Disease Awareness and Treatment Preferences in Vitiligo: A Cross-sectional Study in China.

In China, there is a lack of data regarding the awareness and treatment preferences among patients with vitiligo and their families. To address this gap, a cross-sectional questionnaire-based study was conducted to investigate disease awareness and treatment preferences in Chinese patients with vitiligo. The study also evaluated willingness to pay, using 2 standardized items, and assessed quality of life, using the Dermatology Life Quality Index (DLQI) score. Data from 307 patients with vitiligo (59.3% women, mean age 28.98 years, range 2-73 years) were analysed. Of these patients, 44.7% had insufficient knowledge of vitiligo, particularly those from rural areas or with low levels of education. Mean DLQI total score was 4.86 (5.24 for women and 4.30 for men). Among the most accepted treatments were topical drugs, phototherapy, and systemic therapy. Patients were relatively conservative about the duration and cost of treatment, with only 27.7% willing to pay more than 10,000 Chinese yuan renminbi (CNY) for complete disease remission. High level of education, high income, skin lesions in specific areas, and skin transplantation therapy predicted higher willingness to pay. Insufficient knowledge was associated with a higher burden of disease. In order to reduce the disease burden and improve treatment adherence it is crucial to enhance disease awareness and take into account patient preferences.

Identification of Sitogluside as a Potential Skin-Pigmentation-Reducing Agent through Network Pharmacology.

Many traditional Chinese medicines (TCMs) with skin-whitening properties have been recorded in the Ben-Cao-Gang-Mu and in folk prescriptions, and some literature confirms that their extracts do have the potential to inhibit pigmentation. However, no systematic studies have identified the specific regulatory mechanisms of the potential active ingredients. The aim of this study was to screen the ingredients in TCMs that inhibit skin pigmentation through a network pharmacology system and to explore underlying mechanisms. We identified 148 potential active ingredients from 14 TCMs, and based on the average "degree" of the topological parameters, the top five TCMs (Fructus Ligustri Lucidi, Hedysarum multijugum Maxim., Ampelopsis japonica, Pseudobulbus Cremastrae Seu Pleiones, and Paeoniae Radix Alba) that were most likely to cause skin-whitening through anti-inflammatory processes were selected. Sitogluside, the most common ingredient in the top five TCMs, inhibits melanogenesis in human melanoma cells (MNT1) and murine melanoma cells (B16F0) and decreases skin pigmentation in zebrafish. Furthermore, mechanistic research revealed that sitogluside is capable of downregulating tyrosinase (TYR) expression by inhibiting the ERK and p38 pathways and inhibiting TYR activity. These results demonstrate that network pharmacology is an effective tool for the discovery of natural compounds with skin-whitening properties and determination of their possible mechanisms. Sitogluside is a novel skin-whitening active ingredient with dual regulatory effects that inhibit TYR expression and activity.

Traditional Asian Herbs in Skin Whitening: The Current Development and Limitations.

In Asia, the market for whitening cosmetics is expanding rapidly, more and more people prefer to use natural products. Driven by natural product demand and technical advances, herbal research is also developing fast. Lots of studies reported that Asian herbal reagents can reduce melanogenesis, these findings provide evidence for the whitening application of Asian herbs. However, the current development status and challenges of herbal research need attention too. By reviewing these studies, different problems in studying herbal formulas, extracts, and active ingredients were presented. One of the most influential troubles is that the components of herbs are too complex to obtain reliable results. Thus, an understanding of the overall quality of herbal research is necessary. Further, 90 most cited Asian herbal studies on whitening were collected, which were conducted between 2017 and 2020, then statistical analysis was carried out. This work provided a comprehensive understanding of Asian herbal research in skin whitening, including the overall status and quality, as well as the focuses and limitations of these studies. By proactively confronting and analyzing these issues, it is suggested that the focus of herbal medicine research needs to shift from quantity to quality, and the new stage of development should emphasize transformation from research findings to whitening products.

