High charge of cerebroid nests in nodular melanomas predicts tumor aggressiveness and high mutational tumoral burden: a pilot study.

Purpose: Even today, melanoma is a highly aggressive neoplasm with a high mortality rate. The nodular type is very aggressive and has cerebroid nests of melanocytes (CNMs) at the growth edge, morphologically similar to the poorly differentiated neoplastic epithelial cell clusters described in colorectal, breast, and endometrioid endometrial cancers. Patients and methods: We selected 25 nodular melanomas (NMs) with known molecular profiles, of which the entire paraffin-embedded lesion was available. We counted CNMs under a microscopic at a magnification of 20x (i.e., a microscopic field with a major axis of 1 mm). Based on the number of CNMs in the area, melanomas were classified into three groups: G1 (CNMs ranging from 0 to 4), G2 (CNMs ranging from 5 to 9), and G3 (CNMs ≥ 10). The presence of CNMs and their counts were compared with molecular and histopathological data. Results: Seventeen (NMs) were grouped as G1 (68%), 5 as G2 (20%), and 3 as G3 (12%) based on CNMs count. The presence of CNMs correlated with epithelioid cell morphology (p < 0.05), Clark IV and V levels (p < 0.05), vascular invasion (p < 0.05), and biological mutants (p < 0.05). Melanomas with ≥ 10 CNMs more frequently show ulceration (p < 0.02) and the BRAF V600E mutation (p < 0.02). Conclusion: CNMs count has a predictive role regardless of tumor size; their association with the BRAF V600E mutation suggests their predictive significance in response to biologics. However, further investigations are needed to strengthen this hypothesis.

Melanocyte lineage dynamics in development, growth and disease.

Melanocytes evolved to produce the melanin that gives colour to our hair, eyes and skin. The melanocyte lineage also gives rise to melanoma, the most lethal form of skin cancer. The melanocyte lineage differentiates from neural crest cells during development, and most melanocytes reside in the skin and hair, where they are replenished by melanocyte stem cells. Because the molecular mechanisms necessary for melanocyte specification, migration, proliferation and differentiation are co-opted during melanoma initiation and progression, studying melanocyte development is directly relevant to human disease. Here, through the lens of advances in cellular omic and genomic technologies, we review the latest findings in melanocyte development and differentiation, and how these developmental pathways become dysregulated in disease.

The Effect of Fractional Carbon Dioxide Laser on Melanogenesis in Human Melanocytes and Vitiligo Mouse Models.

Introduction: Vitiligo is an acquired skin pigmentation disorder, the cause of which is poorly understood. Researchers in this field are dedicated to exploring novel treatments for achieving re-pigmentation. Methods: Mice were randomly selected and divided into control, model, and model+laser groups. Evaluate the impact of different levels of carbon dioxide laser irradiation on tyrosinase activity, melanocyte viability, and melanin content. Results: In this study, it was found that the cell viability and melanin content were significantly enhanced in human melanocytes after treatment with different energy densities of fractional carbon dioxide laser. In addition, laser-treated vitiligo mouse models showed mild pathological changes. Discussion: Therefore, we believe that fractional carbon dioxide laser may be a potential adjunctive modality for treating vitiligo.

Establishment of Primary Cell Cultures from Canine Oral Melanomas via Fine-Needle Aspiration: A Novel Tool for Tumorigenesis and Cancer Progression Studies.

Oral melanomas are the most common oral malignancies in dogs and are characterized by an aggressive nature, invasiveness, and poor prognosis. With biological and genetic similarities to human oral melanomas, they serve as a valuable spontaneous comparative model. Primary cell cultures are widely used in human medicine and, more recently, in veterinary medicine to study tumorigenesis, cancer progression, and innovative therapeutic approaches. This study aims to establish two- and three-dimensional primary cell lines from oral canine melanomas using fine-needle aspiration as a minimally invasive sampling method. For this study, samples were collected from six dogs, represented by four primary oral melanomas and five lymph nodal metastases. The cells were digested to obtain single-cell suspensions, seeded in flasks, or processed with Matrigel® to form organoids. The cell cultures were characterized through flow cytometry using antibodies against Melan-A, PNL2, and Sox-10. This technique offers a minimally invasive means to obtain cell samples, particularly beneficial for patients that are ineligible for surgical procedures, and enables the establishment of in vitro models crucial for comparative studies in mucosal melanoma oncology. To the best of our knowledge, this is the first work establishing neoplastic primary cell cultures via fine-needle aspiration in dogs.

