Neuroblastoma (NB) is a common neural crest-derived extracranial solid cancer in children. Among all childhood cancers, NB causes devastating loss of young lives as it accounts for 15% of childhood cancer mortality. Neuroblastoma, especially high-risk stage 4 NB with MYCN amplification has limited treatment options and associated with poor prognosis. This necessitates the need for novel effective therapeutic strategy. JARID1B, also known as KDM5B, is a histone lysine demethylase, identified as an oncogene in many cancer types. Clinical data obtained from freely-accessible databases show a negative correlation between JARID1B expression and survival rates. Here, we demonstrated for the first time the role of JARID1B in the enhancement of stem cell-like activities and drug resistance in NB cells. We showed that JARID1B may be overexpressed in either MYCN amplification (SK-N-BE(2)) or MYCN-non-amplified (SK-N-SH and SK-N-FI) cell lines. JARID1B expression was found enriched in tumor spheres of SK-N-BE(2) and SK-N-DZ. Moreover, SK-N-BE(2) spheroids were more resistant to chemotherapeutics as compared to parental cells. In addition, we demonstrated that JARID1B-silenced cells acquired a decreased propensity for tumor invasion and tumorsphere formation, but increased sensitivity to cisplatin treatment. Mechanistically, reduced JARID1B expression led to the downregulation of Notch/Jagged signaling. Collectively, we provided evidence that JARID1B via modulation of stemness-related signaling is a putative novel therapeutic target for treating malignant NB.

Objective: To compare the therapeutic effectiveness of oral corticosteroids with that of adrenocorticotrophic hormone for infantile spasms.Methods: PubMed, Embase, Scopus, and the Cochrane library were searched to retrieve studies published before December 2018 to identify pediatric patients with a diagnosis of infantile spasms. The interventions of oral corticosteroids and adrenocorticotrophic hormone were compared. We included only randomized controlled trials that reported the cessation of spasms as treatment response. The primary outcome was clinical spasm cessation on day 13 or 14. The secondary outcomes were the resolution of hypsarrhythmia, side effects, continued spasm control, spasm relapse rate, and subsequent epilepsy rate. Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses, the study‐level quality assessment was conducted using the Cochrane risk‐of‐bias tool.Results: After extensive review, 39 articles were included for meticulous evaluation. Five randomized controlled trials with a total of 239 individuals were eligible for further analysis. No significant difference was detected between the corticosteroids and adrenocorticotrophic hormone in the cessation of clinical spasms (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.16 to 1.81; P = 0.32). The subgroups of high‐dose prednisolone versus adrenocorticotrophic hormone and low‐dose prednisone versus adrenocorticotrophic hormone also exhibited no significant difference. Furthermore, the two subgroups did not differ in terms of hypsarrhythmia resolution, side effects, relapse rate, or subsequent epilepsy rate.Interpretation: This meta‐analysis suggests that high‐dose prednisolone is not inferior to adrenocorticotrophic hormone and that it be considered a safe and effective alternative treatment.

Multiple acyl-CoA dehydrogenase deficiency (MADD), an autosomal recessive metabolic disorder of fatty acid metabolism, is mostly caused by mutations in the ETFA, ETFB or ETFDH genes that result in dysfunctions in electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone dehydrogenase (ETFDH). In β-oxidation, fatty acids are processed to generate acyl-CoA, which is oxidised by flavin adenine dinucleotide and transfers an electron to ETF and, through ETFDH, to mitochondrial respiratory complex III to trigger ATP synthesis. Coenzyme Q10 (CoQ10) is believed to be a potential treatment that produces symptom relief in some MADD patients. CoQ10 acts as a key regulator linking ETFDH and mitochondrial respiratory complex III. Our aim is to investigate the effectiveness of CoQ10 in serving in the ETF/ETFDH system to improve mitochondrial function and to reduce lipotoxicity. In this study, we used lymphoblastoid cells with an ETFDH mutation from MADD patients. ETFDH dysfunction caused insufficient β-oxidation, leading to increasing lipid droplet and lipid peroxide accumulation. In contrast, supplementation with CoQ10 significantly recovered mitochondrial function and concurrently decreased the generation of reactive oxygen species and lipid peroxides, inhibited the accumulation of lipid droplets and the formation of the NOD-like receptor family pyrin domain-containing three (NLRP3) inflammasome, and reduced interleukin-1β release and cell death. These results clarify the causal role of CoQ10 in coupling the electron transport chain with β-oxidation, which may promote the development of CoQ10-directed therapies for MADD patients.