Anti-melanogenic effect of exosomes derived from human dermal fibroblasts (BJ-5ta-Ex) in C57BL/6 mice and B16F10 melanoma cells.

Exosomes are involved in intercellular communication by transferring cargo between cells and altering the specific functions of the target cells. Recent studies have demonstrated the therapeutic effects of exosomes in several skin diseases. However, understanding of the effects of exosomes on anti-pigmentation is limited. Therefore, we investigated whether BJ-5ta exosomes (BJ-5ta-Ex) derived from human foreskin fibroblasts regulate melanogenesis and delineated the underlying mechanism. Interestingly, treatment with BJ-5ta-Ex induced decreased melanin content, tyrosinase (TYR) activity, and expression of melanogenesis-related genes, including microphthalmia-related transcription factor (MITF), TYR, tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2). In addition, BJ-5ta-Ex downregulated the cAMP/PKA and GSK-3ß/ß-catenin signaling pathways and upregulated the MAPK/ERK signaling pathway. Notably, treatment with BJ-5ta-Ex inhibited α-melanocyte-stimulating hormone-induced melanosome transport and decreased the expression of key proteins involved in melanosome transport, namely, rab27a and melanophilin (MLPH). To further confirm the depigmenting effects of BJ-5ta-Ex, we conducted experiments using a three-dimensional reconstituted human full skin model and ultraviolet B (UVB)-irradiated mouse model. Treatment with BJ-5ta-Ex improved tissue brightness and reduced the distribution of melanosomes. In UVB-irradiated mouse ears, BJ-5ta-Ex reduced the number of active melanocytes and melanin granules. These results demonstrate that BJ-5ta-Ex can be useful for the clinical treatment of hyperpigmentation disorders.

Needleless laser injector versus needle injection for skin enhancement and rejuvenation effect of dermal filler.

BACKGROUND AND OBJECTIVES: A needleless laser-induced microjet injector is a novel transdermal drug delivery system that can rapidly inject a very small and precise drug dose into the skin with minimal pain and downtime. In this study, we aimed to compare the laser-induced microjet injection versus needle injection of polylactic acid/hyaluronic acid filler for skin enhancement and rejuvenation. PATIENTS AND METHODS: A 24-week prospective, single-center, assessor-blinded, randomized, split-face study was conducted. The enrolled patients underwent one treatment session of dermal filler injection using a laser-induced microjet injector on one half of the face or a traditional needle injection on the other half of the face. Evaluation was conducted at baseline before treatment and at 4, 12, and 24 weeks after treatment. RESULTS: A single treatment of filler injection with a laser-induced microjet injector resulted in similar improvements in skin hydration and elasticity as a single treatment of filler injection by using manual needle injection, with reduced pain, side effects, and decreased treatment time. CONCLUSIONS: Laser-induced microjet injector enabled not only the application of a controlled dose and filler depth but also even distribution, improved clinical efficacy, reduced pain and side effects, and sufficient time for clinicians to perform treatment.

Full-thickness skin rejuvenation by a novel dual-length microneedle radiofrequency device: A proof-of-concept study using human skin.

BACKGROUND: A novel dual-length microneedle radiofrequency (DLMR) device has been developed to achieve full-thickness skin rejuvenation by stimulating the papillary and reticular dermis simultaneously. This device's dual-level targeting concept need to be validated on human skin, although its clinical efficacy has been demonstrated in a previous study. OBJECTIVES: This study evaluated the dual-depth targeting capability and the ability to induce rejuvenation in each layer of vertical skin anatomy, that is, the epidermis, papillary dermis, and reticular dermis, using full-thickness human facial skin samples. METHODS: Human facial skin samples were obtained from 13 Asian patients who had facelift surgery. To validate the dual-depth targeting concept, DMLR-treated skin samples were analyzed using a digital microscope, thermal imaging, and hematoloxylin and eosin (H&E) staining immediately after DLMR application. On samples stained with H&E, Masson's tricrome, and Verhoeff-Van Gieson, histological observation and morphometric analysis were performed. Total collagen assay (TCA) and quantitative real-time polymerase chain reaction (qPCR) were used to assess changes in total collagen content and mRNA expression levels of collagen types I/III and vimentin, respectively. RESULTS: The DLMR device successfully induced thermal stimulation in the papillary and reticular dermis. The thickness, stacks, and dermal-epidermal junction convolution of the epidermis treated with DLMR were significantly increased. Collagen bundles in the dermis treated with DLMR exhibited a notable increase in thickness, density, and horizontal alignment. Dermal collagen levels were significantly higher in the morphometric and TCA data, as well as in the qPCR data for dermal matrix proteins. CONCLUSIONS: Our DLMR device independently and precisely targeted the papillary and reticular dermis, and it appears to be an effective modality for implementing full-thickness rejuvenation.

