RESUMEN
OBJECTIVE: To explore the central sensitization mechanism of pain in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We randomly divided 40 adult male SPF SD rats, aged 3ï¼4 weeks and weighing 250ï¼350 g, into a normal control and a CP/CPPS model group. After modeling, we analyzed the state of infiltration of CD4+T cells into the L5ï¼S2 spinal cord and detected the expression levels of GFAP and CR3 in the spinal cord tissue using flow cytometry, real-time fluorescent quantitative PCR (RT-qPCR) and immunofluorescence staining. RESULTS: Compared with the normal controls, the CP/CPPS model rats showed dramatically increased expression of CD4+T cells in the mononuclear cells of the L5ï¼S2 spinal cord tissue (P < 0.01), mRNA expressions of interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) secreted from the Th1 cells, interleukin (IL)-17 and retinoic acid-associated orphan receptor (ROR) γt secreted from the Th17 cells, cytokines IL-6 and IL-1ß, and chemokines CCL2, CCL20 and CXCL10 (P < 0.01), and expressions of the molecular markers of Th1 and Th17 cells IFN-γ and IL-17 and those of astrocytes and microglias GFAP and CR3. CONCLUSIONS: CD4+T cells, specifically Th1 and Th17 cells, infiltrate L5ï¼S2 spinal cord neurons in CP/CPPS model rats. The inflammatory factors secreted from these cells may damage the neuronal cells, affect nervous conduction, promote central sensitization and activate astrocytes and microglias, leading to the development and progression of pain.
Asunto(s)
Sensibilización del Sistema Nervioso Central , Células Th17 , Animales , Masculino , Dolor Pélvico , Ratas , Ratas Sprague-Dawley , Médula EspinalRESUMEN
BACKGROUND: Peroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth. In addition, previous studies report that PRDXs play critical roles in the occurrence and development of carcinomas. However, few studies have conducted systematic analysis of PRDXs in cancers. Therefore, the present study sought to explore the molecular characteristics and potential clinical significance of PRDX family members in pan cancer and further validate the function of PRDX6 in bladder urothelial carcinoma (BLCA). METHODS: A comprehensive analysis of PRDXs in 33 types of cancer was performed based on the TCGA database. This involved an analysis of mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, both the gain and loss of function strategies were used to assess the importance and mechanism of PRDX6 in the cell cycle of BLCA. RESULT: Analysis showed abnormal expression of PRDX1-6 in several types of cancer compared to normal tissues. Univariate Cox proportional hazard regression analysis showed that expression levels of PRDX1, PRDX4 and PRDX6 were mostly associated with poor survival of OS, DSS and PFI, and PRDX2 and PRDX3 with favorable survival. In addition, the expression of PRDX genes were positively correlated with CNV and negatively with methylation. Moreover, analysis based on PharmacoDB dataset showed that the augmented levels of PRDX1, PRDX3 and PRDX6 were significantly correlated with EGFR/VEGFR inhibitor drugs. Furthermore, knocking down of PRDX6 inhibited growth of cancer cells through the JAK2-STAT3 in bladder cell lines. CONCLUSIONS: PRDXs are potential biomarkers and therapeutic targets for several carcinomas, especially for BLCA. In addition, PRDX6 could regulate proliferation of cancer cell via JAK2-STAT3 pathway and involve into the process of cell cycle in BLCA.