Genome-wide DNA methylation of lesional and peri-lesional skin in vitiligo: a comparative and integrated analysis of multi-omics in Chinese population.

Several studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investigated DNA methylation levels in six lesional skin, six peri-lesional skin, and eight healthy skin samples using an Illumina 850 K methylation chip. We then integrated DNA methylation data with transcriptome data to identify differentially methylated and expressed genes (DMEGs) and analyzed their functional enrichment. Subsequently, we compared the methylation and transcriptome characteristics of all skin samples, and the related genes were further studied using scRNA-seq data. Finally, validation was performed using an external dataset. We observed more DNA hypomethylated sites in patients with vitiligo. Further integrated analysis identified 264 DMEGs that were mainly functionally enriched in cell division, pigmentation, circadian rhythm, fatty acid metabolism, peroxidase activity, synapse regulation, and extracellular matrix. In addition, in the peri-lesional skin, we found that methylation levels of 102 DMEGs differed prior to changes in their transcription levels and identified 16 key pre-DMEGs (ANLN, CDCA3, CENPA, DEPDC1, ECT2, DEPDC1B, HMMR, KIF18A, KIF18B, TTK, KIF23, DCT, EDNRB, MITF, OCA2, and TYRP1). Single-cell RNA analysis showed that these genes were associated with cycling keratinocytes and melanocytes. Further analysis of cellular communication indicated the involvement of the extracellular matrix. The expression of related genes was verified using an external dataset. To the best of our knowledge, this is the first study to report a comprehensive DNA methylation profile of clinical vitiligo and peri-lesional skin. These findings would contribute to future research on the pathogenesis of vitiligo and potential therapeutic strategies.

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.

Hematological parameters in patients with acnes.

OBJECTIVE: To compare complete blood count (CBC) parameters and inflammatory factors in the patients with different grade of acne vulgaris and healthy controls. METHODS: A total of 20 patients were enrolled in this study. Patients were divided into mild group and moderate-to-severe group based on the acne severity, and compared to controls. Inflammatory factors (TNF-α, IL-6, IL-8, and IL1-α) detected by ELISA and complete blood count parameters (MPV, NLR, dNLR, PLR, LMR, and SII) obtained by routine blood tests were compared among the three group. RESULTS: All CBC parameters were not significantly elevated in patients with acne compared to healthy controls. However, the present studies have found that the inflammatory factors in acne patients were significantly elevated relative to healthy controls, and increase with the acne grade. CONCLUSIONS: Inflammatory factors are convenient parameters to show inflammatory response to acne vulgaris, and may be a new clinical method for judging the acne grades of objectively. Considering the use of antibiotic, we believe that this metric worth further study.

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.

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.

Efficacy of topical steroids in preventing radiation dermatitis: A systematic review and meta-analysis.

To evaluate the relative efficacy of topical steroids in preventing radiation dermatitis (RD). Multiple databases including Medline, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), China Biological Medicine (SinoMed), and Wanfang Database were searched for randomized controlled trials (RCTs) of RD prevention in patients with cancer from inception to November 26, 2021, followed by an update on June 1, 2021. Six RCTs evaluating the efficacy of topical steroids in preventing RD in a total of 661 patients with cancer were included. RD incidence was lower with topical steroids compared with placebo at week 3 (relative risk [RR] = 0.68, 95% confidence interval [CI]: 0.31-1.50) and at radiation therapy (RT) completion (RR = 0.97, 95% CI: 0.93-1.00). Topical steroids demonstrated a less risk of developing dermatitis of Radiation Therapy Oncology Group (RTOG) grades 2 and 3 at the completion of RT (RR = 0.66, 95% CI: 0.55-0.80 and RR = 0.54, 95% CI: 0.38-0.77, respectively). However, topical steroids did not reduce RTOG grades 1 and 2 dermatitis at week 3(RR = 0.73, 95% CI: 0.45-1.14 and RR = 0.66, 95% CI: 0.27-1.60, respectively). Notably, the use of topical steroids did not decrease RD incidence when patients received combined chemotherapy (RR = 0.60, 95% CI: 0.42-0.86), and an obvious reduction in the incidence of RD at RT completion was found when patients used the topical steroids twice-daily (RR = 0.66, 95% CI: 0.47-0.93, P = 0.02). Topical steroids reduced RD incidence in patients receiving RT. Thus, twice-daily topical steroids may be recommended for patients at the beginning of RT.

