Hyperhomocysteinemia and Endothelial Dysfunction in Multiple Sclerosis

Dubchenko, Ekaterina; Ivanov, Alexander; Spirina, N N; Smirnova, N F; Melnikov, Mikhail; Boyko, A. N.; Gusev, E I; Kubatiev, A. A.

doi:10.3390/brainsci10090637

Cited by 19 publications

(14 citation statements)

References 74 publications

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“…This could interfere with the reaction of T lymphocytes and B lymphocytes, natural killer cells, and adhesion molecules ( 15 , 39 , 40 ). Th17 cells interfere with the BBB by producing pro-inflammatory IL-17 and migrate to the CNS by expression of the chemokine receptor CCR-6 (CD196) ( 18 ). Hcy could indirectly influence the function of the BBB by promoting the differentiation of Th17 cells ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Hcy is seen to be able to induce the destruction of the blood-brain barrier (BBB) and to regulate the function of adaptive immune system cells (15)(16)(17). Recently, the role of Hcy in many autoimmune diseases has attracted great attention of researchers, particularly demyelinating diseases of the nervous system, such as multiple sclerosis (18). Hcy levels in patients with multiple sclerosis was higher than that of healthy people, and hyperhomocysteinemia may be related to disease progression and disability severity in patients with multiple sclerosis (19,20).…”

Section: Introductionmentioning

confidence: 99%

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Serum Homocysteine Level Is a Predictor of Relapse and Prognosis in Patients With First-Attack Neuromyelitis Optica Spectrum Disorders

Zhang

Zhou

et al. 2021

Front. Neurol.

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Background: Many patients with neuromyelitis optica spectrum disorders (NMOSD) experience the adverse consequences of relapse and disability aggravation. Thus, it is necessary to identify sensitive and reliable biomarkers for early prognosis. This study investigated whether serum homocysteine (Hcy) level was associated with the risk of relapse or poor prognosis in first-attack NMOSD patients.Methods: We enrolled 161 first-attack NMOSD patients in this retrospective study. We reviewed their medical records and evaluated their initial Expanded Disability Status Scale (EDSS). Clinical outcomes were measured by the final EDSS and the relapse rate. The association between Hcy levels and EDSS score at last follow-up was analyzed by binary logistic regression. The association between Hcy levels and relapse rate was assessed by Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was used to predict the target value of Hcy reduction.Results: Compared with the high Hcy group, the final EDSS score in the low Hcy group was significantly lower (median: 0.5 vs. 2.5, P < 0.001). The relapse rate differed significantly between these groups (30.6 vs. 50.0%, P = 0.023). Multivariate analysis showed that the initial EDSS score (odds ratio [OR] 3.03, 95% confidence interval [CI] 2.07–4.45, P < 0.001) and serum Hcy level (OR 1.13, 95%CI 1.04–1.22, P = 0.002) were significantly associated with poor prognosis in NMOSD patients. Additionally, multivariate analysis showed that serum Hcy level (hazard ratio 1.06, 95%CI 1.04–1.09, P < 0.001) was an independent predictor of the risk for relapse in NMOSD. The 12-month relapse rate of the high Hcy group was 34.8%, and 50% of high Hcy patients relapsed within 35 months after the first onset. A serum Hcy level exceeding 14.525 μmol/L indicated a high risk of relapse, with a sensitivity of 43.7%, specificity of 90.0%, and area under the ROC curve of 0.674 (95%CI 0.59–0.76, P < 0.001).Conclusion: Serum Hcy level is an independent predictor of relapse and poor prognosis in first-attack NMOSD patients. Early monitoring and reduction of serum Hcy levels may be of great significance in the prevention of disease relapse and severe disability.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum Homocysteine Level Is a Predictor of Relapse and Prognosis in Patients With First-Attack Neuromyelitis Optica Spectrum Disorders

Zhang

Zhou

et al. 2021

Front. Neurol.

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“…Here, we present results that are consistent with this observation. Leukocyte transendothelial migration occurs in the micron-sized spaces in the venules of the specific capillaries produced by migrating white blood cells 22 and is closely associated with the inflammatory response, multiple sclerosis and other regulatory abnormalities 23 , 24 . However, there is no evidence that the differentially expressed CNV genes GNA12, MYL12A, and MYL12B in leukocyte transendothelial migration are significantly correlated with occult LNM, and the underlying mechanism needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

CNV Analysis of the Correlation between Preoperative Lymph Node Metastasis and Prognosis of Early Tongue Cancer

