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Melanosomal pH is important for the synthesis of melanin as the rate‐limiting enzyme, tyrosinase, is very pH‐sensitive. The soluble adenylyl cyclase (sAC) signaling pathway was recently identified as a regulator of melanosomal pH in melanocytes; however, the melanosomal proteins critical for sAC‐dependent regulation of melanosomal pH were undefined. We now systematically examine four well‐characterized melanosomal membrane proteins to determine whether any of them are required for sAC‐dependent regulation of melanosomal pH. We find that OA1, OCA2, and SLC45A2 are dispensable for sAC‐dependent regulation of melanosomal pH. In contrast, TPC2 activity is required for sAC‐dependent regulation of melanosomal pH and melanin synthesis. In addition, activation of TPC2 by NAADP‐AM rescues melanosomal pH alkalinization and reduces melanin synthesis following pharmacologic or genetic inhibition of sAC signaling. These studies establish TPC2 as a critical melanosomal protein for sAC‐dependent regulation of melanosomal pH and pigmentation. [ABSTRACT FROM AUTHOR]

Vitiligo is a skin disorder with melanocyte destruction caused by complex interplay between multiple genetic and environmental factors. Recent studies have suggested DNA methylation is involved in the melanocyte damage, but the underlying mechanism remains unknown. To explore the abnormal DNA methylation patterns in vitiligo lesional and nonlesional skin, and the mechanism of DNA methylation involved in vitiligo pathogenesis. Initially, the genome-wide aberrant DNA methylation profiles in lesional and nonlesional skin of vitiligo were detect via Illumina methylation EPIC 850k Beadchip. Subsequently, a comprehensive analysis was conduct to investigate the genomic characteristics of differentially methylated regions (DMRs). Furthermore, the effects of key aberrant methylated genes on cell apoptosis and function of both melanocytes and keratinocytes were further identified and validated by western bloting, ELISA, and immunofluorescence. Compared with nonlesional skins, we discovered 79 significantly differentially methylated CpG sites in vitiligo lesions. These DMRs were mainly located in the gene body and the TS1500 region. Annexin A2 receptor (ANXA2R), a crucial gene in cell apoptosis, was hypermethylated in vitiligo lesions. Furthermore, we showed that ANXA2R displayed hypermethylation and low expression levels in both keratinocytes and melanocytes of vitiligo patients, and the hypermethylated-triggered downregulation of ANXA2R under oxidative stress induced melanocyte apoptosis, and inhibited the secretion of stem cell factor (SCF) from keratinocytes thus impaired the survival of melanocytes. Our study illustrates the DNA methylation modification in vitiligo, and further demonstrates the molecular mechanism of hypermethylated ANXA2R in the dysfunction of melanocytes under oxidative stress. • Our study provides a map of abnormal DNA methylation in vitiligo lesions, and clarifying its role in disease development. • Clarifying the role of hypermethylated gene ANXA2R in vitiligo by inducing melanocyte apoptosis. • Revealing hypermethylated ANXA2R in vitiligo inhibiting the secretion of stem cell factor from keratinocytes thus impairing melanocyte survival. [ABSTRACT FROM AUTHOR]

This study presents the effects of treating polystyrene (PS) cell culture plastic with oxidoreductase enzyme laccase and the catechol substrates caffeic acid (CA), L-DOPA, and dopamine on the culturing of normal human epidermal melanocytes (NHEMs) and human embryonal carcinoma cells (NTERA-2). The laccase–substrate treatment improved PS hydrophilicity and roughness, increasing NHEM and NTERA-2 adherence, proliferation, and NHEM melanogenesis to a level comparable with conventional plasma treatment. Cell adherence dynamics and proliferation were evaluated. The NHEM endpoint function was quantified by measuring melanin content. PS surfaces treated with laccase and its substrates demonstrated the forming of polymer-like structures. The surface texture roughness gradient and the peak curvature were higher on PS treated with a combination of laccase and substrates than laccase alone. The number of adherent NHEM and NTERA-2 was significantly higher than on the untreated surface. The proliferation of NHEM and NTERA-2 correspondingly increased on treated surfaces. NHEM melanin content was enhanced 6-10-fold on treated surfaces. In summary, laccase- and laccase–substrate-modified PS possess improved PS surface chemistry/hydrophilicity and altered roughness compared to untreated and plasma-treated surfaces, facilitating cellular adherence, subsequent proliferation, and exertion of the melanotic phenotype. The presented technology is easy to apply and creates a promising custom-made, substrate-based, cell-type-specific platform for both 2D and 3D cell culture. [ABSTRACT FROM AUTHOR]

ALK‐fused Spitz melanocytic neoplasms are a distinct subgroup of melanocytic lesions exhibiting unique histopathologic characteristics. These lesions often manifest as exophytic or polypoid tumors, characterized by fusiform‐to‐epithelioid melanocytes arranged in a nested, fascicular, or plexiform growth pattern. Several fusion partners of the ALK gene have been identified in spitzoid melanocytic neoplasms, with TPM3 and DCTN1 being the most prevalent. Less common fusion partners include NPM1, TPR, CLIP1, GTF3C2, EEF2, MYO5A, KANK1, and EHBP1. The MLPH gene, which encodes melanophilin (MLPH), playing a crucial role in regulating skin pigmentation by acting as a linker between RAB27A and myosin Va during melanosome transport, has also recently been recognized as a rare fusion partner of ALK in Spitz melanocytic neoplasms. Currently, there exists a sparse documentation within English literature, illustrating a limited number of cases featuring MLPH::ALK fusion in Spitz melanocytic neoplasms. In this report, we present two additional cases, including a previously unreported instance of Spitz melanoma, contributing to the expanding knowledge on ALK‐fused Spitz melanocytic neoplasms. In addition, we provide a comprehensive review of the clinical, histopathologic, and molecular features observed in documented cases with this novel fusion. [ABSTRACT FROM AUTHOR]

Limited studies using animal models with a few natural mutations in melanophilin (Mlph) provided partial functions of Mlph in melanosome trafficking. To investigate cellular functions of Mlph, especially ZnF motif of Mlph, we analyzed all three Mlph knockout (KO) quail lines, one and two base pair (bp) deletions as models for total KO, and three bp deletion causing deletion of one Cysteine (C84del) in the ZnF motif. All quail lines had diluted feather pigmentation with impaired dendritogenesis and melanosome transport in melanocytes. In vitro studies revealed capability of binding of the ZnF motif to PIP3, and impairment of PI3P binding and mislocalization of MLPH proteins with ZnF motif mutations. The shortened melanocyte dendrites by the C84del mutation were rescued by introducing WT Mlph in vitro. These results revealed the diluted feather pigmentation by Mlph mutations resulted from congregation of melanosomes in the cell bodies with impairment of the dendritogenesis and the transport of melanosomes to the cell periphery. This study presents the essential functions of the ZnF motif in sorting of the melanophilin protein and novel functions of melanophilin in dendritogenesis in melanocytes. [ABSTRACT FROM AUTHOR]

