CircRNA circ_POLA2 overexpression suppresses cell apoptosis by downregulating PTEN in glioblastoma.

The oncogenic role of circ_POLA2 has only been explored in lung cancer, whereas the role of which in glioblastoma (GBM) is unclear. Our research explored the involvement of circ_POLA2 in GBM. Circ_POLA2 and phosphatasetensinhomolog (PTEN) mRNA levels in GBM and paired nontumor tissues collected from 58 GBM patients were analyzed by real-time quantitative PCR (RT-qPCR). Circ_POLA2 and PTEN were overexpressed in GBM cells to study their interaction by RT-qPCR and Western blot. The roles of circ_POLA2 and PTEN in regulating GBM cell apoptosis were explored using cell apoptosis assay. Our data revealed that circ_POLA2 was upregulated and PTEN was downregulated in GBM. PTEN showed an inverse correlation to circ_POLA2 across GBM tissues, In GBM cells, circ_POLA2 overexpression decreased PTEN accumulation, but PTEN overexpression failed to significantly affect circ_POLA2 expression. Moreover, PTEN reduced the inhibitory effects of circ_POLA2 on GBM cell apoptosis. Circ_POLA2 is overexpressed in MCL and might promote GBM cell apoptosis through downregulating PTEN.

Neuroprotective effect of ceftriaxone in a rat model of traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of mortality and disability in children and young adults worldwide. Neurologic impairment is caused by both immediate brain tissue disruption and post-injury cellular and molecular events that worsen the primary neurologic insult. The ß-lactam antibiotic ceftriaxone (CTX) has been reported to induce neuroprotection in animal models of diverse neurologic diseases via up-regulation of GLT-1. However, no studies have addressed the neuroprotective role of CTX in the setting of TBI, and whether the mechanism is involved in the modulation of neuronal autophagy remains totally unclear. The present study was designed to determine the hypothesis that administration of CTX could significantly enhance functional recovery in a rat model of TBI and whether CTX treatment could up-regulate GLT-1 expression and suppress post-TBI neuronal autophagy. The results demonstrated that daily treatment with CTX attenuated TBI-induced brain edema and cognitive function deficits in rats. GLT-1 is down-regulated following TBI and this phenomenon can be reversed by treatment of CTX. In addition, we also found that CTX significantly reduced autophagy marker protein, LC3 II, in hippocampus compared to the TBI group. These results suggest that CTX might provide a new therapeutic strategy for TBI and this protection might be associated with up-regulation of GLT-1 and suppression of neuronal autophagy.

Vitamin D receptor activation influences the ERK pathway and protects against neurological deficits and neuronal death.

Previous studies have demonstrated that global cerebral ischemia (GCI) causes neurological deficits and neuronal cell apoptosis. Calcitriol, a biologically active metabolite of vitamin D, exerts its endocrinological influence via nuclear vitamin D receptor. It is being assessed as an emerging therapeutic strategy in models of various medical conditions, including acute brain injury. The purpose of the present study was to investigate the neuroprotective effects of calcitriol on GCI and further refine the potential underlying mechanisms. A total of 145 male rats were assigned to 5 groups as follows: Sham group, GCI group, calcitriol treatment group, PD98059 treatment group and vehicle-treated group. Brain water content and neurologic severity score were assessed to evaluate the brain edema and neurological deficits of rats. Histopathological changes and ultrastructures of cells were observed via hematoxylin and eosin stain and transmission electron microscopy, respectively. Immunofluorescent staining and western blot analysis were used to assess the expression of proteins and their co-localization at the molecular level. The results demonstrated that post-GCI administration of calcitriol attenuated brain edema and improved neurological function in rats. Calcitriol also caused marked extracellular signal-regulated kinase 1/2 pathway activation, and thereby attenuated neuronal apoptosis. The present study provided novel clues for understanding the mechanisms by which calcitriol exerts its neuroprotective activity in a rat model of GCI.

