Vitiligo is an immune-mediated disease characterized by depigmentation of the skin. Although transcriptomic studies have advanced the mechanistic understanding of the disease, comprehensive proteomic characterization of vitiligo-affected skin is lacking. This study aimed to investigate proteomic alterations in non-segmental vitiligo. Punch biopsies (2 mm) were collected from lesional (n = 10), perilesional (n = 62), and non-lesional skin (n = 62) from patients with vitiligo and from demographically matched (age, sex, and anatomical site) healthy controls (n = 12). Proteomic profiling was performed using mass spectrometry, and the data were analyzed in pairwise comparisons. The proteomic analyses quantified a total of 4556 proteins, including 40 differentially expressed proteins (false discovery rate <0.05). The comparison between lesional and healthy skin revealed the highest number of differentially expressed proteins, which were predominantly associated with inflammatory and immune-related processes, including TNF-α signaling, complement pathways, and signal transducer and activator of transcription 6 signaling. The comparison between lesional and non-lesional skin showed differences in protein quantification related to melanocyte differentiation and keratinocyte stress responses. These proteins included protein O-fucosyltransferase 1, which is involved in melanocyte development via Notch-1 signaling, and keratin 6B, which is implicated in keratinocyte migration during wound repair. This study provides insights into vitiligo pathophysiology, identifying proteins that, to our knowledge, have not previously been associated with vitiligo.

The treatment for refractory non-segmental vitiligo (RNSV) remains unsatisfactory, particularly for acral vitiligo (AV) and phototherapy platform-stage vitiligo (PPV), despite the numerous treatment modalities available for vitiligo. The efficacy of a triple combination therapy comprising a 308-nm excimer lamp, a fractional CO2 laser, and a topical formulation was examined in this study. A better topical formulation and fractional CO2 laser settings were tested on 64 fresh human foreskin samples. At 15 mJ pulse energy and 10% coverage, the fractional CO2 laser and topical halometasone cream achieved a more widespread and consistent distribution with minimal side effects. The clinical trial included 98 individuals with 158 RNSV lesions. A total of 46 patients with 98 AV lesions and 52 with 60 PPV lesions were randomly assigned to T and C groups. T groups received fractional CO2 laser, plastic-wrapped halometasone cream, and 308-nm excimer lamp therapy. The C group received 308-nm excimer lamp, topical calcineurin inhibitor and halometasone cream (without fractional CO2 laser). A twice-weekly 308-nm excimer lamp therapy was used for three months. In the T group of PPV, 50% of lesions were successful at the conclusion of the research, while only 10% of lesions in the C group of PPV were successful (P ≤ 0.000). Success was attained by 8.16% of lesions in the T group of AV, while only 6.12% of lesions in the C group of AV were successful (P = 0.425). The PPV is definitively influenced by the tripartite combination therapy of a 308-nm excimer lamp, topical halometasone cream, and fractional CO2 laser. The treatment duration of PPV can be shortened and the phototherapy platform stage can be avoided. Conversely, the combination treatment did not yield satisfactory results for vitiligo in the acral region.

Melanogenesis and pigmentation are crucial processes for normal skin and hair, and they are regulated by complex factors. Unlike epidermal pigmentation, follicular melanogenesis depends on cyclic replenishment from a bulge melanocyte stem cell reservoir, making its functional decline generally irreversible yet clinically reversible under rare conditions. Herein, we systematically review the core biological processes governing follicular pigmentation, including embryonic specification, niche homing, cyclic lineage migration, and microenvironmental signaling networks. We further integrate emerging single-cell and spatial omics findings to propose a novel, three-stage chronological model of canities, bridging mouse-derived mechanisms with human clinical evidence. There are multiple conditions that lead to hair graying, such as aging, premature hair graying, the stem cell niche environment, and the biological variety of melanocytes and hair follicles, with aging being the most common factor among these. In brief, the exact mechanisms of hair pigmentation and depigmentation remain elusive. Herein, we review the physiology and pathology of hair pigmentation and depigmentation, and summarize the mechanisms that might be affected during human hair graying.

