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Clinical, Cosmetic and Investigational... 2024Vitiligo is an autoimmune disease characterized by loss of skin pigmentation and currently has no effective treatment. This study aimed to investigate the function of...
BACKGROUND
Vitiligo is an autoimmune disease characterized by loss of skin pigmentation and currently has no effective treatment. This study aimed to investigate the function of SIRT7, being an important desuccinylase mediating multiple disease progression, and its mechanism in vitiligo progression.
METHODS
Normal human melanocytes (NHM) PIG1 and vitiligo human melanocytes (VHM) PIG3V were utilized in this research. The role of sirtuin 7 (SIRT7) and Ezrin (EZR) on melanin synthesis was investigated by detecting tyrosinase activity, melanin content, α-MSH levels, and the protein levels of melanin-related markers. The function of EZR was identified via rescue experiments, while the underlying mechanism was investigated via bioinformatic analysis, co-immunoprecipitation (co-IP), immunoprecipitation (IP), and Western blot techniques.
RESULTS
Results showed that only SIRT7 was highly expressed in vitiligo human melanocytes, where knockingdown SIRT7 translated into increased melanin synthesis in melanocytes. Mechanistically, SIRT7 knockdown promoted the succinylation of EZR at the Lys (K)60 site. Moreover, overexpressing EZR induced higher melanin synthesis in melanocytes, while its knocking down exerted the opposite effect by inhibiting SIRT7 knockdown-induced melanin synthesis.
CONCLUSION
SIRT7 inhibited melanin synthesis in melanocytes by suppressing the succinylation of EZR. These findings are envisaged to provide a novel theoretical basis for vitiligo treatment.
PubMed: 38933605
DOI: 10.2147/CCID.S462280 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Melanoma, primarily caused by solar ultraviolet (UV) radiation, can be prevented by the use of sunscreens. However, the use of synthetic sunscreens raises environmental...
Melanoma, primarily caused by solar ultraviolet (UV) radiation, can be prevented by the use of sunscreens. However, the use of synthetic sunscreens raises environmental concerns. Natural compounds with antioxidant photoprotective properties and cytotoxic effects against cancer cells can be promising for the prevention and treatment of melanoma with less environmental effect. This study focuses on essential oil (EO) for photoprotection and antitumor applications. EO was hydrodistilled from leaves with a 0.59% yield. Gas chromatography-mass spectrometry detected monoterpenes and sesquiterpenes. Nanoemulsions were prepared with (NE-EO) and without EO (NE-B) using the phase inversion method, showing good stability, spherical or oval morphology, and a pseudoplastic profile. Photoprotective activity assessed spectrophotometrically showed that the NE-EO was more effective than NE-B and free EO. Antioxidant activity evaluated by DPPH and ABTS methods indicated that pure and nanoemulsified EO mainly inhibited the ABTS radical, showing IC 40.72 and 5.30 µg/mL, respectively. Cytotoxicity tests on L-929 mouse fibroblasts, NGM human melanocyte, B16-F10 melanoma, and MeWo human melanoma revealed that EO and NE-EO were more cytotoxic to melanoma cells than to non-tumor cells. The stable NE-EO demonstrates potential for melanoma prevention and treatment. Further research is required to gain a better understanding of these activities.
PubMed: 38931388
DOI: 10.3390/ph17060721 -
Life (Basel, Switzerland) May 2024Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity....
BACKGROUND
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited.
METHODS
Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide.
RESULTS
A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5-20) prior to the initiation of afamelanotide and 120 min (IQR, 60-240) after treatment ( < 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment.
CONCLUSIONS
This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.
PubMed: 38929673
DOI: 10.3390/life14060689 -
Life (Basel, Switzerland) May 2024The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses...
Pattern Analysis of Benign and Malignant Atypical Melanocytic Skin Lesions of Palms and Soles: Variations of Dermoscopic Features According to Anatomic Site and Personal Experience.
The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. A dataset of 471 aMPPLs-excised in the suspect of malignancy-was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the "fingers area" (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most "difficult" to diagnose, the was poorly recognized and patterns often misinterpreted. Regarding the aMPPL of the "heel area", the ( = 0.014) and ( = 0.001) significantly discriminated benign cases, while ( = 0.002) and ( = 0.025) malignant ones. In aMPPLs of the "plantar arch", the ( = 0.012) was significant for benignity and , or for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas.
PubMed: 38929643
DOI: 10.3390/life14060659 -
International Journal of Molecular... Jun 2024Chitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma,...
