Study on the Mechanism of BMSCs in Regulating NF-κB Signal Pathway by Targeting miR-449a to Improve the Inflammatory Response to Peripheral Nerve Injury.

OBJECTIVE: To evaluate the mechanism of Bone Marrow Mesenchymal Stem Cells (BMSCs) in regulating NF-κB signal pathway by targeting miR-449a. METHODS: Stem cells were transfected by over-expressing and inhibiting miR-449a to detect the levels and viability of miR-449a in stem cells after transfection. Stem cells and neurons were co-cultured in vitro to evaluate the in vitro mechanism of stem cells over-expressing miR-449a on neurons. RESULTS: After the addition of neurons, the neuronal activity of miR-449a over-expression group increased significantly, the expression of NF-κB signal pathway proteins (IκBα, p50, and p65) decreased, and the inflammatory cytokines (TNF-α and IL-1ß) decreased significantly (P<0.05). In vivo experiments in rats also showed that rats were unresponsive, did not chirp or elude after being stimulated. After stem cell therapy, the weight and response of rats gradually returned to normal levels. miR-449a expression significantly increased in the stem cell + miR-449a over-expression group, expression of NF-κB signal pathway proteins (IκBα, p50, and p65) decreased, inflammatory cytokines (TNF-α and IL-1ß) significantly decreased, and cell activity significantly increased (P<0.05). CONCLUSIONS: BMSCs can modulate NF-κB signaling pathway by targeting miR-449a, so as to reduce the inflammatory response to peripheral nerve injury and repair nerve injury.

MicroRNA-140 silencing represses the incidence of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative condition leading to severe disability from progressive impairments in cognitive functions including memory and learning. Non-coding microRNAs (miRNAs or miRs) have been linked to the pathogenesis of AD. The present study aimed to investigate the clinical significance and biological function of miR-140 in AD. First, we examined the expression of miR-140 and PINK1 in brain tissues of the established AD model rats and neurons cultured with Aß-derived diffusible ligands (AßDDLs). We identified an interaction between miR-140 and PINK1, and measured spatial learning and memory abilities of the model rats using the Morris water maze (MWM) test. After ectopic expression and depletion experiments in neurons and AD rats, we measured the levels of reactive oxygen species (ROS), and mitochondrial membrane potential (MMP), along with mTOR expression and phosphorylation, and autophagy-related factors. Results showed up-regulation of miR-140 and down-regulation of PINK1 in AD model rats and neurons. PINK1 was verified to be a direct target of miR-140, and silencing of miR-140 suppressed mitochondrial dysfunction, and enhanced autophagy in AD model rats and neurons, as supported by decreased levels of mTOR expression and phosphorylation, ß-amyloid p-Tau (Ser396), p-Tau (Thr231), Tau and ROS, and increased MMP levels and expression of Beclin 1 expression and LC3-II/LC3-I. Collectively, functional suppression of miR-140 enhanced autophagy and prevented mitochondrial dysfunction by upregulating PINK1, ultimately suggesting a novel therapeutic target for AD.

CACNA1C rs1006737 SNP increases the risk of essential hypertension in both Chinese Han and ethnic Russian people of Northeast Asia.

ABSTRACT: Voltage-gated Ca2+ channels play a key role in the regulation of arterial tone and blood pressure. The aim of this study was to determine whether the association of calcium voltage-gated channel subunit alpha1 C (CACNA1C) rs1006737 with essential hypertension (EH) exists in both Chinese Han and ethnic Russian populations of Northeast Asia. We used a case-control study of 2 ethnic groups in the same latitude geographical area to investigate the association between the susceptibility of EH and rs1006737 polymorphism. A total of 1512 EH patients and 1690 controls in Chinese Han people (Heilongjiang Provence, China), 250 EH patients, and 250 controls in ethnic Russian people (Chita, Russia), participated in this study. All participants were genotyped using the TaqMan SNP genotyping assay (Agena Company). Baseline characteristics and the minor allele frequencies of rs1006737 vary substantially among common Chinese Han and ethnic Russian people. Allele A was found to be a risk factor for EH in Chinese Han [(odds ratio) OR 1.705, (confidence interval) 95% CI: 1.332-2.182, P < .001] and ethnic Russian (OR 1.437; 95% CI: 1.110-1.860, P = .006). The GA genotype was significantly associated with an increased risk of hypertension (OR 1.538, 95% CI: 1.188-1.991, P = .001) for Chinese Han people, and the AA genotype (OR 2.412, 95% CI: 1.348-4.318, P = .003) for ethnic Russian people. The results of this study indicate that the A allele of the variant rs1006737 in the CACNA1C gene may be a useful genetic marker for EH risk prediction in Chinese Han and ethnic Russian populations.

Correlations of Post-stroke Depression with Inflammatory Response Factors.

BACKGROUND: We aimed to investigate the correlations of the inflammatory response factors, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (CRP), with patients with post-stroke depression (PSD), so as to provide a basis for the treatment and prevention of PSD for patients. METHODS: The clinical laboratory data of 60 patients with PSD in The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China from July 2016 to July 2017 and those of another 60 stroke patients without PSD admitted in the same period were analyzed retrospectively. The expression levels of inflammatory response factors in the two groups of patients and in PSD patients with different levels of depression were compared and analyzed via statistical methods. Multiple Logistic regression analysis was used to determine whether inflammatory response factors were independent risk factors for PSD patients. RESULTS: The expression levels of IL-6, TNF-α and CRP in patients with PSD were significantly increased compared with those in patients without PSD, and the differences were statistically significant (t=6.429, t=6.355, t=5.792, P<0.001). The levels of IL-6, TNF-α and CRP had statistically significant differences between any two groups of mild, moderate and severe PSD patients (P<0.05). Results of multiple Logistic regression analysis revealed that the odds ratio (OR) values of inflammatory factors (IL-6, TNF-α and CRP) were 1.160, 1.099 and 1.248, respectively, and the corresponding p values were 0.020, 0.039 and 0.007 in patients of observation group, indicating the above three inflammatory response factors were independent risk factors for PSD. CONCLUSION: The clinic control on the expression levels of inflammatory response factors (IL-6, TNF-α and CRP) are extremely important for the treatment and prevention of PSD.