Artificial intelligence-based prescription of personalized scalp cosmetics improved the scalp condition: efficacy results from 100 participants.

Background: Scalp-related symptoms such as dandruff and itching are common with diverse underlying etiologies. We previously proposed a novel classification and scoring system for scalp conditions, called the scalp photographic index (SPI); it grades five scalp features using trichoscopic images with good reliability. However, it requires trained evaluators.Aim: To develop artificial intelligence (AI) algorithms for assessment of scalp conditions and to assess the feasibility of AI-based recommendations on personalized scalp cosmetics.Methods: Using EfficientNet, convolutional neural network (CNN) models (SPI-AI) ofeach scalp feature were established. 101,027 magnified scalp images graded according to the SPI scoring were used for training, validation, and testing the model Adults with scalp discomfort were prescribed shampoos and scalp serums personalized according to their SPI-AI-defined scalp types. Using the SPI, the scalp conditions were evaluated at baseline and at weeks 4, 8, and 12 of treatment.Results: The accuracies of the SPI-AI for dryness, oiliness, erythema, folliculitis, and dandruff were 91.3%, 90.5%, 89.6%, 87.3%, and 95.2%, respectively. Overall, 100 individuals completed the 4-week study; 43 of these participated in an extension study until week 12. The total SPI score decreased from 32.70 ± 7.40 at baseline to 15.97 ± 4.68 at week 4 (p < 0.001). The efficacy was maintained throughout 12 weeks.Conclusions: SPI-AI accurately assessed the scalp condition. AI-based prescription of tailored scalp cosmetics could significantly improve scalp health.

Wearable and Wavelength-Tunable Near-Infrared Organic Light-Emitting Diodes for Biomedical Applications.

Near-infrared organic light-emitting diodes (NIR OLEDs) have significant potential for wearable phototherapeutic applications because of the unique properties of the OLEDs, including their free-form electronics and the excellent biomedical effects of NIR emission. In spite of their tremendous promise, given that the majority of NIR OLEDs in previous research have relied on the utilization of an intrinsically brittle indium tin oxide (ITO) electrode, their practicality in the field of wearable electronics is inherently constrained. Here, we report wearable and wavelength-tunable NIR OLEDs that employ a high-performance NIR emitter and an innovative architecture by replacing the ITO with a silver (Ag) electrode. The NIR OLEDs permit wavelength tuning of emissions from 700 to 800 nm and afford stable operation even under repeated bending conditions. The NIR OLEDs provide a lowered device temperature of 37.5 °C even during continuous operation under several emission intensities. In vitro experiments were performed with freshly fabricated NIR OLEDs. The outcomes were evaluated against experimental results performed using the same procedure utilizing blue, green, and red OLEDs. When exposed to NIR light irradiation, the promoting effect of cell proliferation surpassed the proliferative responses observed under the influence of visible light irradiation. The proliferation effect of human hair follicle dermal papilla cells is clearly related to the irradiation wavelength and time, thus underscoring the potential of wavelength-tunable NIR OLEDs for efficacious phototherapy. This work will open novel avenues for wearable NIR OLEDs in the field of biomedical application.

Cell proliferation effect of deep-penetrating microcavity tandem NIR OLEDs with therapeutic trend analysis.

Long wavelengths that can deeply penetrate into human skin are required to maximize therapeutic effects. Hence, various studies on near-infrared organic light-emitting diodes (NIR OLEDs) have been conducted, and they have been applied in numerous fields. This paper presents a microcavity tandem NIR OLED with narrow full-width half-maximum (FWHM) (34 nm), high radiant emittance (> 5 mW/cm2) and external quantum efficiency (EQE) (19.17%). Only a few papers have reported on biomedical applications using the entire wavelength range of the visible and NIR regions. In particular, no biomedical application studies have been reported in the full wavelength region using OLEDs. Therefore, it is worth researching the therapeutic effects of using OLED, a next-generation light source, and analyzing trends for cell proliferation effects. Cell proliferation effects were observed in certain wavelength regions when B, G, R, and NIR OLEDs were used to irradiate human fibroblasts. The results of an in-vitro experiment indicated that the overall tendency of wavelengths is similar to that of the cytochrome c oxidase absorption spectrum of human fibroblasts. This is the first paper to report trends in the cell proliferation effects in all wavelength regions using OLEDs.

