Solar Lentigines Research Articles

Dermoscopic-Histopathological Correlation of Eccrine Poroma: An Observational Study.

Eccrine poroma (EP) is a benign adnexal neoplasm that can be pigmented in 17% of cases. Four histopathological variants of EP exist. Dermoscopically, EP can mimic many other skin neoplasms. To provide a dermoscopic-histopathological correlation of EP, classifying the clinical and dermoscopic features of EPs on the basis of their histopathological subtype, in an attempt to better characterize these entities. A single-center retrospective study was conducted. Clinical data were collected; patients were classified on the basis of the 4 histopathological variants of EPs. Dermoscopic images were reviewed. A dermoscopic-histopathological correlation was performed, and the results were compared with literature data. Twenty-six lesions were included, both pigmented and nonpigmented. Three of the 4 histopathological variants were identified. Different dermoscopic features were observed for each distinct histopathological subtype of EP. The lesions mimicked different types of other skin neoplasms, in particular: nonpigmented hidroacanthoma simplex resembled nonmelanoma skin cancer; pigmented hidroacanthoma simplex appeared like a seborrheic keratosis or a solar lentigo; EPs sensu stricto presented as pink nodules if nonpigmented and were similar to seborrheic keratosis if pigmented; dermal duct tumors appeared as pigmented nodular lesions. Distinct dermoscopic features appeared to be recurrent in each histopathological variant. Dermoscopy can provide important clues for the diagnosis of EP; the final diagnosis is allowed by histopathology. To achieve a correct diagnosis of EP, because of its clinical and dermoscopic variability, surgical excision is recommended.

Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines.

Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk. To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors. We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case-Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age- and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer-Lemeshow test. The final model included the number of naevi ≥2mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71-4·54] in the Australian study and 2·56 (95% CI 2·23-2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76-0·83) in the Australian study and 0·73 (95% CI 0·70-0·75) in the Leeds study. The Hosmer-Lemeshow test P-value was 0·30 in the Australian study and <0·001 in the Leeds study. This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self-assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically-assessed whole-body naevi and solar lentigines, and self-assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions.

564 Melasolv, a skin lightening compound with different mechanisms to regulate skin pigmentation

The pigmentation of human skin (nevi, senile lentigines, melasma, etc) is regulated by a complex process involving the synthesis and distribution of melanin. Overexpression of melanin is induced by the off-balance between the signals which regulates melanin synthesis, this can be caused due to a response to external or internal stimulus that often affects the genes related to melanogenesis. To date, many studies have focused on developing direct enzymatic inhibitors of tyrosinase in order to achieve a skin-lightening effect. However, it was also reported that these direct inhibitors could be converted to quinone derivatives by tyrosinase-catalyzed oxidation, which lead to undesirable outcomes. Therefore, we have studied intrinsic inhibitory factors of melanogenesis in skin with the objective to achieve a lightening effect without the undesirable potential side effects. It was reported that non-coding RNAs including H19, miR125b and WIF1 were decreased in hyper-pigmented skin such as melasma and nevi. And it was found out that melanogenesis could be inhibited by increasing these lightening genes expression in normal human epidermal melanocytes and keratinocytes. Our group showed that the 3, 4, 5-trimethoxy cinnamate thymol ester (TCTE, Melasolv®), synthesized from gallic acid, is a lightening active which decreases tyrosinase protein formation by regulating the MITF. Likewise, we have also observed that Melasolv significantly decreased melanogenesis by increasing expression of the lightening genes H19, miR125b and WIF1 in the skin cells. Finally, we have confirmed the lightening effect of Melasolv in 3D human skin equivalent. Nonetheless, since Melasolv is not a direct inhibitor of tyrosinase enzymatic activity, it is extremely unlikely that nocive quinone derivatives conversions occur. From these results, we have proposed Melasolv as an active for lightening effects with a safer profile, when considering undesirable effects, to treat pigmentary disorder and uneven skin color.

