Searches / Cutaneous And Ocular Toxicology[JOURNAL]

Cutaneous And Ocular Toxicology[JOURNAL]

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Audio-vestibular abnormalities in patients with rosacea: a prospective case-control study.

Tosun M, Kekül Sapcı M, Yasak Güner R … +3 more , Bora A, Altuntaş EE, Akyol M

Cutan Ocul Toxicol · 2026 Feb · PMID 41720755 · Publisher ↗

BACKGROUND: Rosacea is a chronic inflammatory dermatosis characterized by neurovascular dysregulation and systemic inflammatory features that may extend beyond the skin and potentially affect highly vulnerable sensory or... BACKGROUND: Rosacea is a chronic inflammatory dermatosis characterized by neurovascular dysregulation and systemic inflammatory features that may extend beyond the skin and potentially affect highly vulnerable sensory organs such as the inner ear. To investigate audiologic and vestibular functions in patients with rosacea and to explore whether subclinical alterations may be detected compared with healthy controls. METHODS: In this prospective, age- and sex-matched case-control study, 53 patients with rosacea and 58 healthy controls were enrolled. All participants underwent pure-tone audiometry and the Video Head Impulse Test (vHIT). Disease severity, disease duration, sex, Demodex mite count, and rosacea subtypes were recorded. Data were analyzed using appropriate statistical tests. RESULTS: Compared with controls, patients with rosacea had significantly higher air-conduction thresholds in both ears (left:  < 0.001; right:  < 0.001). In contrast, bone-conduction thresholds did not show clinically meaningful between-group differences; the small numerical difference observed for the left ear was not statistically significant ( = 0.084), and right bone-conduction thresholds were similar between groups ( 0.331). On vHIT, vestibulo-ocular reflex (VOR) gains were significantly reduced in the left anterior ( < 0.001) and right posterior ( = 0.001) semicircular canals in the rosacea group. No significant associations were identified between vestibular parameters and disease severity, disease duration, Demodex count, rosacea subtype, or sex. CONCLUSION: These findings suggest that patients with rosacea may exhibit subtle audiologic and vestibular functional differences compared with healthy individuals. However, given the case-control design and the limited magnitude of the observed differences, these results should be interpreted cautiously, and audiovestibular evaluation may be considered primarily in symptomatic patients or selected subgroups rather than as a routine screening approach.

Kaposi's sarcoma in individuals living with HIV: comparative assessment of AI-based clinical responses using a standardized questionnaire set.

Altunisik Toplu S, Altunisik N, Turkmen D

Cutan Ocul Toxicol · 2026 Jun · PMID 41693335 · Publisher ↗

OBJECTIVE: To comparatively evaluate the clinical responses of three digital platforms (ChatGPT 5.2, DeepSeek, Consensus) in terms of responsiveness, accuracy, and clinical applicability, using a standardized set of ques... OBJECTIVE: To comparatively evaluate the clinical responses of three digital platforms (ChatGPT 5.2, DeepSeek, Consensus) in terms of responsiveness, accuracy, and clinical applicability, using a standardized set of questions on HIV-related Kaposi's sarcoma. Kaposi's sarcoma is a cutaneous malignancy; therefore, the relationship of this study to toxicology is indirect and methodological, focusing on information synthesis rather than toxicological evaluation. METHODS: Ten clinical questions titled 'Kaposi's Sarcoma in HIV-Infected Patients - Standard Questionnaire' were administered to each platform in separate sessions, and responses were recorded. Answers were independently evaluated by three field experts (one Infectious Diseases and Clinical Microbiology specialist and two Dermatology specialists) using a four-point accuracy scale. Quantitative analyses focused on response availability and accuracy distribution across platforms. Qualitative characteristics, including citation practices, visual support, and presentation of clinical decision algorithms, were assessed descriptively. FINDINGS: Chat GPT and Consensus answered all questions (10/10), whereas DeepSeek failed to generate a response to the KS-IRIS question due to a technical error (9/10). Comparison of accuracy category distributions across platforms revealed no statistically significant difference (Pearson chi-square test, p = 0.663). The median accuracy score was 1 (excellent) for all three platforms, with an interquartile range of 1-2. Qualitative analysis demonstrated that consistent citation of sources was observed only in Consensus, visual support was exclusive to ChatGPT, and structured clinical decision-making algorithms were most prominent in ChatGPT outputs. CONCLUSION: Although quantitative accuracy was comparable across platforms when assessed using a standardized Kaposi's sarcoma question set, notable differences were identified in qualitative features, including evidence presentation, visual support, and clinical decision structure. Artificial intelligence and literature-based digital platforms may support clinicians in complex conditions such as HIV related Kaposi's sarcoma. However, their outputs should be interpreted alongside current clinical guidelines and expert judgment.