2021

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Objective: To investigate the relationship between preoperative concealed lymph node metastasis (LNM) and prognosis in patients with early tongue cancer. Methods: According to preoperative lymph node dissection, 41 patients with tongue cancer were divided into the LNM group (n=19) and the non-LNM group (n=22). Analysis of single nucleotide variation (SNV), tumor mutation burden (TMB), mutant allele tumor heterogeneity (MATH), aneuploidy and copy number variation (CNV) was performed to identify differentially expressed genes (DEGs) related to LNM. While KEGG analysis was conducted to reveal the CNV differentially expressed genes and main enriched pathways, the correlation between pathways and genes was analyzed by hierarchical clustering. The clinical information of LNM and data on overall survival (OS) rate were obtained from The Cancer Genome Atlas (TCGA), and survival analysis was performed based on combined LNM information. Results: We observed significant correlations for the mTOR signaling pathway, Hippo signaling pathway and Wnt signaling pathway with the LNM group, while leukocyte transendothelial migration and cytokine-cytokine receptor interaction were markedly correlated with the non-LNM group. Moreover, TNFRSF10C was identified as the main DEG in the leukocyte transendothelial migration pathway. TCGA-based validation revealed that the disease-free survival (DFS) of the non-LNM group was significantly higher than that of the LNM group (P<0.005) when TNFRSF10C CNV was set to a log2 ratio>-0.163. Conclusion:The differential expression of TNFRSF10C in leukocyte transendothelial migration, an immune-related pathway, is associated with LNM and DFS. The TNFRSF10C CNV log2 ratio could potentially serve as an indicator of good prognosis for tongue cancer patients with non-LNM after neck dissection.

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“…In addition (29). Hcy plays an important role in structural instability and degeneration of myelin sheath by inhibiting methyl donors, which may have an adverse effect on disease progression (30)(31)(32).…”

Section: P-valuementioning

confidence: 99%

Analysis of Predictive Risk Factors in Aquaporin-4-IgG Positive Highly Active Neuromyelitis Optica Spectrum Disorders

Zhang

Zhou

et al. 2021

Front. Neurol.

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Neuromyelitis optica spectrum disorders (NMOSDs) are inflammatory diseases with a high risk of recurrence and progressive disability, and it is crucial to find sensitive and reliable biomarkers for prognosis and the early prediction of relapse. Highly active NMOSD is defined as two or more clinical relapses within a 12-month period. In this study, we analyzed independent risk factors among patients with aquaporin-4 (AQP4)-IgG positive highly active NMOSD. In this retrospective study, we analyzed the data of 94 AQP4-IgG positive patients with highly active NMOSD and 105 AQP4-IgG positive controls with non-highly active NMOSD. In order to rule out possible effects of previous treatments (such as glucocorticoids, immunoglobulin, and immunosuppressants), we focused on the first-attack NMOSD patients admitted to our hospital. Clinical data, including the age of onset, gender, comorbidities, and serum analysis and cerebrospinal fluid (CSF) analysis results, were collected, after which logistic regression models were used to determine the associations between the clinical factors and relapse outcomes. The prevalence of connective tissue disease and the proportion of antinuclear antibody (ANA)-positivity were higher in the highly active NMOSD group than in the control group. The leukocyte counts, homocysteine (Hcy) levels, CSF leukocyte counts, protein concentrations, IgG indexes, and 24h IgG synthesis rates were also higher in the highly active NMOSD group. The results of multivariate analysis indicated that connective tissue disease comorbidity (OR = 5.953, 95% CI: 1.221–29.034, P = 0.027), Hcy levels (OR = 1.063, 95% CI: 1.003–1.126, P = 0.04), and 24h IgG synthesis rate (OR = 1.038, 95% CI: 1.003–1.075, P = 0.034) may be independent risk factors for AQP4-IgG positive highly active NMOSD relapse after adjusting for various variables. Comorbidity of connective tissue disease, Hcy levels, and 24h IgG synthesis rate may be independent risk factors for AQP4-IgG positive highly active NMOSD.

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Hyperhomocysteinemia and Endothelial Dysfunction in Multiple Sclerosis

Cited by 19 publications

References 74 publications

Serum Homocysteine Level Is a Predictor of Relapse and Prognosis in Patients With First-Attack Neuromyelitis Optica Spectrum Disorders

Serum Homocysteine Level Is a Predictor of Relapse and Prognosis in Patients With First-Attack Neuromyelitis Optica Spectrum Disorders

CNV Analysis of the Correlation between Preoperative Lymph Node Metastasis and Prognosis of Early Tongue Cancer

Analysis of Predictive Risk Factors in Aquaporin-4-IgG Positive Highly Active Neuromyelitis Optica Spectrum Disorders

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