Actinic Lentigines Display an Abnormal Distribution and Accumulation of Melanin in Enlarged Macromelanosomes within Keratinocytes.

Dissecting the clinical and pathophysiological complexity of fundus tessellation.

A metrological framework for in vivo quantification of depth-resolved melanin distribution using ultrasound-guided photoacoustic microscopy

Skin aging commonly manifests as deepening wrinkles, loss of elasticity, and weakened barrier function, resulting from the long-term accumulation of multiple biological processes. Dermal fibroblasts, as the primary source of extracellular matrix, not only provide structural support but also play an active role in aging. On one hand, they undergo intrinsic aging due to telomere shortening, mitochondrial decline, and dysregulation of signaling pathways (e.g., TGF-β, mTOR). On the other hand, they release inflammatory cytokines and proteases via the senescence-associated secretory pattern (SASP), disrupting keratinocyte function, melanin distribution, immune surveillance, and even microvascular and adipose tissue functions. This destabilizes the matrix equilibrium and exacerbates inflammation, creating a vicious cycle. While strategies like dasatinib/quercetin, rapamycin, or retinol show promise, they remain constrained by transdermal efficiency and targeting limitations. This review aims to elucidate these mechanisms and interactions, providing insights for developing more effective anti-aging interventions.

Melanocytes are important components of the inner-ear cellular architecture. However, limited morphological research hinders our understanding of inner-ear function. Here, we characterize the morphology of inner-ear melanocytes and cells often misidentified as melanocytes. Immunofluorescence, smart-seq, transmission/field emission scanning electron microscopy, and immunoelectron microscopy are used. Cells previously referred to as "perivascular macrophage-like melanocytes" are not observed in the stria vascularis and are actually macrophages; along with melanocytes, they constitute intermediate cells. Cells with a "black ball" appearance in the vestibule are identified as macrophages. We examine variation in melanocytes or macrophages with age, strain, and cisplatin injury. Kir4.1 expression and the greater noise resistance observed in pigmented mice suggest melanocyte functions. Based on melanin distribution in Pou3f4y/- mice, we hypothesize that melanocytes migrate from the modiolus along Reissner's membrane area to the stria vascularis, following a base-to-apex gradient. These findings provide novel ultrastructural and immunological insights into inner-ear function.

The oral mucosa color varies from white to red-purple in light-skinned individuals. Pigmented lesions resulting from excess melanin deposition can appear brown, blue, grey, or black, depending on the amount and distribution of melanin in the tissues. To ensure an accurate diagnosis, it's crucial to identify whether the discolored mucosal areas are caused by an adverse drug reaction (ADR) to a particular medication. Patients exhibiting these lesions need to be carefully monitored, and thorough follow-up is necessary to avoid any potential misdiagnosis.

Abnormal pigmentation plays an important role in various skin diseases and in studies of whitening efficacy.Three-dimensional pigmented epidermis-on-a-chip models provide a crucial in vitro platform for exploring melanin production and regulation in skin. However, dynamic and non-invasive quantitative assessment of melanin distribution remains difficult with traditional histological methods. In this study, an AI-assisted objective evaluation framework was established for three-dimensional pigmented epidermis-on-a-chip models based on brightfield images. Melanin regions were segmented using the MEM-ViT algorithm, and their morphological features were extracted to build a multi-indicator comprehensive analysis system for determining the "good/poor" status of the model. The results showed 98% consistency between algorithmic predictions and manual annotations, demonstrating the reliability and generalization capability of the proposed method. The framework enabled accurate segmentation of melanin regions and standardized evaluation of model quality without staining. This method provides a rapid, non-invasive, and standardized approach for evaluating 3D pigmented epidermis-on-a-chip models. It offers a useful technical pathway for drug efficacy research, whitening mechanism analysis, and objective assessment of skin pigmentation-related disorders.

