Dermatologic Therapy

Extracellular vesicles (EVs) secreted from adipose-derived stem cells (ADSCs) are known to exhibit collagen synthesis and migration activity in fibroblasts. These EVs can be used as a regenerative medicine and for cosmetic medicinal materials. Royal jelly (RJ) is produced from the hypopharyngeal and mandibular glands of honeybees (nurse bee), which contains apicin and 10-hydroxy-2-decenoic acid, compounds that promote fibroblast proliferation and collagen and elastin synthesis. Here, we investigated whether RJ could further enhance the physiological function of ADSC-EVs on fibroblasts. The findings confirmed that lyophilized RJ and enzyme-treated RJ enhanced the secretion of EVs by ADSCs, increasing the proliferation, migration, and collagen synthesis of fibroblasts compared to those induced by conventional ADSC-EVs. Bioinformatics analysis was conducted using various software programs, based on the data obtained from comprehensive gene expression and small RNA profiling analyses through next-generation sequencing; the results suggested that the RJ treatment of ADSC-EVs significantly enhanced the expression of genes related to extracellular matrix composition. Our findings suggest that the ADSC-EVs qualitatively altered using RJ could offer a more effective therapeutic material for regenerative and cosmetic medicine than conventional ADSCs-EVs.

Melasma is a challenging pigmentation disorder to treat, and although low-fluence 1064 nm picosecond ND-YAG lasers have shown potential for treating benign pigmented disorders, data on the use of this laser for melasma treatment are currently insufficient. In this prospective split-face study, twenty-four patients with melasma on the face were enrolled and randomly assigned to receive treatment on one side of the face either with a low-fluence 1064 nm picosecond ND-YAG laser or with a low-fluence PTP mode 1064 nm Q-switched ND-YAG laser. Laser treatment was performed 5 times at intervals of 2 weeks, with evaluation conducted before each treatment and 2 months after the completion of 5 treatments. Clinical pictures using a standardized, digital photographic system and dermoscopy were taken on each day of the visit. The modified melasma area severity index (mMASI), melanin index (MI), dermoscopic scores of the pigmentary and vascular elements in melasma, pain during laser treatment, and patient satisfaction score were recorded. Twenty-one participants completed the study, and from week 2 in both groups, a significant decrease in mMASI and MI were confirmed. Although no statistically significant difference was observed, the decrease in mMASI and MI were greater in the 1064 nm picosecond ND-YAG laser group than in the 1064 nm Q-switched ND-YAG laser group. The 1064 nm picosecond ND-YAG laser group showed significant improvement in the pseudoreticular network and globular pattern of dermoscopic features between week 0 and week 16, while significant improvement in the globular pattern was shown in the 1064 nm Q-switched ND-YAG laser group. No significant difference was observed between the two groups in terms of the patient satisfaction score and pain during laser treatments. Notably, no adverse events were observed in either group. In conclusion, our study demonstrated that a low-fluence 1064 nm picosecond ND-YAG laser is as effective and safe in the treatment of melasma as a low-fluence PTP mode 1064 nm Q-switched ND-YAG laser.

Background. Itch can be transmitted by two parallel pathways, histaminergic and nonhistaminergic. Histaminergic itch is transmitted by a subgroup of mechano-insensitive C-fibers, while nonhistaminergic itch by a subgroup of polymodal C-fibers. Experimental models are used to study pruritus: histamine for the histaminergic itch by antagonizing the histamine H1-receptors, and BAM8-22 and cowhage for the nonhistaminergic by activating Mas-related G protein-coupled receptors and protease-activated receptors, respectively. This study aims to evaluate the antipruritic effects of topical doxepin (H1-receptor antagonistic effect) on histaminergic and nonhistaminergic itch induced by histamine, BAM8-22, and cowhage. Methods. This study was conducted on 22 healthy subjects. Histamine, BAM8-22, cowhage, and vehicle were applied to 4 areas on the forearms. After 7 days, the same substances were applied after  hour-pretreatment with doxepin. After the application of pruritogens, itch and pain intensities were assessed for 9 minutes, followed by the measurement of superficial blood perfusion (SBP), mechanical and thermal sensitivities. Results. Application of histamine, BAM8-22, and cowhage all induced itch as compared to a vehicle. The pretreatment with doxepin almost abolished the histamine-induced itch and modestly reduced BAM8-22- and cowhage-induced itch. Histamine induced a higher SBP compared to the other conditions. Doxepin reduced SBP induced by each pruritogen, even though SBP of histamine remains the highest. Conclusion. Doxepin cream abolished histaminergic itch by antagonizing the peripheral H1-histamine receptors. Moreover, doxepin reduced nonhistaminergic itch and related neurogenic inflammation. Further studies are needed to elucidate the molecular mechanisms underlying this peripheral modulation of nonhistaminergic itch by a topically applied H1-antagonist. This trial is registered with NCT04588532.

