Search Results (14)

Background: Lentigo maligna (LM) represents melanoma in situ and predominantly affects elderly individuals, typically arising on chronically sun-exposed skin of the head and neck. Although LM is characterized by slow horizontal growth and generally favourable prognosis, progression to invasive lentigo maligna melanoma may occur, making timely and effective treatment essential. Surgical excision remains the standard of care; however, advanced age, comorbidities, lesion size, and cosmetic or functional considerations may limit surgical feasibility. Case presentation: We report the case of a 93-year-old woman with no prior history of skin cancer who presented with a gradually enlarging pigmented lesion on the forehead. Clinical examination revealed an irregularly pigmented macule measuring 25 × 27 mm. Multiple mapping biopsies confirmed melanoma in situ of the lentigo maligna type, with adnexal extension and no evidence of dermal invasion. Given the patient’s advanced age and lesion location, a non-surgical approach was selected. Topical imiquimod 5% cream was applied five times per week for 12 weeks to the visible lesion and to a 20 mm margin around it. The patient was monitored closely throughout the treatment. Local inflammatory reactions were mild to moderate, consisting mainly of erythema, crusting, and superficial erosion, without systemic adverse effects. At treatment completion, marked clinical improvement with near-complete resolution of pigmentation was observed. Follow-up dermoscopic evaluation demonstrated only minimal residual granular pigmentation. Post-treatment mapping biopsies confirmed complete histological clearance of atypical melanocytic cells. Conclusions: This case illustrates that topical imiquimod may serve as a safe and effective alternative to surgery in carefully selected elderly patients with lentigo maligna. Close clinical follow-up and histological confirmation of clearance are essential to ensure treatment success and durable outcomes. Full article

Background and Objectives: Vitiligo is a chronic autoimmune skin disorder characterized by the loss of pigmentation, resulting in depigmented patches due to the destruction of melanocytes. This condition can lead to considerable psychological distress, and research indicates a possible connection with major depressive disorder (MDD). Nonetheless, the depth and nature of this association, particularly within the Saudi population, have not been thoroughly investigated. This case–control study seeks to explore the relationship between vitiligo and depressive symptomatology, evaluate the severity of depressive symptoms in vitiligo patients compared to control subjects, and examine the association between the clinical severity of vitiligo (assessed using the Vitiligo Area Scoring Index, VASI) and depressive symptoms (measured using the PHQ-9, a validated screening instrument based on DSM criteria). Materials and Methods: A total of 700 participants were included, comprising 340 individuals with vitiligo and 360 controls with other skin conditions. Participants completed a web-based questionnaire that collected sociodemographic data and included the PHQ-9 assessment. The severity of vitiligo was determined using the VASI. Statistical analysis involved using the computer program IBM Statistical Program for Social Sciences (SPSS) (version 26.0). Results: The average PHQ-9 score was significantly higher for patients with vitiligo (8.28 ± 7.36) compared to controls (6.30 ± 4.70, p = 0.028). While the overall rates of mild to severe depression were comparable (41.5% in vitiligo patients versus 40.3% in controls, p = 0.748), vitiligo patients exhibited higher occurrences of moderately severe depression (11.8%) and severe depression (10.9%) compared to controls (5.8% and 0.8%, respectively; p < 0.001). A weak, yet significant, positive correlation was found between VASI and PHQ-9 scores (ρ = 0.184, p < 0.001). The vulgaris and segmental types of vitiligo exhibited the highest median depression scores (PHQ-9: 11 and 9, respectively; p < 0.001). Logistic regression analysis indicated that those with genital vitiligo had greater odds of experiencing depression (OR = 12.10, p = 0.039), while those with universalis vitiligo faced even higher odds (OR ≈ 26,837.84, p = 0.001). Interestingly, higher VASI scores were linked to lower odds of depression (OR = 0.927, p = 0.029). Additionally, the risk of depression significantly increased with higher income levels and among individuals aged 50 years and older. Conclusions: Although the overall prevalence of depression was not significantly different between vitiligo patients and controls, the degree of depressive symptoms was notably more severe in those with vitiligo. Specific clinical subtypes, particularly genital and universalis vitiligo, were found to be more closely associated with an increased risk of depression. These results highlight the importance of regular mental health screenings and customized psychosocial support in dermatological care, especially for high-risk groups. Full article

