Efficacy of combined treatment with human adipose tissue stem cell-derived exosome-containing solution and microneedling for facial skin aging: A 12-week prospective, randomized, split-face study.

BACKGROUND: Studies have reported promising results of mesenchymal stem cell therapies for skin aging. However, in the use of mesenchymal stem cells, some drawbacks including rarely possible tumorigenicity and low engraftment rates have limited their widespread clinical use. Adipose tissue stem cell-derived exosomes (ASCEs) are emerging as effective cell-free therapeutic agents. AIMS: It was evaluated the clinical efficacy of combining the application of human ASCE-containing solution (HACS) with microneedling to treat facial skin aging. METHODS: A 12-week, prospective, randomized, split-face, comparative study was conducted. Twenty-eight individuals underwent three treatment sessions separated by 3-week intervals and were followed up for 6 weeks after the last session. At each treatment session, HACS and microneedling were administered to one side of the face, and normal saline solution and microneedling were administered to the other side as a control. RESULTS: The Global Aesthetic Improvement Scale score was significantly higher on the HACS-treated side than on the control side at the final follow-up visit (p = 0.005). Objective measurements obtained by different devices including PRIMOS Premium, Cutometer MPA 580, Corneometer CM 825, and Mark-Vu confirmed greater clinical improvements in skin wrinkles, elasticity, hydration, and pigmentation on the HACS-treated side than on the control side. The results of the histopathological evaluation were consistent with the clinical findings. No serious adverse events were observed. CONCLUSIONS: These findings demonstrate that combined treatment using HACS and microneedling is effective and safe for treating facial skin aging.

Exosomes derived from human adipose tissue-derived mesenchymal stem cells for the treatment of dupilumab-related facial redness in patients with atopic dermatitis: A report of two cases.

BACKGROUND: Atopic dermatitis is a chronic, pruritic, and inflammatory dermatosis that affects approximately 20% of children and 10% of adults worldwide. Dupilumab facial redness is gaining attention as additional cases are coming to light in the medical literature. OBJECTIVES AND METHODS: Exosomes are nano-sized vesicles that are constantly released by almost all cells. They can travel between cells and transport their cargo (lipids, proteins, and nucleic acids), making them a possible cell-free therapeutic option for various diseases. Herein, we investigated whether topical application of human adipose tissue-derived mesenchymal stem cell-derived exosomes could reduce dupilumab facial redness in patients with severe atopic dermatitis. RESULTS: Two patients with atopic dermatitis and refractory dupilumab facial redness were successfully treated with electroporation-assisted topical application of human adipose tissue-derived mesenchymal stem cell-derived exosomes. Six repeated sessions of treatment, with an interval of 1 week between each session, led to marked improvement in erythematous facial lesions. CONCLUSIONS: We suggest that human adipose tissue-derived mesenchymal stem cell-derived exosomes may serve as an effective agent in the management of dupilumab facial redness. However, further controlled studies with a larger number of patients are necessary to confirm the efficacy and safety of this agent, as well as the optimal treatment protocol.

Tightening and Reduction of Unwanted Submental Fat Using Triple-Layer High-Intensity Focused Ultrasound: Clinical and 3-Dimensional Imaging Analysis.

BACKGROUND: Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence of their use. OBJECTIVE: The authors sought to evaluate the safety and efficacy of a novel triple-layer high-intensity focused ultrasound (HIFU) regimen for SMF reduction. METHODS: Forty Korean subjects with moderate/severe SMF were evaluated after receiving a session of triple-layer HIFU treatments (using 3.0-, 4.5-, and 6.0-mm focusing transducers). The objective evaluation based on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and patients' satisfaction based on the 7-point Subject Self-Rating Scale (SSRS) were determined 8 weeks after treatment. Three-dimensional image analysis was also performed. RESULTS: At the follow-up visit, the proportion of treatment responders defined as subjects with ≥1-point improvement in CR-SMFRS was 62.5%, and the proportion of patients satisfied with appearance of their face and chin (score ≥4 on the SSRS) was 67.5% of the total patients. The results of 3-dimensional analysis were consistent with clinical observations. Only mild and transient side effects were observed for some patients with no serious adverse effects. CONCLUSION: The triple-layer HIFU regimen including the novel 6.0-mm transducer has benefits for tightening and rejuvenation of the area with unwanted SMF, showing reasonable safety profiles.

Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration.

