Folia neuropathologica最新文献

Introduction: MicroRNA (miR)-485-5p has been linked to regulation of neurological disorders. The current study examined miR-485-5p levels in patients with epilepsy secondary to cerebral infarction and investigated its predictive significance.

Material and methods: The Gene Expression Omnibus (GEO) database was employed to screen differentially expressed miRNAs in cerebral infarction and epilepsy. 168 patients with cerebral infarction were enrolled, including 67 patients with secondary epilepsy and 101 patients without secondary epilepsy. Serum miR-485-5p levels were examined by reverse transcription-quantitative real-time PCR (RT-qPCR). Logistic regression analysis was used to explore risk factors for epilepsy secondary to cerebral infarction. The diagnostic and predictive value of miR-485-5p was evaluated by receiver operating characteristic (ROC) analysis. Bioinformatics predicted miR-485-5p target mRNA and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.

Results: The GEO database identified differentially expressed miRNAs including miR-485-5p. miR-485-5p levels were poorly expressed in patients with cerebral infarction ( p < 0.05) and negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score, an indicator of cerebral infarction severity. Additionally, miR-485-5p is a typical indicator for differentiating cerebral infarctions from controls. Serum miR-485-5p was lower in patients with epilepsy secondary to cerebral ischemia compared to non-epilepsy patients and is a potential risk factor for epilepsy secondary to cerebral infarction. The sensitivity and specificity for predicting epilepsy were 74.63% and 80.20%, respectively. KEGG pathway studies revealed miR-485-5p's target mRNA is primarily enriched in the adipocytokine signaling pathway and the AMPK pathway.

Conclusions: miR-485-5p correlates with cerebral infarction severity. Low expression of miR-485-5p is a promising predictive biomarker for epilepsy secondary to cerebral infarction.

Activation of the NogoA/NgR/ROCK pathway limits nerve repair after brain ischemia-reperfusion (I/R) injury. Triptolide displays anti-inflammatory, anti-oxidant, and immunosuppressive effects and is derived from the traditional Chinese medicine Tripterygium wilfordii Hook F. This agent can also penetrate the blood-brain barrier, where it has a neuroprotective effect and ameliorates cerebral I/R injury via an as yet unknown mechanism(s). Here, an animal model of middle cerebral artery occlusion and reperfusion (MCAO/R) was employed to assess triptolide's therapeutic impact on brain I/R injury and the possible mechanism of action. The results indicate that triptolide treatment can decrease cerebral infarction and nerve injury after cerebral I/R injury. Importantly, in vivo and in vitro experiments revealed that treatment with triptolide decreased NogoA, NgR, p75NTR and ROCK2 expression, and upregulated the expression of GAP43 and PSD-95, thus suggesting improved synaptic function. These results indicate that triptolide can promote nerve repair following brain I/R injury by inhibiting NogoA/NgR/ROCK signalling.

Clear cell meningioma (CCM) is a rare subtype of meningioma, especially unusual as a neoplasm of the filum terminale. Clear cell meningioma seems to have a more aggressive nature and a higher risk of recurrence than WHO grade I meningiomas. A 44-year-old woman presented with lower back pain radiating to the left leg and mild weakness in the left leg. Magnetic resonance imaging (MRI) showed a well-demarcated, intradural lesion filling the spinal canal at the L3-S1 levels and compressing the cauda equina. The patient underwent laminectomy from L3 to S1. During the operation, the filum terminale was identified as a structure that was disappearing into the tumor. The filum terminale was cut and the tumor was totally removed in one piece. Pathological findings were indicative of the diagnosis of clear cell meningioma, CNS WHO G2. Postoperative magnetic resonance imaging at 6 months showed no residual mass. Total surgical excision of the CCM of the spinal cord should be chosen as the optimal treatment. In addition, radiological follow-up is equally important due to the high risk of recurrence. Our case is unusual in that the tumor's location was the filum terminale.

Introduction: Glioma is one of the most commonly tumours which occurs in the central nervous system and accounts for nearly 80% of brain tumours, with a significantly high mortality and morbidity. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as EGFR targeted therapy in various types of solid tumours; however, effective treatment for glioma is still limited. Osimertinib is an irreversible, oral third-generation TKI that targets the mutation at T790M, which causes cancer cells to acquire resistance to drugs. Osimertinib could be effective in the treatment of EGFR mutations with minimal effects on the activity of wild-type EGFR. Absent in melanoma 2 (AIM2) is highly expressed in glioma cells, promoting the maturation of pro-cancer cytokines and contributing to progression of glioma. However, the secretion of pro-cancer cytokines of tumour cells has been regarded as the resistance mechanism to EGFR-TKIs, including osimertinib. A high level of these cytokines also indicates a shorter progression-free survival (PFS). As AIM2 regulates the secretion of pro-cancer cytokines, we thought inhibition of AIM2 may contribute to the therapeutic effect of EGFR-TKIs.

