Prolonged cortical silent period is related to poor fitness and fatigue,but not tumor necrosis factor,in Multiple Sclerosis

ObjectivePoor fitness among people with Multiple Sclerosis (MS) aggravates disease symptoms. Whether low fitness levels accompany brain functioning changes is unknown.MethodsMS patients (n = 82) completed a graded maximal exercise test, blood was drawn, and transcranial magnetic stimulation determined resting and active motor thresholds, motor evoked potential latency, and cortical silent period (CSP).ResultsSixty-two percent of participants had fitness levels ranked below 10th percentile. Fitness was not associated with disability measured using the Expanded Disability Status Scale (EDSS). Regression analyses revealed that, cardiorespiratory fitness, when controlling for disease demographics, contributed 23.7% (p < 0.001) to the model explaining variance in CSP. Regression analysis using cardiorespiratory fitness and CSP as predictors showed that CSP alone explained 19.9% of variance in subjective fatigue (p = 0.002). Tumor necrosis factor was not associated with any variable.ConclusionLow fitness was associated with longer CSP in MS. Longer CSP was, in turn, related to greater MS fatigue.SignificanceMS patients had extremely low levels of cardiorespiratory fitness. Poor fitness predicted longer CSP, a marker of greater intracortical inhibition, which was linked to MS fatigue. Future research should examine whether aerobic training could shorten CSP and potentially lessen inhibition of cortical networks.     

Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells

Objective: To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells. Methods: Different concentrations of berberine were used to treat mouse insulinoma(MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro-and anti-apoptosis proteins were detected by western-blotting. Results: The half-maximal inhibitory concentration(IC50) of berberine was 5.7 μmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction(P0.05) in cell number after only 4-h incubation; which reached 50% after 24 h(P0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9-and 4.6-fold after treating with berberine(5 μmol/L) for 8 and 16 h, while 3-and 8.7-fold after 10 μmol/L treatment for 8 and 16 h(P0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1(Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade. Conclusion: High concentration(5 and 10 μmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor(AIF) pathway.     

Comparing physical activity and sedentary behavior levels between deaf and hearing adolescents

BackgroundDeaf adolescents may engage in less physical activity (PA) and longer sedentary time than their hearing peers. Yet, literature comparing PA levels and sedentary time between deaf and hearing control groups, as well as studies examining predictors of PA among deaf adolescents, are lacking.ObjectiveThis cross-sectional survey aimed to compare PA levels and sedentary time between the two groups and examine predictors (i.e., gender and social inclusion) of PA participation among deaf adolescents.MethodsParticipants were 98 deaf and 99 hearing adolescents, who completed the survey measuring the variables of interest.ResultsDeaf adolescents had a higher level of sedentary behavior as well as lower levels of light PA, moderate-to-vigorous PA, and total metabolic equivalent task (MET) than the hearing group. Only a small proportion of participants (deaf: 4%; hearing: 24%) met the World Health Organization's PA recommendation. Gender was found to negatively predict total MET among deaf, while social inclusion was a positive predictor.ConclusionsDeaf adolescents may have restricted PA participation. Measures should be used to promote social inclusion for increasing PA levels of this population.     

可手术非小细胞肺癌患者术前血浆中VEGF/sVEGFR-1比值与长期生存关系的初步探索

目的:检测可手术非小细胞肺癌患者术前血浆中VEGF、sVEGFR-1的表达水平，并分析其与临床病理资料和长期生存的关系。方法:收集98例可手术非小细胞肺癌患者术前静脉血，用ELISA方法检测血浆中VEGF和sVEGFR-1的表达水平，并分析其表达水平与患者临床病理资料和长期生存之间的关系。结果:可手术非小细胞肺癌患者术前血浆中VEGF、sVEGFR-1的表达水平与患者的临床病理资料没有相关性，但是多因素生存分析中，年龄、TNM分期和VEGF/sVEGFR-1比值是可手术非小细胞肺癌患者长期生存的独立预后因子。结论:血浆VEGF/sVEGFR-1比值与可手术非小细胞肺癌患者的长期生存相关，该比值在非小细胞肺癌的意义值得进一步深入研究。     

靶向沉默髓鞘转录因子MyT1对脑胶质瘤细胞恶性生物学行为的影响

目的 探讨靶向沉默髓鞘转录因子1（MyT1）对人脑胶质瘤细胞迁移、侵袭和黏附的影响和相关分子机制。方法 设计特异性靶向沉默MyT1基因的shRNA，包装慢病毒后感染人脑胶质瘤U-118MG和U-87MG细胞，qPCR和Western blot检测两种细胞中MyT1的表达水平，BrdU实验、细胞划痕实验、Transwell实验和细胞黏附实验分别检测两种细胞的迁移、侵袭和黏附能力的变化，qPCR检测细胞黏附和肿瘤转移相关基因的表达水平。结果 在HEK293T细胞中包装了特异性靶向MyT1基因的shRNA慢病毒，并成功感染了U-118MG和U-87MG细胞；两种细胞中MyT1 mRNA和蛋白表达水平均显著下调（均P<0.05），细胞的迁移、侵袭和黏附能力均有一定程度的降低（均P<0.05），细胞黏附相关基因表达水平显著下降，肿瘤转移相关基因表达水平显著上升（均P<0.05）。结论 靶向沉默MyT1基因对人脑胶质瘤U-118MG和U-87MG细胞的迁移、侵袭和黏附能力有抑制作用，其机制可能与调控细胞黏附和肿瘤转移相关基因的表达有关。MyT1基因的表达，可能是脑胶质瘤诊疗的一个潜在靶标。     

Elevation of circulating neutrophil extracellular traps,interleukin (IL)-8, IL-22, and vascular endothelial growth factor in patients with venomous snake mamushi (Gloydius blomhoffii) bites

Mamushi bites cause swelling and pain that extend from the bitten site. The coagulopathic, anti-coagulopathic, and vasculopathic actions of mamushi venom result in various laboratory abnormalities, occasionally with muscular, renal, and other organ damage. We investigated the serum biomarkers that were associated with the pathogenesis of mamushi bites, focusing on markers related to tissue-damage and neutrophil activation. Twenty patients (one case of grade 2, 13 cases of grade 3, and six cases of grade 4 of severity) seen by us in one summer season were enrolled. Peripheral blood samples were taken from the patients on day 0, day 2, and day 7 after mamushi bites. In addition to routine blood examination, serum samples were subjected to enzyme-linked immunosorbent assay for citrullinated histone H3 (CitH3), interleukin (IL)-8, IL-17A, IL-22, vascular endothelial growth factor (VEGF), high mobility group box protein 1 (HMGB1), tumor necrosis factor (TNF)-α, and IL-33. Creatinine kinase (CK) values significantly correlated with prothrombin time (PT) levels, suggesting that muscular damage is associated with exaggerated coagulation and fibrinolysis. In the vast majority of patients, HMGB1, TNF-α, and IL-33 were under detection levels. Neutrophil counts did not correlate with PT or CK, indicating that the coagulation disorder and muscular damage were virtually independent of the neutrophil activation. The neutrophil number significantly correlated with CitH3, a representative marker of neutrophil extracellular traps. Moreover, there were significant correlations between neutrophil number, CitH3, IL-8, IL-22, and VEGF. Our study suggests that there are two major cascades in mamushi bites. One is an already characterized venom effect on coagulation, vessels, and muscles. In the other novel cascade, we propose that neutrophil activation with IL-8 leads to the production of IL-22 and VEGF. This sequential event may contribute to both vascular damage and repair.