Epidermal melanin synthesis determines an individual's skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, a role of cold atmospheric plasma (CAP) on melanin synthesis was proposed due to its tunable ROS generation. Herein, the argon-driven plasma jet kINPen® MED was employed, and its impact on melanin synthesis was evaluated by comparison with known stimulants such as the phosphodiesterase inhibitor IBMX and UV radiation. Different available model systems were employed, and the melanin content of both cultured human melanocytes (in vitro) and full-thickness human skin biopsies (in situ) were analyzed. A histochemical method detected melanin in skin tissue. Cellular melanin was measured by NIR autofluorescence using flow cytometry, and a highly sensitive HPLC-MS method was applied, which enabled the differentiation of eu- and pheomelanin by their degradation products. The melanin content in full-thickness human skin biopsies increased after repeated CAP exposure, while there were only minor effects in cultured melanocytes compared to UV radiation and IBMX treatment. Based on these findings, CAP does not appear to be a useful option for treating skin pigmentation disorders. On the other hand, the risk of hyperpigmentation as an adverse effect of CAP application for wound healing or other dermatological diseases seems to be neglectable. [ABSTRACT FROM AUTHOR]

Pigmented epithelioid melanocytoma is rare cutaneous melanocytic proliferation, characterized by heavily pigmented melanocytes, with a potential for regional node metastasis, but with an overall favorable clinical course. Here, we describe an uncommon case of pigmented epithelioid melanocytoma involving the penis in an adolescent patient. [ABSTRACT FROM AUTHOR]

• CRISPR-Cas9 is a valuable tool for creating XPC-deficient primary melanocytes. • XPC-deficient primary melanocytes (©-XPC-Mel) are hypersensitive to UV. • ©-XPC-Mel pave the way for studying the effects of NER on melanocyte biology. • About 500 proteins are differentially expressed in ©-XPC-Mel compared to ©-Ctrl-Mel. • The balance between pro- and anti-inflammatory signals is disturbed in ©-XPC-Mel. [ABSTRACT FROM AUTHOR]

Ultraviolet radiation can heighten tyrosinase activity, stimulate melanocyte production, impede the metabolism of numerous melanocytes, and result in the accumulation of plaques on the skin surface. α-Arbutin, a bioactive substance extracted from the arbutin plant, has been widely used for skin whitening. In this study, the whitening effect of α-arbutin by inhibiting tyrosinase activity and alleviating the photoaging effect induced by UVB are investigated. The results indicate that α-arbutin can inhibit skin inflammation, and its effectiveness is positively correlated with concentration. Moreover, α-arbutin can reduce the skin epidermal thickness, decrease the number of inflammatory cells, and down-regulate the expression levels of IL-1β, IL-6 and TNF-α, which are inflammatory factors. It also promotes the expression of COL-1 collagen, thus playing an important role in anti-inflammatory action. Network pharmacology, metabolomics and transcriptomics further confirm that α-arbutin is related to the L-tyrosine metabolic pathway and may interfere with various signaling pathways related to melanin and other photoaging by regulating metabolic changes. Therefore, α-arbutin has a potential inhibitory effect on UVB-induced photoaging and possesses a whitening effect as a cosmetic compound. [ABSTRACT FROM AUTHOR]

Aims: Plaque‐type blue naevi are rare melanocytic tumours presenting as large, pigmented plaques at birth or during childhood. There is a risk for malignant transformation, but no larger comprehensive studies exist and the diagnosis is challenging, especially on limited biopsy material. The aim is to describe the clinicopathological features and behaviour of the disease more comprehensively. Methods and results: We retrieved eight plaque‐type blue naevi, presenting as large, pigmented plaques (median = 7 cm; range = 3–26) most frequently affecting the scalp (four) followed by the cheek, arm, abdominal wall and gluteal cleft (one each), with a slight female predilection. Median age at time of biopsy was 39.5 years (range = 15–90), but three tumours had been present at birth and one since childhood. Histopathologically, the tumours were poorly circumscribed and composed of cellular fascicles of uniform spindle cells in a background of variably prominent pigmented dendritic cells affecting dermis and subcutaneous tissues. The majority had mutations in GNAQ. One tumour showed malignant transformation, characterised by an expansile nodule of pleomorphic epithelioid melanocytes with rhabdoid morphology, high mitotic activity and areas of necrosis. This patient developed metastatic melanoma to lymph nodes. All patients are alive with a median follow‐up of 60 months. Conclusion: Plaque‐type blue naevi are diagnostically challenging tumours with risk for malignant transformation. Awareness and familiarity with the salient clinicopathological features are necessary for reliable diagnosis, and long‐term clinical follow‐up is required to monitor for malignant transformation. [ABSTRACT FROM AUTHOR]

Objective: Both piperine and a 308‐nm excimer laser have significant curative effects on vitiligo. This study mainly explored the molecular mechanism of a 308‐nm excimer combined with piperine in regulating melanocyte proliferation. Methods: Epidermal melanocytes were cultured in piperine solution, and the cells were irradiated by an XTRAC excimer laser treatment system at 308‐nm output monochromatic light. Quantitative real‐time polymerase chain reaction (qRT–PCR) and Western blot were for detecting the expression levels of genes or proteins. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and Transwell method was for assessing cell viability and migration capacity. The content of melanin was also detected. Results: The combination of the 308‐nm excimer laser and piperine enhanced the cell proliferation, migration, and melanin production of melanocytes and upregulated the level of miR‐328, and restraint of miR‐328 reversed the influence of the 308‐nm excimer laser and piperine. Secreted frizzled‐related protein 1 (SFRP1) is a direct target gene of miR‐328, and miR‐328 can inhibit the expression of SFRP1 and elevate the protein level of the Wnt/β‐catenin signaling pathway. Conclusion: The 308‐nm excimer laser combined with piperine may be more efficient than piperine alone in the remedy of vitiligo, and the miR‐328/SFRP1 and Wnt/β‐catenin pathways are participated in the proliferation, migration, and melanin synthesis of melanocytes. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is characterized by depigmented patches resulting from loss of melanocytes. Phototherapy has emerged as a prominent treatment option for vitiligo, utilizing various light modalities to induce disease stability and repigmentation. Aims and Methods: This narrative review aims to explore the clinical applications and molecular mechanisms of phototherapy in vitiligo. Results and Discussion: The review evaluates existing literature on phototherapy for vitiligo, analyzing studies on hospital‐based and home‐based phototherapy, as well as outcomes related to stabilization and repigmentation. Narrowband ultra‐violet B, that is, NBUVB remains the most commonly employed, studied and effective phototherapy modality for vitiligo. Special attention is given to assessing different types of lamps, dosimetry, published guidelines, and the utilization of targeted phototherapy modalities. Additionally, the integration of phototherapy with other treatment modalities, including its use as a depigmenting therapy in generalized/universal vitiligo, is discussed. Screening for anti‐nuclear antibodies and tailoring approaches for non‐photo‐adapters are also examined. Conclusion: In conclusion, this review provides a comprehensive overview of phototherapy for vitiligo treatment. It underscores the evolving landscape of phototherapy and offers insights into optimizing therapeutic outcomes and addressing the challenges ahead. By integrating clinical evidence with molecular understanding, phototherapy emerges as a valuable therapeutic option for managing vitiligo, with potential for further advancements in the field. [ABSTRACT FROM AUTHOR]

