Tumstatin attenuates the promotion effect of IL-17 secreted by Th17 cells on the stemness maintenance of glioma cells.

The presence and clinical significance of IL-17 and IL-17-expressing cells have been studied for several cancers, although their correlation with tumor development remains controversial. Peripheral blood was collected from healthy donors and glioma patients to isolate peripheral blood mononuclear cells (PBMCs). The percentage of IL-17-expressing cells and the production of inflammatory cytokines in PBMCs and tissues were measured. Human IL­17 cDNA was then inserted into the pEGFP­N1 plasmid and transfected into the glioma U87MG cell line, and tumstatin was used to block the effect of the IL-17 overexpression. Stem cell transcription factors were evaluated in each group using qRT-PCR and western blotting, and proliferation and migration were detected using colony formation and wound-healing assays. The cells were then subcutaneously inoculated into nude mice to evaluate the growth of glioma. Compared with healthy donors, the PBMCs from glioma patients showed a significant accumulation of IL-17-expressing T cells. Th17 cell differentiation-related cytokines (IL-23, TGF-ß and IL-6) were increased in the tumor microenvironment. IL­17 transfection increased the mRNA and protein expression of stem cell transcription factors in U87MG cells in vitro. The proliferation and migration of U87MG cells were also increased. Moreover, the pEGFP­N1­IL­17­U87MG cells grew more rapidly than other cells. However, tumstatin-treated U87MG cells showed significantly inhibited the effects of IL-17 overexpression. Tumstatin effectively suppressed IL-17-derived U87MG cell growth by downregulating stem cell maintenance factors and inducing proliferation and migration. These findings indicated that IL-17 represents a potential prognostic marker for glioma, while tumstatin has potential in the treatment for glioma.

Mechanism of miR-320 in Regulating Biological Characteristics of Ischemic Cerebral Neuron by Mediating Nox2/ROS Pathway.

This study aimed to explore the mechanism of miR-320 in regulating biological characteristics of ischemic cerebral neuron by mediating Nox2/ROS pathway. Primary neurons were cultured and grouped: normal group (normal primary neurons), negative control (NC) group (ischemic primary neurons, transfected with negative control plasmid), model group (ischemic primary neurons), miR-320 mimic group (ischemic primary neurons, transfected with miR-320-overexpressed plasmid), Nox2 vector group (ischemic primary neurons, transfected with Nox2-overexpressed plasmid), and miR-320 mimic + Nox2 vector group (ischemic primary neurons, co-transfected with miR-320- and Nox2-overexpressed plasmid). Dual-luciferase reporter assay showed that there was the target relationship between miR-320 and Nox2. miR-320 expression was significantly decreased, and Nox2 expression was significantly increased in the rest groups compared with normal group (both P < 0.05). There was a co-localization of miR-320 and Nox2 in the cytoplasm. Cell proliferation, contents of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), and mRNA and protein expressions of Ki67, Bcl-2, and c-myc were significantly declined, and apoptosis rate, contents of malondialdehyde (MDA) and reactive oxygen species (ROS), and caspase-3 mRNA and protein expressions were significantly increased in the rest groups compared with normal group (all P < 0.05). miR-320 promoted cell proliferation; increased contents of SOD, CAT, and GSH-PX; and declined apoptosis and contents of MDA and ROS. Moreover, miR-320 could affect the regulation of Nox2/ROS pathway on ischemic cerebral neuron by negatively regulating Nox2 expression. Overexpressed miR-320 affects the proliferation, apoptosis, and oxidative stress injury of ischemic cerebral neuron by inhibiting Nox2/ROS pathway.

High levels of serum mannose-binding lectins are associated with the severity and clinical outcomes of severe traumatic brain injury.

BACKGROUND: Mannose-binding lectin (MBL) is a key component of innate immunity. The expression of cortical MBL is up-regulated after clinical and experimental head trauma. This study aimed to assess the association of serum MBL levels with injury severity and long-term clinical outcomes after severe traumatic brain injury (STBI). METHODS: Serum MBL levels were measured in 122 patients and 100 healthy controls. Multivariate analyses were used to analyze the relationship between serum MBL levels and trauma severity reflected by Glasgow Coma Scale scores as well as between serum MBL levels and 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score: 1-3). A receiver operating characteristic (ROC) curve was structured to evaluate the prognostic predictive performance of serum MBL levels. RESULTS: Compared with healthy controls, serum MBL levels of patients were markedly elevated. Using multivariate analyses, serum MBL levels were found to be associated closely with Glasgow Coma Scale (GCS) scores and MBL emerged as an independent predictor for 6-month mortality and unfavorable outcome. Under ROC curve, serum MBL levels and GCS scores possessed similar prognostic predictive values. CONCLUSION: Increased serum level of MBL was independently associated with head trauma severity and long-term clinical outcomes of STBI.