The Role of PGC-1α in Aging Skin Barrier Function.

Skin provides a physical and immune barrier to protect the body from foreign substances, microbial invasion, and desiccation. Aging reduces the barrier function of skin and its rate of repair. Aged skin exhibits decreased mitochondrial function and prolonged low-level inflammation that can be seen in other organs with aging. Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), an important transcriptional coactivator, plays a central role in modulating mitochondrial function and antioxidant production. Mitochondrial function and inflammation have been linked to epidermal function, but the mechanisms are unclear. The aim of this review is to discuss the mechanisms by which PGC-1α might exert a positive effect on aged skin barrier function. Initially, we provide an overview of the function of skin under physiological and aging conditions, focusing on the epidermis. We then discuss mitochondrial function, oxidative stress, cellular senescence, and inflamm-aging, the chronic low-level inflammation observed in aging individuals. Finally, we discuss the effects of PGC-1α on mitochondrial function, as well as the regulation and role of PGC-1α in the aging epidermis.

Exosomes Derived from Hypertrophic Scar Fibroblasts Suppress Melanogenesis in Normal Human Epidermal Melanocytes.

Post-burn hypertrophic scars often exhibit abnormal pigmentation. Exosomes play important roles in maintaining normal physiological homeostasis and in the pathological development of diseases. This study investigated the effects of the exosomes derived from hypertrophic scar fibroblasts (HTSFs) on melanocytes, which are pigment-producing cells. Normal fibroblasts (NFs) and HTSFs were isolated and cultured from normal skin and hypertrophic scar (HTS) tissue. Both the NF- and HTSF-exosomes were isolated from a cell culture medium and purified using a column-based technique. The normal human epidermal melanocytes were treated with both exosomes at a concentration of 100 µg/mL at different times. The cell proliferation, melanin content in the medium, apoptotic factors, transcription factors, melanin synthesis enzymes, signaling, signal transduction pathways, and activators of transcription factors (STAT) 1, 3, 5, and 6 were investigated. Compared with the Dulbecco's phosphate-buffered saline (DPBS)-treated controls and NF-exosomes, the HTSF-exosomes decreased the melanocyte proliferation and melanin secretion. The molecular patterns of apoptosis, proliferation, melanin synthesis, Smad and non-Smad signaling, and STATs were altered by the treatment with the HTSF-exosomes. No significant differences were observed between the DPBS-treated control and NF-exosome-treated cells. HTSF-derived exosomes may play a role in the pathological epidermal hypopigmentation observed in patients with HTS.

Up-and-Coming Drugs for the Treatment of Vitiligo.

Vitiligo is a chronic autoimmune disease that causes depigmented patches on the skin. It affects 0.5%-2.0% of the global population. It goes beyond physical appearance, often leading to stigmatization, low self-esteem, and depression, burdening patients with psychosocial challenges. The pathogenesis of vitiligo involves the loss of melanocytes due to autoreactive CD8+ T cells, triggered by environmental stressors and exacerbated by cellular vulnerabilities and immune responses. The release of danger signals and pro-inflammatory factors initiates an immune cascade perpetuating melanocyte destruction, mainly driven by interferon-γ and the C-X-C motif chemokine ligand 9/10-chemokine receptor 3 axis. Long-lasting tissue-resident memory T cells (Trms) and cytokines contribute to lesion persistence. Current treatments focus on topical steroids and tacrolimus, systemic steroids, and phototherapies, but their efficacy remains suboptimal, necessitating the development of new therapeutic options. Building on recent advancements in understanding the immunological mechanisms in vitiligo pathogenesis, with the initiation of Food and Drug Administration approval of topical ruxolitinib, various potential treatment options such as JAK inhibitors, cytokine blockers, and Trm or regulatory T cell targeting agents are being clinically researched and anticipated for vitiligo based on both preclinical and clinical data. This review aims to categorize and summarize the diverse investigational drugs currently undergoing clinical trials for vitiligo. By examining clinical outcomes, it is anticipated that this review will bring hope to dermatologists and patients regarding vitiligo, a condition that has historically posed challenges and transform it into a realm of potential possibilities.

Analysis of granulysin expression in vitiligo and halo-nevus.

