No abstract

Background: Inflammatory damage following stroke aggravates brain damage, resulting in long-term neurological sequelae. The purpose of this study was to identify ways to reduce inflammatory reactions and to accelerate neuron regeneration after cerebral apoplexy. Methods: We formulated a biomimetic vesicle, the leukosome, constituted by liposome, artificial long intergenic noncoding RNA (lincRNA)-EPS, and membrane proteins derived from macrophages and their physical-chemical characteristics were evaluated. Migration distance and cytotoxic levels were measured to determine the effect of lncEPSleukosomes on lipopolysaccharide-activated microglia. An in vivo transient middle cerebral artery occlusion/reperfusion (tMCAO) model was established in mice, which were treated with lncEPS-leukosomes. Vesicle seepage, infiltration of inflammatory cells, cytotoxic levels in the cerebrospinal fluid, and neural stem cell (NSC) density were measured. Results: Biomimetic vesicles with a homogeneous size increased lincRNA-EPS levels in activated microglia by 77.9%. In vitro studies showed that lincRNA-EPS inhibited the migration and cytotoxic levels of activated microglia by 63.2% and 43.6%, respectively, which promoted NSC proliferation and anti-apoptotic ability. In vivo data showed that leukosomes targeted to inflamed sites and lncEPS-leukosomes decreased the infiltration of inflammatory cells and cytotoxic levels by 81.3% and 48.7%, respectively. In addition, lncEPS-leukosomes improved neuron density in the ischemic core and boundary zone after tMCAO. Conclusions: The biomimetic vesicles formulated in this study targeted inflammatory cells and accelerated neuron regeneration by promoting inflammation resolution. This study may provide a promising treatment approach for accelerated neuron regeneration after cerebral apoplexy.

Amyotrophic lateral sclerosis (ALS) is the third most common neurodegenerative disease after Alzheimer's disease (AD) and Parkinson's disease (PD). In order to unravel more genetic etiology of ALS, genome-wide association studies (GWAS) have been conducted. However, the newly identified ALS susceptibility loci exert only very small risk effects and cannot fully explain the underlying ALS genetic risk. A large proportion of the heritability of ALS is still to be explained. Recently, pathway analysis of GWAS has been used to investigate the mechanisms of AD and PD. We think that AD or PD risk pathways may also be involved in ALS. In order to confirm this view, we conducted a pathway analysis of two independent ALS GWAS. We identified multiple classifications of the Kyoto Encyclopedia of Genes and Genomes pathways related to metabolism, immune system and diseases, environmental information processing, genetic information processing, cellular processes, and nervous system and neurodegenerative diseases to be the consistent signals in the two ALS GWAS. On the single pathway level, we identified 12 shared pathways. We compared the findings from ALS GWAS with those of previous pathway analyses of AD and PD GWAS. The results further supported the involvement of AD and PD risk pathways in ALS. We believe that our results may advance the understanding of ALS mechanisms and will be very useful for future genetic studies.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Previous studies have reported that there are causative links between the abnormal regulation of miRNAs and cancer development. Hsa‑miR‑495 has previously been demonstrated to be downregulated, and to function as a tumor suppressor, in numerous types of human cancer. However, the function and molecular mechanism of hsa‑miR‑495 in glioma remains unclear. In the current study, the expression and effects of hsa‑miR‑495 on glioma were evaluated. It was identified that the expression levels of hsa-miR-495 were downregulated in glioma tissues and cell lines. Furthermore, restoration of hsa-miR-495 inhibited glioma cell proliferation and invasion in vitro. Notably, a luciferase reporter assay revealed that hsa‑miR‑495 was able to directly target v‑myb avian myeloblastosis viral oncogene homolog (MYB) in glioma cells. In addition, an RNA interference assay indicated that MYB knockdown inhibited glioma cell proliferation and invasion in vitro. In conclusion, the results of the present study suggested that hsa‑miR‑495 may act as a tumor suppressor gene in glioma by directly inhibiting MYB expression, which may provide a novel therapeutic strategy for the treatment of glioma.

Allicin, a molecule predominantly responsible for the pungent odor and the antibiotic function of garlic, exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of various disorders. The present study aimed to elucidate the effect of allicin in cerebral ischemia/reperfusion (I/R) injury in rats. Rats were subjected to 1.5 h of transient middle cerebral artery occlusion (MCAO), followed by 24 h of reperfusion. Rats were randomly assigned to the sham surgery group, the MCAO group and the MCAO + allicin group. Neurological score, cerebral infarct size, brain water content, neuronal apoptosis, serum tumor necrosis factor (TNF)‑α and myeloperoxidase (MPO) activity were measured. The results suggested that allicin reduced cerebral infarction area, brain water content, neuronal apoptosis, TNF‑α levels and MPO activity in the serum. The results of the present study indicated that allicin protects the brain from cerebral I/R injury, which may be ascribed to its anti‑apoptotic and anti‑inflammatory effects.