Search Results (466)

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

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

Cerium oxide nanoparticles (CeO₂NPs) possess unique physicochemical properties that make them promising compounds for medical and industrial applications. However, variations in synthesis methods, particle size, and surface characteristics may influence their potential toxicity. This study provides a comparative analysis of CeO₂NPs synthesized via three methods (citric, dextran, and uncoated modifications) to evaluate their toxicity, antioxidant mechanisms, and genoprotective potential using a panel of Escherichia coli-based lux-biosensors. Our data indicate that all of the tested CeO₂NPs exhibit high biocompatibility with no significant toxicity or genotoxicity at physiological concentrations (10⁻⁴–10⁻² M). The citrate-modified nanoparticles demonstrated pronounced catalase-mimetic activity, acting as the most effective scavengers against hydrogen peroxide. Conversely, the dextran-modified nanoparticles exhibited the highest antimutagenic potential, reducing dioxidine-induced DNA damage by over 56%. Thus, beyond establishing biocompatibility, this study highlights the potential of using specific CeO₂NP modifications for targeted therapy depending on the oxidative pathway involved. This suggests their potential for application as antioxidant and antimutagenic agents in both human and veterinary medicine. Full article

This study investigated the influence of cocoa-bean amino acid profile on the formation of α,β-unsaturated carbonyls. Some of these heat-derived compounds generated primarily during roasting (often through Strecker degradation and aldol condensation) are of toxicological concern (e.g., the aneugenic 2-phenylcrotonaldehyde and the genotoxic furan-2(5H)-one). Here, their levels were compared by SAFE-GC/MS in cocoa of different origins, before and after roasting. Free amino acid profiles were determined by HPLC-MS/MS. All the investigated roasted beans showed similar total free amino acid contents (10.5–15.0 g·kg⁻¹) and profiles, while α,β-unsaturated aldehyde levels differed markedly between samples, and reached >200 µg·kg⁻¹ after roasting, indicating that amino acid availability alone does not govern their formation. Analysis of a commercial cocoa-free chocolate surrogate, however, revealed much lower amounts of both free amino acids (total 1.6 g·kg⁻¹) and amino-acid-derived α,β-unsaturated aldehydes (total 11 µg·kg⁻¹) than in chocolate, together with only traces of pyrazines (total 72 µg·kg⁻¹). In contrast, furan-2(5H)-one was found at similar levels in chocolate and the cocoa-free product (56–79 µg·kg⁻¹), confirming a completely different pathway where amino acids are not key reagents in its synthesis. Full article

The small molecule SR8278 was initially identified as an antagonist of the REV-ERB (reverse c-ERBAa) nuclear receptor proteins, which play important roles in metabolism and circadian rhythms. Though SR8278 has been shown to have beneficial physiological effects in a variety of different preclinical disease contexts, its impact on gene expression and cell proliferation in keratinocytes has not previously been examined. We therefore carried out an RNA-seq analysis and found that genes involved in the G1/S transition of the cell cycle were significantly impacted by SR8278 treatment, and these effects were confirmed at both the RNA and protein level by RT-qPCR and Western blotting, respectively. Cell proliferation assays showed that SR8278 slowed cell growth but did not induce genotoxic stress or apoptosis. Finally, the use of CRISPR/Cas9 genome editing and siRNA-mediated disruption of REV-ERB gene expression showed that the loss of the REV-ERB proteins did not impact the effect of SR8278 on gene expression and cell proliferation. We conclude that the anti-proliferative effects of SR8278 are not mediated by the REV-ERB proteins, and, thus, care should be taken when interpreting studies involving this compound unless complementary genetic approaches are also shown, particularly in studies involving cell proliferation. Full article

