Search Results (127)

Background: Vitiligo, a chronic depigmentation disorder driven by oxidative stress and immune dysregulation, remains poorly understood mechanistically. The Keap1/NRF2/ARE pathway is critical for melanocyte protection against oxidative damage; however, the role of Cullin-3 (CUL3), a scaffold for E3 ubiquitin ligases that regulate NRF2 degradation, and its interplay with inflammatory mediators in vitiligo pathogenesis are underexplored. This study investigates CUL3, NRF2, and the associated regulatory networks in vitiligo, integrating clinical profiling and computational docking to identify therapeutic targets. Methods: A case-control study compared non-segmental vitiligo patients with age-/sex-matched controls. Lesional skin biopsies were analyzed by qRT-PCR for the expression of CUL3, NRF2, miRNA-146a, FOXP3, NF-κB, IL-6, TNF-α, and P53. Molecular docking was used to evaluate vitexin’s binding affinity to Keap1, validated by root mean square deviation (RMSD) calculations. Results: Patients with vitiligo exhibited significant downregulation of CUL3 (0.27 ± 0.03 vs. 1 ± 0.58; p = 0.013), NRF2 (0.37 ± 0.26 vs. 1 ± 0.8; p = 0.001), and FOXP3 (0.09 ± 0.2 vs. 1 ± 0.3; p = 0.001), alongside the upregulation of miRNA-146a (4.7 ± 1.9 vs. 1 ± 0.8; p = 0.001), NF-κB (4.7 ± 1.9 vs. 1 ± 0.5; p = 0.001), IL-6 (2.8 ± 1.5 vs. 1 ± 0.4; p = 0.001), and TNF-α (2.2 ± 1.1 vs. 1 ± 0.3; p = 0.001). P53 showed no differential expression (p > 0.05). Docking revealed a strong binding of vitexin to Keap1 (RMSD: 0.23 Å), mirroring the binding of the control ligand CDDO-Im. Conclusions: Dysregulation of the CUL3/Keap1/NRF2 axis and elevated miRNA-146a levels correlate with vitiligo progression, suggesting a role for oxidative stress and immune imbalance. Vitexin’s high-affinity docking to Keap1 positions it as a potential modulator of the NRF2 pathway, offering novel therapeutic avenues. This study highlights the translational potential of targeting the ubiquitin–proteasome and antioxidant pathways in the management of vitiligo. Full article

Autoimmune CD8⁺ T cell-driven melanocyte destruction constitutes a key pathogenic mechanism in the development of vitiligo. Therefore, the pharmacological inhibition of CD8⁺ T cell effector functions and skin trafficking is a clinically viable therapeutic strategy. This study investigates leflunomide (LEF), an immunomodulatory drug with established safety in autoimmune diseases, for its therapeutic potential in a tyrosine-related protein (TRP) 2-180-induced vitiligo mouse model. Through flow cytometry, immunofluorescence, ELISA, and histopathological analyses, we systematically evaluated LEF’s effects on T cell regulation, chemokine expression, and cytokine profiles. Key findings demonstrated that LEF (20 mg/kg/day) significantly attenuated depigmentation by reducing CD8⁺ T cell infiltration and suppressing the IFN-γ-driven expression of CXCL9/10. Furthermore, LEF restored CD4⁺/CD8⁺ T cell homeostasis and rebalanced pro-inflammatory (IFN-γ, TNF-α, IL-2) and anti-inflammatory (IL-4, IL-10) cytokines, inducing a shift from Th1 to Th2. These results position LEF as an effective immunomodulator that disrupts the IFN-γ-CXCL9/10 axis and re-establishes immune balance, offering a promising repurposing strategy for halting vitiligo progression. Full article