Picosecond lasers are extensively utilized to treat hyperpigmentation and signs of skin aging. However, the underlying biological mechanisms remain to be elucidated. This study was performed to explore the effects and mechanisms of picosecond laser therapy on melanin clearance and skin rejuvenation in a porcine model. A dual-wavelength (532/1064 nm) picosecond laser was applied to both pigmented and non-pigmented skin of Bama miniature pigs. For pigmentation treatment, 532 nm irradiation was delivered with 3 and 4 mm spot sizes at fluences ranging from 0.4 to 1.0 J/cm², and 1064 nm irradiation was applied with 2, 3, and 4 mm spot sizes at fluences of 1.2 to 3.0 J/cm². For rejuvenation treatment, 1064 nm irradiation (8 mm spot size, 0.4 J/cm²) was employed. Skin samples were collected immediately after treatment and at 7 and 30 days post-irradiation. Hematoxylin and eosin staining and transmission electron microscopy were used to evaluate epidermal morphology and melanosome ultrastructure. Fontana-Masson staining was performed to assess melanin distribution and content, combined with CD163 immunofluorescence to visualize the colocalization of melanin and macrophages. Immunohistochemistry and Western blot analyses were conducted to determine tyrosinase expression levels. Multiplex immunohistochemistry was further applied to detect melanocytic markers (SOX10, MART-1), collagen I/III, growth factors (TGF-β1, GDF11), and barrier-related proteins (filaggrin, claudins). Picosecond laser treatment immediately induced epidermal vacuolization and melanosome disruption, followed by a progressive reduction in epidermal melanin over time, which was more prominent in the 532 nm treatment group compared with 1064 nm. Fontana-Masson and immunofluorescence staining revealed abundant CD163-positive macrophages colocalized with melanin in the dermis on Day 7, indicating active phagocytosis of pigment debris. SOX10- and MART-1-positive melanocytes were rare at Day 0 and absent thereafter in laser-treated skin. Western blot analysis showed that tyrosinase expression was significantly downregulated from Day 7 and remained suppressed through Day 30, suggesting inhibition of melanogenesis. Regarding rejuvenation, dermal collagen I and III slightly decreased at Day 7 but markedly increased by Day 30. TGF-β1 and GDF11 were upregulated following treatment. Filaggrin and claudins increased at Day 7 and declined at Day 30 but remained above baseline, indicating improved barrier integrity. Picosecond lasers effectively induced pigment reduction, immune-mediated clearance and melanogenesis inhibition, while concomitantly promoting dermal regeneration and epidermal barrier repair. These findings provide mechanistic insights into their therapeutic applications in pigmentation disorders and skin aging.

Diseases associated with skin pigmentation include hyperpigmentation and hypopigmentation. Macrophages are involved in melanogenesis and the development of skin pigmentary disorders, and they affect the production and distribution of melanin mainly through phagocytosis and secretion. They can either phagocytose melanin and deposit it in the dermis or secrete a variety of cytokines like interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and some interleukins (ILs) such as IL-1, IL-6, IL-8, and IL-18. The interaction between macrophages and other cells is responsible for the secretion of these cytokines. Macrophages can also promote pigmentation in hyperpigmentation disorders, such as post-inflammatory hyperpigmentation (PIH), drug-induced pigmentation (DIP), senile lentigo (SL), and melasma, as well as hypopigmentation disorders such as vitiligo and halo nevus (HN). In this review, we summarize the role of macrophages in the development of pigmentary diseases and provide new insights for the identification of potential targets for pigmentary diseases.

