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Keywords = solar lentigines

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8 pages, 758 KB  
Brief Report
UVB-/Age-Dependent Upregulation of Inflammatory Factor Interleukin-6 Receptor (IL-6R) in Keratinocytes Stimulates Melanocyte Dendricity
by Daigo Inoue, Koji Ohba and Takako Shibata
Int. J. Mol. Sci. 2025, 26(22), 10971; https://doi.org/10.3390/ijms262210971 - 12 Nov 2025
Viewed by 136
Abstract
Ultraviolet (UV) irradiation stimulates melanogenesis in melanocytes and melanin transfer to keratinocytes, where the former is mediated by pleiotropic factors such as SCF, α-MSH, and endothelin-1 (ET-1) secreted by keratinocytes. Therefore, the interaction between melanocytes and keratinocytes after UVB exposure appears to be [...] Read more.
Ultraviolet (UV) irradiation stimulates melanogenesis in melanocytes and melanin transfer to keratinocytes, where the former is mediated by pleiotropic factors such as SCF, α-MSH, and endothelin-1 (ET-1) secreted by keratinocytes. Therefore, the interaction between melanocytes and keratinocytes after UVB exposure appears to be critical to stimulating melanogenesis. The factors that are responsible for inflammation, one of the key biological processes, are crucial to forming the chronic inflammatory microenvironment in solar lentigines (hereafter called age spots). While chronic inflammation is thought to be involved in hyperpigmentation, the molecular mechanisms through which microinflammation affects melanocyte activation in age spots have not been elucidated. In our study, immunohistochemical analysis showed that the expression of the inflammatory factor IL-6R is enhanced in age spots. Specifically, in cultured keratinocytes irradiated with 10 mJ/cm2 UVB, the expression of IL-6R was upregulated in UVB exposure- and age-dependent manners, and the co-culture of melanocytes with UVB-irradiated keratinocytes further demonstrated that melanocyte dendrites increased in length and number in a keratinocyte-age-dependent manner. Moreover, the suppression of IL-6R function in keratinocytes by an IL-6R-specific neutralizing antibody, Tocilizumab, inhibited melanocyte dendricity. These results indicate that the age- and UVB-dependent upregulation of IL-6R in keratinocytes stimulates melanocyte dendricity, which may also contribute to excessive melanin deposition in age spots. Full article
(This article belongs to the Special Issue Melanin Pigmentation: Physiology and Pathology)
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20 pages, 2124 KB  
Article
Repurposing the Antibiotic D-Cycloserine for the Treatment of Hyperpigmentation: Therapeutic Potential and Mechanistic Insights
by Ye-Jin Lee and Chang-Gu Hyun
Int. J. Mol. Sci. 2025, 26(16), 7721; https://doi.org/10.3390/ijms26167721 - 10 Aug 2025
Viewed by 836
Abstract
Melanin overproduction contributes to hyperpigmentation disorders such as melasma and solar lentigines, leading to increasing demand for safe and effective skin-lightening agents. D-cycloserine (DCS), a known antimicrobial agent, has not been previously evaluated for dermatological applications. This study aimed to explore the potential [...] Read more.
Melanin overproduction contributes to hyperpigmentation disorders such as melasma and solar lentigines, leading to increasing demand for safe and effective skin-lightening agents. D-cycloserine (DCS), a known antimicrobial agent, has not been previously evaluated for dermatological applications. This study aimed to explore the potential of DCS as a novel anti-melanogenic compound and to elucidate its underlying molecular mechanisms in melanogenesis inhibition. The cytotoxicity and anti-melanogenic effects of DCS were assessed in B16F10 melanoma cells stimulated with α-MSH. Cell viability was determined via MTT assays, while melanin content, tyrosinase activity, and the expression levels of MITF, TYR, TRP-1, TRP-2, and major signaling proteins (e.g., CREB, MAPKs, GSK-3β/β-catenin) were evaluated using colorimetric assays and Western blotting. A 3D human skin model was also used to confirm in vitro findings, and a primary skin irritation test was conducted to assess dermal safety. DCS significantly reduced α-MSH-induced melanin content and tyrosinase activity without cytotoxicity at concentrations ≤100 µM. It downregulated MITF and melanogenic enzyme expression and modulated signaling pathways by enhancing ERK activation while inhibiting CREB, JNK, and p38 phosphorylation. Additionally, DCS suppressed β-catenin stabilization via GSK-3β activation. These effects were confirmed in a 3D human skin model, and a clinical skin irritation study revealed no adverse reactions in human volunteers. DCS exerts its anti-melanogenic effect by targeting multiple pathways, including CREB/MITF, MAPK, and GSK-3β/β-catenin signaling. Its efficacy and safety profiles support its potential as a novel cosmeceutical agent for the treatment of hyperpigmentation. Further clinical studies are warranted to confirm its therapeutic utility in human skin pigmentation disorders. Full article
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16 pages, 2412 KB  
Article
Dynamic Network Driver Analysis Identifies Master Factors Associated with Progression of Solar Lentigines
by Deyu Cai, Hong Zhang, Chengming Zhang, Xue Xiao, Xiao Cui, Xuelan Gu and Luonan Chen
Biology 2025, 14(7), 876; https://doi.org/10.3390/biology14070876 - 17 Jul 2025
Viewed by 719
Abstract
Solar lentigines, commonly caused by prolonged ultraviolet exposure, raise the risk of skin disorders and remain challenging to manage due to their complex mechanisms. Understanding the molecular mechanisms driving the progression of solar lentigines is crucial for developing effective protective strategies. In this [...] Read more.
