Rheological properties and preclinical data of novel hyaluronic acid filler containing epidermal growth factor.

Recently, a novel hyaluronic acid (HA) filler containing the epidermal growth factor (EGF) was developed. The objective of this study was to evaluate the rheological properties, preclinical efficacy and biocompatibility of the EGF-containing HA filler (HA-EGF filler) using a photoaged mouse model. The rheological properties of the new HA-EGF filler were assessed. Twenty-four female hairless mice (SKH1) underwent photoaging induction with 8 weeks of ultraviolet-B irradiation. The mice were randomly divided into four groups and intradermally injected 100 µl of phosphate-buffered saline, HA-EGF filler, HA filler or polynucleotide (PN) into the dorsal region. We examined the effect of fillers on photoaged skin by dermoscopic examination. Furthermore, histological evaluation with immunohistochemical staining was performed to determine the biocompatibility and collagen formation at the 10th week. A real-time quantitative polymerase chain reaction analysis and western blot test assessed the expression of collagen I/III, matrix metalloproteinases (MMPs) and transforming growth factor. The viscosity and elasticity of the HA-EGF filler were lower than those of the HA filler. Histological evaluation revealed no significant differences in the collagen synthesis between the HA-EGF, HA and PN filler groups. No inflammation was observed during the experimental period. The HA-EGF filler induced type I/III collagen production and downregulated the expression of MMP-1, 3 and 9. Our results suggest that the novel HA-EGF filler may be an additional therapeutic option for photoaged skin, which works by inducing collagen synthesis. Based on these preclinical results, further well-controlled clinical studies are required.

Evaluating the tolerance and efficacy of laser-assisted delivery of tranexamic acid, niacinamide, and kojic acid for melasma: A single center, prospective, split-face trial.

Although many treatment options are available, the treatment of melasma remains challenging. To investigate the efficacy and safety of combined treatment for melasma with a quality (Q)-switched 1064-nm neodymium: yttrium-aluminum-garnet (Nd:YAG) laser and a topical mixture of tranexamic acid, niacinamide, and kojic acid. Twenty-five patients with melasma were enrolled. One side of the face was treated with low-fluence Q-switched 1064-nm Nd:YAG laser alone, while the other side was treated with a combination of laser treatment and a topical mixture of tranexamic acid, niacinamide, and kojic acid. Each treatment consisted of five sessions at 2-week intervals, and patients were followed up 4 weeks after the last treatment. Overall improvement was assessed using the hemi Melasma Area and Severity Index (MASI) score. A specialized imaging system (Markview®, PSIPLAUS Inc., Suwon, Korea) was used to record images of the patients' faces, and photographic assessment was performed by two independent evaluators at 2, 4, 6, 8, and 12 weeks using a five-point grading scale. Although both sides of the face showed clinical improvement, combination treatment demonstrated a greater improvement in the mean hemi MASI score compared to laser treatment alone. Improvement in melasma at 12 weeks, according to the evaluation of patient images by two independent evaluators, was greater with combination treatment. This study demonstrated that the combination of treatment with a low-fluence Q-switched 1064-nm Nd:YAG laser and a topical mixture of tranexamic acid, niacinamide, and kojic acid would be a good option for melasma treatment.

Treatment of facial pigmented disorders with a 785-nm picosecond Ti:sapphire laser in Asians: A report of three cases.

Since the advent of the theory of selective photothermolysis, the importance of targeting the chromophore and minimizing the surrounding damage has been extensively discussed. Picosecond-domain laser (ps-laser) treatment with a wide range of wavelengths is an emerging option for various pigmented lesions; however, no definitive treatment choice has been confirmed. The authors aimed to investigate the efficacy and safety of a ps-laser with a 785-nm wavelength for the treatment of facial pigmented lesions in Asians. Three Korean patients with facial pigmented lesions were recruited for the study. A 785-nm ps-laser with a fractionated and an unfractionated handpiece was utilized to administer the treatment. The clinical outcome was evaluated by a clinician by comparing pre- and post-treatment photographs. All patients exhibited a significant improvement in pigmented lesions including freckles, lentigines, and melasma, after three to four sessions of treatment. No adverse events, including post-inflammatory hyperpigmentation or hypopigmentation were observed. In conclusion, this novel 785-nm Ti:sapphire ps-laser may be an effective and safe modality for treating pigmented lesions in skin of color.