To characterize changes in retinal pigment epithelium (RPE) melanin distribution after anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD). This prospective study enrolled treatment-naïve nAMD eyes with macular neovascularization (MNV) type 1 and type 2. Eyes were treated with intravitreal faricimab injection every four weeks. Visual acuity and anatomical changes were assessed with multimodal imaging. Polarization-sensitive OCT (PS-OCT) was used to examine the polarimetric entropy, quantitative indicator of melanin distribution, at the RPE segment. Retinal sensitivity was assessed with microperimetry. Twelve patients with MNV type 1 and seven eyes with MNV type 2 were included. Faricimab significantly improved visual acuity and central subfield thickness (p = 0.0064, < 0.0001, respectively). In MNV type 1, faricimab significantly increased mean entropy in the overall Early Treatment Diabetic Retinopathy Study (ETDRS) grid area (p = 0.0386). In the per-grid analysis, entropy of type 1 also significantly increased, whereas type 2 showed significant reduction (p = 0.0071, 0.0389, respectively). As MNV type 2 regresses, high-entropy area corresponding to MNV decreased and low-entropy area surrounding them increased (p = 0.019, 0.0058, respectively), suggesting RPE migration onto MNV. RPE entropy was significantly associated with visual acuity or retinal sensitivity after the treatment (p = 0.00475, 0.0307, respectively). After anti-VEGF treatment for type 1 or type 2 MNV, RPE melanin distribution at the MNV and the surrounding area distinctly changed. They were associated with visual function. The present study supported deterioration of visual function in eyes with type 2 MNV after anti-VEGF treatment resulted not only from subretinal scar formation but RPE atrophy surrounding the MNV.

Post-inflammatory hyperpigmentation (PIH) is a reaction process caused by an increase in melanin or abnormal melanin distribution due to inflammatory skin diseases, skin disease treatments, and external stimuli. Ultraviolet radiation can exacerbate PIH. It stimulates melanocytes, increases melanin production and deposition, and deepens the color and prolongs the duration of PIH. This study aims to investigate the inhibitory effects of Coelonin, an extract from Dendrobium officinale, on melanin production and its underlying mechanisms. Through molecular docking analysis, we found that Coelonin has significantly stronger binding capabilities to tyrosinase (TYR) and melanocortin 1 receptor (MC1R) than kojic acid, a well-known whitening agent. This stronger binding ability suggests that Coelonin may inhibit melanin production by regulating the activity of melanin metabolism-related proteins, thereby exerting its whitening effect. Compared with kojic acid, Coelonin demonstrates superior binding characteristics at the molecular level, providing stronger evidence for its potential as a whitening active ingredient. In cell experiments, Coelonin had no significant effect on the proliferation of B16-F10 melanoma cells within the concentration range of 20-40µM, but it could significantly reduce the intracellular reactive oxygen species (ROS) levels and inhibit TYR activity and melanin production. Western blot results showed that Coelonin could downregulate the expression of TYR, MITF, TRP-1, and TRP-2 proteins. In in vivo experiments, a guinea pig model of PIH was established by Ablative Fractional Resurfacing CO₂ Laser (AFR CO2) combined with UV-B irradiation. It was found that Coelonin treatment could significantly improve skin pigmentation, reduce melanin granule deposition, and did not cause skin inflammation or hyperplasia and other side effects. This study indicates that Coelonin is an efficient and safe melanin synthesis inhibitor and has the potential to be developed as a plant-derived skin whitening agent.

Melasma, a refractory hyperpigmentation disorder, requires noninvasive tools for accurate pathological assessment. This study compared two-photon microscopy (TPM) and reflectance confocal microscopy (RCM) for the invivo characterization of melasma pathology. In this cross-sectional study, TPM and RCM features and imaging clarity were evaluated in 130 melasma patients. Spearman correlation analyses were performed between TPM-quantified epidermal melanin, the melanin index (MI), and the individual typology angle (ITA). Features were also compared between active and stable disease stages. TPM and RCM showed substantial agreement in detecting increased epidermal melanin (κ = 0.651), activated melanocytes at the dermal-epidermal junction (DEJ) (κ = 0.711), and flattened rete ridges (κ = 0.691) (all p < 0.001). TPM excelled in visualizing intracellular melanin distribution, pendulous melanocytes under the DEJ, and solar elastosis, while RCM better identified activated melanocytes at the DEJ. TPM-quantified epidermal melanin content correlated positively with MI and negatively with ITA. RCM-detected dermal inflammatory cells were more prevalent in active than in stable melasma. In conclusion, TPM and RCM synergistically capture critical melasma features, with TPM assessing disease severity via epidermal melanin quantification, whereas RCM reflects disease activity by detecting inflammatory cells. This provides clinicians with tailored imaging tools for precision management.

