Cutaneous and Ocular Toxicology最新文献

Background: Prolonged dermal exposure to nickel (Ni), a heavy metal found in tattoo ink, is associated with allergic contact dermatitis and skin sensitization in susceptible individuals. Although the systemic toxicity of Ni following inhalation and dermal exposure has been documented, limited information exists on the toxicological effects of intradermal exposure. Therefore, this study conducted a risk assessment to evaluate the potential for skin sensitization induction and non-cancer systemic toxicity from intradermal exposure to Ni-containing tattoo ink. A systematic literature review was performed to identify studies relevant to intradermal Ni exposure from tattoo ink.

Materials and methods: Risk characterization was conducted using margin of safety (MOS) calculations for dermal and systemic exposure scenarios. The dermal MOS was calculated by dividing the acceptable exposure level (AEL) by the consumer exposure level (CEL). The AEL was calculated by applying a safety assessment factor of 300 to the Ni no expected sensitization induction level (NESIL) of 401.07 μg/cm²/day. The systemic MOS was calculated by dividing the systemic exposure dose (SED) by an adjusted Office of Environmental Health and Hazard Assessment oral reference exposure level (REL) of 0.0044 mg/kg, accounting for the 40% oral bioavailability.

Results: For dermal exposure, the AEL (1.34 μg/cm²) exceeded the CEL (0.03 μg/cm²), yielding an MOS of 44.67. For systemic exposure, the SED (0.000027 mg/kg/day) was below the adjusted REL, yielding an MOS of 162. Sensitivity analyses confirmed MOS values greater than 1.

Conclusions: Skin sensitization and non-cancer systemic toxicity are not expected from exposure to Ni in tattoo ink.

Background: Management of wound infection and inflammation in diabetic foot is crucial for its treatment. Jiangjunsan has demonstrated potential anti-inflammatory properties and the ability to promote wound healing. This work aimed to investigate the effects of Jiangjunsan wrapping therapy (JJWT) on microbial colonies, levels of inflammatory factors, and regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway (SPW) in diabetic foot wounds.

Methods: Sixty diabetic foot patients were enrolled into a control group (CG) and a treatment group (TG), with 30 patients in each group. CG received topical magnesium sulfate in addition to standard treatment, while TG received JJWT for two weeks. The quantity of wound microbial colonies and levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured before and after treatment, and Western blot analysis was utilized to assess expression levels of PI3K and AKT in wound tissues.

Results: After treatment, TG exhibited a significantly lower microbial colony count than CG (P < 0.05). Both groups showed a great decrease in TNF-α and IL-6 levels post-treatment (P < 0.05), with TG demonstrating lower levels of TNF-α, IL-6, PI3K, and AKT proteins relative to CG (P < 0.05).

Conclusion: JJWT effectively reduced microbial colony counts in diabetic foot patients, markedly suppressed the expression of TNF-α and IL-6, and enhanced wound healing by modulating PI3K/Akt SPW, indicating strong antibacterial and anti-inflammatory properties of Jiangjunsan.

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: p < 0.001; right: p < 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 (p = 0.084), and right bone-conduction thresholds were similar between groups (p = 0.331). On vHIT, vestibulo-ocular reflex (VOR) gains were significantly reduced in the left anterior (p < 0.001) and right posterior (p = 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.

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.

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 p value < 0.05 was considered statistically significant.

Results: Median serum hBD-2 levels were significantly higher in psoriasis and PsA groups compared to controls (p < 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 (p < 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.

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 via 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 (P > 0.05) and nonlinear trends for SSR and UVR (P < 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.

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; p < 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 (n = 20) exhibited significantly higher TyG values (mean 8.95 ± 0.61) compared to those with <10 years of duration (n = 21, mean 8.21 ± 0.54; p = 0.0006). This association was confirmed using the independent samples t-test. Systemic involvement, smoking status, biologic therapy, and pathergy test results showed no significant impact on TyG levels (all p > 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.

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.

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.

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 (n = 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.