ABSTRACT
OBJECTIVE: To explore the mechanism of the action of the miR-576/ALK4 axis on the progression of prostate cancer (PCa). METHODS: PCa cells were transfected with miR-576 mimics/inhibitor, the proliferation and migration distance of the cells were detected by MTT and scratch wound healing assay, respectively. The targeted regulation effect of miR-576 on ALK4 was verified by dual-luciferase reporter assay. The effects of miR-576 on the mRNA and protein expressions and phosphorylation levels of the ALK4 and JAK/STAT signaling pathway factors JAK2 and STAT3 were determined by qPCR and Western blot, respectively. The C4-2 cells were co-treated with sh-ALK4 and Ruxolitinib for measurement of the proliferation and migration of the PCa cells. RESULTS: Bioinformatics analysis and binding site prediction showed that miR-576 was up-regulated in the PCa cells, and dual-luciferase reporter assay revealed its targeted regulation effect on ALK4 and its impact on the phosphorylation levels of JAK2 and STAT3. Overexpressed miR-576 promoted while knocked-down miR-576 inhibited the proliferation and migration of the PCa cells. sh-ALK4 increased the proliferation and migration of the cells, while Ruxolitinib suppressed the promoting effect of sh-ALK4. CONCLUSION: The expression of miR-576 is up-regulated in PCa, inhibits the expression of ALK4, regulates the activity of the JAK and STAT signaling pathways, and promotes the proliferation and migration of PCa cells.
Subject(s)
MicroRNAs , Prostatic Neoplasms , Male , Humans , MicroRNAs/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation , Signal Transduction , Prostatic Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Cell Movement/geneticsABSTRACT
UNLABELLED: Aim and Backgrounds: The accurate diagnosis of lung carcinoma patients with bone metastases is crucial for therapy and the prevention of complications. We performed a systematic review and meta-analysis to evaluate the diagnostic value of serum bone-specific alkaline phosphatase (BALP) in lung carcinoma patients with bone metastases. METHODS: Such databases as PubMed, Embase, Cochrane Library, Web of Science, Ovid, BioMed Central, Biosis previews and four Chinese databases (Chinese Biomedical Literature Database-disc (CBM), Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP) and Wan Fang DATA) were retrieved on computer, and the relevant journals were also manually searched to collect the trials on BALP in diagnosis of lung carcinoma patients with bone metastases. The meta-analysis was conducted by using Meta-Disc 1.4 software. RESULTS: A total of 8 studies were included, and there were 848 lung carcinoma patients diagnosed by gold standard, patients were divided into two groups: 419 cases with bone metastases and 429 cases without bone metastases. The meta-analysis showed that, the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) was 0.48 [95% CI (0.43 to 0.53)], 0.86 [95% CI (0.82 to 0.89)], 3.14 [95% CI (2.47 to 3.99)], 0.62 [95% CI (0.56 to 0.68)], 6.66 [95% CI (4.62 to 9.60)] respectively. And the AUC of SROC was 0.78, (Q*=0.72). CONCLUSION: BALP has greater diagnostic value in detecting lung carcinoma patients with bone metastases. However, further large scale studies are required to confirm the predictive value.
ABSTRACT
OBJECTIVE: To examine the feasibility of autologous uncultured bone-marrow-derived mononuclear cells (BM-MNCs) in combination with microfracture in a full-thickness articular cartilage defect model so as to provide experimental rationales for clinical applications. METHODS: A total of 40 rabbits were divided randomly into groups A, B, C and D (n = 10 each). In groups A and C, 5 ml marrow samples were harvested from left femur and then autologous BM-MNCs isolated. The full-thickness articular cartilage defects were made on femoral intercondylar fossa in right knees of rabbits. Group A: micro-fracture was made on cartilage defect and then autologous uncultured BM-MNCs-autologous fibrin gel complex implanted; Group B:the same micro-fracture was made on cartilage defect and autologous fibrin gel implanted; Group C:the cartilage defect was implanted with autologous uncultured BM-MNCs-autologous fibrin gel complex; Group D:the cartilage defect was implanted with autologous fibrin gel. Five rabbits were sacrificed at Weeks 8 and 12 post-transplantation in each group. And the reparative tissue samples evaluated grossly, histologically and immunohistochemically were graded according to the gross and histological scales. RESULTS: The statistical analyses of histological gradings at Weeks 8 and 12 showed that group A was significantly better than groups B, C and D (P < 0.05), groups B and C were better than group D (P < 0.05) and each group at Week 12 was better than itself at Week 6 (P < 0.05). CONCLUSION: Both of micro-fracture and transplantation of uncultured autologous BM-MNCs plus autologous fiber gel can promote the repair of cartilage defects. The combined use of micro-fracture and autologous uncultured BM-MNCs promotes the regeneration of articular cartilage so that it may provide theoretical rationales for clinical applications.