Background/Objectives: Oleuropein (OLP), the key bioactive in olive leaf extracts, has demonstrated various biological benefits. We previously reported on the pro-melanogenic action with increased dendricity of a patented olive leaf extract (Benolea^®) that was standardized to 16–24% OLP. In this study, purified OLP was evaluated to identify if it might be the bioactive responsible for the stimulating effects on melanocytes. Moreover, previous studies on OLP have never reported the effects on melanocyte dendricity or melanin export in the medium. Methods: Herein, the effect of OLP on melanogenesis was first evaluated using the B16F10 cell model and validated using the physiological model of normal human melanocytes from Caucasian (lightly pigmented; LP) and Asian (moderately pigmented; MP) skin. The effects of OLP on melanin export in LP and MP cells were indirectly evaluated by dendricity indices. Results: OLP lowered the intracellular melanin content in B16F10 cells by 26.36%, 24.48%, and 27.71% at 100, 150, and 200 µg/mL (all p < 0.01), respectively, with no effect on the intracellular melanin contents of LP or MP cells. OLP treatment did not influence tyrosinase activity in B16F10 cells or MP cells but significantly enhanced the activity in LP cells. The measurement of extracellular melanin showed significantly higher levels for all three cells, although the levels were considerably higher in MP cells, after the adjustment for OLP autoxidation observed in the cell-free system, which caused melanin-like brown coloration. Furthermore, OLP induced morphological alterations of extended dendrites of B16F10 cells that were retained in LP and MP cells. The quantitation of the dendricity of cells treated with OLP at 200 μg/mL revealed that the total dendrite length was increased by 35.24% (p < 0.05) in LP cells and by 58.45% (p < 0.001) in MP cells without any change in the dendrite number. Conclusions: This is the first study to demonstrate the novel finding that OLP possesses a hitherto unreported unique capacity to stimulate melanocyte dendricity, hence establishing the efficacy for use in increasing human pigmentation. Our findings show significance, with a potential application of the compound OLP for addressing human hypopigmentation disorders in clinical settings or for cosmetic uses related to sunless tanning. Full article

The increasing use of e-cigarettes (ECs) has raised public health concerns due to the observed cytotoxic effects in both in vitro and in vivo studies. Infants and young children, being particularly vulnerable groups, exhibit heightened susceptibility to potential hazards arising from maternal use of ECs, as well as exposure to second-hand and third-hand aerosols emitted by ECs. Melanocytes are neural-crest-derived cells that regulate multiple biological functions. Melanocyte death, triggered by chemical exposure, is a known etiological cause of pigmentation abnormalities and neurodevelopmental disorders. Prior reports have demonstrated nicotine-induced differential cytotoxicity to neonatal human melanocytes derived from lightly pigmented (LP) and darkly pigmented (DP) donors. We recently reported that the vehicle base propylene glycol (PG) in e-liquid can alter the functions of LP melanocytes. However, to date, the effects of e-liquid flavors on LP and DP cells remain unexplored. Hence, in this preliminary study, a panel of twenty EC refill liquids comprising ten popular flavors (strawberry, grape, banana, vanilla, butterscotch, cinnamon, menthol, chocolate, cola, and tobacco), where each flavored e-liquid contained either 0 or 18 mg/mL nicotine, was examined for in vitro cytotoxicity to neonatal human melanocytes derived from LP and DP donors. Our results reveal that of the ten flavors, five (menthol, cinnamon, vanilla, tobacco, and banana) were highly cytotoxic, with their half-maximal inhibitory concentration (IC₅₀) values within the tested concentration ranges. Moreover, the cytotoxicity of the specific flavors menthol, cinnamon, and vanilla was enhanced in the presence of nicotine, indicative of interactive effects, with nicotine and flavor contributing to greater melanocyte injury. The cytotoxicity of menthol (both with and without nicotine) and cinnamon (without nicotine) e-liquids was found to be higher in LP cells as compared to DP cells. In contrast, nicotine-containing vanilla e-liquid induced higher cytotoxicity in DP cells than LP cells. Only three flavors, cola (without nicotine), strawberry (without nicotine), and chocolate (without nicotine), were non-cytotoxic to both LP and DP cells. The findings that popular flavors in e-liquids induced moderate to high degree of melanocytotoxicity even in the absence of nicotine suggests that ECs are not harmless. This information may assist EC users identify particular flavors in refill liquids that may be detrimental to melanocytes. A first-screen identification of flavors in e-liquids that show a racial/ethnicity dependence can provide a baseline to identify cytotoxicity concentration ranges for popular flavors and help inform the regulatory guidelines for EC toxicity to young children and youth. Full article

