Search Results (2,241)

Lead (Pb) and cadmium (Cd) are common environmental pollutants. Our previous population study revealed a significant positive association between Pb and Cd exposure and the micronuclei frequency among lead smelting workers. However, the underlying mechanisms remain unclear. In this study, human lymphoblastoid TK6 cells were used to investigate the genotoxicity and its mechanisms induced by individual or combined exposure to Pb and Cd. Our results showed that Pb and Cd exposure, alone or in combination, triggered oxidative stress, as evidenced by reduced antioxidant enzyme activity (GSH, SOD and CAT) and increased content of ROS and GSSG. Both metals induced pronounced DNA damage, as shown by elevated Tail DNA% in the Comet assay and γ-H2AX fluorescence intensity. Furthermore, Pb and/or Cd exposure caused inhibition of the DNA repair proteins, including BRCA1, CtIP, RAD52, and XRCC2, indicating impaired DNA repair capacity; and upregulated Bax expression and the Bax/Bcl-2 ratio and Caspase-3 with downregulation of Bcl-2. Notably, Pb and Cd co-exposure produced an antagonistic effect, modulating oxidative stress indicators, cell-cycle arrest, DNA damage markers, DNA repair and apoptosis-related proteins. These findings demonstrate that Pb and Cd induce oxidative stress, DNA damage, inhibition of DNA repair, and apoptosis in TK6 cells. Our study provides new insights into the mechanisms of heavy metal combined exposure–induced genotoxicity and identifies potential molecular targets for intervention. Full article

This study presents a detailed colorimetric evaluation using the CIEL*a*b* system for a novel series of symmetrically structured disazo-stilbene dyes. The synthesis utilized the non-genotoxic 4,4’-diaminostilbene-2,2’-disulfonic acid as the diazotizing component, with the coupling components being N-substituted acetoacetanilide derivatives. The purity of the obtained dyes was confirmed by HPLC analysis. The color analysis was initially conducted on the dyes in solid state (powder) to investigate potential structure–color correlations. Subsequently, these parameters were applied to analyze the performance of the dyes incorporated into acrylic resin films. Titanium dioxide (P.W.6; C.I. 77891) served as the white standard, along with mixtures of dyes in different concentrations that were applied to a cellulosic substrate. The results characterize these compounds as eco-friendly dyes possessing high tinctorial strength and a significant metamerism effect. Full article

Nanosomes—lipid vesicles at the nanoscale—enable the encapsulation of both hydrophilic and lipophilic actives and are increasingly used as skin delivery systems in cosmetic products. Alongside nanoemulsions, polymer nanocapsules, and inorganic nanoparticles (e.g., TiO₂, ZnO, Ag), they can enhance solubility, stability, residence time, and local bioavailability while enabling controlled release. This review summarizes nanocarrier structures, preparation concepts, and skin penetration pathways (transepidermal intercellular/transcellular and transappendageal), and discusses formulation factors that modulate delivery. We highlight applications in UV protection, anti-aging, and fragrance retention, focusing on lipid-based systems (liposomes/nanosomes, ethosomes, niosomes). Safety considerations are critically appraised with reference to EU and FDA frameworks, including physicochemical characterization, dermal penetration, irritation/sensitization, and genotoxicity testing. While most data indicate limited penetration through intact skin for particles ≥20 nm, enhanced uptake may occur under specific conditions (very small size, barrier impairment, mechanical stress), warranting careful risk assessment. We conclude with regulatory and sustainability perspectives and outline research priorities for long-term toxicology, in-use exposure, and standardization of methods. Full article

In the context of the One Health approach, this study assessed the environmental and human health risks posed by 21 chemical elements in soil and in food products (bee pollen, honey, and orange fruits). Data were collected from three cultivated and one uncultivated field, considering the agricultural practices employed. Findings revealed higher metal concentrations in the uncultivated field: Zn > Fe > Pb > Co > Cr > Mn > Ni > Al > Mo > P > B. No significant differences were noted for Ca, Cd, Cu, Sb, Se, and U. The geo-accumulation index indicated moderate Cu accumulation in cultivated fields. Only Hg in uncultivated soil poses a considerable risk at the 95th percentile. Orange fruits showed the lowest metal concentration, whereas bee pollen displayed the highest. In this last product, some elements are present at levels up to 10 times those in other food items, primarily Al, Fe, Zn, and Mn. The hazard quotient for non-genotoxic effects was below 1, indicating low concern. In terms of cancer risk, the levels of Pb and Cd were acceptable, while Ni in beehive products and orange fruits posed a moderate risk. Full article