Background: The multiple coat colors of yaks are mainly determined by melanin synthesized by melanocytes. Comparing the amount and distribution of melanin and melanocytes in the skin of yaks with different coat colours has not yet been described; moreover, studying the expression of melanin-related proteins in the skin of yaks with different coat colors will help to further understand the molecular basis of the regulation of coat color in animals. This study observes the histomorphological structure of white, brown and black yak skin and investigates the expression of melanocyte markers MITF, SOX10, PMEL, TYRP1, DCT, MC1R and KIT, in white, brown and black yak skin. Methods: HE staining and transmission electron microscopy (TEM) were performed for histomorphological observation. Immunofluorescence analyses were performed to assess marker expression. Result: Our results showed that there was no melanin in the skin of white yaks; whereas the melanin formation process was not problematic in brown and black yaks and the formation of brown hair colour could be due to the low number of melanocytes and the fact that melanocytes were mostly early in differentiation.

The distinctive tint that a person's eyes exhibit is known as their eye color. It can include rich browns, vivid blues, enthralling greens, gentle grays, and charming hazels. The amount and distribution of melanin in the iris, the colored portion of the eye, determines the color. Every eye color has an attractive appeal of its own and could vary tremendously from person to person. It's amidst the numerous unique traits that set each person apart. Due to heritage and the distinct gene combination that each person acquires from their parents, everyone has various eye colors. Melanin and lip chrome are the two principal pigments that are involved. Individual variances in the genes governing the creation and distribution of these pigments may contribute to variations in eye color. Thus, the stunning arrays of eye hues we see in the world are determined by a genetic lottery. The eye contributes in object representation along with color, light, and depth perception. This article addresses the frequency of eye color among individuals of various ages. In the current research, seven out of a hundred randomly selected individuals were discovered to have remarkably varied eye colors, reaming with brown and black shades and pertaining to varying age groups. It doesn't seem to gender-specific. It is comprised of five females (♀) and two adolescents (♂) in the age group of Hyderabad, Sindh, Pakistan. Black and brown were the most often noticed hues in the most recent investigation.

In Ayurveda Varna, is considered as marker of good health. The Varna is a parameter useful for healthy and glowing skin. It is influenced by a several circumstances before and after birth. In Ayurveda classics Acharyas mentioned about various factors like Panchmahabhuta, Dosha, Dhatu, Ahara, Agni, genes, are responsible for different varna. The effective and unique concept about beauty in Ayurveda has steered to the exposure of Ayur-cosmaceuticals. The concept of prabha,varna, chhaya described in Ayurveda are inborn being of beauty. A Sanskrit term varna meaning outer appearance, shape, figure, texture of thes kin. Chhaya is the organization whichlimitprabha and varna and it highlight to the complexion. Thus, anything which carries beauty and softness and rejuvenates and maintain the natural texture and tone of the skin along with multiplication of glow, lustre and complexion is known as Varnya. In modern science term Varnya is corelated with term complexion. In human’scomplexion can be described as the natural colour, appearance of the skin, texture especially of the face. A person’s complexion is a biological trait. Melanin is a biological pigment which is mainly responsible for in the tone. Few factors are responsible for colour of the skin apart from melanin pigments are as nutritional, environment and developmental status of granular layer, absorption coefficient of the dermis and epidermis, reflection coefficient of skin surface, content of UV light absorbing component, thickness of overlaying tissue, amongst them melanin is the major determinant of colour and which depends upon racial, ethnic difference, number of melanin, size ,shape, distribution and degradation of melanin. In Ayurveda, Kashyap Samhita is one of the ancient literatures, where a Lehana based unique concept of Swarnaprashan which is prepared with Swarna Bhasma (incinerated gold), Madhu (honey), Ghrita isdescribed. Acharya Kashyap explained benefits of administration of Swarnaprashan is medhavardhak (intellect), agnivardhak(digestion and metabolism), balvardhanam (physical strength), ayuvardhak(longevity), mangalkarak (auspicious), purnyakarak(righteous), vrishyam(aphrodisiac), varnyam(complexion), grahapaham (protection from evil spirits and microorganisms). This review is an effort to research the mode of action of Swarnaprashan in Varnya(complexion) according to Ayurveda and contemporary science.

