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. The literature was reviewed using PubMed, Scopus, and Web of Science databases. 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. 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.
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. 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. 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). 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.
Rosacea is a chronic dermatological condition frequently associated with ocular symptoms and neurological comorbidities such as migraine. This study aimed to compare inflammatory and hematological markers between rosacea patients and healthy controls, and to assess differences in these markers among rosacea patients based on the presence or absence of ocular symptoms and migraine. A total of 150 rosacea patients and age- and gender-matched healthy controls were enrolled. Demographic data and routine hematological parameters were collected for all participants. Neurological evaluations were performed to assess the prevalence of headaches and migraines. Ophthalmological examinations were conducted in the rosacea group to determine ocular involvement. Compared with healthy controls, rosacea patients had higher white blood cell counts (7.22 ± 1.60 vs 6.83 ± 1.38, p = 0.03) and neutrophil counts (p = 0.02), and lower eosinophil counts (p = 0.036), mean corpuscular volume (p < 0.001), and red cell distribution width-standard deviation (p = 0.015). Mean corpuscular hemoglobin concentration was higher in rosacea patients (p = 0.001). Headaches and migraine were more prevalent in rosacea patients than in controls (p < 0.0001 and p = 0.0006, respectively). Ocular symptoms were present in 51.3% of patients and were more frequent in females (p = 0.03) and in those with migraine (p = 0.03). Rosacea was associated with changes in hematological and inflammatory markers, as well as a higher prevalence of migraine and ocular symptoms. These findings support the need for comprehensive evaluation of patients with rosacea.
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. To evaluate isotretinoin-associated reproductive and sexual AEs using FAERS data and identify potential safety signals. 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. 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'. 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.
This narrative review summarizes current practices and emerging technologies on psoriasis with an emphasis on key genetic and molecular mechanisms that contribute to disease pathogenesis and inform therapeutic development. In particular, genetic associations involving HLA-Cw6, IL-12B, and IL-23R are discussed in the context of immune dysregulation and keratinocyte hyperproliferation. The review aims to contextualize how these mechanistic insights have influenced existing treatments and continue to guide the development of therapeutic strategies. This review is based on published experimental studies, clinical trials, and authoritative reviews addressing the genetic, molecular, and immunological aspects of psoriasis. The review discusses therapeutic approaches, including topical agents, phototherapy, and traditional regimens such as Goeckerman therapy, alongside systemic agents and biologics targeting TNF-α, IL-17, and IL-23 pathways. Emerging approaches, including molecular therapeutics and nanotechnology driven drug delivery systems are explored as evolving strategies currently under investigation rather than established standards of care. The reviewed evidence indicates that advances in genetic and molecular understanding have clarified key mechanisms involved in psoriasis pathogenesis. Genetic markers such as HLA-Cw6, IL-12B, and IL-23R highlight the role of immune dysregulation and keratinocyte hyperproliferation, which has guided therapeutic development. Conventional treatments namely topical agents, phototherapy, and traditional regimens such as Goeckerman therapy, remain important, particularly for mild-to-moderate disease and selected patients. Building on these approaches, systemic agents and biologics targeting TNF-α, IL-17, and IL-23 pathways have significantly improved outcomes in moderate-to-severe psoriasis. Current research is now exploring molecular therapeutics and nanotechnology driven drug delivery systems as adjunct strategies to enhance efficacy and reduce systemic toxicity. However, these approaches are still evolving and are not yet established standards of care. Despite ongoing progress, challenges related to long-term safety, accessibility, and sustained disease control remain. Integrating mechanistic insights with evolving therapies and multidisciplinary care will be essential for advancing psoriasis management.
