Epigenetic transcripts of LINC01311 and hsa-miR-146a-5p regulate neural development in a cellular model of Alzheimer's disease.

Emerging evidence has shown that Long noncoding RNAs (LncRNAs) are aberrantly expressed and functionally involved in the development of neurodegenerative disorders. In this work, we investigated the regulatory effects of lncRNA of LINC01311 and its competing endogenous RNA target of hsa-miR-146a-5p in a cellular model of Alzheimer's disease (AD). SH-SY5Y cells were treated with synthetic Βeta-Amyloid Peptide (1-42) (AB1-42) in vitro to induce AD-like neural injuries. Expressions of LINC01311 and hsa-miR-146a-5p were monitored by qRT-PCR. LINC01311 was upregulated and hsa-miR-146a-5p downregulated to examine their functional regulations on AB1-42-induced apoptosis, proliferation slowdown, autophagy, and amyloid precursor protein (APP) accumulations. Hsa-miR-146a-5p was also overexpressed in LINC01311-upregulated SH-SY5Y cells to examine their correlated regulations on AB1-42-induced neural injuries. LINC01311 was downregulated whereas hsa-miR-146a-5p upregulated in AB1-42 treated SH-SY5Y cells. LINC01311 upregulation and hsa-miR-146a-5p downregulation protected AB1-42-induced apoptosis, proliferation slowdown, autophagy, and APP accumulations in SH-SY5Y cells. Hsa-miR-146a-5p overexpression reversed the protection of LINC01311 on AB1-42-induced neural injuries. Our work demonstrated that the epigenetic axis of LINC01311/hsa-miR-146a-5p was involved in the functional regulation of human-lineage neurons in a cellular model of AD, thus suggesting a clinical potential of exploring epigenetic network for treating AD patients.

Bone marrow-derived mesenchymal stem cells-derived exosomes prevent oligodendrocyte apoptosis through exosomal miR-134 by targeting caspase-8.

Ischemic stroke causes severe brain damage and remains one of the leading causes of morbidity and mortality worldwide. The microRNA-134 (miR-134) is involved in regulating the process of ischemia injury in neural cells and brain with ischemia stroke. The role of miR-134 in ischemic stroke remains poorly understood. The purpose of the current study was to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs)-derived exosomal miR-134 on rat oligodendrocytes (OLs) apoptosis and its underlying mechanism of action. The results demonstrated that levels of miR-134 in BMSCs-exosome decreased but increased incaspase-8 after oxygen-glucose deprivation (OGD) treatment. Exosomal miR-134 significantly inhibited apoptosis by decreasing caspase-8 expression and activity in OGD-treated group cultured with BMSCs-exosome and OLs. In addition, the miR-134 mimics decreased caspase-8 expression in OGD-treated OLs, whereas miR-134 inhibitors exacerbated the changes in the expression of the procaspase-8 and caspase-8 cleaved product proteins caused by OGD. The caspase-8 knockdown using caspase-8 small interfering RNA decreased OLs apoptosis, reversing the improvements that the miR-134 inhibited cells apoptosis by targeting caspase-8. Taken together, these results demonstrated that BMSCs-derived exosomes suppressed OLs apoptosis through exosomal miR-134 by negatively regulating the caspase-8-dependent apoptosis pathway and may, therefore, be a novel potential therapeutic target for ischemic stroke treatment.

Effects of Hyperbaric Oxygen Therapy on Inflammasome Signaling after Traumatic Brain Injury.

OBJECTIVE: Neuroinflammation plays an important role in secondary tissue damage after traumatic brain injury (TBI). Recently, the inflammasome-mediated inflammatory pathway has been observed in the inflammatory response of TBI. In this study, we investigated the influence of hyperbaric oxygen therapy (HBOT) on inflammasome activation after TBI. METHODS: The experimental mice were randomly divided into 4 groups as follows: sham-operated normobaric air (21% O2 at one absolute atmosphere), HBOT only, TBI + normobaric air and TBI + HBOT. Following the evaluation of motor deficits and brain edema, the expression of inflammasome components and effectors was measured by qRT-PCR and Western blotting. Moreover, alterations in IL-1ß, IL-18 and high-mobility group box 1 (HMGB1) were calculated by enzyme-linked immunosorbent assay at each time point after injury. RESULTS: HBOT improved motor score and reduced brain edema. Furthermore, it suppressed protein expression of inflammasome components and reduced the levels of IL-1ß and IL-18, accompanied by the reduction of HMGB1 in brain tissues and serum. CONCLUSION: These results suggest that HBOT may alleviate the inflammatory response after TBI by inhibiting the activation of inflammasome signaling.

Expression and clinical significance of nestin in astrocytic tumors.

