Folia neuropathologica最新文献

Introduction: Glioma is one of primary brain tumours which has the worst clinical prognoses of patients. As an alternative chemotherapeutic drug for malignant glioma, the therapeutic effect of cisplatin (CDDP) is devastatingly affected due to resistance in patients. In this study, we investigated the effect of LINC00470/PTEN on the CDDP sensitivity of glioma cells.

Material and methods: Differentially expressed lncRNAs and the downstream regulators in glioma tissue were obtained via bioinformatics analysis. LINC00470 and PTEN mRNA expression levels were detected using qRT-PCR. IC50 values of glioma cells were examined using Cell Counting Kit-8 (CCK-8). Cell apoptosis was revealed by flow cytometry. The expression level of autophagy-related protein was detected by western blot. Intracellular autophagosome formation was detected by immunofluorescence staining, and the methylation level of PTEN promoter was detected via methylation-specific PCR (MSP).

Results: Through the above steps, we found that LINC00470 was highly expressed in glioma cells, and the survival rate of patients was reduced in the presence of high expression of LINC00470. Silenced LINC00470 promoted LC3 II expression and autophagosome formation, and facilitated cell apoptosis to inhibit resistance to CDDP. While silenced PTEN could successfully reverse the previous effects on glioma cells.

Conclusions: Based on the above, LINC00470 repressed cell autophagy by constraining PTEN, thereby enhancing CDDP resistance of glioma cells.

Introduction: In recent years, novel RNAs have been revealed to be regulators in glioma. ADAMTS8 has been reported to be reduced in brain tumours. In this study, we aimed to explore the role of ADAMTS8 in glioma.

Material and methods: Online bioinformatic tools, Gepia and Chinese Glioma Genome Atlas database (CGGA) were used to analyse the differential expression of ADAMTS8, overall survival and disease-free survival rates and the correlations between ADAMTS8 and matrix metallopeptidases (MMP2 and MMP9) in glioma. RT-qPCR and western blot experiments were performed to measure the mRNA and protein expression. ADAMTS8 expression was regulated in cells through transfection. Thereafter, the effect of ADAMTS8 on cells was investigated through the cell viability, apoptosis and transwell experiments. The epithelial-mesenchymal transition (EMT)-related proteins and also MMP2 and MMP9 were examined. The subcutaneous tumour model was established to validate the suppressive role of ADAMTS8 in tumour growth.

Results: ADAMTS8 expression was reduced in glioma tissues and cells. Higher expression of ADAMTS8 was correlated with higher survival rates. ADAMTS8 was correlated with MMP2 and MMP9 in glioma tissues. In glioma cells, overexpression of ADAMTS8 could inhibit the viability, invasion, migration and EMT, and MMP2 and MMP9, but promote the apoptosis of cells. The upregulation of ADAMTS8 could inhibit the tumour growth in vivo.

Conclusions: ADAMTS8 was inhibited in glioma and the higher expression of ADAMTS8 might be related to better prognosis among glioma patients. Overexpression of ADAMTS8 inhibited the development of glioma in vitro and in vivo.

Introduction: Acute cerebral ischemic stroke (AIS) dramatically influences patients' quality of life. lncRNA NORAD (NORAD) has been studied in cerebrovascular diseases, which are potential risk factors for AIS. The specific significance of NORAD is unclear. This study aimed to assess the role of NORAD in AIS, and to provide therapeutic value for its' treatment.

Material and methods: A total of 103 AIS patients and 95 healthy individuals (control) were enrolled into this study. Expression level of NORAD in the plasma of all participants was analyzed by PCR. Diagnostic potential of NORAD in AIS was evaluated by ROC analysis, while Kaplan-Meier and Cox regression analyses were conducted to assess its' prognostic value in AIS.

Results: A significantly increased level of NORAD was observed in AIS patients compared with healthy individuals. The upregulation of NORAD could dramatically discriminate AIS patients from healthy individuals with high sensitivity (81.60%) and specificity (88.40%). NORAD was positively correlated with patients' high-sensitivity C-reactive protein (hs CRP, r = 0.796), matrix metalloproteinase-9 (MMP9, r = 0.757), and NIHSS scores ( r = 0.840), and negatively related to pc-ASPECTS scores ( r = -0.607). Moreover, NORAD upregulation was associated with patients' unfavorable prognosis and served as an independent prognostic biomarker, together with NIHSS and pc-ASPECTS scores of AIS patients.

Conclusions: NORAD was upregulated in AIS, which can discriminate AIS patients, and was closely correlated with severe development and poor prognosis of patients.

Introduction: CD8 + T-cells and MHC-I have been detected in brain gliomas with a significant outcome. The effect of chemotherapies on the crosstalk interaction between CD8 + T-cells and MHC-I has never been explored.

