Evaluation test and analysis of a microneedle and iontophoresis based medical device "CELLADEEP Patch" in skin improvement on ex vivo human-derived skin tissue models.

BACKGROUND: Microneedles are tiny needles, typically ranging from tens to hundreds of micrometers in length, used in various medical procedures and treatments. The tested medical device named "CELLADEEP Patch" a dissolvable microneedle therapy system (MTS), made of hyaluronic acid and collagen. And the iontophoresis technique is also applied in the system. The study aimed to evaluate the effectiveness of the "CELLADEEP Patch" in skin improvement. METHODS: Ex vivo human-derived skin tissue models were used in this study and they were divided into three different groups, namely, the Untreated Group, the Negative Control Group, and the Test Group respectively. The Untreated Group received no treatment measures, the Negative Control Group was exposed to ultraviolet B radiation (UVB) irradiation, and the Test Group was exposed to UVB irradiation and treated with "CELLADEEP Patch". Skin moisture content, transdermal water loss, and skin elasticity were evaluated by three clinical devices. Additionally, histological staining and related mRNA expression levels were also analyzed. RESULTS: The results of skin moisture content, transdermal water loss, and skin elasticity evaluation consistently illustrated that the application of "CELLADEEP Patch" led to remarkable skin improvement. And the analysis of histological staining images also confirmed the effectiveness of the "CELLADEEP Patch", especially for increasing collagen density. Moreover, the upregulation of Collagen type 1 a (COL1A1) and hyaluronan synthase 3 mRNA expression and the decrease of Matrix metalloproteinase 1 (MMP-1) and Interleukin-1 beta (IL-1ß) mRNA expression reflected its wrinkle improvement, moisturizing and anti-inflammation function. CONCLUSION: "CELLADEPP Patch", the MTS combined with the iontophoresis technique, exhibits its effectiveness in moisturizing, skin elasticity improvement, and anti-inflammatory function when applied to ex vivo human-derived skin tissue models in experiments. The study has contributed to the understanding of the "CELLADEPP Patch" and laid the foundation for subsequent animal experiments and clinical trials.

Protective effect of taurine on UVB-induced skin aging in hairless mice.

Taurine, a sulfur-containing amino acid derivative, exists at a high concentration in the skin and is considered to play an important role in maintaining moisture homeostasis. This study investigated the effects of oral taurine supplementation on epidermal moisture content and wrinkle formation, as well as skin taurine content, using ultraviolet B (UVB)-irradiated hairless mice. Wrinkles were induced by exposing hairless mice to UVB radiation (70-100 mJ/cm2). Taurine was dissolved in drinking water at a concentration of 0.3 or 3% (w/v) and given to the mice ad libitum for 2-10 weeks. Taurine was then extracted from the dorsal skin, and the skin taurine content was determined using high-performance liquid chromatography (HPLC). The wrinkles were evaluated using a wrinkle score and the quantitative wrinkle area ratio. The exposure of the mice to UVB radiation for 4 weeks resulted in a decreased moisture content and increased transepidermal water loss (TEWL) in the skin, while taurine supplementation suppressed these changes. Oral supplementation with taurine for 8 weeks ameliorated the development of UVB-induced wrinkle formation. Furthermore, oral taurine supplementation for 4 weeks decreased pre-stablished wrinkles in a dose-dependent manner. Although the UVB radiation reduced the epidermal taurine content, oral taurine supplementation partly restored the taurine content in the epidermis. The present study showed that oral taurine supplementation is able to suppress UVB-induced wrinkle formation, which may be associated with the regulation of moisture content in the epidermis. The beneficial effects of taurine on skin aging may be attributed to its osmoregulatory role.

ARTICLE: Alteration to the Skin Barrier Integrity Following Broad-Spectrum UV Exposure in an Ex Vivo Tissue Model.