Investigating the role of serum human beta defensin-2 in psoriasis and psoriatic arthritis: a case-control study on hBD-2 and CRP, ESR.

Kaya NE, Kurmuş GI, Özdemirel AE … +2 more , Altunay E, Gönül M

Cutan Ocul Toxicol · 2026 Feb · PMID 41689371 · Publisher ↗

INTRODUCTION: Human beta-defensin 2 (hBD-2) is an antimicrobial peptide upregulated by IL-17A and TNF-α, important in skin immunity and inflammation. While hBD-2 is elevated in psoriatic skin, its systemic expression and... INTRODUCTION: Human beta-defensin 2 (hBD-2) is an antimicrobial peptide upregulated by IL-17A and TNF-α, important in skin immunity and inflammation. While hBD-2 is elevated in psoriatic skin, its systemic expression and clinical significance remain unclear, particularly in psoriatic arthritis (PsA). OBJECTIVES: To compare serum hBD-2 levels among patients with psoriasis vulgaris, PsA, and healthy controls, and to evaluate its correlation with disease severity and inflammatory markers. METHODS: This case-control study included 66 patients with psoriasis, 30 with PsA, and 67 healthy controls. Serum hBD-2, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI). A value < 0.05 was considered statistically significant. RESULTS: Median serum hBD-2 levels were significantly higher in psoriasis and PsA groups compared to controls ( < 0.001), but no significant difference was found between the two patient groups (p: 0.223). In the psoriasis group, hBD-2 showed no significant correlation with PASI (r: 0.218, p: 0.095), CRP (r: 0.158, p: 0.277), or ESR (r: 0.129, p: 0.369). CRP and ESR were significantly higher in the PsA group than in other groups ( < 0.001 and p: 0.002, respectively). CONCLUSIONS: Although serum hBD-2 is elevated in psoriasis and PsA, it does not correlate with clinical or laboratory disease activity in psoriasis. These findings suggest that hBD-2 may reflect local cutaneous immune activation rather than systemic inflammation.

Sunlight's hidden hazard: Unveiling the link between solar radiation and suspected presbyopia risk.

Wang D, Pu Y, Zhu H … +9 more , Peng Y, Gao X, Lan Y, Lei J, Chen Y, Wu P, Huo Y, Du S, Li H

Cutan Ocul Toxicol · 2026 Feb · PMID 41685990 · Publisher ↗

BACKGROUND: Presbyopia, a common age-related visual impairment, characterized by difficulty focusing on near objects. Environmental factors, particularly solar radiation, in accelerating presbyopia have not been fully ex... BACKGROUND: Presbyopia, a common age-related visual impairment, characterized by difficulty focusing on near objects. Environmental factors, particularly solar radiation, in accelerating presbyopia have not been fully explored. This study examined the longitudinal relationship between solar radiation exposure (specifically top-of-atmosphere shortwave radiation (rsdt), surface solar radiation (SSR), and ultraviolet radiation (UVR)) and the risk of developing suspected presbyopia in Chinese adults aged ≥ 45 years. METHODS: Data from 14 058 participants in the China Health and Retirement Longitudinal Study (CHARLS) were analyzed over 2015 to 2018. Solar radiation exposure data were obtained from the National Environmental Ecological Science Data Center. Suspected presbyopia was identified self-rated near vision difficulty (score 4-5 on a five-point scale). Time-varying Cox proportional hazards models were employed to estimate hazard ratios for the association between solar radiation metrics and the incidence of suspected presbyopia, adjusting for demographic, socioeconomic, and health-related variables. RESULTS: During follow-up, higher rsdt, SSR, and UVR exposures were each associated with increased suspected presbyopia risk (rsdt: HR 1.47, 95% CI 1.39-1.55; SSR: HR 1.18, 95% CI 1.11-1.25; UVR: HR 1.15, 95% CI 1.11-1.19). Splines indicated linear associations for rsdt ( > 0.05) and nonlinear trends for SSR and UVR ( < 0.001). Subgroup analyses indicated stronger associations in rural residents and smokers. Multi-exposure models confirmed the independent effects of each type of radiation on presbyopia risk. CONCLUSIONS: Higher exposure to solar radiation, including both UV and visible light components, significantly increases the risk of suspected presbyopia in middle-aged and older Chinese adults. These findings highlight the importance of photoprotection strategies, especially for vulnerable subgroups such as rural residents and smokers.

