Cutaneous and Ocular Toxicology最新文献

Objective: This review aims to comprehensively examine and integrate the extant knowledge pertaining to phenylalanine (Phe) and its key metabolites, namely tyrosine (Tyr), phenylpyruvic acid (PPA), phenyllactic acid (PLA), and phenylacetic acid (PAA). The primary focus of this review will be on the emerging pharmacological and cosmetic applications of these metabolites.

Rationale: Phe-derived compounds have garnered increasing attention due to their diverse pharmacological effects, including antioxidant, antimicrobial, anti-inflammatory, and neuromodulatory properties. Their relevance to skin health, pigmentation regulation, microbiome modulation, and mood-related dermatoses provides a compelling basis for reviewing their functional potential in both therapeutic and cosmetic contexts.

Methods: A systematic literature review was conducted using PubMed, Web of Science, and Scopus up to 2025. The review was guided by predefined keywords related to Phe and its metabolites. The inclusion criteria were tailored to encompass experimental, clinical, and translational studies that explore pharmacological or cosmetic applications of Phe.

Main findings: The review presents compelling evidence substantiating the bioactivity of Phe and its metabolites across multiple skin-related pathways. These compounds exhibit promising efficacy in preserving skin homeostasis, regulating pigmentation, harmonizing cutaneous microbiota, and mitigating psychosomatic skin conditions. Their structural and functional diversity renders them versatile agents with extensive translational potential.

Conclusions and implications: The multifunctional nature of Phe-derived compounds presents substantial potential for incorporation into advanced skincare and pharmaceutical formulations. However, limitations persist in safety and toxicological data, particularly concerning prolonged human exposure. Future research should prioritize (i) mechanistic elucidation of biological effects, (ii) standardized toxicological and clinical validation, and (iii) formulation optimization to facilitate safe and effective applications. These endeavors have the potential to bridge the gap between biochemical research and practical innovation, thereby fostering novel solutions for skin health and emotional well-being.

Background: Basal cell carcinoma (BCC) is the most common form of skin cancer, with increasing incidence worldwide. Although anatomical site-based risk stratification is commonly used in clinical practice, the potential role of systemic inflammatory markers in predicting tumor behavior remains unclear.

Objective: To compare the systemic inflammatory markers between patients with BCC and healthy controls, and to assess their association with histopathological subtypes and anatomical risk groups.

Methods: This retrospective analytical study included 55 patients with histopathologically confirmed BCC and 55 age- and sex-matched healthy controls. Hematological parameters, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), were calculated from complete blood counts. Subgroup analyses were performed based on BCC subtype and anatomical risk classification. Receiver operating characteristic (ROC) analysis and logistic regression were used to evaluate predictive performance.

Results: Hemoglobin levels were significantly lower in BCC patients than controls (p = 0.048), but inflammatory indices did not differ between groups. Among BCC subtypes, only hemoglobin varied significantly, with higher levels in the superficial subtype. NLR and SIRI were significantly elevated in patients with high-risk tumors compared to those with low/moderate-risk lesions (p = 0.024 and p = 0.046, respectively). ROC analysis showed modest discriminatory power for NLR (AUC = 0.689) and SIRI (AUC = 0.667), but neither marker was a significant predictor of high-risk status in multivariate logistic regression.

Conclusion: NLR and SIRI were found to be associated with high-risk tumor localization in BCC, indicating their potential utility as supportive tools in preoperative risk assessment.

Objective: Topical anesthetic eye drops are widely used in ophthalmology; however, improper use may result in serious complications, including blindness.

Materials and methods: This descriptive, cross-sectional study examined patients presenting with foreign body sensation, exposure to ultraviolet (UV) radiation, or misuse of topical anesthetic drops at Sina Hospital's Ophthalmology Emergency Department from September 2019 to September 2020. After obtaining informed consent, participants completed questionnaires under the supervision of an ophthalmologist. Patients with anesthetic-related complications received appropriate treatment and were followed up for one month. Data were analyzed using SPSS version 21.

Results: Of 192 patients (185 men and 7 women; mean age: 42.69 ± 12.45 years), 76.56% reported foreign body sensation. The most common symptoms were lacrimation (84.37%) and photophobia (73.95%). Many patients used non-medical remedies such as closing their eyes (63.15%) and applying tea (45.31%). Pharmacy staff (38.27%) and colleagues (33.33%) were the most frequent sources of advice. Tetracaine misuse was significantly more common among patients with a prior history of use (P < 0.001) and was significantly associated with ocular complications, including keratopathy and vision loss (P = 0.011).

Conclusion: Arbitrary use of topical anesthetic drops-often based on non-specialist recommendations-significantly increases the risk of ocular complications. Awareness of potential side effects does not appear to prevent misuse, underscoring the need for stronger educational efforts regarding the risks of topical anesthetics.

Background: Existing research lacks a systematic investigation of the complete gene expression profile in hypertrophic scars (HS). This study aimed to systematically explore the differences in mRNA expression profiles between human HS and normal skin tissues using bioinformatics analysis methods.

