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1.
Eur J Cancer ; 204: 114074, 2024 Jun.
Article En | MEDLINE | ID: mdl-38691877

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.


Skin Neoplasms , Ultraviolet Rays , Humans , Skin Neoplasms/prevention & control , Skin Neoplasms/etiology , Skin Neoplasms/epidemiology , Ultraviolet Rays/adverse effects , Skin Pigmentation/radiation effects , Sunscreening Agents/therapeutic use , Melanoma/prevention & control , Melanoma/etiology , Melanoma/epidemiology , Neoplasms, Radiation-Induced/prevention & control , Neoplasms, Radiation-Induced/etiology , Neoplasms, Radiation-Induced/epidemiology , Risk Factors
2.
Int J Mol Sci ; 25(10)2024 May 10.
Article En | MEDLINE | ID: mdl-38791225

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.


Epidermis , Melanins , Melanocytes , Plasma Gases , Humans , Melanins/metabolism , Melanins/biosynthesis , Melanocytes/metabolism , Melanocytes/drug effects , Plasma Gases/pharmacology , Epidermis/metabolism , Epidermis/drug effects , Epidermis/radiation effects , Ultraviolet Rays , Skin Pigmentation/drug effects , Skin Pigmentation/radiation effects , Cells, Cultured , Reactive Oxygen Species/metabolism , Biopsy , Melanogenesis
3.
Int J Dermatol ; 63(6): 806-815, 2024 Jun.
Article En | MEDLINE | ID: mdl-38685118

BACKGROUND: Acne-induced hyperpigmentation (AIH) may accompany acne vulgaris (AV) inflammation in all skin phototypes. Trifarotene has shown depigmenting properties in vivo. This study evaluated trifarotene plus skincare because it is increasingly recognized that holistic AV management should include skincare and treatments. METHODS: This is a phase IV double-blind, parallel-group study of patients (13-35 years) with moderate AV and AIH treated with trifarotene (N = 60) or vehicle (N = 63) plus skincare regimen (moisturizer, cleanser, and sunscreen) for 24 weeks. Assessments included the AIH overall disease severity (ODS) score, post-AV hyperpigmentation index (PAHPI), exit interviews, photography, and acne assessments. Standard safety assessments were included. RESULTS: Trifarotene 50 µg/g cream improved significantly from baseline in ODS score versus vehicle (-1.6 vs. -1.1, P = 0.03) at Week 12, but scores were comparable between groups at Week 24 (primary endpoint). Trifarotene had a better reduction in PAHPI score at Week 24 (-18.9% vs. -11.3% vehicle, P < 0.01). Lesion count reductions were higher with trifarotene at Week 12 versus vehicle (P < 0.001) and at Week 24 (P < 0.05), as were IGA success rates versus vehicle at Weeks 12 (P < 0.05) and 24 (P < 0.05). Patients agreed that the skincare regimen contributed to less irritation, making treatment adherence easier. Photography showed improvements in pigmentation and erythema across all skin types. AEs were more common in the vehicle group versus trifarotene (30.2 vs. 16.7%, respectively). CONCLUSIONS: In all skin phototypes, there was more rapid improvement in the ODS and PAHPI scores with trifarotene by Weeks 12 and 24, respectively. The combination of trifarotene and skincare correlated with high patient satisfaction and adherence to the treatment protocol.


Acne Vulgaris , Hyperpigmentation , Severity of Illness Index , Skin Care , Skin Pigmentation , Sunscreening Agents , Humans , Acne Vulgaris/complications , Acne Vulgaris/drug therapy , Hyperpigmentation/etiology , Hyperpigmentation/drug therapy , Hyperpigmentation/prevention & control , Double-Blind Method , Female , Male , Adolescent , Adult , Young Adult , Skin Care/methods , Sunscreening Agents/administration & dosage , Skin Pigmentation/drug effects , Skin Pigmentation/radiation effects , Dermatologic Agents/administration & dosage , Dermatologic Agents/adverse effects , Skin Cream/administration & dosage , Retinoids
4.
J Cosmet Dermatol ; 23(5): 1745-1752, 2024 May.
Article En | MEDLINE | ID: mdl-38372022

