While core template type is known to influence stability, the role of polyelectrolyte layer number in governing poly(allylamine hydrochloride) (PAH) desorption remains poorly understood. This study quantitatively assessed PAH desorption from fluorescein isothiocyanate (FITC)-labeled shells of PMCs templated on CaCO₃ or MnCO₃ cores with 7, 9, or 13 layers under varying ionic conditions (distilled water, NaCl 0.2–3.0 M, Na₂SO₄ 0.005–1 M) over 168 h. Short-term incubations revealed no significant layer-dependent desorption differences for either core type. However, prolonged exposure uncovered a non-monotonic relationship for CaCO₃-templated PMCs: 7-layer capsules exhibited high initial but limited subsequent release (<50% increase), 9-layer capsules showed minimal initial dissociation followed by maximal kinetic amplification (up to 2000% increase), and 13-layer capsules displayed intermediate behavior. In contrast, MnCO₃-templated PMCs demonstrated uniformly low initial dissociation with gradual time- and concentration-dependent release irrespective of layer number. These findings establish core template nature as the dominant factor controlling dissociation kinetics, while layer number enables fine-tuning of release profiles—particularly for CaCO₃ systems—providing design principles for controlled-release applications requiring delayed or sustained payload delivery. Full article

Human skin and hair act as multifunctional barriers but are highly sensitive to environmental pollutants originating from air, water, and cosmetic products. Epidemiological studies report that exposure to particulate matter (PM_2.5–PM₁₀), nitrogen oxides (NO_x), and volatile organic compounds increases the risk of skin and hair disorders. For instance, women in high-traffic areas (N = 211) show significantly more pigment spots and nasolabial wrinkles compared to those in rural areas (N = 189), indicating accelerated skin ageing. Children aged 9–11 exposed to PM₁₀, benzene, and NO_x exhibit increased incidence of atopic dermatitis. Systemic exposure to dioxins causes chloracne, while co-exposure to polycyclic aromatic hydrocarbons (PAHs) and UVA radiation elevates skin cancer risk. Psoriasis flares are associated with mean pollutant concentrations over the 60 days preceding flare events in 957 patients, and hyperpigmentation prevalence increases in populations exposed to traffic-related PM and ROS-inducing pollutants. Hair loss is linked to oxidative stress from PM and PAHs absorbed on hair fibers, with in vitro studies showing keratinocyte apoptosis in scalp hair follicles. This review evaluates natural adsorbents such as zeolites, clays, activated carbon, and polyphenol-rich plant extracts for anti-pollution cosmetic formulations. Adsorption capacities range from 60 to 150 mg·g⁻¹ depending on the pollutant, with removal efficiencies of 30–55% in model topical systems. Mechanisms include ion exchange, surface adsorption, hydrophobic interactions, and radical scavenging. Incorporating 2–5% w/w of these adsorbents in cosmetic formulations significantly reduces pollutant deposition on skin and hair. These findings support the development of evidence-based, sustainable anti-pollution cosmetic strategies that quantitatively mitigate environmental stressor effects. Full article

Pulmonary arterial hypertension (PAH) has traditionally been viewed as a vasculocentric disorder, with current therapies failing to reverse vascular remodeling or address pervasive systemic metabolic abnormalities. This review synthesizes emerging evidence to propose a paradigm shift, conceptualizing PAH as a systemic metabolic–immunological network disease. It examines how metabolic dysfunction in peripheral organs (adipose tissue, liver, skeletal muscle) and immunometabolic reprogramming of immune cells (e.g., macrophages, lymphocytes) synergistically drive pathology. These components engage in dynamic crosstalk via circulating mediators (metabolites, adipokines, cytokines), creating a self-amplifying loop that fuel pulmonary vascular inflammation and remodeling. Key mechanisms explored include adipose tissue endocrine dysfunction (contributing to the obesity paradox), hepatic insulin resistance and bile acid signaling, skeletal muscle energy crisis and wasting, and the pivotal roles of macrophage glycolytic polarization and T-cell subset imbalance. Insulin resistance/hyperglycemia emerges as a central hub linking metabolic and immune dysregulation. The review concludes that future therapeutic strategies must move beyond vasodilation to target this systemic network, discussing the potential of repurposed metabolic agents, direct immunometabolic modulators, and integrated lifestyle interventions to disrupt disease progression. Full article

