{"title":"Piceatannol—Can It Be Used to Treat Hyperpigmentation of the Skin?","authors":"Ravi Kumar Rajan","doi":"10.1111/pcmr.70008","DOIUrl":"https://doi.org/10.1111/pcmr.70008","url":null,"abstract":"<p>Over the years, the cosmetic industry has shifted its focus from synthtic to natural compounds. This change is driven not only by the safety profile of natural ingredients but also by increased consumer awareness about the products they use. As a result, many natural skincare products have been launched in recent years. Hyperpigmentation disorders, such as melasma, age spots (solar lentigines), post-inflammatory hyperpigmentation, freckles, and acanthosis nigricans, are significant concerns. These conditions not only pose pathological issues but also affect individuals' self-esteem. Consequently, treating hyperpigmentation by reducing melanogenesis has become a key area of interest in cosmetology. Among various natural compounds, piceatannol (PCT) shows great potential in treating hyperpigmentation. The primary mechanism previously explored is the inhibition of the tyrosinase enzyme, which is one of the most researched strategies for combating melanogenesis. Additionally, PCT has been shown to downregulate MITF expression, a key gene responsible for the transcription of various melanogenic proteins and enzymes. However, beyond these two mechanisms, little is known about how PCT may inhibit melanogenesis. In this review, we aim to bridge that gap. We will explore and speculate on the possible upstream signaling pathways to MITF, such as Nrf, FOXO3a, CREB, MAPK signaling, etc., where PCT could potentially act to inhibit melanogenesis. This review will not only pave the way for future research related to PCT and hyperpigmentation but also highlight pathways that could be targeted for developing cosmetics and treatments for hyperpigmentation disorders.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Conjunctival Melanoma: A Narrative Review of Current Knowledge","authors":"Michail Angelos Papaoikonomou, Leonidas Pavlidis, Zoi Apalla, Athanasios Papas","doi":"10.1111/pcmr.70006","DOIUrl":"https://doi.org/10.1111/pcmr.70006","url":null,"abstract":"<p>This review explores the current literature on conjunctival melanoma, a rare and complex periocular neoplasm, emphasizing the absence of a standardized treatment protocol and the associated management challenges. It examines the clinical, genetic, and histological features of conjunctival melanoma, alongside diagnostic methodologies and treatment strategies, drawing on the most recent bibliographic data. The literature was systematically reviewed using the PubMed database, offering insights into future research directions and highlighting innovative treatment approaches, particularly for advanced-stage disease.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isabella Ribaudo, Michelle Arbesman, Ying Ni, James Isaacs, Lucy Boyce Kennedy, Jennifer Ko, Pauline Funchain, Thach-Giao Truong, Joshua Arbesman
{"title":"Genetic Landscape of Mucosal Melanoma: Identifying Pathogenic Germline Variants","authors":"Isabella Ribaudo, Michelle Arbesman, Ying Ni, James Isaacs, Lucy Boyce Kennedy, Jennifer Ko, Pauline Funchain, Thach-Giao Truong, Joshua Arbesman","doi":"10.1111/pcmr.70007","DOIUrl":"https://doi.org/10.1111/pcmr.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>Mucosal melanomas (MM) are rare but aggressive malignancies, comprising only 1.3% of all melanoma diagnoses, with a poor 5-year survival rate below 20%. MM lacks identifiable risk factors, presents with distinct mutational profiles, and is often diagnosed at an advanced stage, contributing to worse outcomes. This study explores the prevalence of pathogenic germline variants associated with melanoma and general cancer susceptibility in a cohort of 16 MM patients enrolled in the Gross Family Melanoma Registry at Cleveland Clinic between 2017 and 2023. Germline testing was performed using an ≥ 81 gene panel, including 12 genes with established or preliminary melanoma predisposition evidence. Our findings reveal a high prevalence (50%) of pathogenic germline variants among MM patients, with CHEK2 and APC variants identified in 12.5% of cases each, and individual variants detected in MUTYH, ATM, RB1, and RECQL4. These results suggest a germline-driven cancer susceptibility in MM, exceeding the 15% prevalence observed in cutaneous melanoma using the same inclusion criteria.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jean-Matthieu L'Orphelin, Anne Dompmartin, Brigitte Dréno
