Wang Qi,Shi Xulai,Li Ping-Ping,Gao Li,Zhou Yueyuan,Li Luyao,Ye Hao,Fu Xiaoqin,Li Peijun
Background Although previous studies show that microRNAs (miRNAs) can potentially be used as diagnostic markers for epilepsy, there are very few analyses of pediatric epilepsy patients. Methods miRNA profiles using miRNA-seq was performed on plasma samples from 14 pediatric epileptic patients and 14 healthy children. miRNA miR-27a-3p that were significantly changed between two groups were further evaluated. The potential target genes of miR-27a-3p were screened through unbiased mRNA-seq and further validated using Western blot and immunohistochemistry in HEK-293T cells and in the brains of mice with epilepsy induced by lithium chloride–pilocarpine. Results We found 82 upregulated and 76 downregulated miRNAs in the plasma from pediatric patients compared with controls ( p < 0.01), of which miR-27a-3p exhibited a very low p value ( p < 0.0001) and validated in additional plasma samples. Two genes, GOLM1 and LIMK1, whose mRNA levels were decreased ( p < 0.001) with the increase of miR-27a-3p were further validated in both HEK-293T cells and in epileptic mice. Conclusions MiR-27a-3p exhibits potential as a diagnostic and therapeutic marker for epilepsy. We postulate that additional studies on the downstream targets of miR-27a-3p will unravel its roles in epileptogenesis or disease progression. Impact
A total of 158 differentially expressed miRNAs were detected in plasma between epileptic and control children.
Plasma miR-27a-3p was one of the miRNAs with a low p value.
GOLM1 and LIMK1 were validated as downstream target genes of miR-27a-3p.
miR-27a-3p has potential as a diagnostic and therapeutic marker for epilepsy.
Aims Status epilepticus (SE) is the most common neurological emergency in pediatric patients. This study aimed to screen for prognostic biomarkers of SE in the cerebrospinal fluid (CSF) using metabolomics. Methods Ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was conducted to identify prognostic biomarkers in CSF metabolomics by comparing the poor outcome group ( N = 13) with the good outcome group ( N = 15) of children with SE. Differentially expressed metabolites were identified using Mann–Whitney U test corrected by Benjamini-Hochberg and partial least squares discriminant analysis (PLS-DA). Results The PLS-DA model identified and validated significant metabolic differences between the poor and good outcome groups of children with SE (PLS-DA with R 2 Y = 0.992 and Q 2 = 0.798). A total of 49 prognosis-related metabolites were identified. Of these metabolites, 20 including glutamyl-glutamine, 3-iodothyronamine, and L-fucose had an area under the curve (AUC) ≥ 80% in prognostic prediction of SE. The logistic regression model combining glutamyl-glutamine and 3-iodothyronamine produced an AUC value of 0.976, with a sensitivity of 0.863 and specificity of 0.956. Pathway analysis revealed that dysregulation of the citrate cycle (TCA) and arginine biosynthesis may contribute to poor SE prognosis. Conclusions This study highlighted the prognosis-related metabolomic disturbances in the CSF of children with SE and identified potential prognostic biomarkers. A prognostic prediction model combining glutamyl-glutamine and 3-iodothyronamine with high predictive value was established.
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