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.

The multifaceted role of autophagy in skin autoimmune disorders: a guardian or culprit?

Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This dynamic mechanism participates in various biological processes, such as the regulation of cellular differentiation, proliferation, survival, and the modulation of inflammation and immune responses. Recent evidence has demonstrated the involvement of polymorphisms in autophagy-related genes in various skin autoimmune diseases. In addition, autophagy, along with autophagy-related proteins, also contributes to homeostasis maintenance and immune regulation in the skin, which is associated with skin autoimmune disorders. This review aims to provide an overview of the multifaceted role of autophagy in skin autoimmune diseases and shed light on the potential of autophagy-targeting therapeutic strategies in dermatology.

2% supramolecular salicylic acid hydrogel vs. adapaline gel in mild to moderate acne vulgaris treatment: A multicenter, randomized, evaluator-blind, parallel-controlled trial.

OBJECTIVE: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel. METHODS: A multicenter, randomized, assessor-blind and parallel-controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I-II) facial acne vulgaris were recruited in this study over a 16-week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre- and post-treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05. RESULTS: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups. CONCLUSION: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris.

Efficacy and safety of the combination of oral tranexamic acid and intense pulsed light versus oral tranexamic acid alone in the treatment of refractory Riehl's melanosis: A prospective, comparative study.

BACKGROUND: There is no standardized and effective treatment modality for Riehl's melanosis. AIMS: To compare the efficacy and safety of oral tranexamic acid (TXA) combined with intense pulsed light (IPL) versus TXA alone in the treatment of refractory Riehl's melanosis. METHODS: A prospective study of 28 subjects with refractory Riehl's melanosis and Fitzpatrick Skin Types III or IV was conducted. All subjects received oral TXA 500 mg daily and 11 of them were treated in combination with monthly IPL therapy for 6 months. The primary outcome measure was mean melanin index (MI), erythema index (EI) and acquired dermal macular hyperpigmentation area and severity index (DPASI). The Physician Global Assessment (PGA) and patient satisfaction scale were documented. RESULTS: After treatment, DPASI, mean MI, and EI were significantly reduced in both groups. The group treated with combination therapy showed better improvement according to MI (p = 0.0032) and DPASI (p = 0.00468). PGA and patient satisfaction scale showed superior efficacy in the combination group. No significant difference was observed in treatment-related side effects. CONCLUSION: The combination of oral TXA and IPL proves to be a safe and satisfactory treatment strategy for refractory Riehl's melanosis.

S100A9 Exacerbates the Inflammation in Rosacea through Toll-Like Receptor 4/MyD88/NF-κB Signaling Pathway.

Rosacea is a chronic inflammatory skin disorder characterized by immune response-dependent erythema and pustules. S100A9, a proinflammatory alarmin, has been associated with various inflammation-related diseases. However, the specific role of S100A9 in rosacea remains unexplored. Therefore, our objective was to unravel the role of S100A9 in the pathogenesis of rosacea and its underlying molecular mechanisms. In this study, we show that expression levels of S100A9 were elevated in both the lesions and serum of patients with papulopustular rosacea as well as in lesions of the LL37-induced rosacea-like mouse model. Moreover, the upregulation of S100A9 was correlated with clinical severity and levels of inflammatory cytokines. In addition, we demonstrated that S100A9 promoted the production of proinflammatory factors in HaCaT cells by activating toll-like receptor 4/MyD88/NF-κB signaling pathways. Notably, inhibition of S100A9 suppressed the progression of rosacea-like dermatitis and inflammatory responses in the LL37-induced rosacea-like mouse model through toll-like receptor 4/MyD88/NF-κB signaling pathways. In conclusion, this study illustrated that S100A9 participates in the pathogenesis of rosacea by upregulating toll-like receptor 4/MyD88/NF-κB signaling pathways, thereby promoting rosacea-associated skin inflammation. These results not only expand our understanding of the potential role of S100A9 in the development of rosacea but also offer greater insight toward targeted therapies.

Emerging Role of Fibroblasts in Vitiligo: A Formerly Underestimated Rising Star.

Vitiligo is a disfiguring depigmentation disorder characterized by loss of melanocytes. Although numerous studies have been conducted on the pathogenesis of vitiligo, the underlying mechanisms remain unclear. Although most studies have focused on melanocytes and keratinocytes, growing evidence suggests the involvement of dermal fibroblasts, residing deeper in the skin. This review aims to elucidate the role of fibroblasts in both the physiological regulation of skin pigmentation and their pathological contribution to depigmentation, with the goal of shedding light on the involvement of fibroblasts in vitiligo. The topics covered in this review include alterations in the secretome, premature senescence, autophagy dysfunction, abnormal extracellular matrix, autoimmunity, and metabolic changes.

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'.

ALA-PDT promotes IL-1ß secretion from human SZ95 sebocytes via activation of the NLRP3 inflammasome.