{"title":"The Skin Microbiome: A New Key Player in Melanoma, From Onset to Metastatic Stage","authors":"Jean-Matthieu L'Orphelin, Anne Dompmartin, Brigitte Dréno","doi":"10.1111/pcmr.13224","DOIUrl":"https://doi.org/10.1111/pcmr.13224","url":null,"abstract":"<p>The skin microbiome plays a crucial role in maintaining skin health, defending the body against harmful pathogens, and interacting with melanoma. The composition of the skin microbiome can be affected by factors like age, gender, ethnicity, lifestyle, diet, and UV exposure. Certain bacteria like <i>Staphylococcus</i> and <i>Veillonella</i> are important for wound healing, while <i>Cutibacterium acnes</i> can play a role in dermatoses. UV radiation alters the skin microbiome, originates a “UV-resistome” and can lead to skin cancer initiation. Specifically, <i>Staphylococcus epidermidis</i> has shown protective effects against skin cancer, whereas <i>Cutibacterium acnes</i> can induce apoptosis in melanocytes postirradiation. The microbiome also interacts with melanoma treatment, affecting responses to immune checkpoint inhibitors. Strategies like bacteriotherapy, involving the manipulation of the gut microbiome but also the skin microbiome (with the gut–skin axis or through topical treatment) could improve treatment outcomes and show promise in melanoma therapy. Understanding the complex interplay between the skin microbiome, UV exposure, and melanoma development is crucial for developing personalized therapeutic approaches. Investigation into the skin microbiome and its potential role in melanoma progression continues to be an exciting area of research with implications for future therapeutic interventions.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13224","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Zheng, Weihuan Shao, Tongxin Ge, Shengfang Ge, Renbing Jia, Ludi Yang, Ai Zhuang
{"title":"Cancer-Associated Fibroblast Signature Can Predict Prognosis and Therapeutic Responses in Skin Cutaneous Melanoma","authors":"Yue Zheng, Weihuan Shao, Tongxin Ge, Shengfang Ge, Renbing Jia, Ludi Yang, Ai Zhuang","doi":"10.1111/pcmr.70005","DOIUrl":"https://doi.org/10.1111/pcmr.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>Skin cutaneous melanoma (SKCM) is a lethal skin cancer with a poor prognosis and limited response to immunotherapy. Cancer-associated fibroblasts (CAFs) are key contributors to tumor progression, therapy resistance, and immunosuppression. In this study, mRNA sequencing and clinical data from SKCM samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to evaluate the prognostic significance, therapeutic implications, and potential for enhancing immunotherapy through targeting CAFs in SKCM. A CAF-related risk model comprising nine genes was developed, revealing that patients classified as low-risk exhibited superior survival outcomes and increased sensitivity to immunotherapy. Spearman correlation analysis identified significant associations between the risk score and the sensitivity to 40 drugs, as well as resistance to 17 drugs. Additionally, CAFs were categorized into three distinct subgroups in SKCM, with antigen-presenting CAFs (apCAFs) notably suppressing the infiltration of anti-tumor immune cells and strongly correlating with poor prognosis. In summary, the CAF-related risk model offers a robust prognostic tool for SKCM, capable of predicting both survival outcomes and therapeutic sensitivity. Moreover, the pivotal role of apCAFs within the immune microenvironment suggests that targeting these cells may enhance the efficacy of immunotherapy.