Microplastics and polycyclic aromatic hydrocarbons frequently co-occur in aquatic and terrestrial ecosystems, where their combined biological effects remain incompletely understood. Although both stressors exhibit well-documented individual toxicities, co-exposure studies report highly variable outcomes, ranging from enhanced or reduced toxicity to neutral responses. This review synthesizes findings from 45 peer-reviewed studies examining single and combined microplastic–PAH exposures across aquatic vertebrates, invertebrates, plants, microorganisms, and cell-based systems. Rather than introducing novel toxic mechanisms, microplastics primarily modulate the probability, magnitude, and timing of conserved biological response pathways. Across taxa, oxidative stress, metabolic disruption, immune modulation, developmental impairment, and behavioral alterations emerge as recurrent endpoints, with responses strongly shaped by context. Particle size, polymer type, exposure concentration and duration, and organismal traits consistently determine whether microplastics enhance PAH bioavailability, reduce effective exposure through sorption, or result in mixed or negligible effects. Overall, the evidence indicates that microplastics function as dynamic modifiers of chemical stress rather than universal toxicity amplifiers. These findings underscore the limitations of single-contaminant risk frameworks and highlight the need for biology-centered, mixture-based approaches that account for exposure pathways, life-history traits, and conserved stress-response systems in ecological risk assessment. Full article

Background and Clinical Significance: Pulmonary hypertension (PH) is a recognized complication of chronic liver disease, most commonly manifesting as portopulmonary hypertension (POHP) prior to liver transplantation. While the natural history and management of pre-transplant PH are well described, the development of de novo pulmonary arterial hypertension (PAH) following liver transplantation remains exceedingly rare and poorly understood. In such cases, establishing true causality is challenging, and alternative explanations—including previously unrecognized or masked disease—must be carefully considered. This entity poses significant diagnostic and therapeutic challenges and may adversely affect post-transplant outcomes if not promptly recognized and treated. Case Presentation: We report the case of a 46-year-old man with end-stage liver disease secondary to alcohol use who underwent deceased donor liver transplantation without preoperative evidence of PH. His pre-transplant evaluation revealed preserved biventricular function and no measurable PH. Eight days postoperatively, he was readmitted with acute dyspnea, hypoxemia, and signs of right ventricular failure. Transthoracic echocardiography demonstrated severe right ventricular dilation and dysfunction with markedly elevated pulmonary artery systolic pressure. Right heart catheterization confirmed severe PAH. Secondary causes of PH were excluded. The patient was initiated on sildenafil and continuous intravenous epoprostenol, resulting in clinical, echocardiographic, and hemodynamic improvement. Subsequent follow-up demonstrated sustained response to therapy despite concurrent progression of coronary artery disease requiring complex percutaneous intervention. Conclusions: This case highlights a rare presentation of severe PAH occurring shortly after liver transplantation, in the absence of documented pre-transplant PH. While a causal relationship cannot be definitively established, the temporal association raises important clinical considerations. It underscores the need for heightened clinical vigilance for pulmonary vascular disease in post-transplant patients presenting with cardiopulmonary symptoms. Further research is warranted to elucidate the underlying mechanisms, risk factors, and optimal management strategies for PAH diagnosed after liver transplantation. Full article

Pulmonary arterial hypertension (PAH) is characterized by dysfunction and remodeling of the pulmonary artery endothelium and smooth muscle. In heritable PAH, heterozygous loss-of-function mutations in the type II Bone Morphogenetic Protein (BMP) receptor gene (BMPR2) are the most common genetic cause. However, the mechanisms by which reduced BMPR2 levels alter endothelial signaling to drive PAH pathogenesis remain incompletely understood. To determine how BMPR2 levels govern signaling output and endothelial functional responses, we modulated BMPR2 expression in human pulmonary artery endothelial cells (PAECs) and assessed ligand-dependent SMAD1/5/8 signaling, proliferation, and caspase-3/7 activity. We found that BMP9 and BMP10 robustly activated SMAD1/5/8 signaling and promoted proliferation in PAECs, whereas the other ligands in this panel did not elicit a comparable signaling or proliferative response under these assay conditions. A moderate (~50%) reduction in BMPR2 protein levels (an in vitro approximation of haploinsufficiency) attenuated BMP9/10-induced SMAD1/5/8 activation, abolished proliferative responses, and was associated with a modest increase in caspase-3/7 activity, consistent with caspase pathway activation and early stress/injury signaling. Under BMPR2-limiting conditions, BMP9/10 responses became sensitive to Activin type II receptor blockade by bimagrumab, consistent with a context-dependent contribution of Activin type II receptors. Conversely, BMPR2 overexpression enhanced BMP9/10-dependent SMAD signaling and proliferation. Together, these findings support a receptor–dosage model where physiological BMPR2 expression is required to sustain homeostatic BMP9/10 signaling in pulmonary artery endothelium. This framework provides a basis for interpreting context-dependent pathway effects in PAH. Full article