Exosomes are nano-sized vesicles that serve as mediators for cell-to-cell communication. With their unique nucleic acids, proteins, and lipids cargo compositions that reflect the characteristics of producer cells, exosomes can be utilized as cell-free therapeutics. Among exosomes derived from various cellular origins, mesenchymal stem cell-derived exosomes (MSC-exosomes) have gained great attention due to their immunomodulatory and regenerative functions. Indeed, many studies have shown anti-inflammatory, anti-aging and wound healing effects of MSC-exosomes in various in vitro and in vivo models. In addition, recent advances in the field of exosome biology have enabled development of specific guidelines and quality control methods, which will ultimately lead to clinical application of exosomes. This review highlights recent studies that investigate therapeutic potential of MSC-exosomes and relevant mode of actions for skin diseases, as well as quality control measures required for development of exosome-derived therapeutics.

Toxicological evaluation of exosomes derived from human adipose tissue-derived mesenchymal stem/stromal cells.

Several studies report that the therapeutic mechanism of action of mesenchymal stem/stromal cells (MSCs) is mainly mediated by paracrine factors that are released from MSCs such as exosomes. Exosomes are nano-sized extracellular vesicles that are transferred to target cells for cell-to-cell communication. Although MSC-derived exosomes (MSC-exosomes) are suggested as novel cell-free therapeutics for various human diseases, evaluation studies for the safety and toxicity of MSC-exosomes are limited. The purpose of our study was to evaluate the toxicological profile, including skin sensitization, photosensitization, eye and skin irritation, and acute oral toxicity using exosomes derived from human adipose tissue-derived MSCs (ASC-exosomes) in accordance with the OECD guidelines and the principles of Good Laboratory Practice. The ASC-exosomes were classified as a potential non-sensitizer in the skin sensitization test, UN GHS no category in the eye irritation test, and as a skin non-irritant in the skin irritation test, and did not induce any toxicity in the phototoxicity test or in acute oral toxicity testing. Our findings are the first to suggest that ASC-exosomes are safe for use as a topical treatment, with no adverse effects in toxicological testing, and have potential application as a therapeutic agent, cosmetic ingredient, or for other biological uses.

Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis.

Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes' effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD.

Combined treatment of recalcitrant papulopustular rosacea involving pulsed dye laser and fractional microneedling radiofrequency with low-dose isotretinoin.

BACKGROUND: While a considerable number of cases with papulopustular rosacea (PPR) are resistant to conventional medications, therapeutic regimens are not currently established. Pulsed dye laser (PDL) and fractional microneedling radiofrequency (FMR) have previously demonstrated satisfactory results for anti-angiogenesis, anti-inflammation, and dermal remodeling. AIMS: To evaluate the efficacy and safety of novel combination regimen with low-dose oral isotretinoin, PDL, and FMR in the treatment of recalcitrant PPR. PATIENTS AND METHODS: A retrospective study was undertaken for recalcitrant PPR patients to evaluate the clinical course of novel combination regimen. Twenty-five PPR patients who had failed in previous first-line therapies were enrolled. They were treated with three sessions of PDL and FMR consecutively at 4-week intervals, maintaining daily oral administration of 10 mg isotretinoin for 8 weeks. Objective assessments, erythema index measurement, and patients' subjective satisfaction were evaluated at each visit and 16 weeks after the final treatment. RESULTS: At the final follow-up visit, the number of papules and pustules decreased by 71%, and erythema index by 54% compared with baseline (P < 0.05 for both). Physician's global assessment based on rosacea severity score and patients' subjective assessments paralleled with these results. No serious side effect was observed during whole study periods. CONCLUSION: This novel combination regimen demonstrated satisfactory efficacy with reasonable safety profiles for the treatment of recalcitrant PPR.

A Novel Combined Light-Based Treatment of Acne Vulgaris With 1,450-nm Diode Laser and 450-nm Blue Light.

BACKGROUND: Nonablative 1,450-nm diode laser (DL) and visible blue light (BL) have been effectively used for acne with superior safety profiles. OBJECTIVE: To evaluate synergistic effects of sequential DL and BL application for acne. METHODS: A 20-week, randomized split-face study was conducted to compare clinical courses between 2 facial sides either receiving sequential application of DL and BL or BL alone in 24 patients with mild to moderate facial acne vulgaris. Patients were scheduled to receive 3 consecutive sessions at 4-week intervals. Objective assessments, including revised Leeds grades, lesion counts, and sebum output measurements, and patients' subjective satisfaction were investigated. RESULTS: Both combination and BL sides demonstrated steady improvement of inflammatory acne lesions with 62.3% and 35.2% decreases at the 12-week follow-up visit compared with baseline respectively. For noninflammatory lesions and seborrhea, only combination regimen demonstrated improvement. Patients' subjective assessments paralleled objective findings. For safety profiles, no severe adverse effect was observed on both sides, and mild symptoms resolved spontaneously within a day. CONCLUSION: The combination regimen demonstrated synergistic efficacies for acne and seborrhea, with satisfactory safety profiles. Therefore, a few sessions of these light-based applications would be a viable option for acne treatments.