Hyperpigmentation skin disorders are marked by an abnormal accumulation or export of melanin pigment synthesized within melanocytes and pose a significant aesthetic concern. The search for novel natural compounds that exhibit pharmacological potential for treating pigmentation disorders is growing. In this study, kahweol (KW) and cafestol (CFS), two structural analogs of coffee diterpenes, were evaluated and compared for their effects on melanogenesis using B16F10 mouse melanoma cells and primary human melanocytes derived from Asian and African American skin. To the best of our knowledge, there are no reports of the effects of KW and CFS on melanogenesis yet. We first screened nontoxic concentrations of both compounds using an MTS assay after 72 h incubations and subsequently tested their effects on melanin synthesis and export. Cellular tyrosinase activity and cell-free mushroom tyrosinase activity were assayed to study the mechanisms of melanogenesis suppression. Human melanocytes from a moderately pigmented donor (HEMn-MP cells) and from a darkly pigmented donor (HEMn-DP cells) were next examined, and effects on cellular viability, melanin content, cellular tyrosinase activity, and melanin export (quantitated via dendricity) were similarly examined for both compounds. Our results show that KW and CFS did not significantly affect intracellular melanin content but suppressed extracellular melanin in B16F10 cells and dendritic parameters in human melanocytes, indicating their unique capacity to target extracellular melanogenesis and melanin export. Although KW showed a greater extracellular melanogenesis inhibitory capacity in B16F10 cells, in both primary melanocyte cells, CFS emerged as a potent inhibitor of melanin export compared to KW. Together, these results reveal novel modes of action of both compounds and indicate a promise to use CFS as a novel candidate for treating hyperpigmentation disorders of the human skin for clinical and cosmetic use. Additional research is necessary to shed light on the molecular pathways and the efficacy of melanogenesis inhibition by CFS in 3D human skin equivalents and in vivo studies. Full article