Vitiligo and halo nevus are immune-mediated skin diseases that have a similar pathogenesis and involve cellular cytotoxicity mechanisms that are not yet fully understood. In this study, we investigated the expression patterns of the cytolytic molecule granulysin (GNLY) in different cytotoxic cells in skin samples of vitiligo and halo nevus. Skin biopsies were taken from perilesional and lesional skin of ten vitiligo patients, eight patients with halo nevus and ten healthy controls. We analysed the expression of GNLY by immunohistochemistry in CD8+ and CD56+ NK cells. A significantly higher accumulation of GNLY+, CD8+ GNLY+ and fewer CD56+ GNLY+ cells was found in the lesional skin of vitiligo and halo nevus than in the healthy skin. These cells were localised in the basal epidermis and papillary dermis, suggesting that GNLY may be involved in the immune response against melanocytes. Similarly, but to a lesser extent, upregulation of GNLY+ and CD8+ GNLY+ cells was observed in the perilesional skin of vitiligo and halo nevus compared to healthy controls. In this study, we demonstrated for the first time an increased expression of CD8+ GNLY+ T lymphocytes and CD56+ GNLY+ NK cells in lesions of vitiligo and halo nevus, indicating the role of GNLY in the pathogenesis of both diseases.

Transcriptome-wide profiling for melanocytes derived from newborn and adult human epidermis with enhanced proliferation.

The senescence-associated protein p16INK4A acts as a limiter element in cell-cycle progression. The loss of p16INK4A function is causally related to cellular immortalization. The increase in p16INK4A levels with advancing age was demonstrated in melanocytes. However, the characteristic difference between young and senescent melanocytes affecting immortalization of melanocytes remains unclear. In this study, we generated 10 different cell lines in total from newborn (NB) and adult (AD) primary normal human epidermal melanocytes (NHEM) using four different methods, transduction of CDK4R24C and cyclin D1 (K4D), K4D with TERT (K4DT), SV40 T-antigen (SV40T), and HPV16 E6 and E7 (E6/E7) and performed whole transcriptome sequencing analysis (RNA-Seq) to elucidate the differences of genome-wide expression profiles among cell lines. The analysis data revealed distinct differences in expression pattern between cell lines from NB and AD although no distinct biological differences were detected in analyses such as comparison of cell morphology, evaluation of cell proliferation, and cell cycle profiles. This study may provide useful in vitro models to benefit the understanding of skin-related diseases.

Revealing the UV response of melanocytes in xeroderma pigmentosum group A using patient-derived induced pluripotent stem cells.

BACKGROUND: Xeroderma pigmentosum (XP) is characterized by photosensitivity that causes pigmentary disorder and predisposition to skin cancers on sunlight-exposed areas due to DNA repair deficiency. Patients with XP group A (XP-A) develop freckle-like pigmented maculae and depigmented maculae within a year unless strict sun-protection is enforced. Although it is crucial to study pigment cells (melanocytes: MCs) as disease target cells, establishing MCs in primary cultures is challenging. OBJECTIVE: Elucidation of the disease pathogenesis by comparison between MCs differentiated from XP-A induced pluripotent stem cells (iPSCs) and healthy control iPSCs on the response to UV irradiation. METHODS: iPSCs were established from a XP-A fibroblasts and differentiated into MCs. Differences in gene expression profiles between XP-A-iPSC-derived melanocytes (XP-A-iMCs) and Healthy control iPSC-derived MCs (HC-iMCs) were analyzed 4 and 12 h after irradiation with 30 or 150 J/m2 of UV-B using microarray analysis. RESULTS: XP-A-iMCs expressed SOX10, MITF, and TYR, and showed melanin synthesis. Further, XP-A-iMCs showed reduced DNA repair ability. Gene expression profile between XP-A-iMCs and HC-iMCs revealed that, numerous gene probes that were specifically upregulated or downregulated in XP-A-iMCs after 150-J/m2 of UV-B irradiation did not return to basal levels. Of note that apoptotic pathways were highly upregulated at 150 J/m2 UV exposure in XP-A-iMCs, and cytokine-related pathways were upregulated even at 30 J/m2 UV exposure. CONCLUSION: We revealed for the first time that cytokine-related pathways were upregulated even at low-dose UV exposure in XP-A-iMCs. Disease-specific iPSCs are useful to elucidate the disease pathogenesis and develop treatment strategies of XP.

Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis.

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.

Target area treatment ratio of varied lesions in the cultured pure melanocyte transplantation repigmentation of vitiligo: A retrospective study.

Autologous cultured pure melanocyte transplantation (CMT) can be utilized to treat stable vitiligo cases, but clinical data are insufficient to improve its efficacy. To evaluate the influence of various factors on the therapeutic effect of CMT, this single-center retrospective study enrolled stable vitiligo patients who underwent CMT between 2009 and 2020. Univariate and multivariable analysis were used to determine the factors affecting the outcome of repigmentation. The study included 491 patients with long-term follow-up data (6-120 months). It was found that 69.7% of patients achieved an excellent re-color effect and 18.4% achieved a good re-color effect. There were statistically significant differences in pigmentation between patients with stable disease course, vitiligo type, and lesion site. Overall, a significant positive correlation between the target area treatment ratio of varied lesions and the percentage of repigmentation was found. CMT is effective and well tolerated in the treatment of stable vitiligo. Various factors, especially the target area treatment ratio of varied lesions, should be carefully assessed before using CMT. As the target area treatment ratio of varied lesions could further improve the post-operative repigmentation other than type of vitiligo. This clinic trial was approved by Hangzhou Third People's Hospital (number 2023KA015, national clinical record number MR-33-23-034502).

Comparative evaluation of six commercial adult toothpaste formulations reveals cytotoxicity and altered functions in a human oral melanocyte model: an in vitro study.

This study aims to compare six commercial adult toothpaste (labeled as A, B, C, D, E, and F) for cytotoxicity and melanocyte function alterations in vitro using primary human epidermal melanocytes from a Caucasian donor (HEMn-LP cells) as a model of oral melanocytes. Cells were incubated with toothpaste extracts (50% w/v) in culture media at dilutions (1:25, 1:50, 1:100, 1:200, 1:500, 1:800, and 1:1000) for 24 h. MTS and LDH assays were used to assess cytotoxicity. The effects of noncytotoxic toothpaste concentrations on melanocyte functional endpoints were then examined using spectrophotometric methods. All toothpaste showed concentration-dependent cytotoxicity that was heterogeneous across toothpaste containing SLS detergent. IC50 values of cytotoxicity followed the order: A = E > C > B > D > F. To compare toothpaste, they were tested at 1:800 and 1:1000 dilutions that were noncytotoxic after 24 h. None of the toothpaste affected cellular melanin production. However, toothpaste A, C, and D suppressed tyrosinase activity at both dilutions, while toothpaste B suppressed tyrosinase activity only at 1:800 dilution. Toothpaste A, C, E, and F elevated ROS production at 1:800 dilution, with no change at 1:1000 dilution. Toothpaste has a heterogeneous effect on melanocytes. Toothpaste B, E, and F at 1:1000 dilution were the safest as they did not alter melanocyte functions at this dilution, although toothpaste F is the least cytotoxic of these. Future studies are necessary to expand these results in a physiological environment of oral tissue. The findings of this study provide novel insight into the biocompatibility studies of toothpaste on oral melanocytes. They can aid dental practitioners and consumers in selecting noncytotoxic toothpaste that do not contribute to ROS generation by melanocytes in the oral cavity or lead to cytotoxicity and impaired cellular function.

α-Chitosan and ß-Oligochitosan Mixtures-Based Formula for In Vitro Assessment of Melanocyte Cells Response.

Chitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma, and indicates that these molecules can open new perspectives on antiproliferative action and anticancer therapy. This study analyzes how different chitosan conformations, such as α-chitosan (CH) or ß-oligochitosan (CO), with various degrees of deacetylation (DDA) and molar mass (MM), both in different concentrations and in CH-CO mixtures, influence the cellular processes of SK-MEL-28 melanocytes, to estimate the reactivity of these cells to the applied treatments. The in vitro evaluation was carried out, aiming at the cellular metabolism (MTT assay), cellular morphology, and chitinase-like glycoprotein YKL-40 expression. The in vitro effect of the CH-CO mixture application on melanocytes is obvious at low concentrations of α-chitosan/ß-oligochitosan (1:2 ratio), with the cell's response supporting the hypothesis that ß-oligo-chitosan amplifies the effect. This oligochitosan mixture, favored by the ß conformation and its small size, penetrates faster into the cells, being more reactive when interacting with some cellular components. Morphological effects expressed by the loss of cell adhesion and the depletion of YKL-40 synthesis are significant responses of melanocytes. ß-oligochitosan (1.5 kDa) induces an extension of cytophysiological effects and limits the cell viability compared to α-chitosan (400-900 kDa). Statistical analysis using multivariate techniques showed differences between the CH samples and CH-CO mixtures.