Evaluation of the efficacy and safety of the 1064 nm picosecond Nd:YAG laser with a topically applied gold and diamond suspension for facial skin rejuvenation: A pilot study.

To investigate the efficacy and safety of combined treatment with a serum comprising a micro-diamond suspension and micro-gold cage with a 1064 nm picosecond neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for facial skin rejuvenation. Topical serum was applied to the entire face and allowed to penetrate the skin and hair follicles for 20 min. Each participant was then treated with a 1064 nm picosecond Nd:YAG laser on the face. Photographs of each participant were taken at baseline, immediately after treatment, and 2 weeks after treatment using an imaging tool (Mark-Vu®; PSI PLUS, Suwon, Republic of Korea). Global improvement scores by two blinded investigators and participants' satisfaction scores were also assessed. The melanin index (MI), transepidermal water loss (TEWL), and skin hydration were evaluated using a device. Parameters associated with skin rejuvenation were assessed using Mark-Vu®. Adverse events were observed and reported by participants and physicians during the treatment and follow-up visit. At week 2, 40% (4/10) of the participants showed more than moderate clinical improvement in the investigator's global improvement assessment. No significant differences were observed in the MI, TEWL, skin hydration level, or skin parameters of Mark-Vu®. At week 2, 40% of the participants reported a high satisfaction score and minimal side effects. The novel topical facial serum comprising micro-diamond suspension and micro-gold cage is safe and effective when combined with laser treatment for facial rejuvenation.

In vivo quantitative analysis of advanced glycation end products in atopic dermatitis-Possible culprit for the comorbidities?

Advanced glycation end products (AGEs) interact with the membrane-bound receptor for AGEs (RAGE), consequently amplifying the inflammatory response. Soluble receptor for AGE (sRAGE) and endogenous secretory RAGE (esRAGE) act as decoys for AGE and competitively sequester RAGE ligands, thereby serving a cytoprotective role. Our objective was to investigate AGE expression and their receptors in the serum and skin of patients with atopic dermatitis (AD). In this case-control study, the levels of AGE, sRAGE and esRAGE were measured in the blood samples and corneocytes of 29 adult patients with AD and 12 healthy controls by ELISA. Corneocyte AGE levels increased in the AD group (P = .002). Higher corneocyte AGE levels were observed in the severe AD than in the milder form of AD. No significant difference in serum AGE level was observed in patients with AD and healthy controls. Serum sRAGE markedly decreased in patients with AD (P = .007) and serum esRAGE followed a similar trend. In conclusion, dermal accumulation of AGE in AD may have a role in fuelling skin inflammation. The potential after-effects of reduced neutralizer on systemic risk need further evaluation.

Gold nanoshell-mediated photothermal therapy for acne vulgaris.

Acne vulgaris, a common and chronic disorder of the pilosebaceous unit, affects up to 85% of adolescent and young adults. Although the current treatment options are effective, they are associated with unwanted side effects, chronicity, relapses, and recurrences. Recently, the Food and Drug Administration approved topical application of gold microparticles for selective photothermolysis to treat acne vulgaris. Here, we report two cases showing the efficacy of gold nanoshell-mediated photothermal therapy for recurrent acne that were refractory to previous treatments. In both cases, three sessions of photothermal therapy prevented the development of new lesions during a follow-up period of 3-4 months without causing any adverse effects. The two cases reported here demonstrate the possibility of gold nanoshell-mediated photothermal therapy as a safe and effective treatment for recurrent acne vulgaris in Asian patients.

Successful Treatment of Pigmentary Disorders in Asians With a Novel 730-nm Picosecond Laser.

BACKGROUND AND OBJECTIVE: Until recently, quality-switched nanosecond lasers have been the workhorse lasers in treating pigmented lesions. However, the recently commercialized picosecond lasers have provided physicians with a novel method to manage pigmented lesions. Most recently, the first picosecond laser with a 730-nm wavelength was developed to specifically target melanin and melanocytes. STUDY DESIGN/MATERIALS AND METHODS: We report on two Asian patients with freckles, lentigines, and melasma who were successfully treated with a novel 730-nm Ti:Sapphire picosecond laser (Picoway®; Syneron Candela, Corp). The clinical outcome was measured by the global percent of clearance, which was evaluated by blinded observers by comparing the post-treatment photographs with the baseline photographs. RESULTS: In both patients, a significant pigmentary reduction was achieved with only one treatment session. In both patients, the treatments were well tolerated with minimal discomfort even without topical anesthesia. No post-inflammatory hyperpigmentation or repigmentation was observed until the 6-week follow-up. The pigmentary conditions treated included freckles, lentigines, and melasma. Both subjects showed clinical improvement, with the best results observed for the treatment of freckles such that 95% of the lesions achieved excellent response (75-94% lightening). CONCLUSION: The results of this case report indicate that a novel 730-nm Ti:Sapphire picosecond laser may be effective and safe in treating pigmentary disorders in darker-skinned patients. Therefore, further well-designed, prospective clinical trials are warranted to establish the potential of 730-nm picosecond lasers and determine the optimal treatment parameters in comparison to existing laser and light modalities. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Potency and Quality of Reconstituted Botulinum Neurotoxin Type A According to Storage Temperatures.

