RESUMO
Tumor is one of the important factors affecting human life and health in today's world, and scientists have studied it extensively and deeply, among which autophagy and JAK/STAT3 signaling pathway are two important research directions. The JAK/STAT3 axis is a classical intracellular signaling pathway that assumes a key role in the regulation of cell proliferation, apoptosis, and vascular neogenesis, and its abnormal cell signaling and regulation are closely related to the occurrence and development of tumors. Therefore, the JAK/STAT3 pathway in tumor cells and various stromal cells in their microenvironment is often considered as an effective target for tumor therapy. Autophagy is a process that degrades cytoplasmic proteins and organelles through the lysosomal pathway. It is a fundamental metabolic mechanism for intracellular degradation. The mechanism of action of autophagy is complex and may play different roles at various stages of tumor development. Altered STAT3 expression has been found to be accompanied by the abnormal autophagy activity in many oncological studies, and the two may play a synergistic or antagonistic role in promoting or inhibiting the occurrence and development of tumors. This article reviews the recent advances in autophagy and its interaction with JAK/STAT3 signaling pathway in the pathogenesis, prevention, diagnosis, and treatment of tumors.
RESUMO
BACKGROUND: This study aimed to investigate immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in pathogenesis of chronic osteomyelitis (COM). METHODS: Sprague-Dawley (SD) rats were injected with Staphylococcus aureus to establish COM model. 4 weeks later, the lesioned bones were collected and subjected to HE staining for examination of inflammatory infiltration. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IL-2 expression in peripheral blood; flow cytometry was performed to detect CD25+CD4+Foxp3 Treg cells in peripheral blood. The mRNA expression of Foxp3 and CTLA-4 was detected by RT-PCR and the protein expression of STAT5 and p-STAT5 was detected by Western Blotting in CD25+CD4+Foxp3 Treg cells. RESULTS: In COM group, the periosteal thickening was observed in femur, and there were a large number of inflammatory cells in medullary cavity, accompanied by bone destruction. At 1, 2 and 4 weeks, IL-2 expression significantly increased, the proportion of CD4+CD25+FoxP3 Treg cells in peripheral monocytes markedly increased, the mRNA expression of Foxp3 and CTLA-4 and p-STAT5 protein expression increased dramatically in Treg cells as compared to control group (P<0.001). CONCLUSIONS: IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway may be involved in the pathogenesis of COM, and excessive immunosuppression may lead to persistent infectious inflammation, which may become a key target for future treatment of COM.
