Tumor metabolism characterized by aerobic glycolysis makes the Warburg effect a unique target for tumor therapy. Recent studies have found that glycogen branching enzyme 1 (GBE1) is involved in cancer progression. However, the study of GBE1 in gliomas is limited. We determined by bioinformatics analysis that GBE1 expression is elevated in gliomas and correlates with poor prognoses. In vitro experiments showed that GBE1 knockdown slows glioma cell proliferation, inhibits multiple biological behaviors, and alters glioma cell glycolytic capacity. Furthermore, GBE1 knockdown resulted in the inhibition of the NF-κB pathway as well as elevated expression of fructose-bisphosphatase 1 (FBP1). Further knockdown of elevated FBP1 reversed the inhibitory effect of GBE1 knockdown, restoring glycolytic reserve capacity. Furthermore, GBE1 knockdown suppressed xenograft tumor formation in vivo and conferred a significant survival benefit. Collectively, GBE1 reduces FBP1 expression through the NF-κB pathway, shifting the glucose metabolism pattern of glioma cells to glycolysis and enhancing the Warburg effect to drive glioma progression. These results suggest that GBE1 can be a novel target for glioma in metabolic therapy.
BackgroundPoor sleep quality and vitamin D deficiency are common in stroke patients. Our aim was to evaluate the possible association between vitamin D and sleep quality in acute ischemic stroke (AIS) patients.MethodsA total of 301 AIS patients were screened and completed 1-month follow-up. Serum 25-hydroxyvitamin D [25(OH)D] was used to assess the vitamin D status by a competitive protein-binding assay at baseline. All patients were divided into equal quartile according to the distribution of 25(OH)D. One month after stroke, sleep quality was evaluated by using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaire; depression status was confirmed by 17-item Hamilton Depression Scale (HAMD).ResultsThere were 89 (29.6%) AIS patients with poor sleep quality 1-month post-event. Within 24 h after admission, serum 25(OH)D levels were significantly lower in patients with poor sleep quality after stroke (P < 0.001). In the results of multivariate-adjusted logistic regression analysis, the odds ratio (OR) of poor sleep quality was 6.199 (95% CI, 2.066–18.600) for the lowest quartile of 25(OH)D compared with the highest quartile. In patients without depression, reduced 25(OH)D were still significantly associated with poor sleep quality (OR = 8.174, 95% CI = 2.432–27.473). Furthermore, 25(OH)D and HAMD score were combined to enhance the diagnostic accuracy of poor sleep quality, with the area under the receiver operating characteristic curve of 0.775.ConclusionReduced serum levels of vitamin D at admission were independently and significantly associated with poor sleep quality at 1 month after stroke. Our findings suggested the combination of vitamin D and depression status could provide important predictive information for post-stroke sleep quality.
Background: Hemorrhagic transformation (HT) is a severe complication in patients with acute ischemic stroke (AIS). This study was performed to explore and validate the relation between bilirubin levels and spontaneous HT (sHT) and HT after mechanical thrombectomy (tHT). Methods: The study population consisted of 408 consecutive AIS patients with HT and age- and sex-matched patients without HT. All patients were divided into quartiles according to total bilirubin (TBIL) level. HT was classified as hemorrhagic infarction (HI) and parenchymal hematoma (PH) based on radiographic data. Results: In this study, the baseline TBIL levels were significantly higher in the HT than non-HT patients in both cohorts (p < 0.001). Furthermore, the severity of HT increased with increasing TBIL levels (p < 0.001) in sHT and tHT cohorts. The highest quartile of TBIL was associated with HT in sHT and tHT cohorts (sHT cohort: OR = 3.924 (2.051–7.505), p < 0.001; tHT cohort: OR = 3.557 (1.662–7.611), p = 0.006). Conclusions: Our results suggest that an increased TBIL is associated with a high risk of patients with sHT and tHT, and that TBIL is more suitable as a predictor for sHT than tHT. These findings may help to identify patients susceptible to different types and severity of HT.
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