The correlation between the MYBL2/CDCA8 signaling pathway of malignant melanoma.

Objective: Investigating the effects of MYB proto-oncogene like 2 (MYBL2)-mediated regulation of Cell division cycle associated 8 (CDCA8) expression on the biological activity of cutaneous malignant melanoma cells. Methods: A375 cells with MYBL2 and CDCA8 overexpression and knockdown were evaluated using migration, invasion, and proliferation assays. Besides, cell apoptosis was quantified by flow cytometry. To investigate the tumorigenic effects of MYBL2 knockdown in vivo, A375 cells with MYBL2 knockdown were injected in BALB/C nude mice. Results: The levels of MYBL2 and CDCA8 gene expression were notably elevated in A375 cells in comparison to HaCat cells (P < 0.05). Downregulation of MYBL2 led to a notable reduction in the migratory and invasive capability of A375 cells in vitro (P < 0.001). On the contrary, overexpression of MYBL2 enhanced migration and invasion ability (P < 0.001). There existed a positive correlation between CDCA8 and MYBL2 gene and protein expression levels after overexpression or knockdown of MYBL2 (P < 0.001). In the in vivo tumorigenic study, the MYBL2 knockdown group displayed a substantial decrease in tumor volume (P < 0.01) and exhibited decreased CDCA8 expression in tumors in comparison to the control group. Conclusion: We arrived at such a conclusion that MYBL2 promoted the migration, invasion and proliferation ability of cutaneous malignant melanoma cells by targeted regulation of CDCA8 expression in this study.

Effect of 5-Aminolevulinic Acid Photodynamic Therapy with Transfer Factor Capsules in the Treatment of Multiple Plantar Warts.

Background: Plantar warts are a common cutaneous disease of the sole of the foot caused by human papillomavirus. Photodynamic therapy has gained increasing attention in the treatment of plantar warts. Objective: To investigate the effect of photodynamic therapy combined with transfer factor capsules in the treatment of multiple plantar warts. Methods: Sixty-one patients with multiple plantar warts who visited our outpatient department from September 2017 to August 2019 were randomly divided into two groups. Twenty-three patients received photodynamic therapy (treatment group) and thirty-eight received cryotherapy (control group). Both groups also received immune modulator transfer factor capsules. Skin lesion score, numeric rating scale- (NRS-) 10 score, recurrence rate, adverse reactions, and Dermatology Life Quality Index (DLQI) were analyzed in both groups. Results: The mean skin lesion score improved from 13.39 ± 3.88 before treatment to 1.48 ± 2.50 after the last treatment in the treatment group and from 12.47 ± 2.99 before treatment to 4.47 ± 3.67 after the last treatment in the control group. The success rate after 3 months of treatment was 86.96% in the treatment group and 39.47% in the control group. After 3 months of follow-up, the recurrence rate was significantly lower in the treatment group (20%) than in the control group (53.33%). The mean DLQI score at three months after treatment was significantly lower in the treatment group (3.61 ± 1.16) than in the control group (6.31 ± 2.59). Conclusion: Photodynamic therapy combined with immunomodulators significantly increased the cure rate and reduced the recurrence rate of multiple plantar warts compared with traditional cryotherapy combined with immunomodulators.

Differences in clinical characteristics and lesion proteomics between inflammatory linear verrucous epidermal nevus and local verrucous epidermal nevus.

