Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UMLS:C0036572 (
seizures
)
80,221
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Temporal lobe epilepsy (TLE) is common intractable epilepsy that affects the patient's lives. The circular RNA circ_ANKMY2 (circ_ANKMY2) has been reported to be abnormally expressed in TLE. Nevertheless, the role and mechanism of circ_ANKMY2 in TLE are unclear. A human
neuroblastoma
cell line (SK-N-AS) was used for a series of studies. Expression levels of circ_ANKMY2, miR-106b-5p, and Forkhead Box Protein 1 (FOXP1) mRNA in TLE tissues were assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Cell colony formation, proliferation, and apoptosis were determined by cell colony formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), or flow cytometry assays. The levels of FOXP1 protein, Ki67, B cell lymphoma (Bcl-2), Bcl-2 Associated X (Bax), and Cleaved caspase-3 were evaluated by western blot analysis. The relationship between circ_ANKMY2 or FOXP1 and miR-106b-5p was verified with dual-luciferase reporter assay. We observed that circ_ANKMY2 and FOXP1 expression were reduced while miR-106b-5p expression was increased in TLE tissues. Overexpression of circ_ANKMY2 decreased spontaneous recurrent
seizures
(SRSs) in rat TLE model and blocked cell colony formation, proliferation, and induced cell apoptosis in SK-N-AS cells. Importantly, circ_ANKMY2 was verified as a sponge for miR-106b-5p. In addition, miR-106b-5p mimics abolished circ_ANKMY2 elevation-mediated effects on colony formation, proliferation, and apoptosis of SK-N-AS cells. Also, FOXP1 served as a target for miR-106b-5p. And FOXP1 silencing overturned the effects of miR-106b-5p inhibitors on the colony formation, proliferation, and apoptosis of SK-N-AS cells. In sum, circ_ANKMY2 modulated TLE advancement via regulation of FOXP1 expression through sponging miR-106b-5p, and circ_ANKMY2 might be an underlying target for the improvement of TLE.
...
PMID:Circular RNA Circ_ANKMY2 Regulates Temporal Lobe Epilepsy Progression via the miR-106b-5p/FOXP1 Axis. 3309 38
Eslicarbazepine acetate (ESL) is a dibenzazepine anticonvulsant approved as adjunctive treatment for partial-onset epileptic
seizures
. Following first pass hydrolysis of ESL, S-licarbazepine (S-Lic) represents around 95% of circulating active metabolites. S-Lic is the main enantiomer responsible for anticonvulsant activity and this is proposed to be through the blockade of voltage-gated Na
+
channels (VGSCs). ESL and S-Lic both have a voltage-dependent inhibitory effect on the Na
+
current in N1E-115
neuroblastoma
cells expressing neuronal VGSC subtypes including Na
v
1.1, Na
v
1.2, Na
v
1.3, Na
v
1.6, and Na
v
1.7. ESL has not been associated with cardiotoxicity in healthy volunteers, although a prolongation of the electrocardiographic PR interval has been observed, suggesting that ESL may also inhibit cardiac Na
v
1.5 isoform. However, this has not previously been studied. Here, we investigated the electrophysiological effects of ESL and S-Lic on Na
v
1.5 using whole-cell patch clamp recording. We interrogated two model systems: (1) MDA-MB-231 metastatic breast carcinoma cells, which endogenously express the "neonatal" Na
v
1.5 splice variant, and (2) HEK-293 cells stably over-expressing the "adult" Na
v
1.5 splice variant. We show that both ESL and S-Lic inhibit transient and persistent Na
+
current, hyperpolarise the voltage-dependence of fast inactivation, and slow the recovery from channel inactivation. These findings highlight, for the first time, the potent inhibitory effects of ESL and S-Lic on the Na
v
1.5 isoform, suggesting a possible explanation for the prolonged PR interval observed in patients on ESL treatment. Given that numerous cancer cells have also been shown to express Na
v
1.5, and that VGSCs potentiate invasion and metastasis, this study also paves the way for future investigations into ESL and S-Lic as potential invasion inhibitors.
...
PMID:Inhibitory Effect of Eslicarbazepine Acetate and S-Licarbazepine on Na
v
1.5 Channels. 3312 7
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