Milk Protein-Derived Antioxidant Tetrapeptides as Potential Hypopigmenting Agents.

Excessive accumulation of melanin can cause skin pigmentation disorders, which may be accompanied by significant psychological stress. Although many natural and synthetic products have been developed for the regulation of melanogenesis biochemistry, the management of unwanted skin pigmentation remains challenging. Herein, we investigated the potential hypopigmenting properties of peptide sequences that originated from milk proteins such as ĸ-casein and ß-lactoglobulin. These proteins are known to inhibit melanogenesis and their hydrolysates are reported as antioxidant peptides. We synthesize tetrapeptide fragments of the milk protein hydrolysates and investigate the amino acids that are essential for designing peptides with tyrosinase inhibitory and antioxidant activities. We found that the peptide methionine-histidine-isoleucine-arginine amide sufficiently inhibits mushroom tyrosinase activity, shows potent antioxidant activity and effectively impedes melanogenesis in cultured melanocytes via cooperative biological activities. Our findings demonstrate the potential utility of the bioactive tetrapeptide from milk proteins as a chemical alternative to hypopigmenting agents.

Histone Deacetylase 1 and Sirtuin 1 Expression in Psoriatic Skin: A Comparison between Guttate and Plaque Psoriasis.

Abnormal histone modification by histone deacetylases (HDACs), including HDAC1 and sirtuin 1 (SIRT1), has been reported to play an important role in the pathogenesis of psoriasis by altering cell proliferation, differentiation, and inflammation. However, findings on the expression level of HDACs in psoriatic skin lack consistency. We assessed the expression of HDAC1, SIRT1, p63, and proliferating cell nuclear antigen (PCNA) in skin tissues from 23 patients with psoriasis (15 with plaque psoriasis and eight with guttate psoriasis) and five healthy individuals using immunohistochemistry, and analyzed their associations with clinical phenotypes of the disease. The expression of HDAC1 and keratinocyte proliferative markers, such as p63 and PCNA significantly increased, whereas that of SIRT1 decreased in the basal layer (p < 0.05) of the patients with psoriasis compared to those in healthy controls. Among the patients with psoriasis, expression of HDAC1, p63, and PCNA was significantly higher in plaque psoriasis than in guttate psoriasis. There was no significant differences in the level of SIRT1 between the two clinical phenotypes. The findings of this study suggest that histone modifications are involved in the pathogenesis of psoriasis and may contribute to the formation of clinical phenotypes.

Resveratrol Inhibits Particulate Matter-Induced Inflammatory Responses in Human Keratinocytes.

Particulate matter (PM), a major air pollutant, is a complex mixture of solid and liquid particles of various sizes. PM has been demonstrated to cause intracellular inflammation in human keratinocytes, and is associated with various skin disorders, including atopic dermatitis, eczema, and skin aging. Resveratrol is a natural polyphenol with strong antioxidant properties, and its beneficial effects against skin changes due to PM remain elusive. Therefore, in the present study, we investigated the effect of resveratrol on PM-induced skin inflammation and attempted to deduce the molecular mechanisms underlying resveratrol's effects. We found that resveratrol inhibited PM-induced aryl hydrocarbon receptor activation and reactive oxygen species formation in keratinocytes. It also suppressed the subsequent cellular inflammatory response by inhibiting mitogen-activated protein kinase activation. Consequentially, resveratrol reduced PM-induced cyclooxygenase-2/prostaglandin E2 and proinflammatory cytokine expression, including that of matrix metalloproteinase (MMP)-1, MMP-9, and interleukin-8, all of which are known to be central mediators of various inflammatory conditions and aging. In conclusion, resveratrol inhibits the PM-induced inflammatory response in human keratinocytes, and we suggest that resveratrol may have potential for preventing air pollution-related skin problems.

Corrigendum: The Effects of the 3-OH Group of Kaempferol on Interfollicular Epidermal Stem Cell Fate.

[This corrects the article on p. 694 in vol. 30.].

Sandwich-structure transferable free-form OLEDs for wearable and disposable skin wound photomedicine.