Calebin-A, a Curcuminoid Analog Inhibits α-MSH-Induced Melanogenesis in B16F10 Mouse Melanoma Cells

Hyperpigmentation skin disorders comprise melasma, age spots, and post-inflammatory hyperpigmentation. They are characterized by an aberrant upregulation of melanin pigment and pose a significant burden aesthetically. Calebin-A (CBA) is a natural curcuminoid analog derived from turmeric root (Curcuma longa) but, unlike curcumin, it has not been explored yet for anti-melanogenic activity. Hence, in the current study, we studied CBA for its effects on α-melanocyte stimulating hormone (αMSH)-stimulated melanogenesis in B16F10 mouse melanoma cells. Our results showed that CBA (20 μM) significantly suppressed αMSH-stimulated melanogenesis after 48 h treatment. The underlying mechanisms of CBA’s anti-melanogenic activity were studied, and it was shown that CBA did not affect either intracellular tyrosinase activity or the direct activity of tyrosinase enzyme. Additionally, CBA did not affect intracellular α-glucosidase activity but significantly inhibited direct α-glucosidase activity. CBA also directly scavenged 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals, consistent with potent antioxidant activity but did not inhibit intracellular reactive oxygen species (ROS). CBA increased acidification of cellular organelles and inhibited maturation of melanosomes by significantly reducing the number of mature melanosomes. Our results indicate that CBA may hold promise as a pigmentation inhibitor for hyperpigmentation disorders for cosmetic use by targeting pathways other than tyrosinase inhibition. Further studies to delineate the molecular signaling mechanism of melanogenesis inhibition and test anti-melanogenesis efficacy of CBA in human skin melanocytes and skin equivalents are warranted.

Do We Utilize Our Knowledge of the Skin Protective Effects of Carotenoids Enough?

Due to their potential health-promoting effects, carotenoids have drawn both scientific and public attention in recent years. The primary source of carotenoids in the human skin is diet, mainly fruits, vegetables, and marine product, but they may originate from supplementation and topical application, too. In the skin, they accumulate mostly in the epidermis and act as a protective barrier to various environmental influences. Namely, the skin is exposed to numerous environmental factors, including ultraviolet radiation (UVR), air pollution, and smoking, that cause oxidative stress within the skin with consequent premature (extrinsic) aging. UVR, as the most prominent environmental factor, may cause additional detrimental skin effects, such as sunburn, DNA damage, and skin cancer. Therefore, photoprotection is the first line intervention in the prevention of premature aging and skin cancer. Numerous studies have demonstrated that carotenoids, particularly β-carotene, lycopene, lutein, and astaxanthin, have photoprotective effects, not only through direct light-absorbing properties, but also through their antioxidant effects (scavenging reactive oxygen species), as well as by regulation of UV light-induced gene expression, modulation of stress-dependent signaling, and/or suppression of cellular and tissue responses like inflammation. Interventional studies in humans with carotenoid-rich diet have shown its photoprotective effects on the skin (mostly by decreasing the sensitivity to UVR-induced erythema) and its beneficial effects in prevention and improvement of skin aging (improved skin elasticity and hydration, skin texture, wrinkles, and age spots). Furthermore, carotenoids may be helpful in the prevention and treatment of some photodermatoses, including erythropoietic protoporphyria (EPP), porphyria cutanea tarda (PCT) and polymorphous light eruption (PMLE). Although UVR is recognized as the main etiopathogenetic factor in the development of non-melanoma skin cancer (NMSC) and melanoma, and the photoprotective effects of carotenoids are certain, available studies still could not undoubtedly confirm the protective role of carotenoids in skin photocarcinogenesis.

Melanocyte Activation Mechanisms and Rational Therapeutic Treatments of Solar Lentigos