BACKGROUND: Chronic nonextreme sun exposure induces two mechanisms of skin pigmentation, causing immediate darkening and delayed tanning. A new molecule, 2-mercaptonicotinoyl glycine (2-MNG), has been shown in vitro to inhibit both immediate darkening and new melanin synthesis via covalent conjugation of the thiol group of 2-MNG to melanin precursors. OBJECTIVE: To evaluate 2-MNG in preventing both mechanisms in vivo. METHODS: In a randomized, intra-individual and controlled study, 33 subjects with melanin-rich skin were exposed to UV daylight on designated areas on the back and treated with a cosmetic formula containing 0.5% or 1% 2-MNG alone or 0.5% 2-MNG in association with lipohydroxy acid (LHA, 0.3%) plus Mexoryl-SX (MSX, 1.5%). The respective vehicles were used as controls and 4-n-butyl-resorcinol (4-n-BR, 2.5%) as a positive reference. RESULTS: 2-MNG alone significantly reduced immediate darkening and inhibited new melanin production when compared with vehicle, with higher performance at 1% than at 0.5%. 2-MNG at 0.5% in association with LHA and MSX showed significantly higher performance than 2-MNG 0.5% alone. 2-MNG at 0.5% and 1% showed significantly better performance than 4-n-BR. CONCLUSIONS: 2-MNG inhibited both UV-induced skin pigmentation mechanisms in vivo. The association of 2-MNG with LHA plus MSX showed the highest efficacy on melanin-rich skin with pigmentation induced by UV exposure.


Glycine , Skin Pigmentation , Ultraviolet Rays , Humans , Adult , Ultraviolet Rays/adverse effects , Female , Skin Pigmentation/drug effects , Skin Pigmentation/radiation effects , Male , Glycine/pharmacology , Glycine/administration & dosage , Glycine/analogs & derivatives , Melanins/radiation effects , Healthy Volunteers , Young Adult , Middle Aged , Sunbathing , Skin/radiation effects , Skin/drug effects , Skin/metabolism
5.
Pigment Cell Melanoma Res ; 37(3): 378-390, 2024 May.
Article En | MEDLINE | ID: mdl-38343115

We have discovered that human vitiligo patients treated with narrow-band UVB (NBUVB) demonstrated localized resistance to repigmentation in skin sites characterized by distinct cellular and molecular pathways. Using immunostaining studies, discovery-stage RNA-Seq analysis, and confirmatory in situ hybridization, we analyzed paired biopsies collected from vitiligo lesions that did not repigment after 6 months of NBUVB treatment (non-responding) and compared them with repigmented (responding) lesions from the same patient. Non-responding lesions exhibited acanthotic epidermis, had low number of total, proliferative, and differentiated melanocyte (MC) populations, and increased number of senescent keratinocytes (KCs) and of cytotoxic CD8+ T cells as compared with responding lesions. The abnormal response in the non-responding lesions was driven by a dysregulated cAMP pathway and of upstream activator PDE4B, and of WNT/ß-catenin repigmentation pathway. Vitiligo-responding lesions expressed high levels of WNT10B ligand, a molecule that may prevent epidermal senescence induced by NBUVB, and that in cultured melanoblasts prevented the pro-melanogenic effect of α-MSH. Understanding the pathways that govern lack of NBUVB-induced vitiligo repigmentation has a great promise in guiding the development of new therapeutic strategies for vitiligo.


Epidermis , Melanocytes , Skin Pigmentation , Vitiligo , Vitiligo/pathology , Vitiligo/radiotherapy , Vitiligo/metabolism , Humans , Epidermis/pathology , Epidermis/metabolism , Epidermis/radiation effects , Skin Pigmentation/radiation effects , Melanocytes/pathology , Melanocytes/metabolism , Melanocytes/radiation effects , Ultraviolet Therapy/methods , Keratinocytes/metabolism , Keratinocytes/pathology , Keratinocytes/radiation effects , Ultraviolet Rays , Female , Male , Wnt Signaling Pathway , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 4/genetics
6.
Dermatol Surg ; 50(5): 459-466, 2024 May 01.
Article En | MEDLINE | ID: mdl-38335306

BACKGROUND: Fractional nonablative lasers (NAFLs) have demonstrated efficacy and safety for treating dermatologic conditions in patients with darker skin phototypes. Nonablative lasers are preferred in darker skin tones due to lower risk of postinflammatory hyperpigmentation. OBJECTIVE: This review aims to identify the ideal laser options and parameters for treating common dermatologic conditions in patients with skin types IV-VI. MATERIALS AND METHODS: A comprehensive literature search was conducted on PubMed in May 2023. Of 1,065 articles were identified, and 40 articles met the inclusion criteria. The studies were classified based on design, dermatologic condition, and skin phototype of patients, and assigned levels of evidence according to the Modified Criteria of the Oxford Center of Evidence Based Medicine. RESULTS: Strong level 1 evidence supports the treatment of melasma and atrophic scars using NAFL. Moderate level 2 evidence was found for using NAFL in acne vulgaris, striae, and skin rejuvenation; 45% of the studies examined skin types III-IV, 20% III-V, 7.5% II-IV, 5% II-V, 5% IV alone, and 2.5% I-IV. CONCLUSION: Further research is needed to determine the optimal treatment modalities and parameters for skin types V and VI. Appropriate device selection and conservative treatment settings are crucial for optimizing outcomes and minimizing adverse events.


