The underestimated role of mitochondria in vitiligo: From oxidative stress to inflammation and cell death.

Vitiligo is an acquired depigmentary disorder characterized by the depletion of melanocytes in the skin. Mitochondria shoulder multiple functions in cells, such as production of ATP, maintenance of redox balance, initiation of inflammation and regulation of cell death. Increasing evidence has implicated the involvement of mitochondria in the pathogenesis of vitiligo. Mitochondria alteration will cause the abnormalities of mitochondria functions mentioned above, ultimately leading to melanocyte loss through various cell death modes. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in mitochondrial homeostasis, and the downregulation of Nrf2 in vitiligo may correlate with mitochondria damage, making both mitochondria and Nrf2 promising targets in treatment of vitiligo. In this review, we aim to discuss the alterations of mitochondria and its role in the pathogenesis of vitiligo.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Expert consensus on perioperative integrated skincare for noninvasive energy-based device aesthetic procedures in clinical practice in China.

BACKGROUND: Noninvasive energy-based device (NI-EBD) aesthetic procedures has recently gained widespread usage for treating various skin conditions, enhancing skin texture and performing rejuvenation-related procedures. However, practically all NI-EBD procedures result in variable degrees of damage to the skin barrier, inducing pathological and physiological processes such as oxidative stress and inflammation, and only a small percentage of individuals possess the innate ability to restore it. OBJECTIVE: To introduce the concept of integrated skincare and establish standardized operational procedures for perioperative integrated skincare, and furnish a theoretical basis for clinical diagnosis and treatment performed by professional medical aestheticians. METHODS: The author leveraged domestic and international guidelines, clinical practice expertise and evidence-based research, adapting them to suit the specific circumstances in China. RESULTS: The consensus were provided four parts, including concept and essence of integrated skincare, integrated skincare significance during the perioperative phase of NI-EBD procedures, active ingredients and functions of effective skincare products, standardized perioperative skincare procedure for NI-EBD procedures and precautions. For the standardized perioperative skincare procedure, four recommendations were listed according to different stages during NI-EBD procedures. CONCLUSION: These recommendations create the 'Expert Consensus on Perioperative Integrated Skincare for Noninvasive Energy-Based Device Aesthetic Procedures in Clinical Practice in China'.

Application of integrated skincare in medical aesthetics: A literature review.

Integrated skincare combines clinically proven skincare products with professional medical aesthetics to provide a comprehensive solution for beauty pursuers. Studies have demonstrated that a combination of medical aesthetic procedures and maintenance therapies is more effective than either treatment alone. This review outlines the current applications of integrated skincare, including different regimens of energy-based aesthetic devices and active ingredients in cosmeceuticals or chemical peels. Additionally, the benefits and limitations of integrated skincare are discussed. Lastly, this review highlights the potential for improved satisfaction and long-term maintenance of the desired outcomes through appropriate integrated skincare procedures.

Tranexamic acid inhibits melanogenesis partially via stimulation of TGF-ß1 expression in human epidermal keratinocytes.

Oral tranexamic acid (TA) has been an effective treatment for melasma with unclear mechanism. The present study aimed to demonstrate the effect of TA on melanogenesis via regulation of TGF-ß1 expression in keratinocytes. We firstly determined the expression level of TGF-ß1 in TA-treated keratinocyte-conditioned medium (KCM). Then, the mRNA and protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1) of human epidermal melanocytes (NHEMs) in the presence of TA-treated KCM were evaluated via RT-PCR and western blot analysis. Moreover, melanin content and tyrosinase activity were quantified. TGF-ß1 gene was knocked down by small interfering RNA (siRNA) in keratinocytes. The mRNA and protein levels of TGF-ß1 in keratinocytes were significantly increased after TA treatment. Melanin contents, tyrosinase activity, protein and mRNA levels of TYR, MITF and TRP-1 were downregulated in NHEMs in the presence of TA-treated KCM. Knockdown of TGF-ß1 in keratinocytes could attenuate the inhibitory effect of TA-treated KCM on melanogenesis. TA could stimulate TGF-ß1 expression in keratinocytes, which further inhibits melanogenesis through the paracrine signalling.

Treatment of linear and whorled nevoid hypermelanosis using QS 694-nm ruby laser.