Dynamic changes to the skin barrier’s molecular structure and ceramide profile are well-documented in skin conditions such as atopic dermatitis and psoriasis. Pathological and environmental factors have been shown to impair barrier integrity and demonstrate shifts in ceramide composition in the skin. However, the relationship between acute and prolonged sun exposure and its effects on skin barrier homeostasis is insufficiently investigated. This study aims to uncover new scientific evidence to elucidate the relationship of UV irradiation with the skin barrier using an ex vivo tissue model following simulated UVA/UVB exposure. Fresh ex vivo human skin pretreated either with or without a broad-spectrum sunscreen was exposed to either a physiological or elevated UV condition. Following eight days in culture, structural and molecular changes were evaluated. UV irradiated skin displayed epidermal cell death and altered expression of key barrier proteins. TEM analysis demonstrated disruption to adherens junctions and dissociation between tissue layers following both physiological and extensive UV exposures. An effective broad-spectrum sunscreen containing essential skin ceramides completely protected the skin from such changes. This is one of the first works demonstrating a clear correlation of altered skin barrier integrity using a physiologically relevant dose in an ex vivo tissue model. Our findings also further support the additional importance and benefits of sun protection among the consumers. J Drugs Dermatol. 20(4 Suppl):s23-28. doi:10.36849/JDD.S589D.

ARTICLE: Efficacy of Ceramide-Containing Formulations on UV-Induced Skin Surface Barrier Alterations.

The human skin, particularly the stratum corneum, serves as a protective barrier against exogenous factors, including ultraviolet radiation (UVR) and pathogen invasions. The impact of UVR on skin cancer and photoaging has been extensively studied. However, the direct impact of UVR on skin barrier integrity under clinical settings remains poorly explored. Due to their benefits in reducing inflammation and promoting skin barrier repair, ceramide-containing formulations can provide added photoprotection benefits. In this study, the efficacy of a ceramide-containing sunscreen and moisturizer were evaluated in preventing UV-induced skin surface barrier changes. Expert grading, instrumental, and tape-stripping assessments demonstrated that UVR induced erythema and hyperpigmentation and caused changes in skin cells surface morphological organization and maturation. Treatment with a ceramide-containing sunscreen and moisturizing cream routine reduced erythema and hyperpigmentation, improved skin hydration, and maintained normal superficial skin cells morphology and turnover after UVR. Our results indicate that barrier-enforcing lipids formulations can provide additional benefits in patient’s daily routine by strengthening the barrier and improving skin health overall against chronic sun exposure. J Drugs Dermatol. 20(4 Suppl):s29-35. doi:10.36849/JDD.S589E.

The Role of Autophagy in Skin Fibroblasts, Keratinocytes, Melanocytes, and Epidermal Stem Cells.

Human skin acts as a barrier to protect our bodies from UV rays and external pathogens and to prevent water loss. Phenotypes of aging, or natural aging due to chronic damage, include wrinkles and the reduction of skin thickness that occur because of a loss of skin cell function. The dysregulation of autophagy, a lysosome-related degradation pathway, can lead to cell senescence, cancer, and various human diseases due to abnormal cellular homeostasis. Here, we discuss the roles and molecular mechanisms of autophagy involved in the anti-aging effects of autophagy and the relationship between autophagy and aging in skin cells.

Non-invasive quantitative measures of qualitative grading effectiveness as the indices of acute radiation dermatitis in breast cancer patients.

BACKGROUND: Recent improvement of machinery evaluation for the skin changes in various therapies enabled us to evaluate fine changes quantitatively. In this study, we performed evaluation of the changes in radiation dermatitis (RD) using quantitative and qualitative methods, and verified the validity of the conventional qualitative assessment for clinical use. METHODS: Forty-three breast cancer patients received conventional fractionated radiotherapy to whole breast after breast-conserving surgery. Erythema, pigmentation and skin dryness were evaluated qualitatively, and biophysical parameters of RD were measured using a Multi-Display Device MDD4 with a Corneometer for capacitance, a Tewameter for transepidermal water loss (TEWL), a Mexameter for erythema index and melanin index. Measurements were performed periodically until 1 year. RESULTS: The quantitative manifestations developed serially from skin erythema followed by dryness and pigmentation. Quantitative measurements detected the effects of irradiation earlier than that of qualitative indices. However, the grades of the domains in RD by qualitative and quantitative assessment showed similar time courses and peak periods. However, no significant correlation was observed between the skin dryness grade and skin barrier function. In contrast to serial increase in pigmentation grades, melanin index showed initial decrease followed by marked increase with significant correlation with pigmentation grades. CONCLUSION: Subjectively and objectively measured results of RD were almost similar course and peak points through the study. Therefore, validity of the conventional qualitative scoring for RD is confirmed by the present quantitative assessments. Instrumental evaluations revealed the presence of modest inflammatory changes before radiotherapy and long-lasting skin dryness, suggesting indication of intervention for RD.