Solar lentigines, commonly caused by prolonged ultraviolet exposure, raise the risk of skin disorders and remain challenging to manage due to their complex mechanisms. Understanding the molecular mechanisms driving the progression of solar lentigines is crucial for developing effective protective strategies. In this study, we introduced a novel method, Dynamic Network Driver (DND), which identifies upstream regulators that drive disease progression by integrating the Dynamic Network Biomarker (DNB) approach with network control theory. By applying DND to multi-omics data from solar lentigines subjects, we (1) identified the key drivers associated with solar lentigo progression, with their functions involved in differentiation and dermal–epidermal junction; and (2) highlighted ARNT2 and TBX2 as significant master factors supported by in vitro validation in melanocytes and pigmented 3D living skin equivalent models. These results demonstrate the potency of DND for uncovering the molecular mechanisms behind solar lentigines and informing therapeutic strategies. In summary, the DND approach identified novel drivers of solar lentigo progression, acting as new markers for spot mitigation in 3D spot mimic models. Full article
(This article belongs to the Special Issue Physiology and Pathophysiology of Skin)
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27 pages, 5721 KB  
Article
Cutaneous Changes Beyond Psoriasis: The Impact of Biologic Therapies on Angiomas and Solar Lentigines
by Florin Ciprian Bujoreanu, Diana Sabina Radaschin, Ana Fulga, Laura Bujoreanu Bezman, Carmen Tiutiuca, Mihaela Crăescu, Carmen Pantiș, Elena Niculet, Alina Pleșea Condratovici and Alin Laurențiu Tatu
Medicina 2025, 61(4), 565; https://doi.org/10.3390/medicina61040565 - 22 Mar 2025
Viewed by 1612
Abstract
Background and Objectives: Psoriasis is a chronic inflammatory skin disease, and biologic therapies have revolutionized treatment by targeting key cytokine pathways. While these therapies effectively control psoriatic lesions, their impact on other cutaneous structures, such as cherry angiomas and solar lentigines, remains [...] Read more.
Background and Objectives: Psoriasis is a chronic inflammatory skin disease, and biologic therapies have revolutionized treatment by targeting key cytokine pathways. While these therapies effectively control psoriatic lesions, their impact on other cutaneous structures, such as cherry angiomas and solar lentigines, remains unclear. Angiomas are benign vascular proliferations influenced by systemic inflammation and hormonal factors, whereas solar lentigines are UV-induced pigmentary lesions associated with aging and sun exposure. This study aimed to assess the impact of biologic therapies on the development of these lesions in psoriasis patients. Materials and Methods: This retrospective observational study was conducted over a five-year period (2019–2024) at a tertiary dermatological center in Southeastern Europe. Clinical and demographic data, including treatment history, were extracted from medical records, while digital dermoscopy was used to assess lesion progression. Statistical analyses evaluated associations among biologic therapy classes, systemic inflammation, and cutaneous lesion development. Results: Angioma prevalence was significantly higher among postmenopausal women and those with osteoporosis, suggesting a hormonal influence on vascular proliferation. Patients with psoriatic arthritis had a greater angioma burden, reinforcing the role of chronic inflammation in angiogenesis. IL-23 inhibitors were linked to increased angioma formation compared to TNF-α inhibitors, while methotrexate and UVB therapy appeared to have a protective effect. Solar lentigines were more frequent in postmenopausal women and in patients with systemic inflammatory conditions. In contrast, smoking and moderate alcohol consumption were associated with lower lesion counts. Conclusions: Our findings suggest that biologic therapies, particularly IL-23 inhibitors, may contribute to angiogenesis and pigmentary changes in psoriasis patients, highlighting the influence of systemic inflammation on vascular and melanocytic activity. Additionally, TNF-α inhibitors and NSAIDs were associated with an increased prevalence of solar lentigines, while methotrexate and UVB therapy appeared to have a protective effect. Given these associations, further research is needed to elucidate the underlying mechanisms and refine treatment strategies to optimize dermatologic care for psoriasis patients. Full article
(This article belongs to the Special Issue Psoriasis: Pathogenesis and Therapy)