Zinc oxide (ZnO), silver (Ag) and titanium dioxide (TiO₂) nanoparticles (NPs), are three of the most widely manufactured NPs, while composite NPs have gained popularity due to their enhanced properties. NP release in environmental matrices increases chances of bioavailability and subsequent impact on human health. The current study focuses on manufacturing, characterization and cyto-genotoxic assessment of Ag, ZnO/Ag, TiO₂ and TiO₂/Ag NPs with and without humic acids (HAs), aiming for a holistic approach that leads to a comprehensive profile of said NPs. It entails (a) the synthesis of the aforementioned NPs via single-nozzle Flame Spray Pyrolysis (SN-FSP); (b) the characterization of NPs (in powder form and in dispersion media) using Powder X-ray Diffraction (PXRD), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS); and (c) the assessment of their genotoxicity and cytotoxicity against human lymphocytes in presence of two HAs, thus simulating actual environmental conditions, and without HAs, through the cytokinesis block micronucleus assay (CBMN) with cytochalasin-B. No genotoxicity was observed in any case, whereas cytotoxicity induction varied depending on the NP and the presence or absence of the two HAs. Therefore, it is indispensable to evaluate the toxic profile of NPs considering different environmental scenarios, while conducting an integrated characterization of NPs. Full article

Atrial septal defect (ASD) has become increasingly common in the USA and now affects 1 in 11.3 children in some places, but space–time analysis has not been applied to this emerging trend. ASD rate (ASDR) data were obtained from the National Birth Defects Prevention Network 2003–2020. Substance (cigarettes, alcohol, cannabis, analgesics, cocaine) use data were obtained from the National Survey of Drug Use and Health. Income data were obtained from the US Census. Analysis was limited to the Non-Hispanic White population by technical factors. Time-sequential univariate and bivariate maps were prepared for both covariates and outcomes and their combinations. Spatial regression of the ASDR was performed using the R package splm. A total of 7.6% of data was interpolated by linear regression. A total of 110,107 ASD cases were identified amongst 17,751,437 live births in 27 US states across 10 reporting periods. Time series maps showed that ASDR showed concordant patterns with indices of cannabis use rather than other substances. This was confirmed by multivariate spatial regression where cannabis and cannabinoids alone were found to significantly relate to ASDR, with p = 0.00002 for cannabidiol. Cannabis legal status similarly tracked with ASDR. Compared to states where cannabis was not legal, ASDR was more prevalent in cannabis-legal states (OR = 2.73 (2.66, 2.80); E-Value 4.90 (lower C.I. 4.76)). Twenty-seven of 34 (79.4%) E-values were >9 (high range) and 34/34 were > 1.25 (causal threshold). Data show that cannabis, including cannabis legalization, is driving the US ASD epidemic. While most high-ASDR states have high rates of cannabis use, Midwestern states where cannabis is farmed, such as Kentucky, Tennessee and Missouri, do not, suggesting other routes of exposure, potentially implicating environmental contamination. ASD is a bellwether marker for cannabinoid teratogenicity, indicating that communities should carefully control cannabinoid exposure and limit transgenerational cannabinoid genotoxicity more generally. Full article

Leaves of Actinidia chinensis Planch. var. deliciosa (A.Chev.) A.Chev. (A. deliciosa) represent agro-industrial byproducts with potential for valorization. The present study evaluated the metabolomics profiling, cytotoxicity, genotoxicity, and antigenotoxicity of the methanolic extract of A. deliciosa leaves. The metabolomics profiling was determined using an untargeted metabolomic approach employing UPLC-HRMS. Cytotoxicity, genotoxicity, and antigenotoxicity were assessed in Chinese hamster ovary K1 (CHO-K1) cells using the in vitro cytokinesis-block micronucleus (CBMN) assay. The metabolic profile of A. deliciosa leaf extracts revealed the presence of three major classes of secondary/specialized metabolites: proanthocyanidins, flavonols, and triterpenoid saponins. Medium-polar metabolites were monomeric fla-van-3-ols, such as (+)-catechin and (−)-epicatechin, oligomeric procyanidins and prodelphinidins, and flavonols. Certain glycosylated flavonols and their derivatives, such as myricetin, quercetin, and kaempferol. Low-polarity metabolites were characterized by low-polarity triterpenoids such as maslinic, corosolic, oleanolic, and ursolic acids. At concentrations of 37.5, 75, and 150 µg/mL, the extract did not significantly increase micronuclei frequency compared to untreated control cells, indicating an absence of genotoxic potential. Moreover, co-treatment of CHO-K1 cells with the extract and mitomycin C (MMC) at 0.025 µg/mL resulted in a significant reduction in micronuclei formation induced by MMC at concentrations of 75 and 150 µg/mL, suggesting antigenotoxic activity likely associated with the phytochemical constituents presented in the extract. Full article

