Efficacy and safety of a "radical" surgical strategy in the treatment of parasagittal sinus meningioma.

Background: No standardized criteria for surgical resection of parasagittal sinus meningiomas (PSM) have been established, and different surgical strategies have been proposed. The aim of the present study was to investigate the efficacy and safety of a "radical" surgical strategy in the treatment of PSM. Methods: The clinical histories, radiological findings, pathologic features, and surgical records of 53 patients with PSM admitted by the same surgical team using the "radical" surgical strategy were retrospectively analyzed between 2018 and 2023. Results: Among the 53 PSM cases, 16 (30.2%) had a patent sinus proper, 28 (52.8%) had partial obstruction of the sinus proper, and 9 (17.0%) had complete obstruction of the sinus proper before the operation. During operation, Simpson grade I resection was performed in 34 (64.2%) cases and Simpson grade II in 19 (35.8%) cases. Postoperative pathologic examination suggested tumors of WHO grade I in 47 (88.7%) cases, WHO grade II in 4 (7.5%) cases, and WHO grade III in 2 (3.8%) cases. Postoperative complications primarily included a small amount of delayed intracerebral hemorrhage in 3 (5.7%) cases, exacerbation of cerebral edema in 3 (5.7%) cases, exacerbation of motor and sensory deficits in 4 (7.5%) cases, and intracranial infection in 2 (3.8%) cases. There were no cases of death or new-onset neurological dysfunction. Dizziness and headache symptoms improved to varying degrees, and a seizure-free status was achieved postoperatively. Excluding one case lost to follow-up, the average follow-up period was 33 months, and there were no cases of recurrence. Conclusion: A "radical" strategy for the surgical management of PSM is effective, safe, and simple to perform, provided that the sagittal sinus is properly managed and its associated veins are protected.

E3 ligase Nedd4L promotes macrophage M1 polarization and exacerbates brain damage by TRAF3/TBK1 signaling pathway after ICH in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) is a serious medical problem, and promising strategy is limited. Macrophage initiated brain inflammatory injury following ICH, but the molecular mechanism had not been well identified. E3 ligase Nedd4L is implicated in the pathogenesis of the inflammatory immune response. METHODS: In the present study, we detected the levels of Nedd4L in macrophages following ICH. Furthermore, Macrophage M1 polarization, pro-inflammatory cytokine production, BBB disruption, brain water content and neurological function were examined in ICH mice. RESULTS: Here, we demonstrated that E3 ligase Nedd4L levels of macrophage increased following ICH, promoted M1 polarization inflammation by TRAF3. Nedd4L promoted BBB disruption, as well as neurological deficits. Inhibition of Nedd4L significantly attenuated M1 polarization in vivo. Inhibition of Nedd4L decreased TRAF3 and TBK1 levels, and subsequent phosphorylation of p38 and NF-κB p65 subunit following ICH. CONCLUSIONS: Our data demonstrated that Nedd4L was involved in the pathogenesis of ICH, which promoted inflammatory responses and exacerbated brain damage by TRAF3 following ICH.

MiR-325-3p functions as a suppressor miRNA and inhibits the proliferation and metastasis of glioma through targeting FOXM1.

Glioma is a malignant brain tumor exhibiting high levels of proliferation and metastasis, and these have been related to its poor prognosis and high mortality rate. MicroRNA (miRNA)-325-3p exhibits tissue-specific expression profiles and is aberrantly expressed in multiple types of malignant tumors. Our research focuses on determining the function and mechanism of action of miR-325-3p in glioma. The relative expression levels of miR-325-3p in glioma tumor tissues and cell lines were verified by qRT-PCR. The effect of 325-3p on glioma tumor cell behavior was assessed using CCK-8 assays, EDU staining, colony formation assays, flow cytometry, transwell invasion assays, and a xenograft model. In addition, we searched for miR-325-3p targets, and their potential mechanism of action was demonstrated using a reporter assay and rescue experiments. Results showed that the expression levels of miR-325-3p in glioma cancer tissues and tumor cell lines were significantly lower than that of normal paired adjacent tissue or normal cell lines. Functional experiments illustrated that tumor proliferation, migration and invasion were suppressed via upregulation of miR-325-3p. To assess whether FOXM1 is a target of miR-325-3p, we examined this hypothesis using a luciferase report assay and then found that miR-325-3p could modulate the expression of FOXM1. Furthermore, the functional role of miR-325-3p was also confirmed in a xenograft model using nude mice. Together, our data demonstrated that in glioma, miR-325-3p may inhibit cancer cell growth through the suppression of FOXM1 and could be a promising new target for treating this type of brain cancer.

MiRNA-494 enhances M1 macrophage polarization via Nrdp1 in ICH mice model.