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.

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.

Zinc finger and BTB domain-containing 7C (ZBTB7C) expression as an independent prognostic factor for colorectal cancer and its relevant molecular mechanisms.

Currently, colorectal cancer (CRC) predictions are based on an early diagnosis and the tumor-node-metastasis (TNM) stage, but the outcomes of patients with the same cancer type are difficult to predict. Novel molecular tests for the early diagnosis and stratification of CRC patients must be devised. After our initial bioinformatics screen, we examined zinc finger and BTB domain-containing 7C (ZBTB7C). To date, few studies have investigated ZBTB7C in CRC, necessitating further analyses of its expression and regulatory mechanism in CRC. ZBTB7C mRNA and protein expression was detected in CRC and corresponding non-CRC tissues. We evaluated the relationship between clinical prognosis and ZBTB7C protein levels using Cox regression analysis and Kaplan-Meier curves. A receiver operating characteristic (ROC) curve was generated to verify the diagnostic performance of ZBTB7C levels in CRC. Several bioinformatics techniques were applied to analyze the potential molecular mechanism of ZBTB7C. Low mRNA and protein levels of ZBTB7C were detected in tumor tissues from CRC patients. The survival curve predicted a poor prognosis for CRC patients exhibiting low ZBTB7C expression (P=0.001). According to the univariate Cox regression analysis, older age, a high TNM stage and low ZBTB7C expression were responsible for poor outcomes in CRC patients. The multivariate analysis further revealed ZBTB7C as an independent prognostic factor for CRC (P=0.015). The area under the curve of ZBTB7C expression for CRC diagnosis was 0.970 (95% confidence interval, 0.9447-0.9946; P < 0.0001). According to in silico analyses, genes coexpressed with ZBTB7C are associated mainly with the Ras and Wnt signaling pathways. Overall, ZBTB7C is downregulated in CRC and represents an early diagnostic marker and independent prognostic factor for CRC. ZBTB7C may be functionally mediated by different pathways or targeting miRNAs.

SFRP5 inhibits the migration and invasion of melanoma cells through Wnt signaling pathway.

BACKGROUND: Secreted frizzled-related protein 5 (SFRP5) plays a key role in the development and progression of multiple tumors. However, the role and underlying mechanisms of SFRP5 in melanoma cells remain unknown. MATERIALS AND METHODS: We used immunohistochemistry and Western blot analysis to detect the expression of SFRP5 in melanoma tissues and melanoma cells, respectively. Furthermore, both in vitro and in vivo assays were used to determine the effect of SFRP5 on malignant behavior in melanoma cells. RESULTS: We found that SFRP5 was markedly downregulated in melanoma tissues and cell lines. The SFRP5 overexpression exhibited no effect on the proliferation and apoptosis of melanoma cells but markedly suppressed the migration and invasion of melanoma cells in vitro. Regarding mechanisms, the SFRP5 overexpression inhibited the migration and invasion of melanoma cells by suppressing the epithelial-mesenchymal transition process and decreasing the matrix metalloproteinase-2/9 expression through the Wnt signaling pathway. Finally, in a xenograft animal model, we illustrated that the SFRP5 overexpression suppressed the tumor growth by decreasing angiogenesis and declined lung metastasis. CONCLUSION: This study suggests that SFRP5 expression could be potentially useful in the invasion and metastasis of melanoma and serve as a putative promising target for human melanoma therapy.