Material and methods: We first established AIM2 inhibition and overexpression in cells. Then, the viability rate of cells was calculated by cell counting kit-8 (CCK-8) method, and apoptotic ratio of cells were measured by flow cytometry. The expression of inflammatory-related genes was detected using quantitative polymerase chain reaction (qPCR), concentrations of inflammatory-related factors were measured using enzyme-linked immunosorbent assay (ELISA). The expression of Wnt/b-catenin and EGFR/Ras/Mitogen-activated protein kinase kinase 1 (MEK) signalling pathway components was detected using western blotting.

Results: We found that inhibition of AIM2 enlarged the effect of osimertinib on the upregulation of inflammatory gene expression and secretion of these genes, increasing apoptosis. In addition, we also found that AIM2 could enhance the effect of osimertinib on reducing the expression of the Wnt/b-catenin and EGFR/Ras/MEK signalling pathways, resulting in the inhibition of cellular proliferation, and exerting an anti-tumour effect. These effects were also observed using in vivo experiments.

Conclusions: AIM2 presents a potential therapeutic target in treatment of glioma.

Introduction: The objective of this study was to investigate the expression of serum miR-7 and erythrocyte sedimentation rate (ESR) levels in patients with acute herpes zoster (HZ) and their evaluation value for postherpetic neuralgia (PHN).

Material and methods: A total of 98 patients with acute HZ and 97 healthy people were enrolled in this study. The levels of miR-7 and ESR were analyzed in patients with HZ and healthy people. According to whether PHN occurred within 3 months after lesion regression, the patients were divided into HZ patients with PHN and HZ patients without PHN, and the levels of miR-7 and ESR of the two groups were analyzed. The clinical indicators of the PHN and non-PHN groups were analyzed by univariate and multivariate analysis, and the risk factors affecting PHN were evaluated. ROC curves were established to evaluate the diagnostic value of miR-7 and ESR in PHN.

Results: Compared with the healthy control group, miR-7 and ESR levels of patients with HZ showed a significant downward and upward trend, respectively. Compared with the patients without PHN, patients with PHN had decreased miR-7 and increased ESR. MiR-7 and ESR were significantly correlated with clinical indicators such as VAS scores in patients with HZ. Multivariate logistic regression analysis showed that miR-7 and ESR were independent factors influencing the occurrence of PHN. ROC analysis revealed that the combination of miR-7 and ESR had high clinical diagnostic accuracy for PHN.

Conclusions: The reduction of miR-7 and the increase of ESR are independent risk factors for PHN in HZ patients, and the ROC curve constructed based on the clinical expression levels of miR-7 and ESR showed high clinical diagnostic value for PHN.

Peripheral neuropathies with involvement of the autonomic nervous system are a recognized cause of gastrointestinal dysmotility. We describe a patient with chronic intestinal pseudo-obstruction (CIPO) in the course of chronic inflammatory demyelinating neuropathy and a complicated diagnostic procedure. Diagnostics and therapy of CIPO continue to pose a significant challenge for clinicians. The disease should be considered in patients presenting with clinical features of intestinal obstruction without radiological evidence of a mechanical obstacle. In these patients, the diagnosis is usually confirmed by histological examination of a full-thickness intestinal biopsy. However, the high rate of misdiagnosis means that CIPO patients may not be treated properly and may undergo unnecessary abdominal surgery.

Oxidative stress and disturbances of mitochondrial function in the brain play a crucial role in Alzheimer's disease (AD). However, little is known about the dynamics of these changes in different parts of the brain at the early stage of AD. This study aimed to determine the expression of genes encoding superoxide dismutases (SOD1, SOD2), poly(ADP-ribose) polymerases (PARPs) and sirtuins (SIRTs). Moreover, transcription of genes related to mitochondrial electron transport complexes (ETC) and biogenesis in the brain cortex of 4-, 6- and 12-month-old transgenic AD Tg mice was analyzed. We observed significant decreases in mRNA of Sod2, Parp1 and Sirt1 in the 3-month-old AD Tg mice and upregulation of Parp1 in the 6-month-old AD Tg mice by qPCR analysis. Then, mt-CytB and mt-Co1 (complex III and IV) mRNA levels were increased in 12- and 6-month-old AD brains, respectively. These changes were linked to lower cytochrome c oxidase activity in 3- and significantly in 6-month-old AD Tg mice. Moreover, transcription of several genes involved in mitochondria biogenesis, such as Nfe2L2 and Tfam, was upregulated respectively in the 3- and 6-month-old AD Tg mice. Expression of genes encoding PGC1 and NRF2 was significantly downregulated in 12-month-old AD Tg mice. In summary, our data identified significant changes in gene expression of Sod2, Parp1 and Sirt1 at an early age (3-6-month-old AD mice) then Ppargc1, Nfe2L2 and Sirt1 at a later age. Recognizing these alterations may be important in better understanding the complexity of pathology in AD. Moreover, our results could be helpful in consideration of appropriate target(s) in neuroprotection.

