Schisandrin B Inhibits Cell Viability and Malignant Progression of Melanoma Cells via Wnt/ß-catenin Signaling Pathway.

BACKGROUND: Melanoma is of great interest due to its aggressive behavior and less favorable prognosis. The need for the development of novel drugs for the treatment of melanoma is urgent. Considerable evidence indicated that Schisandrin B (Sch B), a bioactive compound extracted from Schisandra chinensis, has numerous anti-tumor properties in multiple malignant tumors. A few studies have reported the effect of Sch B on melanogenesis in the melanoma B16F10 cell line; however, the specific anti-tumor effects and mechanisms need to be further explored. OBJECTIVE: This study aimed to investigate the effects of Sch B on the cell viability, migration, invasion, and cell cycleblocking of melanoma cells and explore its potential anti-tumor mechanism in vitro and in vivo. METHODS: Melanoma cells (A375 and B16) were treated with different concentrations of Sch B (0, 20, 40, 60, or 80 µM), with dimethyl sulfoxide (DMSO) as control. The inhibitory effect of Sch B on A375 and B16 melanoma cells was verified by crystal violet assay and CCK8 assay. The flow cytometry was performed to observe cell cycle blocking. The effect of Sch B on the migration and invasion of melanoma cells was detected by wound healing assay and transwell assay, respectively. Western blot analysis was used to determine protein expression levels. The growth of the A375 melanoma xenograft-treated groups and immunohistochemical staining were conducted to assess the anti-tumor effect of Sch B in vivo. RESULTS: The crystal violet assay and CCK8 assay showed that Sch B significantly inhibited melanoma cell viability in a dose-dependent manner. Meanwhile, the flow cytometry analysis revealed that Sch B induced melanoma cell cycleblocking at the G1/S phase. In addition, the wound healing assay and transwell assay showed that Sch B inhibited the migration and invasion of melanoma cells. Furthermore, by establishing an animal model, we found that Sch B significantly inhibited the growth of melanoma in vivo. The potential mechanism could be that Sch B inhibited the activity of the Wnt/ß-catenin signaling pathway. CONCLUSION: These findings indicated that Sch B inhibits the cell viability and malignant progression of melanoma cells via the Wnt/ß-catenin pathway and induces cell cycle arrest. Our study suggests that Sch B has potential as a bioactive compound for the development of new drugs for melanoma.

Effect of 30% Supramolecular Salicylic Acid Peel on Skin Microbiota and Inflammation in Patients with Moderate-to-Severe Acne Vulgaris.

INTRODUCTION: Thirty-percent supramolecular salicylic acid (SSA), a modified salicylic acid preparation, is a safe and effective treatment for moderate-to-severe acne vulgaris (AV). However, its mechanism of action remains unclear. We aimed to analyze the role of 30% SSA peels on skin microbiota and inflammation in patients with moderate-to-severe AV. METHODS: A total of 28 patients were enrolled and received 30% SSA peels biweekly for 2 months. The Global Acne Grading System (GAGS) score, skin water content, transepidermal water loss (TEWL), pH, and sebum levels were assessed. Skin microbial samples and perilesional skin biopsies were obtained at the onset and 2 weeks after treatment completion. Samples were characterized using a high-throughput sequencing approach targeting a portion of the bacterial 16S ribosomal RNA gene. RESULTS: After treatment, patients showed a significant improvement in their GAGS score and skin barrier indicators (P < 0.05). The GAGS score was positively associated with both the sebum concentration (R = 0.3, P = 0.027) and pH (R = 0.39, P = 0.003). Increased expression of caveolin-1 and decreased expression of interleukin (IL)-1a, IL-6, IL-17, transforming growth factor beta, and toll-like receptor 2 were observed in the skin tissue after treatment. The richness and evenness of the cutaneous microbiome decreased after treatment and the Staphylococcus proportion decreased significantly (P < 0.05), whereas the Propionibacterium proportion tended to decrease (P = 0.066). CONCLUSIONS: On the basis of analyses of the skin barrier and microbiota, we speculate that the 30% SSA peel may have a therapeutic effect in patients with moderate-to-severe AV by improving the skin microenvironment and modulating the skin microbiome, thus reducing local inflammation.

Alantolactone Inhibits Melanoma Cell Culture Viability and Migration and Promotes Apoptosis by Inhibiting Wnt/ß-Catenin Signaling.

