Recent growing evidence suggested that particulate matter 2.5 (PM2.5) has strong toxic effects on skin systems. However, the possible effects and the mechanisms of PM2.5 on vitiligo remain poorly understood. Therefore, the present study aimed to further investigate the effects and possible mechanisms of PM2.5 on vitiligo. Human keratinocytes (HaCaT cells) and human melanocytes (PIG1 cells and PIG3V cells) were exposed to PM2.5 (0-200 µg/ml) for 24 h. The cell viability of the three cell lines was measured by a Cell Counting Kit-8 assay. The secretions of stem cell factor (SCF) and basic fibroblast growth factor (bFGF) in HaCaT cells were evaluated by ELISA. The melanin contents, cellular tyrosinase activity, apoptosis, cell migration, malondialdehyde (MDA) contents, superoxide dismutase (SOD) levels, glutathione peroxidase (GSH-Px) levels and related protein expressions in PIG1 cells and PIG3V cells were evaluated by a NaOH assay, DOPA assay, Annexin V-FITC/Propidium Iodide staining, MDA assay, SOD assay, GSH-Px assay and western blotting, respectively. It was demonstrated that PM2.5 exposure inhibited cell viability of all three cell lines (HaCaT, PIG1 and PIG3V cells). PM2.5 exposure attenuated the secretions of SCF and bFGF in HaCaT cells. Moreover, PM2.5 exposure attenuated the activation of tyrosinase and melanogenesis, inhibited cell migration, and induced apoptosis and oxidative stress injury in PIG1 cells and PIG3V cells. In addition, PM2.5 exposure caused upregulated cytosolic cytochrome C and activated caspase-3 in PIG1 cells and PIG3V cells. Furthermore, PM2.5 exposure activated the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 signaling pathway. The present results suggested that PM2.5 exposure could inhibit the secretions of SCF and bFGF in keratinocytes, and cause oxidative stress injury and melanin metabolic disorder in melanocytes. Therefore, PM2.5 could be a new risk factor for vitiligo. PM2.5 induces apoptosis, oxidative stress injury and melanin metabolic disorder in human melanocytes

Tumor suppressor gene O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been reported in melanoma. However, the clinical and prognostic significance of MGMT promoter methylation in patients with melanoma remained to be determined. A systematic search was performed to identify eligible papers published. The overall odds ratios (ORs) or hazard ratios and their 95% confidence intervals were calculated. Final 12 eligible publications involving Caucasian population were performed in this study, including 1,071 metastatic melanoma patients, 154 primary melanoma patients, and 211 normal controls. MGMT promoter methylation was significantly higher in primary or metastatic melanoma than in normal controls (p<0.05). No difference of MGMT promoter methylation was found in primary and metastatic melanoma (p=0.432). When metastatic melanoma was compared to normal controls, subgroup analysis showed the correlation between MGMT promoter methylation and different sample materials (tissue: OR=7.01, p<0.001 and blood: OR=12.04, p=0.005). MGMT promoter methylation was not associated with response to drug therapy and the prognosis in overall survival and progression-free survival for multivariate analysis. Our results show that MGMT promoter methylation may be correlated with the increased risk of primary or metastatic melanoma. Based on blood samples, MGMT promoter methylation may become a noninvasive biomarker for the detection of metastatic melanoma. Further additional clinical studies are necessary.

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Background: Omalizumab is a humanized anti-immunoglobulin (Ig)E monoclonal antibody that is effective for some patients with chronic spontaneous urticaria (CSU) who do not respond to antihistamines. However, the mechanism by which omalizumab improves urticaria remains obscure. Gut microbiome plays a role in the pathogenesis of allergies. Here, we aimed to investigate differences in gut microbiome of adolescent CSU patients before and after omalizumab treatment, which has not been reported until date. Methods: Ten adolescent patients with CSU were given 300 mg omalizumab subcutaneously in three treatment sessions at 4-week intervals. The personal and clinical factors of patients before and after treatment were collected. Urticaria Activity Score (UAS7) was applied to evaluate the efficacy of omalizumab treatment every 4 weeks during the follow-up period. Fecal samples were collected before treatment and at 12 weeks after the first treatment. Total DNA of the gut microbiota in all fecal samples were extracted. The 16S rRNA gene-targeted sequencing technology was used for the analysis of the diversity and distribution of gut microbiome, followed by bioinformatics analysis. Results: UAS7 scores decreased significantly after each omalizumab treatment sessions compared with the baseline (all P < 0.0001). The dominant bacteria in fecal samples before and after treatment were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level. Alpha diversity analysis showed no significant difference before and after omalizumab treatment (P > 0.05) whereas beta diversity analysis revealed significant difference in the bacterial abundance before and after omalizumab treatment (P < 0.01) in adolescent patients with CSU. The relative abundance of Alphaproteobacteria and Betaproteobacteria at the class level and Burkholderia, Rhodococcus, and Sphingomonas at the genus level decreased significantly after omalizumab treatment (linear discriminant analysis > 4, P < 0.05). The functional prediction results showed that the differences noted before and after treatment were mainly in the dioxin and xylene degradation pathways, which were more abundant in adolescent patients with CSU before omalizumab treatment.Conclusions: Omalizumab is effective in treating CSU and can reduce the abundance of Alphaproteobacteria and Betaproteobacteria, which may help improve the treatment outcomes of CSU in adolescent patients.