Free-form optoelectronic devices can provide hyper-connectivity over space and time. However, most conformable optoelectronic devices can only be fabricated on flat polymeric materials using low-temperature processes, limiting their application and forms. This paper presents free-form optoelectronic devices that are not dependent on the shape or material. For medical applications, the transferable OLED (10 µm) is formed in a sandwich structure with an ultra-thin transferable barrier (4.8 µm). The results showed that the fabricated sandwich-structure transferable OLED (STOLED) exhibit the same high-efficiency performance on cylindrical-shaped materials and on materials such as textile and paper. Because the neutral axis is freely adjustable using the sandwich structure, the textile-based OLED achieved both folding reliability and washing reliability, as well as a long operating life (>150 h). When keratinocytes were irradiated with red STOLED light, cell proliferation and cell migration increased by 26 and 32%, respectively. In the skin equivalent model, the epidermis thickness was increased by 39%; additionally, in organ culture, not only was the skin area increased by 14%, but also, re-epithelialization was highly induced. Based on the results, the STOLED is expected to be applicable in various wearable and disposable photomedical devices.

Molecular Mechanisms of Dermal Aging and Antiaging Approaches.

The dermis is primarily composed of the extracellular matrix (ECM) and fibroblasts. During the aging process, the dermis undergoes significant changes. Collagen, which is a major component of ECM, becomes fragmented and coarsely distributed, and its total amount decreases. This is mainly due to increased activity of matrix metalloproteinases, and impaired transforming growth factor-ß signaling induced by reactive oxygen species generated during aging. The reduction in the amount of collagen hinders the mechanical interaction between fibroblasts and the ECM, and consequently leads to the deterioration of fibroblast function and further decrease in the amount of dermal collagen. Other ECM components, including elastic fibers, glycosaminglycans (GAGs), and proteoglycans (PGs), also change during aging, ultimately leading to a reduction in the amount of functional components. Elastic fibers decrease in intrinsically aged skin, but accumulate abnormally in photoaged skin. The changes in the levels of GAGs and PGs are highly diverse, and previous studies have reported conflicting results. A reduction in the levels of functional dermal components results in the emergence of clinical aging features, such as wrinkles and reduced elasticity. Various antiaging approaches, including topicals, energy-based procedures, and dermal fillers, can restore the molecular features of dermal aging with clinical efficacy. This review summarizes the current understanding of skin aging at the molecular level, and associated treatments, to put some of the new antiaging technology that has emerged in this rapidly expanding field into molecular context.

Resveratrol as a Multifunctional Topical Hypopigmenting Agent.

Melanin is produced in melanocytes and stored in melanosomes, after which it is transferred to keratinocytes and, thus, determines skin color. Despite its beneficial sun-protective effects, abnormal accumulation of melanin results in esthetic problems. A range of topical hypopigmenting agents have been evaluated for their use in the treatment of pigmentary disorders with varying degrees of success. Hydroquinone (HQ), which competes with tyrosine, is the main ingredient in topical pharmacological agents. However, frequent occurrence of adverse reactions is an important factor that limits its use. Thus, efforts to discover effective topical hypopigmenting agents with less adverse effects continue. Here, we describe the potential of resveratrol to function as an effective hypopigmenting agent based on its mechanism of action. Resveratrol is not only a direct tyrosinase inhibitor but an indirect inhibitor as well. Additionally, it can affect keratinocytes, which regulate the function of melanocytes. Resveratrol regulates the inflammatory process of keratinocytes and protects them from oxidative damage. In this way, it prevents keratinocyte-induced melanocyte stimulation. Furthermore, it has a rescuing effect on the stemness of interfollicular epidermal cells that can repair signs of photoaging in the melasma, a typical pigmentary skin disorder. Overall, resveratrol is a promising potent hypopigmenting agent.

The increase of interfollicular epidermal stem cells and regulation of aryl hydrocarbon receptor and its repressors in the skin through hydroporation with anti-aging cocktail.