Efficacy of microneedling versus fractional Er:YAG laser in facial rejuvenation.

BACKGROUND: Microneedling and fractional lasers have been used in facial rejuvenation with acceptable results and low adverse effects. AIMS: To compare the efficacy of microneedling with fractional Er:YAG in facial skin rejuvenation. PATIENTS/METHODS: This study was planned as a split-face clinical trial. Volunteers were randomly allocated to receive three monthly treatments on each side of the face, one with fractional Er:YAG laser and one with microneedling. The assessments included investigating clinical outcomes by two blinded dermatologists accompanied by measuring skin biophysical characteristics including cutaneous resonance running time (CRRT) and transepidermal water loss (TEWL). Moreover, possible adverse effects, downtime, and patients' satisfaction were recorded at baseline, 1 month after each treatment, and 3 months after the last treatment session. The protocol was approved by the Iranian Registry of Clinical Trials (IRCT20160820029436N3). RESULTS: Of the 32 selected volunteers, 24 subjects completed the study. The clinical assessment showed a significant improvement of the face appearance along with a significant reduction in dyschromia, and periorbital wrinkling (P-value < .05), with both procedures without any considerable difference between two methods. Moreover, the patients showed substantial satisfaction with both modalities with no statistically significant difference. Mean TEWL and CRRT values also decreased significantly in both groups with no considerable difference. The downtime was significantly shorter in the microneedling-treated side. There were no long-lasting or severe adverse effects after treatment with both methods. CONCLUSION: Microneedling and fractional Er:YAG laser have comparable efficacy in facial rejuvenation, but little downtime of the former makes it preferable for many patients.

Administration of Apple Polyphenol Supplements for Skin Conditions in Healthy Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

This clinical study was performed to evaluate the effects of continuous apple polyphenol (AP) administration on facial skin conditions and pigmentation induced by ultraviolet (UV) irradiation in healthy women participants. Participants (n = 65, age 20-39 years) were randomized to receive tablets containing AP (300 or 600 mg/day) or placebo in a double-blinded, placebo-controlled clinical trial. Continuous administration of AP for 12 weeks significantly prevented UV irradiation induced skin pigmentation (erythema value, melanin value, L value), although a dose-dependent relationship was not clearly observed. In contrast, no significant differences were detected between the groups with regard to water content and trans-epidermal water loss. Our study demonstrated that APs and their major active compounds, procyanidins, have several health benefits. Here, we report that continuous administration of AP for 12 weeks alleviated UV irradiation induced skin pigmentation, when compared with placebo, in healthy women.

Galectin-3 regulates UVB-induced inflammation in skin.

