Melatonin protects against rotenone-induced cell injury via inhibition of Omi and Bax-mediated autophagy in Hela cells

Parkinson's disease is the second most common neurodegenerative disease, and environmental toxins such as rotenone play an important role in causing degeneration of dopaminergic neurons. Melatonin, a major secretory product of pineal, is recently reported to protect against rotenone-induced cell death in animal models. Yet, the mechanism involved in this protection needs to be elucidated. Here, we report that rotenone treatment (0-100 μM) decreased cell survival of Hela cells in a dose-dependent manner. At concentrations ranging from 0.1 to 100 μM, rotenone induced a dose-dependent increase in the expression of microtubule-associated protein 1 light chain 3 (LC3)-II, a protein associated with the autophagosomal membrane. Knockdown of Bax or Omi using shRNA inhibited 1 μM rotenone-induced autophagy. To determine whether melatonin would protect cells against rotenone-induced cell death and autophagy, we pretreated Hela cells with 250 μM melatonin for 24 hr in the presence of rotenone. Melatonin inhibited Bax expression and the release of the omi/HtrA2 into the cytoplasm induced by 1 μM rotenone. Melatonin 250 μM treatment also suppressed cell death induced by 0.1-100 μM rotenone and protected against the formation of LC3-II in cells exposed to 1 μM rotenone. This work demonstrates a novel role for melatonin as a neuroprotective agent against rotenone.     

Retinoic Acid and Human Olfactory Ensheathing Cells Cooperate to Promote Neural Induction From Human Bone Marrow Stromal Stem Cells

The generation of induced neuronal cells from human bone marrow stromal stem cells (hBMSCs) provides new avenues for basic research and potential transplantation therapies for nerve injury and neurological disorders. However, clinical application must seriously consider the risk of tumor formation by hBMSCs, neural differentiation efficiency and biofunctions resembling neurons. Here, we co-cultured hBMSCs exposed to retinoic acid (RA) with human olfactory ensheathing cells (hOECs) to stimulate its differentiation into neural cells, and found that hBMSCs following 1 and 2 weeks of stimulation promptly lost their immunophenotypical profiles, and gradually acquired neural cell characteristics, as shown by a remarkable up-regulation of expression of neural-specific markers (Tuj-1, GFAP and Galc) and down-regulation of typical hBMSCs markers (CD44 and CD90), as well as a rapid morphological change. Concomitantly, in addition to a drastic decrease in the number of BrdU incorporated cells, there was a more elevated synapse formation (a hallmark for functional neurons) in the differentiated hBMSCs. Compared with OECs alone, this specific combination of RA and hOECs was significantly potentiated neuronal differentiation of hBMSCs. The results suggest that RA can enhance and orchestrate hOECs to neural differentiation of hBMSCs. Therefore, these findings may provide an alternative strategy for the repair of traumatic nerve injury and neurological diseases with application of the optimal combination of RA and OECs for neuronal differentiation of hBMSCs.     

血浆ox-LDL在阿尔茨海默病患者中的临床研究

目的探讨氧化低密度脂蛋白(oxidized Low density lipoprotein,ox-LDL)与阿尔茨海默病(Alzheimer’s dis-ease,AD)患者认知功能损害的关系。方法运用简易精神状态检查量表(mini mental state examination,MMSE)检测入组患者认知功能,将其分为3组,即正常组(NC组,37例)、血管性痴呆组(VD组,41例)、阿尔茨海默病组(AD组,48例),分别用酶联免疫吸附试验(enzyme-linked immunosorbnent assay,ELSIA)测定3组患者血浆ox-LDL的浓度。结果 NC组、VD组、AD组患者血浆ox-LDL浓度分别为(47.46±10.04)μg/L、(60.95±11.78)μg/L、(112.25±17.81)μg/L,AD组患者血浆ox-LDL浓度显著高于VD组,差异有统计学意义(P<0.01);相关分析显示,AD患者血浆ox-LDL浓度与MMSE得分呈负相关(r=-0.574,P<0.01);对AD患者各个认知领域的分值与血浆ox-LDL水平进行多元线性回归分析显示,血浆ox-LDL水平与AD患者记忆力、定向力、注意力和计算能力呈负相关。结论血浆ox-LDL浓度测定有可能作为判断AD患者认知功能损害的生化指标,亦可作为AD与VD鉴别诊断的生物学指标。     

奥卡西平对癫癎患儿外周血MDR1表达的影响

目的通过比较奥卡西平(oxcarbazepine,OXC)和卡马西平(carbamazepine,CBZ)对癫癎患儿外周血多药耐药基因1(MDR1)表达的影响,初步探讨长期应用OXC治疗癫癎对患儿外周血MDR1的诱导作用。方法 48例癫癎患儿分为2组,26例口服OXC,22例口服CBZ,治疗时间均超过12个月;25例无癫发作患儿为空白对照组。选择用药前、用药后6个月及12个月三个时间点,应用RT-PCR法测定患儿外周血MDR1-mRNA的表达。结果 OXC组和CBZ组外周血MDR1-mRNA表达在用药后6个月、12个月较对照组增高(P<0.01);OXC组和CBZ组患儿外周血MDR1-mRNA表达在用药后6个月及12个月较开始服药前均有增高(P<0.05);OXC组在用药6个月及12个月后外周血MDR1-mRNA表达和卡马西平组比较差异无统计学意义(P>0.05)。结论长期口服OXC和CBZ均会增加癫癎患儿外周血MDR1基因的表达。     