To characterize the pathobiology of solar lentigos (SLs), analyses by semiquantitative RT-PCR, Western blotting, and immunohistochemistry revealed the upregulated expression of endothelin (EDN)-1/endothelin B receptors (EDNBRs), stem cell factor (SCF)/c-KIT, and tumor necrosis factor (TNF)α in the lesional epidermis, which contrasted with the downregulated expression of interleukin (IL) 1α. These findings strongly support the hypothesis that previous repeated UVB exposure triggers keratinocytes to continuously produce TNFα. TNFα then stimulates the secretion of EDNs and the production of SCF in an autocrine fashion, leading to the continuous melanogenic activation of neighboring melanocytes, which causes SLs. A clinical study of 36 patients with SLs for six months treated with an M. Chamomilla extract with a potent ability to abrogate the EDN1-induced increase in DNA synthesis and melanization of human melanocytes in culture revealed a significant improvement in pigment scores and color differences expressed as L values. Another clinical study using a tyrosinase inhibitor L-ascorbate-2-phosphate 3 Na (ASP) demonstrated that L values of test lotion (6% APS)-treated skin significantly increased in SLs and in non-lesional skin with a significantly higher ΔL value in SLs when compared with non-lesional skin. The sum of these findings strongly suggests that combined topical treatment with EDN signaling blockers and tyrosinase inhibitors is a desirable therapeutic choice for SLs.

Cosmeceutical efficiency by some plant extracts used traditionally for skin care in inhibiting tyrosinase activity in a human epidermal melanocyte (HEM) cell line

The progression of age and dark spots on human skin is undesirable as it indicates the reduction of skin beauty. The melanin produced by melanocytes is responsible for the associated darkening of the skin. Tyrosinase modulates the melanogenesis process and is a therapeutic target for skin disorders such as hypopigmentation and hyperpigmentation. The aim of the study was to evaluate the efficiency of plant extracts in maintaining the cells health and tyrosinase enzyme function using a human epidermal melanocyte (HEM) cell line. Ethanol extracts of Cassipourea flanaganii (Schinz) Alston, Chenopodium album L., Clausena anisata (Willd.) Hook.f ex Benth and Rorippa nasturtium-aquaticum (L.) Hayek were observed to be non-toxic to melanocytes at a concentration of 15 μg/mL. There was no significant difference between the extracts and the positive control in inhibiting cellular tyrosinase activity with IC50 values ranging between 1.42 and 1.55 μg/mL. The observed anti-tyrosinase activity of the plant extracts against the cell lines contribute positively in achieving the desired skin complexion while providing photo protection. Therefore, plant extracts that are efficient and safe to use can be incorporated into formulations intended for beauty enhancement.

A Prospective Randomized Controlled Study of Oral Tranexamic Acid for the Prevention of Postinflammatory Hyperpigmentation After Q‐Switched 532‐nm Nd:YAG Laser for Solar Lentigines

Q-switched (QS) 532-nm Nd:YAG laser is one of the treatment options for solar lentigines (SLs). However, the high incidence of postinflammatory hyperpigmentation (PIH) is concerning, especially in dark-complexioned skin. Tranexamic acid (TA) can decrease melanogenesis and has been used to treat melasma. The aim of this study is to evaluate the efficacy and safety of oral TA for PIH prevention and clearance in patients with SL treated with QS 532-nm Nd:YAG laser. Forty patients with SL treated with QS 532-nm Nd:YAG laser were enrolled in this randomized controlled trial. They were randomly assigned to be receive oral TA 1,500 mg daily or placebo for 6 weeks. Results were evaluated by blinded investigators using digital photographs, dermatoscopy, colorimetry, physician grading scores, and patient satisfaction scores at baseline, 2nd, 4th, 6th, and 12th weeks. The incidence of PIH, relative melanin value, lightness index, and clinical improvement scores were not significantly different between the two groups. However, the TA group had a significantly lower incidence of dermatoscopic finding of pigmented granules, which correspond to PIH at 6th and 12th weeks (P = 0.038 and 0.013, respectively). Homogenous light brown pigmentation under dermatoscopy was significantly associated with higher clinical improvement. Oral TA therapy starting at the first day postlaser treatment is not effective for PIH prevention after QS 532-nm Nd:YAG laser in SL. However, PIH clearance, as assessed dermatoscopically, is significantly improved by oral TA at 6th and 12th week. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Identification of Risk Factors for Multiple Non-Melanoma Skin Cancers in Italian Kidney Transplant Recipients.