BACKGROUND: Galectin-3 is widely expressed in many immunocytes and epithelial cells including skin keratinocytes. Galectin-3 can regulate immunological or inflammatory processes and plays a proinflammatory role in some disease models. Galectin-3 has a role in disorders related to ultraviolet (UV) photodamage such as apoptosis, skin squamous cell carcinoma and basal cell carcinoma. However, the evidence of galectin-3 in UVB-induced skin inflammation is still limited and the underlying molecular mechanism remains elusive. OBJECTIVE: We aimed to investigate the effects of galectin-3 in human epidermal keratinocytes and in mice after UVB irradiation. METHODS: Primary human epidermal keratinocytes with galectin-3 knockdown were used as the in vitro model. ELISA, QPCR, and western blotting were applied to evaluate the released cytokine, mRNA and protein expression. Histologic analysis, measurement of erythema and transepidermal water loss (TEWL) were applied to evaluate UVB-induced skin damage in galectin-3 knockout mice. RESULTS: In UVB-irradiated human keratinocytes, galectin-3 knockdown downregulated the UVB-induced ASC crosslinking, cleavage of caspase-1, and formation of active IL-1ß. Galectin-3 knockdown also decreased UVB-induced production of reactive oxygen species, p38 phosphorylation, and COX2 expression in human keratinocytes. After four days of UVB irradiation, galectin-3 knockout mice showed reduced gross erythema, histologic features of tissue inflammation, quantified levels of erythema and TEWL compared to wild type mice. The skin tissue lysate also showed less expression of active IL-1ß and COX2 in galectin-3 knockout mice. CONCLUSION: Galectin-3 may play a positive regulatory role in UVB-induced skin inflammation.

Effects of 308 nm excimer light treatment on the skin microbiome of atopic dermatitis patients.

BACKGROUND: The skin microbiome has been implicated in the pathophysiology of atopic dermatitis (AD). Although 308 nm excimer light treatment is an effective phototherapy for AD, its effects on the skin microbiome currently remain unclear. Therefore, we investigated the effects of the excimer light treatment on the skin bacterial and fungal microbiome of lesional skin of AD. METHODS: Swab samples were collected from 11 healthy controls, non-lesional and lesional skin of 11 AD patients. The excimer light treatment was administered to the lesional skin. The composition of the skin microbiome, the clinical score and skin barrier function of the lesional skin were examined before and after the treatment. The composition of the skin microbiome was determined by sequencing bacterial 16S and fungal internal transcribed spacer regions. RESULTS: The excimer light treatment significantly changed the composition of the bacterial microbiome in the lesional skin of AD, as well as improved the clinical score and skin barrier function. The treatment increased the relative abundance of the phylum Cyanobacteria and decreased that of the phylum Bacteroidetes in lesional skin. At the species level, the treatment significantly decreased the relative abundance of Staphylococcus aureus (S aureus) in lesional skin. There was also a significant correlation between the reduction of S aureus and improvement of the clinical outcomes. CONCLUSION: Our findings suggest that alterations of the skin microbiome with excimer light treatment, specifically the decrease in the abundance of S aureus, are partly involved in the improvement of AD lesions.

Evaluation of autologous adipose-derived stem cells vs. fractional carbon dioxide laser in the treatment of post acne scars: a split-face study.

BACKGROUND: Scarring is a distressing outcome of acne, as it causes cosmetic and psychological problems to the patients. Unfortunately no single treatment is satisfactory; instead, employing multiple modalities may have better outcome. Autologous adipose tissue-derived adult stem cells (AT-ASCs) and their secretory factors can stimulate collagen synthesis; angiogenesis and migration of fibroblasts thus regenerate damaged tissues. Also, conventional treatments for acne scarring, such as lasers and topical regimens, induce new collagen synthesis via activation of dermal fibroblasts or growth factors. The aim of the study was to verify the effectiveness of AT-ASCs for the treatment of acne scarring vs. the fractional carbon dioxide laser (FxCR). SUBJECTS AND METHODS: Split face comparative study included 10 adult patients with post-acne scars on both sides of the face. One side received AT-ASCs single injection while the other received three sessions of FxCR. Scars were then assessed using the global scoring system Goodman and Baron, scar area percent using NIH ImageJ software and functional assessment by measuring the transepidermal water loss (TEWL) and skin hydration. Both sides were followed for three months. RESULTS: A significant improvement in the degree of scar severity, scar area percent, skin hydration, and TEWL after 3 months of treatment on both sides of the face with insignificant differences between both treatment modalities, provided that AT-ASCs treatment was employed once vs. three sessions of FxCR. CONCLUSION: One injection of AT-ASCs is as effective as three sessions of FxCR in the treatment of atrophic acne scars.

In vivo Change of Keratin-Bound Molecules in the Human Stratum Corneum following Exposure to Ultraviolet Radiation.