Acne Vulgaris , Melanosis , Humans , Acne Vulgaris/complications , Acne Vulgaris/therapy , Melanosis/therapy , Skin Pigmentation/radiation effects , Rejuvenation , Skin Diseases/therapy , Laser Therapy/instrumentation , Laser Therapy/adverse effects , Laser Therapy/methods , Cicatrix/etiology , Cicatrix/therapy , Striae Distensae/therapy , Skin Aging/radiation effects
7.
J Eur Acad Dermatol Venereol ; 37 Suppl 4: 3-11, 2023 Apr.
Article En | MEDLINE | ID: mdl-36994912

BACKGROUND: Solar light induces or aggravates hyperpigmentation issues. The contribution of UVA1, as well as visible light (VL), especially high-energy blue-violet visible (HEV) light, is now clearly established. OBJECTIVES: This work aimed at determining the relative contribution of UVA1, HEV and VL wavelength bands and their sub-domains in pigmentation induction. METHODS: Two clinical studies using solar simulators equipped with specific bandpass physical filters were carried out. Volunteers (FSPT III-IV) were exposed on the back to UVA1 + HEV (350-450 nm), UVA1 (350-400 nm), HEV (400-450 nm) or part of UVA1 + HEV (370-450 nm) in Study 1 (n = 27) and to VL (400-700 nm), HEV (400-450 nm), Blue (400-500 nm), Green (500-600 nm) and Green+Red (500-700 nm) domains in Study 2 (n = 25). Pigmentation level was assessed by visual scoring and colorimetry at different time points postexposure, up to Day 43. RESULTS: Induced pigmentation was detected in all exposed conditions, peaking at 2 h and thereafter progressively decreasing but remaining persistent up to Day 43. In Study 1, UVA1 showed an additive effect with HEV, with a significant contribution coming from the Longest UVA1 rays (370-400 nm). Study 2 demonstrated that 24 h postexposure, the Blue domain accounted for 71% of VL-induced pigmentation, the HEV one for 47%, the Green one for 37% and the Green+Red one for 36%, confirming no significant effect for Red light. CONCLUSIONS: Altogether, these results underline the need for UVA1 photoprotection up to 400 nm and highlight the importance of protecting the skin from solar VL wavelengths and especially from HEV, Blue and Green light, to limit induced pigmentation.


Light , Skin Pigmentation , Suntan , Humans , Color , Skin/radiation effects , Skin Pigmentation/radiation effects , Ultraviolet Rays , Suntan/radiation effects
8.
J Cosmet Dermatol ; 22(4): 1261-1265, 2023 Apr.
Article En | MEDLINE | ID: mdl-36756716

BACKGROUND: Laser has been long accepted as a solution for excess or unwanted hair growth yet traditional lasers are not always ideal for safe and effective outcome for all skin types and hair characteristics. A diode laser module combining three wavelengths (755, 810, and 1064 nm) in a single pulse was developed to provide a fast and long-term solution for subjects with various profiles. AIMS: To evaluate the safety and efficacy of a Triple wavelength diode laser module for hair removal treatment in all skin types (Fitzpatrick I-VI). SUBJECTS AND METHODS: This was a prospective, dual centered, single-arm study. Subjects were treated with a novel diode laser module. Thirty-six subjects were enrolled, sixteen with Fitzpatrick skin types I-IV (46%) and twenty with Fitzpatrick skin types V-VI (54%). Treatment areas were axilla and bikini lines. Subjects underwent 4 treatment sessions at 6 weeks ± 5 days intervals and attended a follow-up visit 3 months after the last treatment session. 2D digital photographs were taken at baseline and at the follow-up visit, and a hair count was conducted by three blinded evaluators. RESULTS: A significant reduction in hair count between baseline and the 3-month follow-up visit was observed in both axilla and bikini lines for all skin types. The mean hair reduction was 41.5 ± 19.4% and 48.1 ± 20.9% in the axilla and bikini line, respectively. A significant hair reduction was also observed within skin type groups; mean hair reduction 45.5 ± 16.9% and 40.3 ± 17.2% in skin types I-IV and V-VI, respectively, indicating similar efficacy for both light and dark skin types. No serious adverse events were reported. CONCLUSIONS: This study demonstrates that the Soprano Titanium laser platform is safe and effective for hair removal treatment in all skin types.