The TyG Index as a surrogate marker of insulin resistance in Behçet's disease: a case-control study.

Akar ZA, Kaya K, Tel Kankılıç A … +2 more , Altaş M, Karakoyun Ö

Cutan Ocul Toxicol · 2026 Jun · PMID 41678271 · Publisher ↗

BACKGROUND: Behçet's disease is a chronic systemic vasculitis characterized by persistent inflammation and endothelial dysfunction, both of which contribute to metabolic disturbances such as insulin resistance. Insulin r... BACKGROUND: Behçet's disease is a chronic systemic vasculitis characterized by persistent inflammation and endothelial dysfunction, both of which contribute to metabolic disturbances such as insulin resistance. Insulin resistance and the resulting microvascular impairment may exacerbate tissue injury underlying key dermatologic and ocular manifestations of the disease. The triglyceride-glucose (TyG) index has recently emerged as a practical biomarker of insulin resistance, yet its role in Behçet's disease has not been studied extensively. OBJECTIVE: To evaluate the ability of the TyG index to differentiate patients with Behçet's disease from healthy controls and to assess its relationship with disease duration and systemic involvement, providing novel insight into metabolic dysregulation in Behçet's disease. METHODS: A total of 41 patients with Behçet's disease and 41 age-, sex-, and BMI-matched healthy controls were included. The TyG index was calculated using fasting triglyceride and glucose levels. Receiver operating characteristic (ROC) analysis was conducted to assess diagnostic performance, and subgroup analyses were performed based on disease duration (<10 vs. ≥10 years) and presence of systemic involvement. RESULTS: The TyG index was significantly higher in BD patients compared to healthy controls (8.57 ± 0.64 vs. 7.72 ± 0.42;  < 0.001). ROC analysis demonstrated high diagnostic accuracy with an AUC of 0.86, and a cutoff value of 7.731 yielded 85% sensitivity and 100% specificity. Among patients with Behçet's disease, those with a disease duration of ≥10 years ( = 20) exhibited significantly higher TyG values (mean 8.95 ± 0.61) compared to those with <10 years of duration ( = 21, mean 8.21 ± 0.54;  = 0.0006). This association was confirmed using the independent samples -test. Systemic involvement, smoking status, biologic therapy, and pathergy test results showed no significant impact on TyG levels (all  > 0.05). CONCLUSION: The TyG index is a promising biomarker for insulin resistance in Behçet's disease and may reflect cumulative inflammatory and metabolic burden that contributes to microvascular tissue injury, including in skin and ocular structures. Its use may aid in identifying patients at elevated cardiometabolic and microvascular risk, particularly those with long-standing disease.

Investigation of systemic inflammatory biomarkers associated with high-density lipoprotein and risk analysis in Xanthelasma Palpebrarum.

