Using bioinformatics technology to mine the expression of serum exosomal miRNA in patients with traumatic brain injury.

Introduction: Traumatic brain injury (TBI) is considered the most common traumatic neurological disease, is associated with high mortality and long-term complications, and is a global public health issue. However, there has been little progress in serum markers for TBI research. Therefore, there is an urgent need for biomarkers that can sufficiently function in TBI diagnosis and evaluation. Methods: Exosomal microRNA (ExomiR), a stable circulating marker in the serum, has aroused widespread interest among researchers. To explore the level of serum ExomiR after TBI, we quantified ExomiR expression levels in serum exosomes extracted from patients with TBI using next-generation sequencing (NGS) and explored potential biomarkers using bioinformatics screening. Results: Compared with the control group, there were 245 ExomiR (136 up-regulated and 109 down-regulated) in the serum of the TBI group that changed significantly. We observed serum ExomiRs expression profiles associated with neurovascular remodeling, the integrity of the blood-brain barrier, neuroinflammation, and a cascade of secondary injury, including eight up-regulated ExomiRs (ExomiR-124-3p, ExomiR-137-3p, ExomiR-9-3p, ExomiR-133a-5p, ExomiR-204-3p, ExomiR-519a-5p, ExomiR-4732-5p, and ExomiR-206) and 2 down-regulated ExomiR (ExomiR-21-3p and ExomiR-199a-5). Discussion: The results revealed that serum ExomiRs might become a new research direction and breakthrough for the diagnosis and pathophysiological treatment of patients with TBI.

PTEN Loss Enhances Error-Prone DSB Processing and Tumor Cell Radiosensitivity by Suppressing RAD51 Expression and Homologous Recombination.

PTEN has been implicated in the repair of DNA double-strand breaks (DSBs), particularly through homologous recombination (HR). However, other data fail to demonstrate a direct role of PTEN in DSB repair. Therefore, here, we report experiments designed to further investigate the role of PTEN in DSB repair. We emphasize the consequences of PTEN loss in the engagement of the four DSB repair pathways-classical non-homologous end-joining (c-NHEJ), HR, alternative end-joining (alt-EJ) and single strand annealing (SSA)-and analyze the resulting dynamic changes in their utilization. We quantitate the effect of PTEN knockdown on cell radiosensitivity to killing, as well as checkpoint responses in normal and tumor cell lines. We find that disruption of PTEN sensitizes cells to ionizing radiation (IR). This radiosensitization is associated with a reduction in RAD51 expression that compromises HR and causes a marked increase in SSA engagement, an error-prone DSB repair pathway, while alt-EJ and c-NHEJ remain unchanged after PTEN knockdown. The G2-checkpoint is partially suppressed after PTEN knockdown, corroborating the associated HR suppression. Notably, PTEN deficiency radiosensitizes cells to PARP inhibitors, Olaparib and BMN673. The results show the crucial role of PTEN in DSB repair and show a molecular link between PTEN and HR through the regulation of RAD51 expression. The expected benefit from combination treatment with Olaparib or BMN673 and IR shows that PTEN status may also be useful for patient stratification in clinical treatment protocols combining IR with PARP inhibitors.

Different changes in granulocyte-colony stimulating factor and its correlation with inflammatory biomarkers in patients after traumatic brain injury.

OBJECTIVE: This study analyzed changes in granulocyte-colony stimulating factor (G-CSF) and its correlation with leukocyte and neutrophil counts in patients after traumatic brain injury (TBI). METHODS: Sixty TBI patients were included retrospectively. The serum levels of G-CSF, tumor necrosis factor-α (TNF-α), and peripheral leukocyte and neutrophil counts at different time points were measured and analyzed, and the 6-month functional outcomes were monitored. RESULTS: The levels of G-CSF in mild and moderate TBI groups were higher than the control at the first three time points. G-CSF in the severe TBI group increased slowly and peaked at day 7, and was only significantly different from the control at day 7 and 14. The leukocyte and neutrophil counts of the mild group gradually decreased, but a second increase after day 4 was observed in the severe group. The cell counts were higher in the severe group compared to other groups. A positive correlation between G-CSF and leukocyte and neutrophil counts was observed in the severe group at day 1. G-CSF positively correlated with TNF-α in the severe group at day 4 and 7. In severe patients with a good outcome, G-CSF level at day 7 was significantly higher than those with a poor outcome. CONCLUSION: The G-CSF levels in the severe TBI group exhibited a different pattern from those in the mild and moderate TBI groups, and these levels positively correlated with inflammatory biomarkers. Higher G-CSF levels in severe TBI at day 7 indicated a good outcome at 6 months.

Endothelial Progenitor Cells Correlated with Oxidative Stress after Mild Traumatic Brain Injury.

PURPOSE: Endothelial progenitor cells (EPCs) play a key role in tissue repair and regeneration. Previous studies have shown that infusion of human umbilical cord blood-derived endothelial colony-forming cells improves outcomes in mice subjected to experimental traumatic brain injury (TBI). However, the efficiency of cell transplantation is not satisfactory. Oxidative stress plays a significant role in the survival of transplanted cells following ischemic reperfusion injury. This observational clinical study investigated the correlation between the number of circulating EPCs and plasma levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA). MATERIALS AND METHODS: Peripheral blood samples were collected from 20 patients with mild TBI at day-1, day-2, day-3, day-4, and day-7 post TBI. The number of circulating EPCs and the plasma levels of SOD and MDA were measured. RESULTS: The average of circulating EPCs in TBI patients decreased initially, but increased thereafter, compared with healthy controls. Plasma levels of SOD in TBI patients were significantly lower than those in healthy controls at day-4 post-TBI. MDA levels showed no difference between the two groups. Furthermore, when assessed on day-7 post-TBI, the circulating EPC number were correlated with the plasma levels of SOD and MDA. CONCLUSION: These results suggest that the number of circulating EPCs is weakly to moderately correlated with plasma levels of SOD and MDA at day-7 post-TBI, which may offer a novel antioxidant strategy for EPCs transplantation after TBI.