Laser is being widely used in treating pigmented lesions nowadays. Linear and whorled nevoid hypermelanosis (LWNH) is a rare pigmentary anomaly, and there are only a handful of cases of successful treatment, all with QS 532- and 755-nm laser. The objective of this study was to examine the clinical outcome of QS 694-nm ruby laser in the treatment of LWNH. We report on a 4-year-old boy presented with asymptomatic macular hyperpigmentation over the entire cheek who underwent 3 treatment sessions with QS 694-nm ruby laser. One month after the last treatment, the patient demonstrated significant improvement to the treatment area. Aside from post-procedural purpura lasting approximately 1 week, the patient experienced no serious adverse effects. No recurrence was observed during the 3-month follow-up. Given the excellent results seen in our patients, we recommended the use of QS 694-nm ruby laser as a safe and effective treatment in patients with LWNH.

Guideline for the diagnosis, treatment and long-term management of cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is an inflammatory, autoimmune disease encompassing a broad spectrum of subtypes including acute, subacute, chronic and intermittent CLE. Among these, chronic CLE can be further classified into several subclasses of lupus erythematosus (LE) such as discoid LE, verrucous LE, LE profundus, chilblain LE and Blaschko linear LE. To provide all dermatologists and rheumatologists with a practical guideline for the diagnosis, treatment and long-term management of CLE, this evidence- and consensus-based guideline was developed following the checklist established by the international Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group and was registered at the International Practice Guideline Registry Platform. With the joint efforts of the Asian Dermatological Association (ADA), the Asian Academy of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of Chinese Society of Dermatology (CSD), a total of 25 dermatologists, 7 rheumatologists, one research scientist on lupus and 2 methodologists, from 16 countries/regions in Asia, America and Europe, participated in the development of this guideline. All recommendations were agreed on by at least 80% of the 32 voting physicians. As a consensus, diagnosis of CLE is mainly based on the evaluation of clinical and histopathological manifestations, with an exclusion of SLE by assessment of systemic involvement. For localized CLE lesions, topical corticosteroids and topical calcineurin inhibitors are first-line treatment. For widespread or severe CLE lesions and (or) cases resistant to topical treatment, systemic treatment including antimalarials and (or) short-term corticosteroids can be added. Notably, antimalarials are the first-line systemic treatment for all types of CLE, and can also be used in pregnant patients and pediatric patients. Second-line choices include thalidomide, retinoids, dapsone and MTX, whereas MMF is third-line treatment. Finally, pulsed-dye laser or surgery can be added as fourth-line treatment for localized, refractory lesions of CCLE in cosmetically unacceptable areas, whereas belimumab may be used as fourth-line treatment for widespread CLE lesions in patients with active SLE, or recurrence of ACLE during tapering of corticosteroids. As for management of the disease, patient education and a long-term follow-up are necessary. Disease activity, damage of skin and other organs, quality of life, comorbidities and possible adverse events are suggested to be assessed in every follow-up visit, when appropriate.

Impact of treatment delays on vitiligo during the COVID-19 pandemic: A retrospective study.

Due to the COVID-19 pandemic, routine treatments are delayed to some extent and their negative impacts have been widely reported. However, virtually nothing is known about vitiligo in the context of COVID-19. Therefore, we analyzed treatment delays and its impact on vitiligo, aiming to provide suggestions on vitiligo management within this special period. We performed a retrospective cohort study on 322 patients who visited our clinics at least 2 times from January to December 2020, and their medical records and photographs were reviewed. Patients were divided into normal (n = 155) and late group (n = 167) based on whether experienced treatment delays. As for the active cases, the late group showed higher progression rate than normal group (35 of 86 [40.7%] vs. 10 of 81 [12.3%]; p = 0.002). Moreover, we observed higher recurrence rate in delay group than those of normal group (26 of 81[32.1%] vs. 9 of 74 [12.2%]; p = 0.018) among stable cases. Further univariate and multivariate analysis determined treatment delays as the most important independent risk factor for disease progression and recurrence, and maintenance therapy (>2 years) as a protective factor against recurrence. This study, for the first time, revealed the independent adverse impact of treatment delays on the progression and recurrence of vitiligo and indicated the significance of continuous treatment for halting progression and long-term maintenance therapy for preventing recurrence for vitiligo, which should be highly valued in the management of vitiligo during the COVID-19 pandemic.

GPNMB Extracellular Fragment Protects Melanocytes from Oxidative Stress by Inhibiting AKT Phosphorylation Independent of CD44.