BACKGROUND: Melanoma is a highly invasive and metastatic malignant tumor originating from melanocytes and is associated with a poor prognosis. Surgical resection and chemotherapy are currently the main therapeutic options for malignant melanoma; however, their efficacy is poor, highlighting the need for the development of new, safe, and effective drugs for the treatment of this cancer. OBJECTIVE: To investigate the effects of alantolactone (ALT) on the proliferative, migratory, invasive, and apoptotic ability of malignant melanoma cells and explore its potential anticancer mechanism. METHODS: Melanoma cells (A375 and B16) were treated with different concentrations (4, 6, 8, and 10 µmol/L) of ALT, with DMSO and no treatment serving as controls. The effects of the different concentrations of the drug on cell proliferation were assessed by crystal violet staining and CCK-8 assay. The effects on cell migration and invasion were detected by wound healing and Transwell assays, respectively. Flow cytometry was used to evaluate the effects of the drug on apoptosis and the cell cycle. ALT target genes in melanoma were screened using network pharmacology. Western blotting was used to measure the expression levels of the proliferation-related protein PCNA; the apoptosisrelated proteins Bax, Bcl-2, and caspase-3; the invasion and metastasis-related proteins MMP-2, MMP-7, MMP-9, vimentin, E-cadherin, and N-cadherin; and the canonical Wnt signaling pathway-related proteins ß-catenin, c-Myc, and p-GSK3ß. In addition, an l model of melanoma was established by the subcutaneous injection of A375 melanoma cells into nude mice, following which the effects of ALT treatment on malignant melanoma were determined in vivo. RESULTS: Compared with the controls, the proliferative, migratory, and invasive capacity of ALT-treated melanoma cells was significantly inhibited, whereas apoptosis was enhanced (P<0.01), showing effects that were exerted in a dose-dependent manner. The expression levels of the pro-apoptotic proteins Bax and caspase-3, as well as those of the interstitial marker E-cadherin, were upregulated in melanoma cells irrespective of the ALT concentration (P<0.05). In contrast, the expression levels of the anti-apoptotic protein Bcl-2, the proliferation-related protein PCNA, and the invasion and metastasis-related proteins MMP-2, MMP-7, MMP-9, N-cadherin, and vimentin were downregulated (P<0.05). The network pharmacology results indicated that GSK3ß may be a key ALT target in melanoma. Meanwhile, western blotting assays showed that ALT treatment markedly suppressed the expression of ß-catenin as well as that of its downstream effector c-Myc, and could also inhibit GSK3ß phosphorylation. CONCLUSION: ALT can effectively inhibit the culture viability, migration, and invasion of A375 and B16 melanoma cells while also promoting their apoptosis. ALT may exert its anti-melanoma effects by inhibiting the Wnt/ß-catenin signaling pathway. Combined, our data indicate that ALT has the potential as an effective and safe therapeutic drug for the treatment of melanoma.

30% supramolecular salicylic acid peels effectively treats acne vulgaris and reduces facial sebum.

BACKGROUND: Acne is a chronic inflammatory skin disease with high incidence and recurrence. AIM: To study the efficacy of 30% supramolecular salicylic acid (SSA) in the treatment of acne, especially its effect on facial sebum secretion and the skin barrier. METHODS: Chemical peeling treatment with SSA using self-contrast was performed every 2 weeks for a total of four treatments in 25 patients. VISIA photographs and skin parameter measurements were recorded at every treatment, with a 2-week follow-up after the last treatment. We performed skin biopsy and immunohistochemical staining to detect sterol response element-binding proteins (SREBPs), fatty acid synthase (FAS), and cyclooxygenase 2 (COX2), which are important factors involved in the regulation of sebum metabolism. RESULTS: The global acne-grading system (GAGS) score of patients with acne decreased with 30% SSA treatment. The sebum level in the nose (p < 0.001), chin (p < 0.001), left cheek (p < 0.05), and right cheek (p < 0.05) improved significantly with increasing number of treatments. The T-zone sebum level (p < 0.001) improved more than the U-zone (p < 0.01). The VISIA index porphyrin score also reduced (p < 0.001). Skin hydration (p < 0.001), transepidermal water loss (TEWL) (p < 0.05), and pH value (p < 0.01)-reflecting the skin barrier-were also improved. Immunohistochemistry showed decreased expression of SREBPs, FAS, and COX2. CONCLUSION: Peels with 30%SSA effectively treated acne and reduced facial sebum secretion without damaging the skin barrier. Reduction of sebum showed cumulative effect, which suggests that multiple 30%SSA chemical peels are beneficial to acne patients.

Alcohol consumption and the risk of rosacea: A systematic review and meta-analysis.