Background and objectives: Non-melanoma skin cancers (NMSCs) represent the most frequently encountered malignancy in organ transplant recipients and their incidence increases proportionally to the duration of immunosuppression. Furthermore, patients of this group often develop multiple and more aggressive cancers and, to date, risk factors for the development of multiple NMSCs have not been yet established. The present study aimed to identify risk factors for multiple NMSCs in a cohort of Italian kidney transplant recipients (KTRs). Materials and Methods: We consecutively included all KTRs referring to two post-transplant outpatient clinics of North-Western Italy between 2001 and 2017. In this cohort, we evaluated different clinical (endogenous and exogenous) risk factors in order to establish their correlation with NMSCs. Results: 518 KTRs were included, of which 148 (28.6%) developed keratinocyte cancers, with a single tumor in 77 subjects, two skin cancers in 31 patients, 3 in 21 patients, whereas at least 4 NMSCs developed in 19 KTRs. We observed an increased risk of the development of cutaneous neoplasms for the male gender, old age at transplantation (>50 years), light phototype, solar lentigo, history of sunburns, or chronic actinic damage. Considering patients affected by multiple keratinocyte neoplasms, we observed a significant association of actinic damage and solar lentigo with an increased risk of NMSCs; their significance was confirmed even at the multivariable model. Conclusions: Our results confirm the role played by chronic cutaneous actinic damage in carcinogenesis on KTRs and highlight the significance of individualized periodic dermatological screening.

UV irradiation-induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines.

Wnt/β-catenin signalling promotes melanogenesis in melanocytes and also induces melanocytogenesis from melanocyte stem cells (McSCs). Previous study reported that WNT1, a ligand which activates Wnt/β-catenin signalling pathway, was more highly expressed in the epidermis at SLs than in normal skin areas, suggesting that WNT1 causes hyperpigmentation. To elucidate the mechanism by which WNT1 expression is increased in SLs, we examined the methylation of 5-carbon of cytosine (5mC), that is 5-methylcytosine (5mC) level, in a region within the WNT1 promoter; the methylation of the region was known to negatively regulate WNT1 gene expression. We used an immortalized cell line of human interfollicular epidermal stem cells to analyse the effect of UVB irradiation on DNA methylation level of WNT1 promoter and found that UVB irradiation caused demethylation of WNT1 promoter and promoted WNT1 mRNA expression. It was also found that UVB irradiation reduced the expression of DNA methyltransferase 1 (DNMT1), an enzyme responsible for maintaining methylation patterns during cell division. Pathological analysis of SLs and non-SL regions in the human skin revealed that both DNMT1 expression and 5mC level were decreased at SLs compared to non-SL skins. Furthermore, bisulphite sequencing showed that the methylated CpG level in WNT1 promoter was also lower at SLs than in non-SL skins. Thus, in the skin exposed to a high amount of UV rays, excessive expression of WNT1 is thought to be caused by the demethylation of WNT1 promoter, and the upregulated WNT1 promotes melanocytogenesis and melanogenesis, then resulting in SL formation.

Natural Tyrosinase Inhibitors: Role of Herbals in the Treatment of Hyperpigmentary Disorders.

Cutaneous pigmentation plays critical role in determining the color of skin along with photo protection of skin from dreadful effects of ultraviolet radiations. Conversely, abnormal accumulation of melanin is responsible for hyper pigmentary disorders such as melasma, senile lentigines and freckles. Because of the visible nature of dermatologic diseases, they have a considerable psychosomatic effect on affected patients. Tyrosinase inhibitors are molecules that interrelate in some way with the enzyme to prevent it from working in the normal manner. Past many decades witnessed the quest for the development of natural tyrosinase inhibitors due to imperative role played by tyrosinase in the process of melanogenesis and fungi or fruit enzymatic browning. Mechanism of pigmentation is characterized by the intact process of the synthesis of specialized black pigment within melanosomes. Melanin is synthesized by a cascade of enzymatic and chemical reactions. For this reason, melanin production is mainly controlled by the expression and activation of tyrosinase. In the current article, we discussed tyrosinase inhibitors from the natural sources, which can be an essential constituent of cosmetics products and depigmenting agents for the treatment of hyperpigmentory disorders.

A Prospective Study in the Treatment of Lentigines in Asian Skin Using 532 nm Picosecond Nd:YAG Laser.

