Abstract. MicroRNAs (miRs) are a class of endogenous small non-coding RNAs that have been revealed to negatively mediate the expression of their target genes at the post-transcriptional level. Recently, particular miRs have demonstrated an involvement in the pathogenesis of Alzheimer's disease (AD). However, the specific role of miR-135b in AD has yet to be elucidated. The present study aimed to investigate the neuroprotective role of miR-135b, in addition to its underlying mechanism. Herein, reverse transcription-quantitative polymerase chain reaction was conducted to determine miR-135b expression levels in the peripheral blood samples of patients with AD and age-matched normal controls. The data of the present study revealed that the expression levels of miR-135b were significantly reduced in the peripheral blood of AD patients compared with normal controls (P<0.01). In vitro MTT analyses identified that the overexpression of miR-135b significantly enhanced the proliferation of hippocampal cells (P<0.01). Furthermore, in vivo analysis using a Y-maze test indicated that injection with miR-135b mimics into the third ventricle of anesthetized SAMP8 mice significantly enhanced their learning and memory capacities (P<0.01). Molecular mechanism investigations identified β-site APP-cleaving enzyme 1 (BACE1) as a direct target gene of miR-135b, and the latter was identified to negatively mediate the protein expression levels of BACE1 in hippocampal cells, in addition to hippocampal tissues, of SAMP8 mice. Based on the aforementioned findings, we propose that miR-135b has a neuroprotective role via direct targeting of BACE1 and, thus, may be used for the treatment of AD.

Activated microglia are capable of facilitating amyloid-β (Aβ) accumulation via the release of inflammatory factors, thus resulting in the exacerbation of Alzheimer's disease (AD). MicroRNAs (miRs) participate in the activation of microglia, which is associated with AD. Insulin-like growth factor 1 (IGF1) is a neuroprotective, anti-inflammatory factor, which is able to accelerate clearance of Aβ peptides. The present study aimed to investigate the precise role of miR‑206 and IGF1 in lipopolysaccharide (LPS)‑induced microglial inflammation. The expression levels of miR‑206 and IGF1 were detected in 60 peripheral blood samples from patients with AD and matched age subjects using quantitative polymerase chain reaction. A dual luciferase reporter gene assay was used to indicate the relationship between miR‑206 and IGF1. In addition, the role of miR‑206 was determined by gain and loss of function experiments in LPS‑treated microglia. The results demonstrated that miR‑206 upregulation enhanced LPS‑induced inflammation and Aβ release in microglia by directly targeting the 3'-untranslated region of IGF1. These effects were attenuated following treatment with exogenous IGF1, thus indicating that the miR‑206/IGF1 signaling pathway may be considered a novel therapeutic target for the treatment of AD‑associated microglial inflammation.

The aim of this study was to investigate the association between MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and the development of ischemic stroke in a Chinese population. Between May 2013 and January 2015, 335 patients with ischemic stroke and 335 health control subjects were enrolled in this study. The MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. By multivariate logistic regression analysis, the CC genotype of MMP9 rs3918242 was shown to be associated with a significantly increased risk of ischemic stroke when compared with the TT genotype [OR (95%CI) = 5.47 (2.64-12.38)]. The TC+CC genotype of MMP9 rs3918242 was furthermore found to be associated with an elevated risk of ischemic stroke in higher BMI individuals [OR (95%CI) = 1.81 (1.03-3.22)]. The findings of this study suggest that the MMP9 rs3918242 polymorphism is associated with an elevated risk of ischemic stroke and that this gene polymorphism interacts with BMI in the risk of ischemic stroke.

Higenamine, a plant-based alkaloid, exhibits various properties, such as antiapoptotic and antioxidative effects. Previous studies proved that higenamine possesses potential therapeutic effects for ischemia/reperfusion (I/R) injuries. However, the role of higenamine in cerebral I/R injury has not been fully evaluated. Therefore, we aimed to investigate the effect of higenamine on cerebral I/R injury and the potential mechanism. Our data showed that higenamine ameliorated oxygen-glucose deprivation/reperfusion (OGD/R)induced neuronal cells injury. Induction of reactive oxygen species and malonaldehyde production, and the inhibition of superoxide dismutase and glutathione peroxidase activity caused by OGD/R were attenuated by higenamine. In addition, higenamine inhibited the increases in caspase-3 activity and Bax expression, and inhibited the decrease in Bcl-2 expression. Furthermore, higenamine elevated the expression levels of p-Akt, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2). The inhibitor of PI3K/Akt (LY294002) abolished the protective effects of higenamine on OGD/R-induced neuronal cells. These findings indicated that higenamine protects neuronal cells against OGD/R-induced injury by regulating the Akt and Nrf2/HO-1-signaling pathways. Collectively, higenamine might be considered as new strategy for the prevention and treatment of cerebral I/R injury. K E Y W O R D S cell apoptosis, cerebral ischemia/reperfusion injury, higenamine, oxidative stress J Cell Biochem. 2019;120:3757-3764.wileyonlinelibrary.com/journal/jcb

The mechanisms of epilepsy remain incompletely understood. Rac1 (ras-related C3 botulinum toxin substrate 1) belongs to the Rho family of small GTPases. Rac1 play important roles in cytoskeleton rearrangement and neuronal synaptic plasticity, which had also been implicated in epilepsy. However, little is known regarding the expression of Rac1 in the epileptic brain or whether Rac1-targeted interventions affect the progression of epilepsy. The aim of this study was to investigate the expression profile of Rac1 in brain tissues from patients suffering from temporal lobe epilepsy (TLE) and experimental epileptic rats and determine the possible role of Rac1 in epilepsy. We demonstrated that the expression of Rac1 is significantly increased in TLE patients and in lithium-pilocarpine epilepsy model animals compared to the corresponding controls. Rac1 inhibitor NSC23766 reduced the severity of status epilepticus during the acute stage in a lithium-pilocarpine animal model. Consistent with these results, the latent period of a PTZ kindling animal model also increased. Our results demonstrated that the increased expression of Rac1 may contribute to pathophysiology of epilepsy.

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Interferon (IFN)-inducible protein 16 (IFI16) regulates human immunodeficiency virus replication by inducing innate immune responses as a DNA sensor. Human T-lymphotropic virus type 1 (HTLV-1), a delta retrovirus family member, has been linked to multiple diseases. Here, we report that IFI16 expression is induced by HTLV-1 infection or HTLV-1 reverse transcription intermediate (RTI) ssDNA90 transfection. IFI16 overexpression decreases HTLV-1 protein expression, whereas IFI16 knockdown increases it. Furthermore, the knockdown of IFI16 is followed by impaired innate immune responses upon HTLV-1 infection. In addition, IFI16 forms a complex with ssDNA90 and enhances ssDNA90-triggered innate immune responses. Collectively, our data suggest a critical role for IFI16 during HTLV-1 infection by interacting with HTLV-1 RTI ssDNA90 and restricting HTLV-1 replication.