Primary intracranial melanocytoma is an uncommon benign pigmented tumor arising from leptomeningeal melanocytes. Neuroimaging characteristics of central nervous system melanocytoma are distinct from similarly presenting intracranial neoplasms and can aid in diagnosis prior to histopathological examination. In rare cases, there may be more than one lesion present. We report a case of a 19-year-old woman presenting with progressively worsening headaches, nausea, emesis, and generalized weakness of 2 months. Imaging revealed tumors in the parietal and ipsilateral medial temporal lobe. The patient underwent gross total resection of the parietal lesion which histopathological assessment revealed to be primary intracranial meningeal melanocytoma. This case highlights the utility of specific imaging criteria such as diffusely increased T1 signal without enhancement in the initial diagnostic evaluation of intracranial melanocytoma. We also describe the clinical characteristics, management strategy, and histopathological features of a rare case of a patient with multiple primary intracranial melanocytoma lesions. [ABSTRACT FROM AUTHOR]

Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB‐induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan‐A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP‐1 and TRP‐2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p‐GSK3β and β‐catenin and the nuclear accumulation of β‐catenin in B16F10 and Melan‐A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis‐related gene expression in melanocytes by regulating the Wnt/β‐catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future. [ABSTRACT FROM AUTHOR]

KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and activation. Blockade of this pathway results in cell depletion, while overactivation leads to mastocytosis or melanoma. Expression defects are associated with pigmentary and mast cell disorders. KIT ligand regulation is complex but efficient targeting of this system would be of significant benefit to those suffering from melanocytic or mast cell disorders. Herein, we review the known associations of this pathway with cutaneous diseases and the regulators of this system both in skin and in the more well‐studied germ cell system. Exogenous agents modulating this pathway will also be presented. Ultimately, we will review potential therapeutic opportunities to help our patients with melanocytic and mast cell disease processes potentially including vitiligo, hair greying, melasma, urticaria, mastocytosis and melanoma. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) facilitate the transfer of proteins, lipids, and genetic material between cells and are recognized as an additional mechanism for sustaining intercellular communication. In the epidermis, the communication between melanocytes and keratinocytes is tightly regulated to warrant skin pigmentation. Melanocytes synthesize the melanin pigment in melanosomes that are transported along the dendrites prior to the transfer of melanin pigment to keratinocytes. EVs secreted by keratinocytes modulate pigmentation in melanocytes [(A. Lo Cicero et al., Nat. Commun. 6, 7506 (2015)]. However, whether EVs secreted by keratinocytes contribute to additional processes essential for melanocyte functions remains elusive. Here, we show that keratinocyte EVs enhance the ability of melanocytes to generate dendrites and mature melanosomes and promote their efficient transfer. Further, keratinocyte EVs carrying Rac1 induce important morphological changes, promote dendrite outgrowth, and potentiate melanin transfer to keratinocytes. Hence, in addition to modulating pigmentation, keratinocytes exploit EVs to control melanocyte plasticity and transfer capacity. These data demonstrate that keratinocyte-derived EVs, by regulating melanocyte functions, are major contributors to cutaneous pigmentation and expand our understanding of the mechanism underlying skin pigmentation via a paracrine EV-mediated communication. [ABSTRACT FROM AUTHOR]

Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been fully investigated and the molecular analysis has been performed. Moreover, the role of paracrine factors derived from epidermis has also been studied. However, the role of dermis has not been fully studied. Thus, in this review, dermis-derived factors including soluble and insoluble components were overviewed and discussed in normal and abnormal circumstances. Dermal factors play an important role in the regulation of melanogenesis in the normal and abnormal mammalian skin. [ABSTRACT FROM AUTHOR]

Olive leaf contains plenty of phenolic compounds, among which oleuropein (OP) is the main component and belongs to the group of secoiridoids. Additionally, phenolic compounds such as oleocanthal (OL) and oleacein (OC), which share a structural similarity with OP and two aldehyde groups, are also present in olive leaves. These compounds have been studied for several health benefits, such as anti-cancer and antioxidant effects. However, their impact on the skin remains unknown. Therefore, this study aims to compare the effects of these three compounds on melanogenesis using B16F10 cells and human epidermal cells. Thousands of gene expressions were measured by global gene expression profiling with B16F10 cells. We found that glutaraldehyde compounds derived from olive leaves have a potential effect on the activation of the melanogenesis pathway and inducing differentiation in B16F10 cells. Accordingly, the pro-melanogenesis effect was investigated by means of melanin quantification, mRNA, and protein expression using human epidermal melanocytes (HEM). This study suggests that secoiridoid and its derivates have an impact on skin protection by promoting melanin production in both human and mouse cell lines. [ABSTRACT FROM AUTHOR]

The fur color of mammals is mainly determined by melanin synthesized by melanocytes. Cell staining includes melanocyte development, melanin synthesis and metabolism, and signal pathways regulating melanin synthesis. Melanocytes can be classified into many types, and these types can be identified by a variety of melanocyte markers. Fur color can judge the physical condition and nutritional status of animals, and different fur colors may have certain influence on animal production. This paper reviews the structural basis and development cycle of mammalian fur color formation, describes the cytochrome process from neural crest to mature melanocytes residing in several tissues, summarizes the types of melanocytes and the markers of each type of melanocytes, and discusses the application of animal coat color in animal production, providing help for analyzing the genetic mechanism of mammalian fur color formation and providing effective suggestions for animal production affected by fur color. [ABSTRACT FROM AUTHOR]

Melanocytes are dendritic cells localized in skin, eyes, hair follicles, ears, heart and central nervous system. They are characterized by the presence of melanosomes enriched in melanin which are responsible for skin, eye and hair pigmentation. They also have different functions in photoprotection, immunity and sound perception. Melanocyte dysfunction can cause pigmentary disorders, hearing and vision impairments or increased cancer susceptibility. This review focuses on the role of melanocytes in homeostasis and disease, before discussing their potential in regenerative medicine applications, such as for disease modeling, drug testing or therapy development using stem cell technologies, tissue engineering and extracellular vesicles. [ABSTRACT FROM AUTHOR]

Melanins are biopolymeric pigments formed by a multi-step oxidation process of tyrosine in highly specialized cells called melanocytes. Melanin pigments are mainly found in the skin, iris, hair follicles, and inner ear. The photoprotective properties of melanin biopolymers have been linked to their perinuclear localization to protect DNA, but their ability to scavenge metal ions and antioxidant properties has also been noted. Interactions between drugs and melanins are of clinical relevance. The formation of drug–melanin complexes can affect both the efficacy of pharmacotherapy and the occurrence of adverse effects such as phototoxic reactions and discoloration. Because the amount and type of melanin synthesized in the body is subject to multifactorial regulation—determined by both internal factors such as genetic predisposition, inflammation, and hormonal balance and external factors such as contact with allergens or exposure to UV radiation—different effects on the melanogenesis process can be observed. These factors can directly influence skin pigmentation disorders, resulting in hypopigmentation or hyperpigmentation of a genetic or acquired nature. In this review, we will present information on melanocyte biology, melanogenesis, and the multifactorial influence of melanin on pharmacological parameters during pharmacotherapy. In addition, the types of skin color disorders, with special emphasis on the process of their development, symptoms, and methods of treatment, are presented in this article. [ABSTRACT FROM AUTHOR]