Clinical Evaluations of a Novel Thread Lifting Regimen Using Barbed Polyglyconate Suture for Facial Rejuvenation: Analysis Using a 3-Dimensional Imaging System.

BACKGROUND: Thread lifting with absorbable sutures has recently gained prominence for rejuvenating ptotic and sagging soft tissues in aging face. A barbed, delayed absorbable polyglyconate monofilament shows significantly high tensile loads with superior flexibility and elasticity. OBJECTIVE: To evaluate the safety and efficacy of novel thread lifting regimen with barbed polyglyconate suture for counteracting the descent and laxity of the aging face. METHODS: A retrospective chart review was conducted for 25 Korean patients with mild to moderate facial skin laxity receiving thread lifting procedures using barbed polyglyconate suture. Dermatologists' objective assessments using a 5-point Global Aesthetic Improvement Scale (GAIS), 3D imaging system, and subjective satisfaction were recorded at baseline and 4 months after treatments. RESULTS: In most patients (84%), GAIS scores were more than score 3 ("improved"), with 40% of score 4 ("much improved") and 24% of score 5 ("excellent") at the follow-up point. Subjective assessments paralleled these patterns. Three-dimensional analysis quantitatively showed volume migration of low face upward, clinically interpreted as facial lifting. No serious adverse effect was observed. CONCLUSION: This novel thread lifting procedure using barbed polyglyconate suture is a safe and effective method for tightening and lifting for aging face with mild to moderate face sagging.

Comparison of novel dual mode vs conventional single pass of a 1450-nm diode laser in the treatment of acne vulgaris for Korean patients: A 20-week prospective, randomized, split-face study.

BACKGROUND: Although a 1450-nm diode laser has been shown to be effective for acne, the conventional high-energy stamp-only regimen is often associated with pain and hyperpigmentation, especially for dark-skinned individuals. AIMS: To evaluate whether the novel dual regimen has clinical advantages for acne treatments compared with conventional regimen in Asian patients. PATIENTS AND METHODS: Twenty-four Korean patients with facial acne were treated with a 1450-nm diode laser through a 20-week, randomized, split-face study. The patients were treated with three consecutive sessions at 4-week intervals. One half of the face received a dual regimen consisting of low-fluence stamping mode (5-6 J/cm2 ) for inflammatory acne lesions only, followed by 4-5 passes of moving mode for the full face. The other side received a single-pass treatment of conventional high-fluence stamp mode (14-15 J/cm2 ). Evaluations for acne, sebum secretion measurements, and safety profiles were performed. RESULTS: At the final 12-week follow-up evaluations, the dual-mode side demonstrated better improvements in both inflammatory and noninflammatory lesion counts, acne severity assessments, and reduction in sebum secretion compared with stamp-only side. Subjective satisfaction for the improvement for acne, seborrhea, and texture correlated well with objective assessments. In addition, degrees of pain and treatment-related side effects were remarkably decreased in the novel dual mode. CONCLUSION: This novel dual regimen of the 1450-nm laser demonstrated improved efficacies for acne and seborrhea with satisfactory safety profiles. Therefore, this regimen would be a viable option for acne treatments either as monotherapy or as combination therapy.

Expression of inflammatory and fibrogenetic markers in acne hypertrophic scar formation: focusing on role of TGF-ß and IGF-1R.