Background and Objectives: This study reports a case of a 62-year-old patient experiencing a significant decline in vision over the past three months. The initial best-corrected visual acuity (BCVA) of 20/20 in both eyes diminished to 20/200 in the right eye (RE) and counting fingers (CF) in the left eye (LE) within this timeframe. The patient was diagnosed with stage 4 ovarian cancer just one month before the significant vision deterioration. Materials and Methods: A thorough ophthalmologic examination revealed a notable progression of cataracts and the presence of subretinal fluid on the posterior pole, accompanied by choroidal thickening. The right eye exhibited multifocal, orange-pigmented, and elevated choroidal lesions, while the left eye’s fundus examination was impeded by dense cataracts. Optical coherence tomography (OCT) revealed bilateral choroidal thickening with overlying folds and subretinal fluid, and ultrasound imaging of the choroidal lesions indicated moderate homogenous internal reflectivity. Results: The patient received a diagnosis of BDUMP (bilateral diffuse uveal melanocytic proliferation), a paraneoplastic syndrome marked by simultaneous, bilateral, painless vision loss and the rapid onset of bilateral cataracts with serous retinal detachments. Despite cataract extraction, the expected visual recovery was not achieved (RE: CF; LE: 2/200, respectively). Plasmapheresis showed some success in stabilizing vision loss attributed to serous retinal detachments. Conclusions: BDUMP necessitates addressing the underlying malignancy for effective treatment. Left untreated, it can lead to near blindness within a year. The prognosis remains grim, with an average survival time ranging from 12 to 15.7 months from the time of diagnosis. Considering this case report, it is crucial to establish effective management plans and further investigate potential treatment methods and predictive markers centered around BDUMP. Collaboration between healthcare professionals and researchers is crucial in addressing the complexities of BDUMP, as the timely diagnosis and treatment of the disease remains a top priority. Full article

Melanocytic skin tumours have been rarely described in pet rabbits, and exposure to UV light in sparsely haired areas has been hypothesised to play a cancerogenic role. Here, we describe a case of cutaneous malignant melanoma arising from the skin of the scrotum in an 8-year-old male wild rabbit, with testicular metastases as an unusual metastatic site for melanoma reported in humans to date. The tumour was nearly 5 cm in size, firm, and highly pigmented, with multifocal superficial ulcerations and large areas of intratumoural necrosis. The adjacent testis was 1.5 cm, multinodular, and black, obscuring tissue morphology. Histologically, the dermis was expanded by an infiltrative, densely cellular neoplasm composed of nests and sheets of polygonal to spindle neoplastic melanocytes, supported by scant fibrovascular stroma. Neoplastic cells showed intermediate N/C ratio, moderate basophilic cytoplasm, often obscured by abundant brownish granular pigment, and eccentric nuclei with prominent nucleoli. Cellular pleomorphism and nuclear atypia were severe, and high mitotic activity was observed. Diffuse dermal lymphovascular invasion was also observed. The testis was delimited by a thin tunica albuginea, and the parenchyma was largely obscured in its morphology by densely packed neoplastic cells. Seminiferous tubules, lined with a thin basement membrane and containing neoplastic and scattered spermatogenic cells, were occasionally observed. Neoplastic cells within the skin and the testis were positive for HMB-45, Melan-A, and S-100. The growing popularity of rabbits as pets allows for a greater ability to accumulate data on the spontaneous occurrence of tumours in these animals. Furthermore, descriptions of the biological aspects of spontaneously occurring tumours may serve to improve current knowledge in animal species and humans in which the same neoplasm may occur. Full article

Melanocytic tumour anatomic location is considered an important prognostic indicator. The cutaneous forms are generally considered benign and may show various biological behaviours. This work reports a rare case of canine cutaneous melanoma showing parietal bone metastasis. Bone invasion in melanocytic tumours is often described in oral or visceral melanomas, but not in cutaneous forms. The patient (dog, male, mixed breed, 12 years) was initially presented for the surgical removal of a cutaneous tumour located on the skin of the carpal region of the right forelimb. Four months after, the patient returned with enlarged lymph nodes and acute respiratory failure. The patient was euthanized due to a decline in physical condition. The necropsy showed metastases in the affected forelimb, regional lymph node, splanchnic organs, parietal bone and meninges. Histopathological examination of tumour tissue samples revealed a mixture of pigmented and non-pigmented spindle and epithelioid melanocytes, while according to immunohistochemistry, the tumours showed a strong immunopositivity for VEGF and MMP-10, and a moderate positivity for MMP-2 expression. This case shows that cutaneous melanocytic tumours may show an aggressive malignant form with positive immunohistochemical reactions for multiple invasiveness factors. Full article