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10 pages, 2597 KB  
Communication
Comparing a Low-Fluence Picosecond 1064 nm Nd:YAG Laser with a 532 nm Nd:YAG Laser for the Treatment of Pigmented Lesions in Chinese Patients: A Retrospective Analysis
by Po-Hsuan Lu, Xiao-Feng Yao, Yang-Chih Lin and Pa-Fan Hsiao
Cosmetics 2024, 11(3), 89; https://doi.org/10.3390/cosmetics11030089 - 3 Jun 2024
Cited by 4 | Viewed by 14354
Abstract
The use of low-fluence picosecond (LFPS) 1064 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers, referred to as laser toning, is increasingly acknowledged as an effective treatment for pigmentation disorders in the Asian skin phenotype. This study aimed to conduct a comparative analysis on [...] Read more.
The use of low-fluence picosecond (LFPS) 1064 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers, referred to as laser toning, is increasingly acknowledged as an effective treatment for pigmentation disorders in the Asian skin phenotype. This study aimed to conduct a comparative analysis on the effectiveness and safety of utilizing LFPS 1064 nm Nd:YAG lasers against picosecond 532 nm Nd:YAG lasers in treating pigmented lesions among Chinese patients. A retrospective photographic analysis and chart reviews were performed on 31 subjects exhibiting Fitzpatrick skin types III–VI who underwent LFPS 1064 nm Nd:YAG or picosecond 532 nm Nd:YAG treatments at a single tertiary center. Utilizing VISIA Complexion Analysis, comparative photographs were taken. Two independent physicians evaluated treatment efficacy using a visual analog scale (VAS) to assess the percentage of pigmentary clearance in standard photographs. Solar lentigines were the most prevalent pigmentary disorder, followed by post-inflammatory hyperpigmentation (PIH), nevus zygomaticus, melasma, freckles, and nevus of Ota. The clinical effectiveness of picosecond 532 nm and LFPS 1064 nm laser treatments proved comparable for lesions on the face, with mean VAS scores of 2.2 ± 1.1 and 1.8 ± 0.8, respectively. There were two cases of PIH in the picosecond 532 nm group, which resolved within one month. Overall, the LFPS 1064 nm laser demonstrates promise as a safe and efficient therapeutic modality for managing pigmented lesions in Chinese patients. Full article
(This article belongs to the Special Issue Treatment for Anti-aging and Rejuvenation)
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7 pages, 1287 KB  
Article
Blue Laser (450 nm) Treatment of Solar Lentigines
by Jacek Szymańczyk, Witold Trzeciakowski, Yurij Ivonyak, Piotr Tuchowski, Artem Bercha and Janusz Szymańczyk
J. Clin. Med. 2021, 10(21), 4919; https://doi.org/10.3390/jcm10214919 - 24 Oct 2021
Cited by 6 | Viewed by 6306
Abstract
This study tested a blue light source for the treatment of solar lentigines. A total of 14 patients with solar lentigines were treated with radiation from a novel, high-power 450 nm blue laser that was created for this project. The group contained eight [...] Read more.
This study tested a blue light source for the treatment of solar lentigines. A total of 14 patients with solar lentigines were treated with radiation from a novel, high-power 450 nm blue laser that was created for this project. The group contained eight patients with solar lentigines on the face, two patients with the lesions on the dorsal of the hands, and four patients with the lesions on the trunk and forearms. The best results (complete recovery) have been achieved for the lesions on the face and dorsal of the hands. The treatment of lesions on the trunk and forearms was not fully satisfying due to the occurrence of slight scarring. This study shows that, in some cases, the use of a blue laser may be an alternative to the use of longer wavelength sources. Full article
(This article belongs to the Section Dermatology)
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11 pages, 1882 KB  
Article
A Randomized Controlled Trial on the Effectiveness of Epidermal Growth Factor-Containing Ointment on the Treatment of Solar Lentigines as Adjuvant Therapy
by Hye One Kim, Hye Ran Kim, Jin Cheol Kim, Seok Young Kang, Min Je Jung, Sung Eun Chang, Chun Wook Park and Bo Young Chung
Medicina 2021, 57(2), 166; https://doi.org/10.3390/medicina57020166 - 13 Feb 2021
Cited by 13 | Viewed by 6554
Abstract
Background and Objective: Little is known about the anti-pigmentation effects of whitening agents on solar lentigines. Epidermal growth factor (EGF) has been used as a booster for wound healing in the skin, and it has been suggested to have anti-pigmentation effects. This [...] Read more.
