Neural stem cell-derived exosome as a nano-sized carrier for BDNF delivery to a rat model of ischemic stroke.

Our previous study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes (hNSC-Exo) in ischemic stroke. Here, we loaded brain-derived neurotrophic factor (BDNF) into exosomes derived from NSCs to construct engineered exosomes (BDNF-hNSC-Exo) and compared their effects with those of hNSC-Exo on ischemic stroke both in vitro and in vivo. In a model of H2O2-induced oxidative stress in NSCs, BDNF-hNSC-Exo markedly enhanced cell survival. In a rat middle cerebral artery occlusion model, BDNF-hNSC-Exo not only inhibited the activation of microglia, but also promoted the differentiation of endogenous NSCs into neurons. These results suggest that BDNF can improve the function of NSC-derived exosomes in the treatment of ischemic stroke. Our research may support the clinical use of other neurotrophic factors for central nervous system diseases.

Effect of differential hypoxia-related gene expression on glioblastoma.

OBJECTIVE: Glioblastoma (GB) is a refractory malignancy with a high rate of recurrence and treatment resistance. Hypoxia-related genes are promising prognostic indicators for GB, so we herein developed a reliable hypoxia-related gene risk scoring model to predict the prognosis of patients with GB. METHOD: Gene expression profiles and corresponding clinicopathological features of patients with GB were obtained from the Cancer Genome Atlas (TCGA; n = 160) and Gene Expression Omnibus (GEO) GSE7696 (n = 80) databases. Univariate and multivariate Cox regression analyses of differentially expressed hypoxia-related genes were performed using R 3.5.1 software. RESULT: Fourteen prognosis-related genes were identified and used to construct a risk signature. Patients with high-risk scores had significantly lower overall survival (OS) than those with low-risk scores. The median risk score was used as a critical value and for OS prediction in an independent external verification GSE7696 cohort. Risk score was not significantly affected by clinical-related factors. We also developed a prediction nomogram based on the TCGA training set to predict survival rates, and included six independent prognostic parameters in the TCGA prediction model. CONCLUSION: We determined a reliable hypoxia-related gene risk scoring model for predicting the prognosis of patients with GB.

Cerebral dopamine neurotrophic factor promotes the proliferation and differentiation of neural stem cells in hypoxic environments.

Previous research found that cerebral dopamine neurotrophic factor (CDNF) has a protective effect on brain dopaminergic neurons, and CDNF is regarded as a promising therapeutic agent for neurodegenerative diseases. However, the effects of CDNF on the proliferation, differentiation, and apoptosis of neural stem cells (NSCs), which are very sensitive to hypoxic environments, remain unknown. In this study, NSCs were extracted from the hippocampi of fetal rats and cultured with different concentrations of CDNF. The results showed that 200 nM CDNF was the optimal concentration for significantly increasing the viability of NSCs under non-hypoxic environmental conditions. Then, the cells were cultured with 200 nM CDNF under the hypoxic conditions of 90% N2, 5% CO2, and 5% air for 6 hours. The results showed that CDNF significantly improved the viability of hypoxic NSCs and reduced apoptosis among hypoxic NSCs. The detection of markers showed that CDNF increased the differentiation of hypoxic NSCs into neurons and astrocytes. CDNF also reduced the expression level of Lin28 protein and increased the expression of Let-7 mRNA in NSCs, under hypoxic conditions. In conclusion, we determined that CDNF was able to reverse the adverse proliferation, differentiation, and apoptosis effects that normally affect NSCs in a hypoxic environment. Furthermore, the Lin28/Let-7 pathway may be involved in this regulated function of CDNF. The present study was approved by the Laboratory Animal Centre of Southeast University, China (approval No. 20180924006) on September 24, 2018.

Upregulated expression of human alpha-defensins 1, 2 and 3 in hypercholesteremia and its relationship with serum lipid levels.

Human alpha-defensins are natural antimicrobial peptides of neutrophils evolved in host defense reactions and circulating nonstressed alpha-defensins may be associated with serum lipid levels. The aim of this work was to examine whether the expression of alpha-defensins 1, 2 and 3 genes are changed and whether this changes are reversed following treatment in patients with hypercholesteremia. A total of 40 individuals of hypercholesteremia group were studied, compared with 40 individuals of normal control group. Protein levels and gene expression levels of alpha-defensins 1, 2 and 3 were significantly higher in patients with hypercholesteremia compared with subjects in normal control group. In patients with hypercholesteremia, protein levels of alpha-defensins 1, 2 and 3 correlated positively with the levels of total cholesterol and low-density lipoprotein cholesterol. Protein levels and gene expression levels of alpha-defensins 1, 2 and 3 were decreased significantly after a treatment with atorvastatin calcium 20mg daily compared with the patients before the treatment. Our results suggest that the expression of alpha-defensins 1, 2 and 3 genes is involved in dyslipidemia in patients with hypercholesteremia.