Sönmezoğlu Hİ, Güner Sönmezoğlu B, Çakır B

Cutan Ocul Toxicol · 2026 Feb · PMID 41655202 · Publisher ↗

PURPOSE: We aimed to investigate the potential role of systemic inflammatory biomarkers associated with high-density lipoprotein cholesterol (HDL) in the pathogenesis of Xanthelasma Palpebrarum (XP). METHODS: HDL, low-de... PURPOSE: We aimed to investigate the potential role of systemic inflammatory biomarkers associated with high-density lipoprotein cholesterol (HDL) in the pathogenesis of Xanthelasma Palpebrarum (XP). METHODS: HDL, low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), lymphocyte, neutrophil, monocyte, platelet and red cell distribution width-standard deviation (RDW-SD) values were obtained from peripheral blood samples of patients who underwent XP excision. Monocyte-to-high-density lipoprotein cholesterol ratio (MHR), lymphocyte-to-HDL cholesterol ratio (LHR), platelet-to-HDL cholesterol ratio (PHR), neutrophil-to-HDL cholesterol ratio (NHR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) were calculated and statistically compared. Multivariate logistic regression and ROC analyses were performed to determine predictive values. RESULTS: The study compared the XP group (63 patients) and the control group (54 healthy individuals), finding no significant differences in age and gender (p = 0.059 and p = 0.406, respectively). Neutrophil, lymphocyte, monocyte, and platelet counts, as well as MHR, LHR, PHR, NHR, and SII values, were significantly higher in the XP group (p < 0.001, p = 0.015, p = 0.042, p = 0.018, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p = 0.016, respectively). HDL levels were significantly lower in the XP group (p < 0.001). Among all parameters, NHR had the highest predictive value with an area under the curve (AUC) of 0.81. NHR (Odds ratio: 1.07) was identified as a potential risk factor for XP. CONCLUSION: This study highlights the potential role of systemic inflammation associated with HDL in the pathogenesis of XP by triggering oxidative stress mechanisms, lipid peroxidation, and tissue-level inflammatory damage, and emphasizes the need to investigate treatments that regulate inflammation in XP therapy.

Development and evaluation of cationic surface-modified hydroxyapatite nanoparticles for enhanced membrane permeation.

Abburu Jayaramu R, Shivally Boregowda S, K S … +4 more , Eshwar S, E K G, K V, Devaraj M

Cutan Ocul Toxicol · 2026 Jan · PMID 41615380 · Publisher ↗

PURPOSE: This study aimed to develop positively charged, metronidazole-loaded hydroxyapatite (MZ-HP) nanoparticles with enhanced membrane interaction, permeation, and therapeutic efficacy through surface charge modulatio... PURPOSE: This study aimed to develop positively charged, metronidazole-loaded hydroxyapatite (MZ-HP) nanoparticles with enhanced membrane interaction, permeation, and therapeutic efficacy through surface charge modulation using cetyltrimethylammonium bromide (CT). METHODS: Mesoporous HP nanoparticles were synthesized from eggshell-derived calcium oxide and loaded with metronidazole, followed by CT coating (1-3.5 mM/g MZ-HP) via physisorption. Drug loading and CT adsorption were confirmed by FTIR and XRD, while SEM and TEM assessed morphology and coating induced structural changes. Particle size and zeta potential were measured using dynamic light scattering to evaluate surface charge modulation. Ex vivo porcine skin permeation studies assessed drug release and permeability. Cytocompatibility was evaluated using an MTT assay on L929 fibroblasts. RESULTS: MZ-HP nanoparticles were successfully formulated with a maximum loading efficiency of 87.2% at an MZ:HP ratio of 0.83 M:1 M, showing a strong positive correlation between drug to carrier ratio and loading efficiency (r = 0.90, P = 0.039). CT coating shifted the surface charge from -28.3 ± 5.12 mV (HP) to -20.5 ± 4.1 mV (MZ-HP) and further to +21.9 ± 3.3 mV (CT-MZ-HP), confirming effective charge reversal. Permeability flux increased from 1.285 to 1.582 mg/h·cm², indicating enhanced interaction with negatively charged biological membranes. Cytotoxicity studies demonstrated improved fibroblast tolerance for CT-MZ-HP (IC₅。 = 184.9 ± 3.12 µg/mL) compared to CT, inferring its short-term dermal safety and enhanced cytocompatibility. CONCLUSION: CT coated MZ-HP nanoparticles provide an effective charge-modulated nanocarrier system with enhanced trans-barrier transport, membrane interaction, intracellular access, and cytocompatibility, supporting their potential as next-generation antimicrobial delivery platforms.

Yangxuebushen Decoction prevents cyclophosphamide-induced hair loss by inhibiting hair follicle apoptosis.