Adipose-derived stem cell exosomes for treatment of dupilumab-related facial redness in patients with atopic dermatitis.

BACKGROUND: Dupilumab facial redness (DFR) is a side effect of dupilumab treatment that has only been recently reported. We previously reported on two patients with DFR who were successfully treated with a topical formulation containing human adipose tissue-derived mesenchymal stem cell-derived exosomes (ASCEs). OBJECTIVES: The study aimed to evaluate the efficacy and safety of ASCEs in DFR. PARTICIPANTS AND METHODS: We performed 12-week prospective study at single center. Twenty adult atopic dermatitis patients diagnosed with DFR were enrolled. They were treated with a topical application of the exosome formulation every week for five consecutive weeks. RESULTS: After exosome treatment, both the average investigator global assessment score and clinical erythema assessment scale scores decreased. 19 patients (95%) were satisfied with the treatment. Compared to baseline, erythema index at week 4 were decreased by 31, 27, 13, and 25 units on the forehead, chin, right and left cheek respectively. The analysis of stratum corneum samples revealed the expression of IL-1α and human thymic stromal lymphopoietin was suppressed after exosome treatment, whereas filaggrin and vascular endothelial growth factor expression increased. CONCLUSIONS: This study suggests topical formulation containing ASCEs can alleviate DFR by downregulating local inflammation and restoring skin barrier function.

A Randomized, Prospective, Split-Face Pilot Study to Evaluate the Safety and Efficacy of 532-nm and 1,064-nm Picosecond-Domain Neodymium:Yttrium-Aluminum-Garnet Lasers Using a Diffractive Optical Element for Non-Ablative Skin Rejuvenation: Clinical and Histological Evaluation.

BACKGROUND: The advent of fractionated picosecond (ps) lasers has provided an opportunity to explore new ways of creating microinjuries in the skin to induce skin rejuvenation. OBJECTIVE: To compare the efficacy and safety of diffractive optical element (DOE)-assisted ps neodymium: yttrium-aluminum-garnet (Nd:YAG) lasers with 532-nm and 1,064-nm wavelengths (532-nm and 1,064-nm Nd:YAG P-DOE) using a novel fractional handpiece for the treatment of photoaged skin. METHODS: An ex vivo guinea pig skin experiment was performed by evaluating the histology of the skin after 532-nm Nd:YAG P-DOE irradiation. A randomized, prospective, split-face study was performed on eight subjects with 532-nm and 1,064-nm Nd:YAG P-DOE. RESULTS: Based on the histological evaluation using ex vivo guinea pig skin, a reasonable safety profile and the potential to generate effective skin rejuvenation was observed using the 532-nm Nd:YAG P-DOE. Results demonstrated that both 532- and 1,064-nm Nd:YAG P-DOE were similarly effective in improving skin texture and skin pores; however, 532-nm Nd:YAG P-DOE was more effective in treating dyspigmentation. CONCLUSION: At a preliminary level, this study revealed that 532-nm and 1,064-nm ps Nd:YAG lasers using DOE fractional technology may improve photoaged skin. In conclusion, 532-nm Nd:YAG P-DOE may be especially beneficial for skin with epidermal pigmentary lesions.

Combination of Non-Ablative Fractional Laser with Q-Switched Laser for the Treatment of Becker's Nevus: Efficacy and Limitations.

Becker's nevus (BN) is a benign hamartoma that may present as a distressing cosmetic problem. The treatment of BN poses a significant challenge as current therapeutic modalities are suboptimal and have an increased risk of adverse effects, such as scarring and dyspigmentation. We present the use of non-ablative fractional laser therapy combined with Q-switched Nd:YAG laser as a possible therapeutic option for BN treatment and review relevant literature to discuss its efficacy and limitations.

Patient Safety Culture and Speaking Up Among Health Care Workers.

