Brain-targeting redox-sensitive micelles for codelivery of TMZ and ß-lapachone for glioblastoma therapy.

Glioblastoma (GBM) is a central nervous system cancer with high incidence and poor survival rates. Enhancing drug penetration of the blood-brain barrier (BBB) and targeting efficacy is crucial for improving treatment outcomes. In this study, we developed a redox-sensitive targeted nano-delivery system (HCA-A2) for temozolomide (TMZ) and ß-lapachone (ß-Lapa). This system used hyaluronic acid (HA) as the hydrophilic group, arachidonic acid (CA) as the hydrophobic group, and angiopep-2 (A2) as the targeting group. Control systems included non-redox sensitive (HDA-A2) and non-targeting (HCA) versions. In vitro, HCA-TMZ-Lapa micelles released 100 % of their payload in a simulated tumor microenvironment within 24 h, compared to 43.97 % under normal conditions. HCA-A2 micelles, internalized via clathrin-mediated endocytosis, showed stronger cytotoxicity and better BBB penetration and cellular uptake than controls. In vivo studies demonstrated superior tumor growth inhibition with HCA-A2 micelles, indicating their potential for GBM treatment.

Chemokine receptor CXCR4 interacts with nuclear receptor Nur77 and promote glioma invasion and progression.

BACKGROUND: Glioma is the most common primary brain tumor. It is prone to progress and have high rate of mortality regardless of radiation or chemotherapy due to its invasive growth features. Chemokine and its receptor CXCL12 and CXCR4 play important roles in cancer metastasis. METHODS: In this study, we investigate the role of CXCR4 in the progression of glioma by various molecular technologies, including qRT-PCR, Western blotting, wound closure assay, transwell assay et al. RESULTS: It was found that CXCR4 was overexpressed in glioma tissues. The expression of CXCR4 was correlated with patients' overall survival. Wound closure assay and transwell invasion assay showed that inhibition of CXCR4 significantly reduced the expression of biomarkers related to the formation of invadopodium, leading to decrease the invasion and migration of glioma tumor cells. Knocking down the nuclear receptor Nur77 remarkably decreased CXCR4 expression and reduced glioma cell invasion and migration. The reduction of glioma cell invasion and migration were observed after Nur77 inhibitor treatment. CONCLUSION: Taken together, these results indicated that CXCR4 is critical in promoting glioma migration and invasion. Inhibition of Nur77 reduces CXCR4 related cancer progression.

Pre-operative prognostic nutrition index and post-operative pneumonia in aneurysmal subarachnoid hemorrhage patients.

Background and objective: Post-operative pneumonia (POP), a common complication, may be associated with prolonged hospitalization and long-term mortality in aneurysmal subarachnoid hemorrhage (aSAH) patients. This study aimed to explore the association between pre-operative prognostic nutrition index (PNI) and POP in aSAH patients. Methods: A total of 280 aSAH patients were enrolled from Nanjing Drum Tower Hospital. PNI was calculated as follows: [10 × albumin(gr/dl)] + [0.005 × absolute pre-operative lymphocyte count (per mm3)]. We utilized multivariate analyses, restricted cubic spline, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to elucidate the role of PNI in POP. Results: Pre-operative PNI levels in the POP group were higher, compared with the non-POP group (41.0 [39.0, 45.4] vs. 44.4 [40.5, 47.3], P = 0.001). When we included PNI as a categorical variable in the multivariate analysis, the levels of PNI were associated with POP (odds ratio, 0.433; 95% confidence interval, 0.253-0.743; P=0.002). In addition, when we included PNI as a continuous variable in the multivariate analysis, the PNI levels were also associated with POP (odds ratio, 0.942; 95% confidence interval, 0.892-0.994; P = 0.028). The level of albumin was also a predictor of the occurrence of POP, with a lower diagnostic power than PNI [AUC: 0.611 (95% confidence interval, 0.549-0.682; P = 0.001) for PNI vs. 0.584 (95% confidence interval, 0.517-0.650; P = 0.017) for albumin]. Multivariable-adjusted spline regression indicated a linear dose-response association between PNI and POP in aSAH participants (P for linearity = 0.027; P for non-linearity = 0.130). Reclassification assessed by IDI and NRI was significantly improved with the addition of PNI to the conventional model of POP in aSAH patients (NRI: 0.322 [0.089-0.555], P = 0.007; IDI: 0.016 [0.001-0.031], P = 0.040). Conclusion: The lower levels of pre-operative PNI may be associated with the higher incidence of POP in aSAH patients. Neurosurgeons are supposed to pay more attention to pre-operative nutrition status in aSAH patients.

Intracranial solitary fibrous tumor mimicking meningioma: A case report.

RATIONALE: Solitary fibrous tumor is a rare mesenchymal tumor. This case report describes the diagnosis and treatment of this tumor. PATIENT CONCERNS: A 31-year-old patient presented with epileptic seizure and headache 1 day prior to the visit and showed transient right limb hemiplegia for 6 hours that was resolved after intravenous infusion of mannitol. DIAGNOSES: Based on imaging, the provisional diagnosis was meningioma. Postsurgical histopathological diagnosis confirmed solitary fibrous tumor. INTERVENTIONS: The lesion was totally excised. The patient improved remarkably after the operation, without any signs of associated limb movement disorder. No epileptic seizure was observed or reported after the operation. OUTCOMES: Postoperation computed tomography (CT) scans showed no obvious residual tumor. The patient was followed up every 3 months for a total of 1 year following the operation, during which time the patient did not complain of headache or seizure. LESSONS: The manifestation of solitary fibrous tumor (SFT) through imaging methods has certain specific findings,butimmunohistochemistry is still very important for confirming the diagnosis.

Nur77 is a promoting factor in traumatic brain injury-induced nerve cell apoptosis.

Traumatic brain injury (TBI) poses a serious threat to human health. TBI has a high mortality rate, resulting in a great burden on the affected individual's family as well as society as a whole. The incidence of craniocerebral fractures continues to rise as both the economy and transportation options grow, making it imperative that the mortality and disability rate of craniocerebral trauma be reduced. Nur77 is a transcription factor of the nuclear receptor superfamily. Following stimulation of extracellular apoptosis, Nur77 is involved in a variety of diseases as a powerful pro-apoptotic molecule. Here, we determined the effect and mechanism of Nur77 in TBI-induced nerve cell apoptosis in vitro and in vivo. We found that Nur77 and Bcl-2 protein expression increased as nerve cell apoptosis increased in TBI tissues. Furthermore, inhibition of Nur77 improved nerve cell injury by regulation of Bcl-2 and downstream pathways in vitro and in vivo.