To evaluate safety and efficacy of treatment with the picosecond Nd:YAG 532 nm forlentigines in Asian skin. This was a prospective, open-label cohort study, using a novel picosecond 532-nm laser for the treatmentof facial lentigines. Subjects received up to three laser treatments every 4-6 weeks and were assessed at 4 and 12 weeks after final treatment. Primary endpoint was degree of improvement in lentigines at 12 weeks after the final treatment, assessed by treating investigator based on Physicians Global Assessment. Secondary end-points included degree of improvement in lentigines at 12 weeks after final treatment, assessed by subject (Subject's Global Assessment), and change in mean relative Melanin index (MI) value at 3 months after final treatment as compared to baseline as assessed by mexameter measurement. A total of 20 patients (3 male, and 17 female) of Asian-descent with Fitzpatrick skin type III and IV, with lentigines on the face were included in this study. A total of 89 lesions were treated with the laser setting of 532-nm, 750 picoseconds, fluence of 0.2-0.5 J/cm 2 , and spot size of 4 mm. One hundred and thirty-seven treatment sessions were given in total. Eighteen patients (90%) achieved a moderate to significant improvement at 12-week follow-up based on a 5-grade physician global assessment scale. The improvement rate of relative MI (MI in the lesion minus normal skin) was 33.30 ± 18.71 and 37.63 ± 19.25% at 4- and 12-week follow-up. Post-inflammatory hyperpigmentation (PIH) occurred in 14 of 137 sessions (10.2%), and hypopigmentation occurred in one patient with five lesions (3.6%). This study demonstrates that using picosecond Nd:YAG laser 532 nm for removal of solar lentigines in darker skin type appears to be safe and effective. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc. Small study group.

Efficacy of D-pigment dermocosmetic lightening product for solar lentigo lesions of the hand: A randomized controlled trial.

Solar lentigo, benign lesions which mostly appear on chronically, sun-exposed surfaces, are associated with ageing. Patients are increasingly requesting a more uniform skin texture, especially for hands. Treatment options include dermoabrasion, intense pulsed light, cryotherapy, peelings, and laser therapy. Topical compounds can be employed, in alternative or associated with dermatologic procedures. The current study was designed to evaluate solar lentigo hyperpigmentation, skin architecture and clinician and patient assessments comparing a dermocosmetic lightening product (active) with a moisturizing product (control) according to clinical, digital and subjective analyses in 72 lesions over 12-month follow up period. Statistically significant differences were observed between the lesions treated with the active compared to the control in terms of papillary brightness (p = 0.03) and contrast (p = 0.03), and in the limitation of dermal-epidermal junction destructuring (p = 0.03) according to dermal-epidermal junction destructuring score at Reflectance Confocal Microscopy. Luminance (p = 0.04) and redness (p = 0.03) were improved at color analysis, and physician and patient evaluations favored the active in efficacy and patient satisfaction investigations. The dermocosmetic lightening product utilized in the current study proved to be more effective, according to clinical, digital and subjective analyses in reducing lesion hyperpigmentation, stabilizing the lesion skin architecture and increasing patient satisfaction compared to the control in a cohort of 36 subjects, over a 12-month period. Beside demonstrating the efficacy of this topical lightening product, we propose a “destructuring score”, which improves the robustness of solar lentigo’s evaluation, and can be used in future studies to standardize the quantitative comparisons of different treatment options.

Reflectance confocal microscopy in the diagnosis of pigmented macules of the face: differential diagnosis and margin definition.

In vivo reflectance confocal microscopy (RCM) is a noninvasive high-resolution skin imaging tool that has become an important adjunct to clinical exam, dermoscopy and histopathology assessment, in the diagnosis and management of pigmented macules of the face. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging and RCM improves the diagnostic accuracy in the differential diagnosis of LM with other macules of the face such as solar lentigo (SL), pigmented actinic keratosis (PAK), seborrheic keratosis (SK) and lichen planus-like keratosis (LPLK). Here we review the state-of-the-art of RCM morphologic descriptors, standardized terminology, and diagnostic algorithms for the RCM assessment of pigmented macules of the face including melanocytic, and nonmelanocytic lesions. Clinical applications of RCM are broad and include diagnosis, assessment of large lesions on cosmetically sensitive areas, directing areas to biopsy, delineating margins prior to surgery, detecting response to treatment and assessing recurrence. The present review is intended to summarize the application of RCM for the correct diagnosis of challenging pigmented facial macules and to evaluate its application in LM margin mapping during the pre surgical phase.