PURPOSE: Although previous research showed the importance of safety culture on health care workers' speaking up behaviors, it is not clear how particular safety culture domains are associated with the speaking up behaviors of hospital staff. Also, researchers have suggested that health care workers' speaking up behaviors vary by profession, but there has been limited research into such differences. Thus, this study examined differences in perceptions of patient safety culture and the promotive and prohibitive speaking up behaviors of health care workers by profession and investigated the relationships between patient safety culture and the two types of speaking up behaviors. METHODS: A descriptive correlational study was conducted using secondary data collected through an online survey of health care workers at a private, nonprofit, tertiary-level teaching hospital in South Korea. The sample (N = 831) consisted of nurses (54.0%), physicians (13.0%), and other licensed and unlicensed hospital personnel (33.0%). Analyses of variance were conducted to examine differences in study variables by profession. Hierarchical regression analyses were conducted to evaluate the effects of the seven patient safety culture factors on promotive and prohibitive voice after controlling for tenure and profession. RESULTS: Perceptions of safety culture and promotive voice behaviors were higher for physicians compared with nurses. Communication openness, reporting patient adverse events, and unit supervisors' and hospital managements' support for patient safety were significant predictors of both types of voice behaviors. CONCLUSION: Hospital administrators and unit managers should create a supportive environment where staff feel free to voice their concerns and suggestions. They should also pay attention to the varying perspectives held by different groups of hospital workers and their different voice behaviors. Knowing which dimensions of patient safety culture are most strongly related to health care workers' voice behaviors can guide patient safety improvement activities in health care organizations.

Innovative Use of Negative Air Ions As an Alternative Therapy for Acne Vulgaris: A Report of Three Cases.

Acne vulgaris is a universal skin disease with multifactorial pathogenesis. Although an extensive range of treatment options exist for acne, a substantial number of patients are still struggling for an optimal treatment option due to the side effects or contraindications to the conventional acne treatment. Negative air ions (NAIs) are electrically charged molecules that naturally exist in the atmosphere. Since they are natural component of air, there are no known side effects and contraindications to their application. Furthermore, among the identified benefits of NAIs, certain mechanisms are related to acne pathogenesis, allowing them to be attractive candidates for acne treatment. Here, we describe three patients with acne who showed considerable clinical improvement after NAI therapy. All of the patients had failed to tolerate traditional acne treatment options. In all three cases, considerable improvement was observed in acne severity and the number of total lesions. Based on the three cases and a review of literature underlying the effects of NAIs, we suggest that NAIs may be a safe and effective alternative therapeutic option for acne vulgaris.

Comparative Analysis of Cutaneous Fungi in Atopic Dermatitis Patients and Healthy Individuals.

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease triggered by diverse factors. Microbes are one of the crucial risk factors for AD development or exacerbation. However, the effect of a fungal burden on AD has been overlooked compared to bacteria. Objective: This study aimed to comparatively analyze cutaneous fungal distribution between AD patients and healthy individuals by polymerase chain reaction (PCR)-based analysis. Methods: Skin samples of AD outpatients and healthy individuals collected at the Chung-Ang University were analyzed. Representative AD-associated fungal genera, Candida, dermatophytes, and Malassezia , were analyzed using specific primer and amplification methods. Amplicons were sequenced, and the fungal distribution of both groups were compared. Results: Totally, 211 patients and 23 healthy individuals were studied. Of the 211 patients, 10.90% (23/211) had Candida species, whereas 0% (0/23) healthy individuals showed its presence. The most frequently detected species in patients was Candida albicans (5.21%) followed by Candida parapsilosis (3.79%). For dermatophytes, 1.42% (3/211) of patients showed positive results, whereas 0% (0/23) healthy individuals showed positive results. Malassezia species were identified in 20.85% (44/211) and 8.70% (2/23) in patients and healthy individuals, respectively. Malassezia restricta was the most frequently identified species in the AD patient group, and the only species found in the healthy control group. Conclusion: The distribution of Candida spp., dermatophytes, and Malassezia spp. are altered with AD development.

A split face study on the effect of an anti-acne product containing fermentation products of Enterococcus faecalis CBT SL-5 on skin microbiome modification and acne improvement.

Antibiotic-resistant Cutibacterium acnes and dysbiosis of the skin microbiome are of increasing concern in acne treatment. Enterococcus faecalis, a widely used probiotic, has shown benefits for acne treatment by exerting antimicrobial activity against C. acnes. Therefore, this study aimed to investigate the efficacy and safety of an E. faecalis CBT SL-5-extract-containing lotion in patients with mild-to-moderate acne. Twenty patients were enrolled in this randomized, placebo-controlled, split-face comparative study. Patients were treated with E. faecalis lotion on one side of the face and a vehicle lotion on the other side for 4 weeks. The efficacy outcome measures included improvement in the investigators' assessment of acne severity, patient satisfaction, changes in skin parameters and diversity of the skin microbiome. The investigators' assessment score was significantly improved on the test side compared to the control side, after 2 weeks (p = 0.009) and 6 weeks (p < 0.0005). However, TEWL and skin hydration were not significantly different between the two groups. The phylogenetic diversity of the skin microbiota decreased over time in the skin samples of test side. In conclusion, E. faecalis CBT SL-5 extract can be a feasible and well-tolerated option for improving acne severity and skin microbiome dysbiosis in mild-to-moderate acne patients.

