Search Results (901)

Background and Objectives: Cerebral radiation necrosis (CRN) is a delayed complication of radiation therapy (RT), that can appear either as radiological findings without clinical symptoms (i.e., asymptomatic CRN) or symptomatic CRN (sCRN). There is currently a knowledge gap regarding CRN-induced epilepsy, a potentially severe manifestation of sCRN. We aim to give a comprehensive overview of the existing literature on CRN-induced epilepsy, including its prevalence, potential risk factors, and treatment options. Materials and Methods: A scoping analysis was performed according to the PRISMA scoping review guidelines. We searched within PubMed and Embase databases and identified relevant clinical studies for inclusion related to CRN-induced epilepsy, based on predefined criteria. Results: In total, 24 studies were identified. CRN-induced epilepsy was a primary outcome in three studies. In the 21 remaining studies, epilepsy was an exploratory outcome or described as part of a small case series. The studies covered various topics in relation to CRN-induced epilepsy, such as the overall clinical manifestations of CRN, the optimization of RT practices to minimize toxicity and improve outcomes, and the effectiveness of laser interstitial thermal therapy (LITT) and bevacizumab. Considerable heterogeneity was seen across studies, particularly concerning the primary tumor types, used definition of CRN and applied RT practices. Conclusions: Epilepsy is a serious clinical symptom in patients with sCRN. However, the current literature is too limited to draw meaningful conclusions regarding its prevalence, risk factors and management. Future research in patients with sCRN should prioritize the evaluation of clinical response to different treatment strategies with particular attention to seizure control. Full article

Crocus sativus L. (saffron), a sterile geophyte of the Iridaceae family, has been traditionally used in culinary and medicinal practices and is currently gaining attention as a source of pharmacologically active metabolites. The main bioactive compounds (BACs) of saffron, crocin, crocetin, picrocrocin, and safranal, are associated with a wide range of biological activities, including anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, antiproliferative, and antidiabetic properties, among others. This review aims to comprehensively and critically summarize the preclinical and clinical evidence for saffron-derived BACs in the context of the most prevalent non-communicable diseases. A literature search of the main scientific databases was conducted to identify peer-reviewed articles on neurodegenerative disorders, cancer, cardiovascular diseases, and diabetes mellitus, with additional topics on ethnopharmacology, phytochemistry, safety, and toxicity. The mechanistic findings include anti-inflammatory, immunomodulatory, antioxidant, antiproliferative, and neuroprotective effects, mediated by activation of the Nrf2 pathway and inhibition of NF-κB. Eligibility criteria were applied, excluding publications focused primarily on food, cosmetics, or technological applications, to prioritize mechanistic and therapeutic endpoints. The findings suggest that BACs from saffron extracts have promising disease-modifying properties and symptom-relieving actions, especially in the case of neurologic disorders, mild cognitive impairment, and some models of metabolic and oncological diseases. Nevertheless, the current variability in study design, dosage, standardization of plant extracts, and sample size limits a conclusive clinical application. More carefully designed studies with a representative number of cases and well-defined plant preparations are needed to validate efficacy, establish structure-activity relationships, and define the prevention and therapeutic potential of saffron in evidence-based pharmacotherapy. Full article

Textile wastewater contains recalcitrant azo dyes and auxiliary chemicals that are resistant to conventional biological treatment, resulting in persistent organic pollution in aquatic ecosystems. While supercritical water oxidation (SCWO) achieves superior chromophore mineralization, its high energy requirements limit industrial scalability. Conversely, biomass-derived activated carbon (BAC) offers a low-cost adsorption solution, but it rapidly becomes saturated with toxic oxidation intermediates. Notably, the literature lacks systematic analyses of hybrid SCWO-BAC systems with integrated thermal energy, which represents a crucial gap in assessing their economic feasibility. This review employed a systematic methodology, selecting studies relevant to the topic from peer-reviewed publications and databases, including Scopus, SciELO, ScienceDirect, and Google Scholar, for critical synthesis. Using SCWO as a pretreatment (which significantly reduces COD load), followed by BAC polishing, results in superior detoxification compared to individual processes. However, three barriers hinder scale-up: (i) chloride ion corrosion in real effluents; (ii) irreversible collapse of BAC pores after multiple regeneration cycles; and (iii) absence of standardized ecotoxicity data for hybrid-treated streams. This work outlines a technological roadmap for integrated supercritical water oxidation and biological activated carbon (SCWO-BAC) systems, targeting economically viable operational parameters for industrial-scale implementation. Full article