BACKGROUND: In clinical practice, one of the most important issues regarding the use of botulinum neurotoxin A (BoNT-A) is the proper storage conditions and the change in potency and quality over time after reconstitution. OBJECTIVE: This study aimed to investigate the change in potency and quality of reconstituted prabotulinumtoxin A (PraBoNT-A) over time when stored at different storage temperatures. MATERIALS AND METHODS: ICR/CD-1 mice and PraBoNT-A were used for the mouse intraperitoneal lethal dose 50% (LD50) test. A thorough quality evaluation of the product was performed. RESULTS: All of the reconstituted PraBoNT-A stored at different temperatures met the evaluation criteria for the suggested limits of estimated potency and for the quality assessment at every evaluated time point. When the stability of reconstituted PraBoNT-A was evaluated by regression analysis, the shelf life of reconstituted PraBoNT-A was found to be 99.24, 73.80, and 16.34 weeks in the case of PraBoNT-A stored at freezing, refrigeration, or room temperatures, respectively. CONCLUSION: Based on the results, the authors conclude that the efficacy and quality of the reconstituted PraBoNT-A product are not compromised at least for a certain period of time and that the shelf life of reconstituted PraBoNT-A is longest when stored at the freezing temperature.

Particulate matter induces pro-inflammatory cytokines via phosphorylation of p38 MAPK possibly leading to dermal inflammaging.

Particulate matter (PM) is known to have harmful effects on human health. Epidemiological studies have suggested that PM exposure is related to skin diseases and extrinsic skin ageing. However, the mechanisms by which PM affects skin are unclear. The aim of this study was to investigate the mechanism of action of PMs on epidermal inflammation and skin ageing using a co-culture of human keratinocytes (HaCaT) and fibroblasts (HDF). SRM 1648a (pmA) and 1649b (pmB), which mainly comprise heavy metals and polycyclic aromatic hydrocarbons, respectively, were used as reference PMs. Cytotoxic effects, activation of AhR, phosphorylation of p38 kinase and ROS generation were examined in PM-treated HaCaT cells. The phosphorylation of p38 MAPK induced by PMs was shown to be critically important for the increases in IL-1α and IL-1ß expression. Moreover, the mRNA and protein expression levels of MMP1 and COX2 were markedly increased in HDF cells co-cultured with PM-treated HaCaT cells. In conclusion, PMs induce the expression of pro-inflammatory cytokines in keratinocytes via the p38 MAPK pathway, and these interleukins increase the expression of MMP1 and COX2 in HDF cells. These results suggest that PMs trigger skin ageing via p38 MAPK activation and interleukin secretion in epidermal keratinocytes.

Development of a Protein Microarray Chip with Enhanced Fluorescence for Identification of Semen and Vaginal Fluid.

The detection of body fluids has been used to identify a suspect and build a criminal case. As the amount of evidence collected at a crime site is limited, a multiplex identification system for body fluids using a small amount of sample is required. In this study, we proposed a multiplex detection platform using an Ag vertical nanorod metal enhanced fluorescence (MEF) substrate for semen and vaginal fluid (VF), which are important evidence in cases of sexual crime. The Ag nanorod MEF substrate with a length of 500 nm was fabricated by glancing angle deposition, and amino functionalization was conducted to improve binding ability. The effect of incubation time was analyzed, and an incubation time of 60 min was selected, at which the fluorescence signal was saturated. To assess the performance of the developed identification chip, the identification of semen and VF was carried out. The developed sensor could selectively identify semen and VF without any cross-reactivity. The limit of detection of the fabricated microarray chip was 10 times better than the commercially available rapid stain identification (RSID) Semen kit.