BACKGROUNDS: Hydroporation is a procedure that involves a subsonic flow of air and microdroplets into the skin. We previously reported that hydroporation treatment with a cocktail solution containing copper-glycyl-L-histidyl-L-lysyl, oligo hyaluronic acid, rhodiola extract, tranexamic acid, and ß-glucan yielded positive effects on skin aging. OBJECTIVES: The aim of this study was to evaluate the effects of hydroporation with anti-aging cocktail on interfollicular epidermal stem cells (IFESCs) and expression of aryl hydrocarbon receptor (AhR)/AhR repressor (AhRR) in the skin. METHODS: Skin samples from six volunteers who were treated with hydroporation were analyzed via confocal microscopic examination. RESULTS: Markers for dermal matrix (procollagen type I and fibrillin-1) and basement membrane (type IV collagen and integrin α6) were increased after treatment. Moreover, there was a significant increase in the expression level of histone deacetylase 1-positive/p63-negative basal cells, which we previously reported as interfollicular epidermal stem cells. The expression level of AhR was significantly decreased, whereas that of AhRR was increased. This indicates an alteration in the interaction between the skin and environment posttreatment. CONCLUSION: Anti-aging hydroporation treatment recovered the stem cell potential of basal cells. Moreover, this treatment decreased AhR and increased AhRR in the skin, which may protect the skin from the harmful environment.

The Effects of the 3-OH Group of Kaempferol on Interfollicular Epidermal Stem Cell Fate.

Background: Kaempferol (3,4',5,7-tetrahydroxyflavone) is a flavonoid known to have a wide range of pharmacological activities. The 3-OH group in flavonoids has been reported to determine antioxidant activities. Objective: We tested whether kaempferol can affect the expression of integrins and the stem cell fate of interfollicular epidermal stem cells. Methods: Skin equivalent (SE) models were constructed, and the expression levels of stem cell markers and basement membrane-related antigens were tested. The immunohistochemical staining patterns of integrins, p63, and proliferating cell nuclear antigen (PCNA) were compared between kaempferol- and apigenin-treated SE models. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of integrins. Results: Kaempferol increased the thickness of the epidermis when added to prepare SEs. In addition, the basal cells of kaempferol- treated SEs appeared more columnar. In the immunohistological study, the expression of integrins α6 and ß1 and the numbers of p63- and PCNA-positive cells were markedly higher in the kaempferol-treated model. However, apigenin showed no effects on the formation of three-dimensional skin models. RT-PCR analysis also confirmed that kaempferol increased the expression of integrin α6 and integrin ß1. Conclusion: Our findings indicated that kaempferol can increase the proliferative potential of basal epidermal cells by modulating the basement membrane. In other words, kaempferol can affect the fate of interfollicular epidermal stem cells by increasing the expression of both integrins α6 and ß1. These effects, in particular, might be ascribed to the 3-OH group of kaempferol.

Avian Collagen Is Useful for the Construction of Skin Equivalents.

As a result of restrictions on animal experimentation, improved skin equivalents (SEs) are needed as alternative test models. This work investigated the effects of avian collagen on the construction of SEs, and to the best of our knowledge is the first study to do so. Hematoxylin and eosin and immunohistochemical staining were used to analyze the SEs. In models containing avian collagen as a dermal equivalent (DE) ingredient, fibroblast proliferation increased by about 60% relative to the control model. Immunohistochemical staining showed that the expression of proliferating cell nuclear antigen (PCNA) and p63 increased in the avian collagen models, while the expression of involucrin, integrin α6, and integrin ß1 remained unchanged. Next, DEs were cryopreserved to allow the easier creation of SEs. Keratinocytes were seeded on thawed DEs, and SEs were constructed. Avian collagen increased the viability of DEs relative to the control. Furthermore, avian collagen increased the expression of PCNA and p63 in keratinocytes on thawed DEs. The results indicate that DEs containing avian collagen can be thawed as needed after cryopreservation. Avian collagen can improve the construction of SEs and be used as part of a dermal kit for SE construction.

The Co-Expression Pattern of p63 and HDAC1: A Potential Way to Disclose Stem Cells in Interfollicular Epidermis.