Background: Numerous plant-derived products have shown notable potential in preclinical studies and traditional use for the management of periodontitis, although clinical studies validating their efficacy remain scarce. The present study investigated the efficacy of a polyherbal phytopreparation as an adjunctive therapy to scaling and root planing (SRP) in patients with periodontitis, and further examined its underlying mechanisms of action, pharmacokinetic behavior, and toxicological profile using in silico approaches. Methods: Eighty patients with moderate periodontitis (stage II, grade A) were randomly assigned to two groups: a control group (n = 40) treated with SRP alone, and an experimental group (n = 40) receiving SRP followed by topical phytotherapeutic treatment with the polyherbal Tinctura paradentoica^®. Efficacy was evaluated using the gingival index, periodontal pocket depth, and cytomorphometric analysis of gingival cells before treatment and one month after. The in silico analysis, guided by HPLC profiling, included MolDock-based docking to assess interactions of bioactive compounds with cyclooxygenase isoforms COX-1 and COX-2 as anti-inflammatory targets, and evaluation of their pharmacokinetic and toxicity properties (ADME/Tox) using SwissADME, ProTox-3.0, and pkCSM. Results: Compared with SRP treatment, the experimental treatment significantly reduced the gingival index and periodontal pocket depth (p < 0.05), as well as the assessed cytomorphometric parameters (nuclear area, perimeter, and Feret’s diameter values) (p < 0.001). Rerank analysis revealed van der Waals-driven isoform selectivity: compact phenolic acids and aglycones favored COX-1, whereas bulky glycosides (e.g., rutin, narcissoside) were optimized for COX-2, with luteolin-7-O-glucoside showing near-balanced engagement. The ADME/Tox analysis indicated generally favorable pharmacokinetic and safety characteristics of phenolic compounds from the phytopreparation, including low systemic absorption and no predicted mutagenicity or skin sensitization potential. Conclusions: The topical application of the polyherbal phytopreparation demonstrated significant potential to enhance the efficacy of conventional SRP therapy by promoting the regression of gingival inflammation in patients with moderate periodontitis, further supported by in silico findings. Full article

Background: Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, exhibits therapeutic potential for various conditions, including inflammation, pain, and skin disorders, making it a promising candidate for the topical treatment of psoriasis. However, its poor water solubility and instability limit its therapeutic efficacy. This study focuses on the development and characterization of CBD-loaded nanoemulsions using argan oil as the lipid phase, with and without a chitosan coating, which serves as a stabilizing and functional biopolymer. Methods: Nanoemulsions (NE) and chitosan-stabilized nanoemulsions (CS-NE), both without CBD (serving as controls), and CBD-loaded variants (CBD-NE and CBD-CS-NE) were prepared and characterized for their physicochemical properties, including pH, droplet size, polydispersity index (PDI), zeta potential (ζ-potential), and viscosity at various shear rates and temperatures. Stability was assessed over time, and drug release behavior was investigated through in vitro diffusion and ex vivo skin permeation studies, followed by kinetic modeling. Safety was evaluated through in vitro cytotoxicity assays using HaCaT keratinocyte cells, as well as in vivo toxicity studies using Caenorhabditis elegans (C. elegans). Results: The chitosan-coated formulations exhibited enhanced physical stability, nanoscale droplet size, a positive surface charge, and increased viscosity. Release studies demonstrated that CBD-CS-NE enabled controlled and sustained drug release, with a strong correlation to the Higuchi model, indicating diffusion-controlled permeation. Cytotoxicity assays indicated that CBD-CS-NE was non-toxic to cultured cells, while in vivo testing with C. elegans revealed sensitivity to chitosan-coated systems. Conclusions: These findings highlight the potential of CBD-loaded argan oil nanoemulsions, particularly those stabilized with chitosan, as potential topical delivery systems for managing psoriasis. Full article