Hair Removal , Low-Level Light Therapy , Skin Pigmentation , Humans , Hair , Hair Removal/adverse effects , Hair Removal/methods , Lasers, Semiconductor/adverse effects , Lasers, Semiconductor/therapeutic use , Prospective Studies , Treatment Outcome , Low-Level Light Therapy/adverse effects , Low-Level Light Therapy/methods , Axilla , Abdomen , Skin Pigmentation/radiation effects , Sunburn/etiology , Suntan/radiation effects
9.
J Photochem Photobiol B ; 228: 112405, 2022 Mar.
Article En | MEDLINE | ID: mdl-35189578

Our exposure to blue light from artificial sources such as indoor lights (mainly light-emitting diodes [LEDs]) and electronic devices (e.g., smartphones, computer monitors, and television screens), has increased in recent years, particularly during the recent coronavirus disease 2019 lockdown. This radiation has been associated to skin damage across its potential in generating reactive oxygen species in both the epidermis and the dermis, skin water imbalances and of potential activating melanin production. These circumstances make it important to determine whether current blue light exposure levels under artificial illumination and electronic devices exposure can cause the previously indicated disorders as compared to solar UV and visible radiation in a typical summer day. Blue light accounted for 25% of the sun's rays, approximately 30% of radiation emitted by electronic devices, and approximately from 6% to 40% of that emitted by indoor lights. The reference equations showed that the sun was the main source of effective irradiance for immediate and persistent pigmentation as well as for potential oxidative stress in our skin. Effective blue light exposure to artificial devices is significantly lower than the solar contribution. However, its contribution must be considered as accumulative dose effect, and especially in people with hypersensitivity promoting skin hyperpigmentation.


Light , Melanins/metabolism , Oxidative Stress/radiation effects , Ultraviolet Rays , Electronics , Humans , Skin Pigmentation/radiation effects
10.
Molecules ; 27(2)2022 Jan 11.
Article En | MEDLINE | ID: mdl-35056769

Dermal macrophages containing melanin increase skin pigmentation since dermal melanin removal is slower than epidermal melanin removal. Lymphatic vessels are also involved in melanin clearance. We evaluated whether radiofrequency (RF) irradiation induced an increase in HSP90, which promotes lymphangiogenesis by activating the BRAF/MEK/ERK pathway and decreasing tyrosinase activity, in the UV-B exposed animal model. The HSP90/BRAF/MEK/ERK pathway was upregulated by RF. Tyrosinase activity and the VEGF-C/VEGFR 3/PI3K/pAKT1/2/pERK1/2 pathway, which increase lymphangiogenesis, as well as the expression of the lymphatic endothelial marker LYVE-1, were increased by RF. Additionally, the number of melanin-containing dermal macrophages, the melanin content in the lymph nodes, and melanin deposition in the skin were decreased by RF. In conclusion, RF increased HSP90/BRAF/MEK/ERK expression, which decreased tyrosinase activity and increased lymphangiogenesis to eventually promote the clearance of dermal melanin-containing macrophages, thereby decreasing skin pigmentation.


Lymphangiogenesis/radiation effects , Radio Waves , Skin Pigmentation/radiation effects , Ultraviolet Rays , Biomarkers , Extracellular Signal-Regulated MAP Kinases/metabolism , HSP90 Heat-Shock Proteins , Hyperpigmentation/etiology , Hyperpigmentation/metabolism , Hyperpigmentation/pathology , Immunohistochemistry , Macrophages/immunology , Macrophages/metabolism , Macrophages/radiation effects , Melanins/biosynthesis , Models, Biological , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , Signal Transduction/radiation effects , Vascular Endothelial Growth Factor C/metabolism , Vascular Endothelial Growth Factor Receptor-3/metabolism
11.
Dermatol Surg ; 48(1): 109-113, 2022 01 01.
Article En | MEDLINE | ID: mdl-34608097

