Search Results (54,539)

Visible-light preconditioning may complement sunscreen use by enhancing intrinsic DNA damage responses. We pre-irradiated Hs27 human dermal fibroblasts with 505 nm blue–green light (5.0 mW/cm², 3–10 min; 0.9–3.0 J/cm²) before UVB irradiation (20 mJ/cm²). At 505 nm, the residual cyclobutane pyrimidine dimer (CPD) burden measured 24 h after UVB was reduced when UVB followed immediately or after 3–24 h (with residual CPDs falling to approximately 67% of the UVB-alone level—an approximately 33% reduction—at the most effective 3.0 J/cm², 24 h condition), whereas protection was lost by 48 h. Under the 0 h interval condition, CPDs were also quantified immediately after UVB to compare the early CPD signal with the 24 h residual endpoint; all three visible wavelengths (505, 470 and 630 nm) lowered the immediate post-UVB signal, but only 505 nm preconditioning sustained the protective effect at the 24 h endpoint. Blue light (470 nm) produced a limited delayed benefit, whereas red light (630 nm) did not confer consistent protection and increased the residual CPD burden under selected conditions. Non-toxic 505 nm exposure primed an amplified NRF2/ARE response to subsequent UVB; XPC and XPD mRNAs rose at 2–6 h, while XPA and XPB declined early. Together, these findings support further evaluation of 505 nm blue–green light as a proof-of-concept, device-oriented strategy for timed photoprotection against UVB-induced photoaging; because these findings were obtained in a single dermal fibroblast model, they will require validation in keratinocytes and more complex skin systems before any practical application. Full article

Breast cancer remains a major global health burden. Dactylospongia species have been explored for their cytotoxic potential. This study aims to evaluate the cytotoxic potential of compounds derived from the marine sponge Dactylospongia elegans. Dactylospongia elegans were collected from the Lembeh Strait, macerated using methanol, then partitioned to an ethyl acetate fraction. The cytotoxic activity of these fractions was assessed using MDA-MB-231 cells while toxicity testing was done using the BSLT. TLC was carried out to determine the groups of compounds, while LC-MS/MS was used to predict active compounds contained in the ethyl acetate fractions. In silico studies were conducted as preliminary studies to determine the antitumor mechanism. The ethyl acetate fraction and F4 subfraction of Dactylospongia elegans exhibited cytotoxicity toward MDA-MB-231 cells with IC₅₀ values of 15.72 and 41.76 µg/mL, respectively. The BSLT indicated the strongest toxicity belongs to the F6 subfraction (LC₅₀ = 32.831 µg/mL). TLC analysis confirmed the presence of major secondary metabolites as terpenoids, steroids, and alkaloids, then confirmed with LC-MS/MS including 5-epi-illimaquinone and calciferol. Molecular docking revealed that calciferol exhibited the strongest binding affinity toward tyrosine kinase and p53–MDM2 receptors, with binding energies of −10.13 and −10.28 kcal/mol, respectively. These findings suggest that Dactylospongia elegans contains bioactive constituents with potential anticancer activity, particularly against TNBC. Full article

Microplastics are increasingly recognized as prevalent contaminants in freshwater ecosystems, where they interact with a wide range of co-occurring pollutants, including heavy metals, pesticides, pharmaceuticals, and persistent organic pollutants. Evidence indicates that microplastics can act as vectors, enhancing pollutant mobility and facilitating trophic transfer, while also modulating toxicity through synergistic or antagonistic effects. Ecotoxicological studies reveal adverse impacts on aquatic organisms, ranging from physiological stress and impaired reproduction to altered community dynamics, with implications for ecosystem functioning and human health. Despite growing knowledge, significant gaps remain in understanding long-term environmental behavior, standardized methodologies, and risk assessment frameworks. This review synthesizes current findings on microplastic–pollutant interactions in freshwater systems, highlights emerging ecotoxicological risks, and identifies critical research needs to inform effective management and policy interventions. Full article

