Cutaneous and Ocular Toxicology最新文献

Background: Actinic keratosis (AK) is a common premalignant skin condition linked to chronic ultraviolet (UV) exposure and oxidative stress. Systemic biomarkers of redox imbalance in AK remain underexplored.

Aims: To assess systemic oxidative stress in AK using plasma thiol-disulfide homeostasis (TDH) and ischemia-modified albumin (IMA).

Methods: This cross-sectional study included 42 patients with clinically diagnosed AK and 42 age- and sex-matched healthy controls. Native thiol, total thiol, disulfide concentrations, and derived redox indices (Index-1, -2, -3) were measured using a spectrophotometric assay. IMA levels were assessed via the albumin-cobalt binding test. Statistical comparisons and correlation analyses were performed.

Results: Native thiol, total thiol, and disulfide levels were significantly lower in the AK group (p = 0.001), whereas disulfide-based indices showed no significant differences. IMA concentrations were significantly elevated in AK patients (p = 0.001). IMA levels were negatively correlated with native (r = -0.312, p = 0.044) and total thiol (r = -0.309, p = 0.046) values. Patients with Fitzpatrick Type IV skin exhibited significantly higher lesion counts than those with Types II and III (p < 0.05).

Conclusion: AK patients show systemic oxidative imbalance, with reduced thiols and elevated IMA, reflecting persistent UV-induced redox stress and protein oxidation. TDH and IMA may have potential utility as systemic indicators of oxidative stress in AK. Limitations include cross-sectional design, modest sample size, and unmeasured confounders. Future longitudinal and interventional studies should assess causality and antioxidant-based therapies.

Purpose: Ionizing radiation-induced glaucoma (IRG) is an uncommon yet vision-threatening complication that presents primarily as neovascular glaucoma (NVG) after high-dose exposure and normal-tension glaucoma (NTG) after low-dose exposure. Despite increasing recognition, its dose-response relationship, mechanisms, and optimal management remain poorly defined. This review evaluates the clinical spectrum, pathogenesis, and therapeutic approaches of IRG to inform future research and practice.

Methods: A systematic literature search of PubMed/MEDLINE, Embase, Scopus, and the Cochrane Database (1964-2024) was conducted following PRISMA guidelines. Among 7256 screened articles, 37 studies fulfilled the inclusion criteria.

Results: NVG typically develops following ocular radiotherapy exceeding 30 Gy, particularly in patients with uveal melanoma, and is characterized by retinal ischemia, neovascularization, and secondary intraocular pressure elevation. NTG arises from chronic low-dose exposure (< 1 Gy), producing optic nerve injury and visual field loss without elevated pressure. Anti-VEGF therapy can temporarily control NVG progression, whereas trabeculectomy, glaucoma drainage devices, and cyclodestructive procedures are variably employed but often limited by postoperative complications and inconsistent outcomes. The lack of consensus-driven protocols and heterogeneity across studies underscore ongoing clinical challenges.

Conclusions: IRG represents a dose-dependent entity with distinct phenotypes and mechanisms. Current therapies provide partial benefit but remain unsatisfactory in terms of durability and standardization. Advancing the field will require mechanistic studies to clarify radiation-induced optic neuropathy and vascular injury, alongside well-designed trials to establish preventive strategies and evidence-based treatment algorithms.

Background: Pumpkin extracts are rich in vitamins and bioactive compounds, offering antioxidative, anti-inflammatory, and wound-healing properties, making them valuable in dermatology and cosmetics, however pumpkin pulp extracts have not been evaluated before for their cutaneous biological activities.

Methods and results: This study evaluated the biological activity of methanolic pumpkin pulp extracts from six Serbian accessions of Cucurbita (C.) maxima and C. moschata on normal keratinocytes (HaCaT) and melanoma (FemX) cells. The extracts showed no cytotoxicity to normal cells up to 1000 μg/mL and exhibited concentration-dependent cytotoxicity to melanoma cells (determined by MTT assay). They also demonstrated antioxidative effects against H₂O₂-induced oxidative stress in H₂DCFDA assay, and reduced tumor necrosis factor -α/interferon-gamma-γ-induced expression of pro-inflammatory cytokine interleukine-1β in HaCaT cells, as shown in the cell-based ELISA assay. Sun protection factor (SPF) calculations for all six accessions confirmed the photoprotective potential of the extracts, with noticeable differences in SPF values between species and varieties. The highest SPF value was observed in the C. moschata variety.