BACKGROUND: Ubiquitination-mediated M1/M2 macrophage polarization plays important roles in the pathogenesis of immune disease. However, the regulatory mechanism of ubiquitination during M1/M2 macrophage polarization following intracerebral hemorrhage (ICH) has not been well studied. METHODS: In the experiment, macrophages were administered with erythrocyte lysates, and then miR-494-, Nrdp1-, and M1/M2-related markers were analyzed. Brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed. RESULTS: We found that miR-494 levels increased while Nrdp1 levels decreased in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3'-untranslated region. MiR-494 attenuated C/EBP-ß activation and downstream proinflammatory factor production. Upregulation of Nrdp1 in macrophages significantly promoted M2 macrophage polarization via ubiquitinating and activating C/EBP-ß. Moreover, the results indicated that miR-494 could enhance M1 macrophage polarization, promote brain edema, and impair neurological functions in ICH mice. CONCLUSIONS: Taken together, our results demonstrated that Nrdp1 contributed to M1/M2 macrophage polarization and neuroinflammation via ubiquitination and activation of C/EBP-ß in ICH. miR-494 may provide a promising therapeutic clue for ICH.

Dendritic cells transduced with glioma-expressed antigen 2 recombinant adenovirus induces specific cytotoxic lymphocyte response and anti-tumor effect in mice.

INTRODUCTION: Glioma is an aggressive common cancer with high mortality worldwide. Up to date, the effective medical therapeutical strategy is limited. Numerous previous studies have indicated that glioma-expressed antigen 2 (GLEA2) might be an attractive prognostic glioma biomarker. METHODS: In this experiment, dendritic cells (DCs) transduced with GLEA2 recombinant adenovirus were utilized to generate cytotoxic lymphocytes (CTLs) in vitro. Additionally, trimera mice were immunized with the transduced DCs to generate CTLs in vivo. RESULTS: The data demonstrated that GLEA2 transduced DCs could effectively generate specific CTL response against glioma without lysing autologous lymphocytes. Moreover, GLEA2 transduced DCs significantly attenuated the tumor growth and prolonged the life span of tumor bearing mice. CONCLUSIONS: These findings suggested that DCs transduced with GLEA2 recombinant adenovirus could generate effective CTL mediated anti-tumor response, and might represent insight in glioma therapy.

Overexpression of miR-1283 Inhibits Cell Proliferation and Invasion of Glioma Cells by Targeting ATF4.

It is well known that activating transcription factor 4 (ATF4) expression is closely associated with progression of many cancers. We found that miR-1283 could directly target ATF4. However, the precise mechanisms of miR-1283 in glioma have not been well clarified. Our study aimed to explore the interaction between ATF4 and miR-1283 in glioma. In this study, we found that the level of miR-1283 was dramatically decreased in glioma tissues and cell lines, the expression of ATF4 was significantly increased, and the low level of miR-1283 was closely associated with high expression of ATF4 in glioma tissues. Moreover, introduction of miR-1283 significantly inhibited proliferation and invasion of glioma cells. However, knockdown of miR-1283 promoted the proliferation and invasion in glioma cells. Bioinformatics analysis predicted that the ATF4 was a potential target gene of miR-1283. Luciferase reporter assay demonstrated that miR-1283 could directly target ATF4. In addition, knockdown of ATF4 had similar effects with miR-1283 overexpression on glioma cells. Upregulation of ATF4 in glioma cells partially reversed the inhibitory effects of miR-1283 mimic. Overexpression of miR-1283 inhibited cell proliferation and invasion of glioma cells by directly downregulating ATF4 expression.

MCP-1-mediated activation of microglia promotes white matter lesions and cognitive deficits by chronic cerebral hypoperfusion in mice.

Microglia activation played a vital role in the pathogenesis of white matter lesions (WMLs) by chronic cerebral hypoperfusion. In addition, hypoxia induced up-regulated expression of MCP-1, promotes the activation of microglia. However, the role of MCP-1-mediated microglia activation in chronic cerebral ischemia is still unknown. To explore that, chronic cerebral hypoperfusion model was established by permanent stenosis of bilateral common carotid artery in mice. The activation of microglia and the related signal pathway p38MAPK/PKC in white matter, and working memory of mice were observed. We found that stenosis of common carotid arteries could induce MCP-1-mediated activation of microglia through p38MAPK/PKC pathway and white matter lesions. Taken together, our findings represent a novel mechanism of MCP-1 involved in activation of microglia and provide a novel therapeutical strategy for chronic cerebral hypoperfusion.

Sinomenine enhances microglia M2 polarization and attenuates inflammatory injury in intracerebral hemorrhage.

Microglia polarization plays a vital role in brain inflammatory injury following intracerebral hemorrhage (ICH). Previous studies have shown that sinomenine possesses potential immunoregulatory capabilities. However, microglia polarization's exact mechanisms in ICH remain uncertain. Therefore, we examined the role of sinomenine on microglia polarization and brain inflammation following ICH. For the experiment, autologous blood models were constructed in C57/BL6 mice. Markers of classically activated (M1) and alternatively activated (M2) microglia were detected by real-time polymerase chain reaction, immunofluorescence, and flow cytometry. Microglial toxicity was assessed using MTT and FACS assays. In addition, the neurological deficit and cerebral water content of ICH mice were also observed. Sinomenine attenuated M1 markers while promoting M2 markers of microglia. Sinomenine also protected hippocampal neurons from indirect toxicity mediated by ICH-treated microglia. Additionally, administration of sinomenine inhibited matrix metalloproteinase (MMP) 3/9 expression, cerebral water content, and neurological deficit. Therefore, sinomenine protected brain function following ICH, perhaps via M2 microglia phenotype induction and MMP 3/9 inhibition. This result suggests that sinomenine is a promising therapeutical strategy in ICH.