Introduction: Vitiligo is an acquired disorder characterized by the progressive loss of functional melanocytes, resulting in depigmented macules and patches on the skin. It affects a significant portion of the world's population, with no specific gender or geographic predilection. Aim: To explore the current understanding of the association between vitiligo and COVID-19. Material and methods: This is a cross-sectional comparative research of 90 vitiligo patients, separated into two groups: those with COVID-19 confirmed by PCR and those without, gathered in 2018 before the pandemic. Al-Sadar teaching hospital in Al Basra gathered data from March 2021 to May 2022. Vitiligo patients with other infections were excluded. Wood's test was used to confirm vitiligo (VASI score). Age, gender, site of vitiligo, number of lesions, and family history were gathered for all patients in both groups. Results: Patients with vitiligo and COVID-19 had mild (70.27%), moderate (18.92%), and severe (10.81%) infections. Significant differences were found in age, duration, and VASI score, with younger patients and lower VASI scores in the Vitiligo + COVID-19 group. Females (60.6%) were more affected, and lower limbs (66.7%) were the most common site of vitiligo lesions in COVID-19 patients. Conclusions: 70.27% of vitiligo and COVID-19 patients had mild infections, 18.92% had moderate infections, and 10.81% had severe infections. Patients with both disorders were younger, had shorter vitiligo durations, and lower VASI scores than those with just one. Females were more likely to have both disorders, and lower limb vitiligo was more prevalent. Family history did not affect either group. [ABSTRACT FROM AUTHOR]

Limbal epithelial progenitor cells (LEPC) rely on their niche environment for proper functionality and self-renewal. While extracellular vesicles (EV), specifically small EVs (sEV), have been proposed to support LEPC homeostasis, data on sEV derived from limbal niche cells like limbal mesenchymal stromal cells (LMSC) remain limited, and there are no studies on sEVs from limbal melanocytes (LM). In this study, we isolated sEV from conditioned media of LMSC and LM using a combination of tangential flow filtration and size exclusion chromatography and characterized them by nanoparticle tracking analysis, transmission electron microscopy, Western blot, multiplex bead arrays, and quantitative mass spectrometry. The internalization of sEV by LEPC was studied using flow cytometry and confocal microscopy. The isolated sEVs exhibited typical EV characteristics, including cell-specific markers such as CD90 for LMSC-sEV and Melan-A for LM-sEV. Bioinformatics analysis of the proteomic data suggested a significant role of sEVs in extracellular matrix deposition, with LMSC-derived sEV containing proteins involved in collagen remodeling and cell matrix adhesion, whereas LM-sEV proteins were implicated in other cellular bioprocesses such as cellular pigmentation and development. Moreover, fluorescently labeled LMSC-sEV and LM-sEV were taken up by LEPC and localized to their perinuclear compartment. These findings provide valuable insights into the complex role of sEV from niche cells in regulating the human limbal stem cell niche. [ABSTRACT FROM AUTHOR]

Les nævus sont des lésions cutanées, parfois muqueuses, bénignes, faites de l'accumulation de mélanocytes dans la peau. Ils peuvent être présents à la naissance, ce sont les nævus congénitaux, observés chez environ 1 % des nouveau-nés. Ils sont alors de taille variable, de quelques millimètres à plusieurs dizaines de centimètres, uniques ou multiples. Seules les présentations dermatologiques sévères en termes de surface et de nombre sont associées à un risque accru de mélanome qui reste faible, autour de 1 à 2̊ % dans les présentations les plus sévères. Ces situations sont aussi caractérisées par le risque d'atteinte systémique et en particulier neurologique, et par la problématique esthétique parfois majeure. Il n'est pas nécessaire de surveiller les nævus congénitaux de petite taille, qui ne présentent pas de risque particulier. Il n'y a pas d'indication à procéder de manière systématique à l'exérèse des nævus congénitaux, cependant si une lésion est jugée suspecte, elle sera retirée pour être analysée. Les patients atteints de nævus multiples et ou de grande ou très grande taille seront pris en charge de façon multidisciplinaire, depuis leur naissance incluant au minimum le dermatologue, le pédiatre, le chirurgien plasticien et le psychologue. Le suivi permet de dépister les complications médicales éventuelles, dermatologiques, neurologiques et de développement, et psychosociales, de répondre et guider la demande d'amélioration esthétique. Congenital melanocytic nevi are benign lesions made of melanocytes. They are present at birth, in about 1% of neonates. They may be single or numerous, of various sizes, from few millimeters to several centimeters. Only widespread and numerous lesions may be associated to an increased risk of melanoma occurrence, and/or neurological symptoms. In such instances, cosmetic concern is almost always a serious issue. Small size congenital nevi do not need any specific treatment or follow-up. Rarely a worrying lesion will be removed to be histologically analyzed. Large and multiple congenital nevi need multidisciplinary follow-up including dermatologists, pediatricians, plastic surgeons, psychologists in order to screen for possible complications and to adapt surgical procedures for cosmetic reasons. [ABSTRACT FROM AUTHOR]

Melanin synthesis involves the successful coordination of metabolic pathways across multiple intracellular compartments including the melanosome, mitochondria, ER/Golgi, and cytoplasm. While pigment production offers a communal protection from UV damage, the process also requires anabolic and redox demands that must be carefully managed by melanocytes. In this report we provide an updated review on melanin metabolism, including recent data leveraging new techniques, and technologies in the field of metabolism. We also discuss the many aspects of melanin synthesis that intersect with metabolic pathways known to impact melanoma phenotypes and behavior. By reviewing the metabolism of melanin synthesis, we hope to highlight outstanding questions and opportunities for future research that could improve patient outcomes in pigmentary and oncologic disease settings. [ABSTRACT FROM AUTHOR]

Background and Aim: Melanocytes are cells in the skin, hair, and eyes that generate pigment called melanin, which is primarily responsible for the pigmentation of these structures. These melanocytes, known as the Cochlear Melanocyte, are also present in the human ears (especially in the cochlea) and play a significant role in fostering endocochlear potential and preventing the odds of hearing loss. The current study investigated the relationship of skin pigment with cochlear function through distortion product otoacoustic emission in Indian skin type. Methods: A total of 120 participants aged between 17 to 25 were included using a purposive sampling technique. The subjects were further grouped based on a questionnaire on Fitzpatrick Skin Phototype (FSP) developed by Thomas Fitzpatrick (1975) and categorized as type III- type VI suitable for Indian skin types. Along with routine audiometric evaluations, the cochlear functioning was assessed using distortion product otoacoustic emissions. The standard group research design was used, and as data was normally distributed, multivariate analysis of variance was used to compare across groups. Results: The results of multivariate analysis of variance (MANOVA) showed no significant differences across the four groups for both amplitude and the slope of distortion product otoacoustic emissions. Conclusion: The present study using otoacoustic emissions revealed that the skin pigmentation did not affect cochlear functioning in the Indian population (type III through type VI) as seen in type I and II. [ABSTRACT FROM AUTHOR]