Background and Objective: Little is known about the anti-pigmentation effects of whitening agents on solar lentigines. Epidermal growth factor (EGF) has been used as a booster for wound healing in the skin, and it has been suggested to have anti-pigmentation effects. This study aimed to evaluate the effect and safety of EGF-containing ointment for treating solar lentigines with a Q-switched (QS) 532 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (Bluecore company, Seoul, Republic of Korea). Materials and Methods: Subjects who underwent QS 532 nm Nd:YAG laser treatment of solar lentigines were randomly assigned to treatment with an EGF ointment or petrolatum. After the laser procedure, the subjects were administered the test ointment twice a day for 4 weeks. The physician’s assessment of the degree of pigment clearance and patient’s satisfaction were assessed after 4 and 8 weeks. Additionally, the melanin index (MI), erythema index (EI), transepidermal water loss (TEWL), and post-inflammatory hyperpigmentation (PIH) were evaluated. This trial was registered with ClinicalTrials.gov (NCT04704245). Results: The blinded physician’s assessment using 5-grade percentage improvement scale and patient’s satisfaction were significantly higher in the study group than in the control group at the 4th and 8th weeks. The MI was significantly higher in the control group than in the study group at the 4th and 8th weeks. The EI and TEWL did not differ significantly between the two groups at either time point. The incidence of PIH was higher in the control group (37.5%) than in the EGF group (7.14%) at the 8th week. Conclusions: The application of EGF-containing ointment on facial solar lentigines with a QS 532 nm Nd:YAG laser showed efficient and safe therapeutic effects, with less PIH. Thus, EGF-containing ointment could be suggested as the promising adjuvant treatment strategy with a QS laser for solar lentigines. Full article
(This article belongs to the Section Dermatology)
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13 pages, 316 KB  
Article
Clinical Characteristics in Early Childhood Associated with a Nevus-Prone Phenotype in Adults from Tropical Australia: Two Decades of Follow-Up of the Townsville Preschool Cohort Study
by Ramez Barsoum and Simone L. Harrison
Int. J. Environ. Res. Public Health 2020, 17(22), 8680; https://doi.org/10.3390/ijerph17228680 - 23 Nov 2020
Cited by 4 | Viewed by 3402
Abstract
Having numerous melanocytic nevi increases melanoma risk. Few studies have enumerated nevi in children and re-examined them as adults. We aimed to determine if childhood nevus-counts predict nevus-prone adults, and further explore the relevance of host-factors and sun-exposure. Fifty-one Caucasian residents of Townsville [...] Read more.
Having numerous melanocytic nevi increases melanoma risk. Few studies have enumerated nevi in children and re-examined them as adults. We aimed to determine if childhood nevus-counts predict nevus-prone adults, and further explore the relevance of host-factors and sun-exposure. Fifty-one Caucasian residents of Townsville (19.16° S, Queensland, Australia) had full-body nevus-counts aged 1–6 and 21–31 years-old. Sun-exposure was determined from questionnaires. Children in the upper-quartile of nevus-counts acquired nevi more rapidly than those in the bottom-quartile (13.3 versus 4.7 nevi/year; p < 0.0005). Children sunburnt before 7 years-old acquired more incident nevi by adulthood (238 versus 126, p = 0.003) particularly if sunburn was severe (321 versus 157.5, p = 0.003) or erythema occurred annually (380 versus 132, p = 0.008). Fair-skinned, freckled children with some nevi ≥ 3 mm, solar lentigines, or a family history of melanoma acquired more incident nevi than children without these attributes. Nevus-prone adults exhibit distinguishing features earlier in life (<7 years-old in Queensland) than has been shown previously. In addition to intervening with sun-protection counselling early enough to reduce risk, being able to reliably triage children into high- and low melanoma-risk groups may inform more efficacious and cost-effective targeted-screening in melanoma-prone populations. Further longitudinal research is needed to confirm that these attributes can reliably separate risk-groups. Full article
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