Competing endogenous RNA network analysis of the molecular mechanisms of ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a serious neurological disease that largely results in long-term disability and death. Extensive evidence has indicated that the activation of inflammation and ferroptosis significantly contribute to the development of IS pathology. However, the underlying molecular mechanism remains unclear. In this study, we aimed to identify potential biomarkers associated with IS through the construction of a competing endogenous RNA (ceRNA) network and to investigate the possible inflammatory and ferroptosis-related molecular mechanisms. RESULTS: We identified 178 differentially expressed target messenger RNAs (DETmRNAs) associated with IS. As revealed through enrichment analysis, the DEmRNAs were mainly enriched in the inflammatory signaling pathways and also related to ferroptosis mechanism. The CIBERSORT algorithm showed immune infiltration landscapes in which the naïve B cells, naïve T cells, and monocytes had statistically different numbers in the cerebral infarction group compared with the control group. A ceRNA network was constructed in this study involving 44 long non-coding RNAs (lncRNAs), 15 microRNAs (miRNAs), and 160 messenger RNAs (mRNAs). We used the receiver operating characteristic (ROC) analysis to identify three miRNAs (miR-103a-3p, miR-140-3p, and miR-17-5p), one mRNA (TLR4), and one lncRNA (NEAT1) as the potential key biomarkers of the ceRNA network. The key mRNA and lncRNA were shown to be highly related to the ferroptosis mechanism of IS. The expression of these key biomarkers was also further validated by a method of quantitative real-time polymerase chain reaction in SH-SY5Y cells, and the validated results were consistent with the findings predicted by bioinformatics. CONCLUSION: Our results suggest that the ceRNA network may exert an important role in the inflammatory and ferroptosis molecular mechanisms of IS, providing new insight into therapeutic IS targets.

Effects of non-invasive brain stimulation on motor function after spinal cord injury: a systematic review and meta-analysis.

BACKGROUND: In recent years, non-invasive brain stimulation (NIBS) has been used for motor function recovery. However, the effects of NIBS in populations with spinal cord injury (SCI) remain unclear. This study aims to conduct a meta-analysis of the existing evidence on the effects and safety of NIBS against sham groups for motor dysfunction after SCI to provide a reference for clinical decision-making. METHODS: Two investigators systematically screened English articles from PubMed, MEDLINE, Embase, and Cochrane Library for prospective randomized controlled trials regarding the effects of NIBS in motor function recovery after SCI. Studies with at least three sessions of NIBS were included. We assessed the methodological quality of the selected studies using the evidence-based Cochrane Collaboration's tool. A meta-analysis was performed by pooling the standardized mean difference (SMD) with 95% confidence intervals (CI). RESULTS: A total of 14 randomized control trials involving 225 participants were included. Nine studies used repetitive transcranial magnetic stimulation (rTMS) and five studies used transcranial direct current stimulation (tDCS). The meta-analysis showed that NIBS could improve the lower extremity strength (SMD = 0.58, 95% CI = 0.02-1.14, P = 0.004), balance (SMD = 0.64, 95% CI = 0.05-1.24, P = 0.03), and decrease the spasticity (SMD = - 0.64, 95% CI = - 1.20 to - 0.03, P = 0.04). However, the motor ability of the upper extremity in the NIBS groups was not statistically significant compared with those in the control groups (upper-extremity strength: P = 0.97; function: P = 0.56; and spasticity: P = 0.12). The functional mobility in the NIBS groups did not reach statistical significance when compared with the sham NIBS groups (sham groups). Only one patient reported seizures that occurred during stimulation, and no other types of serious adverse events were reported. CONCLUSION: NIBS appears to positively affect the motor function of the lower extremities in SCI patients, despite the marginal P-value and the high heterogeneity. Further high-quality clinical trials are needed to support or refute the use and optimize the stimulation parameters of NIBS in clinical practice.

Transcutaneous Electrical Stimulation for Neurogenic Bladder After Spinal Cord Injury: A Systematic Review and Meta-Analysis.