Mucosal Melanoma of Palate: A Case Report with Review of Literature.

The World Health Organisation defines mucosal malignant melanoma as a malignant tumour of melanocytes or of melanocyte progenitors. Due to the lack of symptoms and unknown etiology, mucosal malignant melanoma may go undiagnosed. The surgeon can find it challenging to come up with a definitive treatment strategy because of its rarity and rapid spread. In this case study, a 57-year-old female patient with hyperpigmented gingiva and palate diagnosed pathologically and immunohistochemically as malignant melanoma underwent surgical excision and a modified radical neck dissection.

Molecular Pathways Regulating Circadian Rhythm and Associated Diseases.

Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. Light plays an important role in the regulation of circadian rhythm in human body. When light from the outside enters the eyes, cones, rods, and specialized retinal ganglion cells receive the light signal and transmit it to the suprachiasmatic nucleus of the hypothalamus. The central rhythm oscillator of the suprachiasmatic nucleus regulates the rhythm oscillator of tissues all over the body. Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. As the largest organ in the human body, skin plays an important role in the peripheral circadian rhythm regulation system. Like photoreceptor cells in the retina, melanocytes express opsins. Studies show that melanocytes in the skin are also sensitive to light, allowing the skin to "see" light even without the eyes. Upon receiving light signals, melanocytes in the skin release hormones that maintain homeostasis. This process is called "photoneuroendocrinology", which supports the health effects of light exposure. However, inappropriate light exposure, such as prolonged work in dark environments or exposure to artificial light at night, can disrupt circadian rhythms. Such disruptions are linked to a variety of health issues, emphasizing the need for proper light management in daily life. Conversely, harnessing light's beneficial effects through phototherapy is gaining attention as an adjunctive treatment modality. Despite these advancements, the field of circadian rhythm research still faces several unresolved issues and emerging challenges. One of the most exciting prospects is the use of the skin's photosensitivity to treat diseases. This approach could revolutionize how we think about and manage various health conditions, leveraging the skin's unique ability to respond to light for therapeutic purposes. As research continues to unravel the complexities of circadian rhythms and their impact on health, the potential for innovative treatments and improved wellbeing is immense.

A Nude Mouse Model of Xenografted Hypertrophic Scar Cells to Test Therapeutics in the Skin.

BACKGROUND: Existing animal models for testing therapeutics in the skin are limited. Mouse and rat models lack similarity to human skin in structure and wound healing mechanism. Pigs are regarded as the best model with regards to similarity to human skin; however, these studies are expensive, time-consuming, and only small numbers of biologic replicates can be obtained. In addition, local-regional effects of treating wounds that are closely adjacent to one-another with different treatments make assessment of treatment effectiveness difficult in pig models. Therefore, here, a novel nude mouse model of xenografted porcine hypertrophic scar (HTS) cells was developed. This model system was developed to test if supplying hypo-pigmented cells with exogenous alpha melanocyte stimulating hormone (α-MSH) will reverse pigment loss in vivo. METHODS: Dyschromic HTSs were created in red Duroc pigs. Epidermal scar cells (keratinocytes and melanocytes) were derived from regions of hyper-, hypo-, or normally pigmented scar or skin and were cryopreserved. Dermal fibroblasts (DFs) were isolated separately. Excisional wounds were created on nude mice and a grafting dome was placed. DFs were seeded on day 0 and formed a dermis. On day 3, epidermal cells were seeded onto the dermis. The grafting dome was removed on day 7 and hypo-pigmented xenografts were treated with synthetic α-MSH delivered with microneedling. On day 10, the xenografts were excised and saved. Sections were stained using hematoxylin and eosin hematoxylin and eosin (H&E) to assess xenograft structure. RNA was isolated and quantitative real-time polymerase chain reaction (qRT-PCR) was performed for melanogenesis-related genes TYR, TYRP1, and DCT. RESULTS: The seeding of HTSDFs formed a dermis that is similar in structure and cellularity to HTS dermis from the porcine model. When hyper-, hypo-, and normally-pigmented epidermal cells were seeded, a fully stratified epithelium was formed by day 14. H&E staining and measurement of the epidermis showed the average thickness to be 0.11 ± 0.07 µm vs. 0.06 ± 0.03 µm in normal pig skin. Hypo-pigmented xenografts that were treated with synthetic α-MSH showed increases in pigmentation and had increased gene expression of TYR, TYRP1, and DCT compared to untreated controls (TYR: 2.7 ± 1.1 vs. 0.3 ± 1.1; TYRP1: 2.6 ± 0.6 vs. 0.3 ± 0.7; DCT 0.7 ± 0.9 vs. 0.3 ± 1-fold change from control; n = 3). CONCLUSIONS: The developed nude mouse skin xenograft model can be used to study treatments for the skin. The cells that can be xenografted can be derived from patient samples or from pig samples and form a robust dual-skin layer containing epidermis and dermis that is responsive to treatment. Specifically, we found that hypo-pigmented regions of scar can be stimulated to make melanin by synthetic α-MSH in vivo.

