AP collagen peptides (APCPs) promote hair growth by activating the GSK-3ß/ß-catenin pathway and improve hair condition.

AP collagen peptides (APCPs) are enzymatically decomposed collagen peptides that contain tri-peptides such as glycine-proline-hydroxyproline. We found that APCPs increased the proliferation of both human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). APCPs also stimulated the secretion of several growth factors, including IGFBP-6, PDGF-AB, PIGF and VEGF in hDPCs. Moreover, APCPs enhanced the phosphorylation of Akt(Ser473), GSK-3ß(Ser9) and ß-catenin(Ser675), indicating the activation of the GSK-3ß/ß-catenin signalling pathway. Ex vivo culture of human hair follicles (hHFs) tissue and in vivo patch assay revealed that APCPs promoted the elongation of hHFs and the induction of new hair shafts. In a mouse model, APCPs significantly promoted the transition from telogen to anagen phase and prolonged anagen phase, resulting in increased hair growth. APCPs also improved the thickness, amino acid content (cystine and methionine) and roughness of mouse hair. Taken together, these findings demonstrate that APCPs accelerate hair growth and contribute to overall hair health. Therefore, APCPs have the potential to be utilized as a food supplement and ingredient for preventing hair loss and maintaining hair health.

One-Year Safety Evaluation of New Hyaluronic Acid Fillers (YYS Series): A Prospective, Multicenter, Observational Study.

BACKGROUND: With the continuous increasing availability of new filler products, each hyaluronic acid filler brand has distinctive pharmacokinetics, which may be associated with different complications. Therefore, the long-term safety of new generations of fillers should be evaluated. OBJECTIVE: This prospective, multicenter, observational, postmarketing study ( ClinicalTrials.gov identifier: NCT04738019) aimed to investigate the incidence of delayed-onset nodules and adverse reactions after the injection of new hyaluronic acid fillers (YYS series) into the facial skin. METHODS: Subjects scheduled to receive an injection YYS series filler were followed up for 52 weeks. The authors aimed to determine the incidence of a self-reported delayed-onset nodule-a visible or palpable nodule or mass at the injection site that was detected beyond the 14th day following the injection-during the 1-year follow-up period. RESULTS: Among the 1,022 subjects who received an injection of the YYS series, the incidences of delayed-onset nodules were 0% for YYS 360, YYS 540, and YYS 720. A 0.21% incidence (1 delayed hypersensitivity reaction) of a delayed-onset adverse reaction was noted for YYS 720, although none were reported for YYS 360 and YYS 540. CONCLUSION: In this study, a notably low frequency of adverse reactions associated with the YYS series was observed.

Efficacy and Safety of PrabotulinumtoxinA in Subjects With Benign Masseteric Hypertrophy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Phase 3 Trial and Open-Label Extension Study.

BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 ( n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.

Ozonated Sunflower Oil (OSO) Alleviates Inflammatory Responses in Oxazolone-Induced Atopic Dermatitis (AD)-Like Mice and LPS-Treated RAW 264.7 Cells.

Ozone, a highly reactive oxidant molecule, is widely used as a complementary therapy for various skin diseases, including wound healing, pressure ulcers, diabetic foot, and infections. However, there is limited research on the effectiveness of ozone for atopic dermatitis (AD). Ozonated sunflower oil (OSO) is an active ingredient obtained from partially ozonated sunflower oil (SO). OSO markedly reduced the LPS-induced increase in IL-1ß and nitric oxide (NO) levels in RAW 264.7 mouse macrophage cells. Oxazolone (OXZ) was applied to hairless mice to induce AD-like skin symptoms and immune response. OSO significantly alleviated the OXZ-induced increases in the number of infiltrating mast cells, epidermal thickness, AD symptoms, thymic stromal lymphopoietin (TSLP), and filaggrin, as well as the serum levels of NO, IgE, IL-1ß, and TNF-α. Furthermore, OSO inhibited the IL-4/STAT3/MAPK pathway and the expression of NF-κB. Our results suggest that OSO treatment could relieve AD-mediated skin damage through its anti-inflammatory and antioxidant activities. Therefore, it can be used as a therapeutic agent against AD-related skin diseases.

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.

Long-pulsed 1,064-nm gallium arsenide laser surgical device treatment for improving symptoms of onychomycosis: a comparative analysis.