OBJECTIVES: This review aims to assess the efficacy of transcutaneous electrical nerve stimulation (TENS) for neurogenic bladder after spinal cord injury (SCI). MATERIALS AND METHODS: A systematic search was conducted of seven electronic data bases from inception to Dec 31, 2022, to identify randomized controlled trials that studied TENS for neurogenic bladder after SCI. The primary outcomes were maximum cystometric capacity (MCC) and residual urine volume (RUV). Secondary outcomes included maximum detrusor pressure, flow rate, and bladder diary. Random effects models were used in all analyses. RESULTS: Eleven trials involving 881 participants were included. Meta-analysis showed that TENS in addition to conventional treatment had larger MCC (mean difference [MD] 50.55 ml, 95% CI 27.81-73.29, p＜0.0001) and lower RUV (MD -22.96 ml, 95% CI -33.45 to -12.47, p＜0.0001) than did conventional treatment only. Compared with magnetic stimulation, no differences were observed with TENS for MCC (MD -14.49 ml, 95% CI -48.97 to 19.98, p = 0.41) and RUV (MD 25 ml, 95% CI -61.79 to 111.79, p = 0.57). There also were no differences in MCC (MD -7.2 ml, 95% CI -14.56 to 0.16, p= 0.06) and (MD -5.2 ml, 95% CI -60.00 to 49.60, p = 0.851) when compared with solifenacin succinate and pelvic floor biofeedback, respectively. CONCLUSIONS: TENS may be an effective treatment option for neurogenic bladder after SCI.

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning.

JOURNAL/nrgr/04.03/01300535-202412000-00028/figure1/v/2024-04-08T165401Z/r/image-tiff Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal cord injury. They can greatly affect nerve regeneration and functional recovery. However, there is still limited understanding of the peripheral immune inflammatory response in spinal cord injury. In this study, we obtained microRNA expression profiles from the peripheral blood of patients with spinal cord injury using high-throughput sequencing. We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus (GEO) database (GSE151371). We identified 54 differentially expressed microRNAs and 1656 differentially expressed genes using bioinformatics approaches. Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways, such as neutrophil extracellular trap formation pathway, T cell receptor signaling pathway, and nuclear factor-κB signal pathway, were abnormally activated or inhibited in spinal cord injury patient samples. We applied an integrated strategy that combines weighted gene co-expression network analysis, LASSO logistic regression, and SVM-RFE algorithm and identified three biomarkers associated with spinal cord injury: ANO10, BST1, and ZFP36L2. We verified the expression levels and diagnostic performance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve. Quantitative polymerase chain reaction results showed that ANO10 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients. We also constructed a small RNA-mRNA interaction network using Cytoscape. Additionally, we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal cord injury patients using the CIBERSORT tool. The proportions of naïve B cells, plasma cells, monocytes, and neutrophils were increased while the proportions of memory B cells, CD8+ T cells, resting natural killer cells, resting dendritic cells, and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects, and ANO10, BST1 and ZFP26L2 were closely related to the proportion of certain immune cell types. The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal cord injury and suggest that ANO10, BST1, and ZFP36L2 are potential biomarkers for spinal cord injury. The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200066985, December 12, 2022).

Relationship between the matrix metalloproteinase-9 gene polymorphisms and ischemic stroke.

BACKGROUND: In recent years, with the further research of human genome scanning, the relationship between matrix metalloproteinase-9 (MMP-9) gene polymorphisms and many diseases has aroused increased attention. But there is little research on the relationship between MMP-9 gene polymorphisms and ischemic stroke (IS). This study was conducted to evaluate the relationships between the rs3918242 and rs17577 polymorphisms in the MMP-9 gene and IS in a Chinese population. METHODS: 152 cases of IS patients and 152 healthy controls were enrolled in this study. All subjects were genotyped for the MMP-9 rs3918242 and rs17577 polymorphisms by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP) and restriction analysis. RESULTS: Rs3918242 showed genotypes TT, TC, and CC, and rs17577 exhibited genotypes AA, AG, and GG. The MMP-9 polymorphisms rs3918242 and rs17577 exhibited complete linkage. Our study found there was no significant difference in genotype and allele between rs3918242 and rs17577 between patients and controls. The MMP-9 gene rs3918242 and rs17577 polymorphisms are not significantly correlated with IS risk. Genetic polymorphisms vary among ethnic and regional populations. CONCLUSION: Our results suggest that MMP-9 rs3918242 is completely linked to rs17577, while the rs3918242 and rs17577 polymorphisms are not significantly associated with the risk of IS. Genetic polymorphisms vary among ethnic and regional populations.