The toxic actions of 2-monochloropropane-1,3-diol (2-MCPD) are still less well understood than those of 3-monochloropropane-1,2-diol (3-MCPD). The toxic effects of 2-MCPD on the heart, especially at the proteomic level, were recently investigated by researchers in a subacute (28 days, in 2017) and in a subchronic (90 days, in 2024) oral toxicity rat study. Here, we set out to perform an updated analysis and re-evaluation of these proteomic in vivo data in a comparative manner and in the context of 2-MCPD metabolism, focusing in particular on mitochondrial energy metabolism and the maintenance of the structural integrity and function of the heart. The aim of our project was to develop further reasonable, toxicologically relevant research hypotheses for future studies addressing this topic in order to shed more light on the—so far—rather limited knowledge of the toxicological properties and modes of action of 2-MCPD. Our updated data analysis and comparative re-evaluation revealed strong indications of cytoskeletal protein deregulation, indicative of cardiomyocyte degeneration, and the deregulation of enzyme proteoforms linked to carbohydrate utilization and mitochondrial functions. This led us to hypothesize that reactive metabolites of 2-MCPD, other than those formed from 3-MCPD, could impair mitochondrial pyruvate utilization and mitochondrial energy production, potentially resulting in cardiac functional heart failure in rats at doses slightly higher than 10 mg 2-MCPD per kg bw/day. Thus, we postulate the intermediate formation of some putative aldehydic and acidic metabolites following oral 2-MCPD exposure that might be causative of cardiotoxicity in rats. Full article

The cosmetic and personal care industry is increasingly shifting toward plant-derived ingredients that combine multifunctional biological activity with favorable safety and sustainability profiles. Trigonella foenum-graecum L. (fenugreek), a leguminous plant traditionally used in food and medicine, has recently attracted growing attention as a potential cosmetic and cosmeceutical ingredient. This review provides a comprehensive and critical synthesis of current knowledge on fenugreek in the context of skin and hair care applications. First, the phytochemical profile of fenugreek relevant to cosmetics is examined, with emphasis on polyphenols and flavonoids, steroidal saponins, alkaloids (notably trigonelline), and mucilage-rich galactomannans. The biological activities of these constituents are then discussed in relation to key cutaneous and scalp mechanisms, including antioxidant defense, anti-inflammatory and antimicrobial effects, anti-glycation and dermal matrix protection, skin hydration and barrier support, as well as hair growth promotion and scalp health. Particular attention is given to recent in vitro, ex vivo, and emerging clinical evidence supporting anti-aging, moisturizing, and hair-care claims. Current formulation strategies and green extraction technologies enabling the incorporation of fenugreek-derived ingredients into topical products are reviewed, alongside considerations of safety, toxicity, and regulatory status under EU cosmetic legislation. Finally, existing research gaps are identified, highlighting the need for standardized extracts, robust clinical validation, and advanced omics-based approaches. This review highlights fenugreek’s strong potential as a versatile plant-based ingredient in cosmetics, despite remaining understudied in topical applications. Full article

