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The present study aimed to investigate the function of the single nucleotide polymorphism (SNP) rs41291957 in the prognosis of intracerebral hemorrhage (ICH). In addition, the molecular mechanisms underlying the role of microRNA (miR)‑143, Toll‑like receptor 2 (TLR2) and interleukin‑16 (IL‑16) were studied in patients with ICH that carried different alleles in the locus of the rs41291957 SNP. Kaplan‑Meier survival curves were calculated for 182 patients with ICH, genotyped as CC, presenting a cytosine in both chromosome, CT, presenting both variants, and TT, presents a thymine in both chromosomes. In addition, the possible regulatory relationships between miR‑143 and TLR2/IL‑16 were studied using computational analysis, luciferase assays and western blot assay. In addition, the inflammatory profiles of cerebrospinal fluid (CSF) and serum samples collected from the subjects were compared. The patients genotyped as TT presented the lowest survival rate, while patients genotyped as CC presented the highest survival rate. TLR2 mRNA was identified as a potential target of miR‑143, while IL‑16 showed no direct interaction with miR‑143. The above regulatory relationships were further investigated using cells transfected with miR‑143 precursor or TLR2 small interfering RNA. In addition, the expression levels of inflammatory factors, such as tumor necrosis factor α, interferon, IL‑6, IL‑10 and NF‑L‑6, were highest in the CSF/serum samples collected from patients genotyped as TT and lowest in patients genotyped as CC. By contrast, the expression levels of miR‑143 showed an opposite trend in the expression of the above inflammatory factors. The rs41291957 SNP, located in the promoter region of miR‑143, reduced the expression of miR‑143 and upregulated the expression of the pro‑inflammatory factor TLR2, eventually leading to a poorer prognosis in patients with ICH.

The present study analyzed gene expression arrays to identify differentially-expressed genes (DEGs) between mycophenolate mofetil (MMF)‑treated and placebo‑treated patients with symptomatic carotid artery stenosis (SCAS). In addition, the key genes involved in the pharmacology of MMF treatment in patients with SCAS were identified. The gene expression dataset was obtained from a Gene Expression Omnibus database, which included 9 MMF‑treated and 11 placebo‑treated samples. The DEGs were identified between MMF and placebo groups using R software. Furthermore, a protein‑protein interaction (PPI) network of the identified DEGS was constructed. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the 19 most significant DEGs. A total of 210 DEGs between the MMF and placebo groups were screened and their PPI was constructed. GO function analysis revealed that the 19 DEGs were predominantly involved in the tyrosine phosphorylation of signal transducer and activator of transcription‑5 protein, which is closely associated with the activation of T cells. The KEGG pathway analysis suggested that the main metabolic pathways of the 19 DEGs were associated with the pharmacological functioning of MMF in activated T cells. In conclusion, the present study identified numerous key DEGs associated with SCAS, and the results suggested that v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog and apelin may serve important roles in the MMF treatment of SCAS.

The present study was designed to investigate the role of microRNA-451 (miRNA-451) on cerebral ischemia-reperfusion and to explore its possible mechanism. The expression of miRNA-451 was downregulated in rats with cerebral ischemia-reperfusion. In an in vitro model of cerebral ischemia-reperfusion, the downregulation of miRNA-451 increased inflammation, demonstrated by increased levels of tumor necrosis factor α, interleukin (IL)-1b, IL-6 and IL-18. However, the upregulation of miRNA-451 expression decreased inflammation in the same in vitro model of cerebral ischemia-reperfusion. In addition, it was found that the downregulation of miRNA-451 induced the expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88 (MyD88) and nuclear factor-κB (NF-κB)/p65. Moreover, the administration of a MyD88 inhibitor, ST 2825, reduced the expression of MyD88 and NF-κB/p65 in the in vitro model of cerebral ischemia-reperfusion, inhibiting the effects of miRNA-451 upregulation on inflammation. A TLR4 inhibitor, TAK-242, was used to reduce the expression of TLR4 in the in vitro model of cerebral ischemia-reperfusion. TAK-242 suppressed the effects of miRNA-451 downregulation on inflammation. The present study suggested that miRNA-451 regulated cerebral ischemia-reperfusion-induced inflammation, which is mediated through the TLR4/MyD88/NF-κB signaling pathway.

Traumatic brain injury (TBI) is a major health and socioeconomic problem as it is associated with high rates of mortality and morbidity worldwide. Regulatory T cells (Tregs) have been reported to reduce inflammatory response in several diseases, including myasthenia gravis, viral myocarditis and cerebral infarction. The present study investigated the role of Tregs in mediating neuro-protective effects in a mouse model of TBI. Initially, Treg levels were determined, and compared between the controlled cortical impact (CCI) model for moderate TBI and the sham group, by using flow cytometry and ELISA. Afterwards, the number of Tregs was upregulated (by injection) and downregulated (by depletion), respectively, to elucidate the effect of Tregs in the presence of an inflammatory reaction and a deficient neurological function and consequently, in the prognosis of TBI in the mouse. The expression of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6)] and anti-inflammatory cytokines [IL-10, transforming growth factor (TGF)-β] in blood and brain tissues was also measured in the five groups: Μice receiving a saline injection, mice experiencing Treg depletion, small-dose (SD Tregs, 1.25×105), and mice receiving different doses of Tregs: Moderate-dose (MD Tregs, 2.5×105) and large-dose (LD Tregs, 5×105), using ELISA and PCR. Co-cultures of Tregs and microglia were performed to evaluate the expression of pro-inflammatory cytokines and observe the interaction between the two types of cells. The regulation patterns in JNK-NF-κB pathway by Tregs were also evaluated by western blot analysis. Treg levels were significantly reduced in TBI mouse group on the 3rd day after TBI (P

Small interfering RNAs (siRNAs) are small non-coding RNAs, comprising 21-23 nucleotides that regulate gene expression by transcriptionally repressing their complementary mRNAs. In particular, Krüppel-like factor 8 (KLF8) has been postulated to function as a tumor activator in various cancer cells, but not in glioblastoma. In the present study, we investigated the anti-tumorigenic effect of KLF8 siRNA in glioblastoma cells. U251 human glioblastoma cells were transfected with KLF8 siRNA and assayed for in vitro proliferation, cell cycle and cell apoptosis. The transfection of KLF8 siRNA reduced expression of KLF8 in the glioblastoma cells. KLF8 siRNA also reduced in vitro proliferation and enhanced cell apoptosis. These results indicate that KLF8 siRNA has an anti-tumorigenic effect on glioblastoma cells and suggest the possible use of KLF8 siRNA for the treatment of glioblastoma.