Circ_0000020 elevates the expression of PIK3CA and facilitates the malignant phenotypes of glioma cells via targeting miR-142-5p.

BACKGROUND: Multiple circular RNAs (circRNAs) have been recently described as crucial oncogenic factors or tumor suppressors. This study aimed to investigate the role of circ_0000020 in glioma progression. METHODS: Circ_0000020 and miR-142-5p expressions in glioma samples were assessed through qRT-PCR, and then the association between pathological indexes and circ_0000020 expressions was analyzed. Functional experiment was performed with human glioma cell lines U251 and U87. Gain-of-function and loss-of-function models were established. CCK-8 assay was used to detect glioma cell proliferation. Transwell assay was used to examine glioma cell migration and invasion. The regulatory relationships among circ_0000020, miR-142-5p and phosphatidylinositol 3-kinase C (PIK3CA) were investigated by bioinformatics analysis, luciferase reporter assay, qRT-PCR and Western blot. In vivo tumorigenesis assay was performed with nude mice to further validate the demonstrations of in vitro experiments. RESULTS: Circ_0000020 expression in glioma samples was remarkably increased compared with that in normal brain tissues and its high expression was associated with unfavorable pathological indexes. Circ_0000020 overexpression remarkably accelerated proliferation, migration and invasion of glioma cells. Accordingly, circ_0000020 knockdown suppressed the malignant phenotypes of glioma cells. Circ_0000020 overexpression significantly reduced miR-142-5p expression by sponging it, and circ_0000020 could enhance the expression of PIK3CA, which was a target gene of miR-142-5p. CONCLUSIONS: Circ_0000020 promotes glioma progression via miR-142-5p/PIK3CA axis.

Neuroserpin extends the time window of tPA thrombolysis in a rat model of middle cerebral artery occlusion.

Tissue-type plasminogen activator (tPA) is characterized as an effective drug for early thrombolytic therapy in acute cerebral infarction (ACI). However, tPA will increase the risk of hemorrhage if it is used beyond the treatment time window. The study aims to explore the effects of neuroserpin (NSP) on the time window of tPA thrombolysis in ACI and the underlying mechanism. The middle cerebral artery occlusion (MCAO) model was constructed in rats, which were randomly divided into six groups: sham operation group, infarction group, 1-hour thrombolysis group, 1-hour thrombolytic + NSP intervention group, 4-hour thrombolytic group, and 4-hour thrombolysis + NSP intervention group. The neurological changes in rats were evaluated by modified neurological severity scores and rota-rod test. The brain edema and cerebral infarction area were evaluated by dry-wet method and triphenyl tetrazolium chloride staining. The blood-brain barrier (BBB) integrity was examined by Evans blue method. The expressions of malondialdehyde, superoxide dismutase, and glutathione peroxidase in brain were also investigated. The expression of caspase-3 and Bcl-2 in brain tissue and apoptosis of neurons were examined by Western blot analysis and toluidine blue staining. tPA thrombolysis significantly attenuated the neurological impairment in rats with MCAO at 1 hour. Conversely, the effect of tPA thrombolysis at 4 hours after MCAO did not significantly help the recovery of neurological function. However, a combination of tPA treatment and NSP treatment at 4 hours after MCAO markedly ameliorated the neurological impairment, cerebral edema, cerebral infarction volume, BBB injury, oxidative stress products, and neuron apoptosis. NSP can probably expand the time window for tPA treatment to reduce neurological impairment in ACI.

Increase in age at onset of moyamoya disease in China over 25 years.

BACKGROUND: To explore whether the age at onset (AAO) of Chinese patients with moyamoya disease (MMD) increased over time due to a reduced exposure to leptospiral infection. METHODS: We performed an independent, multicenter, retrospective study based on data from patients with MMD who initially attended four tertiary hospitals in Hubei, China, from 1996 to 2020. After stratifying the year of MMD onset into five periods (1996-2000, 2001-2005, 2006-2010, 2011-2015, and 2016-2020), we analyzed the temporal trends in AAO and compared different classes of AAO (early-onset, < 20 years; intermediate-onset, 20-49 years; late-onset, ≥ 50 years) in each period. RESULTS: We included 1858 patients in this study, with 878 women and 980 men. Their median (IQR) AAO was 47 (39-55) years. The case AAO significantly increased at the rate of 0.94 years per year (r = 0.406, p < .0001), while no trend was observed in birth years through time (p = .512). The birth cohorts who grew up in the leptospirosis epidemic years was stably susceptible to MMD. The median (IQR) AAO has increased significantly from 26 (14-37) years (1996-2000) to 51 (43-57) years (2016-2020) (p < .0001). The proportion of early-onset MMD was significantly higher in 1996-2000 (33.3%, p < .0001) and 2001-2005 (10.4%, p < .001). The AAO shows an aging trend that the proportion of late-onset MMD went from 4.5% (2001-2005) to 54.5% (2016-2020) (p < .0001). CONCLUSIONS: The AAO of MMD was increasing during a recent 25-year period in China, which may reflect a birth cohort effect that resulted from environmental changes. The disparity risk of birth cohorts with MMD changed with leptospirosis epidemics, suggesting leptospiral exposure might be a potential risk factor.

Clinical Efficacy of Endoscopic Infratentorial Supracerebellar Approach for Pineal Region Tumors: A Retrospective Case-Control Study.

Tumors in the pineal region are deep, with complex surrounding anatomy, adjacent to important blood vessels and nerve structures, and surgical resection is difficult and risky. In this paper, we reviewed the literature to understand the epidemiology and clinical manifestations of pineal region tumors in the country and study the clinical indications, related problems, and successful experiences of patients with pineal region tumors treated by the transtentorial-superior approach. The clinical data of 80 patients with pineal region tumors were selected as the retrospective research objects and divided into the control group and the treatment group, with 40 cases in each group, according to the random number table method. The control group was treated using the endoscopic transtentorial approach (Poppen approach), while the treatment group was treated with the endoscopic supratentorial approach (Krause approach). The inflammatory factors, inflammatory stress response, postoperative neurological dysfunction, clinical efficacy, and poor prognosis were observed and compared between the two groups. Tumor resection and recurrence were used to compare the clinical outcomes of tumors in the pineal region. The extent of surgical resection was 100% higher in both groups, and the treatment group was comparable to the control group. The prognosis of patients after the operation was poor. Nausea and vomiting, visual disturbance, upper vision paralysis, and ataxia in the treatment group were significantly lower than those in the control group, with no statistical significance (P > 0.05). At the same time, the bone window can be reduced to reduce trauma and provide a certain reference for patients to choose a safe and complete resection method.