Methods: GSE236983 and GSE229848 were downloaded from Gene Expression Omnibus (GEO) to screen differentially expressed genes (DEGs). Protein-protein interaction (PPI) network was constructed using STRING (search tool for recurring instances of neighboring genes), followed by gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DEGs. Three surgical samples of HSs and adjacent normal skin tissues were selected from 3 HS patients for comparative analysis of DEGs.

Results: Venn diagram of two datasets showed an intersection, revealing 31 DEGs. GO enrichment results unveiled that DEGs were mainly involved in keratinization, keratinization cell differentiation, epidermal cell differentiation (ECD), and skin development. Cellular components (CCs) were mainly enriched in cell desmosomes, intermediate filament cytoskeleton (IFC), keratin filament (KF), and intermediate filament (IF). KEGG analysis signified that the main involved pathways encompassed tight junctions, extracellular matrix-receptor interaction, arachidonic acid metabolism, and terpenoid backbone biosynthesis. mRNA levels of 10 core genes (MVD, ACAT2, HMGCS1, HMGCR, FASN, MSMO1, DHCR7, DHCR24, and AACS) in HS and normal skin tissues were different (P < 0.05), with MVK showing non-significant differences (P > 0.05).

Conclusion: this study identified ten core DEGs associated with HS through systematic bioinformatics analysis. These genes are involved in biological processes and cellular components such as keratinization, cell differentiation, lipid metabolism, cholesterol biosynthesis, and cell adhesion.

Purpose: There are various ethical issues and humane concerns regarding the use of animal models for toxicity testing. Ocular toxicology is a less explored field of toxicology. To address these pertinent issues, this review presents perspectives on alternative models for assessing ocular toxicological effects of environmental chemicals and pharmaceuticals.

Methods: The literature was reviewed using PubMed, Scopus, and Web of Science databases.

Results: Ocular tissue serves as a route of exposure to toxic chemicals and pharmaceuticals. Toxicological studies on the eyes have remained an ignored area of research. Interestingly, the historically prominent Draize test for eye irritation is found numerous references as a method for assessing irritability and corrosivity of pharmaceuticals and chemicals. Ocular tissues, like other tissues, are reported to tend to absorb chemicals and metabolize them. The bovine corneal opacity and permeability (BCOP) test (OECD TG 437) and EpiOcular (OECD TG 492) are known alternative in vitro tests used to measure the irritability or corrosivity potential of surfactants, detergents, acids, isopropanol, and metal oxides. Zebrafish serves as an excellent research model for the study of ocular toxicological effects of environmental toxicants due to its retinal anatomy, which resembles that of humans. Its rapid development and transparency in early life stages facilitate the observation of minute changes. Zebrafish adults when exposed to cypermethrin for 9 days reported apoptosis in retinal cells. Likewise, its embryo (4-5 days post fertilization) upon exposure to triphenyltin showed impaired development of retinal axon. When exposed to environmental toxins such as pharmaceuticals, pesticides, heavy metals, and industrial substances, cells in zebrafish undergo oxidative stress, inflammation, and mitochondrial dysfunction. Besides, reduction in photoreceptors, and damage to retinal ganglion cells (RGCs), and optic nerve have also been reported. These injurious effects result in severe eye conditions, including glaucoma, diabetic retinopathy, and toxic optic neuropathies. Research using zebrafish also enables scientists to effectively assess the therapeutic potential of substances which could mitigate or avert toxin-related injury to the eyes.

Conclusion: This review emphasizes the significance of alternative models in ocular toxicology research. It also highlights distinct contribution of alternative models to linking exposure of environmental toxins with ocular diseases. Their application not only increases our understanding of visual health but also opens new avenues for the development of innovative therapies and preventive strategies.

Purpose: The purpose of this study was to evaluate the effects of a bovine colostrum-based gel (CG) and a carnosine-based gel (BepanGel, BG) on wound healing in a full-thickness excisional wound model in rats.

Materials and methods: Male Sprague-Dawley rats (n = 27) were randomly assigned to three groups (n = 9 for each): Control (0.9% NaCl), CG, and BG. Four standardized full-thickness excisional wounds were created on the dorsal surface of each rat. Treatments were applied topically once daily for 14 days. Wound surface area measurements were performed on days 3, 7, and 14. Histopathological assessments and immunohistochemical analyses (Caspase-3, TGF-α, TNF-α, and VEGF expression) were conducted at each time point.

Results: By day 14, wound surface area values in the BG (0.059 ± 0.034) and CG (0.073 ± 0.063) groups were significantly lower than in the control group (0.128 ± 0.074; p < 0.05)(p < 0.05). No significant difference was found between BG and CG (p > 0.05). Histopathologically, epithelialization, fibrosis, and angiogenesis were significantly improved, while edema, hemorrhage, and inflammatory infiltration were reduced in the treatment groups (p < 0.05). Immunohistochemical analysis revealed that BG and CG were associated with downregulation of Caspase-3 (BG: 0.50 ± 0.16; CG: 0.90 ± 0.16) and TNF-α (BG: 1.60 ± 0.16; CG: 1.20 ± 0.20), while upregulating VEGF (BG: 2.70 ± 0.15; CG: 2.60 ± 0.16) and TGF-α expression (BG: 2.20 ± 0.20; CG: 1.60 ± 0.16).