Alzheimer's disease (AD), the most common contributor to dementia, is a growing global health problem. This study aimed to investigate the role of lemur tyrosine kinase 2 (LMTK2) in AD as well as its relevant mechanism. To establish an in vitro cell model, PC12 cells were challenged with 20 µmol/l Ab 25-35 for 24 h. RT-qPCR and western blot examined LMTK2 mRNA and protein expressions. With the application of CCK-8, TUNEL, iron colorimetric assay kit and DCFH-DA, the viability, apoptosis, Fe 2+ and ROS content in PC12 cells were assessed. Besides, the expressions of oxidative stress-, apoptosis-, ferroptosis- and Nrf2/ARE signalling-related proteins were evaluated with western blot. Moreover, commercial kits examined SOD, MDA and CAT contents. The results manifested that LMTK2 expression was noticeably downregulated in Ab 25-35 -treated PC12 cells. Notably, LMTK2 overexpression exhibited inhibitory effects on oxidative stress, apoptosis and ferroptosis in PC12 cells exposed to Ab 25-35 . The upregulated Nrf2, NQO1 and HO-1 expressions in LMTK2 overexpressed-PC12 cells with Ab 25-35 induction revealed that LMTK2 overexpression could activate the Nrf2/ARE signalling pathway. What is more, a series of cellular experiments further testified that ML385, a specific Nrf2 inhibitor, partly hindered the protective role of LMTK2 overexpression against Ab 25-35 -triggered oxidative stress, apoptosis and ferroptosis in PC12 cells. In conclusion, LMTK2 overexpression alleviated the ferroptosis, oxidant damage and apoptosis in PC12 cells exposed to Ab 25-35 through the activation of the Nrf2/ARE signalling pathway, indicating the potential target of LMTK2 in the treatment of AD.

Introduction: LncRNA LBX2-AS1 drives the development of various cancers, but the exact mechanism whereby LBX2-AS1 affects glioblastoma (GBM) progression is unaddressed. This study intended to delineate the regulatory mechanism of LBX2-AS1 in GBM metastasis and angiogenesis.

Material and methods: LBX2-AS1 level in GBM was assessed by bioinformatics methods. The lncRNA-transcription factor (TF)-mRNA trios were predicted using the lncMAP database. Correlation between genes was predicted by Pearson analysis. The binding relationship was predicted by JASPAR. Levels of LBX2-AS1 and its downstream genes were assayed via qRT-PCR. Changes in expressions of VEGF-A, IL4R, and epithelial-mesenchymal transition (EMT)-associated proteins were assessed through western blot. GBM cell proliferation, migration, and invasion were assayed through CCK8, colony formation, and Transwell experiments. In vitro angiogenesis capacity was evaluated via a HUVEC tube formation experiment. The regulatory relationship between various genes was verified through radioimmunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and dual-luciferase assays.

Results: LBX2-AS1 was elevated in GBM, and in vitro experiments demonstrated the stimulatory effect of LBX2-AS1 on GBM cell proliferation, invasion, migration, and angiogenesis. We observed that LBX2-AS1 activated IL4R expression by binding the transcription factor NFKB1, thus promoting the progression of GBM. Rescue experiments illustrated that silencing IL4R or NFKB1 reversed the impact of forced LBX2-AS1 expression on GBM cells.

Conclusions: This study revealed the mechanism of the LBX2-AS1/NFKB1/IL4R axis in driving GBM metastasis and angiogenesis, which may help to improve the regulatory network of GBM malignant progression and provide potential targets for GBM treatment.

Introduction: Cerebral ischemia-reperfusion (CI/R) injury commonly occurs in ischemic stroke (IS) patients. The study examined the role of long non-coding RNA (lncRNA) TINCR in a middle cerebral artery occlusion and reperfusion (MCAO/R) induced rat model and oxygen-glucose deprivation/re-oxygenation (OGD/R) induced neuron cell models.

Material and methods: Rats were treated with MCAO/R to induce IS animal models and neural stem cells (NSCs) were treated with OGD/R to establish cell models. The neurological function, cerebral infarction area, and inflammation of rats were evaluated. Cell proliferation, migration and apoptosis were assessed. Target association between TINCR and miR-125b-5p was verified. Based on the competing endogenous RNA (ceRNA) regulatory network, the rescue experiments were done in NSCs via cell transfection.

Results: In MCAO/R rats, downregulated expression of lncRNA TINCR was tested, accompanied by neurological dysfunction and cerebral infarction. TINCR overexpression in rats led to the recovery of neurological dysfunction and cerebral infarction, while inflammation and apoptosis were inhibited. In accordance with in vivo experiment results, declined TINCR was also tested in OGD/R treated NSCs. The rescue experiments demonstrated that TINCR overexpression promoted NSC proliferation and migration, but suppressed cell apoptosis and inflammation. TINCR serves as a ceRNA of miR-125b-5p, and miR-125b-5p abolished the protective role of TINCR in OGD/R cell models.

Conclusions: LncRNA TINCR attenuated CI/R injury through competitively binding to miR-125b-5p.