BACKGROUND: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for pilosebaceous inflammatory diseases, such as acne vulgaris. In this study, we explored ALA-PDT's mechanisms against acne in vitro. METHODS: We treated human SZ95 sebocytes with ALA (0.2 mM) and subjected them to varied PDT doses (0, 5, 10, 20 J/cm²) over 12 h. We assessed cell viability post-treatment using the Annexin V FITC/PI apoptosis kit. ROS accumulation in the sebocytes was detected with a DCFDA probe. We quantified NLRP3 and caspase-1 mRNA via quantitative PCR and determined IL-1ß release following ALA-PDT by ELISA. Western blotting helped identify the levels of proteins associated with pyroptosis (NLRP3, caspase-1, and IL-1ß). To elucidate the mechanisms, we re-evaluated these parameters after administering various concentrations of NAC antioxidants (0, 0.4, 2, 10 mM) and the caspase inhibitor Z-VAD-FMK (0, 5, 10, 20 µM). RESULTS: Increasing PDT dose inversely affected SZ95 sebocyte survival, with a corresponding rise in ROS and pyroptosis-related proteins (NLRP3, caspase-1, and IL-1ß). Furthermore, NAC and Z-VAD-FMK modulated the expression and secretion of these molecules in a dose-responsive manner. CONCLUSION: Our findings suggest ALA-PDT's potential mechanism of action on sebaceous glands could involve ROS induction, leading to NLRP3 inflammasome assembly, thereby heightening caspase-1 activation and IL-1ß secretion. This cascade may amplify the local inflammatory response to break chronic inflammation in acne vulgaris treatment.

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.

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.

The Emerging Role of Visible Light in Melanocyte Biology and Skin Pigmentary Disorders: Friend or Foe?

Electromagnetic radiation, notably visible light (VL), has complicated effects on human skin, particularly pigmentation, which have been largely overlooked. In this review, we discuss the photobiological mechanisms, pathological effects, clinical applications and therapeutic strategies of VL at varying wavelengths on melanocyte biology and skin pigmentary disorders. Different VL wavelengths may impose positive or negative effects, depending on their interactions with specific chromophores, photoaging, ROS production, circadian rhythm and other photon-mediated reactions. Further in vivo and in vitro studies are required to establish the pathologic mechanisms and application principles of VL in pigmentary disorders, as well as optimal photoprotection with coverage against VL wavelengths.

A case of junctional epidermolysis bullosa intermediate with collagen XVII deficiency treated with dupilumab.

Inherited epidermolysis bullosa is a heterogeneous group of hereditary skin diseases characterized by skin (mucosa) fragility, which leads to blistering. Junctional epidermolysis bullosa is associated with mutations in genes expressing proteins of the dermo-epidermal junction. Dupilumab, an antibody that directly targets interleukin (IL)-4 receptor alpha, may be an effective treatment for dystrophic epidermolysis bullosa. We describe a case of junctional epidermolysis bullosa that improved with dupilumab.

Unveiling the mystery of Riehl's melanosis: An update from pathogenesis, diagnosis to treatment.

Riehl's melanosis is a hyperpigmentation disorder that has a significant psychological and social impact on individuals. In the past 10 years, new categories have been developed, raising questions about how to classify Riehl's melanosis. The mechanism of this disease remains unclear, although the type IV hypersensitivity response caused by allergic sensitization, as well as genetic, ultraviolet radiation, and autoimmune factors, is to blame. Clinical manifestation, dermoscopy, reflectance confocal microscopy, patch/photopatch testing, histopathology, and a novel multimodality skin imaging system have been used for the diagnosis. A variety of therapies including topical skin-lightening agents, oral tranexamic acid, glycyrrhizin compound, chemical peels, and lasers and light therapies (intense pulsed light, 1064-nm Q-Switched Nd: YAG laser, 755-nm PicoWay laser, nonablative 1927-nm fractional thulium fiber laser, new pulsed-type microneedling radiofrequency), with improved effectiveness. The latest findings on possible biomarkers and their relationship to other autoimmune diseases were also summarized.

590 nm LED Irradiation Improved Erythema through Inhibiting Angiogenesis of Human Microvascular Endothelial Cells and Ameliorated Pigmentation in Melasma.

Melasma is a common refractory acquired pigmentary skin disease that mainly affects middle-aged women. The pathogenesis of melasma is still uncertain, while abnormal vascular endothelial cells may play a role. We previously demonstrated the yellow light of light-emitting diodes (LED) could inhibit melanogenesis through the photobiomodulation (PBM) of melanocytes and keratinocytes. In the current study, we investigated the effect of 590 nm LED on the function of human microvascular endothelial cells (HMEC-1). We revealed 0-40 J/cm2 590 nm LED had no toxic effect on HMEC-1 in vitro. 590 nm LED irradiation significantly reduced cell migration, tube formation, as well as the expression of vascular endothelial growth factor (VEGF) and stem cell factor (SCF), a pro-melanogenic factor. Moreover, we illustrated that 590 nm LED inhibited the phosphorylation of the AKT/PI3K/mTOR signaling pathway, and the inhibitory effect on HMEC-1 could be partially reversed by insulin-like growth factor 1 (IGF-1), an AKT/PI3K/mTOR pathway agonist. Besides, we conducted a pilot clinical study and observed a marked improvement on facial erythema and pigmentation in melasma patients after amber LED phototherapy. Taken together, 590 nm LED inhibited HMEC-1 migration, tube formation and the secretion of VEGF and SCF, predominantly through the inhibition of the AKT/PI3K/mTOR pathway, which may serve as a novel therapeutic option for melasma.