Eyelid neoplasms are among the most common periocular conditions in dogs and can lead to significant ocular morbidity if left untreated. Although surgical excision with blepharoplasty remains the standard of care, cytoreduction combined with cryosurgery has emerged as a less invasive alternative that preserves eyelid integrity. This prospective study evaluated 30 dogs with eyelid masses treated by cytoreductive excision followed by two freeze-thaw cycles delivered via a contact CO2 cryosurgical unit. Risk factors, tumor types, pre- and postoperative ophthalmic signs were assessed and graded according to severity. Preoperative and postoperative findings included ocular discharge, conjunctival hyperemia, and blepharospasm. Postoperative ophthalmic signs were transient, resolving within 72 h. Depigmentation changes (leukoderma and leukotrichia) resolved spontaneously within 30 days. Histopathological analysis identified melanoma (30%), squamous cell carcinoma (16.7%), and sebaceous adenoma (16.7%) as the most prevalent tumor types. Tumor recurrence was observed in only one case (3.3%), involving a melanoma. These results suggest that cytoreduction combined with cryosurgery is a safe, time-efficient, and effective option for canine eyelid neoplasms, particularly for small or superficial tumors where preserving eyelid structure is a priority.

Waardenburg syndrome (WS) is a neurocristopathy primarily characterized by congenital hearing loss and multisystem pigmentary abnormalities. We report a 12-year-old Han Chinese girl who presented with moderate-to-severe sensorineural hearing loss, a wide nasal root, diffuse hypopigmentation of the hair, and facial freckles-features partially similar to the WS phenotype. However, her calculated W-index was 1.87, below the diagnostic threshold for dystopia canthorum (>1.95), and her overall clinical presentation did not meet the diagnostic criteria for any WS subtype. Whole-exome sequencing (WES) and subsequent familial Sanger sequencing identified a homozygous GJB2 variant, c.109G > A (p.Val37Ile), in the proband, with both parents confirmed as heterozygous carriers. Based on the integrated clinical and genetic evidence, the patient was diagnosed with GJB2-related autosomal recessive nonsyndromic hearing loss (DFNB1A). Her WS-like features were interpreted as a possible phenocopy. This case highlights that in patients with hearing loss exhibiting incomplete or atypical WS features, comprehensive genetic testing-including analysis of GJB2-is crucial to differentiate phenocopies, establish an accurate etiology, and provide a basis for precise diagnosis and genetic counseling.

The Kitl/c-Kit signaling axis centrally controls mammalian melanocyte development, survival and cutaneous pigment homeostasis. Most known pathogenic Kitl variants are dominant and usually cause multi-system lesions, with variable phenotypic severity among alleles. Here, we comprehensively characterized a novel spontaneous recessive Kitl mutation in C3H/He mice that induces localized hair graying limited to the forehead, abdomen and paws. Linkage mapping positioned the mutation within a 5.05 Mb interval on chromosome 10, and molecular assays verified an intron 3 IAP retrotransposon insertion driving abnormal splicing and inclusion of a 42-bp cryptic exon. This mutant allele is provisionally designated Kitl[m1Yzcm]. Mutant hair follicles were morphologically intact yet melanin-free; c-Kit and DCT immunostaining showed undetectable follicular melanocyte lineage signals, suggesting localized hair graying may arise from defective melanoblast colonization or alternative post‑migratory melanocyte defects, rather than impaired melanin synthesis.This novel Kitl[m1Yzcm]mutant provides a mouse model for investigating mechanisms of localized cutaneous depigmentation and supporting pre‑clinical drug development.