This study evaluates the effects of dietary lipid levels on growth performance, hematological health, and muscle composition of juvenile Arapaima gigas. We tested five isonitrogenous diets (451.7 g kg⁻¹ of crude protein) with increasing lipid levels (6%, 10%, 14%, 18%, and 22%). A total of 600 juvenile A. gigas (80.0 ± 10.5 g; 21.8 ± 1.0 cm) were distributed into 20 tanks (500 L; n = 4; 30 fish per tank) in an indoor open system. The fish were fed to apparent satiety four times daily for 60 days. As dietary lipid levels increased, all growth parameters and lipid content in both the whole body and muscle declined. The diet containing 6% lipids resulted in the maximum final weight, weight gain, feed intake, and the lowest feed conversion rate. However, a maximum lipid level of up to 10.26%, with a gross energy-to-protein ratio of 10.15 kcal g⁻¹ in the diet, as determined through polynomial regression analysis, can be used for juvenile A. gigas without significantly affecting weight gain. Diets with high lipid content (18% and 22% lipids) resulted in the lowest survival rates, highest feed conversion rates, lowest condition factor, visible skeletal protrusions, scale depigmentation, and impaired blood biochemistry. The content of eicosapentaenoic acid, docosahexaenoic acid, n-3, and the n-3:n-6 ratio increased in the muscle lipid fraction (mg g⁻¹ of total lipids) in response to higher dietary lipid levels; however, this does not represent an overall improvement in the meat quality, since the total lipid content in the muscle (g of lipid per 100 g of muscle) was reduced due to impaired growth in fish fed high-lipid diets. Notably, the experimental diets also differed in fatty acid composition, which may have influenced some of the physiological and compositional responses observed. Diets with 6% lipids are recommended to provide optimal growth performance, and a maximum dietary lipid level of up to 10.26% is advised to ensure successful A. gigas farming without impairing weight gain. Full article

Background/Objectives: Vitiligo is an autoimmune condition causing melanocyte destruction and skin depigmentation. First-line treatments for vitiligo include topical medications and phototherapy; however, access and utilization of these treatments vary, particularly in pediatric patients. This study evaluates nbUVB use in pediatric versus adult vitiligo patients to better understand utilization in the pediatric population. Methods: A retrospective chart review study was conducted, collecting demographics and treatment characteristics for 102 adults and 19 children with vitiligo treated with nbUVB phototherapy at one institution. Statistical analysis included comparisons for categorical variables made using Chi-squared test or Fisher’s exact test, as appropriate, and using a non-parametric Mann–Whitney U test for continuous variables. Results: On average, adults underwent nbUVB for 23.8 months (range 0.5–418, median 9), while children had an average duration of 14.8 months (range 2–60, median 8). The average number of nbUVB sessions for adults was 83.8, whereas children had an average of 33.5 sessions. Overall, 59.6% of adults and 60.0% of children experienced repigmentation with nbUVB. Conclusions: Retrospective analysis indicated that the duration and frequency of nbUVB sessions varied widely among both adults and children. While the average duration of treatment was comparable between the groups, children underwent fewer sessions on average. This may reflect differences in physician recommendation, scheduling constraints, or treatment adherence. Despite this variability, most pediatric patients exhibited repigmentation, supporting nbUVB efficacy. Our results suggest nbUVB is underutilized in pediatric vitiligo. Addressing obstacles to access is crucial for improving treatment outcomes and quality of life. Full article

The 2,4-dihydroxyphenyl group is commonly present in the chemical structures of potent tyrosinase inhibitors. Based on this observation, a series of 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole compounds 1–13 were designed and synthesized as potential tyrosinase inhibitors. Among these, compounds 5 and 9 strongly inhibited mushroom tyrosinase activity. Particularly, compound 9 exhibited nanomolar IC₅₀ values regardless of the substrate used, whereas kojic acid yielded IC₅₀ values of 15.99–26.18 μM. Kinetic studies on mushroom tyrosinase revealed that compounds 5 and 9 competitively inhibited tyrosinase activity, findings further corroborated by in silico docking analysis. In B16F10 cell-based experiments, both compounds effectively inhibited the cellular tyrosinase activity and melanin formation. These inhibitory effects were confirmed through in situ cellular tyrosinase activity assays. Compound 9 exhibited strong antioxidant activity by scavenging radicals, suggesting that its ability to reduce melanin production may be attributed to a combination of its antioxidant and tyrosinase inhibitory properties. Additionally, five compounds, including compound 5, demonstrated effective depigmentation activity in vivo in zebrafish embryos, and their depigmentation efficacy was similar to that of kojic acid, even at concentrations hundreds of times lower. These findings suggest that 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole compounds may be promising anti-melanogenic agents. Full article

This paper reports three novel KIT variants likely responsible for previously unexplained white patterning phenotypes observed in three groups of horses. White spots and markings may have substantial consequences on the value and health of domesticated horses. This study aims to elucidate the genetic mechanisms underlying depigmented coat colors to aid in producing prosperous herds. Aligned whole genome sequences were manually screened to identify three polymorphisms in a family of Anglo-Arabian horses (N = 7), a family of Warmblood horses (N = 5), and a single stock-type mare with unexplained white markings. Sanger sequencing confirmed the presence of the variants, and in silico predictive programs were used to predict the functional impacts of each. We propose to term the novel variants W37, W38, and W39, respectively, per convention. The W37 polymorphism was always observed in the presence of one W35 allele, suggesting complete linkage. All three variants were predicted to alter or remove the KIT protein active domain, repressing typical protein folding and impacting pathways that upregulate pigmentation. The severe predicted impact on biological function suggests that these variants may cause increased white spotting, providing a possible explanation for the depigmentation phenotypes observed in affected individuals. Full article

