Adjunctive Treatment With Eslicarbazepine Acetate for Adults and Children With Focal-Onset Epilepsy: A Meta-Analysis.

Background: The efficacy and tolerability of eslicarbazepine acetate (ESL) in adults and children with focal-onset epilepsy (FOE) according to the dose remain to be validated. A meta-analysis based on randomized controlled trials (RCTs) was therefore conducted as a summary. Methods: Relevant RCTs were collected by systematic searching the electronic databases of PubMed, Cochrane's Library, Embase, Wanfang and CNKI from inception to May 16, 2022. The random-effect model was adopted to pool the results by incorporating the possible heterogeneity. Efficacy outcomes including responsive rate and effective rate, defined as cases with 50 and ≥75% reduction in seizure frequency compared to baseline, were determined, respectively. Incidence of severe adverse events (AE) leading to drug discontinuation was also evaluated. Results: Ten studies including 2,565 people with epilepsy contributed to the meta-analysis. For adults, ESL 400 mg/d did not improve the response rate or the effective rate; ESL 800 mg/d was associated with improved response rate (odds ratio [OR] 2.16, 95% confidence interval [CI]: 1.65-2.83, p < 0.001) and effective rate (OR 2.16, 95% CI: 1.41-3.30, p < 0.001) without significantly increased severe AE (OR 1.58, 95% CI: 0.90-2.78, p = 0.11); ESL 1,200 mg/d improved response rate (OR 2.49, p < 0.001) and effective rate (OR 3.09, p = 0.04), but significantly increased severe AE (OR 3.72, p < 0.001). For children, ESL also did not significantly improve the response rate (OR 1.76, p = 0.22) or the effective rate (OR 2.17, p = 0.13). Conclusion: ESL 800 mg/d is effective and well-tolerated as adjuvants for adults with FOE. Efficacy of ESL in children with FOE should be further evaluated.

Mannose inhibits proliferation and promotes apoptosis to enhance sensitivity of glioma cells to temozolomide through Wnt/ß-catenin signaling pathway.

BACKGROUND: Temozolomide (TMZ) is generally applied for glioma treatment, while drug resistance of TMZ limits its therapeutic efficacy. Mannose exerts evident anti-tumor effect. We intended to investigate whether mannose enhanced TMZ sensitivity to glioma and examined the underlying mechanism. METHODS: MTT and clone formation assays were performed to detect cell viability and proliferation. Cell apoptosis was measured by flow cytometry. The protein and gene expression levels were detected by Western blot and qRT-PCR assays. Xenograft glioma model was established to explore the influence of mannose in vivo. RESULTS: Mannose inhibited glioma cell growth, which was facilitated by knockdown of phosphomannose isomerase (PMI) while reversed by overexpression of PMI. Mannose enhanced the sensitivity of glioma cells to TMZ, indicated by the further inhibited cell viability and colony formation and the aggravated cell apoptosis, which was reversed by overexpression of O6-methylguanine DNA methyltransferase (MGMT). Furthermore, mannose and TMZ inhibited MGMT expression and Wnt/ß-catenin activation. Moreover, activating Wnt/ß-catenin pathway blocked anti-proliferative effect induced by mannose and TMZ, which was further suppressed by overexpressed MGMT. Mannose inhibited glioma growth, suppressed Ki67 and downregulated MGMT and ß-catenin in vivo. CONCLUSION: Mannose inhibited MGMT to enhance sensitivity of glioma cells to TMZ, with Wnt/ß-catenin pathway involvement. Our data suggested that mannose could be an innovative agent to improve glioma treatment, particularly in TMZ-resistant glioma with high MGMT.

Metabolic Control of Epilepsy: A Promising Therapeutic Target for Epilepsy.

Epilepsy is a common neurological disease that is not always controlled, and the ketogenic diet shows good antiepileptic effects drug-resistant epilepsy or seizures caused by specific metabolic defects via regulating the metabolism. The brain is a vital organ with high metabolic demands, and epileptic foci tend to exhibit high metabolic characteristics. Accordingly, there has been growing interest in the relationship between brain metabolism and epilepsy in recent years. To date, several new antiepileptic therapies targeting metabolic pathways have been proposed (i.e., inhibiting glycolysis, targeting lactate dehydrogenase, and dietary therapy). Promising strategies to treat epilepsy via modulating the brain's metabolism could be expected, while a lack of thorough understanding of the role of brain metabolism in the control of epilepsy remains. Herein, this review aims to provide insight into the state of the art concerning the brain's metabolic patterns and their association with epilepsy. Regulation of neuronal excitation via metabolic pathways and antiepileptic therapies targeting metabolic pathways are emphasized, which could provide a better understanding of the role of metabolism in epilepsy and could reveal potential therapeutic targets.

2-Deoxy-D-Glucose Exhibits Anti-seizure Effects by Mediating the Netrin-G1-KATP Signaling Pathway in Epilepsy.

Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) has been reported to exert antiepileptic effects by upregulating KATP subunits (kir6.1 and kir6.2). We evaluated whether 2-DG exhibits anti-seizure effect by mediating the netrin-G1-KATP signaling pathway in epilepsy. In a mouse epilepsy model induced by lithium chloride-pilocarpine, 2-DG intervention increased the mRNA and protein expression levels of kir6.1 and kir6.2, and these increases were significantly reversed after knocking down netrin-G1 expression. Similarly, in cultured neurons with a magnesium-free medium, we found that the frequency of spontaneous postsynaptic potentials (SP) was increased, and in the meanwhile, expression levels of kir6.1 and kir6.2 were increased after pretreatment with 2DG. These effects were remarkably reversed after knocking down netrin-G1. Thus, our findings show that 2DG exhibits anti-seizure effects through the netrin-G1-KATP signaling pathway.