ABSTRACT
Long noncoding RNA (lncRNA) LINC00461 (LINC00461) is reported to be related to glioma progression. However, the mechanism of LINC00461 in glioma remains unclear. Expression of LINC00461, miRNA (miR)-216a, and aquaporin 4 (AQP4) was detected using real-time quantitative PCR (RT-qPCR) and western blotting. Proliferation, temozolomide (TMZ) resistance, migration, and invasion were assessed by MTT, colony formation, and transwell assays, respectively. The target binding among miR-216a, LINC00461, and AQP4 was confirmed by the luciferase reporter assay. The tumor growth was monitored in the xenograft experiment. LINC00461 was upregulated, and miR-216a was downregulated in glioma tissues and cells, and LINC00461 upregulation was correlated with large tumor size, higher WHO grade and recurrence, and poor overall survival. LINC00461 knockdown suppressed cell viability, abilities of cell cloning and migration and invasion, and TMZ resistance in glioma. Mechanically, LINC00461 was confirmed to sponge miR-216a to affect AQP4 expression. Rescue assays verified that miR-216a downregulation or AQP4 upregulation abrogated the inhibitory effect of LINC00461 knockdown on cell proliferation, migration, invasion, and TMZ resistance in vitro. Moreover, LINC00461 downregulation blocked the glioma tumor growth in vivo. In conclusion, LINC00461 knockdown inhibits glioma cell proliferation, migration, invasion, and TMZ resistance through miR-216a/AQP4 axis, suggesting LINC00461 as an oncogene in glioma progression.
ABSTRACT
OBJECTIVE: The central mechanisms underlying postherpetic neuralgia (PHN) pain remains unknown. The primary purpose of this study was to identify microstructural white matter changes closely related to the PHN pain by means of diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) analysis. METHODS: DTI data of the brains were obtained from 8 PHN patients and 8 healthy controls (HC) that were matched in age, gender, and educational level. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were separately compared between the two groups using TBSS analysis to detect subtle microstructural changes. Partial correlation analyses were also conducted to evaluate the association between the altered DTI measures and clinical features. RESULTS: Average diffusion indices of white matter skeletons in the whole-brain showed no significant difference between the two groups. However, compared to the HC group, patients with PHN pain revealed reductions in localized FA and AD values in white matter underlying insula, occipital lobe, cerebellum, precentral gyrus, and many other regions, but without distinct change in regional MD and RD levels. In addition, decline of FA and AD values in patients represented significant negative correlations with PHN pain duration when the effect of VAS scores were excluded. CONCLUSION: The current study suggest that there exists altered microstructure integrity of white matter in multiple brain regions in patients with PHN, and these changes increase in size as the duration of the pain increases. These findings might provide a new insight into the mechanism of PHN pain in brain.
Subject(s)
Neuralgia, Postherpetic/pathology , White Matter/pathology , Adult , Aged , Brain/pathology , Case-Control Studies , Female , Humans , Male , Middle AgedABSTRACT
Oxidative stress and inflammation play an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The present study aimed to evaluate the effect of salvianolic acid A (SalA) on EBI after SAH via its antioxidative, anti-inflammatory, and anti-apoptotic effects. The intraperitoneal administration of SalA (10 and 50 mg/kg/day) significantly alleviated EBI (including neurobehavioral deficits, brain edema, blood-brain barrier permeability, and cortical neuron apoptosis) after SAH in rats. SalA treatment also reduced the post-SAH elevated levels of reactive oxygen species level and malondialdehyde. Further, SalA increased glutathione peroxidase enzymatic activity and the concentrations of glutathione and brain-derived neurotrophic factor in brain cortex, at 24 h after SAH. In addition, SalA also decreased the release of inflammation cytokines (i.e., TNF-α, IL-1ß, IL-6, and IL-8) in SAH rats. Expressions of cell apoptosis-related proteins were also regulated by SalA treatment in SAH rats. Meanwhile, SalA also modulated Nrf2 signaling, and the phosphorylation of ERK and P38 MAPK signaling in SAH rats. These results indicated that the administration of SalA may ameliorate EBI and provide neuroprotection after SAH in rat models.