BACKGROUND: Onychomycosis is the most common infective nail disease, and treatment includes topical and systemic antifungal medications. Recently, laser therapy has emerged as a therapeutic option for patients who are unable to take oral antifungal agents. We investigated the effectiveness and safety of a novel long-pulsed 1,064-nm gallium arsenide (GaAs) laser surgical device for onychomycosis. METHODS: This 24-week single-center, single-blind, active-controlled exploratory clinical study comparatively evaluated the long-pulsed 1,064-nm GaAs laser (Healer1064) with the short-pulsed Nd:YAG laser surgical device in 20 participants randomly assigned to receive either test or control treatment at 4-week intervals during the 12-week treatment period. The rate of clinical improvement was evaluated by two independent dermatologist evaluators using the Onychomycosis Severity Index-score (OSI-score) and Turbidity Scale with standard photographs. Overall improvement and patient satisfaction were evaluated. Safety evaluation included pain intensity and adverse events. RESULTS: In 44 (test: 25; control: 19) cases in 19 participants who completed treatment, the clinical improvement rate in the test and control groups was 52.00% (13/52 cases) and 44.44% (9/19 cases), respectively, with significantly lower pain scores in the test than the control group for every treatment visit (P < 0.05) and without severe adverse events. CONCLUSIONS: The novel long-pulsed 1,064-nm GaAs laser showed greater, albeit nonsignificant, clinical improvement and was associated with less pain during treatment. Thus, the Healer1064 can provide satisfactory treatment outcomes through painless and effective improvement in onychomycosis symptoms.

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.

The effect of low-intensity cold atmospheric plasma jet on photoaging-induced hyperpigmentation in mouse model.

BACKGROUND: Cold atmospheric plasma (CAP) produces reactive oxygen/nitrogen species (RONS) in the target and can induce cytoprotective effects by activating hormesis-related pathways when its intensity is in the low range. OBJECTIVES: The aim of this study is to evaluate the effect of low-intensified CAP (LICAP) on skin with photoaging-induced hyperpigmentation in an animal model. METHODS: Changes in cell viability and RONS production following LICAP treatment were measured. For the in vivo study, 30 hairless mice underwent antecedent photoaging induction followed by the allocated therapy (i.e., LICAP, topical ascorbic acid (AA), or both). During the first 4 weeks of the treatment period (8 weeks), ultraviolet (UV)-B irradiation was concurrently administered. Visual inspection and measurement of the melanin index (MI) were performed to assess the change in skin pigmentation at Weeks 0, 2, 4, 6, and 8. RESULTS: RONS production increased linearly until the saturation point. Cell viability was not significantly affected by LICAP treatment. At Week 8, MI was significantly decreased in every treatment group compared with the values at Week 0 and Week 4. The treatment effect of the concurrent therapy group was superior to that of the LICAP and AA groups. CONCLUSION: LICAP appears to be a novel modality for photoprotection and pigment reduction in photodamaged skin. LICAP treatment and topical AA application seem to exert a synergistic effect.

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.

Exosomal delivery of TRAIL and miR­335 for the treatment of hepatocellular carcinoma (Review).

Liver cancer is the sixth most prevalent type of cancer worldwide and accounts for the third most frequent cause of cancer­associated mortality. Conventional anticancer drugs display limited efficacy owing to their short half­life, poor solubility and inefficient drug delivery. Despite advancements being made in drug discovery and development for the treatment of hepatocellular carcinoma (HCC), drug inefficacy and drug continue to pose significant obstacles to effective treatment. Therefore, it is imperative that novel treatment strategies be developed with the aim of developing anticancer treatments without any side­effects and with long­term durability. Extracellular vesicles, such as exosomes, intercellular communication agents which have the ability to carry heterogenous molecules with high penetrability, low immunogenicity and longer durability, may provide a versatile natural delivery system. The present review article illustrates the innovative treatment strategy using exosomes as a delivery agent for two distinct anticancer candidates, i.e., tumor necrosis factor­related apoptosis­inducing ligand and microRNA­335. The aim of the present review was to present a unique strategy for the development of an exceptional anticancer treatment therapy exploiting exosomes as a delivery vehicle which may be used for HCC.

Cryolipolysis for abdominal subcutaneous fat reduction: A prospective, multicenter, single arm, clinical study.