Mycosis fungoides (MF) is a subtype of primary cutaneous T-cell lymphoma (CTCL) with an indolent course that rarely progresses. Histologically, the lesions display a superficial lymphocytic infiltrate with epidermotropism of neoplastic T-cells. Hypopigmented MF is a rare variant that presents with hypopigmented lesions and is more likely to affect young patients. The etiology of the hypopigmentation is unclear. The aim of this study was to assess melanocyte loss in MF through immunohistochemistry (IHC) with SOX10. Twenty cases were evaluated, including seven of the hypopigmented subtype. The neoplastic epidermotropic infiltrate consisted predominantly of CD4+ T-cells in 65% of cases; CD8+ T-cells were present in moderate to abundant numbers in most cases. SOX10 IHC showed a decrease or focal complete loss of melanocytes in 50% of the cases. The predominant neoplastic cell type (CD4+/CD8+), age, race, gender, histologic features, and reported clinical pigmentation of the lesions were not predictive of melanocyte loss. A significant loss of melanocytes was observed in 43% of hypopigmented cases and 54% of conventional cases. Additional studies will increase our understanding of the relationship between observed pigmentation and the loss of melanocytes in MF. Full article

Benolea^® (EFLA^®943) is a standardized dry olive leaf extract (DOLE) considered safe for food consumption and has demonstrated superior pharmaceutical benefits such as antioxidant, anti-obesity, and anti-hypertensive activities. However, there is no study on its effects on melanogenesis yet. Disruption in the sequence of steps in melanogenesis can lead to hypopigmentary disorders which occur due to reduced production or export of pigment melanin in the skin. There is a need for safe and nontoxic therapeutics for the treatment of hypopigmentation disorders. Herein, we studied the effects of DOLE over a concentration range of 10–200 µg/mL on melanin synthesis and melanin secretion in B16F10 mouse melanoma cells and MNT-1 human melanoma cells and validated our results in primary human melanocytes (obtained from lightly pigmented (LP) and moderately pigmented (MP) cells) as well as their cocultures with keratinocytes. The capacity of melanocytes to export melanosomes was also estimated indirectly by the quantitation of melanocyte dendrite lengths and numbers. Our results show that DOLE significantly enhanced levels of extracellular melanin in the absence of effects on intracellular melanin, demonstrating that this plant extract’s pro-melanogenic activity is primarily based on its capacity to augment melanin secretion and stimulate melanocyte dendricity. In summary, our preliminary results demonstrate that DOLE may hold promise as a pro-pigmenting agent for vitiligo therapy and gray hair treatment by its exclusive and novel mechanism of functioning as a dendrite elongator. Further studies to elucidate the mechanisms of action of the pro-melanogenic activity and effects of DOLE on melanosome export as well as the last steps of melanogenesis are warranted. Full article

Hypopigmentation disorders due to an underproduction of the pigment melanin by melanocytes cause uneven skin coloration, while in hair follicles they cause grey hair. There is a need for novel materials which can stimulate melanogenesis in the skin and hair for personal care use. While titanium dioxide, gold and silver nanoparticles have been extensively used for applications in cosmetic and personal-care products (PCP), the use of relatively inert platinum nanoparticles (PtNPs) has remained underappreciated. PtNPs have been reported to be a mimetic of the enzyme catechol oxidase with small size PtNPs reported to exhibit a higher catechol oxidase activity in a cell-free system, but no testing has been conducted in melanocytes to date. Herein, we have investigated if PtNPs of two sizes (SPtNP: 5 nm; LPtNP: 50 nm) might have an effect on melanogenesis. To this end, we have used MNT-1 human melanoma cells and primary human melanocytes from moderately-pigmented skin (HEMn-MP). Both SPtNP and LPtNP were nontoxic over a concentration range 6.25–25 μg/mL, hence these concentrations were used in further experiments. Both PtNPs stimulated higher extracellular melanin levels than control; SPtNP at concentrations 12.5 and 25 μg/mL significantly stimulated higher levels of extracellular melanin as compared to similar concentrations of LPtNP in MNT-1 cells, in the absence of ROS generation. The effects of PtNPs on melanin secretion were reversible upon removal of PtNPs from the culture medium. The results of primary particle size-specific augmentation of extracellular melanin by SPtNPs were also validated in HEMn-MP cells. Our results thus provide a proof-of-principle that SPtNP might hold potential as a candidate for the treatment of white skin patches, for sunless skin-tanning and for use in anti-greying hair products in cosmetics. Full article