Ozone Therapy Attenuates NF-κB-Mediated Local Inflammatory Response and Activation of Th17 Cells in Treatment for Psoriasis.

Ozone therapy has been widely used to treat many skin diseases, including infections, allergic dermatosis, and skin ulcers. However, its efficacy as a treatment for psoriasis is unclear. In this study, we explored the clinical efficacy and the underlying molecular mechanisms of ozone therapy on psoriasis. We found that topical ozone treatment significantly decreased patients' psoriasis area and severity index (PASI) scores and the expression of psoriasis-associated cytokines in their peripheral blood CD4+ T cells. In the IMQ-induced psoriasis mouse model, topical ozone treatment significantly inhibited the formation of IMQ-induced psoriasis-like lesions and the expression of psoriasis-associated inflammatory factors. High-throughput sequencing confirmed that IMQ-induced activation of toll-like receptor 2 (TLR2)/ nuclear factor-κB (NF-κB) signaling pathway was significantly suppressed in psoriasis-like lesions after topical ozone treatment. Furthermore, the activation of spleen T helper (Th) 17 cells was blocked in the mouse model; this was associated with the downregulation of cytokines and NF-κB pathways upon topical ozone treatment. Ozone therapy can attenuate local inflammatory reactions and the activation of Th17 cells in psoriasis by inhibiting the NF-κB pathway. Our results show that ozone therapy is effective in treating psoriasis. We recommend further evaluations for its clinical applications.

Ozone therapy promotes the differentiation of basal keratinocytes via increasing Tp63-mediated transcription of KRT10 to improve psoriasis.

Psoriasis is a chronic immune-mediated inflammatory dermatosis. Recently, ozone therapy has been applicated to psoriasis treatment; however, the mechanism by which ozone therapy improves psoriasis remains unclear. The excessive proliferation and the differentiation of basal keratinocytes have been considered critical issues during pathological psoriasis process, in which keratin 6 (KRT6) and KRT10 might be involved. In the present study, KRT6, IL-17 and IL-22 protein within psoriasis lesions was decreased, while KRT10 and Tp63 protein in psoriasis lesions was increased by ozone treatment in both patient and IMQ mice psoriatic tissues. In the meantime, ozone treatment down-regulated KRT6 mRNA and protein expression while up-regulated KRT10 mRNA and protein expression within IL-22 treated primary KCs; the cell viability of KCs was suppressed by ozone treatment. Moreover, Tp63 bound to KRT10 promoter region to activate its transcription in basal keratinocytes; the promotive effects of ozone on Tp63 and KRT10 were significantly reversed by Tp63 silence. Both TP63 and KRT10 mRNA expression were significantly increased by ozone treatment in psoriasis lesions; there was a positive correlation between Tp63 and KRT10 expression within tissue samples, suggesting that ozone induces the expression of Tp63 to enhance the expression of KRT10 and the differentiation of keratinocytes, therefore improving the psoriasis. In conclusion, the application of ozonated oil could be an efficient and safe treatment for psoriasis; ozone promotes the differentiation of keratinocytes via increasing Tp63-mediated transcription of KRT10, therefore improving psoriasis.

Topical ozone therapy restores microbiome diversity in atopic dermatitis.

BACKGROUND: Staphylococcus aureus (S. aureus) accounts for 90% of the microbiome in atopic dermatitis (AD) lesions and plays a role in disease flare-ups and worsens disease outcome. Ozone treatment can improve AD conditions by its bactericidal effect on S. aureus. OBJECTIVE: To study the effects of topical ozone therapy on microbiome diversity in AD lesions and explore potential probiotic pathogens correlated with AD progression. METHODS: Patients with moderate to severe bilateral skin lesions in AD were recruited. Randomized split sides were performed. One side was treated with ozone hydrotherapy followed by ozonated oil; while the contralateral side with tap water and basal oil. Patients' SCORAD scores and modified EASI were recorded before and after treatments. The microbiological compositions in targeting sites were determined using 16S rDNA sequencing. RESULTS: After three-day ozone therapy, patients showed a significant decrease in SCORAD scores and inflammatory cell infiltration in AD lesions. The micro-ecological diversity was higher in the non-lesional as compared with lesional areas (p < 0.05), which was also negatively correlated with the severity of AD (r = -0.499, p < 0.05). The proportion of S. aureus in AD lesions was positively correlated with the severity of AD (r = 0.564, p = 0.010), which was decreased after ozone treatment (p = 0.07). Ozone therapy showed an increase in microbiological diversity with a significant increase in the proportion of Acinetobacter (p < 0.05). CONCLUSION: Topical ozone therapy is highly effective for treatment for AD. It can change the proportional ratio of Staphylococcus and Acinetobacter, thereby restoring the microbiological diversity in AD lesions.