BACKGROUND AND OBJECTIVES: Picosecond (ps) fractional lasers create small wounds, presumably by laser-induced optical breakdown. We studied a ps fractional laser in the treatment of wrinkles and mottled pigment. MATERIALS AND METHODS: This was a single center, prospective, open-label clinical trial. Patients with at least 2 facial areas, with visible wrinkles and dyschromia, were enrolled in the study and received 3 treatments at monthly intervals and appeared at 3 follow-up visits at 1, 3, and 6 months after treatment. The laser is an 800 ps fractional system with nominal 10 mm macrospot diameter. Both 532 nm and 1,064 nm wavelengths were applied in each subject. Wrinkle and pigmentation clearance were assessed by 2 blinded investigators using a 5-point clearance scale. Skin improvement was assessed by investigators using the 5-point Global Aesthetic Improvement (GAI) Scale based on before/after photographs for the following categories: (1) fine lines/wrinkles and (2) pigmentation. RESULTS: A total of 18 healthy subjects at a single site were enrolled. At least moderate pigmentation and fine line/wrinkles improvement were observed in 93% and 79% of patients at 1 month after the last treatment according to GAI, respectively. Pigment clearance approached a mean of approximately 40%. CONCLUSION: A ps 1,064/532 fractional laser achieves reduction in fine lines and pigment.


Laser Therapy/methods , Skin Aging/radiation effects , Skin Pigmentation/radiation effects , Esthetics , Face , Female , Follow-Up Studies , Healthy Volunteers , Humans , Laser Therapy/instrumentation , Middle Aged , Prospective Studies , Rejuvenation , Treatment Outcome
12.
Clin Breast Cancer ; 22(2): e224-e231, 2022 02.
Article En | MEDLINE | ID: mdl-34400081

BACKGROUND: In the current study, we sought to evaluate and compare the objective changes in biophysical parameters and patient-reported outcomes following radiation therapy (RT) in patients with breast cancer who underwent breast-conserving surgery (BCS) or modified radical mastectomy (MRM). MATERIALS AND METHODS: Patients older than 18 years, with stage I to III breast cancer, who were expected to receive RT were recruited between August 2015 and March 2019. Skin hydration, sebum content, pigmentation, and elasticity of the irradiated and unirradiated breast or chest wall were assessed using a noninvasive bioengineering device. Assessments were performed before the initiation of RT (T0); after the 5th (T1), 15th (T2), and 25th (T3) fractions; and 1 (T4) and 3 months (T5) after the completion of RT. Patient-reported outcomes were also evaluated using Radiation Dermatitis Assessment for Breast Cancer 11. RESULTS: Hydration and sebum levels on the irradiated breast decreased during RT and had not returned to baseline at T5. Erythema on the irradiated breast increased two-fold between T0 and T3, and melanin levels were significantly higher than those at baseline and those of the contralateral unirradiated breast until T5 (106.0 vs. 115.8, P = .03). More than half of the patients continued to report skin color changes, dryness, and pain after RT. The erythema in the irradiated site at T1 was significantly higher in the MRM group than in the BCS group (P for interaction = .04), while there were no significant differences in the changes of the other parameters. CONCLUSION: RT-induced changes in hydration, sebum, and melanin, and the majority of patient-reported pain, color changes, and dryness, even 3 months after the completion of treatment. There were no remarkable differences in the measurable skin parameters according to the surgery type, with the exception of erythema, which was higher in the MRM group 1 week after the start of RT.


Breast Neoplasms/radiotherapy , Radiotherapy, Adjuvant/adverse effects , Skin Diseases/chemically induced , Skin Diseases/diagnosis , Adult , Aged , Breast Neoplasms/pathology , Female , Humans , Hydrogen-Ion Concentration , Middle Aged , Prospective Studies , Skin/radiation effects , Skin Pigmentation/radiation effects
13.
Molecules ; 26(24)2021 Dec 17.
Article En | MEDLINE | ID: mdl-34946730