Cisplatin is an effective platinum-based chemotherapeutic agent used to treat a variety of cancers. However, its clinical utility is limited by dose-dependent neurotoxicity, yet no approved neuroprotective strategy currently exists. Our integrated cellular, metabolic, and in vivo approaches unraveled the neuroprotective potential of Areca catechu ethyl acetate extract (AC-EA) against cisplatin-induced neurotoxicity. Importantly, AC-EA did not reduce cisplatin-induced cytotoxicity in A549 lung cancer cells. In HT22 hippocampal neurons, AC-EA restored cell viability, suppressed reactive oxygen species generation, preserved mitochondrial-associated fluorescence, and attenuated phosphorylated histone H2AX (γH2AX)-marked DNA damage. AC-EA was associated with increased pNRF2 expression, consistent with activation of NRF2-dependent antioxidant signaling, suppressed inducible nitric oxide synthase iNOS (inducible nitric oxide synthase )-mediated neuroinflammation, and prevented the depletion of total AKT (protein kinase B) protein. Untargeted metabolomics and Caenorhabditis elegans survival assays were performed for mechanistic and in vivo validation. Metabolomics data showed restoration of several critical amino acids, including L-tyrosine and β-alanine, disrupted by cisplatin. Moreover, C. elegans studies confirmed in vivo activation of antioxidants via the SKN-1/GST-4 (glutathione S-transferase 4) pathway. While AC-EA shows neuroprotective potential, arecoline’s toxicity demands caution. To our knowledge, this is the first study to demonstrate the neuroprotective activity of A. catechu against cisplatin-induced neurotoxicity, laying the foundation for developing plant-derived adjunct therapies for chemotherapy-associated neuropathy. Full article

The removal of phenol from contaminated effluents presents an industrial challenge owing to its toxicity at trace concentrations. Multi-walled carbon nanotubes (MWCNTs) have been studied as adsorbents for this purpose, given their high adsorption capacity and ease of separation. This work presents a theoretical phenomenological and numerical analysis of mass transport coupled to phenol adsorption on MWCNTs (external diameter $d_{ext}=50$ nm), parameterized using published experimental equilibrium data acquired under neutral pH conditions at 298 K. The mathematical model incorporates an effective pore diffusivity ($D_e=3.213\times {10}^{-10}$ m²/s) derived from pore structure parameters and describes three distinct scenarios: (1) pure physical adsorption via a modified Fick’s Second Law; (2) coupled diffusion–reaction with 0.5-order kinetics, herein treated as an empirical kinetic ansatz with phenomenological divergence from lumped empirical models (PFO/PSO); and (3) a parametric and sensitivity analysis on particle size (1–100 nm) and inlet concentration (1–5 mg/L). Numerical solutions confirm a Thiele modulus $\varphi \ll 1$ across the tested range, indicating a kinetically controlled regime with effectiveness factor $\eta \approx 1.0$, and validate the theoretical scaling $\varphi \propto C_s^{-0.25}$. During effluent polishing operations (reduction from 5 to 1 mg/L), the relative diffusive resistance increases by 49.5%, suggesting proportional increases in contact time or adsorbent dosage are required. A one-at-a-time (OAT) sensitivity analysis on $D_e$, $\kappa$, and $k_{obs}$ confirms that the kinetically controlled regime is preserved across plausible parameter ranges. The nanoscale architecture of MWCNTs reduces theoretical intraparticle diffusional resistance by several orders of magnitude relative to macroscopic granular adsorbents. We emphasize that these conclusions describe theoretical mass-transport advantages; experimental and pilot-scale validation under realistic, multi-component wastewater conditions remains an essential step before industrial deployment. Full article

Gymnaconitum gymnandrum, a Tibetan medicinal herb, is distributed across high-altitude regions of China. Despite its high toxicity, it exhibits analgesic, anti-inflammatory, antitumor, and other pharmacological activities. It is used topically for skin conditions and orally for rheumatism. Its main bioactive components are alkaloids. A new organic amine alkaloid has been isolated from the plant and structurally identified using HRMS, NMR, and X-ray diffraction. Full article