The role and mechanism of Asian medicinal plants in treating skin pigmentary disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Chloasma, senile plaques, vitiligo and other pigmentary disorders seriously affect patients' appearance and life quality. Medicinal plant is the product of long-term medical practice worldwide, with the advantages of outstanding curative properties and less side effects. Recently, research were made to explore the value of medicinal plants in the treatment of pigmentary disorders, and remarkable results were achieved. AIM OF THE REVIEW: This review outlines the current understanding of the role and potential mechanisms of medicinal plants (including active ingredients, extracts and prescriptions) in pigmentary disorders, especially Chinese medicinal plants, provides the preclinical evidence for the clinical benefits. This study hopes to provide comprehensive information and reliable basis for exploring new therapeutic strategies of plant drugs in the treatment of skin pigmented diseases. METHODS: The literature information was obtained from the scientific databases (up to Oct, 2017), mainly from the PubMed, Web of Science and CNKI databases, and was to identify the experimental studies on the regulating melanogenesis role of the active agents from herbal medicine and the involved mechanisms. The search keywords for such work included: "pigmentary" or "pigmentation", "melanogenesis", and "traditional Chinese medicine" or "Chinese herbal medicine", "herb", "medicinal plant". RESULTS: We summarized the function of medicinal plants involved in melanogenesis, especially Chinese medicine. It was reported that the active ingredients, extracts, or prescriptions of medicinal plants can regulate the expression of genes related to melanogenesis by affecting the signaling pathways such as MAPK and PKA, thereby regulating pigment synthesis. Some of them can promote melanogenesis (such as isoliquiritigenin, geniposide; Cornus officinalis Siebold & Zucc., Eclipta prostrata (L.) L.; the Bairesi complex prescription, etc.). While others have the opposite effect (such as biochanin A, Gomisin N; Panax ginseng C.A. Meyer, Nardostachys chinensis Bat.; Sanbaitang, etc.). CONCLUSION: Asian medicinal plants, especially their active ingredients, have multilevel effects on melanogenesis by regulating melanogenesis-related genes or signaling pathways. They are of great clinical value for the treatment of skin pigmentary disorders. However, the experimental effect, safety, and functional mechanism of the medicinal plants require further determination before studying their clinical efficacy.

Ganoderma lucidum polysaccharide reduces melanogenesis by inhibiting the paracrine effects of keratinocytes and fibroblasts via IL-6/STAT3/FGF2 pathway.