Acne vulgaris is a universal skin disease and it may leave a scar when the original skin lesion disappears. These scars can cause cosmetic problems and psychological burden, leading to poor quality of life of patients. Acne scars are classified into atrophic scars and hypertrophic scars. As most of the acne scars are atrophic, many studies have been conducted focusing on the treatment of atrophic lesions. This study was conducted to investigate the underlying pathogenesis of acne hypertrophic scars by identifying roles of fibrogenetic and inflammatory markers. Skin biopsy samples were obtained from hypertrophic scars of face and back and from adjacent normal tissues as control group. Some samples from back were immature hypertrophic scars and the other samples were in mature stages. Immunohistochemistry staining and quantitative PCR were performed for fibrogenetic and inflammatory markers. Both in mature and immature hypertrophic scars, vimentin and α-SMA were increased. Production of TGF-ß3 protein as well as transcription of TGF-ß3 was also significantly elevated. In contrast, expression of TGF-ß1 showed no increase. Instead, expression levels of SMAD2 and SMAD4 were increased. Elevations of CD45RO, TNF-α and IL-4 and reduction of IL-10 were observed. In immature hypertrophic scars, IGF-1R and insulin-degrading enzyme expression were increased. Increased apoptosis was observed in immature stages of hypertrophic scars but not in mature stages. Elevations of TGF-ß3, SMAD2 and SMAD4 in hypertrophic scars and increase of IGF-1R in immature stages may give some clues for acne hypertrophic scar formation.

Epidemiological and clinical features of rosacea in Korea: A multicenter cross-sectional study.

Rosacea is a common chronic inflammatory skin condition. Although several epidemiological and etiologic studies with large sample sizes have been conducted on Caucasians, such data regarding Asian populations are lacking. A total of 580 patients diagnosed with rosacea were enrolled from October 2014 to February 2015 at 14 general hospitals. Questionnaires, including the standard classification and grading system, were used for evaluation. The average age of the patients was 47.9 years. While 83.8% of patients revealed a single subtype, 16.2% of patients revealed mixed subtypes showing two or more subtypes simultaneously. Erythematotelangiectatic rosacea (ETR) was the most prevalent subtype. ETR combined with papulopustular rosacea showed the highest proportion in the mixed subtype group. Mild severity was revealed in 71.9% of patients. The most common aggravating factor was emotional changes (51.7%), followed by stress (48.4%). Approximately half of the patients (47.4%) showed relatively low awareness of rosacea. By identifying the epidemiological and etiologic features in Korea, we can suggest valuable clinical avenues for research, education and awareness among rosacea patients.

Clinical and Histological Evaluations of Enlarged Facial Skin Pores After Low Energy Level Treatments With Fractional Carbon Dioxide Laser in Korean Patients.

BACKGROUND: Enlarged facial pores can be an early manifestation of skin aging and they are a common aesthetic concern for Asians. However, studies of improving the appearance of enlarged pores have been limited. OBJECTIVE: The authors aimed to study the application of CO2 fractional laser treatment in patients with enlarged facial pores. METHODS: A total of 32 patients with dilated facial pores completed 3 consecutive sessions of low energy level treatments with a fractional CO2 laser at 4-week intervals. Image analysis was performed to calculate the number of enlarged pores before each treatment session and 12 weeks after the final treatment. RESULTS: After application of laser treatments, there was a significant decrease in the number of enlarged pores. The mean number of enlarged pores was decreased by 28.8% after the second session and by 54.5% at post-treatment evaluation. Post-treatment side effects were mild and transitory. Histological and immunohistochemical analyses demonstrated clear increases in the number of collagen fibers and the expression of transforming growth factor-ß1. CONCLUSION: The short-term results showed that treatment with low energy level CO2 fractional laser therapy could be a safe and effective option for patients with Fitzpatrick skin Types III and IV who are concerned with enlarged pores.

Histologic analyses on the response of the skin to 1,927-nm fractional thulium fiber laser treatment.

BACKGROUND: The histologic responses to varied parameters of 1,927-nm fractional thulium fiber laser treatment have not yet been sufficiently elucidated. OBJECTIVE: This study sought to evaluate histologic changes immediately after 1,927-nm fractional thulium fiber laser session at various parameters. METHODS: The dorsal skin of Yucatan mini-pig was treated with 1,927-nm fractional thulium fiber laser at varied parameters, with or without skin drying. The immediate histologic changes were evaluated to determine the effects of varying laser parameters on the width and the depth of treated zones. RESULTS: The increase in the level of pulse energy widened the area of epidermal changes in the low power level, but increased the dermal penetration depth in the high power level. As the pulse energy level increased, the increase in the power level under the given pulse energy level more evidently made dermal penetration deeper and the treatment area smaller. Skin drying did not show significant effects on epidermal changes, but evidently increased the depth of dermal denaturation under both high and low levels of pulse energy. CONCLUSION: These results may provide important information to establish treatment parameters of the 1,927-nm fractional thulium fiber laser for various skin conditions.

Combination of platelet rich plasma in fractional carbon dioxide laser treatment increased clinical efficacy of for acne scar by enhancement of collagen production and modulation of laser-induced inflammation.