Psoriasis is an inflammatory skin disorder characterized by epithelial hyperplasia and infiltration of inflammatory cells. Several immunological therapies have been developed for its treatment, including IL-17 inhibitors such as secukinumab, ixekizumab and bimekizumab. The safety profile of IL-17 inhibitors includes infectious diseases, gastrointestinal disorders, headaches, and cutaneous conditions such as eczema. Here, we report the first case of vitiligo, a depigmenting skin disorder characterized by the selective loss of melanocytes, occurring during treatment with bimekizumab. This case involved a 42-year-old man who achieved complete skin clearance of psoriasis plaques under bimekizumab therapy. After 11 months of treatment, he developed vitiligo patches on his face. These lesions resolved following discontinuation of bimekizumab, minipulse therapy and ruxolitinib cream application. Vitiligo occurrence has been previously observed with other IL-17 inhibitors, including secukinumab and ixekizumab (11 other cases). Although IL-17 is believed to play a role in the pathophysiology of vitiligo, its exact mechanism remains unclear. Paradoxal vitiligo may represent a class effect of IL-17 inhibitors, particularly in patients with psoriasis. This potential adverse effect should be considered, especially in patients with a personal or family history of vitiligo or other depigmentation disorders. Interestingly, stability or even repigmentation has been observed in patients who continued anti-IL-17 therapy, regardless of whether they received symptomatic treatment. Given the efficacy of anti-IL17 inhibitors in psoriasis, the risk-benefit balance should be carefully discussed in this context.

Retinoblastoma (RB) and oculocutaneous albinism (OCA) are genetically independent disorders whose coexistence is exceptionally rare, with an estimated theoretical frequency of 1 in 800 million births.

Vitiligo is a chronic autoimmune depigmentation skin disorder characterized by the acquired loss of melanocytes, with a complex multifactorial pathophysiology. Among the potential predisposing factors, some drugs, including monoclonal antibodies, have been associated to disease onset.

Vitiligo and melasma frequently coexist, creating a treatment dilemma, since agents effective for one condition can destabilize the other, and no consensus currently exists on safe management. We conducted a scoping literature review (through June 2023) on treatment of patients with concomitant vitiligo and melasma, followed by a two-round international e-Delphi survey (22 experts from 14 countries; consensus defined as ≥ 70% agreement) and a final online consensus meeting. Only one study supported the safe use of oral tranexamic acid for melasma in vitiligo patients. Expert consensus favored prioritizing vitiligo treatment, particularly when active, while incorporating patient's preferences. Targeted phototherapy is suitable for localized facial lesions of vitiligo, and non-facial vitiligo can be treated alongside melasma after covering the face. Topical calcineurin inhibitors, ruxolitinib, tretinoin, corticosteroids, and oral tranexamic acid can be used. Lasers and chemical peels were recommended only with caution by experienced pigment specialists. Until there is enough scientific evidence, hydroquinone would be replaced by other safer cosmetic lightening agents (e.g., niacinamide, ascorbic acid, thiamidol, melasyl), which show comparable efficacy with less theoretical risk. This first international consensus offers practical, patient-centered guidance for managing coexisting vitiligo and melasma, emphasizing individualized, disease-activity-based treatment sequencing. Trial Registration: PROSPERO reference number: RD42023395586 Significance. Depigmenting agents used for melasma inhibit melanogenesis, a mechanism that can further compromise the already-stressed melanocyte populations characteristic of vitiligo. This consensus gives clinicians an expert-informed pathway through a common but understudied comorbidity. It also identifies a clear research gap: controlled, mechanistic comparisons of hydroquinone against newer tyrosinase inhibitors specifically in vitiligo-prone skin are still lacking.

Morphological defects in Nellore cattle, including abnormalities in conformation, feet and legs, navel structure, pigmentation, and craniofacial development, negatively impact productivity, welfare, and long-term herd sustainability. This comprehensive review aimed to synthesize existing genetic and genomic evidence on these defects in purebred Nellore cattle. Studies were identified through searches of Web of Science, PubMed, and SciELO up to September 2025. Eligible studies included genetic or genomic analyses of morphological defects in purebred Nellore cattle. The methodological characteristics and limitations of the included studies were evaluated descriptively. Results were synthesized using a narrative descriptive approach due to heterogeneity in phenotypes and methodologies. A total of 89 studies were included. This review summarizes phenotype definitions and scoring systems (e.g., MES, EPMURAS, MERCOS) used in breeding programs. Most reported heritability estimates ranged from approximately 0.10 to 0.68 across traits and analytical scales, with liability-scale estimates for binary defects reaching 0.54 for depigmentation. Genetic correlations with growth traits were generally favorable or weak, whereas evidence regarding reproductive traits was limited and less consistent. Linear models are widely used to analyze morphological defects but may underestimate genetic variance for categorical and unbalanced traits, whereas threshold models offered improved theoretical suitability at higher computational cost. Key limitations across studies included evaluator subjectivity, imbalanced score distributions, limited phenotypic granularity, and environmental heterogeneity. Morphological defects show sufficient genetic variability to support inclusion in genetic evaluations. Standardized phenotyping protocols, improved scoring strategies, and expanded genomic analyses are needed to enhance selection accuracy and animal welfare in Nellore cattle.