This narrative review aims to highlight and analyze the supervision of precision robotic surgical interventions. These are autonomous, closed-loop procedures, assisted by images and managed by intelligent digital tools. These administered procedures are designed to be safe and reliable, adhering to the principles of minimal invasiveness, precise positioning, and non-toxicity. Thus, a precision intervention uses non-ionizing imaging-assisted robotics, controlled by a precise positioning device, forming an autonomous procedure augmented by artificial intelligence tools and supervised by digital twins. This intelligent digital management procedure allows staff to plan, train, predict, and execute interventions under human supervision. Patient safety and staff efficiency are linked to non-ionizing imaging, minimal invasiveness through image guidance, and strict delimitation of the intervention zone through precise positioning. This study includes, successively, sections covering an introduction, therapeutic and surgical interventions, imaging strategies integrating diagnostic and assistance functions, intelligent digital tools including digital twins and artificial intelligence, image-guided procedures including autonomous and precision robotic surgical interventions increased by machine learning, as well as augmented healthcare monitoring, and a discussion and conclusions of the review. All topics addressed in this analysis are supported by examples from the literature. Full article

Background: Pentamidine isethionate (PTM) and miltefosine (MF) are clinically relevant antiparasitic agents whose use is limited by toxicity, emerging resistance, and the lack of effective co-delivery strategies. Tetronic^® 1307 (T1307), an amphiphilic and thermoresponsive block copolymer, was investigated as a carrier to enable their combination therapy. Methods: PTM and MF were formulated in T1307-based micelles and thermoresponsive gels. The systems were characterized by small-angle neutron scattering (SANS), dynamic light scattering (DLS), and nuclear magnetic resonance spectroscopy (NMR). Antiparasitic activity was evaluated against Leishmania major promastigotes. Results: MF formed stable micelles that efficiently incorporated PTM, generating a “drug-in-drug” architecture. While T1307 alone showed limited PTM loading, MF promoted mixed micelle formation and enhanced PTM incorporation. At physiological temperature and adequate copolymer concentrations, drug-loaded micelles formed thermoreversible gels suitable for topical application. The combined formulations preserved drug activity and exhibited synergistic effects against L. major. Conclusions: T1307 is a promising platform for the co-delivery of PTM and MF, enabling synergistic combination therapy and thermoresponsive gel formation with potential to reduce systemic toxicity and improve treatment administration. Full article

Zeolites are microporous aluminosilicate minerals widely recognized for their adsorption and ion-exchange properties. Their capacity to capture toxic heavy metals has prompted growing interest in their use as anti-pollution agents in skin care formulations. This study investigates zeolite-based creams through an in vitro permeation test using Franz diffusion cells within a Quality by Design (QbD) framework. A 2 × 2 × 2 full factorial design was applied to evaluate the effects of three critical factors: membrane type (Strat-M^® vs. silicone), dosage (10 vs. 20 mg), and dosage regimen. The adsorption and retention of five heavy metals, cadmium (Cd), cobalt (Co), chromium (Cr), lead (Pb), and nickel (Ni), were assessed over 12 h using an in vitro membrane model. The cream containing Zeolite demonstrated significantly higher adsorption of Cr, Co, and Cd compared to placebo and membrane controls, while Ni and Pb exhibited less consistent patterns. No sampling of the receptor compartment was performed; therefore, the analysis focused on metal residues in the donor and membrane compartments. Statistical analyses confirmed the significance of these findings, and graphical trends further supported zeolite’s selective adsorption behavior. Overall, the results provide mechanistic and statistical evidence supporting zeolite as a promising active ingredient for the development of anti-pollution skin care formulations and offer a methodological framework for assessing metal adsorption in topical products. Full article