Sun Y, Wei Y, Ren H … +1 more , Shi X

Cutan Ocul Toxicol · 2026 Jan · PMID 41615374 · Publisher ↗

BACKGROUND: Alopecia is a skin condition that can impose a substantial psychological burden on affected individuals, and chemotherapy-induced alopecia remains one of the most distressing adverse effects of anticancer tre... BACKGROUND: Alopecia is a skin condition that can impose a substantial psychological burden on affected individuals, and chemotherapy-induced alopecia remains one of the most distressing adverse effects of anticancer treatment. Since antiquity, medicinal plants have been widely used in traditional Chinese medicine to support hair growth. In the present study, we investigated whether Yangxuebushen Decoction (YXBSD) could promote hair regrowth and mitigate alopecia in a cyclophosphamide (CYP)-induced mouse model. METHODS: A CYP-induced alopecia model was established in C57BL/6J mice ( = 5). Mice were allocated to a control group, a CYP group, and a CYP + YXBSD intervention group. The effects of YXBSD on hair growth and related biological processes were assessed through macroscopic observation and histopathologic evaluation, as well as TUNEL staining, immunofluorescence, immunohistochemistry, and real-time fluorescence quantitative PCR to examine hair follicle structure, apoptosis, inflammation, and oxidative stress. RESULTS: YXBSD significantly promoted hair growth in CYP-treated mice, improved hair follicle architecture, increased the proportion of hair follicles in the growth phase (from 15% to 30%), and reduced apoptosis of hair follicle cells (from 30% to 20%). In parallel, YXBSD markedly suppressed the expression of inflammatory mediators (TNF-α, IL-6, and IL-1β) in skin tissue, decreased the oxidative stress marker malondialdehyde (MDA), and increased the activity of the antioxidant enzyme superoxide dismutase (SOD). Consistent with these changes, YXBSD upregulated the proliferation marker Ki-67 while downregulating the apoptosis-related protein p53. CONCLUSION: YXBSD effectively alleviated CYP-induced alopecia by inhibiting apoptosis in hair follicle cells while concurrently reducing inflammation and oxidative stress, thereby promoting the recovery of hair follicle structure and function. These findings suggest that YXBSD has potential as an adjuvant intervention for chemotherapy-induced alopecia.

Assessment of cardiovascular risk in lichen planus cases with epicardial adipose tissue thickness and plasma atherogenic index.

Yıldız S, Daye M, Sertdemir AL … +5 more , Uyar M, Dursun R, Özer İ, Temiz SA, Sahin AT

Cutan Ocul Toxicol · 2026 Jun · PMID 41607199 · Publisher ↗

BACKGROUND: Lichen planus (LP) is an idiopathic, chronic, inflammatory dermatosis that can affect the skin, its appendages, and mucous membranes. Chronic inflammatory dermatoses may contribute to metabolic complications... BACKGROUND: Lichen planus (LP) is an idiopathic, chronic, inflammatory dermatosis that can affect the skin, its appendages, and mucous membranes. Chronic inflammatory dermatoses may contribute to metabolic complications and increase cardiovascular risk. This study aimed to evaluate cardiovascular risk in patients with LP by assessing the Plasma Atherogenic Index (PAI) and Epicardial Adipose Tissue (EAT) thickness. METHODS: A case-control study was conducted, including a total of 150 individuals, comprising 75 patients with LP and 75 age-, sex-, and body mass index (BMI)-matched controls. Lipid profiles were analyzed, and the PAI (log10[triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C)]) was calculated. EAT thickness was measured using transthoracic echocardiography. RESULTS: In the study, 40% of participants were male and 60% female in both groups. Dyslipidemia was identified in 66.7% of the case group and 50.7% of the control group, with the presence of dyslipidemia being significantly higher in the LP group ( < 0.05). Among the cases, 82.7% were in the high, 6.7% in the moderate, and 10.7% in the low cardiovascular risk category. PAI values and mean EAT thickness were significantly higher in the LP group than in controls (both  < 0.05). CONCLUSIONS: The findings support an association between LP and markers of increased subclinical cardiovascular risk rather than established cardiovascular disease. Early recognition and regular screening for cardiometabolic risk factors in dermatology practice, as well as multidisciplinary collaboration with cardiologists, may help prevent long-term cardiovascular complications in patients with LP.

extract in wound healing: exploring its potential and comparison with conventional topical therapies.