Our previous study found that Ganoderma lucidum polysaccharide (GLP), bioactive ingredients from Ganoderma lucidum, protected fibroblasts from photoaging. However, whether GLP can affect melanogenesis in melanocytes through regulating paracrine mediators that secreted by keratinocytes and fibroblasts is unclear. We aimed to investigate the efficacy and mechanisms of action of GLP in melanogenesis by regulating paracrine effects of keratinocytes and fibroblasts. The effect of GLP on cell viability affected by GLP was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After an immortal keratinocyte line (HaCaT) and primary fibroblasts (FB) were treated with GLP, the supernatants of HaCaT and FB cells were collected and cocultured with an immortalized melanocyte line (PIG1). The expression levels of melanogenesis-associated genes in PIG1 cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Furthermore, FRS-2, ERK, JNK, and p38 phosphorylation levels were measured. Then, major melanogenic paracrine mediators in HaCaT and FB cells treated with GLP were evaluated by qRT-PCR and enzyme-linked immunosorbent assay (ELISA). In addition, the expression of IL-6 and STAT3 was examined in HaCaT and FB cells. GLP was not cytotoxic to HaCaT and FB cells. The supernatants of GLP-treated HaCaT and FB cells downregulated the expression levels of MITF, TYR, TYRP1, TYRP2, RAB27A, and FSCN1 genes and inhibited the phosphorylation of FRS-2, ERK, JNK, and p38 in PIG1 cells. GLP also decreased FGF2 secretion in HaCaT and FB cells. Moreover, GLP reduced IL-6 expression and STAT3 phosphorylation in HaCaT and FB cells. GLP reduced melanogenesis in melanocytes by inhibiting the paracrine effects of keratinocytes and fibroblasts via IL-6/STAT3/FGF2 pathway.

Article Effect and Mechanism of Ganoderma lucidum Polysaccharides on Human Fibroblasts and Skin Wound Healing in Mice.

OBJECTIVE: To investigate the effects of Ganoderma lucidum polysaccharides (GL-PS) on human fibroblasts and skin wound healing in Kunming male mice and to explore the putative molecular mechanism. METHODS: Primary human skin fibroblasts were cultured. The viability of fibroblasts treated with 0, 10, 20, 40, 80, and 160 µg/mL of GL-PS, respectively were detected by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-Htetrazolium bromide (MTT). The migration ability of fibroblasts treated with 0, 10, 20, and 40 µg/mL of GL-PS were measured by transwell assay. The secretion of the C-terminal peptide of procollagen type I (CICP) and transforming growth factor-ß1 (TGF-ß1) in the cell supernatant was tested by enzyme-linked immunosorbent assay. The expression of ß-catenin was detected by Western blot. Furthermore, the Kunming mouse model with full-layer skin resection trauma was established, and was treated with 10, 20, and 40 mg/mL of GL-PS, respectively as external use. The size of the wound was measured daily, complete healing time in each group was recorded and the percentage of wound contraction was calculated. RESULTS: Compared with the control group, 10, 20, and 40 µg/mL of GL-PS significantly increased the viability of fibroblasts, promoted the migration ability of fibroblasts, and up-regulated the expressions of CICP and TGF-ß1 in fibroblasts (Plt;0.05 or Plt;0.01). The expression of ß-catenin in fibroblasts treated with 20 and 40 µg/mL of GL-PS was significantly higher than that of the control group (Plt;0.01). Furthermore, after external use of 10, 20, and 40 mg/mL of GL-PS, the rates of wound healing in mice were significantly higher and the wound healing time was significantly less than the control group (Plt;0.05 or Plt;0.01). CONCLUSION: A certain concentration of GL-PS may promote wound healing via activation of the Wnt/ß-catenin signaling pathway and up-regulation of TGF-ß1, which might serve as a promising source of skin wound healing.

Facial nevus depigmentosus getting remarkable repigmentation by treatment with a 308-nm excimer laser: A case report.

Nevus depigmentosus (ND) is a rare, congenital, nonprogressive depigmented lesion with irregular outline. To date, the few therapeutic approaches that have been developed to treat ND have yielded unsatisfactory results. We reported on a 6-month-old girl who presented with a ND on the right side of her face for 5 months. Treatment with a 308-nm excimer laser was started once a week at 300 mJ/cm2 and then was increased by 50-100 mJ/cm2 in each subsequent session until post-treatment erythema occurred. After 10 treatments, repigmentation in the lesion was evident and remained stable 1 month later at follow up. This case supports that the 308-nm excimer laser may be a good choice for the treatment of ND.

The antibacterial effect of topical ozone on the treatment of MRSA skin infection.