Skin disorders among elderly population without comorbidities: a hospital based study

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Aging is a permanent and progressive degenerative process which affects all organs of the body, including skin. There is a structural and physiologic transformation that arises as a result of intrinsic aging along with extrinsic damage which makes elderly skin more vulnerable to dermatologic disorders. In this study, we set out to determine the frequency and pattern of dermatological diseases in geriatric patients without chronic systemic illness and comorbidities like diabetes mellitus, hypertension and cardiac illness.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; We enrolled 350 patients of the age 60 years and above who were not suffering from any chronic systemic disease for the study. Baseline information and clinical examination were done to make the diagnosis.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The male: female ratio in our study was 1.14:1. The mean age of presentation was 68 year. The minimum age of patient was 60 years and maximum was 92 years. The most frequently encountered diseases in patients were eczematous dermatitis, fungal infections, scabies, xerosis and pruritus. Among eczemas, seborrheic dermatitis was the most common. Very few patients of solar lentigenes, skin tags and seborrheic keratosis came for dermatological consultation.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Eczemas were the most common dermatological disease in elderly in our study and pruritus was the most frequent complaint for which elderly visited skin Out Patient Department. Most of the diseases could possibly have been prevented.&lt;/p&gt;

766 NRF2-mediated inhibition of UVB-induced hyperpigmentation by topical sulforaphane is dependent on upregulation of IL6Rα expression on keratinocytes

Oxidative stress underlies many hyperpigmentation conditions, such as solar lentigines, melasma, and postinflammatory melanoderma. We previously reported that nuclear factor erythroid 2-related factor 2 (NRF2) signaling, a key redox regulator, is impaired in solar lentigines and topical application of NRF2 agonist sulforaphane (SF) improves hyperpigmentation in photodamaged human skin. Experiments in a mouse model of UVB-induced hyperpigmentation replicated clinical findings and provided evidence for an additional preventative benefit of SF. Interleukin 6 (IL-6) is a pleiotropic cytokine that is rapidly produced by keratinocytes and fibroblasts following UVB exposure. Furthermore, IL-6-/- mice are more sensitive to UVB irradiation. Herein, we report that topical application of 1 μmole SF daily for 5 days a week for a total of 4 weeks upregulated IL-6Rα expression on keratinocytes in C57BL/6 WT mouse skin. To investigate the impact of IL-6Rα signaling on NRF2 mediated prevention of UVB-induced hyperpigmentation, we utilized a tamoxifen-inducible keratinocyte specific IL-6Rα knock out mouse model (K14-Cre-ERT2IL-6Rαfl/fl). Ears of WT (n=14) and K14-Cre-ERT2IL-6Rαfl/fl (n=10) mice were exposed to UVB (80 mJ/cm2) once daily 5 times a week for 2 to 4 weeks. Prior to each UVB treatment, SF was topically applied to one ear and the other received vehicle or no treatment. In K14-Cre-ERT2IL-6Rαfl/fl mice, skin darkness increased by two-fold in half the time required for WT controls (2 versus 4 weeks). Notably, in contrast to WT controls, topical SF failed to prevent UVB-induced hyperpigmentation in K14-Cre-ERT2IL-6Rαfl/fl mice. Taken together, this suggests that the interplay between NRF2 and IL-6Rα signaling is a potential therapeutic target for hyperpigmentation disorders that are induced or exacerbated by UV exposure.

Cells to Surgery Quiz: April 2019

Cells to Surgery Quiz: April 2019

The dermoscopic features of facial aging among Egyptians: A comparative study between males and females.