Vitiligo is a chronic autoimmune disorder with a multifactorial etiology, typically manifesting as localized or generalized hypopigmentation or depigmentation of the skin and mucous membranes. The pathogenesis of vitiligo is complex and significantly impacts patients’ quality of life. Although traditional treatments such as hormone therapy, topical medications, and laser therapy can help control the disease to some extent, their outcomes remain unsatisfactory. Therefore, ongoing research is crucial to explore and develop novel treatment strategies while assessing their efficacy and safety. This review aims to classify and summarize various new candidate drugs for vitiligo currently undergoing clinical trials, providing a reference for clinical practice. Recent advancements in the understanding of the pathogenesis of vitiligo have facilitated the development of potential treatment strategies, such as Janus kinase inhibitors, cytokine blockers, and agents targeting tissue-resident memory or regulatory T cells. These emerging therapies offer hope to patients with vitiligo, though further investigation is needed to confirm their safety, efficacy, and optimal treatment regimens. Full article

The depletion of the ozone layer has intensified ultraviolet (UV) radiation exposure, leading to oxidative stress, DNA damage, inflammation, photoaging, and skin cancer. Medicinal plants, widely used in Traditional Herbal Medicine (THM), particularly in Traditional Chinese Medicine (TCM), have demonstrated significant therapeutic potential due to their well-characterized active compounds and established photoprotective effects. This review systematically evaluates 18 medicinal plants selected based on their traditional use in skin-related conditions and emerging evidence supporting their efficacy against UV-induced skin damage. Their bioactive components exert antioxidant, anti-inflammatory, DNA repair, and depigmentation effects by modulating key signaling pathways, including Nrf2/ARE-, MAPK/AP-1-, PI3K/Akt-, and MITF/TYR-related melanogenesis pathways. Moreover, novel drug delivery systems, such as exosomes, hydrogels, and nanoemulsions, have significantly enhanced the stability, bioavailability, and skin penetration of these compounds. However, challenges remain in standardizing plant-derived formulations, elucidating complex synergistic mechanisms, and translating preclinical findings into clinical applications. Future interdisciplinary research and technological advancements will be essential to harness the full therapeutic potential of medicinal plants for UV-induced skin damage prevention and treatment. Full article

Fifteen compounds (1–15) constructed on a hybrid structure combining a β-phenyl-α,β-unsaturated carbonyl template and a 2-aminothiazol-4(5H)-one scaffold were designed and synthesized as potential novel anti-tyrosinase substances. Two compounds (10 and 15) showed more potent inhibition against mushroom tyrosinase than kojic acid, and the inhibitory activity of 10 (IC₅₀ value: 1.60 μM) was 11 times stronger than that of kojic acid. Lineweaver–Burk plots indicated that these two compounds were competitive inhibitors that bound to the mushroom tyrosinase active site, which was supported by in silico experiments. Compound 10 was an anti-tyrosinase and anti-melanogenic substance in B16F10 cells and was more potent than kojic acid, without cytotoxicity. Compound 15 exhibited the most potent effect on zebrafish larval depigmentation and showed a depigmentation effect comparable to kojic acid, even at a concentration 200 times lower. Compounds 8 and 10 exhibited strong antioxidant capacities, scavenging 2,2-diphenyl-1-picrylhydrazyl, (2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid)⁺ radicals, and reactive oxygen species. Hybrid compounds 10 and 15 are potential therapeutic agents for skin hyperpigmentation disorders. Full article