BACKGROUND: Rosacea is a chronic inflammatory skin disease that affects people's life quality. It has been found to be related to many detrimental factors including ultraviolet exposure. However, the association between alcohol consumption and rosacea has long been debated. AIMS: To elucidate this association, we conducted a systematic review and meta-analysis. METHODS: We performed a systematic search of the literature published before February 16, 2021 on PubMed, Embase, and the Cochrane database and used a meta-analytic approach to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). RESULTS: Finally, 14 eligible studies were identified, and alcohol consumption was not found to be a risk factor for rosacea. However, in subgroup analysis, alcohol consumption increased the risk of phymatous rosacea (PhR) and the pooled OR was 4.17 (95% CI = 1.76-9.91). CONCLUSION: Overall, our study showed that alcohol consumption was a risk factor in phymatous rosacea (PhR). More studies of rosacea investigating sex distribution, alcohol intake levels, and types of alcoholic beverages consumed are needed in the future.

Hey1 promotes migration and invasion of melanoma cells via GRB2/PI3K/AKT signaling cascade.

Increasing evidence indicates that Notch signaling regulates multiple intracellular biological processes in malignant melanoma. Whereas how Notch signaling is transduced to influence melanoma cell behaviors remains largely elusive. Here we show that the Notch signaling downstream target Hey1 promotes migration and invasion of melanoma cells via the GRB2/PI3K/AKT pathway. First, bioinformatics tools, immunohistochemistry, and Western blotting analysis showed that the expression of Hey1 is increased in melanoma. Then, both in vivo and in vitro experiments showed that Hey1 promotes the malignant behaviour of the melanoma cells. High-throughput RNA-sequencing analysis revealed that inhibition of Hey1 results in decreased GRB2 expression in melanoma cells. Last, functional experiments confirmed that Hey1 positively regulates GRB2/PI3K/AKT pathway to influence migration and invasion of melanoma cells. In summary, our results suggest that Hey1 promotes the invasion and metastasis of melanoma cells by regulating GRB2/PI3K/AKT pathway. Our study provides potential therapeutics in tumor biology.

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/ß-catenin signaling.

Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Hence, we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo. In this study, we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo. Compared with that in normal epidermal melanocytes (PIG1), the expression of SFRP5 was increased in vitiligo melanocytes (PIG3V). To investigate the effect of SFRP5 on melanin synthesis, PIG1 cells were infected with recombinant SFRP5 adenovirus (AdSFRP5), and PIG3V cells were infected with recombinant siSFRP5 adenovirus (AdsiSFRP5). The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor (MITF) and its target proteins via suppression of the Wnt/ß-catenin signaling pathway. Accordingly, SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V cells. Moreover, SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor (TCF/LEF) in PIG1 cells. Furthermore, this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the ß-catenin agonist, SKL2001. The inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse model. Hence, our results indicate that SFRP5 can inhibit melanogenesis in melanocytes. Additionally, our findings showed that SFRP5 plays a vital role in the development of vitiligo, and thus may serve as a potential therapeutic target for vitiligo.

Transcriptome and Differential Methylation Integration Analysis Identified Important Differential Methylation Annotation Genes and Functional Epigenetic Modules Related to Vitiligo.

Vitiligo is an pigmentation disorder caused by a variety of pathogenic factors; its main pathophysiological conditions include oxidative stress, immune activation, and genetic background. Additionally, DNA methylation is often associated with the pathogenesis of vitiligo; however, the underlying mechanism remains unknown. In the present study, we used the Human Methylation 850K BeadChip platform to detect DNA methylation changes in the vitiligo melanocytes. We then integrated the results with the transcriptome data of vitiligo melanocytes and lesions to analyse the correlation between differentially methylated levels and differentially expressed genes. The results showed that there was a significant negative correlation between methylation levels and differentially expressed genes. Subsequently, we enriched GO and KEGG based on methylated differentially expressed genes (MDEGs) using R package ClusterProfiler, and the results were closely related to the pathogenesis of vitiligo. In addition, we also constructed a PPI network of MDEGs and excavated three important functional epigenetic modules, involving a total of 12 (BCL2L1, CDK1, ECT2, HELLS, HSP90AA1, KIF23, MC1R, MLANA, PBK, PTGS2, SOX10, and TYRP1) genes. These genes affect melanocyte melanogenesis, cellular oxidative stress and other important biological processes. Our comprehensive analysis results support the significant contribution of the status of DNA methylation modification to vitiligo, which will help us to better understand the molecular mechanism of vitiligo and explore new therapeutic strategies.