Few studies have evaluated facial photoaging by dermoscopy. Only one study has been performed among Egyptians. To study and compare the dermoscopic features of facial aging in males and females and to relate these features to clinical criteria. This study included 217 subjects divided into two groups; 117 males and 100 females. Each group was classified into three subgroups according to age. The dermoscopic features were reported according to dermoscopy photoaging scale (DPAS) criteria besides diffuse erythema and seborrheic keratosis and were related to significant clinical factors. The most prominent DPAS features in males were yellowish discoloration, hypo-hyperpigmented macules, superficial wrinkles, criss-cross wrinkles, and deep wrinkles. The most prominent DPAS findings in females were yellow papules, hypo-hyperpigmented macules, solar lentigo, and superficial wrinkles. A significant difference between males and females was detected regarding yellowish discoloration, white lines, hypo-hyperpigmented macules, senile comedones, telangiectasia, all wrinkle types, and DPAS score besides diffuse erythema and seborrheic keratosis. The DPAS score and the dermoscopic features were more prominent with male gender, increase in age, sun exposure, Glogau's scale, and smoking and were detected early in skin phototypes II and III. We found a significant difference in various dermoscopic features in males compared to age-matched females. Also, we detected increase in DPAS features and score with male gender, aging, sun exposure, Glogau's scale, and smoking. Therefore, dermoscopy is an objective technique that detects selectively photoaging in males and females that aids in proper choice of various targeted treatment modalities.

Glabridin smartPearls – Silica selection, production, amorphous stability and enhanced solubility

Glabridin, a compound in the root extract of Glycyrrhiza glabra, has been identified as an effective tyrosinase inhibitor. Applied on skin, melanin synthesis is inhibited, making glabridin an interesting candidate for skin whitening or for the treatment of age spots. However, main obstaclefor its practical use is its low dermal bioavailability, caused by its poor water solubility. In this work smartPearls technology was used to increase the glabridins water solubility. smartPearls consist of silica particles with mesopores in which actives can be loaded. By this, actives are stabilized in amorphous state and simultaneously finely distributed in nm-range. Both amorphization and nanoization are well known approaches to increase saturation solubilities. In smartPearls these approaches are combined. In the first step, glabridin smartPearls formulation was developed, screening systematically the suitability of 4 different silicas varying in their pore sizes (3, 6, 10, 17 nm). Also, most suited filling level of glabridin was determined (25, 50, 80% referred to total pore volume of respective silica). Silica loading was performed by the immersion-evaporation method, resulting in pores filled with glabridin from bottom to top. By light microscopy, dynamic scanning calorimetry and X-ray diffraction the sample with 6 nm pore size and filling levels of 25% and 50% have been verified to be completely amorphous. Highest physical storage stability of 7 months up to now was obtained for the 25% filled sample. In the next step, concept of increased saturation solubility for smartPearls was proven. Dissolution profiles were recorded in situ for glabridin smartPearls and compared to glabridin raw drug powder. Both saturation solubility and dissolution velocity were remarkably improved. The water solubility for example increased by a factor of more than 4. This makes glabridin smartPearls promising for creating skin products with improved dermal bioavailability.

Whitening effect of l-ascorbate-2-phosphate trisodium salt on solar lentigos

Little is known about the anti-pigmenting effects of whitening agents on solar lentigos (SLs), which comprise ~ 60% of hyperpigmented facial lesions of Asian subjects. Lotions with or without 6% L-ascorbate-2-phosphate trisodium salt (APS) [test lotion (TL) and placebo lotion (PL), respectively] were applied twice daily for 24 weeks in a double-blind half-face study of 27 Japanese females with SLs on both sides of their faces. Pigmentation scores were evaluated using a photo-scale and the skin colors were assessed using a color difference meter and a mexameter for SLs and the non-lesional surrounding skin (NLS). Although the pigmentation scores were not significantly different between the TL and PL-treated SLs after 24 weeks, the L values of TL-treated SLs and NLS increased significantly with a significantly higher △L value in SLs than in NLS. In contrast, the L values of PL-treated SLs and NLS remained unchanged after the treatment. The number of subjects with > 2.0 △L was 7 of 27 (TL) and 0 of 27 (PL) in SLs and 3 of 27 (TL) and 0 of 27 (PS) in NLS. In contrast, the melanin index in TL-treated SLs and NLS significantly decreased with a significantly higher △melanin index in SLs than in NLS. Similarly, the melanin index of PL-treated SLs and NLS were significantly decreased with a significantly higher △melanin index in SLs than in NLS. These findings strongly indicate that APS has a weak but significant anti-pigmenting effect on SLs and a significant whitening effect even on normally pigmented healthy skin.