Exploring the Influence of Cold Plasma on Epidermal Melanogenesis In Situ and In Vitro.

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.

Unveiling the Potential of Ultrasonic-Assisted Ethanol Extract from Sargassum horneri in Inhibiting Tyrosinase Activity and Melanin Production in B16F10 Murine Melanocytes.

BACKGROUNDS: Melanogenesis, regulated by genetic, hormonal, and environmental factors, occurs in melanocytes in the basal layer of the epidermis. Dysregulation of this process can lead to various skin disorders, such as hyperpigmentation and hypopigmentation. Therefore, the present study investigated the effect of ultrasonic-assisted ethanol extract (SHUE) from Sargassum horneri (S. horneri), brown seaweed against melanogenesis in α-melanocyte-stimulating hormone (MSH)-stimulated B16F10 murine melanocytes. METHODS: Firstly, yield and proximate compositional analysis of the samples were conducted. The effect of SHUE on cell viability has been evaluated by using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After that, the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes were examined. Western blot analysis was carried out to investigate the protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2). In addition, the effect of extracellular signal-regulated kinase (ERK) on the melanogenesis process was assessed via Western blotting. RESULTS: As per the analysis, SHUE contained the highest average yield on a dry basis at 28.70 ± 3.21%. The findings showed that SHUE reduced the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes. Additionally, the expression levels of MITF, TRP1, and TRP2 protein were significantly downregulated by SHUE treatment in α-MSH-stimulated B16F10 murine melanocytes. Moreover, SHUE upregulated the phosphorylation of ERK and AKT in α-MSH-stimulated B16F10 murine melanocytes. In addition, experiments conducted using the ERK inhibitor (PD98059) revealed that the activity of SHUE depends on the ERK signaling cascade. CONCLUSION: These results suggest that SHUE has an anti-melanogenic effect and can be used as a material in the formulation of cosmetics related to whitening and lightening.

Review of the comparative pathological and immunohistochemical features of human and canine cutaneous melanocytic neoplasms.

Melanocytic neoplasms originate from melanocytes and melanoma, the malignant form, is a common canine neoplasm and the most aggressive human skin cancer. Despite many similarities between these neoplasms in both species, only a limited number of studies have approached these entities in a comparative manner. Therefore, this review compares benign and malignant melanocytic neoplasms in dogs and humans, exclusively those arising in the haired skin, with regard to their clinicopathological, immunohistochemical and molecular aspects. Shared features include spontaneous occurrence, macroscopic features and microscopic findings when comparing human skin melanoma in the advanced/invasive stage and canine cutaneous melanoma, immunohistochemical markers and several histopathological prognostic factors. Differences include the apparent absence of active mutations in the BRAF gene in canine cutaneous melanoma and less aggressive clinical behaviour in dogs than in humans. Further studies are required to elucidate the aetiology and genetic development pathways of canine cutaneous melanocytic neoplasms. Evaluation of the applicability of histopathological prognostic parameters commonly used in humans for dogs are also needed. The similarities between the species and the recent findings regarding genetic mutations in canine cutaneous melanomas suggest the potential utility of dogs as a natural model for human melanomas that are not related to ultraviolet radiation.