This study evaluates the efficiency of 20 Natural Deep Eutectic Solvents (NADES) formulations for extracting curcuminoids and other bioactive compounds from turmeric and emphasize their ability to preserve and enhance antioxidant, antimicrobial, antidiabetic, and skin depigmentation effects. The NADES formulations, prepared using choline chloride (ChCl) combined with sugars, carboxylic acids, glycerol, amino acids, urea, polyols, and betaine, were assessed for their extraction efficiency based on the total phenolic content and curcumin concentration. Fourier transform infrared spectroscopy was employed to characterize the synthesized NADES and confirm their chemical composition. Bioactivity evaluations included antioxidant assays (ABTS and DPPH), antidiabetic tests (α-amylase inhibition), antimicrobial assays, and skin depigmentation (tyrosinase inhibition). The results demonstrated that NADES significantly enhanced the extraction efficiency and bioactive properties of turmeric extracts compared to water as a conventional green solvent. NADES 18 (ChCl/1,2-propanediol/water 1:1:1) and NADES 19 (glycerol/betaine/water 1:1:3) exhibited the highest extraction yields, with curcumin concentrations of 30.73 ± 1.96 mg/g and 31.70 ± 2.02 mg/g, respectively, outperforming water (26.91 ± 1.72 mg/g), while NADES 17 (ChCl/1,2-propanediol/water 0.5:3:0.5:5) and NADES 20 (glycerol/lysine/water 1:1:3) exhibited the most potent antioxidant activity. Furthermore, NADES 14 (ChCl/lactic acid/water 1:2:5) demonstrated the strongest tyrosinase inhibition (98.7%), supporting its potential for skin-brightening applications, including notable α-amylase inhibition exceeding 90%. This study aligns with the principles of green chemistry, as NADES are effective and sustainable solvents for natural product extraction. The presenting benefits of improved extraction efficiency and enhanced bioactivities position NADES as a promising and eco-friendly approach for developing efficient bioactive compound extraction methodologies. Full article

Background and Objectives: Age-related macular degeneration (AMD) is the leading cause of low vision and legal blindness in adults in developed countries. Wet AMD can be successfully treated using vascular endothelial growth factor (VEGF) inhibitors; however, dry AMD currently has no effective treatment. The purpose of this study is to analyze the efficacy of intraocular injection of plasma rich in growth factors (PRGF) in an AMD mouse model induced by intraperitoneal administration of sodium iodate. Materials and Methods: Intravitreal application of PRGF (experimental group) and saline (control group) was performed immediately after intraperitoneal injection of sodium iodate. Retinographies were performed at 2 and 7 days after treatment administration. The eyes were retrieved for histological and immunohistological analysis. Statistical analysis was performed to compare the outcomes between the study groups. Results: In comparison to saline solution, PRGF significantly decreased the depigmentation of the RPE, showing a more reddened retina. PRGF intravitreal treatment significantly reduced the glial fibrillary acidic protein (GFAP) stained processes, suggesting a significant reduction in the risk of scar formation. Moreover, the myofibroblast invasion into the RPE cell layer was significantly reduced in the PRGF-treated group of mice. There was a tendency for better preservation of the photoreceptors in the PRGF group. Conclusions: Within the limitations of this study, intravitreal injection of PRGF provided significant protection against the degeneration of the photoreceptors and the RPE induced by the systemic administration of NaIO₃. Full article

Background: Melasma is a challenging, acquired hyperpigmentary disorder. The gold standard treatment is Kligman’s formulation, which contains hydroquinone, tretinoin, and dexamethasone, but its long-term use is limited by the risk of exogenous ochronosis. Cysteamine, a tyrosinase inhibitor, reduces melanocyte activity and melanin production, showing strong depigmenting effects in patients resistant to Kligman’s formulation. Nonetheless, clinical studies have yielded inconsistent efficacy results. This meta-analysis aimed to assess the efficacy of cysteamine in treating melasma and to identify potential factors that may impact its therapeutic outcomes. Methods: A systematic search of PubMed, Embase, Web of Science, and CENTRAL, from the earliest record until August 2024, was conducted. Randomized controlled trials and quasi-randomized design studies related to topical cysteamine on melasma patients were included. The primary outcome was MASI or mMASI assessment after treatments. The current meta-analysis was conducted with a random-effects model. Subgroup analyses and meta-regressions were performed based on baseline MASI, disease duration of melasma, patient age, and sample size of the included studies. Funnel plots and Duval and Tweedie’s trim and fill method were adopted to assess the publication bias. Results: Eight studies were included for quantitative analysis. The analysis of MASI after topical cysteamine demonstrated a significant decrease compared to the placebo (p = 0.002). Compared to other melasma treatments, cysteamine did not show superior efficacy in mMASI (p = 0.277). The treatment efficacy of hydroquinone, modified Kligman’s formula, and tranexamic acid mesotherapy for melasma was not statistically different when compared to cysteamine (p = 0.434). Further analyses showed no benefit when allowing extended cysteamine application time (p < 0.0001). The meta-regression revealed the efficacy of cysteamine decreased as the duration of melasma increased (coefficient = 0.38, p = 0.0001, R² = 0.99). The funnel plot displayed some asymmetry. The trim and fill method suggested the adjusted effect size was 0.607 (95% CI = −0.720 to 1.935). Conclusions: Cysteamine exhibited efficacy in treating melasma patients; however, its depigmentation effect was comparable to hydroquinone-based regimens, tranexamic acid mesotherapy, and modified Kligman’s formula. Using cysteamine in patients with a short duration of melasma may result in better efficacy. Full article