PURPOSE: This study aimed to investigate the expression and clinical significance of nestin in human astrocytic tumors. METHODS: Indirect immunofluorescent staining and flow cytometry were used to quantitatively detect the nestin content in 35 specimens, including 3 normal brain tissues, 29 astrocytic tumor (AT) tissues, and 3 peritumoral tissues. RESULTS: In normal brain tissues, nestin expression was extremely low. Nestin expression was significantly positively correlated with the histological grade of astrocytic tumors (p<0.05, rs=0.83). Nestin content in the peritumoral tissues was between the levels of nestin in tumor tissue and in normal brain tissue (p<0.01). Nestin expression was unrelated to the patient's gender, age, tumor location, size, etc. (p>0.05). CONCLUSION: The application of flow cytometry in the determination of nestin content could improve the accuracy of early cancer diagnosis. This method would be helpful for developing a reference range that is closely related to the pathological grading of ATs through routine assessments of nestin in many patients. Additionally, through examining nestin levels in peritumoral tissues, the invasiveness of ATs can be clarified.

[Treatment of recurrent malignant gliomas by surgery combined with recombinant adenovirus-p53 injection].

OBJECTIVE: To evaluate the efficacy and toxicity of combination therapy with surgery and recombinant adenovirus-p53 injection of recurrent malignant gliomas. METHODS: 38 patients with recurrent malignant gliomas were included in this study. Among them, 18 patients of combined treatment group had Ommaya reservoirs placed into the tumor cavities after the resection of the tumors and received regular recombinant adenovirus-p53 injections after the operation. The other 20 patients received surgery alone. RESULTS: The 6-month and 1-year survival rates after the combination therapy were 66.7% (14/18) and 44.4% (8/18), respectively. The median survival time was 9.7 months. Compared with the surgery-alone group, the combined treatment group achieved significant improvement (P < 0.05). The Karnofsky score was significantly improved at 6 months after the combination therapy compared with that before the treatment (P < 0.05). CONCLUSION: The recombinant adenovirus-p53 injection is safe and effective in treatment of recurrent malignant gliomas. The combination therapy of surgery and recombinant adenovirus-p53 injection may improve the life quality and the prognosis in patients with recurrent malignant gliomas.

Relationship between plasma cortisol levels and stress ulcer following acute and severe head injury.

OBJECTIVE: This study was designed to investigate the relationship between plasma cortisol levels and stress ulcer following acute severe head injury. PATIENTS AND METHODS: The plasma cortisol levels were prospectively measured by radioimmunoassay in 68 patients following acute head injury. The diagnosis of stress ulcer was based on clinical evidence and was confirmed by endoscopic examination. RESULTS: Patients with stress ulcer and gastrointestinal bleeding (n = 30, 44.1%) were older than those without stress ulcer(38.2 +/- 7.9 vs. 28.3 +/- 9.7 years, p < 0.01). The combined rate of poor recovery and death in the stress ulcer patients (70.0%) was significantly higher than in the nonulcer patients (42.1%, p = 0.02). On each of the first 3 days following the head injury, the average plasma cortisol levels in the stress ulcer patients were higher than in the nonulcer patients (p < 0.01). Univariate analysis showed a positive relationship between plasma cortisol on admission and stress ulcer (r = 0.329, p = 0.01). Logistic regression analysis revealed that plasma cortisol levels on admission (OR = 2.326, 95% CI = 1.982-2.466) and age (OR = 1.064, 95% CI = 0.861-1.219) were independent predictors of stress ulcer. CONCLUSIONS: The data showed that acute severe head injury was associated with a significant increase in plasma cortisol. Plasma levels of cortisol and age were independent predictors of stress ulcer following acute head injury.

Rapid Recovery of Spontaneous Spinal Epidural Hematoma without Surgical Treatment: Case Report and Literature Review.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is a relatively uncommon yet potentially disabling neurologic emergency. The classical presentation includes a severe acute attack, sometimes radiating pain at the back, interscapular, or neck areas, followed by neurologic deficits. The main treatment is surgical, and self-healing cases are rare. CASE DESCRIPTION: A 17-year-old female was admitted to the neurosurgery department with neck pain, myasthenia of the limbs, and difficulty moving. Mild neck pain had developed 1 week prior with no obvious predisposing causes. The patient had suddenly suffered severe neck pain during normal walking and developed rapid paralysis of her limbs. There was no recent history of trauma, infection, or drug administration. Magnetic resonance imaging performed 1 hour after the onset of limb paralysis demonstrated a large spinal epidural hematoma that extended from C4 to C6. However, 9 hours after the initial onset of severe neck pain, her symptoms completely ceased. Magnetic resonance imaging demonstrated that the SSEH had nearly dissipated. CONCLUSIONS: Most cases of SSEH with spontaneous resolution are located on the upper thoracic and cervical spine. Surgery is the standard of care for these patients but can occasionally be deferred if the patient demonstrates significant rapid improvement.

Recombinant human erythropoietin improves functional recovery in patients with severe traumatic brain injury: A randomized, double blind and controlled clinical trial.