Excess melanin deposition in the skin causes cosmetic problems. HSP70 upregulation decreases microphthalmia-associated transcription factor (MITF) expression, which eventually decreases tyrosinase activity and melanogenesis. Ultraviolet (UV) radiation upregulates p53, which increases the melanocortin receptor (MC1R) and MITF. Furthermore, HSP70 decreases p53 and radiofrequency irradiation (RF) increases HSP70. We evaluated whether RF increased HSP70 and decreased p53, consequently decreasing the MITF/tyrosinase pathway and melanogenesis in UV-B radiated animal skin. Various RF combinations with 50, 100, and 150 ms and 5, 10, and 15 W were performed on the UV-B radiated mouse skin every 2 d for 28 d. When RF was performed with 100 ms/10 W, melanin deposition, evaluated by Fontana-Masson staining, decreased without skin crust formation in the UV-B radiated skin. Thus, we evaluated the effect of RF on decreasing melanogenesis in the HEMn and UV-B radiated skin at a setting of 100 ms/10 W. HSP70 expression was decreased in the UV-B radiated skin but was increased by RF. The expression of p53, MC1R, and MITF increased in the UV-B radiated skin but was decreased by RF. The expression of p53, MC1R, and MITF increased in the α-MSH treated HEMn but was decreased by RF. The decreasing effects of RF on p53, MC1R, CREB and MITF were higher than those of HSP70-overexpressed HEMn. The decreasing effect of RF on p53, MC1R, CREB, and MITF disappeared in the HSP70-silenced HEMn. MC1R, CREB, and MITF were not significantly decreased by the p53 inhibitor in α-MSH treated HEMn. RF induced a greater decrease in MC1R, CREB, and MITF than the p53 inhibitor. Therefore, RF may have decreased melanin synthesis by increasing HSP70 and decreasing p53, thus decreasing MC1R/CREB/MITF and tyrosinase activity.


HSP70 Heat-Shock Proteins/biosynthesis , Melanins/biosynthesis , Radio Waves , Skin Pigmentation/radiation effects , Ultraviolet Rays , Up-Regulation/radiation effects , Animals , Male , Mice
14.
Curr Probl Dermatol ; 55: 354-373, 2021.
Article En | MEDLINE | ID: mdl-34698025

In photodermatology, UV radiation is the component of the solar system that has attracted the most interest as it represents the greatest risk of skin damage from solar exposure. Efficient protection strategies have therefore been developed to protect skin against powerful solar radiation. Recently, there has been increasing evidence to suggest that less energetic radiation, such as visible light and infrared radiation, might also influence skin physiology. Yet, it remains unclear, regarding risk assessment, whether visible light irradiation induces positive or negative effects in skin and when appropriate protection is needed. This review focuses primarily on blue light as part of the visible spectrum and sets out current mechanistic understanding of the benefits and risks of blue-light exposure to skin. Furthermore, it discusses phototherapies and potential strategies for protecting against detrimental effects of blue light such as hyperpigmentation and premature skin aging.


Light/adverse effects , Skin Aging/radiation effects , Skin Pigmentation/radiation effects , Humans , Risk Assessment , Skin/metabolism , Skin/radiation effects
15.
Int J Mol Sci ; 22(19)2021 Sep 27.
Article En | MEDLINE | ID: mdl-34638746

A 308 nm monochromatic excimer light (MEL) is widely used to treat patients with vitiligo. However, dose optimization still needs to be clarified. This study aimed to obtain objective evidence regarding various doses of MEL irradiation, induced cell level changes in vitro, and skin level alterations in vivo. Cultured human keratinocytes were irradiated with MEL using various doses. After irradiation at low doses, stem cell factor, endothelin-1, and glycoprotein nonmetastatic melanoma protein B, factors that activate and protect melanocytes, were found to be significantly elevated in keratinocytes. After irradiation using medium and high doses, inflammatory cytokines were induced. The amount of ATP released and the level of inflammasome activation, which are known to be related to interleukin-1ß activation, were also increased. The back skin of guinea pigs and mice were irradiated with MEL at varying doses. After irradiation, an increase of epidermal melanin and epidermal melanocytes was confirmed, using the minimal erythemal dose or less. In rhododendrol-induced leukoderma guinea pigs, a much lower dose of MEL irradiation was effective, when compared with the effective dose for control guinea pigs. Our results suggest that a lower irradiation dose of MEL might be sufficient and more suitable for repigmentation in vitiligo treatment.


Keratinocytes/metabolism , Melanocytes/metabolism , Skin Pigmentation/radiation effects , Ultraviolet Therapy , Vitiligo , Animals , Cell Line , Female , Guinea Pigs , Humans , Mice , Vitiligo/metabolism , Vitiligo/radiotherapy
16.
Int J Mol Sci ; 22(19)2021 Oct 03.
Article En | MEDLINE | ID: mdl-34639063