Material and methods: The protein expression profiling of CD8 cytotoxic T-cells and the gene expression assay of MHC-I in 35 patients diagnosed with WHO grade 4 astrocytoma were performed. The impact of these two factors on tumor recurrence was analyzed.

Results: IDH was wildtype in 13 tumors. MHC-I protein expression was absent or low in 34 tumors and dense in a single case. MHC-I gene expression was upregulated in 10 tumors and 25 tumors showed MHC-I gene downregulation. Temozolomide (TMZ) was given to 24 patients and 11 patients received TMZ plus other chemotherapies. No statistically significant association was observed between IDH mutation and CD8 + T-cells ( p = 0.383). However, this association was significant in recurrence-free interval (RFI) ( p = 0.012). IDH-wildtype tumors with highly infiltrated CD8 + T-cells or IDH-mutant tumors with low CD8 + T-cells showed late tumor recurrence. There was a statistically significant difference in RFI between tumors with different MHC-I expression and CD8 + T-cell counts after treatment with TMZ or TMZ plus ( p = 0.026).

Conclusions: No association between IDH mutation and CD8+ cytotoxic T-cell was found. IDH is directly linked to tumor recurrence regardless of CD8 + T-cells infiltration. TMZ plus other adjuvants is proved to be more effective in improving patient survival and delaying tumor recurrence, as compared to using TMZ alone. Nonetheless, none-TMZ adjuvants may increase tumor sensitization to cytotoxic T-cells more than TMZ.

BCOR is expressed in a new brain tumour entity, i.e. 'CNS tumour with BCOR internal tandem duplication' (HGNET BCOR) but not in several other high grade paediatric brain tumours investigated. Immunohistochemical detection of BCOR expression may therefore serve as a potential diagnostic marker. Nevertheless, in rare paediatric glioma cases recurrent EP300-BCOR fusions were detected, which resulted in strong BCOR immunopositivity. We have therefore examined other, not analysed so far, types of central nervous system (CNS) tumours, pineoblastoma and germinoma, to assess a potential involvement of BCOR in these tumours. Levels of BCOR RNA expression were investigated by NanoString nCounter system analysis in a series of altogether 66 high grade paediatric tumours, including four pineoblastoma cases. Immunohistological detection of BCOR was performed in eight pineoblastoma, five germinoma and four atypical teratoid rhabdoid tumours (ATRTs), all located in the pineal region. We detected BCOR expression in all pineoblastomas, at the RNA and protein levels, but not in germinomas and ATRTs. Further analysis of pineoblastoma samples did not reveal the presence of either BCOR internal tandem duplication or BCOR fusion involvement. Positive immunohistological BCOR nuclear reaction in pineoblastoma may therefore differentiate this type of tumour from other high grade tumours located in the pineal region.

Transactivation (TAR) DNA binding protein 43 kDa (TDP-43) inclusions frequently occur as a comorbid pathology in several neurodegenerative disorders, including Alzheimer's disease, Huntington's disease, Lewy body disease, and progressive supranuclear palsy, and may appear in association with nondegenerative neurological etiology, for example neoplastic, paraneoplastic, traumatic, or infectious. Relationships between various pathological proteins and mechanisms associated with TDP-43-induced neurodegeneration are still not fully understood. Thus, overlap of distinct neuropathological mechanisms frequently leads to greater brain atrophy and a more severe clinical course, suggesting the importance of co-pathologies in ante-mortem diagnosing and treatment. The present review aims to discuss the incidence, morphology, and role of TDP-43 pathology in the context of other dominant, hallmark pathologies, referred to as secondary TDP-43 proteinopathies. The previous part (Part 1) focused on common neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, and Lewy body disease, while the present part (Part 2) discusses TDP-43 pathology in rare neurodegenerative diseases and neurological diseases with nondegenerative etiology.

Involving in the immune response after cerebral infarction, astrocytes could secrete large amounts of pro- and anti-inflammatory factors. The aim of this study is to investigate the effect of Wnt3a intervention on the inflammatory response of oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/R) astrocyte model, and to provide a new target for immunoprotective treatment of cerebral infarction. We constructed the OGD/R rat astrocyte model, the astrocytes were treated by different concentrations of glucose (25, 50, 100 mM) intervened with/without Wnt3a (25 µg/ml). Microscope was used to observe the cell survival in rat astrocytes. The relative expression of inflammatory factors (TNF-a, IL-6, HIF-a) in rat astrocytes was detected by qRT-PCR. The expression of inflammatory factors such as TNF-a, IL-6 and HIF-a in rat astrocytes was increased after OGD/R treatment. The Wnt3a intervention promoted cell survival and decreased the expression of inflammatory factors in rat astrocytes induced by OGD/R. There is a neuroprotective effect that Wnt3a intervention could reduce inflammatory response in the OGD/R rat astrocyte model.