ABSTRACT
Objective:To investigate the intervention effect of ventricular zone expressed PH domain-containing 1 (VEPH1) on epithelial mesenchymal transition (EMT) and proliferation of human cutaneous melanoma (CM) cells based onthe transforming growth factor-β (TGF-β) signaling pathway.Methods:The melanoma cells were cultured in vitro. After transfecting the melanoma cells with overexpression or interference plasmids of VEPH1 or TGF-β overexpression plasmids, or treating the cells with SB-431542 (TGF-β pathway inhibitor), we detected the expression of genes and proteins relevant to VEPH1, TGF-β, and EMT by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot to observe the effect of these proteins on CM cell proliferation. Results:qRT-PCR results showed that the expression of VEPH1 in melanoma cells (B16-BL6, B16 and A375 cells) was significantly lower than that in HaCaT cells, and the lowest expression was found in A375 cells, so A375 cells were selected for follow-up experiments. After transfection with VEPH1 overexpression plasmid or SB-431542, the mRNA and protein expression of E-cadherin in A375 cells were significantly increased, the mRNA and protein expressions of TGF-β, Smad4, N-cadherin and vimentin were significantly decreased, and the cell proliferation was significantly decreased ( P<0.05). Compared with the VEPH1 vector group, the expression of TGF-β, Smad4 and N-cadherin in the VEPH1 vector+ SB-431542 group was significantly reduced ( P<0.05); the expression of E-cadherin was increased, and the cell proliferation was also significantly decreased ( P<0.05). The expression of TGF-β, Smad4, N-cadherin and vimentin were increased after co-transfection with VEPH1 vector, while the expression of E-cadherin was decreased, and the cell proliferation was also enhanced ( P<0.05). The expression of VEPH1 in A375 cells was significantly decreased after transfection with si-VEPH1 plasmid, while that in SB-431542 and TGF-β vector group was not significantly decreased. Conclusions:VEPH1 can inhibit human CM cells by the intervention on TGF-β signaling pathway. This study reveals the potential of VEPH1 as a diagnostic, prognostic and therapeutic target for CM.
ABSTRACT
Tumor microenvironments (TMEs) are closely related to tumor resistance. TMEs are divided into cellular components and acellular components. The cellular components include tumor-associated macrophages, tumor-associated fibroblasts, mesenchymal stem cells, etc., which can enhance tumor resistance through recruitment and secretion of a variety of protective cytokines; acellular components such as extracellular matrix, hypoxia and acidification, etc., can mediate drug resistance by constructing physical barriers, affecting tumor cell growth and metabolism. Studying the mechanisms of TME-mediated drug resistance and reshaping TMEs can provide new strategies for anti-tumor therapy.
ABSTRACT
Objective:To test the reliability and validity of the Early Symptom Measurement of Post-Stroke Depression-Short Form (ESMPSD-SF).Methods:Totally 325 patients with early stage stroke were investigated by the demographic questionnaire and the Early Symptom Measurement of Post-Stroke Depression-Short Form. Exploratory factors, confirmatory factor analysis and reliability analysis were used to establish the reliability and validity of the scale.Results:Exploratory factor analysis extracted four factors: "low", "guilt", "emotional" and "wakefulness", which explained 74.228% of the total variation of depression. All the model fit indexes of confirmatory factor analysis and the standardized factor loadings of each item were up to standard, and the variances explained by each item were within acceptable range. The internal consistency reliability of the total scale was 0.866, the internal consistency of the domains ranged from 0.649 to 0.882, the corrected item-total correlation coefficient ranged from 0.401 to 0.676, and the item-subscale correlation coefficient ranged from 0.647 to 0.923.Conclusions:ESMPSD-SF demonstrated good reliability and validity and can be used to screen depressive symptoms in patients with early stage stroke.