Autophagy is involved in the degradation of melanosomes and the determination of skin color. TLR4 and tumor necrosis factor (TNF) signaling upregulates NF-kB expression, which is involved in the upregulation of mTOR. The activation of mTOR by UV-B exposure results in decreased autophagy, whereas radiofrequency (RF) irradiation decreases TLR4 and TNF receptor (TNFR) expression. We evaluated whether RF decreased skin pigmentation by restoring autophagy by decreasing the expression of TLR4 or TNFR/NF-κB/mTOR in the UV-B-irradiated animal model. UV-B radiation induced the expressions of TNFR, TLR, and NF-κB in the skin, which were all decreased by RF irradiation. RF irradiation also decreased phosphorylated mTOR expression and upregulated autophagy initiation factors such as FIP200, ULK1, ULK2, ATG13, and ATG101 in the UV-B-irradiated skin. Beclin 1 expression and the expression ratio of LC3-I to LC3-II were increased by UV-B/RF irradiation. Furthermore, melanin-containing autophagosomes increased with RF irradiation. Fontana-Masson staining showed that the amount of melanin deposition in the skin was decreased by RF irradiation. This study showed that RF irradiation decreased skin pigmentation by restoring melanosomal autophagy, and that the possible signal pathways which modulate autophagy could be TLR4, TNFR, NF-κB, and mTOR.


Autophagy/radiation effects , Melanins/biosynthesis , Melanosomes/metabolism , Radio Waves , Skin Pigmentation/radiation effects , Ultraviolet Rays , Biomarkers , Cells, Cultured , Gene Expression Regulation/radiation effects , Humans , Immunohistochemistry , NF-kappa B/metabolism , Receptors, Tumor Necrosis Factor/genetics , Receptors, Tumor Necrosis Factor/metabolism , Skin Pigmentation/genetics , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Toll-Like Receptor 4/metabolism
17.
Curr Probl Dermatol ; 55: 157-169, 2021.
Article En | MEDLINE | ID: mdl-34698042

In 1978, the FDA Advisory Panel proposed both indoor and natural sunlight SPF testing methods but reverted to indoor testing only in 1993. Today's sunscreen sun protection and broad-spectrum claims are based on mandated clinical tests using solar simulators and in vitro spectrophotometers. This research evaluated the protection of 10 high-SPF (30-110), broad-spectrum sunscreen products, as well as 6 sun-protective fabrics against natural sunlight in Arequipa, Peru. Each of the 17 subjects was exposed to natural sunlight for 1 h and 59 min under clear skies, with temperatures and humidity similar to those in an indoor clinical laboratory. Test sites were photographed 16-24 h later. Four dermatologists evaluated the photographs for erythema and persistent pigment darkening (PPD). Perceptible sun-induced skin injury (sunburn and/or pigmentation) was detected at 97% of the sunscreen-protected scores. The most sun-sensitive subjects obtained the least erythema protection. The higher the SPF was, the higher the erythema protection, but the intensity of PPD was also higher. The 2 sunscreens using only FDA-approved sunscreen filters rated 30 SPF and 45+ SPF performed poorly: Eighty-one percent of the 136 scores were graded 1 minimal erythema dose or higher erythema, achieving, at a maximum, SPF of 5-7 in natural sunlight. Sun-protective fabrics tested provided excellent sun protection. The erythema and PPD observed through the sunscreens in less than 2 h are incongruous with the broad-spectrum, high-SPF sunscreen claims. Reapplying these sunscreens and staying in the sun longer, as stated on the product labels, would have subjected the subjects to even more UV exposure. High-SPF, broad-spectrum sunscreen claims based on indoor solar simulator testing do not agree with the natural sunlight protection test results.


Protective Clothing/standards , Sun Protection Factor/methods , Sunlight/adverse effects , Sunscreening Agents/chemistry , Textiles/standards , Drug Evaluation, Preclinical/methods , Drug Evaluation, Preclinical/standards , Erythema/etiology , Erythema/prevention & control , Female , Healthy Volunteers , Humans , Male , Peru , Skin/drug effects , Skin/radiation effects , Skin Pigmentation/drug effects , Skin Pigmentation/radiation effects , Sun Protection Factor/standards , Sunscreening Agents/administration & dosage , Sunscreening Agents/standards
18.
Photochem Photobiol Sci ; 20(10): 1299-1307, 2021 Oct.
Article En | MEDLINE | ID: mdl-34559384