BACKGROUND: Verrucous epidermal nevus (VEN) are keratinocytic epidermal nevus that appear at birth or in early childhood. They exhibit a range of manifestations, depending on the patient's age. VEN are rarely encountered in clinical practice, and the systemic and comprehensive clinical characteristics of VEN have not been well investigated. Furthermore, the association between tandem mass tag (TMT)-based quantitative proteomics and the VEN phenotype is still unclear. OBJECTIVES: This study investigated the differences in the clinical characteristics and lesion proteomics between inflammatory linear VEN (ILVEN) and local VEN. METHODS: This retrospective study enrolled 125 patients with histopathologically diagnosed VEN who presented to our hospital between 2019 and 2021. We collected the clinical data of all patients with VEN using a self-designed questionnaire. The expression of proteins in VEN lesions was analyzed using TMT proteomics technology. RESULTS: In total, there were 125 patients with VEN that were evaluated, including 67 (53.60%) patients with local VEN and 58 (46.40%) with ILVEN. No significant differences were found in sex, onset age, and lesion location between patients with local VEN and those with ILVEN (all P > 0.05). Significant differences were found in the onset site and pruritus scores between patients with ILVEN and those with local VEN (all P < 0.05). According to the TMT proteomics results, 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. The top 10 differentially expressed proteins between ILVEN and local VEN lesions were OGN, NT5C3A, ADD1, OLFML1, DHRS1, CALML5, SAMHD1, SFRP2, SPRR1B, and SERPINB13. The upregulated proteins are mainly involved in neutrophil activation, neutrophil-mediated immunity, and p53 signaling pathway (hsa04115). The downregulated proteins are mainly involved in cellular response to cytokine stimulus, cell adhesion, Th1 and Th2 cell differentiation. In total, based on the differentially expressed proteins between ILVEN and local VEN, five pathways that may be associated with the pathogenesis of inflammation, including CAMs (P = 0.006), Th1 and Th2 cell differentiation (P = 0.017), PPAR signaling pathway (P = 0.023), Th17 cell differentiation (P = 0.024), and p53 signaling pathway (P = 0.041). CONCLUSIONS: Clinical data of the patients revealed that ILVEN lesions presented with intense pruritus and inflammatory change. Differentially expressed proteins between ILVEN and local VEN are mainly involved in multiple inflammation related pathways associated with the pathogenesis mechanisms of pruritus. LIMITATIONS: The small sample size in clinical characteristic and proteomics study is one of the most significant limitations in our study. The inflammation associated proteins and signal pathways in the pathogenesis of pruritus in ILVEN is not explored. SIGNIFICANCE: In this study, we found the lesions of ILVEN patients presented with intense pruritus and inflammational change. A total of 89 proteins were up or downregulated with at least 1.3-fold (upregulated: 38, downregulated: 51; P < 0.05) in ILVEN lesions relative to VEN lesions. On the other hand, the etiology of itch in ILVEN mainly associated with inflammation, but the exact mechanisms was still unclear. We found the differentially expressed proteins between ILVEN and local VEN enriched five pathways that may be associated with the pathogenesis of inflammation and pruritus.

Overexpression of CDCA8 promotes the malignant progression of cutaneous melanoma and leads to poor prognosis.

Cutaneous melanoma is very aggressive and results in high mortality rates for cancer patients. Determining molecular targets is important for developing novel therapies for cutaneous melanoma. Cell division cycle associated 8 (CDCA8) is a putative oncogene that is upregulated in multiple types of cancer. The present study aimed to examine the role of CDCA8 in cutaneous melanoma, with a focus on the association of its expression to prognosis and metastasis. First, the mRNA expression of CDCA8 in cutaneous melanoma tissues was investigated using the ONCOMINE and Gene Expression Omnibus (GEO) databases. Furthermore, the relationship between the expression of CDCA8 and cutaneous melanoma patient survival was analyzed using a Kaplan­Meier plot and Log Rank test. In addition, the effects of CDCA8 on proliferation, migration and invasion of cutaneous melanoma cell lines were investigated using reverse transcription­quantitative polymerase chain reaction (RT­qPCR), Cell Counting kit­8, colony formation assay, wound healing and Matrigel assay. Finally, the expression levels of key proteins related to the Rho­associated coiled­coil­containing protein kinase (ROCK) signaling pathway were measured by western blot assay. The results demonstrated that CDCA8 was overexpressed in cutaneous melanoma tissues and cells lines compared with normal tissues, and high expression of CDCA8 was significantly associated with poorer prognosis in patients with cutaneous melanoma. In in vitro experiments, CDCA8 knockdown inhibited A375 and MV3 cell proliferation, migration and invasion. In addition, CDCA8 knockdown reduced the phosphorylation levels of ROCK1 and myosin light chain, two downstream effector proteins of the ROCK pathway. In summary, the present findings suggested that CDCA8 may be a promising therapeutic target for the treatment of cutaneous melanoma.

[Detection of ADAR1 gene mutation in a family with dyschromatosis symmetrica hereditaria].

OBJECTIVE: To detect mutation of ADAR1 gene in a family affected with dyschromatosis symmetrica hereditaria. METHODS: Clinical data and blood samples of the family were collected. Potential mutation of the ADAR1 gene were scanned in 3 patients and 3 unaffected members by PCR amplification and direct sequencing. The coding sequences of the ADAR1 were also screened in 50 normal controls. RESULTS: A frameshift mutation (c.2252insG) of the ADAR1 gene was identified in all of the 3 patients. The same mutation was not found in the 3 unaffected members and 50 normal cases. CONCLUSION: The frameshift mutation of ADAR1 gene (c.2252insG) is probably responsible for the disease in this family.