Repeat expansion cerebellar ataxias comprise a genetically and mechanistically heterogeneous group of neurodegenerative disorders unified by the pathological expansion of short tandem repeats (STRs) beyond a disease-causing threshold. Depending on their genomic localization, these expansions can lead to toxic protein gain-of-function, as in polyglutamine (polyQ) cerebellar ataxias, or to RNA-mediated toxicity and repeat-associated non-AUG (RAN) translation, for which recent evidence supports a major pathogenic role in non-coding spinocerebellar ataxias (SCAs). Despite these distinct upstream mechanisms, disruption of neuronal homeostasis occurs through converging pathogenic processes, including proteostasis impairment, transcriptional dysregulation, and mitochondrial dysfunction, leading to progressive neuronal loss. Importantly, impaired autophagy has been consistently reported across multiple repeat expansion ataxias, including both dominant SCAs and recessive conditions, such as Friedreich’s ataxia, suggesting that impairment of this pathway may represent a shared downstream event in disease progression. Indeed, in polyQ cerebella ataxias, the accumulation of misfolded and aggregation-prone proteins places a substantial burden on cellular quality control systems, particularly the ubiquitin-proteasome system and autophagy. Similarly, in non-coding SCAs, toxic RNA species and RAN-derived peptides might interfere with protein clearance mechanisms and contribute to cellular stress. In this review, we will discuss the evidence supporting autophagy impairment as a convergent pathogenic pathway in repeat expansion cerebellar ataxias. Full article

Diabetic foot ulcers (DFUs) constitute a significant global health burden; however, the influence of environmental heavy metals toxicity on their pathogenesis remains insufficiently investigated, particularly within low- and middle-income countries. This systematic review, conducted in strict accordance with PRISMA 2020 guidelines, assesses the impact of heavy metals exposure on the development, progression, and wound-healing kinetics of DFUs. A comprehensive search across PubMed/MEDLINE, Embase, Scopus, and Web of Science identified 32 eligible original studies. Quality appraisal was performed using the Newcastle-Ottawa Scale and SYRCLE’s Risk of Bias tool. Synthesized epidemiological and toxicological data consistently indicate that chronic exposure to non-essential heavy metals, specifically cadmium and lead, significantly augments DFU prevalence and clinical severity, demonstrating a 64% increase in DFU prevalence for each 1 µg/L increase in blood cadmium concentration. Mechanistically, these xenobiotics induce a ‘chronic inflammatory lock’ characterized by severe oxidative stress, sustained NLRP3 inflammasome activation, and the suppression of protective Metallothionein 2A (MT2A) pathways, thereby impeding microvascular angiogenesis. Conversely, deficiencies in essential trace elements, such as zinc and selenium, actively impair extracellular matrix maintenance. Advanced therapeutic interventions, including metal-ion-releasing hydrogels, cell-free exosome therapies, and systemic EDTA chelation, demonstrate significant potential to counteract heavy-metal-induced cellular suppression and facilitate tissue repair. This review underscores the imperative of integrating environmental toxicant screening and targeted detoxification strategies into standard multidisciplinary diabetic foot management. Full article

Background/Objectives: Chronic exposure to endocrine-disrupting chemicals has been increasingly recognized as a potential contributor to cancer progression. Monobutyl phthalate (MBP), a major metabolite of dibutyl phthalate, is widely detected in human biological samples, yet its long-term impact on anaplastic thyroid cancer (ATC) has not been systematically investigated. Methods: CAL-62 cells were continuously exposed to an environmentally relevant concentration of MBP (10 nM) over 3 months to establish a chronic exposure model that mimics long-term environmental exposure. Transcriptomic profiling was integrated with network toxicology to identify key molecular pathways and hub genes, followed by molecular docking and Western blot validation. Results: Chronic MBP exposure significantly enhanced cell viability, proliferation, colony formation, and tumorsphere formation, indicating promotion of malignant phenotypes. Transcriptomic profiling revealed extensive molecular remodeling characterized by activation of inflammation-associated pathways, including cytokine–cytokine receptor interaction, IL-17, TNF, and JAK–STAT signaling, accompanied by suppression of p53- and mTOR-related pathways. Integrated analysis identified 57 overlapping KEGG pathways, with IL6 and CSF2 emerging as central hub genes. Molecular docking demonstrated favorable binding affinities between MBP and representative target proteins, including IL6, TP53, CASP3, BCL2, and PPARG. Western blot analysis further confirmed increased IL6 and BCL2 expression together with decreased TP53, CASP3, and PPARG expression following chronic MBP exposure. Conclusions: Chronic environmentally relevant MBP exposure promotes ATC malignant progression through coordinated inflammation-associated molecular network remodeling accompanied by suppression of apoptosis-related signaling. Integrating network toxicology with transcriptomic profiling provides an effective systems-level strategy for identifying biologically relevant molecular networks underlying chronic environmental toxicant exposure. Full article