Bladder cancer (BCa) arises from the interaction between environmental exposures and the host’s immunity and microbiome. Once considered sterile, the urinary tract is now known to harbor a resident urinary microbiome (UM) that dynamically interacts with the immune system and is influenced by systemic immunomodulatory effects of the gut microbiome (GM) brought on by the emerging gut–bladder axis. Accumulating evidence links alterations in UM and GM leading to BCa development, progression, and recurrence. Loss of protective taxa (e.g., Lactobacillus, Bifidobacterium and Ruminococcus) and enrichment of pro-inflammatory or genotoxic bacteria (e.g., Fusobacterium, Acinetobacter, Prevotella and Enterobacteriaceae) are associated with immune evasion and systemic inflammation. Microbial metabolites, especially short-chain fatty acids (SCFAs), play a key role in shaping tumor immunity and show diagnostic and prognostic potential, with specific microbial signatures correlating with recurrence risk, survival, and treatment response. Therapeutically, growing evidence suggests that microbiome composition influences immunotherapy response, highlighting opportunities for microbiome-based interventions. This review aims to summarize the rationale to implement microbial modulation strategies (e.g., dietary modulation, probiotics, fecal microbiota transplantation (FMT), and emerging synbiotic or postbiotic approaches) while addressing their current limitations and future requirements in order to develop microbiome-guided therapies, diagnostics and prognostic tools for BCa. Full article

Transposable elements (TEs) are major contributors to genome plasticity and can reshape gene regulation through stress-responsive activation and the formation of TE-gene chimeric transcripts. Although therapeutic stress is known to perturb transcriptional networks in cancer cells, its impact on canonical TE transcription and TE-gene chimera formation in esophageal squamous cell carcinoma (ESCC) remains poorly defined. To address this, we performed a comprehensive transcriptome-wide analysis of TE expression and TE-gene chimeric transcripts in KYSE150 ESCC cells following combined 125I radiation and carfilzomib treatment. The TE analysis showed 148 dysregulated TEs, characterized by ERV1 LTR element enrichment and distinct treatment-control sample separation, indicating structured remodeling of the TE transcriptome. We identified 301 significant TE-gene chimeric events, indicating category-specific remodeling with an increase in TE-initiated and TE-exonic chimeras and a decrease in TE-terminal events. The TE families that underwent the most transcriptional changes were not those that drove chimeric events, indicating that global TE activation does not passively cause chimera remodeling. The gene repression was strongly associated with chimeric transcripts, and gene expression changes were negatively correlated with chimerism frequency. SPANXN1, IL1RL1, and RSAD2, strongly downregulated genes, produced novel TE-derived isoforms and were high-potential functional candidates. Epigenetic context analysis showed considerable overlap between exonized chimeras and candidate cis-regulatory elements, suggesting a potential association with regulatory genomic contexts. Pathway enrichment analysis showed synchronized transcriptomic reprogramming and cell cycle and DNA repair pathway activation and autophagy inhibition. In esophageal cancer cells, concurrent genotoxic and proteotoxic stress causes complex TE remodeling, linking traditional TE transcriptional alterations to structured TE-gene chimera development and stress-related transcriptome reprogramming. Full article

The increasing adoption of biopolymeric and nanostructured coatings for horticultural produce has emerged as a sustainable strategy to mitigate postharvest losses and extend shelf life. However, while their technological performance has been extensively documented, comprehensive and integrative assessments of biosafety, potential human health implications, and environmental risks profiles are still insufficiently explored. This review critically analyzes recent advances in polysaccharide, protein, and lipid-based coatings, including nanoenabled systems incorporating metallic nanoparticles and bioactive agents. The mechanisms underlying gas barrier properties, antimicrobial activity, and preservation efficacy are discussed alongside degradation pathways in composting, soil, and aquatic environments. Particular attention is given to nanoparticle release, migration potential, gastrointestinal fate, and toxicological endpoints such as oxidative stress, genotoxicity, endocrine disruption, and immunomodulation. Ecotoxicological evidence across trophic levels, from microorganisms and invertebrates to fish and amphibians, is examined, highlighting sublethal and mechanistic biomarkers relevant to environmental risk assessment. Regulatory frameworks from major agencies are also compared to contextualize current safety standards and limitations. Overall, although biopolymeric coatings represent promising alternatives to conventional plastics, their life-cycle impacts, transformation products, and nano-related uncertainties require comprehensive, multilevel risk evaluation to ensure truly sustainable and safe postharvest applications. Full article

