Cutaneous and Ocular Toxicology最新文献

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.

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 Posidonia oceanica (PO) leaf extract in standardized full-thickness mice wounds, compared with alginate hydrogel (AH), fusidic acid + Centella asiatica 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 P. oceanica as a promising marine-derived therapeutic candidate for wound care.

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.

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.

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 p < 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 (p < 0.05). These alterations became progressively more severe with increasing PAP grade (p < 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 (p < 0.001). ROC analysis revealed that the total mean and composite scores were strong predictors of PAP (AUC = 0.739, p = 0.013 and AUC = 0.812, p = 0.004, respectively). Additionally, meibography scores, meibomian gland expressibility, and morphological features such as dropout and ghost glands were significantly associated with PAP (p < 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.

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.

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.