Targeting melanogenesis through tyrosinase inhibition represents a key therapeutic strategy, highlighting the need for novel molecules capable of modulating melanin synthesis and/or serving as fluorescent probes for cellular and melanoma tracking. In this study, two curcumin (CUR) derivatives, CUR-C3-PP 1 and CUR-CO-PP 2, were designed and successfully synthesized by strategic integration of a 4-(piperazin-1-yl)phenol pharmacophore into CUR skeleton. In vitro enzymatic assays against Agaricus bisporus tyrosinase (AbTYR) revealed that derivatives CUR-C3-PP 1 and CUR-CO-PP 2 amplified the diphenolase inhibitory capacity (IC50 values of 51.20 μM and 12.89 μM, respectively) when compared to parent curcumin (IC50 = 168.57 μM). Notably, CUR-CO-PP 2 emerged as the most potent candidate, significantly eclipsing native CUR and outperforming the standard inhibitor kojic acid (KA). Enzyme kinetics and molecular docking simulations rationalized this enhanced profile, and the mechanism of inhibitory effects for compounds CUR-C3-PP 1 and CUR-CO-PP 2. Cellular assays highlighted that CUR-C3-PP 1 retained functional intrinsic luminescence, displaying selective accumulation and intense fluorescence within the cytoplasm of B16-F10 melanoma cells alongside preferential cytotoxicity. Screening in zebrafish (Danio rerio) embryos confirmed that both derivatives maintain an excellent biocompatibility profile up to 20 μM. In vivo, both compounds elicited robust, dose-dependent depigmentation, with CUR-CO-PP 2 closely approaching the efficacy of the control 1-phenyl-2-thiourea (PTU). Collectively, our findings demonstrate that the imaging and anti-melanogenic properties of curcuminoids can be independently optimized through rational linker modification, establishing CUR-C3-PP 1 as a promising fluorescent tracer for imaging and CUR-CO-PP 2 as a candidate for depigmenting therapies.

Sargassum is a large and diversified genus of marine brown algae that is distributed widely in tropical and subtropical areas. They have been used for centuries in Asian countries, and have demonstrated a variety of health advantages, including anti-cardiovascular disease, anti-osteoarthritis, anti-cancer, anti-inflammatory, antioxidant, and hypopigmentation effects. However, the putative anti-diabetic, anti-Alzheimer's, and anti-Parkinson's diseases activities of various Sargassum spp. have not been investigated and compared thoroughly. Thus, the purpose of this study was to examine the anti-diabetic, anti-Alzheimer's, and anti-Parkinson's diseases' activities of ten Sargassum and one myagroides species collected off the Korean coast. In this study, we examined the inhibitory activity of 70% ethanolic extract of the Sargassum and myagroides species against protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, peroxynitrite (ONOO[-]), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), BACE1, MAO-A, and MAO-B. Among the Sargassum and myagroides species tested, S. hemiphyllum, S. filicinum, and S. miyabei showed potent PTP1B inhibitory activity (IC50 values of 2.11, 1.87, and 6.49 μg/mL, respectively), α-glucosidase inhibitory activity (IC50 values of 3.67, 2.30, and 11.12 μg/mL, respectively), and ONOO[-] scavenging activity, with IC50 values of 2.07, 4.49, and 2.46 μg/mL, respectively. Moreover, S. miyabei exhibited the highest BACE1 and BChE inhibitory activity, with IC50 values of 3.38 and 39.76 μg/mL, respectively. The highest MAO-A inhibitory activity was seen in S. miyabei, S. serratifolium, and S. macrocarpum, with IC50 values of 16.91, 12.46, and 14.02 μg/mL, respectively. Therefore, our findings showed that Sargassum species have health benefits and may be useful in treating diabetes and neurological disorders.