The exosomes derived from keratinocytes can have a substantial impact on melanogenesis by influencing melanocytes. MicroRNAs (miRNAs) encapsulated within exosomes are implicated in the control of melanogenesis, particularly when under the influence of UVB irradiation. This investigation explores UVB-induced exosomal miRNAs from keratinocytes as potential regulators of melanogenesis. UVB-irradiated, keratinocyte-derived exosomes were observed to augment melanogenesis in melanocytes, resulting in an upregulation of MITF, TRP1, TRP2, and TYR expression compared to non-UVB-irradiated exosomes. Additionally, a subset of exosomal miRNAs was differentially selected and confirmed to exert both enhancing and inhibitory effects on melanogenesis through functional assays. Notably, hsa-miR-644a, hsa-miR-365b-5p, and hsa-miR-29c-3p were found to upregulate melanogenesis, while hsa-miR-18a-5p, hsa-miR-197-5p, and hsa-miR-4281 downregulated melanogenesis. These findings suggest the involvement of keratinocyte-derived exosomal miRNAs in melanogenesis regulation within melanocytes. The expression levels of exosomal miRNAs from keratinocytes exhibited a UVB-dependent increase, indicating a potential role for these miRNAs as regulators of melanogenesis in response to UVB irradiation. Furthermore, melanogenesis was found to be dependent on exosomes derived from keratinocytes. This underscores the potential of UVB-induced exosomal miRNAs derived from keratinocytes as regulators of melanogenesis. Moreover, this study unveils a significant role for exosomes in melanocyte pigmentation, presenting a novel pathway in the intricate process of melanogenesis. [ABSTRACT FROM AUTHOR]

Background. Vitiligo is a dermatological disorder characterized by the depletion of melanocytes. The key to its treatment lies in the promotion of melanin regeneration. The Wnt/β-catenin signalling pathway assumes a pivotal role in this regenerative process. Fire needle therapy (FNT), a traditional Chinese medical technique, has emerged as a promising intervention. Methods. We analyzed gene expression associated with the Wnt/β-catenin signalling pathway in both normal skin and the lesions of patients with vitiligo in the Gene Expression Omnibus database (GEO database). Furthermore, we evaluated the gene expression of this pathway and assessed the effects of FNT on pigmentation and its influence on the Wnt/β-catenin signalling pathway in a vitiligo mouse model. Results. Compared to that of the normal skin, the mRNA levels of WNT10A, WNT10B, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5B, WNT7B, and LEF1 displayed significant decreases in the lesions of patients with vitiligo. Moreover, vitiligo mouse skin lesions improved following FNT, and the number of melanocytes and melanin levels increased. In addition, posttreatment, genes associated with the Wnt/β-catenin signalling pathway were revealed to be upregulated. Conclusion. FNT may play an important role in promoting pigmentation in vitiligo through modulation of the Wnt/β-catenin signalling pathway. This adds to the growing body of literature supporting the use of FNT to treat vitiligo. This, in turn, may inform clinical practice and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Cutaneous melanoma arises from skin melanocytes and has a high risk of metastatic spread. Despite better prevention, earlier detection, and the development of innovative therapies, melanoma incidence and mortality increase annually. Major clinical risk factors for melanoma include fair skin, an increased number of nevi, the presence of dysplastic nevi, and a family history of melanoma. However, several external inducers seem to be associated with melanoma susceptibility such as environmental exposure, primarily unprotected sun experience, alcohol consumption, and heavy metals. In recent years, epidemiological studies have highlighted a potential risk of β-hexachlorocyclohexane (β-HCH), the most studied organochlorine pesticide, causing cancer induction including melanoma. Methods: We evaluated in vitro the impact of this pollutant on epidermal and dermal cells, attempting to describe mechanisms that could render cutaneous cells more prone to oncogenic transformation. Results: We demonstrated that β-HCH impacts melanocyte biology with a highly cell-type specific signature that involves perturbation of AKT/mTOR and Wnt/β-catenin signaling, and AMPK activation, resulting in lowering energy reserve, cell proliferation, and pigment production. Conclusions: In conclusion, long-term exposure to persistent organic pollutants damages melanocyte metabolism in its function of melanin production with a consequent reduction of melanogenesis indicating a potential augmented skin cancer risk. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The occurrence of vitiligo following COVID‐19 infection and vaccination is well‐documented. The mitochondrial dysfunction of melanocytes in vitiligo and the potential impact of RDV on mitochondria raise concerns about RDV possibly causing vitiligo. [ABSTRACT FROM AUTHOR]

Epidermal melanocytes are continuously exposed to sunlight‐induced reactive oxygen species (ROS) and oxidative stress generated during the synthesis of melanin. Therefore, they have developed mechanisms that maintain normal redox homeostasis. Cytoglobin (CYGB), a ubiquitously expressed intracellular iron hexacoordinated globin, exhibits antioxidant activity and regulates the redox state of mammalian cells through its activities as peroxidase and nitric oxide (NO) dioxygenase. We postulated that CYGB functions in the melanogenic process as a regulator that maintains oxidative stress within a physiological level. This was examined by characterizing normal human melanocytes with the knockdown (KD) of CYGB using morphological and molecular biological criteria. CYGB‐KD cells were larger, had more dendrites, and generated more melanin granules in the advanced stages of melanogenesis than control cells. The expression levels of major melanogenesis‐associated genes and proteins were higher in CYGB‐KD melanocytes than in wild type (WT) cells. As expected, CYGB‐KD melanocytes generated more ROS and NO than WT cells. In conclusion, CYGB physiologically contributes to maintaining redox homeostasis in the melanogenic activity of normal melanocytes by controlling the intracellular levels of ROS and NO. [ABSTRACT FROM AUTHOR]

The human red hair color (RHC) trait is caused by increased pheomelanin (red‐yellow) and reduced eumelanin (black‐brown) pigment in skin and hair due to diminished melanocortin 1 receptor (MC1R) function. In addition, individuals harboring the RHC trait are predisposed to melanoma development. While MC1R variants have been established as causative of RHC and are a well‐defined risk factor for melanoma, it remains unclear mechanistically why decreased MC1R signaling alters pigmentation and increases melanoma susceptibility. Here, we use single‐cell RNA sequencing (scRNA‐seq) of melanocytes isolated from RHC mouse models to define a MC1R‐inhibited Gene Signature (MiGS) comprising a large set of previously unidentified genes which may be implicated in melanogenesis and oncogenic transformation. We show that one of the candidate MiGS genes, TBX3, a well‐known anti‐senescence transcription factor implicated in melanoma progression, binds both E‐box and T‐box elements to regulate genes associated with melanogenesis and senescence bypass. Our results provide key insights into further mechanisms by which melanocytes with reduced MC1R signaling may regulate pigmentation and offer new candidates of study toward understanding how individuals with the RHC phenotype are predisposed to melanoma. [ABSTRACT FROM AUTHOR]