We hypothesized that baseline immune status, specifically the Th17/Treg axis, influences therapeutic outcomes. This study aimed to investigate the correlation between serum interleukin-17 (IL-17) and peripheral blood regulatory T cells (Tregs), Vitiligo Area Scoring Index (VASI), and the efficacy of 308 nm excimer light therapy by comparing an active treatment group of progressive vitiligo patients (subdivided into effective and ineffective subgroups) with a control group of stable vitiligo patients. Key variables investigated included baseline and post-treatment IL-17, Treg cell levels, and VASI scores. A total of 117 patients with progressive vitiligo treated with 308 nm excimer light were divided into ineffective (n = 31) and effective (n = 86) groups based on 6-month outcomes. An additional 35 patients with stable vitiligo were recruited as a control group. Serum IL-17, Treg cell levels, and VASI scores were measured at baseline and after 6 months of therapy for progressive vitiligo patients, and once for stable vitiligo patients. These parameters were compared between groups. Changes from baseline were analyzed. Risk factors for treatment failure were analyzed using logistic regression based on baseline parameters, and receiver operating characteristic (ROC) curves evaluated the exploratory predictive value of baseline IL-17 and Treg cells. At baseline, the ineffective progressive vitiligo group had significantly higher IL-17 and VASI scores, and lower Treg cell levels compared to the effective group (p < 0.05). After 6 months of treatment, the effective group showed a significant decrease in IL-17 and VASI, and an increase in Treg cells (P < 0.05), while the ineffective group showed no significant changes. Post-treatment IL-17 and Treg levels in the ineffective group remained significantly different from the effective group (p < 0.05). Patients with stable vitiligo had significantly lower IL-17 and higher Treg cell levels compared to both progressive vitiligo groups at baseline (p < 0.05). Baseline VASI scores correlated positively with baseline IL-17 and negatively with baseline Treg cells (p < 0.05). Multivariate logistic regression identified baseline autoimmune comorbidities, baseline VASI scores, IL-17, and Treg cells as independent predictors for treatment failure (p < 0.05). ROC analysis revealed optimal cutoff values of 21.15 ng/L for baseline IL-17 (sensitivity 80.65%, specificity 79.07%, AUC 0.875) and 3.75% for baseline Treg cells (sensitivity 83.87%, specificity 74.42%, AUC 0.818). Combined detection of baseline markers achieved a sensitivity of 80.65%, a specificity of 95.35% and an AUC of 0.921. These exploratory predictive models are internally derived and require external validation. Baseline and post-treatment serum IL-17 and Treg cell levels, along with VASI scores, correlate with 308 nm excimer light therapy outcomes in progressive vitiligo. These baseline biomarkers, particularly IL-17 and Treg cells, are associated with treatment response. Distinct biomarker profiles exist between progressive and stable vitiligo. Combined baseline marker testing improves the evaluation of treatment potential.
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. 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. 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. 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. 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.
The purpose of this study is to evaluate the pre-clinical safety and tolerability of a new ophthalmic viscoelastic device (OVD) containing bacterial-derived hyaluronic acid (HA) using an aqueous exchange model in rabbits. Intraocular pressure (IOP) and central corneal thickness (CCT) were measured to assess the ocular response of OVD use during cataract surgery. OVDs containing bacterial-sourced sodium hyaluronate (HA) (Healon EndoCoat brand) were used to exchange approximately 100 µL of the aqueous humor in 6 NZW rabbit eyes in vivo. IOP, central corneal thickness (CCT) and clinical ophthalmic examinations were measured in both eyes at post-operative 12 and 24 hours and days 3, 4, 8, 28 and 90. There were no significant differences in the IOP and CCT measurements after aqueous exchange between HEALON EndoCoat and HEALON EndoCoat PRO OVDs. IOP returned to baseline values in both the test and control eyes by 24 hrs. CCT showed no difference between test and control eyes after day 8 and remained the same through days 28 and 90. Early postoperative results showed expected corneal haze, conjunctival congestion and swelling, and inflammatory cells in the anterior chamber of both eyes after aqueous exchange. By day 8, the ocular findings were similar between the two study eyes and within the normal range typically reported. The results of this pre-clinical investigation support the safety and tolerability of the new bacterial-derived OVD in rabbits. There were no statistical differences in IOP and CCT measurements between the two OVDs whether the study endpoints occurred at 7 days or 3 months. Although the study was carried out for 90 days, no statistical differences in clinical performance were observed between OVDs after 7 days, indicating that a testing period that extends out to 90 days may not be medically necessary for pre-clinical studies.
This study evaluates the acute toxicity and wound-healing effects of bene gum on a dorsal wound model in rats. An excisional neck wound was created in twenty-four Sprague Dawley rats, and they were randomly assigned to four cages: normal saline (A); 0.2 ml of intrasite gel (B); 2.5% bene gum (C), or 5% of bene gum (D). After two weeks, skin samples from the healed area and serum were obtained for histological and biochemical investigations. The topical application of Bene gum (2.5 and 5%) did not show any overt sign of toxicity (local irritation or swelling); yet, it accelerated wound recovery, indicated by lower wound size and a faster rate of wound closure (90.32 and 93.36%, respectively). The histological evaluation of healed skin from bene gum (2.5% and 5%)-treated rats revealed increased deposition of tissue collagen, increased blood capillaries in the granulated tissue areas, and other histologic features consistent with fibroblast activity. Bene gum application increased angiogenetic factors (TGF-β1) by 9.68% and 54.66%, and hydroxyproline/collagen deposition by 41.62% and 97.12%, respectively, relative to vehicle control. The antioxidant and anti-inflammatory effects of bene gum (2.5 and 5%) were confirmed by its up-regulating effects on endogenous superoxide dismutase and catalase enzymes, interleukin-10, while down-regulating the malondialdehyde (MDA) and pro-inflammatory chemicals (reduced interleukin-6 by 31.40% and 67.11%, and tumor necrosis factor-α by 42.10% and 63.18%, resp.), suggesting modulation of inflammatory mediators associated with wound healing. The outcomes back up the traditional use of bene gum as an effective wound healer.