Nanomaterials are gaining increasing importance in various scientific and technological fields, including ecological strategies for environmental remediation, such as the treatment of soils contaminated with petroleum hydrocarbons. This study aimed to evaluate the effectiveness of hydrocarbon-contaminated soil remediation using graphene oxide nanoparticles (GO-NPs) and zinc oxide nanoparticles (ZnO-NPs) in combination with bacterial consortium inoculation and phytoremediation with Lolium perenne. The study was conducted in two stages: laboratory-scale biodegradation experiments and semi-technical scale phytoremediation. The laboratory stage determined optimal nanomaterial doses based on respirometric and chromatographic analyses. During phytoremediation, the contents of total petroleum hydrocarbons (TPHs) and polycyclic aromatic hydrocarbons (PAHs) in soil, roots, and shoots were monitored. Biomass growth was recorded, and environmental toxicity was assessed using Phytotoxkit, Microtox, and Ostracodtoxkit tests. The addition of nanomaterials significantly enhanced soil remediation, with improvements in TPH and PAHs removal resulting from microbial biodegradation in both stages and, additionally, in the phytoremediation stage, from phytoextraction by plants. TPH biodegradation reached up to 81.85% in GO-NP variants and 80.9% in ZnO-NP treatments, while PAHs reached 73.19% and 70.66%, respectively. The biomass of Lolium perenne increased by 28.63% in GO-NP variants and by 22.21% in ZnO-NP treatments compared to the control. Total accumulation of TPH increased by 80.86% and 74.15%, and PAHs by 71.26% and 65.35%. Nanomaterial-amended variants also showed a reduction in toxicity units to 2.50–3.30. These results indicate that combining nanomaterials with bioaugmentation significantly enhances phytoremediation efficiency while reducing soil toxicity. Full article

Countless environmental pollutants and xenobiotics, are widespread and linked to hazardous effects, including breast cancer. Due to their lipophilic properties, these accumulate in fat tissue, such as breast adipose tissue. However, little is still known about their combined effects and distribution within the breast microenvironment. Alterations in fatty acid metabolism can be a biomarker for cancer progression and a potential bioindicator of pollutant exposure. In this study, the fatty acid profile and levels of organochlorine and organophosphate pesticides (OCPs and OPPs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), organophosphate esters (OPEs), polycyclic aromatic hydrocarbons (PAHs) and synthetic musks (SMs) were measured in 48 breast adipose tissue samples from breast cancer and healthy patients (controls). Twelve xenobiotics were detected at high frequency rates, and the distribution profile of these pollutants differed between cohorts. In total, 163 correlations were identified between specific fatty acids and breast cancer patients’ data, with distinct correlation patterns between cohorts. Fatty acids show the potential to be biomarkers of the presence of lipophilic xenobiotics in the breast microenvironment; however, more studies are needed. This preliminary study is the first to analyze OPPs, OPEs, and PAHs in breast adipose tissue and report associations between xenobiotics and specific fatty acids. Full article

Fire smoke, rich in toxic ultrafine particles and polycyclic aromatic hydrocarbons (PAHs), poses significant health risks to first responders and vulnerable populations. In this study, a reproducible combustion–smoke simulation platform was developed to mechanistically quantify fire behavior, particle emissions, and PAH toxicity under controlled heat flux and oxygen conditions. Consistent combustion and smoke emissions were achieved by measuring heat release rate, particle mass, particle number concentration, and PAH concentration, with an overall average coefficient of variation below 15%. Systematic experiments with representative biomass (pine, oak) and plastics (PVC, polystyrene) demonstrate that fuel composition, heat flux, and oxygen availability jointly govern particle formation and PAH partitioning. Regardless of the combustion factors, ultrafine particles dominated the particle number concentration (55.5–86.2%). Plastic combustion generated 7 to 59 times particle mass, up to 260 times higher PAH emissions, and up to 58,500 times greater PAH toxic equivalent quotient (PAH-TEQ) than wood. Oxygen-deficient and smoldering regimes shifted emissions toward fine and ultrafine particles enriched in high-molecular-weight PAHs, revealing a coupled physical–chemical hazard not captured by bulk PM metrics alone. These results establish a quantitative framework linking combustion regime, particle size, and PAH toxicity, providing critical insight for exposure assessment, PPE design, and mitigation strategies in ventilation-limited and mixed-fuel fire scenarios. Full article