In Ayurveda Varna, is considered as marker of good health. The Varna is a parameter useful for healthy and glowing skin. It is influenced by a several circumstances before and after birth. In Ayurveda classics Acharyas mentioned about various factors like Panchmahabhuta, Dosha, Dhatu, Ahara, Agni, genes, are responsible for different varna. The effective and unique concept about beauty in Ayurveda has steered to the exposure of Ayur-cosmaceuticals. The concept of prabha, varna, chhaya described in Ayurveda are inborn being of beauty. A Sanskrit term varna meaning outer appearance, shape, figure, texture of the skin. Chhaya is the organization which limit prabha and varna and it highlight to the complexion. Thus, anything which carries beauty and softness and rejuvenates and maintain the natural texture and tone of the skin along with multiplication ofglow, lustre and complexion is known as Varnya. In modern science term Varnya is correlated with term complexion. In human’s complexion can be described as the natural colour, appearance of the skin, texture especially of the face. A person’s complexion is a biological trait. Melanin is a biological pigment which is mainly responsible for in the tone. Few factors are responsible for colour of the skin apart from melanin pigments are as nutritional, environment and developmental status of granular layer, absorption coefficient of the dermis and epidermis, reflection coefficient of skin surface, content of UV light absorbing component, thickness of overlaying tissue, amongst them melanin is the major determinant of colour and which depends upon racial, ethnic difference, number of melanin, size, shape, distribution and degradation of melanin. In Ayurveda, Kashyap Samhita is one of the ancient literatures, where a Lehana based unique concept of Swarnaprashan which is prepared with Swarna Bhasma (incinerated gold), Madhu (honey), Ghrita is described. Acharya Kashyap explained benefits of administration of Swarnaprashan is medhavardhak (intellect), agnivardhak (digestion and metabolism), balvardhanam (physical strength), ayuvardhak (longevity), mangalkarak (auspicious), purnyakarak (righteous), vrishyam (aphrodisiac), varnyam (complexion), grahapaham (protection from evil spirits and microorganisms). This review is an effort to research the mode of action of Swarnaprashan in Varnya(complexion) according to Ayurveda and contemporary science.

Melanin is ubiquitous in nature, and how the arrangement and concentration of melanin affect its optical and thermal properties aids in understanding the role of melanin in natural systems and technological applications. In this study, a model system consisting of silica and melanin particles with different compositions and degrees of mixing is designed to study the impact on light absorption. The structures are generated using coarse‐grained molecular dynamics simulations, and their optical properties were calculated using finite‐difference time‐domain simulations. The results show that the supraballs with uneven distribution of melanin particles (strongly demixed) exhibit higher absorption (in the range of 360–1000 nm) at melanin concentrations of 40%–80%. Even for a simulation box with a thickness of 16 μm, the strongly demixed samples with melanin concentrations of 50%–100% absorb almost 80% of the total input light at 360–1000 nm. Since light absorption also correlates with thermal heat, thermal heat maps are presented for these systems as a function of melanin concentration and particle distribution. The fundamental knowledge of how melanin distribution alters power absorption will inform the development of photothermally responsive materials for medical applications (photothermal agents), sensors/communication devices, and coatings.