Conclusion: Both colostrum-based and carnosine-based gels enhanced wound healing by promoting epithelial regeneration, collagen formation, and angiogenesis while modulating inflammation and apoptosis. BepanGel showed slightly superior performance in several parameters, suggesting its potential as an effective topical agent in wound management.

Objective: In this study, we aimed to examine the responses given by ChatGPT (OpenAI), Copilot (Microsoft), and Gemini (Bard) artificial intelligence applications to questions about the active ingredient isotretinoin in terms of accuracy, readability, applicability, and understandability.

Material and methods: The readability of the answers given by the artificial intelligence programs was evaluated using the Flesch-Kincaid ease score, and the applicability and understandability levels were evaluated using the Patient Education Materials Evaluation Tool scales. The accuracy of the answers was compared by two dermatologists who scored them between 1 and 5.

Results: No significant difference was found between the groups in terms of Flesch Kincaid reading ease scores (p = 0.671), and all three programs were found to be at a difficult level of reading. In the Patient Education Materials Evaluation Tool scales, it was observed that Gemini and ChatGPT rates were >70% and there was a significant difference in favor of these programs between the groups (p < 0.001). In the accuracy scores of the answers, Gemini (4.90 ± 0.31) and ChatGPT (4.60 ± 0.69) had high scores and there was a significant difference between the groups (p < 0.001).

Conclusion: While the AI chatbots we used in the study demonstrated reasonable accuracy in answering questions about isotretinoin, they performed limited in terms of readability and usability. These findings suggest that AI programs alone are not sufficient for patient education and need to be improved to simplify responses.

Cutaneous squamous cell carcinoma (cSCC) lacks effective and well-tolerated pharmacological options for long-term management, highlighting the need for multi-target natural agents. In this study, we hypothesized that a flavonoid-rich extract from Dalbergia odorifera exerts (DOE) anti-cSCC effects by regulating apoptosis-related pathways. To test this hypothesis, we employed an integrated strategy combining UPLC-based chemical profiling, network pharmacology prediction, and in vitro and in vivo validation. UPLC analysis identified five major flavonoids in DOE-Luteolin, Naringenin, Butein, Liquiritigenin, and Formononetin. Network pharmacology predicted the involvement of key pathways, including PI3K/AKT, MAPK, and EGFR. Experimental validation, however, was focused on apoptosis-related markers Bax and Bcl-2, providing partial support for the predicted mechanisms. In vitro, DOE significantly reduced cell viability and colony-forming ability. Migration was decreased by more than 80%, and apoptosis increased substantially at higher doses. These findings were confirmed by qRT-PCR and Western blot analyses, which showed a downregulation of Bcl-2 and upregulation of Bax, consistent with the proapoptotic mechanism predicted by network pharmacology. In vivo, using a DMBA/croton oil-induced cSCC mouse model, DOE administration resulted in dose-dependent tumor inhibition and improved body weight loss, thymus, and spleen indices. DOE, as a flavonoid extract, significantly inhibits cell proliferation, migration, and promotes apoptosis in cSCC, positioning it as a promising candidate for further development as a complementary or adjuvant therapeutic strategy.

Introduction: The cytotoxic effects of bentonite and zeolite 4A nanoparticles (NPs), as well as their nanocomposite (NC), were investigated in human melanoma (G361) cells. Although both materials have demonstrated anticancer potential, their effects on melanoma remain insufficiently explored. This study aimed to evaluate the cellular responses induced by bentonite and zeolite 4A NPs, individually and in combination, in G361 cells.

Methods: Physicochemical characterization was performed using X-ray diffraction (XRD), X-ray fluorescence (XRF), and scanning electron microscopy (SEM). IC₅。 values were determined for bentonite NPs, zeolite 4A NPs, and the NC. Cell viability was assessed using the MTT assay, while apoptosis was evaluated through caspase-3 activity measured by ELISA.

Results: All treatments exhibited dose-dependent cytotoxicity in melanoma cells. Notably, the NC demonstrated a strong synergistic interaction, enhancing cytotoxic effects and enabling reduced effective concentrations. Despite the pronounced cytotoxicity observed in the NC group, no significant increase in caspase-3 activity was detected compared to control. These findings suggest the involvement of caspase-independent cell death mechanisms, particularly necrotic or non-classical apoptotic processes.

Conclusion: The bentonite/zeolite 4A nanocomposite exerts synergistic cytotoxic effects in melanoma cells. While the results highlight its therapeutic potential, further mechanistic studies are required to clarify the underlying pathways prior to clinical translation.