Conclusion: Significant variations in biological activities among the examined accessions were noted, with C. maxima extracts showing pronounced antioxidant and antiinflammatory properties while C. moschata extract showed the highest SPF values. These findings represent the first report on the skin-beneficial effects of pumpkin pulp extracts, identifying them as sustainable sources of safe, bioactive compounds with antioxidant, anti-inflammatory, and photoprotective properties for dermatological or cosmetic applications.

Background: . . . . Isotretinoin is widely used to treat acne vulgaris. Although primarily targeting the skin, it exerts systemic effects, including rare cardiac manifestations such as arrhythmia. Electrocardiography (ECG) is the standard tool for rhythm monitoring. The frontal QRS-T angle, a novel ECG-based parameter, reflects ventricular depolarisation-repolarisation heterogeneity and has been recognised as a predictor of arrhythmic events. This study aimed to evaluate electrophysiological and biochemical changes associated with isotretinoin, focusing on the frontal QRS-T angle, basic ECG parameters, hemograms, and lipid profiles.

Methods: Forty patients receiving oral isotretinoin (0.5-1 mg/kg/day) for acne vulgaris were prospectively followed. The frontal QRS-T angle, ECG parameters, hemograms, lipid values, heart rate, and blood pressure were recorded at baseline, 3 months, and 6 months.

Results: At 6 months, statistically significant increases were observed in the frontal QRS-T angle and QRS duration, though both remained within accepted reference ranges. P wave duration, PR interval, QTc interval, heart rate, and blood pressure showed no significant changes. Lipid alterations were notable: HDL decreased, while total cholesterol, LDL, and triglycerides increased significantly. Hematological analysis showed stable leukocyte counts, with platelets rising transiently at 3 months and declining at 6 months.

Discussion: .Isotretinoin therapy was associated with measurable changes in cardiac electrophysiology and lipid metabolism. The frontal QRS-T angle may provide an early ECG marker of arrhythmic risk, supporting its inclusion in dermatologic pharmacovigilance. Concurrent lipid alterations may enhance arrhythmic vulnerability, underscoring the importance of cardiac and metabolic monitoring during isotretinoin treatment.

Introduction: Although omalizumab is a highly effective treatment against chronic spontaneous urticaria (CSU), the treatment duration for response varies among patients. Thus, determining easy-to-access predictive biomarkers of omalizumab response is essential.

Objective: This study aimed to investigate the value of baseline hematological and inflammatory parameters and patient-specific features as predictive markers of response to standard-dose omalizumab.

Methods: This single-center retrospective cohort study was conducted on 242 patients with CSU treated with omalizumab 300 mg every 4 weeks for at least 6 months between 2014 and 2025. The demographics, clinical features, treatment responses, and baseline laboratory tests were assessed. Response to omalizumab was evaluated based on the weekly Urticaria Activity Score (UAS7). Patients were categorized as early responder (ER, within 3 months), late responder (LR, after 3 months), and nonresponder (NR).

Results: Of patients, 180 (74.4%) were classified as ER, 28 (11.6%) as LR, and 34 (14%) as NR. ERs had higher white blood cell (WBC) and lymphocyte counts (p = 0.047 and p = 0.005, respectively) and lower mean platelet volume (MPV)/lymphocyte ratio (MPVLR) (p = 0.008). LRs had higher mean corpuscular hemoglobin concentration (MCHC) and platelet/lymphocyte ratio (PLR) (p = 0.023 and p = 0.014, respectively) and lower MPV levels (p = 0.043). The platelet distribution width (PDW) was higher in the NRs (p = 0.011). Red cell distribution width-coefficient of variation (RDW-CV) [odds ratio (OR): 0.793, 95% confidence interval (CI): 0.641-0.980, p = 0.032], WBC count (OR: 1.418, 95% CI: 1.093-1.840, p = 0.009), and PDW (OR: 0.813, 95% CI: 0.693-0.954, p = 0.011) were found to be the independent predictors of responders. The lymphocyte count (OR: 1.713, 95% CI: 1.122-2.613, p = 0.013) and MPVLR (OR: 0.427, 95% CI: 0.218-0.837, p = 0.013) were independent predictors of ER, whereas MCHC (OR: 2.368, 95% CI: 1.522-3.686, p < 0.001) and PLR (OR: 1.010, 95% CI: 1.003-1.017, p = 0.003) were independent predictors of LR. The receiver operating characteristic curve analysis results showed that the predictive strengths of RDW-CV, WBC count, PDW, lymphocyte count, MPVLR, MCHC, and PLR were low (the area under the curve values 0.634, 0.620, 0.672, 0.656, 0.621, 0.649, and 0.624, respectively; all p < 0.05), suggesting the limited use of these parameters in clinical practice.