BACKGROUND: Platelet-rich plasma (PRP) which contains large amounts of growth factors has been tried to enhance therapeutic efficacy of laser treatment for acne scar with unknown underlying mechanism. OBJECTIVES: The present study was conducted to investigate the molecular mechanism of increased clinical efficacy of PRP when combined with fractional laser treatment for treating acne scars. METHODS: Subjects with mild to moderate acne scars were treated with two sessions of fractional CO2 laser therapy given with and without co-administration of PRP. Skin biopsy specimens were obtained at baseline, 1, 3, 7, and 28 days for investigation of molecular profiles associated with skin changes produced by laser plus PRP treatment. RESULTS: The PRP treatment increased clinical efficacy with decreased severity of adverse effects such as erythema, swelling and oozing. Productions of TGFß1 and TGFß3 proteins were more highly elevated on the PRP-treated side of the face compared to the control side at day 28. Furthermore, PRP-treated side showed significant increase of c-myc, TIMP, and HGF expression. Experimental fibroblast culture model was also used. PRP administration after laser irradiation increased expressions of p-Akt, TGFß1, TGFß3, ß-catenin, collagen 1, and collagen 3 in both dose-dependent and time dependent manners in fibroblast. Moreover, we acquired clinical and histological data through randomized control clinical trial. CONCLUSION: Taken together with human study results combined with the data from cell experiments we suggest that PRP treatment increased fibrogenetic molecules induced by fractional CO2 laser, which have association with clinical effect. Lasers Surg. Med. 50:302-310, 2018. © 2017 Wiley Periodicals, Inc.

Comparison between Er:YAG laser and bipolar radiofrequency combined with infrared diode laser for the treatment of acne scars: Differential expression of fibrogenetic biomolecules may be associated with differences in efficacy between ablative and non-ablative laser treatment.

BACKGROUND AND OBJECTIVE: Fractional Er:YAG minimizes the risk associated with skin ablation. Infrared diode laser and radiofrequency have suggested comparable improvements in acne scar. We compared the clinical efficacy of Er:YAG laser and bipolar radiofrequency combined with diode laser (BRDL) for the treatment of acne scars. Moreover, acute molecular changes of cytokine profile associated with wound healing have been evaluated to suggest mechanisms of improvement of acne scar. STUDY DESIGN: Twenty-four subjects with mild-to-moderate acne scars were treated in a split-face manner with Er:YAG and BRDL, with two treatment sessions, 4 weeks apart. Objective and subjective assessments were done at baseline, 1, 3, 7 days after each treatment and 4 weeks after last treatment. Skin biopsy specimens were obtained at baseline, 1, 3, 7, 28 days after one session of treatment for investigation of molecular profile of acute skin changes by laser treatment. RESULTS: Investigator's Global Assessment representing the improvement degree shows 2.1 (50%) in fractional Er:YAG and 1.2 (25%) in BRDL. Er:YAG induced the later and higher peak expression of TGFßs and collagenases, whereas BRDL induced earlier and lower expression of TGFß and collagenases, relatively. PPARγ dropped rapidly after a peak in Er:YAG-treated side, which is associated with tissue inhibitor of metalloproteinase (TIMP) expression. We observed higher expression of TIMP after Er:YAG treatment compared with BRDL by immunohistochemistry, which may be associated with the expression of upregulation of collagen fibers. CONCLUSION: The superior efficacy of Er:YAG to BRDL in the treatment of acne scars may be associated with higher expression of collagen which is associated with differential expression of TGFßs, collagenases, PPARγ, and TIMP. Lasers Surg. Med. 49:341-347, 2017. © 2016 Wiley Periodicals, Inc.

Clinical and Histologic Effects of Fractional Microneedling Radiofrequency Treatment on Rosacea.

BACKGROUND: Fractional microneedling radiofrequency (FMR) is an emerging treatment modality, but its effect on rosacea has not been studied yet. OBJECTIVE: To investigate the potential impact of FMR treatment on clinical improvement and histologic changes in rosacea patients. MATERIALS AND METHODS: A 12-week, prospective, randomized, split-face clinical trial was conducted. Two sessions of FMR were performed on one side of the cheeks with 4-week interval and the other side remained untreated. Erythema index from DermaSpectrometer and a* value from Spectrophotometer CM-2002 were measured at each visit for the objective measurement of erythema. Histologic analysis of skin samples was also carried out. RESULTS: Clinical evaluation and photometric measurement revealed the reduction of redness in the treated side compared with untreated side and baseline. Erythema index decreased 13.6% and a* value decreased 6.8% at Week 12 compared with baseline. Reduced expression of markers related to inflammation, innate immunity, and angiogenesis was observed in immunohistochemical staining of tissue obtained after FMR treatment. CONCLUSION: Fractional microneedling radiofrequency treatment showed modest clinical and histologic improvement of rosacea, and it might be used as an alternative or in combination with other treatment methods.