2-Mercaptomethylbenzo[d]imidazole (2-MMBI) derivatives were designed and synthesized as tyrosinase (TYR) chelators using 2-mercaptomethylimidazole scaffolds. Seven of the ten 2-MMBI derivatives exhibited stronger inhibition of mushroom TYR activity than kojic acid. Their ability to chelate copper ions was demonstrated through experiments using the copper chelator pyrocatechol violet and assays measuring TYR activity in the presence or absence of exogenous CuSO₄. The inhibition mechanisms of derivatives 1, 3, 8, and 9, which showed excellent TYR inhibitory activity, were elucidated through kinetic studies and supported by the docking simulation results. Derivatives 3, 7, 8, and 10 significantly inhibited cellular TYR activity and melanin production in B16F10 cells in a dose-dependent manner, with stronger potency than kojic acid. Furthermore, in situ, derivatives 7 and 10 showed stronger inhibitory effects on B16F10 cell TYR activity than kojic acid. Six derivatives, including 8, showed highly potent depigmentation in zebrafish larvae, outpacing kojic acid even at 200–670 times lower concentrations. Additionally, all derivatives could scavenge for reactive oxygen species without causing cytotoxicity in epidermal cells. These results suggested that 2-MMBI derivatives are promising anti-melanogenic agents. Full article

Background: Vitiligo is a complex disorder characterized by skin depigmentation; the canonical Wnt signaling pathway that involves β-catenin plays a crucial role in promoting the melanin production in melanocytes. Targeted inhibition of the Janus kinase JAK-STAT pathway can effectively diminish the secretion of the chemokine C-X-C motif ligand CXCL10, thereby safeguarding melanocytes. Ferula has been applied as a treatment regimen for a long period; however, its use for the treatment of vitiligo has not been previously documented. Methods: CCK-8 assay, Intracellular melanin content assay, Tyrosinase activity assay, Western blotting, qRT-PCR, and ELISA methods were employed. Using molecular docking verified the inhibitory effects of feshurin on the JAK1. Results: The sesquiterpene coumarin feshurin was separated from Ferula samarcandica. Feshurin was shown to induce GSK-3β phosphorylation, resulting in the translocation of β-catenin into the nucleus. This translocation subsequently upregulated the transcription of microphthalmia-associated transcription factor (MITF), leading to increased tyrosinase activity and melanin production. In addition, feshurin inhibited the production of chemokine CXCL10 via the JAK-STAT signaling pathway, which was verified by molecular docking. Conclusions: Based on these findings, it can be concluded that feshurin exhibits significant potential for the development of novel anti-vitiligo therapeutics. Full article

Crop monitoring is a fundamental practice in seaweed aquaculture. Seaweeds are vulnerable to several threats such as ice-ice disease (IID) causing a whitening of the thallus due to depigmentation. Crop condition assessment is important for minimizing yield losses and improving the biosecurity of seaweed farms. The recent influence of modern technology has resulted in the development of precision aquaculture. The present study focuses on the exploitation of spectral reflectance in the visible and near-infrared regions for characterizing the crop condition of two of the most cultivated Eucheumatoids species: Kappaphycus alvareezi and Eucheuma denticulatum. In particular, the influence of spectral resolution is examined towards discriminating: (a) species and morphotypes, (b) different levels of seaweed health (i.e., from healthy to completely depigmented) and (c) depigmented from silted specimens (thallus covered by a thin layer of sediment). Two spectral libraries were built at different spectral resolutions (5 and 45 spectral bands) using in situ data. In addition, proximal multispectral imagery using a drone-based sensor was utilised. At each experimental scenario, the spectral data were classified using a Random Forest algorithm for crop condition identification. The results showed good discrimination (83–99% overall accuracy) for crop conditions and morphotypes regardless of spectral resolution. According to the importance scores of the hyperspectral data, useful wavelengths were identified for discriminating healthy seaweeds from seaweeds with varying symptoms of IID (i.e., thalli whitening). These wavelengths assisted in selecting a set of vegetation indices for testing their ability to improve crop condition characterisation. Specifically, five vegetation indices (the RBNDVI, GLI, Hue, Green–Red ratio and NGRDI) were found to improve classification accuracy, making them recommended for seaweed health monitoring. Image-based classification demonstrated that multispectral library data can be extended to photomosaics to assess seaweed conditions on a broad scale. The results of this study suggest that proximal sensing is a first step towards effective seaweed crop monitoring, enhancing yield and contributing to aquaculture biosecurity. Full article