Plasticity of language pathways in patients with low-grade glioma A diffusion tensor imaging study

Knowledge of the plasticity of language pathways in patients with low-grade glioma is important for neurosurgeons to achieve maximum resection while preserving neurological function. The current study sought to investigate changes in the ventral language pathways in patients with low-grade glioma located in regions likely to affect the dorsal language pathways. The results revealed no significant difference in fractional anisotropy values in the arcuate fasciculus between groups or between hemispheres. However, fractional anisotropy and lateralization index values in the left inferior longitudinal fasciculus and lateralization index values in the left inferior fronto-occpital fasciculus were higher in patients than in healthy subjects. These results indicate plasticity of language pathways in patients with low-grade glioma. The ventral language pathways may perform more functions in patients than in healthy subjects. As such, it is important to protect the ventral language pathways intraoperatively.     

Growth and differentiation of neural stem cells in a three-dimensional collagen gel scaffold

Collagen protein is an ideal scaffold material for the transplantation of neural stem cells. In this study, rat neural stem cells were seeded into a three-dimensional collagen gel scaffold, with suspension cultured neural stem cells being used as a control group. Neural stem cells, which were cultured in medium containing epidermal growth factor and basic fibroblast growth factor, actively expanded and formed neurospheres in both culture groups. In serum-free medium conditions, the processes extended from neurospheres in the collagen gel group were much longer than those in the suspension culture group. Immunofluorescence staining showed that neurospheres cultured in collagen gels were stained positive for nestin and differentiated cells were stained positive for the neuronal marker βIII-tubulin, the astrocytic marker glial fibrillary acidic protein and the oligodendrocytic marker 2’,3’-cyclic nucleotide 3’-phosphodiesterase. Compared with neurospheres cultured in suspension, the differentiation potential of neural stem cells cultured in collagen gels increased, with the formation of neurons at an early stage. Our results show that the three-dimensional collagen gel culture system is superior to suspension culture in the proliferation, differentiation and process outgrowth of neural stem cells.     

Hyperbaric oxygen therapy improves cognitive functioning after brain injury

Hyperbaric oxygen therapy has been widely applied and recognized in the treatment of brain injury; however, the correlation between the protective effect of hyperbaric oxygen therapy and changes of metabolites in the brain remains unclear. To investigate the effect and potential mechanism of hy- perbaric oxygen therapy on cognitive functioning in rats, we established traumatic brain injury models using Feeney＇s free falling method. We treated rat models with hyperbaric oxygen therapy at 0.2 MPa for 60 minutes per day. The Morris water maze test for spatial navigation showed that the average escape latency was significantly prolonged and cognitive function decreased in rats with brain injury. After treatment with hyperbaric oxygen therapy for 1 and 2 weeks, the rats＇ spatial learning and memory abilities were improved. Hydrogen proton magnetic resonance spectroscopy analysis showed that the N-acetylaspartate/creatine ratio in the hippocampal CA3 region was sig- nificantly increased at 1 week, and the N-acetylaspartate/choline ratio was significantly increased at 2 weeks after hyperbaric oxygen therapy. Nissl staining and immunohistochemical staining showed that the number of nerve cells and Nissl bodies in the hippocampal CA3 region was significantly increased, and glial fibrillary acidic protein positive cells were decreased after a 2-week hyperbaric oxygen therapy treatment. Our findings indicate that hyperbaric oxygen therapy significantly im- proves cognitive functioning in rats with traumatic brain injury, and the potential mechanism is me- diated by metabolic changes and nerve cell restoration in the hippocampal CA3 region.     

State-Dependent Effects of Prefrontal Repetitive Transcranial Magnetic Stimulation on Emotional Working Memory

BackgroundA growing body of findings illustrates the importance of state-dependency in studies using brain stimulation.ObjectiveWe aimed to investigate the effects of tDCS priming followed by rTMS applied over the right dorsolateral prefrontal cortex (DLPFC) on emotional working memory.MethodsIn a randomized single-blind within-subjects design, participants performed an emotional 3-back task at baseline and after tDCS priming (anodal, cathodal) and subsequent low-frequency rTMS (active, sham) of the right DLPFC. Stimuli consisted of words related to the distinct emotion categories fear and anger as well as neutral words.ResultsTask accuracy increased for fear-related words and decreased for neutral words across stimulation conditions. No general state-dependent effects of prefrontal rTMS on working memory were found. We further showed a detrimental effect of negative emotional content on working memory performance.ConclusionsOur findings support a hemispheric lateralization of emotion processing by demonstrating that the withdrawal-related emotion fear is associated with the right DLPFC and contribute to clarifying the interaction between working memory and emotion.     

无痛结肠镜下大肠息肉切除1229例临床效果观察

结肠镜下进行大肠息肉切除共2 256例,分为无痛组1 229例和常规组1 027例。无痛组治疗时间为(14.2±2.8)min,常规组为(18.1±3.2)min(P<0.05);成功率无痛组为97.25%,常规组为92.36%,(P<0.05);满意程度无痛组明显提高(P<0.05);腹痛腹胀、血管迷走反射和术中体动等不良反应无痛组显著低于常规组(P<0.01);舌后坠、头晕等不良反应无痛组显著高于常规组(P<0.01或0.05);肠道穿孔等严重并发症发生率两组无明显差异。