Melanoma is one of the most severe cancers due to its great potential to form metastasis. Recent studies showed the importance of mechanical property assessment in metastasis formation which depends on the cytoskeleton dynamics and cell migration. Although cells are considered purely elastic, they are viscoelastic entities. Microrheology atomic force microscopy (AFM) enables the assessment of elasticity and viscous properties, which are relevant to cell behavior regulation. The current work compares the mechanical properties of human neonatal primary melanocytes (HNPMs) with two melanoma cell lines (WM793B and 1205LU cells), using microrheology AFM. Immunocytochemistry of F-actin filaments and phosphorylated focal adhesion kinase (p-FAK) and cell migration assays were performed to understand the differences found in microrheology AFM regarding the tumor cell lines tested. AFM revealed that HNPMs and tumor cell lines had distinct mechanical properties. HNPMs were softer, less viscous, presenting a higher power-law than melanoma cells. Immunostaining showed that metastatic 1205LU cells expressed more p-FAK than WM793B cells. Melanoma cell migration assays showed that WM73B did not close the gap, in contrast to 1205LU cells, which closed the gap at the end of 23 h. These data seem to corroborate the high migratory behavior of 1205LU cells. Microrheology AFM applied to HNPMs and melanoma cells allowed the quantification of elasticity, viscous properties, glassy phase, and power-law properties, which have an impact in cell migration and metastasis formation. AFM study is important since it can be used as a biomarker of the different stages of the disease in melanoma. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Clobetasol has demonstrated remarkable results in treating melasma within a short time frame; however, its use is limited because of the risk of local side effects. To date, there is no controlled trial on sequential clobetasol/hydroquinone for melasma. This study aimed to investigate the tolerability and efficacy of 0.05% clobetasol followed by 4% hydroquinone (CLOB‐HQ) in comparison to the isolated use of 4% hydroquinone (HQ).A double‐blinded, randomized clinical trial involving 50 women with facial melasma was performed. They were directed to apply 0.05% clobetasol every night for 14 days, followed by 4% hydroquinone for 46 days (CLOB‐HQ group), or the use of hydroquinone for 60 days (HQ group). Evaluations were carried out at inclusion, and after 14 and 60 days of treatment, measuring modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life scale (MELASQoL), and colorimetry. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator.There was no difference in the main outcomes at D14 and D60 (P > 0.1). For CLOB‐HQ, the mean (CI 95%) reduction in mMASI was 13.2% (5.1–21.3%) and 43.1% (32.2–54.0%) at D14 and D60, and for HQ, they were 10.6% (5.9–27.5%) and 44.8% (33.2–52.3%). The MELASQoL, colorimetric luminosity, and GAIS showed a progressive improvement for both groups despite no difference between them. No severe side effects were identified. No cases of telangiectasias, atrophy, or perioral dermatitis were associated with the use of CLOB.The sequential CLOB‐HQ regimen was safe and well tolerated, even though its efficacy was not different from HQ after 14 or 60 days of treatment. Based on these findings, the use of clobetasol 14 days before hydroquinone is not advisable for the treatment of melasma. [ABSTRACT FROM AUTHOR]

Melanosis of the urinary bladder, so-called melanosis vesicae, is a rare condition characterized by dark, velvety bladder mucosa observed by cystoscopy examination. Up to 20 examples have been reported in the English literature, and the etiology of this disease still needs to be discovered. We present an 82-year-old woman with a history of pelvic organ prolapse-associated urinary symptoms. The patient was found to have pigmented urinary bladder mucosa on cystoscopy and underwent a total hysterectomy and bladder mucosal biopsy. Histologically, pigmented granules were evident in the bladder stroma and epithelium, highlighted by Periodic Acid-Schiff (PAS) stain, suggestive of lipofuscin in nature. We outline the diagnostic features of bladder melanosis, discuss the diagnostic mimickers, and thoroughly review the literature on the subject. [ABSTRACT FROM AUTHOR]

Hypertension is known to be a multifactorial disease associated with abnormalities in neuroendocrine, metabolic, and hemodynamic systems. Poorly controlled hypertension causes more than one in eight premature deaths worldwide. Hydrochlorothiazide (HCT) and furosemide (FUR), being first-line drugs in the treatment of hypertension, are among others the most frequently prescribed drugs in the world. Currently, many pharmacoepidemiological data associate the use of these diuretics with an increased risk of adverse phototoxic reactions that may induce the development of melanoma and non-melanoma skin cancers. In this study, the cytotoxic and phototoxic potential of HCT and FUR against skin cells varied by melanin pigment content was assessed for the first time. The results showed that both drugs reduced the number of metabolically active normal skin cells in a dose-dependent manner. UVA irradiation significantly increased the cytotoxicity of HCT towards fibroblasts by approximately 40% and melanocytes by almost 20% compared to unirradiated cells. In the case of skin cells exposed to FUR and UVA radiation, an increase in cytotoxicity by approximately 30% for fibroblasts and 10% for melanocytes was observed. Simultaneous exposure of melanocytes and fibroblasts to HCT or FUR and UVAR caused a decrease in cell viability, and number, which was confirmed by microscopic assessment of morphology. The phototoxic effect of HCT and FUR was associated with the disturbance of redox homeostasis confirming the oxidative stress as a mechanism of phototoxic reaction. UVA-irradiated drugs increased the generation of ROS by 10–150%, and oxidized intracellular thiols. A reduction in mitochondrial potential of almost 80% in melanocytes exposed to HCT and UVAR and 60% in fibroblasts was found due to oxidative stress occurrence. In addition, HCT and FUR have been shown to disrupt the cell cycle of normal skin cells. Finally, it can be concluded that HCT is the drug with a stronger phototoxic effect, and fibroblasts turn out to be more sensitive cells to the phototoxic effect of tested drugs. [ABSTRACT FROM AUTHOR]

Melanocytes in the skin and other organs generate the tumor known as malignant melanoma (MM). It has a high degree of malignancy, a deprived prognosis, and a propensity for local recurrence and distant metastasis. Although there have been tremendous advancements in MM management choices over the past ten years, there are still a dearth of clinically viable therapy alternatives and no internationally accepted treatment standard. The prognosis of MM patients has recently improved thanks to the development of immunotherapy and targeted therapy. As a result, this article examines the most recent findings from studies on the non-surgical treatment methodologies for MM and its preventive measures. [ABSTRACT FROM AUTHOR]

