Hispidulin Enhances Temozolomide (TMZ)-Induced Cytotoxicity against Malignant Glioma Cells In Vitro by Inhibiting Autophagy.

Temozolomide (TMZ), an oral alkylating agent, is the widely used first-line chemotherapeutic reagent for glioma in clinical practice. However, TMZ-induced autophagy is another cellular process favoring glioma cell survival. This study aimed to explore whether hispidulin can facilitate TMZ-induced cell death of glioma. The MTT assay showed that coadministration with hispidulin and TMZ could significantly decrease the viability of glioma U87MG cells. Meanwhile, hispidulin administration was also observed to promote TMZ-induced apoptosis. Furthermore, additional hispidulin treatment further elevated TMZ-induced expression of Bax, cleaved-caspase-9, and cleaved-caspase-3 protein but decreased Bcl-2 protein expression in U87MG cells. We also observed that hispidulin suppressed TMZ-induced autophagy to promote apoptosis, as showed by decreased AVOs and LC3B-I/II protein expression. These results collectively suggested that the combination of hispidulin and TMZ could improve the antitumor efficiency of TMZ against malignant gliomas.

Development and Multi-Data Set Verification of an RNA Binding Protein Signature for Prognosis Prediction in Glioma.

Objective: Increasing evidence emphasizes the clinical implications of RNA binding proteins (RBPs) in cancers. This study aimed to develop a RBP signature for predicting prognosis in glioma. Methods: Two glioma datasets as training (n = 693) and validation (n = 325) sets were retrieved from the CGGA database. In the training set, univariate Cox regression analysis was conducted to screen prognosis-related RBPs based on differentially expressed RBPs between WHO grade II and IV. A ten-RBP signature was then established. The predictive efficacy was evaluated by ROCs. The applicability was verified in the validation set. The pathways involving the risk scores were analyzed by ssGSEA. scRNA-seq was utilized for evaluating their expression in different glioma cell types. Moreover, their expression was externally validated between glioma and control samples. Results: Based on 39 prognosis-related RBPs, a ten RBP signature was constructed. High risk score distinctly indicated a poorer prognosis than low risk score. AUCs were separately 0.838 and 0.822 in the training and validation sets, suggesting its well performance for prognosis prediction. Following adjustment of other clinicopathological characteristics, the signature was an independent risk factor. Various cancer-related pathways were significantly activated in samples with high risk score. The scRNA-seq identified that risk RBPs were mainly expressed in glioma malignant cells. Their high expression was also found in glioma than control samples. Conclusion: This study developed a novel RBP signature for robustly predicting prognosis of glioma following multi-data set verification. These RBPs may affect the progression of glioma.

Comparison of surgical clipping and endovascular coiling in the treatment of oculomotor nerve palsy caused by posterior communicating artery aneurysm.

Oculomotor nerve palsy (ONP) caused by posterior communicating aneurysm (PcomAA) is mainly treated by surgical clipping or endovascular coiling. However, there are still some controversies about which treatment method could provide the more beneficial prognosis. This study aimed to compare ONP recovery rate between surgical clipping and endovascular coiling in patients diagnosed as PcomAA combined with ONP, and explore the potential risk factors of ONP recovery.The clinical data of 152 patients with ONP caused by PcomAA were retrospectively analyzed. Diameter of aneurysm, different treatment methods (surgical clipping or endovascular coiling), subarachnoid hemorrhage (SAH), degree of preoperative ONP, time from ONP onset to treatment, as well as degree of ONP symptom recovery were collected from medical records. All patients were followed up for at least 1 year.One hundred twelve patients underwent surgical clipping and 40 patients received endovascular coiling. There were no significant differences in age, gender, aneurysm diameter, hypertension, dyslipidemia, time from ONP symptom onset to treatment, SAH, and preoperative ONP degree between the 2 groups (all P > .05). Time to complete or partial recovery was 86.7 ±â€Š35.7 days for patients receiving surgical clipping and 132.6 ±â€Š37.5 days for patients receiving endovascular coiling, respectively (Log rank test, P < .001). The recovery rate was 94.6% in the surgical clipping group and 65.0% in the endovascular coiling group. The difference between the two groups was statistically significant (P < .001). Postoperative ONP recovery in the surgical clipping group was significantly superior to that of patients in the endovascular coiling group (HR, 2.625; 95% CI: 1.423-4.841; P = .002). Time from ONP symptom onset to treatment exerted the obvious effect on the ONP prognosis (HR, 0.572; 95% CI: 0.384-0.852; P = .006). In addition, the ONP recovery in patients with SAH before surgery was also independently associated with ONP prognosis (HR, 1.276; 95% CI, 1.043-1.562; P = .018). There was no treatment-related death in either group, and postoperative complications were within the manageable range.The recovery rate and recovery degree of ONP after surgical clipping was significantly better than that of endovascular coiling in PcomAA patients combined with ONP. The postoperative ONP recovery was associated with preoperative spontaneous SAH and time from ONP onset to treatment.

Insight Into the Role of Ferroptosis in Non-neoplastic Neurological Diseases.

Ferroptosis is an iron-dependent form of cell death characterized by the accumulation of intracellular lipid reactive oxygen species (ROS). Ferroptosis is significantly different from other types of cell death including apoptosis, autophagy, and necrosis, both in morphology and biochemical characteristics. The mechanisms that are associated with ferroptosis include iron metabolism, lipid oxidation, and other pathophysiological changes. Ferroptosis inducers or inhibitors can influence its occurrence through different pathways. Ferroptosis was initially discovered in tumors, though recent studies have confirmed that it is also closely related to a variety of neurological diseases including neurodegenerative disease [Alzheimer's disease (AD), Parkinson's disease (PD), etc.] and stroke. This article reviews the definition and characteristics of ferroptosis, the potential mechanisms associated with its development, inducers/inhibitors, and its role in non-neoplastic neurological diseases. We hope to provide a theoretical basis and novel treatment strategies for the treatment of central nervous system diseases by targeting ferroptosis.