PUVA is a treatment that combines oral methoxypsoralen (8-MOP) with ultraviolet radiation A (UVA). It is used for severe psoriasis and the early stages of T-cell lymphoma. X-rays are an effective treatment for skin cancers. Both treatments are in higher doses used to treat skin malignancies and simultaneously increase the risk of keratinocyte cancer. The main objective of this study was to test whether a few PUVA or X-ray treatments could delay the development of ultraviolet radiation (UVR)-induced skin tumors in a well-established hairless mouse model. Three groups of immunocompetent mice (total, N = 75) were included in the study. All groups were UVR-exposed during the study period. In addition, one group was treated with PUVA and another group was treated with X-rays at days 45, 52, 90 and 97. A control group was treated with UVR only. We recorded when the first, second and third skin tumors were induced in each mouse. Skin tumors developed significantly earlier in both the PUVA and X-ray groups (median, 188 days) than in the control mice (median, 215 days; p < 0.001). Therefore, a few X-ray and PUVA treatments both significantly accelerated the development of skin tumors in hairless mice, compared to UVR controls. Neither treatment showed a delay of UVR-induced skin tumors and caution should be exercised before applying these treatments to sun-damaged skin.


Methoxsalen/adverse effects , Skin Neoplasms/etiology , Ultraviolet Rays , Animals , Immunocompromised Host , Kaplan-Meier Estimate , Methoxsalen/chemistry , Methoxsalen/pharmacology , Mice , Mice, Hairless , Neoplasms, Radiation-Induced/etiology , Skin/pathology , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Skin Pigmentation/drug effects , Skin Pigmentation/radiation effects , X-Rays
19.
Am J Clin Dermatol ; 22(6): 829-836, 2021 Nov.
Article En | MEDLINE | ID: mdl-34468934

Acne vulgaris is a common inflammatory disease. Among patients with darker skin phototypes (Fitzpatrick III-VI), the inflammatory processes of acne stimulate excess melanogenesis and abnormal melanin deposition, leading to pigmentary sequelae known as post-inflammatory hyperpigmentation and post-inflammatory erythema in all skin tones, although post-inflammatory hyperpigmentation is more common in darker skin and post-inflammatory erythema in lighter skin. These pigmentary alterations can be long lasting and are often more distressing to patients than the active acne lesions. This article discusses what is known about acne-related pigmentation, much of which is extrapolated from general study of nonspecific pigment deposition. Because dyspigmentation poses both a significant clinical concern to patients and a therapeutic challenge to clinicians, we formed a working group consisting of pigmentary experts with the aim of increasing awareness and education of acne-related pigmentary sequelae.


Acne Vulgaris/complications , Hyperpigmentation/therapy , Skin Pigmentation/immunology , Acne Vulgaris/immunology , Anti-Inflammatory Agents/therapeutic use , Combined Modality Therapy/methods , Dermabrasion/methods , Dermatologic Agents/therapeutic use , Humans , Hyperpigmentation/immunology , Hyperpigmentation/pathology , Low-Level Light Therapy/instrumentation , Low-Level Light Therapy/methods , Melanins/antagonists & inhibitors , Melanins/biosynthesis , Skin/immunology , Skin/pathology , Skin Pigmentation/drug effects , Skin Pigmentation/radiation effects
20.
J Photochem Photobiol B ; 222: 112276, 2021 Sep.
Article En | MEDLINE | ID: mdl-34358884

Despite decades of research, the role of elevated solar ultraviolet-B radiation (UVBR; 280-315 nm) in shaping amphibian populations remains ambiguous. These difficulties stem partly from a poor understanding of which parameters of UVBR exposure - dose, irradiance, and time interval - determine UVBR exposure health risk, and the potentially erroneous assumption that effects are proportional to the dose of exposure, irrespective of the administered regime (Bunsen-Roscoe Law of Reciprocity; BRL). We tested if the BRL holds with respect to UVBR-induced physiological effects in amphibians by acutely exposing tadpoles of the Australian green tree frog (Litoria caerulea) to a combination of different UVBR irradiances and doses in a fully factorial experiment. The BRL was invalid across all metrics assessed, with UVBR irradiance influencing the effects of a given dose on growth, coloration and burst swimming performance of larvae. We demonstrated some of the first empirical evidence for beneficial physiological effects of UVBR exposure in a larval amphibian, with improvements in growth, burst swimming performance and survival at the highest UVBR doses, contrary to hypotheses. Our findings demonstrate the species-specific nature of amphibian responses to UVBR, and the importance of UVBR irradiance in influencing the long-term physiological effects of a given dose of radiation. This work enhances our understanding of which parameters of complex UVBR exposures determine amphibian health risk.


Larva/radiation effects , Ultraviolet Rays , Animals , Anura/growth & development , Australia , Larva/growth & development , Larva/physiology , Skin Pigmentation/radiation effects , Species Specificity , Swimming
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