Lactiplantibacillus plantarum LP28 (LP28), isolated from traditional Taiwanese dried tofu, has been demonstrated to have substantial probiotic potential because it increases the production of short-chain fatty acids (SCFAs) and strengthens anti-inflammatory responses. In this study, the safety of LP28 was assessed using both in vitro and in vivo approaches, including whole-genome sequence analysis, the Ames bacterial reverse mutation assay, a chromosomal aberration test, a rodent peripheral blood micronucleus test, a 28-day subacute oral toxicity assay, and an assessment of hemolytic activity. In vitro phenotypic evaluation revealed that LP28 exhibited no hemolytic activity and was susceptible to all the tested antibiotics except kanamycin. In vivo assessments revealed no significant alterations in reticulocyte counts or micronuclei incidence in ICR mice, and SD rats exhibited no subacute toxicity at an oral LP28 dosage of 2000 mg/kg body weight/day for 28 days. Moreover, a whole-genome sequence analysis of LP28 revealed the absence of antimicrobial resistance genes, harmful virulence factors, and genes associated with biogenic amine synthesis. Additionally, the presence of genes involved in stress responses (e.g., acid, bile salt, heat, osmotic, and oxidative stresses) and adhesion-related genes was confirmed. Furthermore, LP28 contains six genes (plnA, plnE, plnF, plnJ, plnK, and plnN) that encode bacteriocin precursor peptides, suggesting the potential for enhanced probiotic effects through the production of antimicrobial plantaricins. These findings highlight the potential of LP28 as a safe and effective probiotic for human consumption. Full article

Oxidative stress is one of the major contributors to DNA damage and genomic instability, emphasizing the importance of identifying natural compounds with antioxidant genoprotective potential. Cedrus atlantica essential oil (EO) has been widely reported to possess antioxidant properties and potential genoprotective effects due to the presence of a cohort of antioxidant compounds, including polyphenols and terpenes. Nevertheless, its effects on DNA integrity remain poorly understood. The present study aimed to evaluate the genotoxic and antigenotoxic effects of C. atlantica EO in human peripheral blood mononuclear cells (PBMCs) using the alkaline Comet assay. PBMCs were exposed to increasing concentrations of the EO (0.2–3% w/v) under basal conditions and in the presence of hydrogen peroxide (H₂O₂, 25 µM) as an oxidative DNA-damaging agent. Genetic damage was quantified by visual score, and arbitrary units were converted into a percentage of DNA in the comet tail. The EO was characterized by gas chromatography–mass spectrometry. The results showed that C. atlantica EO did not induce detectable genotoxic effects under the experimental conditions and within the tested concentration range (0.2–3% w/v). H₂O₂ exposure markedly increased DNA strand breaks, whereas co-treatment with the EO significantly attenuated H₂O₂-induced oxidative DNA damage, particularly at intermediate concentrations. The chemical characterization analysis revealed a sesquiterpene-rich profile dominated by cedrene- and himachalene-type compounds. Overall, these findings indicate that C. atlantica EO exerts antigenotoxic effects against oxidative DNA damage, supporting its genoprotective potential in moderate concentrations. Full article