This study examines 36 wild Asteraceae species that are traditionally used as food in Sicily and Bulgaria, highlighting their ethnobotanical, nutritional, and pharmacological relevance. Some taxa, such as Cichorium intybus, Silybum marianum, Artemisia vulgaris, Taraxacum officinale, and Tussilago farfara, are integral to the Mediterranean and Balkan diets, enhancing nutrition through their fiber, minerals, and bioactive compounds. This ethnobotanical survey revealed a clear geographic pattern in species usage: 13 species were found to be consumed solely in Bulgaria, 18 solely in Sicily, and five species in both regions. The distribution highlights the existence of shared culinary traditions that have been distinctly adapted to the unique ecological conditions present in each locale. The main metabolite classes identified include flavonoids, phenolic acids, lignans, and sesquiterpene lactones, all of which are associated with antioxidant, anti-inflammatory, hypolipidemic, and anticancer properties. Specific taxa within the investigated group were found to contain alkaloids that warrant toxicological attention. Some species within the studied group contain alkaloids that may pose toxicity risks. T. farfara is known to accumulate pyrrolizidine alkaloids, which are associated with liver damage and potential genotoxic effects, highlighting the importance of thorough toxicological evaluations before recommending these plants for consumption. This study also demonstrates how common culinary processes, such as boiling and blanching, significantly impact the concentration, stability, and safety profile of these bioactive compounds. Overall, the research supports the promotion of wild Asteraceae species as valuable and sustainable nutritional and nutraceutical resources. This approach aligns with efforts to preserve biodiversity and maintain traditional Mediterranean and Balkan food practices, integrating both ecological and cultural sustainability. Full article

Natural compounds are increasingly recognized as valuable sources of pharmacologically active agents for cancer therapy. Among them, plant-derived triterpenoids attract attention due to their structural diversity and broad biological activity. Roburic acid (RA), a tetracyclic triterpenoid, has previously been shown to exert antiproliferative effects in colorectal cancer (CRC) cells with limited cytotoxicity. In the present study, we investigated the cellular mechanisms underlying RA activity in CRC cells, focusing on cell cycle regulation, mitochondrial function, apoptosis, oxidative stress, and DNA integrity. RA treatment markedly suppressed CRC cell proliferation, resulting in G₀/G₁ cell cycle arrest and downregulation of key proliferation markers. Mitochondrial analysis revealed an early reduction in mitochondrial membrane potential (MMP) following RA exposure, indicating mitochondrial dysfunction. Importantly, these effects occurred in the absence of intracellular reactive oxygen species (ROS) generation and without induction of DNA strand breaks, demonstrating a non-pro-oxidant and non-genotoxic profile of RA. Apoptotic features were observed mainly at higher concentrations and after prolonged exposure and were strongly dependent on cell line and assay type. Overall, RA limits CRC cell growth predominantly through cytostatic mechanisms, including cell cycle arrest and mitochondrial modulation, while apoptosis is a secondary, context-dependent response. The lack of oxidative stress and genotoxicity distinguishes RA from many conventional cytotoxic agents and supports its further investigation as a non-genotoxic anticancer compound. Full article

Cellular senescence (CSEN) is caused by a variety of factors that trigger complex molecular pathways. These include telomere shortening, oncogene activation and replicative stress, as well as DNA damage caused by genotoxic anticancer drugs and endogenous and exogenous genotoxins. Here, we review the induction of CSEN by exogenous genotoxic insults resulting from food and environmental exposures. The available data show that genotoxins/carcinogens in tobacco smoke and smokeless tobacco, in the environment, in food, beverages and life-style products induce CNS. The exposures include N-nitroso compounds, polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, acrylamide, heavy metals, fine dust, mycotoxins, phytotoxins, and phycotoxins. Also, heme in red meat contributes to CSEN as it catalyzes the formation of genotoxic species in the colon. Induction of CSEN by external genotoxins/carcinogens is bound on the DNA damage response pathway (DDR), which relies on activation of the ATM/ATR-CHK2/CHK1-p53-p21 axis and the p53-independent p16/p14 axis, eliciting cyclin-dependent kinase inhibition and permanent cell cycle arrest. Other factors that can be involved are DREAM, MAPK, cGAS/Sting, and NF-κB. The accumulation of non-repaired DNA damage triggering CSEN following external genotoxic exposures may contribute significantly to the amelioration of senescent cells and organ failure with age in humans. Senescent cells drive, via the senescence-associated secretory phenotype (SASP), inflammation that is involved in many diseases, including cancer. Although most of the studies were performed with in vitro cell systems, the consequences of CSEN induction by genotoxic nutritional components and environmental exposures seem to be underestimated. Since CSEN correlates with aging, it is reasonable to conclude that exogenous genotoxic pollutants contribute significantly to the aging process through CSEN induction. In light of these findings, it is deduced that reducing genotoxin exposures and using “rejuvenation” supplements (senotherapeutics) are reasonable strategies to counteract cellular senescence and the aging process. Full article