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. 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. 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. 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.
Cadmium causes systemic inflammation and retinal damage, posing a serious threat to visual and public health. Cadmium is a harmful heavy metal that builds up in body tissues and cause systemic inflammation and organ damage. This research sought to explore the impact of subacute cadmium exposure on retinal morphology and inflammatory cytokine levels. A total of fourteen male Wistar albino rats were randomized into control and cadmium-exposed groups within the scope of the experiment. 3 mg/kg cadmium (CdCl2) was administered intraperitoneally to the subjects in the cadmium group for 15 days. At the end of study, serum IL-6 and TNF-α levels were determined by ELISA method. In addition, retinal tissues were examined histopathologically after Hematoxylin and Eosin staining. Retinal apoptotic changes were assessed by semi-quantitative immunohistochemical analysis of Bax and Bcl-2 expression in the inner and outer nuclear layers. According to the findings, cadmium exposure caused a statistically significant increase in serum IL-6 and TNF-α levels. Histopathological examination revealed a marked decrease in the thickness of the inner plexiform layer (IPL), inner nuclear layer (INL), and outer nuclear layer (ONL), as well as focal vacuolization and cellular disorganization. Cadmium exposure significantly increased Bax immunoreactivity and the Bax/Bcl-2 ratio in both the INL and ONL, while significantly decreasing Bcl-2 expression. In conclusion, cadmium exposure increased the systemic inflammatory response, leading to significant histopathological damage in the retinal layers and a dominant proapoptotic Bax/Bcl-2 balance, thereby triggering cellular apoptosis.
To evaluate the changes in aberrometry values on corneal topography and the function of the meibomian glands following therapeutic Botulinum toxin type A injections in patients with blepharospasm and hemifacial spasm. This retrospective interventional study included 24 eyes of 17 patients treated with Botulinum toxin type A for blepharospasm and hemifacial spasm. Corneal topography and meibography were performed before treatment and at 1 month. Botulinum toxin type A was injected bilaterally in seven patients and unilaterally in ten patients, totaling 24 treated eyes. There were no significant differences between pre- and post-injection measurements of flat keratometry (K1) (p = 0.585), steep keratometry (K2) (p = 1.000), mean keratometry (Kmean) (p = 0.809), corneal astigmatism (p = 0.641), astigmatism axis (p = 0.647), central corneal thickness (p = 0.631), anterior chamber depth (p = 0.127), and anterior chamber volume (p = 0.747). However, the root mean square of higher-order aberrations (RMS-HOA) (p = 0.018) and RMS-quadrafoil (Z44) (p = 0.012) significantly increased one month after the injection. Although increases were also observed in RMS-coma (Z31) (p = 0.225), RMS-trefoil (Z3³) (p = 0.147), secondary astigmatism (p = 0.433), and RMS-spherical aberration (Z40) (p = 0.150), these changes did not reach statistical significance. After the injection, there was a statistically significant reduction in tear break-up time (TBUT) (p = 0.041), Ocular Surface Disease Index (OSDI) score (p = 0.041), and the area of the meibomian glands (mm2) (p < 0.001). Botulinum toxin A injection into the orbicularis oculi in both groups may decrease meibomian glands and tear function, increasing corneal aberrations and reducing visual quality after 1 month.
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. 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. 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). 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.