The threadsail filefish, Stephanolepis cirrhifer, is an economically important marine species. However, wild catches have sharply decreased over the past 20 years, causing S. cirrhifer to be added to the IUCN Red List of Threatened Species. Accordingly, this study seeks to promote technological development for artificial breeding and early life-stage farming by defining the morphological characteristics of ontogenesis. The fertilized eggs, with a diameter of 0.62 ± 0.01 mm, were spherical and sticky and contained multiple oil globules of varying sizes. The embryonic development was observed and divided into eight phases, which were cleavage, blastocyst, gastrula, neurula, organogenesis, muscular contraction, heart pulsation, and hatching. At 3 days post-hatching (dph), the yolk sac was completely absorbed. The eye developed rapidly, and the mouth fissure and anus initially formed. Some larvae were fed on S-rotifers (Brachionus plicatilis). At 6–8 dph, the upper and lower jaws of larvae were gradually covered by leathery skin, and the head-to-body proportion increased. At 14–16 dph, the fin differentiation occurred in the dorsal, anal, and pectoral fins, with widespread distribution of yellow and melanin on the body surface. Swim bladder was clear. The swimming ability of larva was enhanced, resulting in an obvious clustering phenomenon. At 22–25 dph, the end of the notochord continued to tilt upwards, forming a tail fin. The trunk was evenly distributed with protruding circular punctate scales. The snout was covered with leathery epidermis, and the mouth began to round. At 40–45 dph, the juvenile completed metamorphosis, with horizontal dark stripes appearing on the trunk. Pigmented spots appeared on the tail fins. The counts of dorsal and anal fin spines were 34–36 and 32–34 dph, respectively. During the development of larvae and juveniles, the growth parameters, such as total length, standard length, body height, and body weight, were made as growth curves. The slopes of growth curves were calculated. We found two inflexion points occurring in the growth curves, which may be associated with metamorphosis and transitions in feeding habits. These results enrich the biological understanding of filefish species while providing guidance for artificial propagation and fry production in S. cirrhifer.

Alpinia officinarum Hance is a traditional herb in Xinjiang for the treatment of vitiligo, and galangin (GA) is a flavonoid isolated from its roots. However, its therapeutic mechanism remains unclear. In this study, 1-phenyl-2-thiourea (PTU) was used to establish a vitiligo model in zebrafish. After successful modeling, different concentrations of GA (1 and 2μM) were administered, and the distribution of melanin granules was observed by assaying the melanin content, masson-fontana staining and tyrosinase activity. Transcriptomic analysis and molecular docking were used to identify potential GA-related pathways and targets for improving vitiligo. In addition, we evaluated the proliferation of B16F10 cells by PTU induction and also observed cellular melanin distribution using masson-fontana staining. Finally, Western blot was performed to detect the proteins of the relevant pathways. The results showed that GA significantly increased melanin production and tyrosinase activity in depigmented zebrafish. In addition, we found that GA decreased ROS and MDA levels and increased the expression of GSH, CAT and T-SOD. In addition, transcriptome analysis indicated that GA likely acts through the mitogen-activated protein kinase (MAPK) signaling pathway. GA has a strong binding affinity for important targets.GA significantly increased the expression of genes such as mapk8b, mapk14a, mapk3, mitf, tyr, tyrp1b, tyrp1a, dct, and oca2, and decreased the expression of genes such as expression of genes such as raf1 and egfr. In addition, GA enhanced the viability of B16F10 cells, increased intracellular melanin content, and increased the expression of proteins such as p38, JNK1/2/3, TYR, MITF, TRP1, TRP2, and so on. GA increases melanin production and distribution, improves tyrosinase activity, upregulates the expression of related genes and proteins through activation of MAPK and tyrosine metabolic pathways, downregulates oxidative stress, and then regulates changes in melanin synthesis to improve vitiligo.

Transcriptome profiles of the skin associated with the color of the black and white coat of Angora goats