Herpesvirus of turkey (HVT) is commonly used as a vaccine to protect chickens against Marek’s disease. Following vaccination, HVT infects feathers where it can be detected in all chicken lines examined. Unlike the parental Brown line (BL), Smyth line (SL) chickens develop vitiligo, due to autoimmune destruction of melanocytes in feathers. Previous reports showed a strong inflammatory response in Smyth chickens’ feathers at vitiligo onset, that subsided once melanocytes were destroyed, and depigmentation was complete. Here, we questioned whether the local autoimmune response in the Smyth model influences HVT infection and persistence in feathers. For this, one-day-old SL and BL chickens were vaccinated with Newcastle disease (rHVT-ND). Vitiligo was scored and HVT loads in pigmented and non-pigmented growing feathers were quantified regularly over 20 weeks. Chickens of both lines showed moderate HVT loads in feathers. At the onset of active vitiligo, the HVT load was significantly higher in SL compared to BL feathers. However, no difference in HVT loads was noticed between pigmented and non-pigmented feathers from SL chickens. Therefore, surprisingly, the inflammatory response in feathers of SL chickens did not inhibit HVT infection and persistence, but on the contrary, temporarily promoted HVT infection in feathers. Full article

Hibiscus syriacus L. exhibited promising potential as a new source of food and colorants containing various anthocyanins. However, the function of anthocyanins from H. syriacus L. has not been investigated. In the current study, we evaluated whether anthocyanins from the H. syriacus L. varieties Pulsae and Paektanshim (PS and PTS) inhibit melanin biogenesis. B16F10 cells and zebrafish larvae were exposed to PS and PTS in the presence or absence of α-melanocyte-stimulating hormone (α-MSH), and melanin contents accompanied by its regulating genes and proteins were analyzed. PS and PTS moderately downregulated mushroom tyrosinase activity in vitro, but significantly decreased extracellular and intracellular melanin production in B16F10 cells, and inhibited α-MSH-induced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. PS and PTS also attenuated pigmentation in α-MSH-stimulated zebrafish larvae. Furthermore, PS and PTS activated the phosphorylation of extracellular signal-regulated kinase (ERK), whereas PD98059, a specific ERK inhibitor, completely reversed PS- and PTS-mediated anti-melanogenic activity in B16F10 cells and zebrafish larvae, which indicates that PS- and PTS-mediated anti-melanogenic activity is due to ERK activation. Moreover, chromatography data showed that PS and PTS possessed 17 identical anthocyanins as a negative regulator of ERK. These findings suggested that anthocyanins from PS and PTS inhibited melanogenesis in vitro and in vivo by activating the ERK signaling pathway. Full article

To investigate whether ocular albinism type 1 (OA1) is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of OA1 in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR), immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that OA1 mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of OA1 in the melanocytes’ pigmentation, we transfected the OA1 into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of OA1 significantly increased the expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TRP1) and premelanosome protein (PMEL). However, the tyrosinase-related protein 2 (TRP2) level was attenuated. By contrast, the level of glycoprotein non-metastatic melanoma protein b (GPNMB) was unaffected by OA1 overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected OA1. Therefore, we propose that OA1 may participate in the formation of coat color by regulating the level of MITF and the number, size, motility and maturation of melanosome. Full article