Temporomandibular disorder (TMD) is recognized as a major public health problem, causing pain and physiological and psychosocial limitations. In this context, the present in vitro study investigated the synthesis of a hyaluronic acid (HA) hydrogel with hydrocortisone (Hyd), designed to enhance joint lubrication by reducing mechanical friction and delivering the anti-inflammatory drug. The hydrogels were prepared with 3% HA (30 mg/mL) and Hyd—0.125% (1.25 mg/mL), 0.250% (2.5 mg/mL), 0.500% (5 mg/mL), or 1% (10 mg/mL). Physicochemical analyses included Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TGA), rheological tests (frequency, amplitude, and temperature ramp scans), and field emission scanning electron microscopy (FESEM), performed before and after sterilization and cycling. In addition, cytocompatibility was evaluated by protocol OECD 129 and confocal microscopy, as well as genotoxicity (OECD487) in mouse macrophages (RAW 264.7 strain) per 24 h of exposure. FTIR demonstrated the spectral signatures of the compounds with no covalent interactions between the drugs, as well thermal stability on TGA. Rheology demonstrated that Hyd protected the HA structure after autoclaving, maintaining viscoelastic properties. SEM confirmed homogeneous porous morphology. Biological assays showed cell viability > 70%, but with a dose-dependent increase in genotoxicity (4–17 micronuclei). Confocal analysis revealed increasing cytotoxicity at high Hyd concentrations, indicating a balance between biocompatibility and adverse effects at concentrations ≤ 0.5%. Among the tested formulations, the 3% HA + 0.250% Hyd hydrogel provided the best balance of viscoelastic stability, cytocompatibility, and low genotoxicity, supporting its potential as a dual-function intra-articular candidate for TMD therapy. Full article

The growing demand for sustainable food preservation drives interest in edible nanoemulsions encapsulating bioactive compounds. This study developed casein–lecithin-based nanoemulsions combining carvacrol (CV)—a compound with potent antimicrobial and moderate antioxidant activity—with vitamin E (VitE)—a powerful antioxidant—as multifunctional food coatings. Three formulations were prepared via homogenization: NE-CV (2% CV), NE-VitE (2% VitE), and NE-CV/VitE (1% each). Physicochemical characterization revealed monomodal size distributions (22.7–57.7 nm), with successful encapsulation confirmed by FTIR. NE-CV/VitE exhibited intermediate particle size (34.4 nm) and zeta potential (−19.8 mV). Antioxidant activity followed NE-VitE > NE-CV/VitE > NE-CV, with the co-encapsulated system preserving VitE’s radical scavenging (EC₅₀ 10.76 µL/mL, DPPH). Remarkably, NE-CV/VitE demonstrated enhanced antibacterial activity against E. coli, requiring half the CV concentration (0.07 mg/mL) versus NE-CV alone (0.15 mg/mL), while maintaining CV dose-dependent activity against S. aureus (0.30 mg/mL). Nanoencapsulation significantly reduced CV cytotoxicity in human lymphocytes at concentrations up to 50 μg/mL (48.8% cytostasis vs. 58.9% for free CV), with no genotoxic effects observed within this range, while preserving full bioactivity. In fresh minced pork over 6-day refrigerated storage, NE-CV/VitE coating maintained pH stability (5.65–5.75), preserved red color (a* values 6.24 vs. 4.99 uncoated), reduced lipid oxidation (TBARS 0.74 vs. 0.82 mg MDA/kg), and achieved a 99% reduction (2-log) in total viable counts versus uncoated controls. The CV/VitE co-encapsulated nanoemulsion represents an integrated, safe, and effective multifunctional preservation technology with synergistic antimicrobial enhancement and uncompromised antioxidant protection, offering a natural alternative for comprehensive food quality preservation. Full article

The use of cytostatic drugs for cancer treatment is currently the main weapon in the fight against cancer; however, prolonged exposure of healthcare personnel can cause adverse toxic effects. Objective: To determine the genotoxicity caused by exposure to cytostatic drugs, using the comet assay, in workers in the oncology department of a tertiary hospital in northern Peru. Methodology: Descriptive, quantitative, correlational, and cross-sectional study. The population consisted of two groups of workers: exposed (n = 40) and unexposed (n = 40). The alkaline lysis comet DNA technique was used on peripheral blood cells; tailing moment and tailing percentage indicators were evaluated. Results: Using nonparametric tests, the percentage and tail moment showed no significant differences, with p values of 0.8928 and 0.4675, respectively. The distribution observed in the group exposed to cytostatic drugs (pharmacists and pharmacy technicians) compared to the control group showed a normal distribution, with a tail moment of 8.29 vs. 3.03 and a percentage of tail of 37.12 vs. 23.24, respectively. Multivariate analysis showed that the tail moment variable was 11.56% greater in the group of pharmacists and pharmacy technicians (p = 0.0119) compared to the other participants. Conclusions: Although no significant difference was found, a trend toward a higher percentage and tail moment was observed in the group exposed to cytostatic drugs. Furthermore, the group of pharmacists and pharmacy technicians, compared to the other professions, showed significantly greater damage. Full article