The long-term preservation of historical documents in archival environments is critically challenged by the accumulation of hazardous gases—formaldehyde (HCHO), benzene (C₆H₆), and radon (Rn)—which originate from collection materials and pose severe health risks to personnel. In this work, we systematically investigate, via first-principles theory, the potential of Au- and Ru-doped PtSe₂ monolayers as resistive-type gas sensors for the detection of these pollutants. Atomic-scale substitutional doping at the Se site is modeled to establish the doped PtSe₂ configurations, and the structural stability, electronic properties, adsorption behavior, charge transfer characteristics, and recovery kinetics of the doped systems are comprehensively evaluated and compared. Our findings, through comprehensive comparison, reveal that Ru-PtSe₂ outperforms its Au-doped counterpart across all key performance metrics, positioning it as a promising candidate for hazardous gas monitoring in archival environments. The key innovation of this work lies in the systematic comparative assessment of noble metal dopants on PtSe₂ monolayers, identifying Ru as a superior choice to Au and providing a theoretical foundation for designing high-performance, recyclable 2D material-based gas sensors tailored for cultural heritage preservation applications. Full article

Levofloxacin is an antibiotic belonging to the fluoroquinolone family. N-Demethyllevofloxacin, a metabolite and an impurity of levofloxacin, features a secondary amine that is susceptible to N-nitrosation, raising concerns about the formation of a potentially toxic nitrosamine. The corresponding N-nitrosamine was synthesized in two steps and characterized using HRMS, NMR spectroscopy, IR spectroscopy, UV absorption and emission spectroscopies and powder X-ray diffraction. This work provides a reliable reference for the quantitation and control of nitrosamine impurities associated with levofloxacin in chemical and pharmaceutical contexts. Full article

Aflatoxin contamination of cereal grains represents a serious food safety concern due to the toxic and carcinogenic properties of aflatoxins produced mainly by Aspergillus species. The present study aimed to evaluate the antifungal and antiaflatoxigenic potential of lactic acid bacteria (LAB) cell-free supernatants as a natural approach for controlling aflatoxin-producing fungi in wheat grains. A total of fifty fungal isolates recovered from agricultural samples were screened for their aflatoxigenic potential using phenotypic and molecular approaches. The toxigenic isolates were identified as Aspergillus flavus (AF) and Aspergillus parasiticus (AP), and their aflatoxigenic potential was confirmed by PCR amplification of aflatoxin biosynthesis-related genes (nor-1 and aflR). The antifungal activity of selected LAB strains was evaluated against the identified Aspergillus isolates using the agar diffusion method. The obtained results demonstrated that LAB cell-free supernatants exhibited significant antifungal activity, with variations among strains. Among the tested LAB strains, Lactobacillus plantarum P3 and Lactobacillus acidophilus ATCC 20552 showed the highest inhibitory activity against both fungal species. Furthermore, LAB treatments significantly reduced fungal-induced wheat grain damage and decreased aflatoxin accumulation during storage. Application of 100% LAB supernatants resulted in a remarkable reduction in total aflatoxins, reaching more than 99% reduction compared with untreated controls. The inhibitory effect decreased with increasing dilution of the supernatants, indicating a concentration-dependent antifungal and antiaflatoxigenic activity. The findings demonstrate that LAB-derived metabolites can effectively suppress the growth of aflatoxin-producing Aspergillus species and limit aflatoxin biosynthesis. Therefore, LAB cell-free supernatants represent a promising biological control strategy for improving cereal safety and reducing mycotoxin contamination in food systems. Full article

This research explores the production of activated carbon from a lignocellulosic precursor, corn cobs, as a potential method for the removal and adsorption of phenolic and nitrophenolic compounds. Colombia is a major corn producer, with a national production of 1,559,194 tons in 2024. Currently, approximately 0.5 to 3.2 kg of corn residue per kg of product is not commercially utilized. The objective is to focus on the removal of phenol, 2-nitrophenol, 4-nitrophenol, and 2,4-dinitrophenol from simulated solutions to evaluate the adsorption capacity under optimal conditions. Phenolic and nitrophenolic compounds are considered highly toxic molecules for the environment, especially in the plastics and agrochemical production sectors. These compounds are pollutants in wastewater due to their impact on aquatic life and human health. This not only contributes to the utilization of residual biomass but also to the circular economy by promoting its valorization in environmental remediation processes. The diameter and average volume of the pores are large enough to promote rapid diffusion kinetics of the phenolic compounds within the pore structure, which varies from 0.207 to 0.544 cm³ g⁻¹, and their adsorption capacity. The most adsorbed phenol was found to be 4-nitrophenol, with up to 97 mg of contaminant (4-nitrophenol) adsorbed per gram of activated carbon (sample designated AC-TK), at initial concentrations ranging from 0.0 ppm to 3.0 ppm. Furthermore, magnetite plays a crucial role in the adsorption of 2-nitrophenol. With this compound, up to 86 mg of 2-nitrophenol per gram of activated carbon was adsorbed at a concentration of 14 ppm, whereas without magnetite, a smaller amount was adsorbed at lower initial concentrations (ppm) for the same compound. Full article