BACKGROUND/OBJECTIVES: Ultraviolet (UV) radiation damages the stratum corneum (SC) and disrupts the skin barrier. The damaged skin changes in the molecular composition of the SC, including its water content. However, it is difficult to examine the in vivo SC changes with existing methods, so those have not been well characterized. Therefore, we investigated in vivo changes of UV-induced SC damage using confocal Raman spectroscopy. METHOD: We irradiated the volar forearm of 10 subjects with 0.5, 1, and 1.5 minimal erythemal doses of UV radiation. Then, we examined erythema, the transepidermal water loss (TEWL), the water content, the natural moisturizing factor (NMF), and the lipids of the skin. RESULTS: After UV irradiation, erythema and TEWL of the skin were both increased. The bound water content of the SC was also increased following UV irradiation. The NMF of the SC revealed different tendencies. All free amino acids (FAAs) of the NMF were increased after UV irradiation, except proline. trans-urocanic acid, pyrrolidone carboxylic acid, lactate, and urea, which are NMF components produced by the subsequent catabolism of FAAs and sweat, were decreased after UV irradiation. The amount of ceramide in the SC was also decreased after UV exposure, while cholesterol was increased. CONCLUSIONS: The bound water content of the SC was increased by UV exposure along with increasing TEWL, several NMF components, and cholesterol. These in vivo results for UV-damaged SC obtained via Raman spectroscopy could be applied to research with regard to protecting the SC from UV radiation and treating UV-damaged SC.

The Protective Role of Astaxanthin for UV-Induced Skin Deterioration in Healthy People-A Randomized, Double-Blind, Placebo-Controlled Trial.

Skin is a major safeguard tissue in humans. Because biological barrier function is deteriorated by several kinds of stresses including exposure to ultra-violet (UV) rays, the protection and treatment of skin conditions by dietary supplements are important. We therefore evaluated the effects of dietary supplementation with an algal food-derived antioxidant, astaxanthin, on UV-induced skin deterioration. Twenty-three healthy Japanese participants were recruited to a 10-week double-blind placebo-controlled study. They were assigned to the astaxanthin group supplemented with a capsule containing 4 mg of astaxanthin or the placebo group. To assess the protective role of astaxanthin for UV-induced skin deterioration, we determined the minimal erythema dose (MED) and analyzed UV-induced changes of moisture and transepidermal water loss (TEWL) at baseline and after 9 weeks of supplementation. Subjective skin conditions were assessed by the visual analog scale. The astaxanthin group showed increased MED compared with placebo. In addition, the astaxanthin group had a reduced loss of skin moisture in the irradiated area compared with placebo. Subjective skin conditions for “improvement of rough skin” and “texture” in non-irradiated areas were significantly improved by astaxanthin. Astaxanthin seems protective against UV-induced skin deterioration and helps maintain healthy skin in healthy people.

Epidermal barrier and oxidative stress parameters improve during in 311 nm narrow band UVB phototherapy of plaque type psoriasis.