Objective: To develop and evaluate the efficacy of WS Biotin, a novel water‐soluble form of D‐Biotin, for cosmetic use. Methods: A new encapsulated form of D‐Biotin was developed with the purpose of improving the water solubility of biotin. This novel form of encapsulated biotin was characterized by its physicochemical properties: particle size, D‐Biotin content and solubility in water. Also, proliferation and gene expression in vitro tests in cell culture were performed to evaluate its effectiveness in promoting hair growth, an ELISA test was conducted for hair keratinization and skin lightening property was tested by analysing the intracellular melanin content. Results: The developed WS Biotin microcapsules exhibit a particle size range of 2–30 μm with D‐Biotin content of ~50% (w/w). The water solubility of WS Biotin was found to be 20‐fold greater than free biotin. The obtained in vitro results indicated that WS Biotin enhances the expression of hair‐related keratins in hair follicle keratinocytes, as well as the expression of hair growth‐promoting genes in dermal papilla cells. Moreover, the melanin content in UVA‐exposed epidermal melanocytes was reduced upon exposure to WS Biotin. Conclusion: In this work, a novel form of encapsulated biotin, WS Biotin, was developed in order to improve the water solubility of free biotin and was found to be effective for cosmetic use in both hair and skin applications. [ABSTRACT FROM AUTHOR]

Background: Paclitaxel (PTX) is a microtubule‐stabilizing antineoplastic that has been shown to damage healthy tissues like the skin. Hyperpigmentation can be found among the adverse effects caused by PTX, but the literature is limited and the mechanisms driving PTX‐induced pigmentary alterations are unknown. Objectives: This study aimed to describe the pigmentary alterations caused by PTX and to determine the effects of PTX on melanocytes. Methods: Pigmentary skin alterations were measured in 20 gynecological cancer patients under PTX treatment by using specific probes, which determine the melanin index and the pigmentation level. Melanocytes were incubated with paclitaxel to analyze melanogenesis markers gene expression, melanin content, and transcription factors activation. Results: Paclitaxel induced alterations in the skin pigmentation with no visible clinical manifestations. Gynecological cancer patients under paclitaxel treatment had an increase in the melanin index and pigmentation levels. In vitro, PTX exposure to melanocytes increased the expression of melanogenesis markers, melanin content, and induced activation of ERK and MITF. Conclusions: The results suggest that PTX alters pigmentation in patients with no clinically visible manifestations, and these alterations might be driven by its capacity to stimulate melanogenesis on melanocytes through the MITF activation pathway. [ABSTRACT FROM AUTHOR]

The pathogenesis of dyschromatosis symmetrica hereditaria (DSH) has not been well defined. In this study, we sought to investigate the influence of the ADAR1 gene on DSH both in vitro and in vivo. Morpholino knockdown of adar1 in zebrafish produced phenotypes characterized by polarity changes, and abnormal migration and distribution of melanocytes. Differential expression of C‐KIT and distinct patterns of apoptosis between hyperpigmented and hypopigmented areas in DSH patient were detected by means of immunohistochemical methods and TUNEL assays, respectively. This study revealed that adar1 knockdown in a zebrafish model resulted in abnormal migration and changes in the cell polarity of melanocytes, and provided novel insight into the mechanism of DSH pathogenesis. [ABSTRACT FROM AUTHOR]

Cochlear melanocytes are intermediate cells in the stria vascularis that generate endocochlear potentials required for auditory function. Human PAX3 mutations cause Waardenburg syndrome and abnormalities of skin and retinal melanocytes, manifested as congenital hearing loss (~ 70%) and hypopigmentation of skin, hair and eyes. However, the underlying mechanism of hearing loss remains unclear. Cochlear melanocytes in the stria vascularis originated from Pax3-traced melanoblasts and Plp1-traced Schwann cell precursors, both of which derive from neural crest cells. Here, using a Pax3-Cre knock-in mouse that allows lineage tracing of Pax3-expressing cells and disruption of Pax3, we found that Pax3 deficiency causes foreshortened cochlea, malformed vestibular apparatus, and neural tube defects. Lineage tracing and in situ hybridization show that Pax3+ derivatives contribute to S100+, Kir4.1+ and Dct+ melanocytes (intermediate cells) in the developing stria vascularis, all of which are significantly diminished in Pax3 mutant animals. Taken together, these results suggest that Pax3 is required for the development of neural crest cell-derived cochlear melanocytes, whose absence may contribute to congenital hearing loss of Waardenburg syndrome in humans. [ABSTRACT FROM AUTHOR]

Depigmenting products are increasingly used to counteract skin hyperpigmentation and related psychosocial issues. This study aimed to compare different depigmenting agents—4-butylresorcinol; bakuchiol; tranexamic acid; ascorbyl glucoside; α-arbutin; and ascorbic acid—for photoreactivity; tyrosinase inhibition; and safety. Photoreactivity was assessed using the Reactive Oxygen Species assay. In vitro tyrosinase inhibition was compared, and cell viability was assessed in B-16V melanocytes to evaluate safety. Results showed 4-butylresorcinol, ascorbyl glucoside, and α-arbutin are non-photoreactive, while for ascorbic acid and bakuchiol it was not possible to reach conclusive results due to the lack of specificity of the ROS assay. 4-Butylresorcinol, acting as a competitive inhibitor, displayed potent tyrosinase inhibition, followed by ascorbic acid and bakuchiol. Both 4-butylresorcinol and bakuchiol reduced cell viability in a concentration-dependent manner. The insights obtained in this work support the development of depigmenting products by providing useful scientific guidance on the photostability, tyrosinase inhibitory efficacy, and skin safety of depigmenting agents. [ABSTRACT FROM AUTHOR]

Modeling metastasis in animal systems has been an important focus for developing cancer therapeutics. Xenopus laevis is a well‐established model, known for its use in identifying genetic mechanisms underlying diseases and disorders in humans. Prior literature has suggested that the drug, ivermectin, can be used in Xenopus to induce melanocytes to convert into a metastatic melanoma‐like state, and thus could be ideal for testing possible melanoma therapies in vivo. However, there are notable inconsistencies between ivermectin studies in Xenopus and the application of ivermectin in mammalian systems, that are relevant to cancer and melanoma research. In this review, we examine the ivermectin‐induced phenotypes in Xenopus, and we explore the current uses of ivermectin in human research. We conclude that while ivermectin may be a useful drug for many biomedical purposes, it is not ideal to induce a metastatic melanocyte phenotype in Xenopus for testing the effects of potential melanoma therapeutics. [ABSTRACT FROM AUTHOR]

GM1 gangliosidosis is an autosomal recessive hereditary disease resulting from deficiency of the enzyme β-galactosidase, which leads to massive accumulation of GM1 gangliosides in various tissues. Dermal melanocytosis is the persistence of dendritic melanocytes in the dermis: usually present as a Mongolian spot in the sacral region, it tends to spontaneously regress. A very extensive dermal melanocytosis both in the dorsal and ventral region and in the limbs, persistent and with an extensive tendency, is sometimes associated with gangliosidosis and can be a revealing sign of the disease. We describe the case of a 7-month-old girl in whom extensive dermal melanocytosis led to the early diagnosis of GM1 gangliosidosis. [ABSTRACT FROM AUTHOR]