Acyclovir is an antiviral drug effective against infections caused by herpes simplex and varicella zoster viruses. It is given intravenously to treat serious infections such as herpes encephalitis. High acyclovir concentrations could cause toxicity, observed mainly as nephrotoxicity and, to a lesser extent, neurotoxicity. Acyclovir nephrotoxicity is primarily attributed to the crystallization of acyclovir within the renal tubules, although additional mechanisms may also contribute. However, the mechanism of acyclovir-induced neurotoxicity is unknown. Acyclovir is mainly eliminated from the body through renal excretion; however, around 15–20% of acyclovir is metabolized subsequently by alcohol and aldehyde dehydrogenase to the main metabolite 9-carboxymethoxymethylguanine (CMMG), and around 2% is metabolized by aldehyde oxidase to the minor metabolite, 8-hydroxyl acyclovir. It has been suggested that CMMG levels above 10 µmol/mL in the serum and 1 µmol/mL in the cerebrospinal fluid are highly associated with neurotoxicity. Studies have shown that there is a potential contribution of CMMG to acyclovir-induced neurotoxicity and of the acyclovir aldehyde to nephrotoxicity. In this narrative review, we approach the topic of acyclovir metabolites and their association with acyclovir toxicity. Moreover, we identify the research gap of the mechanisms by which these metabolites contribute to toxicity. Full article

Exogenous toxic compounds in foods, arising from agricultural practices, environmental contamination, industrial processing, and packaging migration, remain a major global concern for food safety. These contaminants include mycotoxins, veterinary drug residues, antibiotics, pesticides, per- and polyfluoroalkyl substances, heterocyclic aromatic amines, and polycyclic aromatic hydrocarbons, which have multiple adverse effects on human and animal health. The continued presence of these substances highlights the need for reliable exposure assessment, strengthened regulatory frameworks, and advanced analytical methodologies. Food matrices introduce variability in analytical performance, making sample preparation a critical and often limiting step. Conventional extraction techniques such as solid-phase extraction, liquid–liquid extraction, and Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) are still widely applied. Moreover, recent advances have highlighted sustainable alternatives aligned with the principles of green analytical chemistry. In this context, this review provides a comprehensive overview of recent advances (2020–2025) in environmentally friendly extraction techniques for determining exogenous toxic compounds in food samples analyzed by liquid chromatography coupled with mass spectrometry (LC–MS), including their sustainability. Special attention is given to the chemical nature and toxicological relevance of major exogenous organic contaminant families (specialized categories such as hormones and packaging-derived bisphenols were excluded due to distinct migration and metabolic pathways; however, these topics exceed the scope of this manuscript), the analytical challenges associated with different food matrices, and the evolution of extraction and cleanup techniques. Overall, this review integrates analytical robustness, matrix effects, and green metrics to support the development of reliable and more sustainable sample preparation strategies. Full article

This study investigates the evolution of public sentiment and discourse surrounding artificial intelligence through a comprehensive multi-method analysis of 28,819 Reddit comments spanning March 2015 to May 2024. Addressing three research questions—(1) what dominant topics characterize AI discourse, (2) how has sentiment changed over time, particularly following ChatGPT 5.2’s release, and (3) what linguistic patterns distinguish positive from negative discourse—we employ 28 distinct analytical techniques to provide validated insights into public AI perception. Methodologically, the study integrates VADER sentiment analysis, Linguistic Inquiry and Word Count (LIWC) analysis with regression validation, dual topic modeling using Latent Dirichlet Allocation and Non-negative Matrix Factorization for cross-validation, four-dimensional tone analysis, named entity recognition, emotion detection, and advanced NLP techniques including sarcasm detection, stance classification, and toxicity analysis. A key methodological contribution is the validation of LIWC categories through linear regression (R² = 0.049, p < 0.001) and logistic regression (61% accuracy), moving beyond the descriptive statistics typical of prior linguistic analyses. Results reveal a pronounced decline in positive sentiment from +0.320 in 2015 to +0.053 in 2024. Contrary to expectations, sentiment decreased following ChatGPT’s November 2022 release, with negative comments increasing from 31.9% to 35.1%—suggesting that direct exposure to powerful AI capabilities intensifies rather than alleviates public concerns. LIWC regression analysis identified negative emotion words (β = −0.083) and positive emotion words (β = +0.063) as the strongest sentiment predictors, confirming that affective rather than technical engagement drives public AI attitudes. Topic modeling revealed nine coherent themes, with facial recognition, algorithmic bias, AI ethics, and social media misinformation emerging as dominant concerns across both LDA and NMF analyses. Network analysis identified regulation as a central hub (degree centrality = 0.929) connecting all major AI concerns, indicating strong public appetite for governance frameworks. These findings contribute to theoretical understandings of technology risk perception, provide practical guidance for AI developers and policymakers, and demonstrate validated computational methods for tracking public opinion toward emerging technologies. Full article