BACKGROUND: Psoriasis is a multi-systemic inflammatory disease that results from dysregulation between epidermal keratinocyte homeostasis and both innate and acquired immunity. Epidermal barrier defect has been described in psoriatic lesions. Furthermore an imbalance between pro-oxidative stress and antioxidant defense mechanisms are known in psoriasis patients. AIM: The aim of this study was to address the link between disease activity, epidermal barrier and systemic oxidative stress in the course of 311 nm narrow band ultraviolet B (NB-UVB) therapy of psoriasis. The dynamic of systemic oxidative stress parameters as well as local transepidermal water loss (TEWL) and stratum corneum hydration (SCH) was characterized before and after 311 nm NB-UVB therapy on the plaques of psoriasis vulgaris in comparison to untreated non-affected volar forearm sites of the same patients. MATERIAL AND METHODS: 22 patients with plaque type psoriasis vulgaris and 25 gender- and age-matched healthy controls were enrolled. We assessed the psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI) for monitoring disease activity, severity and self-perceived DLQI impact as patient related outcome parameter. We measured non-invasively TEWL (Tewameter TM 300) and SCH (Corneometer CM 825) and the end product of lipid peroxidation - malondialdehyde (MDA), Reactive oxygen species (ROS), ascorbyl radicals (Asc) and detoxifying activity of catalase (CAT) were measured in the peripheral blood with spectrophotometric and EPR spectroscopy methods. RESULTS: Disease activity improved in all patients compared to baseline witnessed by significant decrease in PASI; (from 14.1 to 10.4; p < 0.0001) and DLQI (from 11.7 to 8.1; p < 0.0001). At baseline TEWL-values were significantly (p < 0.0001) higher on psoriatic plaques (16.8 g/h/m2) in comparison to uninvolved skin (5.3 g/h/m2); with a decrease at both sites after NB-UVB phototherapy. SCH was significantly lower at psoriatic plaque s (4.7AU) compared to uninvolved sskin (42.4AU) and increased after treatment (8.6AU) (p < 0.0001). Interestingly, SCH decrease slightly during therapy at uninvolved skin (40.6AU). ROS and Asc declined during therapy in parallel to a decrease in MDA. A mild decrease in the antioxidative enzyme CAT activity which did not reach the significance was observed. CONCLUSION: The presented data is shows that a clinical improvement of psoriatic plaques under NB-UVB therapy, shown in with a decreased PASI and reflected by an increase in quality of life has beneficial effects on epidermal barrier function, SCH and improvement of systemic oxidative stress parameters (ROS, MDA and Asc). We assume that the general improvement in the oxidative stress parameters along with epidermal barrier parameters reflects mainly the improvement of disease activity which overwrites the possible negative pro-oxidative effects of the UV treatment.

Application of water-soluble polyvinyl alcohol-based film patches on laser microporated skin facilitates intradermal macromolecule and nanoparticle delivery.

The intradermal delivery of biologics has long been recognized as attractive approach for cutaneous immunotherapy, particularly vaccination. Although intradermal (i.d.) or subcutaneous (s.c.) injection provide reproducible dosing and good cost- and delivery efficiency, the major objective to avoid sharps and the need for enhanced storage stability have renewed the interest in alternative needle-free delivery strategies. This study presents a new concept for the delivery of macromolecules and nanoparticles to viable skin layers with a high density of professional antigen-presenting cells (APCs). Stable polyvinyl alcohol (PVA) polymer films as well as PVA blends with carboxymethyl cellulose (CMC) or cross-linked carbomer were prepared using an easily-scalable film casting technique. Fluorescein isothiocyanate (FITC) and rhodamine B-labeled dextrane 70 kDa (RD70), used as small and macromolecular model substances, or polystyrene (PS)-nano- and microparticles with diameters of 0.5 µm and 5 µm were directly incorporated into the polymer formulations at varying concentrations. The assembly of the polymer films with an occlusive backing tape created a film patch that provided a fast drug release upon dissolution of the water-soluble film and facilitated an intradermal drug delivery on laser microporated skin. The minimally-invasive P.L.E.A.S.E.® laser poration system (Pantec Biosolutions, Ruggell, Liechtenstein) provided access to viable skin layers by thermally ablating the superficial tissue with a pulsed Er:YAG laser (λ = 2.94 µm). In our in vitro study using excised pig skin, laser microporation induced a 4- to 5-fold increase of water transport (TEWL) through excised skin in a Franz diffusion cell compared to intact skin. The TEWL values detected were comparable to in vivo human skin. The increased water transport facilitated the dissolution of all topically applied dry PVA-based film formulations within 6 h. No dissolution of the films was seen on intact skin. The incubation of the film patches on laser microporated skin for 24 h led to a considerable intradermal delivery of RD70 or PS-nanoparticles, which was superior for pure PVA films compared to PVA-CMC or PVA-carbomer blend formulations. No intradermal delivery was observed on intact skin or when larger PS-microparticles with a diameter of 5 µm were investigated. The presented concept provides a unique opportunity to exploit the improved storage stability of sensitive drug molecules in dry film formulations while providing protection and functionality.

A prospective study of the safety and efficacy of a combined bipolar radiofrequency, intense pulsed light, and infrared diode laser treatment for global facial photoaging.