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synonymous but Significant: New Findings of Pathological Variants in Hermansky–Pudlak Syndrome","authors":"Junnosuke Kawaguchi, Ken Okamura, Toru Saito, Yosuke Arai, Sakuhei Fujiwara, Miwa Kitamura, Hideaki Tanizaki, Yutaka Hozumi, Tamio Suzuki","doi":"10.1111/pcmr.13221","DOIUrl":"https://doi.org/10.1111/pcmr.13221","url":null,"abstract":"<div>\u0000 \u0000 <p>Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and systemic complications, including bleeding tendencies. While 11 genes associated with HPS have been identified, cases of HPS5 remain exceedingly rare, particularly in Japan. Here, we report two Japanese patients with novel pathological HPS5 variants, expanding the genetic spectrum of this disorder. Both patients exhibited typical features of mild skin and hair hypopigmentation, and significant ocular involvement. Genetic analysis revealed a heterozygous nonsense variant, NG_008877.1 (NM_181507.2): c.2275G>T, in both patients, inherited from their fathers. Additionally, maternal variants NG_008877.1 (NM_181507.2): c.2952-13G>A and NG_008877.1 (NM_181507.2): c.1128A>G were identified in patient 1 and patient 2, respectively. These variants, initially presumed non-pathogenic, were found to induce alternative splicing, leading to truncated protein production. Our findings highlight the functional importance of synonymous variants and their potential role in HPS. This report represents the first documented case of a synonymous pathogenic variant associated with HPS and underscores the need for comprehensive genetic and transcriptomic analyses in rare genetic disorders.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Zhang, Jian Zhang, Suqing Liu, Zhengzhou Shi, Yijian Zhu, Min Jiang, Leihong Xiang
{"title":"Effectiveness and Safety of Oral Compound Glycyrrhizin Followed by Phototherapy for the Treatment of Progressive Vitiligo in Children","authors":"Li Zhang, Jian Zhang, Suqing Liu, Zhengzhou Shi, Yijian Zhu, Min Jiang, Leihong Xiang","doi":"10.1111/pcmr.13226","DOIUrl":"https://doi.org/10.1111/pcmr.13226","url":null,"abstract":"<div>\u0000 \u0000 <p>Childhood vitiligo, distinct from its adult counterpart, presents unique treatment challenges. Glycyrrhizin inhibits the release of high-mobility group box 1 (HMGB1) protein from keratinocytes, preventing melanocyte apoptosis and autophagy. Furthermore, the orally administered compound glycyrrhizin (OCG) effectively treats various autoimmune disorders, demonstrating long-term efficacy, safety, and tolerability. This study compared the efficacy of OCG and oral prednisone (OP), followed by phototherapy, in patients with progressive childhood vitiligo at 52 weeks' follow-up. Fifty children with vitiligo were randomized into two groups according to treatment: OCG (50–150 mg/day) followed by phototherapy (<i>n</i> = 25) and OP (5–10 mg/day) followed by phototherapy (<i>n</i> = 25). At Week 24, a halt in disease progression (HDP) was observed in 20 (80%) patients in the OCG group and 21 (84%) in the OP group, with no significant difference (<i>p</i> > 0.99)<i>.</i> However, the mean time to achieve HDP was significantly shorter in the OP group than in the OCG group (14.73 ± 4.84 vs. 19.13 ± 4.82 weeks; <i>p</i> < 0.01). In addition, serum HMGB1 concentrations were significantly reduced after treatment with OCG at Week 24 (3.02 ± 0.83 vs. 0.95 ± 0.36 ng/mL [<i>p</i> < 0.01]; OP, 2.79 ± 0.16 vs. 1.03 ± 0.34 ng/mL [<i>p</i> < 0.01]). The decline in Vitiligo Area Scoring Index (VASI) score at the end of follow-up (i.e., Week 52) did not show a statistically significant difference between the OCG and OP groups (52.31% ± 14.86% vs. 55.71% ± 21.23%; <i>p</i> = 0.55). The therapeutic response of the clinical markers of progression was good and comparable between the OCG and OP groups. OCG demonstrated similar efficacy to OP followed by phototherapy in controlling disease activity and promoting repigmentation in children with vitiligo at 52 weeks of follow-up.</p>\u0000 <p>\u0000 <b>Trial Registration:</b> ChiCTR2400086844</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saskia Tauch, Joschka Hey, Bettina Kast, Nicolas Gengenbacher, Lena Weiß, Melanie Sator-Schmitt, Sabrina Lohr, Alexander Brobeil, Peter Schirmacher, Jochen Utikal, Hellmut G. Augustin, Christoph Plass, Peter Angel