Identification of novel candidate variants including COL6A6 polymorphisms in early-onset atopic dermatitis using whole-exome sequencing.

BACKGROUND: The prevalence of atopic dermatitis has increased over the last 10 years. Atopic dermatitis tends to run in families and commonly begins to manifest in childhood. The prevalence of atopic dermatitis is as high as 20% in children. Thus, early diagnosis and treatment of atopic dermatitis are important. Understanding its genetic basis is also needed to facilitate early detection. METHODS: To identify family-specific candidate genetic variants associated with early-onset atopic dermatitis in Koreans, we carried out whole-exome sequencing of three separate families with this condition. Additional validation was performed in 112 AD patients and 61 controls using Sanger sequencing. RESULTS: We focused on both common functional variants with a minor allele frequency higher than 1% and rare variants with a minor allele frequency less than 1%. The relevance of the respective variants was supported by a program that could predict whether the mutations resulted in damaged protein function. Fourteen overlapping genes were identified during exome sequencing. Three variants of the COL6A6 gene appeared in all three families and were in close proximity to atopic dermatitis-related loci on chromosome 3q21. The homozygous frequency for the rs16830494 minor allele (AA) and the rs59021909 (TT) allele and the rs200963433 heterozygous (CT) frequency were all higher in AD cases compared to controls in a population-based case-control study. CONCLUSION: Identifying family-specific COL6A6 polymorphisms and genetic variants of other candidate genes associated with AD using WES is a novel approach. Our study suggests that COL6A6 variants may be risk factors for atopic dermatitis. This study provides a genetic basis for early-onset AD diagnosis in Korean patients and the development of new therapies. TRIAL REGISTRATION: Trial registration number: IRB NO. C2008030 (133); Name of registry: The collection research of clinical data and patient blood to identify genetic and protein biomarker of atopic dermatitis; Date of registration: 09-July-2008. TRIAL REGISTRATION NUMBER: IRB NO. C2015258 (1716); Name of registry: The collection study of patient blood and clinical data for the development of the prognosis prediction and early diagnosis of atopic dermatitis; Date of registration: 15-jan-2016.

The pinhole method using an erbium: YAG laser for the treatment of papular acne scars.

Papular acne scars are skin-colored or hypopigmented, soft and elevated lesions of the chin and trunk. Papular scars are one of the most difficult acne scars to treat. Herein, we reported two patients with papular acne scars on the chin that were successfully treated by the pinhole method using an Erbium (ER):YAG laser. Good cosmetic results were achieved in both patients. The side effects included mild, intra-, and post-procedural pain and erythema that resolved spontaneously within 2 weeks. The pinhole method with an Er:YAG laser could potentially be used as a safe and effective treatment for papular acne scars.

Adiponectin corrects premature cellular senescence and normalizes antimicrobial peptide levels in senescent keratinocytes.

Stress-induced premature senescence or aging causes dysfunction in the human somatic system. Adiponectin (Acrp30) plays a role in functional recovery, especially with adenosine 3',5'-monophosphate (AMP)-activated protein kinase (AMPK) and silent mating type information regulation 2 homolog 1 (SIRT1). Acrp30 stimulation reduced the premature senescence positive ratio induced by hydrogen peroxide (H2O2) and restituted human ß-defensin 2 (hBD-2) levels in senescent keratinocytes. Acrp30 recovered AMPK activity in senescent keratinocytes and increased SIRT1 deacetylation activity. As a result, FoxO1 and FoxO3 transcription activity was recovered. Additionally, Acrp30 stimulation suppresses NFκB p65, which induces abnormal expression of hBD-2 induced by H2O2. In the present study, we have shown that Acrp30 reduces premature senescence and recovers cellular function in keratinocytes. These results suggest a role for Acrp30 as an anti-aging agent to improve impaired skin immune barriers.

Delayed immunologic complications due to injectable fillers by unlicensed practitioners: our experiences and a review of the literature.

For a number of years, there have been unauthorized practitioners who have been illegally injecting substances. In this series of cases, delayed type hypersensitivity reactions occurred after having unknown material fillers injected by unlicensed practitioners. When injecting an unknown material, there can be a severe immune reaction due to the unknown number of antigens in the material, and therefore may act as a much stronger superantigen than conventional filler materials. It appears that the adverse effects in these cases are more severe and have tendency to break out after a longer period of time in comparison with those caused by approved fillers, likely due to operative technique and use of unverified materials. It is important to recognize the danger of such illegal procedures and to increase awareness of the public, as this has evolved into a significant public health issue.