Akın I, Ozturan YA, Cengiz Z … +6 more , Erdogan O, Epıkmen ET, Ipek E, Canlı K, Benek A, Cevik O

Cutan Ocul Toxicol · 2026 Jun · PMID 41569283 · Publisher ↗

INTRODUCTION: Wound healing is a complex, multistage process regulated by inflammatory, oxidative, regenerative processes, and marine-derived compounds are increasingly recognized for their therapeutic potential. OBJECTI... INTRODUCTION: Wound healing is a complex, multistage process regulated by inflammatory, oxidative, regenerative processes, and marine-derived compounds are increasingly recognized for their therapeutic potential. OBJECTIVE: This study evaluated the wound-healing efficacy of an aqueous (PO) leaf extract in standardized full-thickness mice wounds, compared with alginate hydrogel (AH), fusidic acid + cream (FM), and untreated controls (NC). MATERIALS AND METHODS: Ninety-six (6-8-week-old) male BALB/c mice were randomized into four groups; four 4-mm dorsal wounds were created on each animal, and treatments were applied topically once daily for 14 days. Wound healing was assessed by planimetric wound area measurements, histological evaluations, biochemical analysis of oxidative stress, inflammatory biomarkers and growth factors, hydroxyproline levels, and gene expression analysis of MMP-2 and MMP-9. RESULTS: Application of PO extract significantly reduced wound areas from day 3 onward compared with NC and FM groups, with effects comparable to AH group by day 14. PO treatment increased epithelialization, fibroblast growth factor, and hydroxyproline levels, while reducing macrophage infiltration, oxidative stress, and inflammatory cytokines. Genomic analyses further indicated that topical PO extract significantly downregulated the expression of MMP-2 and MMP-9, supporting balanced extracellular matrix remodeling. CONCLUSIONS: PO extract promoted wound healing comparable to AH and superior to FM treatment, providing the first in vivo evidence for as a promising marine-derived therapeutic candidate for wound care.

Emerging therapeutic and cosmeceutical applications of phenylalanine and its metabolites.

Liao Z, Parumasivam T, Xiao Z … +4 more , Zhu X, Yeoh YK, Ye X, Tan TC

Cutan Ocul Toxicol · 2026 Mar · PMID 41532887 · Publisher ↗

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... 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.

Alternative models for evaluation of ocular toxicological effects of environmental chemicals and pharmaceuticals: a review.

Choudhary S, Parveen N, Javed M … +3 more , Jindal G, Suramya S, Raisuddin S

Cutan Ocul Toxicol · 2026 Mar · PMID 41525051 · Publisher ↗

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 rev... 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 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.

Impact of topical prostaglandin analogs on meibomian gland morphology and its association with prostaglandin-associated periorbitopathy.

Altin Ekin M, Yagmurlu E, Arıkan G

Cutan Ocul Toxicol · 2026 Mar · PMID 41504771 · Publisher ↗

OBJECTIVE: To evaluate morphological and functional alterations of the meibomian glands in eyes treated with unilateral prostaglandin analogs (PGAs) and their association with prostaglandin-associated periorbitopathy (PA... OBJECTIVE: To evaluate morphological and functional alterations of the meibomian glands in eyes treated with unilateral prostaglandin analogs (PGAs) and their association with prostaglandin-associated periorbitopathy (PAP), aiming to clarify the underlying mechanisms and clinical implications of PGA-induced periocular toxicity. METHODS: This cross-sectional study included 72 patients using unilateral topical PGAs for at least 3 months. The fellow untreated eyes served as controls. Each eye underwent standardized grading for eyelid margin abnormalities, meibomian gland expression, meibography scores, and gland morphology. PAP severity was graded using an established scale. ROC curve and correlation analyses assessed predictive relationships between meibomian gland parameters and PAP. RESULTS: Compared with untreated eyes, PGA-treated eyes showed significantly higher eyelid margin abnormality scores, meibomian gland expression grades, meibography scores, and meibomian gland loss areas (all  < 0.05). Morphological alterations, including distorted, tortuous, hooked, dropout, short, thin, and ghost glands, were significantly more frequent in treated eyes, alongside increased rates of abnormal gaps, fluffy areas, and absent lid margin extension ( < 0.05). These alterations became progressively more severe with increasing PAP grade ( < 0.001). Composite score (r = 0.51), ghost (r = 0.47), dropout (r = 0.45), and total mean score (r = 0.42) were most strongly correlated with PAP severity ( < 0.001). ROC analysis revealed that the total mean and composite scores were strong predictors of PAP (AUC = 0.739,  = 0.013 and AUC = 0.812,  = 0.004, respectively). Additionally, meibography scores, meibomian gland expressibility, and morphological features such as dropout and ghost glands were significantly associated with PAP ( < 0.05). CONCLUSION: Topical PGA use is associated with significant meibomian gland dysfunction and morphological damage, which worsens with increasing PAP severity. These findings highlight a potential diagnostic role for detailed meibomian gland assessment in monitoring PGA-induced ocular surface toxicity and may contribute to improved therapeutic management in glaucoma patients.