Various treatment methods are used for noninvasive body contouring. To evaluate the efficacy and safety of a newly designed cryolipolysis device using a three-dimensional cooling method for abdominal fat reduction. Twenty-five participants with clinically apparent abdominal fat tissue participated in the study. The thickness of fat tissue below the umbilicus level was measured using a caliper at baseline and 12 weeks after the first treatment. The height of abdominal subcutaneous fat tissue on ultrasonography and participant satisfaction were assessed at every visit for 16 weeks. All adverse events (AEs) during the study period were recorded. p values <0.05 were considered statistically significant. Twenty-four participants completed this study; the mean BMI of participants was 29.34 ± 2.36 kg/m2 . The mean thickness of abdominal subcutaneous fat was significantly lower at 12 weeks (40.4 ± 6.8 mm, p < 0.001) than at baseline (49.3 ± 8.5 mm). Differences in the height of abdominal subcutaneous fat compared to that at baseline were 1.02 ± 0.41 cm (12 weeks, p < 0.001) and 1.13 ± 0.44 cm (16 weeks, p < 0.001). Rates of abdominal subcutaneous fat reduction at 12 and 16 weeks compared to that at baseline were 28.45% and 31.13%, respectively. The ratio of abdominal circumference to hip circumference at 12 and 16 weeks was significantly decreased compared to that at baseline. Most participants (95.8%) reported improvement in satisfaction scores at 16 weeks. There were no serious AEs during the entire study period. The study demonstrated the efficacy of a noninvasive cryolipolysis device using a three-dimensional cooling method for reducing abdominal subcutaneous fat.

Transforming growth factor­ß family and stem cell­derived exosome therapeutic treatment in osteoarthritis (Review).

Osteoarthritis (OA), although extensively researched, still lacks an effective and safe treatment. The only current treatment option available for advanced OA is joint replacement surgery. This surgery may pose the risks of persistent pain, surgical complications and limited implant lifespan. Transforming growth factor (TGF)­ß has a crucial role in multiple cellular processes such as cell proliferation. Any deterioration in TGF­ß signaling pathways can have an immense impact on OA. Owing to the crucial role of TGF­ß in cartilage homeostasis, targeting it could be an alternative therapeutic approach. Additionally, stem cell­based therapy has recently emerged as an effective treatment strategy that could replace surgery. A number of recent findings suggest that the tissue regeneration effect of stem cells is attributed to the paracrine secretion of anti­inflammatory and chondroprotective mediators or trophic factors, particularly nanosized extracellular vesicles (i.e., exosomes). Literature searches were performed in the MEDLINE, EMBASE, Cochrane Library and PubMed electronic database for relevant articles published before September 2021. Multiple investigators have confirmed TGF­ß3 as a promising candidate which has the chondrogenic potential to repair articular cartilage degeneration. Combining TGF­ß3 with bone morphogenetic proteins­6, which has synergistic effect on chondrogenesis, with an efficient platform such as exosomes, which themselves possess a chondroprotective function, offers an innovative and more efficient approach to treat injured cartilage. In addition, multiple findings stating the role of exosomes in chondroprotection has also verified a similar fact showing exosomes may be a more favorable choice than the source itself. In the present review, the importance of TGF­ß family in OA and the possibility of therapeutic treatment using stem cell­derived exosomes are described.

Phase I/III Clinical Trial to Evaluate the Safety and Efficacy of a New Botulinum Toxin (HU-014) Versus OnabotulinumtoxinA in Subjects With Moderate-to-Severe Crow's Feet Lines.

BACKGROUND: HU-014, a newly introduced botulinum toxin type A, has not been investigated for its efficacy and safety in crow's feet line (CFL) treatment. OBJECTIVE: Here, we compared the efficacy and safety of HU-014 and onabotulinumtoxinA in CFL treatment. METHODS: This was a randomized, double-blind, active drug-controlled, multicenter, 16-week, Phase I/III study designed to determine the noninferiority of HU-014 compared with onabotulinumtoxinA in moderate-to-severe CFL treatment. In the Phase III study, 290 subjects were randomized at a 1:1 ratio to receive a single treatment of HU-014 or onabotulinumtoxinA. The primary endpoint was the proportion of subjects achieving Grade 0 or 1 in the facial wrinkle scale on maximum smile at Week 4. RESULTS: The primary endpoint was achieved by 72% of the subjects with HU-014 and onabotulinumtoxinA treatments, supporting the noninferiority of HU-014 compared with onabotulinumtoxinA. All secondary efficacy outcomes were achieved by the subjects. The 2 groups showed no significant differences in the safety analysis. CONCLUSION: HU-014 has noninferior efficacy and safety compared with onabotulinumtoxinA in the treatment of CFL.

Efficacy and Safety of a New Botulinum Toxin (HU-014) Versus Existing Onabotulinumtoxin A in Subjects With Moderate to Severe Glabellar Lines.