OBJECTIVE: To investigate the short-term effect of recombinant human erythropoietin (EPO) on patients with severe traumatic brain injury. METHODS: One hundred and fifty-nine patients with severe traumatic brain injury were randomly divided into EPO (n=79) and control group (n=80). EPO group was treated with subcutaneous injection of EPO (100 units/kg) on day 1, 3, 6, 9 and 12 following the brain injury. Glasgow outcome scores (GOS) were used to evaluate the outcomes three months after the treatment. Serum neuron specific enolase (NSE) and S-100ß protein were measured within the first three months after treatment. RESULTS: In the end, 146 patients (75 of the EPO group and 71 of the control group) completed the trial. Three months after the treatment, Good recovery was found in 33.3% of the EPO and 12.6% of the control group patients (p<0.05). Serum NSE and S-100ß protein were decreased gradually in both groups after treatment, but their levels in the EPO group were lower than that of control group (p<0.05). There was no statistically significant difference in blood pressure, hemoglobin levels, pneumonia, sepsis or thromboembolic events between the two groups three months after the treatment (p>0.05). CONCLUSION: Treatment with five doses of recombinant human erythropoietin is associated with an improved functional recovery in patients with severe traumatic brain injury. This treatment does not seem to increase the risk of thromboembolic events or severe infections.

MiR-454 inhibited cell proliferation of human glioblastoma cells by suppressing PDK1 expression.

It has been well documented that aberrant expression of microRNAs is associated with carcinogenesis of glioblastoma (GBM), however the underlying mechanisms are not clear. In this present study, we aimed to clarify the biological function of miR-454 in GBM. MiR-454 was identified to be significantly down-regulated in GBM primary tumors and cell lines. Overexpression of miR-454 in GBM cells resulted in arresting cells at G0/G1 phase and thus inhibiting cell proliferation. Bioinformatic analysis predicted 3-phosphoinositide-dependent protein kinase-1 (PDK1) as a target of miR-454 which acted as a tumor promoter gene. Increased miR-454 significantly repressed PDK1 expression, and then regulating cell proliferation and cell cycle regulators, down-regulation of Cyclin D1 and p-pRb and p21 was up-regulated. Taken together, our study has revealed miR-454 as a tumor suppressor in GBM.

Efficacy of Surgery Combined with Autologous Bone Marrow Stromal Cell Transplantation for Treatment of Intracerebral Hemorrhage.

Bone marrow stromal cells (BMSCs) may differentiate into nerve cells under a certain condition; however, the clinical application for treating nervous system disease remains unclear. The aim is to assess the safety profile, feasibility, and effectiveness of surgery combined with autologous BMSCs transplantation for treating ICH. 206 ICH patients who had received surgical procedure were divided into transplantation (n = 110) or control group (n = 96). For transplantation group, BMSCs were injected into the perihemorrhage area in the base ganglia through an intracranial drainage tube 5.5 (3.01-6.89) days after surgery, followed by a second injection into the subarachnoid space through lumbar puncture 4 weeks later. Neurologic impairment and daily activities were assessed with National Institute Stroke Scale (NIHSS), Barthel index, and Rankin scale before transplantation and 6 months and 12 months after transplantation. Our results revealed that, compared with control group, NIHSS score and Rankin scale were both significantly decreased but Barthel index was increased in transplantation group after 6 months. Interestingly, no significant difference was observed between 12 months and 6 months. No transplantation-related adverse effects were investigated during follow-up assessments. Our findings suggest that surgery combined with autologous BMSCs transplantation is safe for treatment of ICH, providing short-term therapeutic benefits.

Autologous bone marrow mononuclear cell implantation for intracerebral hemorrhage-a prospective clinical observation.

BACKGROUND: This study was designed to assess the clinical effect of bone marrow mononuclear cells including mesenchymal stem cell (MSCs) in patients with intracerebral hemorrhage (ICH). METHODS: One hundred patients were divided into a study (n=60) or a control group (n=40). Bone marrow mononuclear cells from the same patient were injected to the perihemorrhage area in the base ganglia through an intracranial drainage tube 5.9 days after ICH. National Institute Stroke Scale (NIHSSS) and Barthel index was used to assess neurologic impairment and daily activities, respectively, before and 6 months after intervention. RESULTS: Six months after implantation, the NIHSS score in the study group was lower than in the control group (10.09 ± 8.86 vs 14.35 ± 10.14, P<0.01), whereas the Barthel scores were higher (57.39 ± 23.51 vs 46.90 ± 20.29, P<0.01). Neurological and functional improvement was observed in 52 (86.7%) of the study group patients, and in 17 (42.5%) of the control group patients (P=0.001). No allergic or other adverse effects were observed in the study group. CONCLUSION: Autologous bone marrow mononuclear cell implantation reduced neurological impairment and improved activities of daily living in a selected group of ICH patients. Further studies are required to ascertain the long-term safety and efficacy of this treatment.