Fractional Microneedling Radiofrequency Treatment for Acne-related Post-inflammatory Erythema.

Post-inflammatory erythema is a common result of acne inflammation and is cosmetically unacceptable without effective treatment. Fractional microneedling radiofrequency (FMR) has potential for treatment of post-inflammatory erythema. The aim of this study was to evaluate the efficacy and safety of this treatment. A retrospective chart review was undertaken of 25 patients treated with 2 sessions of radiofrequency at 4-week intervals and 27 patients treated with oral antibiotics and/or topical agents. Efficacy was assessed through an investigator's global assessment of photographs, and the analysis of erythema with image analysis software and photometric devices. Histological changes resulting from the treatment were evaluated by skin biopsy. FMR treatment resulted in significant improvements in erythema with no severe adverse effects. Histological study revealed a reduction in vascular markers and inflammation. FMR is a safe and effective treatment for post-inflammatory erythema, with potential anti-inflammatory and anti-angiogenetic properties.

Comparison of clinical and histological effects between lactobacillus-fermented Chamaecyparis obtusa and tea tree oil for the treatment of acne: an eight-week double-blind randomized controlled split-face study.

BACKGROUND: Screening of natural compounds for the development of anti-acne therapeutic agents has been steadily required considering various side effects of acne medications. However, previous studies have mainly focused on experimental tests without clinical trials and histopathological analysis. OBJECTIVES: To compare the clinical efficacy, safety and histopathological changes between Lactobacillus-fermented Chamaecyparis obtusa (LFCO) and existing tea tree oil (TTO). METHODS: A total of 34 patients were instructed to apply 5% LFCO to the involved areas of a randomly allocated side and 5% TTO extract to the other side for 8 weeks in a double-blind split-face clinical trial. RESULTS: After 8 weeks, inflammatory acne lesions were reduced by 65.3% on the LFCO side and by 38.2% on the TTO side. LFCO was also superior to TTO in the onset time of efficacy (p < 0.05). The LFCO side further demonstrated improvement for non-inflammatory lesions (52.6%, p < 0.05), decreased size of sebaceous glands and sebum output reductions. Patients' subjective satisfaction was also higher without severe adverse reactions. Protein expressions of nuclear factor κB decreased earlier on the LFCO side, and those of interleukin-1α (IL-1α), IL-8, insulin-like growth factor 1 receptor and sterol regulatory element-binding protein 1 decreased subsequently. Ultra-performance liquid chromatography/high-resolution mass spectrometry further demonstrated that the contents of dihydroxybenzoic acid, taxifolin and quercetin were increased in LFCO after fermentation. CONCLUSIONS: LFCO treatment was rapid and effective for treating acne lesions compared to TTO. Histopathological findings correlated well with the clinical acne grade and treatment response. This novel natural compound appears to be effective and safe for acne treatment.

Clinical effect of bovine amniotic membrane and hydrocolloid on wound by laser treatment: prospective comparative randomized clinical trial.

Bovine amniotic membrane (BAM) has been regarded as an ideal dressing material because it accelerates epithelization and has anti-inflammatory, anti-angiogenic, and strong analgesic effects. To evaluate the clinical effects of BAM and compare them to that of hydrocolloid dressings on wounds created by ablative laser treatments, 49 subjects with nevi or scars requiring ablative laser treatment were evaluated. To compare efficacy, we divided the body into six areas and included patients with two or more similar skin lesions in the same body area. After ablative laser treatments, BAM and hydrocolloid dressing were applied to the wounds with random allocation. Clinical assessments were performed at baseline, 1, 4, 6, 8, 11, and 13 days after treatment. Histologic changes were assessed by skin biopsy. BAM treatment induced faster epithelization than hydrocolloid treatment (6.7 vs. 9.2 days). Erythema and oozing faded more quickly, and the satisfaction score was higher in BAM-treated sites than it was in hydrocolloid-treated sites, without severe adverse effects. Histologic analysis confirmed epithelization and immunohistochemistry revealed different growth factor profiles between the two treatment modalities. BAM benefits wound healing following ablative laser treatment.