Background/Objectives: DNA polymerase ε (Pol ε), encoded by POLE1, plays a pivotal role in high-fidelity DNA replication and in coordinating DNA repair. While pathogenic exonuclease-domain variants are well established in cancer, biallelic POLE1 variants remain largely unexplored in non-malignant human cells. Methods: Here, we analyzed primary fibroblasts derived from a skin biopsy of a compound-heterozygous patient carrying two POLE1 variants. Western blot analysis confirmed detectable Pol ε protein levels, indicating preserved protein expression despite the underlying variants. Results: Nevertheless, functional alterations were observed across multiple independent assays. Compared with healthy control fibroblasts, this patient-derived Pol ε fibroblast line exhibited reduced clonogenic survival following ionizing radiation. Surviving fractions were consistently lower across radiation doses from 2 to 4 Gy, with an approximately twofold reduction at 2 Gy and progressively greater differences at higher doses. The isoeffect dose corresponding to 10% survival was reduced relative to pooled control fibroblasts. In addition, chromosomal breakage was increased, supporting altered processing of radiation-induced DNA damage in this cellular model. Live-cell imaging and senescence assays revealed delayed proliferation and an increased proportion of senescent or senescence-like cells under baseline and genotoxic stress conditions, including enhanced senescence-associated β-galactosidase activity. Flow-cytometric analysis demonstrated S phase accumulation and G2/M arrest, consistent with replication stress and cell-cycle perturbation. Immunofluorescence staining revealed increased γH2AX foci, consistent with persistent DNA double strand breaks. RAD51 foci formation was not reduced; instead, increased RAD51 recruitment was observed under combined cisplatin and irradiation treatment, arguing against a primary defect in RAD51-mediated homologous recombination. POLE1-variant fibroblasts also showed impaired proliferative recovery, reduced wound closure, increased γH2AX accumulation following cisplatin exposure, suggesting heightened susceptibility to DNA crosslinking stress. Conclusions: Collectively, these findings provide the first functional characterization of a patient-derived POLE1-variant fibroblast cell line and indicate that altered Pol ε function may influence cellular responses to genotoxic stress. While based on primary fibroblasts from a single compound-heterozygous patient, validation in additional patient-derived or isogenic models will be required to determine the broader relevance of these findings. Full article

Tuberculosis (TB) remains a global health issue exacerbated by spreading drug resistance and lengthy treatment regimens. Targeting bacterial DNA-repair pathways, particularly those counteracting host-generated genotoxic stress, represents a promising strategy to sensitize Mycobacterium tuberculosis to existing antibiotics. Through structure-based virtual screening of a compound library, we identified novel small-molecule inhibitors of M. tuberculosis uracil–DNA glycosylase (MtbUng), an enzyme essential for the repair of DNA damage inflicted by macrophage-produced reactive nitrogen species. Experimental validation revealed that four derivatives of usnic acid, a lichen-derived metabolite, significantly inhibited MtbUng activity, with the most potent compound, OL10-88-1, exhibiting IC₅₀ 26 ± 7 µM. Molecular docking suggests that OL10-88-1 inhibits MtbUng by occupying both the active site and the DNA-binding groove, thereby disrupting multiple steps of uracil recognition. The compounds also showed variable inhibitory activity against uracil–DNA glycosylases from Escherichia coli, humans, and vaccinia virus. Our findings establish that the compound could potentially be used in combination therapies to enhance the efficacy of current anti-TB drugs by exploiting the vulnerability of DNA-repair-deficient mycobacteria. Full article

