RESUMEN
Refractory diabetic wounds are associated with high incidence, mortality, and recurrence rates and are a devastating and rapidly growing clinical problem. However, treating these wounds is difficult owing to uncontrolled inflammatory microenvironments and defective angiogenesis in the affected areas, with no established effective treatment to the best of our knowledge. Herein, we optimized a dual functional therapeutic agent based on the assembly of LL-37 peptides and diblock copolymer poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS). The incorporation of PEG-PPS enabled responsive or controlled LL-37 peptide release in the presence of reactive oxygen species (ROS). LL-37@PEG-PPS nanomicelles not only scavenged excessive ROS to improve the microenvironment for angiogenesis but also released LL-37 peptides and protected them from degradation, thereby robustly increasing angiogenesis. Diabetic wounds treated with LL-37@PEG-PPS exhibited accelerated and high-quality wound healing in vivo. This study shows that LL-37@PEG-PPS can restore beneficial angiogenesis in the wound microenvironment by continuously providing angiogenesis-promoting signals. Thus, it may be a promising drug for improving chronic refractory wound healing.
RESUMEN
Integrin-beta 1 (ITGB1) is aberrantly overexpressed or downregulated in solid cancers; however, its prognostic value remains controversial. Therefore, we conducted a meta-analysis to explore whether ITGB1 expression is correlated with overall survival (OS) and the clinicopathological characteristics of patients with solid cancers. We systematically searched the PubMed, Embase, and Web of Science databases for eligible studies published up to June 1, 2017. In total, 22 studies involving 3,666 patients were included. A sensitivity analysis was performed to assess the validity and reliability of the pooled OS. Among the 22 studies, 7 focused on lung cancer, 3 focused on colorectal cancer, 6 focused on breast cancer, 3 involved melanoma, and 3 involved pancreatic cancer. The pooled results showed that high ITGB1 expression was significantly associated with worse OS in lung cancer (pooled hazard ratio [HR]=1.78, 95% CI: 1.19-2.65, p<0.05) and breast cancer (pooled HR=1.88, 95% CI: 1.46-2.42, p<0.01). In addition, a significant association was observed between high ITGB1 expression and disease-free survival in breast cancer (pooled HR=1.63, 95% CI: 1.17-2.25, p<0.001) and pancreatic cancer (pooled HR=2.49, 95% CI: 1.35-4.61, p<0.001). However, high ITGB1 expression was not related to OS in colorectal cancer, pancreatic cancer, or melanoma. The pooled HRs used to evaluate the prognostic value of increased ITGB1 expression in lung cancer, breast cancer, and pancreatic cancer were not significantly altered, which indicates that the pooled results were robust. The results of this study indicate that the prognostic value of decreased ITGB1 expression varies among solid cancers.
RESUMEN
OBJECTIVE: To investigate the inhibitory effect of the Hedgehog signal pathway blocker (cyclopamine) on DU145 cells. METHODS: We interfered DU145 cells with cyclopamine at the concentrations of 1, 10, 50 and 100 micromol/L and detected its inhibitory effect on the cells by MTT colorimetry assay at 24, 48 and 72 hours, as well as its effect on the cell cycle by flow cytometry. We also determined the difference in the mRNA expression of cyclin E between the experimental and control groups by RT-PCR at 48 hours after 50 +/- micromol/L cyclopamine intervention. RESULTS: Cyclopamine inhibited the DU145 cells in a time- and dose-dependent manner, with inhibition rates of 7.42, 12.70 and 59.15% in the 10, 50 and 100 micromol/L groups respectively at 24 hours, significantly different from that of the blank control group (P < 0.05). It markedly suppressed the proliferation of the DU145 cells at >10 micromol/L at 24 hours. Flow cytometry showed an obviously increased proportion of stage G1 cells at the concentration of >10 micromol/L after 48-hour intervention, with statistically significant differences from the G1 cell proportions in the control, 10 micromol/L and 50 micromol/ L groups, which were (52.17 +/- 2.21)%, (60.13 +/- 2.75)% and (74.30 +/- 3.52)% respectively (P < 0.01). The apoptotic peak was elevated with the increased concentration of cyclopamine. The cyclin E mRNA expression of the DU145 cells was decreased by 61.90% at 48 hours after 50 micromol/L cyclopamine intervention as compared with the blank control group (P < 0.01). CONCLUSION: Cyclopamine can inhibit the proliferation of DU145 cells, and the mechanism may be related with its effect of down-regulating the cyclin E mRNA expression of DU145 cells and blocking them in stage G1. Cyclopamine can also induce the apoptosis of DU145 cells.