Study limitations: The limitations of this study included its single-center, retrospective design, lack of external validation, and reliance solely on UAS7 for assessing disease activity.

Conclusions: WBC and lymphocyte counts, RDW-CV, PDW, MPVLR, MCHC, and PLR can be considered when appraising the omalizumab re

Background: Psoriasis is a chronic systemic inflammatory disease mediated by the immune system. Interleukin-23 (IL-23) plays a key role in its pathogenesis by amplifying inflammation, triggering atherogenic dyslipidemia and insulin resistance, and thereby increasing cardiovascular and cerebrovascular risk. This study aimed to evaluate the effect of the IL-23 inhibitors risankizumab and guselkumab, used in psoriasis treatment, on cardiovascular and cerebrovascular risk through the plasma atherogenic index (PAI) and triglyceride-glucose (TyG) index.

Methods: This retrospective study included 110 patients diagnosed with psoriasis and treated with risankizumab (n = 61) or guselkumab (n = 49). Psoriasis Area and Severity Index (PASI) scores, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) levels and fasting blood glucose (FBG) values at baseline and at 6 months of treatment were obtained from patient records. The plasma atherogenic index (PAI) was calculated as log₁。(TG/HDL-C), and the triglyceride-glucose (TyG) index as log₁。(TG × FBG / 2).

Results: In both IL-23 inhibitor groups included in the study, PASI scores, PAI, and TyG index values showed a significant decrease from baseline at the 6th month of treatment (p < 0.05). However, there was no significant difference in the reduction of index levels between the groups (p > 0.05).

Conclusion: IL-23 inhibitors can reduce atherogenic dyslipidemia and insulin resistance alongside dermatological improvement in the treatment of psoriasis. This suggests a potential role for these agents in reducing the risk of cardiovascular and cerebrovascular disease. However, large-scale, long-term studies are needed to confirm these beneficial effects.

Purpose: Methanol toxicity outbreaks have been a recurring problem around the world, and the recent pandemic has contributed to an increase in their incidence. The resulting toxic optic neuropathy may lead to complete permanent blindness. Erythropoietin (EPO) has demonstrated potential neuroprotective and neuroregenerative capabilities, which may improve the outcomes of patients with methanol-induced optic neuropathy (MTON). This work aimed to understand the efficacy and practical applications of EPO in cases of MTON.

Materials and methods: We included all original studies if they had patients with MTON, treated with EPO, and reported the outcomes of interest for clinical questions, including the end visual outcome. MEDLINE, Embase, Cochrane Library, and Web of Science databases were searched with no date restriction to obtain records.

Results: We included 9 articles in our review, with a total of 192 patients, all of whom had been diagnosed with MTON. Erythropoietin treatment started 2 to 29 days after the onset of visual symptoms. Most studies reported an improvement in visual acuity compared to baseline. However, compared to the standard corticosteroid treatment alone, the results of EPO were conflicting. No adverse events were reported.

Conclusion: The result of adding EPO to corticosteroid treatment in the management of MTON had variable improvements in visual acuity. EPO has potential beneficial effects if used early on in the acute phase of exposure to methanol. The role of repeating or maintaining therapy for a longer duration to enhance the protective effects or prevent relapses remains unknown. Future clinical trials to investigate these options.

Objective: This study aimed to investigate the development of a chitosan-alginate hydrogel wound dressing enriched with Hypericum scabrum extract due to its antioxidant and antimicrobial properties. Natural polymer-based hydrogels are ideal for wound healing due to their biocompatibility and capacity for controlled drug delivery.