Comparison of bovine colostrum-based and carnosine-based gels on wound healing in a rat full-thickness excisional model.

Özbeyli A, Yanmaz LE, Özmen Ö

Cutan Ocul Toxicol · 2026 Mar · PMID 41490451 · Publisher ↗

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... 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.

Peripheral inflammation ratios mirror high-risk anatomic sites in basal cell carcinoma: a matched case-control study.

Sarı N, Arslan Ş, Demirbaş A … +1 more , Diremsizoglu E

Cutan Ocul Toxicol · 2026 Mar · PMID 41490232 · Publisher ↗

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... 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 ( = 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 ( = 0.024 and  = 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.

Isotretinoin-related adverse sexual and reproductive outcomes: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS).

Altınöz Güney C, Koç HA

Cutan Ocul Toxicol · 2026 Mar · PMID 41447583 · Publisher ↗

BACKGROUND: Systemic isotretinoin remains the most effective therapy for severe acne and is increasingly prescribed off-label for milder disease and other sebaceous disorders such as rosacea, seborrhea, folliculitis deca... BACKGROUND: Systemic isotretinoin remains the most effective therapy for severe acne and is increasingly prescribed off-label for milder disease and other sebaceous disorders such as rosacea, seborrhea, folliculitis decalvans, and hidradenitis suppurativa. While its mucocutaneous and metabolic adverse events (AEs) are well known, potential sexual and reproductive effects remain underexplored. OBJECTIVES: To evaluate isotretinoin-associated reproductive and sexual AEs using FAERS data and identify potential safety signals. METHODS: Isotretinoin-related AEs were retrieved from the FAERS Public Dashboard and OpenVigil 2.1 between January 1, 2004, and December 31, 2024. OpenVigil enables structured data extraction and applies automated preprocessing, including deduplication of identical reports. Disproportionality analyses (Proportional Reporting Ratio [PRR], Reporting Odds Ratio [ROR], and 95% confidence intervals) were performed to evaluate potential safety signals, assessing whether specific adverse events were reported more frequently with isotretinoin than with other drugs in the database. Four MedDRA System Organ Classes were searched: Reproductive system and breast disorders, Psychiatric disorders, Investigations, and Skin and subcutaneous tissue disorders. AEs with <3 reports were excluded. In total, 92 Preferred Terms (PTs) and 1300 cases were included. Disproportionality analysis (PRR, ROR, 95% CIs) was conducted on 1151 reports where isotretinoin was the primary suspect. Statistical significance was determined using Evans' criteria. RESULTS: Between 2004 and 2024, 53,017 isotretinoin-related reports were submitted to FAERS. Among these, 1300 reproductive and sexual AEs met inclusion criteria. Most reports involved females (59.7%) and individuals aged 18-64 years (58.3%). Disproportionality analysis identified 34 AEs with statistically significant signals. 'Erectile dysfunction', 'decreased libido', and 'loss of libido' were the top three most frequently reported AEs with significant disproportionality signals (Erectile dysfunction: PRR = 4.47 [95% CI 3.88-5.14], ROR = 4.49 [95% CI 3.90-5.17]; Decreased libido: PRR = 3.63 [95% CI 2.89-4.54], ROR = 3.63 [95% CI 2.90-4.55]; Loss of libido: PRR = 4.56 [95% CI 3.57-5.84], ROR = 4.57 [95% CI 3.57-5.85]) with 195, 76, and 64 reports, respectively. Other AEs meeting significance criteria included: 'ovarian cyst', 'sexual dysfunction', 'vulvovaginal dryness', 'infertility', 'endometriosis', 'polycystic ovaries', 'female genital tract fistula', 'genital hypoaesthesia', 'dyspareunia', 'hirsutism', 'cervical dysplasia', 'testicular pain', 'penis disorder', 'anorgasmia', 'prostatitis', 'ovarian cyst ruptured', 'male sexual dysfunction', 'genital anaesthesia', 'premenstrual syndrome', 'perineal fistula', 'penile haemorrhage', 'vaginal disorder', 'varicocele', 'orgasmic sensation decreased', 'vulval disorder', 'testicular torsion', 'vulvovaginal ulceration', 'organic erectile dysfunction', 'spermatozoa abnormal', 'reproductive tract disorder', and 'genital lesion'. CONCLUSIONS: Despite inherent FAERS limitations, including underreporting, reporting bias, and lack of causal inference, our findings underscore the need to monitor sexual and reproductive side effects during isotretinoin therapy. Since such symptoms are often underreported, routine inquiry and patient education are essential to ensure safe and informed use.

