Exosomes are nano-sized vesicles that contain a variety of mRNAs, miRNAs, and proteins. They are capable of being released by a variety of cells and are essential for cell–cell communication. The exosomes produced by cells have shown protective benefits against spinal cord damage (SCI). Recently, it was discovered that M2 macrophages aid in the angiogenesis of numerous illnesses. However, the functional role of M2 macrophage-derived exosomes on SCI is unclear. Here, we investigate the pro-angiogenesis of M2 macrophage-derived exosomes on SCI. We founded that M2 macrophage exosomes alleviated tissue damage and enhanced functional recovery post-SCI. We discovered that M2 macrophage exosome administration increased angiogenesis after SCI in vivo using immunohistochemistry, immunofluorescence labeling, and Western blot analysis. Additionally, the expression of the pro-angiogenesis factors, HIF-1α and VEGF, were enhanced with the treatment of the M2 macrophage exosomes. Furthermore, we found that M2 macrophage exosomes enhanced neurogenesis after SCI in vivo. In vitro, we found that M2 macrophage exosomes can be taken up by the brain endothelial cell line (bEnd.3) and that they enhanced the tube formation, migration, and proliferation of bEnd.3 cells. Furthermore, by using special siRNA to inhibit HIF-1α expression, we observed that the expression of VEGF decreased, and the tube formation, migration, and proliferation of bEnd.3 cells were attenuated with the treatment of HIF-1α-siRNA. In conclusion, our findings reveal that M2 macrophage exosomes improve neurological functional recovery and angiogenesis post-SCI, and this process is partially associated with the activation of the HIF-1/VEGF signaling pathway.
Objective To investigate the clinical efficacy and feasibility of posterior-only debridement, internal fixation, and interbody fusion using titanium mesh in the surgical treatment of thoracolumbar tuberculosis (TB) with spinal epidural abscess. Methods From January 2008 to January 2014, a total of 45 patients (27 male and 18 female) were reviewed. The patients were diagnosed with thoracolumbar TB with spinal epidural abscess. The patients underwent posterior-only debridement, internal fixation, and interbody fusion using titanium mesh. Hence, we assessed the intraoperative and postoperative complications, disease recurrences, kyphosis deformity correction, and neurological improvement following the American Spinal Injury Association (ASIA). We used SPSS 22.0 for the statistical analyses. An independent Student’s t-test was used for the analysis of preoperative and postoperative continuous variables. The value of P (P < 0.05) was considered statistically significant. Results The mean age of patients was 37.76 ± 10.94 years (17–59 years). The mean follow-up time was 82.76 ± 12.56 months (60–128 months). The mean kyphosis Cobb angle preoperative was 29.36 ± 13.29° (5–55°) and postoperative was 3.58 ± 5.44° (− 6–13°), given the value of P (P < 0.001). According to the neurological score by the ASIA scale, there were 3 cases of grade B, 11 cases of grade C, 16 cases of grade D, and 15 cases of grade E preoperatively. The neurological score improved by 1 ~ 2 grades. All patients achieved pain relief and the VAS score significantly reduced at the last follow-up (P<0.05). While 1 patient had cerebrospinal fluid leakage, 1 had a neurological complication, 1 had delayed surgical wound healing, and 1 had a disease recurrence. No pseudoarthrosis or implant failure occurred in our patients. All patients achieved solid bone graft fusion. Conclusion For thoracolumbar TB patients with spinal epidural abscess, posterior-only debridement, internal fixation, and interbody fusion using titanium mesh are safe and effective surgical treatments.
Chronic spinal cord injury (CSCI) is a catastrophic disease of the central nervous system (CNS), resulting in partial or complete loss of neurological function. N6-methyladenosine (m6A) is the most common form of reversible posttranslational modi cation at the RNA level. However, the role of m6A modi cation in CSCI remains unknown. In this study, we established a CSCI model using a water-absorbable polyurethane polymer, with behavioral assessment, electrophysiological analysis, and histochemical staining for validation. Methylated RNA immunoprecipitation sequencing (meRIP-seq) and mRNA sequencing (mRNA-seq) were jointly explored to compare the differences in CSCI spinal tissue and normal spinal tissue. Furthermore, qRT-PCR, western blotting, and immuno uorescence staining were used to analyze m6A modi cation-related proteins. We found that water-absorbable polyurethane polymer well simulated chronic spinal cord compression. BMS scores and electrophysiological analysis showed continuous neurological function decline after chronic compression of the spinal cord. meRIP-seq identi ed 642 differentially modi ed m6A genes, among which 263 genes were downregulated and 379 genes were upregulated. mRNA-seq showed that 1544 genes were upregulated and 290 genes were downregulated after CSCI. Gene Ontology (GO) terms and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were also identi ed. qRT-PCR, western blotting, and immuno uorescence staining showed that Mettl14 was signi cantly upregulated after CSCI. Our study revealed a comprehensive pro le of m6A modi cations in CSCI and may provide a valuable tool for further research on CSCI. study showed that mettl14 was signi cantly overexpressed after CSCI and mainly expressed in neurons, which was further validated by qRT-PCR, western blotting, and immuno uorescence.Our study is not without limitations. First, we obtained whole spinal tissue for meRIP-seq and mRNA-seq. Although the total m6A modi cations were assessed, it was di cult to distinguish m6A methylation changes in speci c cell types. In further in-depth research, extracting speci c cells for veri cation of m6A modi cation and exploring its function would be meaningful. Second, we performed preliminary analyses of differentially expressed genes and enriched GO and KEGG pathways, but their roles in CSCI require further validation through extensive experiments.Collectively, our study analyzed m6A methylation modi cations in spinal cord tissue after CSCI. The results indicated that m6A plays an important role in the process of CSCI. Our research may provide new insights for further study of the CSCI pathological process and potential treatment options. DeclarationsAuthor contributions JH, YC and HL designed the study. CL and JZ carried out most of the experiments and data analysis. YJ, TQ, CD and TW assisted in experiments and data analysis. CL drafted the manuscript, and JH and YC revised the manuscript.
Extrapulmonary tuberculosis (EPTB) is characterized by atypical clinical symptoms, difficulty in diagnosis, a high rate of disability, and a high mortality rate. Early EPTB diagnosis aids recovery. The gold standard for EPTB diagnosis needs surgery, puncture, and other invasive testing to collect a lesion sample for mycobacterium tuberculosis culture and Xpert. However, early diagnosis of EPTB has been challenging due to the lack of specificity and inability of current diagnostic methods to differentiate between active and latent EPTB infections. As a result, there is an urgent clinical need to develop new methods to improve the early detection of EPTB. In this study, we employed bioinformatics and machine learning methods to identify EPTB hallmark genes. Furthermore, we looked at the relationship between these genes and immune cell infiltration. We obtained 97 differentially expressed genes (DEGs) from the analysis. The genes were split into 14 modules by weighted gene co-expression network analysis (WGCNA). Six of the intersecting genes, GBP5, UBE2L6, IFITM3, SERPING1, C1QB, and FCGR1B, were identified as EPTB hub genes at final screening using the last absolute shrinkage and selection operator (LASSO) and random Forest. The presence of some immune cells in EPTB correlated with the expression of these genes.
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