Methods: Methanolic, ethanolic, and aqueous extracts of H. scabrum were evaluated for antioxidant and phenolic content. Cytotoxicity was assessed using MTT assay, and antimicrobial activity was determined by MIC testing. Physicochemical properties, including swelling, drug release, porosity (SEM), and molecular interactions (FTIR), were analysed.

Results: The methanolic extract showed the highest antioxidant activity (95.41%) and phenolic content (118 mg GAE/g). It was non-toxic up to 1000 ppm (73.6% cell viability). When loaded into the hydrogel, MIC decreased from 6.25 mg to 0.781 mg. The hydrogel showed a swelling ratio of 4016.6%, 80% drug release in 48 hours, reduced porosity (32.26% to 11.59%), and confirmed chitosan-alginate interactions via FTIR.

Discussion: The hydrogel formulation demonstrates strong antimicrobial, antioxidant, and biocompatible properties, making it a promising wound dressing. To improve the manuscript, more detailed methodology, statistical support for cytotoxicity, enhanced FTIR visualisation, and inclusion of recent literature and mechanistic discussion are recommended.

Objective: Tislelizumab frequently induces cutaneous immune-related adverse events (cirAEs), among which Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are rare but potentially life-threatening cutaneous reaction. The clinical characteristics of SJS/TEN induced by tislelizumab remain unclear.

Methods: This systematic review aims to clarify the clinical manifestations, therapeutic interventions, and outcomes of tislelizumab-related SJS/TEN in Chinese patients. Published case reports of SJS/TEN induced by tislelizumab were systematically collected (up to 10 May 2025). A total of 21 articles and 22 patients were included.

Results: A total of 22 patients were included, consisting of 14 males and 8 females, aged 42-81 years, with a median age of 71 years and a mean age of 68.59 ± 9.10 years. Lung cancer was the most common primary disease, affecting 12 patients (54.55%). 7 patients were treated with tislelizumab alone, while 15 underwent combination therapy (chemotherapy, radiotherapy, or targeted therapy). The time from treatment initiation to SJS/TEN onset ranged from 12 to 138 days. 20 patients experienced pain to varying degrees, with early symptoms primarily manifesting as erythema and rash. Mucocutaneous involvement was observed in 12 patients, and fever occurred in 11 patients. After drug discontinuation and symptomatic supportive care, the symptoms of 20 patients improved. Two patients died - one of septic shock and another of acute coronary syndrome.

Conclusions: This indicates that tislelizumab-related SJS/TEN mostly occurs days to months after treatment. Clinical practice should strengthen the evaluation and monitoring of early cutaneous adverse reactions, with timely detection and intervention to ensure safe medication use for patients.

Purpose: This study aimed to investigate the chemopreventive potential of the ethanolic extract of Luisia tenuifolia Blume against skin cancer.

Methods: The ethanolic whole-plant extract of Luisia tenuifolia was tested for acute and sub-chronic dermal toxicity according to the OECD guidelines 402 and 411. Its chemopreventive efficacy, along with the antioxidant and histopathological changes, was assessed using DMBA/Croton oil-induced skin cancer model in mice.

Results: The toxicity studies indicated that the extract was safe up to 2000 mg/kg body weight. The 90-day repeated application of the extract at 500, 1000, and 2000 mg/kg b.w. showed no mortality or toxicity observations. Topical application of the extract at 200 and 400 mg/kg b.w. applied 10 minutes before DMBA/Croton oil treatment delayed the tumor onset. Importantly, there was a significant decrease in tumor incidence, tumor burden, tumor yield, decreased lipid peroxidation and restored superoxide dismutase, catalase, and glutathione peroxidase levels in extract-treated mice compared with the control. The histopathological observations further substantiated the chemopreventive effect, revealing a marked reduction in neoplastic alterations.

Conclusion: The ethanolic extract of Luisia tenuifolia was well tolerated up to 2000 mg/kg b.w. and, at 200 and 400 mg/kg b.w., reduced tumor incidence to 80% and 60%, while 5-fluorouracil showed the higher efficacy (50% tumor incidence). Our findings showed the significant chemopreventive activity by enhancing antioxidant defenses and suppressing skin tumorigenesis in mice, warranting further mechanistic and clinical investigations.