The clinical features of photoaging include: skin texture changes, laxity, rhytides, pigmentary changes, and vascular changes such as erythema and telangiectasias. In order to meet patients' increasing demands for improving all aspects of photoaging at one office visit, employing a multi-modality treatment for all aspects of photoaging has become increasingly desirable for the physician and patient alike. We examine a novel device that employs bipolar radiofrequency (RF), intense pulsed light (IPL), and infrared diode laser. These laser and light source treatments are performed sequentially. This study aims to evaluate the clinical efficacy and safety of this device (i.e., ELOS Triniti™). Twenty-six subjects received four ELOS Triniti™ treatments at 1-month intervals. They were followed up 1, 3, and 6 months after completing the treatments. Two blinded dermatologists used a comprehensive grading scale to evaluate the degree of the photoaging in terms of rhytides, laxity, dyschromia, erythema, telangiectasias, and texture. Subjects used a 0-10 grading scale for self-assessment of photoaging. Additionally, we measured the Erythema Index (EI), Melanin Index (MI), transepidermal water loss scores (TEWL), stratum corneum moisture scores (SC), and dermis moisture scores (D) before treatment and 1, 3, and 6 months after treatment. There was a statistically significant improvement in all five aspects of the comprehensive grading scale. Overall, it had excellent efficacy for improving erythema, telangiectasias, and skin texture. It also had a relatively long effect on improving skin laxity; however, it had only a limited ability to improve rhytides and dyschromia. It can mildly to moderately improve the global photoaging. This global effect can be noted 1 month after treatment and becomes most clinically apparent 3 months after treatment. This is maintained at least 6 months after treatment. MI index and SC and D values increased while EI index and TEWL values decreased after the treatment. The subjects' self-assessment improved by 2.7 ± 1.2 points. The overall satisfaction rate was 88%. The degree of pain measured 2.5 ± 1.9 points on average. There was no downtime and no severe side effects reported. The sequential implementation of bipolar radiofrequency based optical combination devices (IPL, IR, diode laser) is effective and safe for global facial photoaging.

Protective effects of the antioxidant extract collected from Styela clava tunics on UV radiation­induced skin aging in hairless mice.

Ultraviolet (UV) radiation is considered a primary cause of skin damage, which is characterized by deep wrinkles, roughness, laxity and pigmentation through oxidative stress and oxidative photodamage. To examine the therapeutic effects of ethanol extract of Styela clava tunics (EtSCT) on UV radiation-induced skin aging in hairless mice, alterations in skin phenotype, histological structures, inflammation, endoplasmic reticulum (ER) stress, oxidative conditions and toxicity were investigated during 13 weeks of UV irradiation and topical application of EtSCT. EtSCT showed high reducing power (3.1%), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (92.7%) and NO scavenging activity (15.6%) due to its high total flavonoids (15.3 mg/ml) and total phenolics (36.8 mg/ml). The topical application of EtSCT suppressed photoaging of the skin of UV-irradiated mice, and this was demonstrated by the inhibition of wrinkle formation, the suppression of the erythema index as well as the prevention of transepidermal water loss. Additionally, the epidermal thickness and adipocytes number were recovered to a similar level as that in the no radiation group in the UV + EtSCT­treated groups compared with the UV + vehicle­treated group, and the expression of collagen I increased. The attenuation of mitogen­activated protein kinase and ER stress signaling pathways activated by reactive oxygen species was also detected in the UV + EtSCT­treated group. Inflammatory responses including the infiltration of mast cells, CD31 expression and interleukin-6 secretion were significantly lower in the UV + EtSCT-treated groups. Moreover, the concentration of malondialdehyde was reduced and the activity of superoxide dismutase was effectively recovered in the UV + EtSCT-treated groups compared with that in the vehicle-treated groups. Liver and kidney toxicity factors were maintained at a constant level. These results suggest that EtSCT has the potential for use as therapeutic drug which protects against skin aging by regulating the skin morphology, histopathological structures, ER stress, inflammation and oxidative conditions.