Background: Octenidine-based antiseptics are increasingly used in neonatal and pediatric care for skin antisepsis and wound care, yet their cutaneous safety has not been systematically profiled. Methods: This scoping review, based on JBI methodology, mapped evidence on skin injuries and local complications in neonates and children after octenidine-based use on intact skin or wounds. Results: Of 242 records, six studies, all conducted in Europe (Germany 66.7%, Switzerland 16.7%, Poland 16.7%), were included (n = 30 patients). Two studies reported intact-skin antisepsis before procedures in 18 neonates while four papers addressed cleansing of traumatic, surgical, or infectious wounds in 12 infants or children. Formulations were mainly octenidine 0.1% with phenoxyethanol 2% (22/30; 73.3%), with aqueous 0.1% (6/30; 20.0%) and alcohol-based 0.1% (2/30; 6.7%) less frequent. Reported events ranged from transient erythema to bullous/erosive dermatitis, subcutaneous edema, fatty tissue necrosis, and phlegmon-like reactions. Management varied from conservative care to surgery, with scarring or contractures in some cases. Conclusion: The available evidence, limited to case reports, case series, a survey and one small cohort, thereby preventing causal inference and incidence or prevalence estimates due to the absence of denominator data, nonetheless indicates injuries with both aqueous and alcohol-based products, raising concern for a potentially compound-related, rather than vehicle-specific, risk. Clinicians should consider judicious use of octenidine, monitor closely, and consider the potential utility of patch testing for delayed allergic reactions. Priority needs include multicenter studies, standardized skin outcomes, detailed exposure reporting, and pharmacovigilance or registries.
The application of nanotechnology to cosmetic formulations has gained recognition due to enhanced stability, efficacy, and aesthetic appeal of products. These engineered nanomaterials are purposefully produced to possess nano-specific properties, whereas traditional microsized particles are manufactured primarily to improve formulation texture. However, their increasing use for beautification and medicinal purposes has raised serious concerns regarding nanocosmetic toxicity. This review highlights the distinct physical and chemical characteristics of nanocosmetics that influence skin penetration, cellular interactions, and potential systemic uptake following dermal application, emphasizing the need for comprehensive toxicity evaluation. This review compiles appropriate peer-reviewed literature from various scientific databases along with regulatory documents from authoritative sources. The review focuses on toxicity assessment approaches for nanocosmetics, including in vitro, in vivo, and alternative methods. Special emphasis is placed on skin irritation and sensitization models, cytotoxicity assays, genotoxicity assessments, and embryonic toxicity tests for evaluating nanocosmetic-associated toxicity. The review summarizes current approaches for evaluating the skin and ocular safety of nanocosmetic ingredients and discusses the influence of nano-specific physicochemical properties on dermal penetration and biological interactions. It also identifies existing data gaps in current regulatory frameworks, particularly concerning nano-specific safety assessment, physicochemical characterization, and dermal exposure evaluation. These findings highlight the importance of adopting comprehensive and standardized toxicity testing strategies for nanocosmetics. The increasing application of nanotechnology in cosmetic formulations necessitates robust toxicity evaluation to ensure consumer safety. Strengthening regulatory frameworks by incorporating nano-specific safety assessment and exposure evaluation is essential to promote the safe use of nanomaterials in cosmetic products while supporting their continued development and commercialization.
This study aimed to evaluate the effects of a topical zinc oxide-Momordica charantia oil formulation on wound healing in diabetic and non-diabetic rats. Twenty-eight female Wistar rats were randomly allocated into four groups (n = 7 each): non-diabetic control (NDC), non-diabetic treated (NDT), diabetic control (DC), and diabetic treated (DT). Three standardized full-thickness excisional wounds were created on the dorsal region of each rat. Treated groups received zinc oxide-M. charantia cream (0.5 g) topically once daily for 21 days, whereas control groups underwent daily saline cleaning. Wound healing was assessed by wound area measurements on days 7, 14, and 21, together with hydroxyproline analysis and histopathological examination. Wound area decreased significantly over time in all groups (p < 0.001). On day 7, residual wound area percentages were significantly lower in DT(51.54 ± 5.23%) and NDT(53.77 ± 3.16%) than in DC(62.42 ± 6.42%) and NDC(63.15 ± 2.43%; p = 0.001). By days 14 and 21, wound areas were markedly reduced in all groups with no significant differences between groups. Hydroxyproline levels increased over time(p = 0.004) and were higher in treated groups, especially NDT on day 7. Histopathology also indicated less inflammation and more organized connective tissue formation in treated groups. Topical zinc oxide-M. charantia oil cream improved early wound closure and collagen-related findings, particularly on day 7. However, wound closure became similar among groups by days 14 and 21. Because a vehicle-matched control cream was not included, these findings should be interpreted as preliminary evidence for the complete formulation and require confirmation in vehicle-controlled and adequately powered studies.
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. 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. 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). 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.