BACKGROUND: Recently, the safety of a new botulinum toxin (HU-014) was confirmed through animal experiments. The evaluation of the efficacy and safety of this newly introduced botulinum toxin is required considering the risk of adverse events (AEs) and need for standardization before its universal use. OBJECTIVE: The aim of this multicenter, double-blind, randomized, parallel, active-controlled phase III clinical trial was to investigate the noninferiority of HU-014 versus existing onabotulinumtoxin A for the treatment of moderate to severe glabellar lines. METHODS: In total, 267 subjects were randomized to either the test (HU-014) or control (onabotulinumtoxin A) group. At the baseline and at weeks 4, 8, 12, and 16, investigator's live assessment, independent photographic assessment, subjects' improvement assessment, subjects' satisfaction assessment, and safety assessment were performed. RESULTS: At week 4, the response rate was 90.15% and 92.31% in the test and control groups, respectively, as per investigator's live assessment while frowning, without a significant difference. Both groups also showed no significant differences in response rates in the other assessments. In addition, no serious AEs were reported. CONCLUSION: HU-014 was noninferior to existing onabotulinumtoxin A in the treatment of glabellar lines at a 1:1 dose ratio, and both products were well tolerated.

The Effects of Fabric Containing Chamaecyparis obtusa Essential Oil on Atopic Dermatitis-Like Lesions: A Functional Clothing Possibility.

BACKGROUND: Essential oil derived from Chamaecyparis obtusa (EOCO) has been used as an alternative treatment for allergy-related diseases due to its immune-modulating characteristics. Clothing has the longest and most intense contact with human skin, and functional fabrics with intrinsic properties have been increasingly implemented in medical applications. Specially designed fabrics may support atopic dermatitis (AD) treatment. In this study, the effects of fabric containing EOCO on AD were investigated using an NC/Nga mouse model. METHODS: The fabric was applied for 6 h per day for 14 days. The therapeutic effects were evaluated according to measurements of skin lesion severity (modified SCORAD score), transepidermal water loss (TEWL), serum IgE and inflammatory cytokine levels, lesion thickness measured after hematoxylin and eosin staining, and immunohistochemical and Western blot analysis for skin epidermal differentiation protein. RESULTS: The EOCO group exhibited significantly reduced modified SCORAD score, TEWL, and serum IgE levels. Among the inflammatory cytokines analyzed, only the mean values of regulated on activation, normal T cell expressed and secreted were observed to be decreased compared with other control groups. The histological analysis of the skin also revealed that the EOCO group expressed reduced epidermal hyperplasia and recovered filaggrin, involucrin, and loricrin expression. CONCLUSIONS: It was confirmed that fabric containing EOCO has anti-atopic and anti-inflammatory properties. The study data show that fabric containing EOCO can be implemented as an alternative functional clothing for people suffering from AD.

Sequential delivery of long-pulsed 755-nm alexandrite laser and long-pulsed 1,064-nm neodymium:yttrium-aluminum-garnet laser treatment for pigmented disorders.

BACKGROUND: Long-pulsed (LP) lasers at pulse durations of 1-300 ms have been used to destroy nests of nevi cells by selectively targeting pigment chromophores. OBJECTIVE: To evaluate dual-wavelength LP laser-induced tissue reactions. METHODS: The patterns of LP 755-nm alexandrite (Alex) and/or 1064-nm neodymium (Nd):yttrium-aluminum-garnet (YAG) laser-induced tissue reactions were macroscopically evaluated using a tattoo-embedded phantom. Additionally, a pilot in vivo human study was performed for common acquired melanocytic nevus, of which dermoscopic images and high-speed cinematographs were obtained. RESULTS: Combinations of Nd:YAG and Alex laser treatments at interpulse intervals of 10 or 20 ms generated round to oval zones of photothermal and photoacoustic injury in two distinctive areas containing disintegrated tattoo particles. Treatment at interpulse intervals of 10 or 20 ms between Alex and Nd:YAG pulses elicited lesser degrees of thermal damage to surrounding tissues, compared to treatment at 100 or 200 ms. Immediately after combined LP laser treatment of human nevus lesions in vivo, Nd:YAG-Alex treatment at a 20-ms interpulse interval exhibited more remarkable crusting and erosive appearances than Alex-Nd:YAG treatment. CONCLUSION: For treating pigmented disorders, sequential delivery of LP Nd:YAG and Alex pulses at short interpulse intervals of 10-20 ms can effectively destroy nests of pigment chromophores.