Background/Objectives: Moderately hypofractionated radiotherapy (MHRT) may shorten treatment duration for cervical cancer but raises concerns regarding toxicity due to substantial interfractional pelvic organ motion. This prospective study evaluated the feasibility, workflow efficiency, dosimetric benefits, and acute toxicities of daily online adaptive radiotherapy (oART)-guided MHRT. Methods: Thirty patients with FIGO 2018 stage IB1–IIB or IIIC1 cervical squamous cell carcinoma receiving definitive chemoradiotherapy were prospectively included between September 2023 and April 2024 (NCT05994300). All patients underwent daily oART, receiving 43.35 Gy in 17 fractions to the pelvic target volume, with a simultaneous integrated boost to 54.40 Gy in 17 fractions for involved lymph nodes. The adaptive workflow consisted of iterative cone-beam computed tomography acquisition, artificial intelligence-assisted contouring, physician review, plan adaptation, and treatment verification. Workflow efficiency, plan selection, target coverage, organ-at-risk (OAR) sparing, treatment completion, early tumor response and acute toxicity were prospectively assessed. Results: A total of 510 adaptive fractions were delivered. The first-attempt adaptation success rate was 99.0%, and adapted plans were selected in 99.4% of fractions. The mean adaptive workflow and total treatment times were 17.3 and 23.3 min per fraction, respectively. Compared with scheduled plans, adapted plans significantly improved target coverage, with V_100% increasing by 7.26% for the planning target volume of the uterus and 8.79% for planning target volume of the cervix (both p < 0.001), while significantly reducing doses to the bladder, rectum, small bowel, bone marrow, and femoral heads. All patients achieved complete clinical response at 3 months. Acute toxicity was generally manageable; Grade ≥ 3 gastrointestinal, genitourinary, and hematologic toxicities occurred in 10%, 0%, and 40% of patients, respectively, including one Grade 4 neutropenia event, and no treatment interruptions. Conclusions: Daily oART-guided MHRT was feasible and efficient, providing improved target coverage and reduced OAR doses compared with scheduled plans. Acute toxicity was acceptable. These findings provide early prospective evidence supporting the feasibility of this treatment strategy and warrant further validation in larger prospective studies with longer follow-up. Full article

VERO cells, derived from the kidney epithelium of the African green monkey, are widely used in virology, but their ability to metabolize xenobiotics is not fully understood. Since cytochrome P450 (CYP) enzymes participate in xenobiotic metabolism, we investigated which CYP genes are expressed in VERO-E6 cells. Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) showed that VERO-E6 cells express CYP3A4, CYP3A5, and CYP3A7. In contrast, CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2D6, and CYP2C9 transcripts were either not detected or at a low detection level. To determine whether the encoded enzymes have the potential to activate aflatoxin B1 (AFB1), we used artificial intelligence (AI)-based structural modeling along with molecular docking. AI modeling suggested that CYP3A enzymes can position AFB1 in an orientation compatible with the formation of the reactive intermediate, and CYP3A4 showed the most favorable predicted interaction (docking score: −16.3 kcal/mol). To demonstrate AFB1 bioactivation, we exposed VERO-E6 cells to 200 nmol/L AFB1. After 10 days, we observed about 40% cell death. Liquid chromatography–tandem mass spectroscopy (LC–MS/MS) analysis confirmed the presence of AFB1-derived DNA adducts, indicating that metabolic activation occurred in these cells. These findings support the presence of CYP-dependent AFB1 bioactivation in VERO-E6 cells. Thus, combining computational and experimental approaches elucidates xenobiotic metabolism in cells where biochemical data are limited. Full article