Facial Pores: Definition, Causes, and Treatment Options.

BACKGROUND: Enlarged skin pores refer to conditions that present with visible topographic changes of skin surfaces. Although not a medical concern, enlarged pores are a cosmetic concern for a large number of individuals. Moreover, clear definition and possible causes of enlarged pores have not been elucidated. OBJECTIVE: To review the possible causes and treatment options for skin pores. METHODS: This article is based on a review of the medical literature and the authors' clinical experience in investigating and treating skin pores. RESULTS: There are 3 major clinical causes of enlarged facial pores, namely high sebum excretion, decreased elasticity around pores, and increased hair follicle volume. In addition, chronic recurrent acne, sex hormones, and skin care regimen can affect pore size. Given the different possible causes for enlarged pores, therapeutic modalities must be individualized for each patient. CONCLUSION: Potential factors that contribute to enlarged skin pores include excessive sebum, decreased elasticity around pores, and increased hair follicle volume. Because various factors cause enlarged facial pores, it might be useful to identify the underlying causes to be able to select the appropriate treatment.

Combined treatment with 595-nm pulsed dye laser and 1550-nm erbium-glass fractional laser for traumatic scars.

Facial scars can be caused by a traumatic event or indeed surgical procedures. Several treatment modalities have been suggested including surgical or resurfacing techniques, autologous fat transfer, and injection of fillers. However, these approaches have varying degrees of success and associated side effects. We report two Korean patients with traumatic scars. Both patients received combined consecutive treatment with 595-nm pulsed dye laser (PDL) and 1550-nm erbium-glass fractional laser. Both patients showed remarkable clinical improvements after a course of sessions. Therefore, simultaneous combined treatment with PDL and fractional laser may be considered a reasonable therapeutic option for traumatic facial scars.

An Analysis of the Filaggrin Gene Polymorphism in Korean Atopic Dermatitis Patients.

Research of the FLG mutation in various ethnic groups revealed non-overlapping mutation patterns. In addition, Japanese and Chinese atopic patients showed somewhat different mutations. These ethnic differences make the research on Korean patients mandatory; however, no systematic research on Korean atopic dermatitis (AD) patients has been performed. This study aims to investigate the genetic polymorphism of FLG in Korean atopic dermatitis patients. The study was made up of three groups including 9 Ichthyosis vulgaris (IV) patients, 50 AD patients and 55 normal controls: the ichthyosis group was incorporated due to the reported association between the FLG mutation and IV. In comparison to other sequencing methods, the overlapping long-range PCR was used. We revealed the genetic polymorphism of filaggrin in Koreans, and at the same time, we discovered nonsense mutations in p.Y1767X and p.K4022X in Korean AD patients. By using FLG sequencing techniques confirmed in this study, new mutations or genetic polymorphisms with ethnic characteristics would be detected and further larger studies of repeat number polymorphisms could be performed.

Skin Barrier Function Is Not Impaired and Kallikrein 7 Gene Polymorphism Is Frequently Observed in Korean X-linked Ichthyosis Patients Diagnosed by Fluorescence in Situ Hybridization and Array Comparative Genomic Hybridization.

X-linked ichthyosis (XLI) is a recessively inherited ichthyosis. Skin barrier function of XLI patients reported in Western countries presented minimally abnormal or normal. Here, we evaluated the skin barrier properties and a skin barrier-related gene mutation in 16 Korean XLI patients who were diagnosed by fluorescence in situ hybridization and array comparative genomic hybridization analysis. Skin barrier properties were measured, cytokine expression levels in the stratum corneum (SC) were evaluated with the tape stripped specimen from skin surface, and a genetic test was done on blood. XLI patients showed significantly lower SC hydration, but normal basal trans-epidermal water loss and skin surface pH as compared to a healthy control group. Histopathology of ichthyosis epidermis showed no acanthosis, and levels of the pro-inflammatory cytokines in the corneal layer did not differ between control and lesional/non-lesional skin of XLI patients. Among the mutations in filaggrin (FLG), kallikrein 7 (KLK7), and SPINK5 genes, the prevalence of KLK7 gene mutations was significantly higher in XLI patients (50%) than in controls (0%), whereas FLG and SPINK5 prevalence was comparable. Korean XLI patients exhibited unimpaired skin barrier function and frequent association with the KLK7 gene polymorphism, which may differentiate them from Western XLI patients.