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that plays an important role in cancer metastasis and osteoblast differentiation. In the skin epidermis, GPNMB is mainly expressed in melanocytes and plays a critical role in melanosome formation. In our previous study, GPNMB was also found to be expressed in skin epidermal keratinocytes. In addition, decreased GPNMB expression was observed in the epidermis of lesional skin of patients with vitiligo. However, the exact role of keratinocyte-derived GPNMB and its effect on vitiligo is still unknown. In this study, we demonstrated that GPNMB expression was also decreased in rhododendrol-induced leukoderma, as seen in vitiligo. The extracellular soluble form of GPNMB (sGPNMB) was found to protect melanocytes from cytotoxicity and the impairment of melanogenesis induced by oxidative stress. Furthermore, the effect of rGPNMB was not altered by the knockdown of CD44, which is a well-known receptor of GPNMB, but accompanied by the suppressed phosphorylation of AKT but not ERK, p38, or JNK. In addition, we found that oxidative stress decreased both transcriptional GPNMB expression and sGPNMB protein expression in human keratinocytes. Our results suggest that GPNMB might provide novel insights into the mechanisms related to the pathogenesis of vitiligo and leukoderma.

Standardizing serial photography for assessing and monitoring vitiligo: A core set of international recommendations for essential clinical and technical specifications.

BACKGROUND: Clinical photography is an important component of the initial assessment and follow-up of patients with vitiligo in clinical practice and research settings. Standardization of this photographic process is essential to achieve useful, high-quality, and comparable photographs over time. OBJECTIVE: The aim is to develop an international consensus for a core set of recommendations for standardized vitiligo clinical photography. METHODS: Based an international meeting of vitiligo experts, a standard operating procedure was developed for vitiligo photography in daily practice and research settings. This protocol was subsequently reviewed by 20 vitiligo experts until agreement was reached. RESULTS: The resulting protocol includes a set of 10 and 15 photographs for clinical practice and research purposes, respectively. The photographic series are based on anatomic units included in the Vitiligo Extent Score. Furthermore, graphic representations of standardized positioning and suggestions for guidelines to standardize the process (background color, lighting, position marking, scales, materials, instruments) for both color and ultraviolet photographs are described. CONCLUSIONS: This consensus-based protocol for vitiligo photography will harmonize imaging for both clinical practice, translational research, and clinical trials. It can improve outcome assessment, foster multicenter collaboration, and promote better communication with patients regarding outcomes of treatment.

Consensus of Chinese experts on protection of skin and mucous membrane barrier for health-care workers fighting against coronavirus disease 2019.

Health professions preventing and controlling Coronavirus Disease 2019 are prone to skin and mucous membrane injury, which may cause acute and chronic dermatitis, secondary infection and aggravation of underlying skin diseases. This is a consensus of Chinese experts on protective measures and advice on hand-cleaning- and medical-glove-related hand protection, mask- and goggles-related face protection, UV-related protection, eye protection, nasal and oral mucosa protection, outer ear, and hair protection. It is necessary to strictly follow standards of wearing protective equipment and specification of sterilizing and cleaning. Insufficient and excessive protection will have adverse effects on the skin and mucous membrane barrier. At the same time, using moisturizing products is highly recommended to achieve better protection.

Hydrogen Sulfide Promotes Cell Proliferation and Melanin Synthesis in Primary Human Epidermal Melanocytes.

BACKGROUND/AIM: Hydrogen sulfide (H2S) has been found to act as a physiological intercellular messenger to regulate cell survival. In this study, we evaluated whether H2S could promote cell proliferation and melanin synthesis in human epidermal melanocytes (HEMs). METHODS: Primary HEMs were cocultured with sodium hydrosulfide (NaHS, the most widely used H2S donor) or endogenously overexpressed with cystathionine-γ-lyase (CSE) gene, which is the most predominant H2S-producing enzyme. Then, cell viability, intracellular melanin content, tyrosinase (TYR) activity, and expression of microphthalmia-associated transcription factor (MITF), TYR, together with TYR-related protein 1 (TRP-1) in both transcript and protein levels, were detected. RESULTS: We first confirmed that NaHS (10-100 µm) increased cell viability, intracellular melanin content, and TYR activity in a dose-dependent manner. Then, we found that endogenous H2S production also promoted cell proliferation, intracellular melanin content, and TYR activity. In addition, we observed the mRNA and protein expression of MITF, TYR, and TRP-1 was significantly up-regulated after NaHS treatment and CSE gene transfection. CONCLUSIONS: This study demonstrates that H2S promotes cell proliferation and melanin synthesis in HEMs, which indicates pharmacologic regulation of H2S may be potential treatment for skin disorders caused by loss of melanocytes or dysfunction of melanogenesis.