{"title":"A Unique Signature for Cancer-Associated Fibroblasts in Melanoma Metastases","authors":"Saskia Tauch, Joschka Hey, Bettina Kast, Nicolas Gengenbacher, Lena Weiß, Melanie Sator-Schmitt, Sabrina Lohr, Alexander Brobeil, Peter Schirmacher, Jochen Utikal, Hellmut G. Augustin, Christoph Plass, Peter Angel","doi":"10.1111/pcmr.70002","DOIUrl":"https://doi.org/10.1111/pcmr.70002","url":null,"abstract":"<p>Cancer-associated fibroblasts (CAFs) represent a central cell population of the tumor microenvironment (TME). Recently, single-cell RNA-sequencing (scRNA-seq) analyses of primary tumors of different cancer entities yielded different classifications of CAF subsets underscoring the heterogeneity of CAFs within the TME. Here, we analyzed the transcriptional signatures of approximately 8400 CAFs and normal fibroblasts by scRNA-seq and compared genetic profiles of CAFs from murine melanoma primary tumors to CAFs from corresponding melanoma lung metastases. This revealed distinct subsets for primary tumor and metastasis-specific CAF populations, respectively. Combined with the spatial characterization of metastasis CAFs at the RNA and protein level, scRNA analyses indicate tumor-dependent crosstalk between neutrophils and CAFs, mediated via SAA3 and IL1b-related signaling pathways, which can be recapitulated in vitro. Analyzing tissue sections of human patient samples, this interaction was found to be present in human melanoma metastasis. Taken together, our data highlight unique characteristics of metastasis CAFs with potential therapeutic impact for melanoma metastasis.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne-Lyse Ducrest, Luis M. San-Jose, Samuel Neuenschwander, Emanuel Schmid-Siegert, Céline Simon, Marco Pagni, Christian Iseli, Hannes Richter, Nicolas Guex, Tristan Cumer, Emmanuel Beaudoing, Mélanie Dupasquier, Pauline Charruau, Pauline Ducouret, Ioannis Xenarios, Jérôme Goudet, Alexandre Roulin
{"title":"Melanin and Neurotransmitter Signalling Genes Are Differentially Co-Expressed in Growing Feathers of White and Rufous Barn Owls","authors":"Anne-Lyse Ducrest, Luis M. San-Jose, Samuel Neuenschwander, Emanuel Schmid-Siegert, Céline Simon, Marco Pagni, Christian Iseli, Hannes Richter, Nicolas Guex, Tristan Cumer, Emmanuel Beaudoing, Mélanie Dupasquier, Pauline Charruau, Pauline Ducouret, Ioannis Xenarios, Jérôme Goudet, Alexandre Roulin","doi":"10.1111/pcmr.70001","DOIUrl":"https://doi.org/10.1111/pcmr.70001","url":null,"abstract":"<p>Regulation of melanin-based pigmentation is complex, involving multiple genes. Because different genes can contribute to the same pigmentation phenotype, the genes identified in model organisms may not necessarily apply to wild species. In the barn owl (<i>Tyto alba</i>), ventral plumage colour ranges from white to rufous, with genetic variation in the melanocortin 1 receptor gene (<i>MC1R</i>) accounting for at least a third of this variation. In the present study, we used transcriptomic data to compare the gene expression profiles of growing feathers from nestlings with different <i>MC1R</i> genotypes. We identified 21 differentially expressed genes, nine of which are involved in melanogenesis, while seven are related to neurotransmitter function or synaptic activity. With the exception of <i>CALB1</i>, all of the differentially expressed genes were upregulated in rufous owls compared to white barn owls. To the best of our knowledge, this study is the first to link melanin production with neurotransmitter-related genes, and we discuss possible evolutionary explanations for this connection.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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