Vitamin D Receptor Activation Influences NADPH Oxidase (NOX2) Activity and Protects against Neurological Deficits and Apoptosis in a Rat Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a worldwide phenomenon which results in significant neurological and cognitive deficits in humans. Vitamin D (VD) is implicated as a therapeutic strategy for various neurological diseases now. Recently, inhibition of the NADPH oxidase (NOX2) was reported to protect against oxidative stress (ROS) production. However, whether alterations in NOX2 expression and NOX activity are associated with calcitriol (active metabolite of VD) treatment following TBI remains unclear. In the present study, rats were randomly assigned to the sham, TBI, and calcitriol-treated groups. Calcitriol was administered intraperitoneally (2 µg/kg) at 30 min, 24 h, and 48 h after TBI insult. We observed that calcitriol treatment alleviated neurobehavioral deficits and brain edema following TBI. At the molecular levels, administration of calcitriol activated the expression of VDR and downregulated NOX2 as well as suppressed apoptosis cell rate in the hippocampus CA1 region of TBI rats. In conclusion, our findings indicate that the protective effects of calcitriol may be related to the modulation of NADPH oxidase and thereby ultimately inhibited the progression of apoptosis. Calcitriol may be promising as a protective intervention following TBI, and more study is warranted for its clinical testing in the future.

Therapeutic effect of exogenous bone marrow­derived mesenchymal stem cell transplantation on silicosis via paracrine mechanisms in rats.

Silicosis is a well-known occupational disease, characterized by epithelial injury, fibroblast proliferation, expansion of the lung matrix and dyspnea. At present, no effective treatment methods for silicosis have been identified. The present study aimed to investigate the protective potential of exogenous bone marrow-derived mesenchymal stem cell (BMSC) transplantation on experimental silica-induced pulmonary fibrosis in rats and analyze the underlying paracrine mechanisms associated with its therapeutic effects. BMSCs were isolated, cultured and passaged from male Sprague-Dawley (SD) rat bone marrow. Third-generation BMSCs were identified by flow cytometry using FITC staining. Following the successful establishment of the silicosis model, exogenous BMSCs were infused into female adult SD rats via the tail vein. Lungs were evaluated using hematoxylin and eosin (H&E) staining. The expression of interleukin-1 receptor antagonist (IL­1RA), interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) protein was detected by immunohistochemistry and western blot analysis. Co-localization of sex determining region Y (SRY) and IL-1RA expression was determined by double-label immunofluorescence. The distribution of transplanted BMSCs was tracked by monitoring the expression of SRY in rats. Treatment with BMSCs was found to protect the lungs against injury and fibrosis by the suppression of upregulated IL-1 and TNF-α protein, via triggering IL-1RA secretion. This mechanism was hypothesized to be mediated by paracrine signaling. These results indicate that the release of IL­1RA from BMSCs via paracrine mechanisms significantly blocks the production and/or activity of IL-1 and TNF-α. The present study provides an experimental basis for cellular therapy in silicosis.

Attenuation of brain edema and spatial learning deficits by the inhibition of NADPH oxidase activity using apocynin following diffuse traumatic brain injury in rats.

Diffuse brain injury (DBI) is a leading cause of mortality and disability among young individuals and adults worldwide. In specific cases, DBI is associated with permanent spatial learning dysfunction and motor deficits due to primary and secondary brain damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a major complex that produces reactive oxygen species (ROS) during the ischemic period. The complex aggravates brain damage and cell death following ischemia/reperfusion injury; however, its role in DBI remains unclear. The present study aimed to investigate the hypothesis that levels of NOX2 (a catalytic subunit of NOX) protein expression and the activation of NOX are enhanced following DBI induction in rats and are involved in aggravating secondary brain damage. A rat model of DBI was created using a modified weight-drop device. Our results demonstrated that NOX2 protein expression and NOX activity were enhanced in the CA1 subfield of the hippocampus at 48 and 72 h following DBI induction. Treatment with apocynin (50 mg/kg body weight), a specific inhibitor of NOX, injected intraperitoneally 30 min prior to DBI significantly attenuated NOX2 protein expression and NOX activation. Moreover, treatment with apocynin reduced brain edema and improved spatial learning function assessed using the Morris water maze. These results reveal that treatment with apocynin may provide a new neuroprotective therapeutic strategy against DBI by diminishing the upregulation of NOX2 protein and NOX activity.