Safety and efficacy of high-intensity focused ultrasound for treatment of periorbital, perioral, and neck wrinkles: Prospective open single-center single-arm confirmatory clinical trial.

Periorbital, perioral, and neck wrinkles are one of the most common concerns of aging skin. We evaluated the efficacy and safety of high-intensity focused ultrasound (HIFU) device with a 5.5-MHz transducer and a 2.0-mm focal depth for improving periorbital, perioral, and neck wrinkles. A total of 102 participants were enrolled, and 34 each were assigned to the periorbital, perioral, and neck groups. All subjects were treated with HIFU three times at 2-week intervals at the corresponding treatment site. Objective measurements and clinical evaluations were performed at 10 and 16 weeks after treatment. Based on the primary efficacy evaluation, the mean Cutometer R7 value was significantly increased at 10 weeks post-treatment compared to baseline in all treated groups. In addition, all other Cutometer values, PRIMOS and Antera 3D camera evaluation results, classification of wrinkle assessment results, and Subject Global Aesthetic Improvement Scale also showed that the periorbital, perioral, and neck wrinkles were significantly improved at 10 and 16 weeks post-treatment. No permanent adverse effects were observed during the follow-up period. HIFU treatment using 5.5-MHz transducers (2.0-mm focal depth) could be an effective and safe treatment modality for the treatment of periorbital, perioral, and neck wrinkles.

Irradiation with 590-nm yellow light-emitting diode light attenuates oxidative stress and modulates UVB-induced change of dermal fibroblasts.

Recently, light-emitting diode (LED)-based devices have emerged as effective and safe tools for the treatment of photoaged skin. However, few studies have been conducted to elucidate the underlying mechanism behind the effect on photoageing of LED light. In this study, we induced photoageing of human dermal fibroblasts (HDFs) with Ultraviolet B (UVB) irradiation and evaluated the ability of 590-nm LED radiation to induce recovery from oxidative stress, restore collagen formation and regulate inflammatory changes. Photoageing was induced in cultured human dermal fibroblasts (HDFs) using UVB irradiation of 50 mJ/cm2 . Then, the photoaged HDFs were irradiated with LED using a custom-built 590-nm LED device which emits light with an intensity of 38 mW/cm2 (irradiated for 900 s with 34.2 J/cm2 of total energy). LED irradiation significantly attenuated UVB-induced reactive oxygen species generation and UVB-induced phosphorylation of JNK, c-Fos and c-Jun. In addition, the procollagen levels were recovered significantly, and MMP-9 levels were significantly suppressed after LED irradiation. The UVB-induced phosphorylation levels of NF-κB and pro-inflammatory enzyme COX-2 also significantly decreased. Our results suggest that 590-nm yellow light irradiation may be an effective and safe anti-oxidative and anti-inflammatory treatment modality for photoaged skin.

Utilization of Ultrasonography in Dermatology: Two Case Reports of Calcinosis Cutis.

Development of newer generation of cost-effective ultrasonic devices in recent years has increased the use of ultrasonography in dermatology. Several lesions can be diagnosed and managed using ultrasonography. Calcinosis cutis involves the deposition of insoluble calcium salts in the cutaneous and subcutaneous tissues. On ultrasonography, it specifically presents as hyperechoic deposits with a posterior acoustic shadowing artifact due to the acoustic properties of calcium. A 62-year-old female patient presented with a solitary, skin-colored, palpable nodule on the inner side of the right lower leg. The lesion was beneath the intact skin and detectable only on palpation. However, ultrasonography demonstrated a clear delineation of the lesion, showing hyperechoic deposits with a posterior acoustic shadow (15 MHz, linear probe). Skin biopsy and curettage were performed, revealing histological features consistent with calcinosis cutis. Four weeks after the procedure, ultrasonography performed to evaluate the outcome of treatment, showed recurrence. Another 18-year-old female patient presented with a skin-colored deep-seated nodule on the left temple. On ultrasonography, linear hyperechoic deposits with a posterior acoustic shadow were visible. Skin biopsy was performed, and histopathologic features showed calcified material in the subcutaneous tissue. These two cases of calcinosis cutis highlight the diagnostic value of ultrasonography in dermatology.