Comparison of efficacy and safety profile for home NB-UVB vs. outpatient NB-UVB in the treatment of non-segmental vitiligo: A prospective cohort study.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of home and outpatient narrowband ultraviolet B light (NB-UVB) for the treatment of non-segmental vitiligo. METHODS: A total of 94 patients with non-segmental vitiligo were enrolled. Forty-eight patients were treated with home NB-UVB, and the other 46 patients were treated with outpatient NB-UVB over a period of 6 months. The efficacy, patient quality of life, and adverse events were assessed at month 3 and month 6 after treatment. RESULTS: There was no significant difference in repigmentation and VASI-reverse (VR) rates between outpatient NB-UVB and home NB-UVB groups. VR was higher in outpatient NB-UVB group at month 3, and similar at month 6. For long-standing vitiligo, VR was higher in the outpatient NB-UVB group compared with home NB-UVB group after 6 months of treatment. In recent vitiligo, the VR was similar between the two groups. Additionally, vitiligo-specific health-related quality-of-life instrument (VitiQoL) score was similar, and the adverse effects were minimal among the two groups. CONCLUSIONS: The efficacy and safety of home NB-UVB and outpatient NB-UVB phototherapy for non-segmental vitiligo were comparable. According to our results, those with long-standing vitiligo may be recommended to receive outpatient NB-UVB phototherapy.

A Promising Generation: Future Academic Leadership of China.

With the world's largest population at 1.3 billion and a rising number of foreigners, China requires physicians and a healthcare system that meets the needs of a large and diverse population. Along with rapid economic and technological advancements, the Medical Administration Division of the National Health and Family Planning Commission remarked that medical services through online appointments and payments have improved its efficacy over the past 2 years. According to the official report from the National Health and Family Planning Commission of the People's Republic of China website, China has so far established a total of 25,000 hospitals and 981,000 community health centers, that includes 17,100 dermatologists and 190,000 residents in training.

Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne.

Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.

Comparison of Moderate and High Energy of a Nano-Fractional Radiofrequency Treatment on a Photoaging Hairless Mice Model.

BACKGROUND: Fractional radiofrequency (FRF) has been widely used in skin rejuvenation. To explore optimal settings, it is important to compare different treatment parameters. OBJECTIVE: This study was designed to compare the effect of moderate-energy and high-energy FRF treatment on a hairless mice model. METHODS: Fifteen photoaged hairless mice were assigned to 3 groups: control, moderate energy, and high energy. Two treatment sessions (T × 1 and T × 2) were performed at 1-month interval. Transepidermal water loss was measured at baseline, immediately, 1, 2, and 4 weeks after T × 1. Skin samples were harvested before each treatment, 1 and 2 months after T × 2. Neocollagenesis was evaluated by hematoxylin and eosin staining, Masson staining, and immunohistochemistry analysis. RESULTS: Transepidermal water loss of high-energy group was significantly higher than the moderate-energy group (p = .008) immediately after T × 1. Remarkable fibroblast proliferation was observed at 1 month after T × 1, followed by significant dermal thickening, and increase of Type I collagen and Type III collagen. There was no significant difference between 2 energy groups in fibroblast proliferation, dermal thickness, and collagen density. CONCLUSION: The effect of moderate-energy treatment was comparable with that of high energy in neocollagenesis, whereas moderate energy yielded less damage to skin barrier function.

Objective evaluation of the effects of intense pulsed light treatment on Asian skin by reflectance confocal microscopy analysis.

This study aimed to evaluate the effect of IPL treatment on Asian skin by reflectance confocal microscopy (RCM) analysis. Ten Asian female volunteers (39~54 years old, Fitzpatrick skin type III~IV) received five monthly IPL treatments. RCM skin images were evaluated, and several skin physiological parameters including thickness of stratum corneum, minimal thickness of epidermis, thickness of basal layer, density of dermal papillae, and mean diameter of papillae capillaries were measured both at baseline and 1 month after the last treatment. Transepidermal water loss (TEWL) was evaluated, as well. Thickness of stratum corneum was 4.80 ± 1.48 µm before IPL treatment and 5.50 ± 1.35 µm after treatment (p = 0.322). Both minimal thickness of epidermis and thickness of basal layer were significantly increased (p = 0.002 and 0.018, respectively) after IPL treatment. Dermal papillae density was significantly increased (p = 0.035), whereas mean capillary diameter was reduced significantly (p = 0.035). TEWL was slightly increased after treatment, while the difference was not significant on either T-zone or U-zone (p = 0.085 on T-zone and p = 0.114 on U-zone). RCM imaging is a feasible method to evaluate the effect of IPL effect on human skin. Moreover, IPL treatment serves to be highly safe in skin rejuvenation.