Vitiligo is characterized by the development of white patches on the skin either due to the loss of functional melanocytes or perturbations in themelanogenesis pathway. In the present study, we investigated the therapeutic potential of herbo-mineral formulation, Melanogrit in neutralizing the white patches in the skin. The study utilized UPLC/MS-QToF technique to determine the diversified phytochemical profile inMelanogrit. Themurine B16F10 cells when treated with Melanogrit underwent morphological changes, including increased angularity, enlarged cell size, and greater dendritic protrusions. To establish an equivalent model to study melanogenesis, we carefully optimized the dosage of α-melanocyte stimulating hormone (αMSH) in B16F10 cells as an alternative to using melanocyte-keratinocyte cocultures. The study determined a sub-optimal dose of αMSH (0.2 nM) in B16F10 cells that does not manifest any measurable effects on melanogenesis. In contrast, Melanogrit when used in conjunction with 0.2 nM αMSH, induced a dose-dependent increase in extracellular and intracellular melanin levels. Melanogrit transcriptionally up-regulated the decisive genes of the melanogenesis pathway, MITF, TYR, and TRP1, which was evident from the increased cellular tyrosine activity. Our findings also demonstrated that Melanogrit ameliorated the MITF protein levels by inhibiting pERK; notably without involving GSK3β in the process. Taken together, our findings strongly suggest that Melanogrit has the potential to stimulate melanogenesis, making it a promising candidate for clinical applications in the treatment of white skin patches that develop in vitiligo patients. [ABSTRACT FROM AUTHOR]

Melanoma is a malignant tumor transforming from normal melanocytes, with strong invasion and low survival rate. Nitidine chloride (NC) is a natural benzophenidine alkaloid extracted from the roots of traditional Chinese medicine zanthoxylum nitidum. In recent years, many studies have found that NC may have strong anti-tumor activity. However, the efficacy of NC against melanoma has rarely been reported, and the potential molecular mechanism remains unknown. Our study explored the effects of NC on the proliferation and apoptosis of human melanoma A375 and A2058 cells. CCK-8 was utilized to detect the effects of different concentrations of NC on the proliferation of A375 and A2058 cells. Within a certain concentration and time range, NC can inhibit the viability of A375 and A2058 cells significantly in a time-dose-dependent manner. In addition, NC-induced apoptosis was confirmed by DAPI staining and flow cytometry analysis of Annexin V-FITC/PI. Moreover, we observed that the ratio of Bax/Bcl-2 in the cytoplasm increases, activating Caspase-3/-9 and ultimately inducing apoptosis via the mitochondrial pathway. Our study indicated that NC has anti-tumor properties against human melanoma cells through inhibiting proliferation and inducing apoptosis. Therefore, the results provide new insights for future work on the utilization of NC in malignant melanoma treatment. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is an acquired disease characterized by progressive skin depigmentation resulting from an autoimmune response targeting epidermal melanocytes. Few studies have shown specific cytotoxic T-lymphocyte response against Melan -- A which is the most specific marker of melanocytes. There are also other studies which have confirmed the presence of residual melanocytes even in the vitiliginous skin. Objectives: To evaluate the melanocyte content in lesional, perilesional [within 2 cm] and distant normal skin of non- segmental vitiligo patients. Materials and Methods: A total of 40 cases of non-segmental were enrolled in the study based on the prevelance of vitiligo in India. After taking informed consent, skin biopsy from the lesional, perilesional and normal skin was sent to pathology for immunohistochemical analysis of melanocyte content in the above zones using Melan -- A marker. Results: All 40 lesional sites were negative for Melan-A staining. The Melan-A positive melanocytes were reduced in immediate perilesional skin compared to distant normal skin. Paired t-test was applied between perilesional skin and normal skin and the result was statistically significant at p<0.001. Conclusion: Melan-A positive residual melanocytes were not present in the lesional skin in our study as opposed to very few studies which confirmed their presence in the vitiliginous skin even in the long standing cases. But there was significant difference between perilesional and normal skin. [ABSTRACT FROM AUTHOR]

Waardenburg Syndrome (WS) is a rare genetic disorder that leads to congenital hearing loss and pigmentation defects. Microphthalmia‐associated transcription factor (MITF) is one of its significant pathogenic genes. Despite the comprehensive investigation in animal models, the pathogenic mechanism is still poorly described in humans due to difficulties accessing embryonic tissues. In this work, we used induced pluripotent stem cells derived from a WS patient carrying a heterozygous mutation in the MITF gene c.626A>T (p.His209Leu), and differentiated toward melanocyte lineage, which is the most affected cell type involved in WS. Compared with the wild‐type cell line, the MITFmut cell line showed a reduced expression of the characteristic melanocyte‐related genes and a lesser proportion of mature, fully pigmented melanosomes. The transcriptome analysis also revealed widespread gene expression changes at the melanocyte stage in the MITFmut cell line. The differentially expressed genes were enriched in melanogenesis and cell proliferation‐related pathways. Interestingly, ion transport‐related genes also showed a significant difference in MITFmut‐induced melanocytes, indicating that the MITF mutant may lead to the dysfunction of potassium channels and transporters produced by intermediate cells in the cochlea, further causing the associated phenotype of deafness. Altogether, our study provides valuable insights into how MITF mutation affects WS patients, which might result in defective melanocyte development and the related phenotype based on the patient‐derived iPSC model. [ABSTRACT FROM AUTHOR]

Background: Melanocytes disappearing from the skin as a result of a mechanism that is still unknown is the defining feature of vitiligo. Because vitiligo targets melanocytes throughout the body, not only those in the skin, the existence of melanocytes in the auditory and vestibular systems raises the possibility that these systems to be affected. There are some discrepancies in the research regarding how vitiligo affects hearing and vestibular systems. Accordingly, this study was conducted to evaluate audiological and vestibular involvement in vitiligo patients. Subjects and methods: A casecontrol study with 19 vitiligo patients and 19 healthy controls was conducted. Basic audiological and vestibular examination were performed on all patients and healthy controls including videonystagmography (VNG), cervical vestibular-evoked myogenic potential (cVEMP), and ocular vestibularevoked myogenic potential (oVEMP). Results: There was a statistically significant difference were found in pure tone audiogram thresholds at 2,4, 8 KHz frequencies, caloric test, cVEMP and oVEMP parameters, between the vitiligo and the control groups. Conclusion: The study concluded that 78.9% of individuals with vitiligo experienced peripheral and/or central vestibular abnormalities, along with/without auditory impairment. [ABSTRACT FROM AUTHOR]

The study investigated the effectiveness of EDN1 and EDN3 cytokines in the differentiation of melanocytes from hESCs. The findings showed that 100 nM EDN1 was more effective in promoting hESC to CD117+/TYR+ melanoblasts compared to 100 nM EDN3. Additionally, maintaining melanoblasts is beneficial for preserving the ability to proliferate. The study found that 10 nM EDN1 helped maintain the proliferation of melanoblasts without over maturing them into melanocytes in the late stage of differentiation. Thus, using 100 nM EDN1 in the initial stage and 10 nM EDN1 in the late stage proved to be an efficient and cost‐effective method for obtaining hESC‐derived melanocytes. The preliminary results suggest that EDN1 promotes melanoblast formation during the initial differentiation stage through its binding to both the EDNRB receptor and EDNRA receptor. This study provides a valuable tool for studying the development of human melanocytes and modelling the biology of disease. [ABSTRACT FROM AUTHOR]