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 β-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/β-oligochitosan (1:2 ratio), with the cell's response supporting the hypothesis that β-oligo-chitosan amplifies the effect. This oligochitosan mixture, favored by the β 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. β-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.
Topics: Chitosan; Melanocytes; Humans; Chitin; Oligosaccharides; Chitinase-3-Like Protein 1; Cell Survival; Cell Proliferation; Cell Line, Tumor; Melanoma
PubMed: 38928474
DOI: 10.3390/ijms25126768 -
Cancers Jun 2024Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence,... (Review)
Review
Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem.
PubMed: 38927967
DOI: 10.3390/cancers16122262 -
Cancers Jun 2024Modern diagnostic procedures, such as three-dimensional total body photography (3D-TBP), digital dermoscopy (DD), and reflectance confocal microscopy (RCM), can improve...
Modern diagnostic procedures, such as three-dimensional total body photography (3D-TBP), digital dermoscopy (DD), and reflectance confocal microscopy (RCM), can improve melanoma diagnosis, particularly in high-risk patients. This study assessed the benefits of combining these advanced imaging techniques in a three-step programme in managing high-risk patients. This study included 410 high-risk melanoma patients who underwent a specialised imaging consultation in addition to their regular skin examinations in outpatient care. At each visit, the patients underwent a 3D-TBP, a DD for suspicious findings, and an RCM for unclear DD findings. The histological findings of excisions initiated based on imaging consultation and outpatient care were compared. Imaging consultation detected sixteen confirmed melanomas (eight invasive and eight in situ) in 39 excised pigmented lesions. Outpatient care examination detected seven confirmed melanomas (one invasive and six in situ) in 163 excised melanocytic lesions. The number needed to excise (NNE) in the imaging consultation was significantly lower than that in the outpatient care (2.4 vs. 23.3). The NNE was 2.6 for DD and 2.3 for RCM. DD, 3D-TBP, or RCM detected melanomas that were not detected by the other imaging methods. The three-step imaging programme improves melanoma detection and reduces the number of unnecessary excisions in high-risk patients.
PubMed: 38927909
DOI: 10.3390/cancers16122204 -
Cancers Jun 2024In this study, we aimed to identify the features of indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to...
In this study, we aimed to identify the features of indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to identify the predictors of growth. We retrospectively evaluated 86 patients with indeterminate lesions treated at our centre from 2016 to 2021. Clinical management involved active surveillance followed by brachytherapy if growth was detected. The lesions were classified into two groups according to whether they grew (small melanomas) or remained stable (choroidal nevi). Growth was detected in 19 (22.1%) lesions. All patients underwent OCTA at baseline. These images were compared to identify the possible predictors of growth. Significant between-group differences were observed in thickness ( = 0.00), greatest basal diameter ( = 0.00), number of risk factors ( = 0.00), symptoms ( = 0.001; relative risk [RR]: 4.3), orange pigment ( = 0.00; RR: 6.02), and ultrasonographic hollowness (Kappa sign); = 0.000; RR: 5.3). The melanomas had significantly more vessels with a diameter ≥ 76.3 µm ( = 0.02; RR: 2.46). The time to growth in these lesions was significantly shorter ( = 0.05) than in lesions with smaller vessels. These findings show that vessel diameter quantified by OCTA can help differentiate between choroidal nevi and small melanomas, when considered together with clinical risk factors.
PubMed: 38927873
DOI: 10.3390/cancers16122167 -
Hematology Reports Jun 2024Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the... (Review)
Review
Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the clinical presentations related to hypopigmentation in hematological disorders, focusing on vitiligo, morphea, and syndromic albinism. Vitiligo, an autoimmune disorder targeting melanocytes, involves interactions between genetic polymorphisms and immune responses, particularly regarding CD8+ T cells and IFN-γ. Drug-induced vitiligo, notably by immune checkpoint inhibitors and small-molecule targeted anticancer therapies, underscores the importance of immune dysregulation. Morphea, an inflammatory skin disorder, may signal hematological involvement, as seen in deep morphea and post-radiotherapy lesions. Syndromic albinism, linked to various genetic mutations affecting melanin production, often presents with hematologic abnormalities. Treatment approaches focus on targeting the immune pathways specific to the condition, and when that is not possible, managing symptoms. Understanding these dermatological manifestations is crucial for the timely diagnosis and management of hematological disorders.
PubMed: 38921184
DOI: 10.3390/hematolrep16020036 -
Current Issues in Molecular Biology May 2024Melanocytes, located in the epidermis' basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV...
Melanocytes, located in the epidermis' basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and β-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and β-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.
PubMed: 38920996
DOI: 10.3390/cimb46060324