Phthalates are a class of compounds commonly used as plasticizers in various industrial and consumer products. In line with the increasing environmental and biological exposure concerns regarding these compounds, this study investigated the dose-dependent effects of diethyl phthalate (DEP) on the liver in a subacute rat model. Diethyl phthalate (DEP) was given orally by gavage to female Wistar albino rats at doses of 100, 300, and 600 mg/kg body weight per day for 21 days in order to assess liver tissue and associated function test levels. Liver function was evaluated by analyzing serum biochemical data. Liver tissues were evaluated using histopathological staining (H&E and Masson’s trichrome staining), immunohistochemical analysis of IL-1β and TGF-β, tissue ELISA for IL-6 and TNF-α, and comet assay to determine DNA damage. DEP exposure was found to cause significant, dose-dependent histopathological changes in liver tissue, including hepatocyte necrosis, cytoplasmic vacuolization, sinusoidal dilation, and vascular congestion. AST levels were significantly increased compared to the control group, while no significant changes were observed in other serum biochemical parameters. Compared to the control group, the expression of pro-inflammatory cytokines (IL-6 and TNF-α), IL-1β, and TGF-β was found to be elevated in the DEP-treated groups, and their levels increased with increasing exposure dose. DEP exposure also caused significant DNA damage in liver tissue. These findings indicate that despite an increase in AST levels observed in subacute DEP exposure, there were limited changes in serum biochemical parameters; serum liver enzymes alone may not fully reflect the extent of hepatic damage, and DEP can cause significant inflammatory, histopathological, and genotoxic effects in liver tissue. Full article

Parkinson’s disease (PD) is a complex neurodegenerative disorder influenced by age, genetic predispositions, and environmental exposures, with a growing global incidence. This review aims to summarize findings from ATSDR Toxicological Profiles, EPA Risk Assessments, and other sources of peer-reviewed literature to examine the potential associations between PD and select metals, pesticides, and chlorinated organic compounds. Additionally, it explores using computational toxicology methods to elucidate the interactions between specific chemicals, associated genes, and their possible roles in PD. A total of 29 substances were identified to be neurotoxic with direct or probable association with PD. Risk of disease onset or symptom exacerbation of PD has been linked to exposures to neurodegenerative metals, pesticides, chlorinated organic compounds, and other environmental toxicants, alongside intrinsic factors such as genetic predisposition and aging. Supporting evidence from neurotoxicological studies directly or possibly associated with PD are summarized in referenced toxicological profiles and EPA risk assessments. Genotoxic endpoints evaluated in exposure-induced neurodegeneration including oxidative stress, DNA strand breaks, mitochondrial dysfunction, impaired DNA repair, and telomere alterations may play a critical role in linking environmental exposures to PD pathogenesis. Although these endpoints represent imperative data gaps between environmental and genetic risk factors for PD, isolating individual substances may not be necessary for prevention, as many co-occur at contaminated sites or within certain occupations. Further research is needed to clarify causal relationships between environmental exposure and genotoxic endpoints seen in neurodegenerative processes that can also be seen in PD for consideration in the development of preventive and therapeutic strategies. Full article

New diarylheptene polyphenols with α-glucosidase inhibitory activity were previously isolated and reported from the aquatic plant Ottelia acuminata var. acuminata. It was used as the template in the present research, and a series of 1,3-bisbenzylphenylphenolic compounds were designed and synthesized. The tyrosinase, α-glucosidase inhibitory effects, antioxidant properties, and whitening effects of these compounds were investigated. Of them, the representative compounds 1 and 2 inhibited the two target enzymes (tyrosinase and α-glucosidase) engaged in skin whitening and aging with comparable IC₅₀ values to the reference drugs as well as antioxidant activities. They showed potent whitening efficacy in zebrafish. In particular, compound 1 had whitening-effect rates of 31% at a concentration of 0.0001% (m/m), and 52% at a concentration of 0.0002% (m/m). Both compounds had more superior whitening efficacy than the commercially available whitening agent phenylethylresorcinol (377), which was used as a positive control. Compounds 1 and 2 did not show any genotoxicity and skin phototoxicity at the test concentrations, and they show promise as new skin-whitening agents. Full article