MicroRNA expression profiling of PPD-B stimulated PBMC from M. bovis-challenged unvaccinated and BCG vaccinated cattle

There is an urgent need to identify additional diagnostic biomarkers for bovine TB to complement existing read-out systems such as interferon-gamma and for predictive markers of vaccine efficacy to accelerate vaccine development. To evaluate the potential of miRNAs as such biomarkers, we have analysed their expression in bovine PPD stimulated PBMC isolated from unvaccinated and BCG vaccinated cattle before and following Mycobacterium bovis (M. bovis) infection. Using a bovine microRNA microarray, miR-155 was found to show a significant up-regulation in expression in early (week 2) and late (week 11) M. bovis post-infection samples from unvaccinated cattle, while in BCG vaccinated cattle up-regulation was observed only in late post-infection samples. No differential expression of miR-155 was observed in pre-infection samples from unvaccinated and vaccinated cattle. These observations suggest that miR-155 could be exploited as a marker distinguishing vaccinated from infected animals (DIVA). Analysis by TaqMan RT-PCR, verified the up-regulation of miR-155 in unvaccinated cattle post-infection. Significant correlation was found between the degree of pathology and miR-155 induction in the experimentally infected cattle, suggesting miR-155 is a biomarker of disease development and/or severity. Induction of miR155 expression in cattle sourced from farms with confirmed bTB that tested positive in the tuberculin skin or interferon-gamma blood test was found to be significantly higher in cattle presenting with more advanced pathology (defined by the presence of visible TB lesions) compared to infected cattle without visible pathology and thus likely to be of lower infectivity than those with more advanced disease. In conclusion, our data indicate that miR-155 has potential both as a diagnostic and prognostic biomarker that could be used to identify animals with advanced pathology and as a DIVA test read-out. Its role in the immune biology of bovine TB will also be discussed.     

慢性肝损伤致肝纤维化过程中微小RNA200家族的表达

目的观察肝组织中微小RNA200(miR-200)家族成员在慢性肝损伤致肝纤维化过程中表达变化并探讨其机制。方法雄性Wistar大鼠皮下注射四氯化碳(CCl4)制备肝纤维化模型,分别在2、4、6、8周处死大鼠测定肝脏指数、血清ALT、AST含量,观察肝组织病理改变,Real-time PCR检测肝组织miR-200a、b、c、141、429mRNA表达变化。结果模型各组大鼠肝脏指数、血清ALT、AST含量显著高于正常对照组(P<0.01),8周模型组肝纤维化明显,8周模型组肝组织中miR-200a、b、c、141、429mRNA表达较正常组显著增加(P<0.05)。结论 miR-200s在慢性肝损伤致肝纤维化过程中的表达变化,提示其参与慢性肝损伤及肝纤维化的发生发展。     

Micro-RNA abundance and stability in human brain: Specific alterations in Alzheimer's disease temporal lobe neocortex

Micro-RNA (miRNA) mediated regulation of messenger RNA (mRNA) complexity in the central nervous system (CNS) is emerging as a critical factor in the control of CNS-specific gene expression during development, plasticity, aging and disease. In these studies, miRNA array and Northern blot based tracking of specific miRNA abundances and decay kinetics in human neural (HN) cells in primary culture and in short post-mortem interval (PMI, ∼1 h) human brain tissues showed a limited stability and relatively short half-life (∼1–3.5 h) for specific brain-enriched miRNAs. In short PMI Alzheimer's disease (AD)-affected temporal lobe neocortex, miRNA-9, miRNA-125b and miRNA-146a were found to be significantly up-regulated, an effect that was not seen in several related neurological disorders. The results suggest (a) that unless specifically stabilized, certain brain-enriched miRNAs represent a rapidly executed signaling system employing highly transient effectors of CNS gene expression, and (b) that in AD temporal lobe neocortex specific brain miRNAs are significantly up-regulated in abundance and strongly correlate with the presence of AD-type neuropatholgical change.     

微小核糖核酸芯片技术在难治性癫(痫)患者脑组织中表达谱

目的:采用微小核糖核酸(miRNA)芯片技术筛选出在难治性癫(痫)患者脑组织中表达有显著差异者,探讨其在难治性癫(痫)发病中的作用及意义.方法:应用miRNA芯片技术获得6例难治性癫(痫)患者及4例对照组脑组织中表达有差异的miRNA,筛选出倍数变化(F/C) ＞1.5且经t检验P＜0.05并对表达有差异的miRNA进行聚类分析.结果:筛选出表达有显著差异的miRNA基因13条,其中上调基因11条,分别是miR-10a、miR-374c、miR-376a、miR-425、miR-9、miR-224、hsa-miR-26a、let-7c、let-7a、miR-23c及miR-378c,下调基因2条,分别是miR-576-5p及miR-199b-5p.结论:建立了难治性癫(痫)患者脑组织和非癫(痫)患者脑组织表达中有差异的miRNA谱,并获得表达显著上调基因11条,显著下调2条,为进一步研究难治性癫(痫)提供了相关依据.     

Promise of resveratrol for easing status epilepticus and epilepsy

Resveratrol (RESV; 3,5,4′-tri-hydroxy stilbene), a naturally occurring phytoalexin, is found at a high concentration in the skin of red grapes and red wine. RESV mediates a wide-range of biological activities, which comprise an increased life span, anti-ischemic, anti-cancer, antiviral, anti-aging and anti-inflammatory properties. Studies in several animal prototypes of brain injury suggest that RESV is an effective neuroprotective compound. Ability to enter the brain after a peripheral administration and no adverse effects on the brain or body are other features that are appealing for using this compound as a therapy for brain injury or neurodegenerative diseases. The goal of this review is to discuss the promise of RESV for treating acute seizures, preventing the acute seizure or status epilepticus induced development of chronic epilepsy, and easing the chronic epilepsy typified by spontaneous recurrent seizures and cognitive dysfunction. First, the various beneficial effects of RESV on the normal brain are discussed to provide a rationale for considering RESV treatment in the management of acute seizures and epilepsy. Next, the detrimental effects of acute seizures or status epilepticus on the hippocampus and the implications of post-status epilepticus changes in the hippocampus towards the occurrence of chronic epilepsy and cognitive dysfunction are summarized. The final segment evaluates studies that have used RESV as a neuroprotective compound against seizures, and proposes studies that are critically needed prior to the clinical application of RESV as a prophylaxis against the development of chronic epilepsy and cognitive dysfunction after an episode of status epilepticus or head injury.