Circular RNA expression alterations are involved in OGD/R-induced neuron injury.

Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNA-gene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up-regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy.

Lithium perchlorate-nitromethane-promoted alkylation of anilines with arylmethanols.

A new application of lithium perchlorate-nitromethane (LPNM) for the formation of aromatic C-N and C-C bonds is introduced. LPNM-promoted reactions of anilines with diarylmethanols selectively generate N-alkylated anilines or mono and double Friedel-Crafts alkylation products under different conditions by changing the reaction time, reaction temperature, and the ratio of the reactants. This method does not require the use of transition metal catalysts to prepare alkylated aniline derivatives.

Effect of Huwentoxin-I on the Fas and TNF apoptosis pathway in the hippocampus of rat with global cerebral ischemia.

Neuronal injury is the most important reason for various brain injuries. Cytosolic Ca(2+) overloading has been proposed as one of the main cellular processes leading to neuronal death during cerebral ischemia. It is well accepted that Ca(2+) channel blockers can protect cerebral neurons from ischemic injury. In the present studies, we investigated the molecular mechanism for the neuro-protective effect of Huwentoxin-I (HWTX-I), a spider toxin selectively blocking N-type voltage-dependent Ca((2+)) channel, on rat models with global cerebral ischemia-reperfusion injury. Our studies demonstrated that HWTX-I could maintain the morphological stability of pyramidal cells in this model. Furthermore, HWTX-I could decrease the concentration of malon-dialdehyde, but increase the activity of superoxide dismutase and glutathione peroxidase. It also reduced the expression level of related factors of Fas and tumor necrosis factor death receptor apoptosis pathways in the hippocampus. In summary, HWTX-I has an obvious neuroprotective effect, which may act through its inhibition on a certain apoptosis pathway.

Aerobic exercise combined with huwentoxin-I mitigates chronic cerebral ischemia injury.

Ca2+ channel blockers have been shown to protect neurons from ischemia, and aerobic exercise has significant protective effects on a variety of chronic diseases. The present study injected huwentoxin-I (HWTX-I), a spider peptide toxin that blocks Ca2+ channels, into the caudal vein of a chronic cerebral ischemia mouse model, once every 2 days, for a total of 15 injections. During this time, a subgroup of mice was subjected to treadmill exercise for 5 weeks. Results showed amelioration of cortical injury and improved neurological function in mice with chronic cerebral ischemia in the HWTX-I + aerobic exercise group. The combined effects of HWTX-I and exercise were superior to HWTX-I or aerobic exercise alone. HWTX-I effectively activated the Notch signal transduction pathway in brain tissue. Aerobic exercise up-regulated synaptophysin mRNA expression. These results demonstrated that aerobic exercise, in combination with HWTX-I, effectively relieved neuronal injury induced by chronic cerebral ischemia via the Notch signaling pathway and promoting synaptic regeneration.

Increased expression of microRNA-21 in peripheral blood mediates the down-regulation of IFN-γ and increases the prevalence of stroke-associated infection.

BACKGROUND: Increasing levels of microRNA (miRNA)-21 can lead to IFN-γ deficiency, thereby suppressing immune function. Whether changes in the peripheral blood expression of miRNA-21 in patients with acute stroke are related to stroke-associated infection (SAI) remains unsettled. METHODS: MiRNA-21 and IFN-γ expression levels in peripheral blood plasma were measured in stroke patients presenting within 24h of symptom onset to assess whether these expression levels are associated with the prevalence of SAI. RESULTS: The stroke with SAI group had significantly higher miRNA-21 expression and lower IFN-γ levels than the stroke without SAI group (p<0.05). A significant negative correlation was observed between miRNA-21 expression and IFN-γ levels (r=-0.303, p=0.026). ROC curves were constructed to measure the performance of the miRNA-21 and IFN-γ to judge SAI. The areas under the ROC curve (AUC) for miRNA-21 and IFN-γ were 0.667 (95% CI, 0.525 to 0.798, p=0.028) and 0.698 (95% CI, 0.558 to 0.816, p=0.005), respectively. The optimal cutoff value was miRNA-21>0.53 and IFN-γ≤72.57pg/ml. There was a significantly different prevalence of SAI between the high miRNA-21 group and the low miRNA-21 group (p=0.008, log rank test). There was also a significant difference between the high IFN-γ group and the low IFN-γ group (p=0.003, log rank test). CONCLUSIONS: Plasma up-regulated miRNA-21 and decreased IFN-γ in acute stroke can be considered new biological predictors for SAI and thus, new therapeutic targets.