Skin can be infected by many types of microorganisms, most commonly by gram­positive strains of Staphylococcus and Streptococcus spp. Treatment of Staphylococcus aureus (S. aureus) infections, particularly that of methicillin resistant Staphylococcus aureus (MRSA), is a challenge in clinical practice. Ozone therapy has proven to be one of the strongest antiseptics against the majority of microorganisms involved in skin infections. The purpose of the present study was to evaluate the microbicidal effects of topical ozone therapy on S. aureus and MRSA, and determine the clinical efficacy of ozone therapy on patients with MRSA skin infection. Microbicidal effects of ozonated oil and ozonated water were determined by plating and Kirby Bauer methods. Clinical efficacy and safety of topical ozone were evaluated in two cases with skin MRSA infection. The killing rates of ozonated oil for S. aureus and MRSA were greater when compared with the control oil group. Almost 100% of S. aureus were eliminated by ozonated oil following 5 min. Almost 100% MRSA were eliminated by ozonated oil following 15 min. In addition, 100% S. aureus and 100% MRSA were eliminated by ozonated water in 1 min. The inhibition zone diameters of ozonated oil for S. aureus and MRSA were 17 and 13 mm, respectively, which were significantly larger than the control group. Both cases of skin MRSA infection were completely healed with ozone therapy. In conclusion, ozone therapy is a potential treatment for S. aureus and MRSA skin infection as it has great efficacy, few side effects and low­costs.

Ganoderma lucidum polysaccharides protect fibroblasts against UVB-induced photoaging.

Ganoderma lucidum has featured in traditional Chinese medicine for >1,000 years. Ganoderma polysaccharides (GL-PS), a major active ingredient in Ganoderma, confer immune regulation, antitumor effects and significant antioxidant effects. The aim of the present study was to investigate the efficacy and mechanism of GL­PS­associated inhibition of ultraviolet B (UVB)­induced photoaging in human fibroblasts in vitro. Primary human skin fibroblasts were cultured, and a fibroblast photoaging model was built through exposure to UVB. Cell viability was measured by MTT assay. Aged cells were stained using a senescence­associated ß-galactosidase staining (SA­ß­gal) kit. ELISA kits were used to analyze matrix metalloproteinase (MMP) ­1 and C­telopeptides of Type I collagen (CICP) protein levels in cellular supernatant. ROS levels were quantified by flow cytometry. Cells exposed to UVB had decreased cell viability, increased aged cells, decreased CICP protein expression, increased MMP­1 protein expression, and increased cellular ROS levels compared with non­exposed cells. However, cells exposed to UVB and treated with 10, 20 and 40 µg/ml GL­PS demonstrated increased cell viability, decreased aged cells, increased CICP protein expression, decreased MMP­1 protein expression, and decreased cellular ROS levels compared with UVB exposed/GL­PS untreated cells. These results demonstrate that GL­PS protects fibroblasts against photoaging by eliminating UVB­induced ROS. This finding indicates GL­PS treatment may serve as a novel strategy for antiphotoaging.

Decreased copper and zinc in sera of Chinese vitiligo patients: a meta-analysis.

Abnormalities of copper (Cu) and zinc (Zn) are involved in the etiology and pathogenesis of vitiligo. However, controversial results exist now on Cu and Zn in serum of vitiligo patients. The purpose of this study is to compare the serum levels of Cu and Zn between vitiligo patients and healthy controls. In the meta-analysis, 16 studies with a total of 891 vitiligo cases and 1682 healthy controls were included. The levels of serum Cu and Zn were compared between groups of case and control. The serum levels of Cu were significantly lower in vitiligo patients than in healthy controls (Z = 4.04, P < 0.0001; standardized mean difference [SMD], -0.9; 95% confidence interval [CI], -1.34 to -0.47). The levels of serum Zn were also significantly lower in vitiligo patients than in healthy controls (Z = 4.88, P < 0.00001; SMD, -1.09; 95% CI, -1.51 to -0.64). These results demonstrate that decreased levels of serum Cu and Zn are generally present in Chinese vitiligo patients. This may offer support for clinical administration of oral Cu and Zn supplements.