Stem cell markers of interfollicular epidermis (IEF) have not been established thus far. The aim of this study is to suggest a new way to disclose IFE-stem cells by combining the expression of histone deacetylases (HDAC) 1 and p63. Immunohistochemical staining of HDAC1 and p63 was performed in six normal human samples. Moreover, a skin equivalent (SE) model was treated with suberoylanilohydroxamic acid (SAHA, an HDAC inhibitor) to elucidate the role of HDAC1. Finally, rapidly adhering (RA) keratinocytes to a type IV collagen, which have been identified to represent epidermal stem cells, were subjected to Western blot analysis with antibodies against HDAC1. In normal samples, there was a minor subpopulation comprised of p63-positive and HDAC1-negative cells in the basal layers. The proportion of this subpopulation was decreased with age. In the SE model, SAHA treatment increased the epidermal thickness and number of p63-positive cells in a dose dependent manner. After SAHA treatment, the expression of differentiation markers was decreased, while that of basement membrane markers was increased. In a Western blot analysis, HDAC1 was not expressed in RA cells. In conclusion, the combination of p63-positive and HDAC1-negative expressions can be a potential new way for distinguishing epidermal stem cells.

Depigmenting Effect of Resveratrol Is Dependent on FOXO3a Activation without SIRT1 Activation.

Resveratrol exhibits not only anti-melanogenic property by inhibiting microphthalmia-associated transcription factor (MITF), but also anti-aging property by activating sirtuin-1 (SIRT1). In this study, the relationship between depigmenting effect of resveratrol and SIRT1/forkhead box O (FOXO) 3a activation and was investigated. Resveratrol suppressed melanogenesis by the downregulation of MITF and tyrosinase via ERK pathway. Results showed that the expression of both SIRT1 and FOXO3a were increased. It is reported that SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress. However in our study, FOXO3a activation appeared earlier than that of SIRT1. Furthermore, the effect of resveratrol on the levels of MITF and tyrosinase was suppressed when melanocytes were pre-treated with SP600125 (JNK inhibitor). However, pre-treatment with SIRT1 inhibitor (EX527, or sirtinol) did not affect the levels of MITF and tyrosinase. Therefore, resveratrol inhibits melanogenesis through the activation of FOXO3a but not by the activation of SIRT1. Although SIRT1 activation by resveratrol is a well-known mechanism of resveratrol-induced antiaging effects, our study showed that not SIRT1 but FOXO3a activation is involved in depigmenting effects of resveratrol.

The effects of hydroporation on melasma with anti-aging cocktail.

BACKGROUND: Jet-M is a device for epidermal peeling and is used to deliver substances by spraying air and microdroplets. Previously, a case was treated with a mixed solution of copper-GHK, oligo-hyaluronic acid, Rhodiola extract, tranexamic acid, and ß-glucan. The results showed significant improvement of aged skin. AIMS: This study was conducted to evaluate the effects of hydroporation on melasma with the formulation in a small group of volunteers. METHODS: Clinical effects were evaluated by both subjective and objective methods including melanin index (MI) and erythema index (EI) measurement. RESULTS: Clinically, pigmentation and erythema were relieved and also both MI and EI decreased. Histopathologic observation revealed that type IV collagen and procollagen were increased in the upper dermis. Furthermore, the number of p63-positive cells is increased along the basement membrane. These results all suggest that hydroporation with GHR formulation induced anti-aging effects by reconstruction of extracellular matrix. CONCLUSION: These findings suggest that the treatment may have depigmenting effects and erythema decreasing effects by enhancing the microenvironment of the skin.

Phlorizin, an Active Ingredient of Eleutherococcus senticosus, Increases Proliferative Potential of Keratinocytes with Inhibition of MiR135b and Increased Expression of Type IV Collagen.

E. senticosus extract (ESE), known as antioxidant, has diverse pharmacologic effects. It is also used as an antiaging agent for the skin and phlorizin (PZ) is identified as a main ingredient. In this study, the effects of PZ on epidermal stem cells were investigated. Cultured normal human keratinocytes and skin equivalents are used to test whether PZ affects proliferative potential of keratinocytes and how it regulates these effects. Skin equivalents (SEs) were treated with ESE and the results showed that the epidermis became slightly thickened on addition of 0.002% ESE. The staining intensity of p63 as well as proliferating cell nuclear antigen (PCNA) is increased, and integrin α6 was upregulated. Analysis of ESE confirmed that PZ is the main ingredient. When SEs were treated with PZ, similar findings were observed. In particular, the expression of integrin α6, integrin ß1, and type IV collagen was increased. Levels of mRNA for type IV collagen were increased and levels of miR135b were downregulated. All these findings suggested that PZ can affect the proliferative potential of epidermal cells in part by microenvironment changes via miR135b downregulation and following increased expression of type IV collagen.