Review of Fractional Nonablative Lasers for the Treatment of Dermatologic Conditions in Darker Skin Phototypes.

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.

2-Mercaptonicotinoyl glycine prevents UV-induced skin darkening and delayed tanning in healthy subjects: A randomized controlled clinical study.

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.

A precise analysis of the relative contribution of UVA1 and visible light colour domains in solar light-induced skin pigmentation.

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.

Novel laser hair removal in all skin types.

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.

The potential role of UV and blue light from the sun, artificial lighting, and electronic devices in melanogenesis and oxidative stress.

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.

Radiofrequency Irradiation Mitigated UV-B-Induced Skin Pigmentation by Increasing Lymphangiogenesis.

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.

Quantitative Changes in Skin Composition Parameters after Radiation Therapy According to Surgery Types Among Patients with Breast Cancer: A Prospective Study.

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.

Study of a 532/1064 Fractional Picosecond Laser for Facial Rejuvenation.

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.

Attenuation Effect of Radiofrequency Irradiation on UV-B-Induced Skin Pigmentation by Decreasing Melanin Synthesis and through Upregulation of Heat Shock Protein 70.

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.

A Lower Irradiation Dose of 308 nm Monochromatic Excimer Light Might Be Sufficient for Vitiligo Treatment: A Novel Insight Gained from In Vitro and In Vivo Analyses.

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.

Evaluating Whether Radiofrequency Irradiation Attenuated UV-B-Induced Skin Pigmentation by Increasing Melanosomal Autophagy and Decreasing Melanin Synthesis.

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.

Blue Light and the Skin.

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.

Assessment of Natural Sunlight Protection Provided by 10 High-SPF Broad-Spectrum Sunscreens and Sun-Protective Fabrics.

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.

The Pathogenesis and Management of Acne-Induced Post-inflammatory Hyperpigmentation.

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.

Few X-ray and PUVA treatments accelerate photocarcinogenesis in hairless mice.

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.

Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi.

Early differential diagnosis between malignant and benign tumors and their underlying intrinsic differences are the most critical issues for life-threatening cancers. To study whether human acral melanomas, deadly cancers that occur on non-hair-bearing skin, have distinct origins that underlie their invasive capability, we develop fate-tracing technologies of melanocyte stem cells in sweat glands (glandular McSCs) and in melanoma models in mice and compare the cellular dynamics with human melanoma. Herein, we report that glandular McSCs self-renew to expand their migratory progeny in response to genotoxic stress and trauma to generate invasive melanomas in mice that mimic human acral melanomas. The analysis of melanocytic lesions in human volar skin reveals that genetically unstable McSCs expand in sweat glands and in the surrounding epidermis in melanomas but not in nevi. The detection of such cell spreading dynamics provides an innovative method for an early differential diagnosis of acral melanomas from nevi.

Ultraviolet-B irradiance and cumulative dose combine to determine performance and survival.

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.

Inhibition of melanogenesis by Aster yomena callus pellet extract in melanoma cells and patients with skin pigmentation.

Plant tissue culture holds immense potential for the production of secondary metabolites with various physiological functions. We recently established a plant tissue culture system capable of producing secondary metabolites from Aster yomena. This study aimed to uncover the mechanisms underlying the potential therapeutic effects of Aster yomena callus pellet extract (AYC-P-E) on photoaging-induced skin pigmentation. Excessive melanogenesis was induced in B16F10 melanoma cells using α-melanocyte stimulating hormone (α-MSH). The effects of AYC-P-E treatment on melanin biosynthesis inducers and melanin synthesis inhibition were assessed. Based on the results, a clinical study was conducted in subjects with skin pigmentation. AYC-P-E inhibited melanogenesis in α-MSH-treated B16F10 cells, accompanied by decreased mRNA and protein expression of melanin biosynthesis inducers, including cyclic AMP response element-binding protein (CREB), tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1), and TRP-2. This anti-melanogenic effect was mediated by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) phosphorylation. Treatment of subjects with skin pigmentation with AYC-P-E-containing cream formulations resulted in 3.33%, 7.06%, and 8.68% improvement in the melanin levels at 2, 4, and 8 weeks, respectively. Our findings suggest that AYC-P-E inhibits excessive melanogenesis by activating MEK/ERK and AKT signaling, potentiating its cosmetic applications in hyperpigmentation treatment.

NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.

Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.

The addition of topical calcipotriol to phototherapy enhance the efficacy of treatment in patients with vitiligo: A systematic review and meta-analysis.

BACKGROUND: Treatment of vitiligo has several challenges. Phototherapy and topical calcipotriol have been reported to be effective in combination with other therapies, but there is no consensus on the combination use. OBJECTIVE: To perform a systematic review and meta-analysis that elucidates the efficacy of the combination of phototherapy and topical calcipotriol. METHODS: This systematic review was performed by searching PubMed, EMBASE, Web of Science, Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI), WanFang and VIP databases for relevant publications till February 28, 2021. Relative risk (RR) and its 95% confidence interval (CI) were used to evaluate the data. Bias assessment, heterogeneity and sensitivity analysis were conducted in this meta-analysis. RESULTS: After screening, nine studies with 700 participants were included. The meta-analysis indicated that the combination of phototherapy and topical calcipotriol showed significantly higher effective rate (RR 1.11, 95% CI 1.02-1.22; p < 0.05) and apparent effective rate (RR 1.35, 95% CI 1.15-1.59; p < 0.01) than phototherapy monotherapy in the treatment of vitiligo. In addition, the side effects were minor, transient and tolerable. CONCLUSIONS: This meta-analysis provides evidence supporting phototherapy combined with topical calcipotriol as a valuable treatment modality for patients with vitiligo, which has better efficacy than monotherapy.