RESUMO
Cancer prevention using natural micronutrition on epigenetic mechanisms primarily revolves around plant extracts. However, the role of macronutrition, including animal peptides, on epigenetic modification in cancer has been elusive. In traditional Chinese medicine, the soft-shelled turtle has a long-history of being a functional food that strengthens immunity through unknown mechanisms. The present study aimed to investigate the impact of soft-shelled turtle peptide on microRNA (miRNA) expression in gastric cancer (GC) cells and to analyze the potential anticancer mechanisms for GC. Affymetrix GeneChip miRNA 3.0 Array and quantitative polymerase chain reaction were used to detect the miRNA expression profile in human GC AGS cells treated with the soft-shelled turtle peptide. The results demonstrated that 101 miRNAs (49 upregulated miRNAs and 52 downregulated miRNAs) were significantly differentially expressed in the AGS cells following soft-shelled turtle peptide treatment. Several tumor suppressor miRNAs were upregulated markedly, including miRNA-375, let-7d, miRNA-429, miRNA-148a/148b and miRNA-34a. Pathway analysis indicated that soft-shelled turtle peptide may function with anticancer properties through the Hippo signaling pathway and the forkhead box O signaling pathway. Therefore, these results demonstrated that soft-shelled turtle peptide has the capacity to influence cancer-related pathways through the regulation of miRNA expression in GC cells.
RESUMO
BACKGROUND: Persistent postsurgical pain, as an important clinical problem, seriously affects the quality of life in patients. However, the mechanism underlying persistent postsurgical pain remains largely unclear. The present study aims to elucidate the involvement of toll-like receptor 4 (TLR4) and its interaction with p38 and interleukin [IL]-1ß signaling in dorsal root ganglion (DRG) in the persistent postsurgical pain. METHODS: Skin and muscle incision and retraction (SMIR) surgery-induced paw withdrawal threshold (PWT) change was determined by applying mechanical stimuli to the plantar surface of the hind paw using von Frey hairs. The PE-10 catheter intrathecal placement was used to deliver LPS-RS, interleukin-1 receptor antagonist, or SB203580. Western blot analysis was performed to measure the expression of the TLR4, mitogen-activated protein kinases family, and IL-1ß in ipsilateral L3 and L4 DRG. Immunofluorescence staining was performed to further investigate the cell type of TLR4 expression. All data were expressed as means ± standard error of the mean and analyzed using SPSS 13.0. RESULTS: The results showed that the SMIR surgery, a rat model of persistent postoperative pain, decreased the ipsilateral 50% PWT, and the decrease lasted for at least 20 d. The expression of TLR4 and phosphorylation of p38 were upregulated in ipsilateral L3 and L4 DRG neurons after SMIR surgery. Pretreatment with LPS-RS, an established TLR4 antagonist, prevented p38 activation and attenuated mechanical allodynia induced by SMIR surgery. In addition, the expression of IL-1ß was significantly increased after SMIR surgery. Blocking IL-1ß by interleukin-1 receptor antagonist significantly improved the decreased PWT evoked by SMIR. Moreover, inhibition of TLR4 or p38 pathway prevented the IL-1ß upregulation and mechanical allodynia induced by SMIR. CONCLUSIONS: These findings suggest that the activation of p38 and IL-1ß signaling pathway via TLR4 mediate mechanical allodynia after SMIR surgery.