Cutaneous squamous cell carcinoma (cSCC) lacks effective and well-tolerated pharmacological options for long-term management, highlighting the need for multi-target natural agents. In this study, we hypothesized that a flavonoid-rich extract from Dalbergia odorifera exerts (DOE) anti-cSCC effects by regulating apoptosis-related pathways. To test this hypothesis, we employed an integrated strategy combining UPLC-based chemical profiling, network pharmacology prediction, and in vitro and in vivo validation. UPLC analysis identified five major flavonoids in DOE-Luteolin, Naringenin, Butein, Liquiritigenin, and Formononetin. Network pharmacology predicted the involvement of key pathways, including PI3K/AKT, MAPK, and EGFR. Experimental validation, however, was focused on apoptosis-related markers Bax and Bcl-2, providing partial support for the predicted mechanisms. In vitro, DOE significantly reduced cell viability and colony-forming ability. Migration was decreased by more than 80%, and apoptosis increased substantially at higher doses. These findings were confirmed by qRT-PCR and Western blot analyses, which showed a downregulation of Bcl-2 and upregulation of Bax, consistent with the proapoptotic mechanism predicted by network pharmacology. In vivo, using a DMBA/croton oil-induced cSCC mouse model, DOE administration resulted in dose-dependent tumor inhibition and improved body weight loss, thymus, and spleen indices. DOE, as a flavonoid extract, significantly inhibits cell proliferation, migration, and promotes apoptosis in cSCC, positioning it as a promising candidate for further development as a complementary or adjuvant therapeutic strategy.
Uremic pruritus (UP) is a common and distressing symptom in hemodialysis patients and may contribute to geriatric syndromes such as impaired sleep, depression, cognitive decline, and functional limitation. Evidence focusing on comprehensive geriatric assessment in older hemodialysis populations remains limited. To evaluate the association between UP severity (5-D Itch Scale) and geriatric syndromes (functional status, cognitive function, depressive symptoms, nutritional status, and sleep quality) in older hemodialysis patients. This cross-sectional study included patients aged ≥65 years who had undergone hemodialysis for at least 6 months. UP was assessed using the 5-D Itch Scale. Comprehensive geriatric assessment comprised Activity of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE), Geriatric Depression Scale-15 (GDS-15), Mini Nutritional Assessment-Short Form (MNA-SF), and Pittsburgh Sleep Quality Index (PSQI). Group comparisons were performed using nonparametric tests, and associations were examined using Spearman correlation. A total of 118 older hemodialysis patients were included; 70.4% (n = 83) reported UP. Vitamin D levels were lower in patients with UP. Compared with patients without UP, those with UP had lower MMSE scores, and higher GDS and PSQI scores. 5-D score correlated positively with age, depressive symptoms, sleep disturbance, and ADL dependency; and negatively with dialysis duration and cognitive function. In older hemodialysis patients, UP is common and is associated with worse sleep quality, more depressive symptoms, lower cognitive performance, and greater functional limitation. Integrating UP screening into routine geriatric assessment may help identify vulnerable patients and guide multidisciplinary symptom management strategies.
To investigate the cytotoxic effects of airborne particulate matter smaller than 2.5 μm (PM2.5) on human conjunctival epithelial cells and to elucidate whether these effects are mediated through activation of the aryl hydrocarbon receptor (AhR) signaling pathway. Human conjunctival epithelial cells were exposed to PM2.5 (0, 12.5, 25, and 50 μg/mL) for 24 hours. Cell viability was assessed using an MTT-based colorimetric assay by measuring absorbance at 450 nm, and intracellular reactive oxygen species (ROS) production was evaluated using DCFH-DA staining followed by quantification of DCF fluorescence intensity. AhR activation was evaluated by analyzing cytoplasmic and nuclear fractions of mRNA via Western blot. The mRNA expression of AhR, its downstream target genes (CYP1A1, CYP1B1, AhRR), and inflammatory cytokines (IL-1β, IL-6, TNF-α) was quantified by real-time PCR. AhR involvement was confirmed using siRNA-mediated AhR knockdown cells. PM2.5 induced dose-dependent reductions in cell viability and significant increases in intracellular ROS at 25 and 50 μg/mL. Western blot analysis showed decreased cytoplasmic AhR and increased nuclear AhR following PM2.5 exposure. PM2.5 significantly upregulated AhR, its target genes, and inflammatory cytokines. In AhR knockdown cells, PM2.5 failed to induce nuclear translocation of AhR, upregulation of target genes, ROS production, or inflammatory cytokine expression, indicating that PM2.5-induced oxidative and inflammatory responses are dependent on AhR signaling. PM2.5 induces cytotoxicity, oxidative stress, and inflammation in human conjunctival epithelial cells through AhR activation. These findings identify AhR as a key molecular mediator of PM2.5-induced ocular surface damage and suggest that targeting AhR pathways may provide a potential therapeutic strategy for preventing air pollution-related ocular surface disease.