Several studies have shown that magnesium can be a useful tool in preventing various skin disorders. However, the mechanism remains unclear. In this study, we analyzed the mechanism by which magnesium improves skin function, focusing on the water channel aquaporin-3 (AQP3), which is a cutaneous functional molecule. Magnesium compounds (magnesium acetate, magnesium chloride, magnesium sulfate, and magnesium lactate) were added to human epidermal keratinocyte HaCaT cells, and the mRNA and protein expression levels of AQP3 were analyzed. We also investigated the mechanism by which magnesium acetate regulates AQP3 expression. Several magnesium compounds were individually added to HaCaT cells, and 6 hours later, the AQP3 mRNA expression level in the treated cells was significantly increased compared to that in the control cells. Among the magnesium compounds, magnesium acetate had a strong effect and markedly increased the AQP3 mRNA expression level by approximately 3.5 times and the protein expression level by approximately 3 times. Magnesium acetate also enhanced the phosphorylation of cAMP response element-binding protein (CREB), which is involved in AQP3 transcription. Furthermore, the increase in AQP3 expression levels induced by magnesium acetate was suppressed by treatment with the protein kinase A (PKA) inhibitor H-89. Magnesium compounds increased the expression level of AQP3 in epidermal keratinocytes and may have a skin-moisturizing effect. The magnesium-induced phosphorylation of CREB may be associated with the activation of the cAMP/PKA pathway. Overall, magnesium compounds may be useful for the prevention and treatment of age-associated xeroderma.

Background. Tranexamic acid (TA) has emerged as a promising treatment for melasma without serious adverse effects. Ethosomes have been reported as the carriers for transdermal drug delivery systems to increase the amount of drug permeation through the skin. However, few studies of the local usage of TA-loaded ethosomes exist. Objectives. To evaluate the efficacy of a mask containing 0.5% TA-loaded ethosomes in the treatment of melasma in the Asian skin. Methods. In a double-blind, placebo-controlled, randomized, prospective study, 88 Asian participants with melasma were randomized 1 : 1 to two groups as follows: the TA or control. The TA group was treated with moisturizing masks with 0.5% TA-loaded ethosomes, and the control was treated with moisturizing masks only. Masks were applied once daily for the first two weeks and once every other day for the third and fourth weeks. The primary outcome was measured by the modified melasma area and severity index (mMASI) and a visual analog scale (VAS) for vessels. The secondary outcomes were VAS for skin texture and satisfaction. Results. The reduction of VAS vessel scores at the end of treatment in the TA group was significantly greater than that in the control group . The mMASI scores and skin texture scores decreased over time in both groups, but no significant differences were found between the two groups . The score of participant satisfaction in the TA group was significantly higher than that in the control group . Conclusions. Masks containing TA-loaded ethosomes appear to be an effective treatment for Asian melasma in terms of angiogenesis and skin texture. It improves the pigmentation to some extent but has no significance. This trial is registered with ChiCTR1900024257.

Background. Radiofrequency treatment improves skin aging-related concerns by promoting collagen production. However, studies of the efficacy of multifrequency radiofrequency (MFRF) are lacking. Objectives. This study aimed to analyze the efficacy of MFRF for patients with aging skin. Methods. Three MFRF treatment sessions were performed for patients with concerns about skin aging. During these sessions, MFRF was applied to the face (but not the forehead). Pores, wrinkles, subjective satisfaction, and side effects were evaluated at the first visit and 4 weeks after the last treatment. Additionally, histological and immunohistochemical evaluations of collagen, elastic fibers, and STRO-1 were performed. Results. Wrinkles and the subjective satisfaction of patients were significantly improved ( and , respectively). However, there was no significant effect on the number of pores (). All side effects that occurred after treatment were tolerable and transient. Histological findings revealed thickening of collagen bundles and elastic fibers. Additionally, increases in collagen I, collagen III, and STRO-1 levels were observed using immunohistochemistry. Conclusions. MFRF treatment uses less energy than the existing radiofrequency equipment and can be an effective clinicopathologic modality for facial rejuvenation.