Hair dyes are widely used across all socioeconomic groups and regions worldwide. However, some studies indicate that these products contain substances known to be toxic to a wide variety of organisms. Moreover, dyeing practices generate effluents that may carry the toxicity of hair dyes into the environment. Due to these facts, there is great concern about the impacts these products may have on the environment, as well as on the health of their users and professionals in the field of cosmetology. This scoping review analyzed 184 publications from major databases (PubMed, SciELO, Scopus, Google Scholar, and MEDLINE). Ultimately, 126 scientific studies published between 1981 and 2024 were included based on methodological rigor and their relevance to the One Health framework. According to the literature, the components of hair dyes can induce adverse responses in biological systems, ranging from reversible topical irritations to severe systemic effects. Among the studies evaluated, more than half reported significant toxicological or genotoxic associations related to oxidative dye components such as p-phenylenediamine and its derivatives. These compounds are frequently associated with various types of human cancers, including breast, prostate, bladder, skin, ocular cancers, and brain tumors. In addition to their effects on humans, hair dyes exhibit ecotoxicity, which may threaten the maintenance of ecosystems exposed to their residues. The reported environmental impacts result from effluent emissions after successive hair washes that release unreacted dye residues. Due to the low biodegradability of these compounds, conventional wastewater treatment methods are often ineffective, leading to environmental accumulation and changes in aquatic ecosystems, soil fertility, and trophic balance. Data on the toxicity of hair dye effluents remain scarce and sometimes contradictory, particularly regarding the effects of their transformation products and metabolites. Overall, the evidence underscores the need for continuous monitoring, updated risk assessments, and the adoption of advanced treatment technologies specific to beauty salon effluents. The information presented in this work may support further studies and guide public management agencies in developing policies for mitigating the impacts of hair dye pollutants within the One Health perspective. Full article

Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data on treatment feasibility, efficacy, and related toxicities, with a specific focus on immune-related adverse events (irAEs). Methods: We conducted a retrospective analysis of patients who completed at least the neoadjuvant sequence of pembrolizumab combined with chemotherapy for early-stage TNBC at Montpellier Cancer Institute from April 2022 to July 2024. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The pathological complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes (ypT0/Tis ypN0). Results: We reviewed data from 92 patient records. The median age at diagnosis was 50 years (range: 27–76). The history of autoimmune disease was noted in 3.2% of patients. Grade 3–4 irAEs were observed in 20% of patients and included hepatitis (8.6%), colitis (3.3%), skin toxicity (2.1%), myocarditis (2%), arthralgia (1%), autoimmune hemolytic anemia (1%), hypothyroidism (1%), and adrenal insufficiency (1%). No treatment-related deaths were reported. Immunotherapy was discontinued due to irAEs in 29.3% of patients in the study population. The pCR rate was 61,1%, with no significant association between the number of neoadjuvant pembrolizumab cycles and the pCR rate (p = 0.7). Patients experiencing grade 3–4 irAEs had a pCR rate of 80%, compared to 56.7% in those without such toxicities (p = 0.079). Initial positivity of antinuclear antibodies (ANA) was not associated with an increased incidence of irAEs. Conclusions: The immune-related adverse events and efficacy data observed in our cohort were broadly comparable to those reported in the KEYNOTE-522 trial, with no treatment-related deaths. Patients with grade 3–4 irAEs tended to have higher pCR rates. Full article