Performance of artificial intelligence large language models (LLMs) in answering frequently asked questions about isotretinoin.

Soysal MÇ

Cutan Ocul Toxicol · 2026 Mar · PMID 41410102 · Publisher ↗

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... 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 ( = 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 ( < 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 ( < 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.

Revealing differentially expressed genes between hypertrophic scars and normal skin tissues by bioinformatic analysis.

Liu H, Xu Y, Han Z

Cutan Ocul Toxicol · 2026 Mar · PMID 41390243 · Publisher ↗

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 be... 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 (, , , , , , , , and ) in HS and normal skin tissues were different ( < 0.05), with showing non-significant differences ( > 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.

Clinical features, complications, and outcomes of topical anesthetic eye drop misuse.

Eslami F, Kakoolvand M, Eslamighayour A

Cutan Ocul Toxicol · 2026 Mar · PMID 41368684 · Publisher ↗

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 exa... 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 ( < 0.001) and was significantly associated with ocular complications, including keratopathy and vision loss ( = 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.

Investigating serum procalcitonin levels in rosacea: a cross-sectional case-control study.

Benar H, Kurmuş GI, Kartal SP … +2 more , Erden G, Gönül M

Cutan Ocul Toxicol · 2026 Mar · PMID 41367360 · Publisher ↗

BACKGROUND: Rosacea is a chronic inflammatory skin disorder involving dysregulated innate immunity and microbial interactions. Procalcitonin (PCT) is a serum biomarker of bacterial inflammation but its role in rosacea re... BACKGROUND: Rosacea is a chronic inflammatory skin disorder involving dysregulated innate immunity and microbial interactions. Procalcitonin (PCT) is a serum biomarker of bacterial inflammation but its role in rosacea remains unclear. OBJECTIVES: To assess serum PCT levels in rosacea patients compared to healthy controls and explore associations with treatment modalities and clinical parameters. METHODS: This case-control study included 60 rosacea patients and 20 age- and sex-matched healthy individuals. Patients were grouped as untreated, topically treated with metronidazole, or systemically treated with doxycycline plus metronidazole. Serum PCT levels were measured by fluorescence immunoassay. Statistical analyses included Kruskal-Wallis, Mann-Whitney U, and multivariate linear regression. RESULTS: Rosacea patients had significantly higher PCT levels than controls (0.18 ± 0.06 vs. 0.12 ± 0.04 ng/mL; p < 0.001). Elevated PCT was observed in untreated and topical-only groups, while systemic treatment was associated with reduced levels (0.10 ± 0.004 ng/mL; p < 0.001), comparable to controls. No differences were found based on sex, smoking, or alcohol use. Multivariate analysis identified systemic therapy as a negative predictor (β = -0.55, p < 0.001) and papulopustular subtype as a positive predictor of elevated PCT (β = 0.23, p = 0.039). CONCLUSIONS: PCT may reflect underlying subclinical inflammation in rosacea and decrease with systemic therapy. These findings support further investigation of PCT as a biomarker in rosacea.
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