Intraoperative lumbar drainage can prevent cerebrospinal fluid leakage during transsphenoidal surgery for pituitary adenomas: a systematic review and meta-analysis.

BACKGROUND: Perioperative cerebrospinal fluid (CSF) leakage is a major complication of pituitary adenomas transsphenoidal surgery. Lumbar drainage (LD) is a common method of treating CSF leakage. But whether intraoperative LD can prevent CSF leakage during the perioperative period of pituitary adenomas transsphenoidal surgery remains controversial. Clarity on the appropriate use of LD is needed. METHODS: A systematic literature review was conducted in the PubMed, EMBASE, and Web of science databases. Articles were included when they compared intraoperative LD with intraoperative no-LD CSF leakage rates during pituitary adenomas transsphenoidal surgery. RESULTS: Overall, 5 studies containing 678 cases met the inclusion criteria. When data were provided on intraoperative CSF leakage rates, the meta-analysis showed a significant difference in favor of intraoperative LD. When data were provided on postoperative CSF leakage rates, the meta-analysis also demonstrated a significant difference in favor of intraoperative LD. CONCLUSIONS: Although the results of this meta-analysis suggest intraoperative LD can reduce the risk of CSF leakage during the perioperative period of pituitary adenomas transsphenoidal surgery, the available evidence is indefinite. To some extent the results suggest intraoperative LD's potential positive role. Further studies that include well-designed prospective, randomized controlled clinical trials are necessary for further verification.

Dishevelled-associated antagonist of ß-catenin homolog 3 (DACT3) suppresses glioma progression though Notch1 signaling pathway in ß-catenin-dependent manner.

The disheveled-associated antagonist of ß-catenin homolog 3 (DACT3) has been recognized as a tumor suppressor in various cancers. However, the function of DACT3 on glioma malignant progression along with potential molecular mechanisms is poorly clarified. This research aimed to investigate how DACT3 contributes to suppressing the progression of glioma. In our investigation, a pronounced decrease in DACT3 expression was observed in glioma tissues. Through the overexpression of DACT3, we noted a significant suppression in the proliferation, invasion, and migration of glioma cells, while concurrently observing an increase in cell adhesion. Our exploration into the molecular mechanisms revealed that DACT3 executes its tumor-suppressive role by impeding the expression of notch 1 intracellular domain (NICD) and translocating into the nucleus by downregulating the expression of ß-catenin. Consequently, this process leads to the suppression of Notch1 signaling. To summarize, our findings reveal the function of DACT3 to inhibit glioma progression via the Notch1 signaling pathway in ß-catenin dependent manner. This study stands as the pioneer in examining the role of DACT3 in glioma progression and comprehensively elucidating its molecular mechanisms in glioma development. Therefore, our results suggest that DACT3 holds promise as both a prognostic factor and a potential biomarker for guiding treatment strategies in glioma patients (Graphical Abstract).

Pan-cancer analysis revealed prognosis value and immunological relevance of RAMPs.

Whether receptor activity-modifying proteins (RAMPs) play a key role in human cancer prognosis and immunity remains unknown. We used data from the public databases, The Cancer Genome Atlas, Therapeutically Applicable Research to Generate Effective Treatments, and the Genotype-Tissue Expression project. We utilized bioinformatics methods, R software, and a variety of online databases to analyze RAMPs. In general, RAMPs were significantly and differentially expressed in multiple tumors, and RAMP expression was closely associated with prognosis, immune checkpoints, RNA-editing genes, tumor mutational burden, microsatellite instability, ploidy, and stemness indices. In addition, the expression of RAMPs is strongly correlated with tumor-infiltrating lymphocytes in human cancers. Moreover, the RAMP co-expression network is largely involved in many immune-related biological processes. Quantitative reverse transcription polymerase chain reaction and Western blot proved that RAMP3 was highly expressed in glioma, and RAMP3 promoted tumor proliferation and migration. RAMPs exhibit potential as prognostic and immune-related biomarkers in human cancers. Moreover, RAMPs can be potentially developed as therapeutic targets or used to enhance the efficacy of immunotherapy.

Machine learning unveils immune-related signature in multicenter glioma studies.

In glioma molecular subtyping, existing biomarkers are limited, prompting the development of new ones. We present a multicenter study-derived consensus immune-related and prognostic gene signature (CIPS) using an optimal risk score model and 101 algorithms. CIPS, an independent risk factor, showed stable and powerful predictive performance for overall and progression-free survival, surpassing traditional clinical variables. The risk score correlated significantly with the immune microenvironment, indicating potential sensitivity to immunotherapy. High-risk groups exhibited distinct chemotherapy drug sensitivity. Seven signature genes, including IGFBP2 and TNFRSF12A, were validated by qRT-PCR, with higher expression in tumors and prognostic relevance. TNFRSF12A, upregulated in GBM, demonstrated inhibitory effects on glioma cell proliferation, migration, and invasion. CIPS emerges as a robust tool for enhancing individual glioma patient outcomes, while IGFBP2 and TNFRSF12A pose as promising tumor markers and therapeutic targets.

Hypocretin-1 suppresses malignant progression of glioblastoma cells through Notch1 signaling pathway.

Hypocretin-1 is a multifunctional neuropeptide that has been identified as a potential antitumor agent for its role in inhibiting tumor growth, including in colon cancer, neuroendocrine tumor, and prostate cancer. However, the role and mechanism of hypocretin-1 in the occurrence and development of malignant glioma have not been well studied. Therefore, we investigated the effect of hypocretin-1 on glioblastoma proliferation, apoptosis, migration and invasion and its mechanism. We found that the hypocretin-1 receptor was expressed in both glioma cell lines and glioma tissues. Hypocretin-1 treatment can inhibit glioblastoma cell proliferation, migration and invasion, and induce cell apoptosis. Meanwhile, hypocretin-1 treatment significantly reduces tumor growth rate and tumor weight. In addition, mechanistic studies have found that hypocretin-1 exerts antitumor effects by inhibiting NOTCH signaling pathway. Overexpression of NICD significantly reversed the antitumor effect of hypocretin on glioblastoma. Taken together, these findings suggest that hypocretin-1 inhibits glioblastoma proliferation, migration and invasion and induces apoptosis in vitro and in vivo through NOTCH signaling pathway.

Multiomics integration reveals the effect of Orexin A on glioblastoma.

Objectives: This study involved a multi-omics analysis of glioblastoma (GBM) samples to elaborate the potential mechanism of drug treatment. Methods: The GBM cells treated with or without orexin A were acquired from sequencing analysis. Differentially expressed genes/proteins/metabolites (DEGs/ DEPs/ DEMs) were screened. Next, combination analyses were conducted to investigate the common pathways and correlations between the two groups. Lastly, transcriptome-proteome-metabolome association analysis was carried out to determine the common pathways, and the genes in these pathways were analyzed through Kaplan-Meier (K-M) survival analysis in public databases. Cell and animal experiments were performed to investigate the anti-glioma activity of orexin A. Results: A total of 1,527 DEGs, 52 DEPs, and 153 DEMs were found. Moreover, the combination analyses revealed that 6, 4, and 1 common pathways were present in the transcriptome-proteome, proteome-metabolome, and transcriptome-metabolome, respectively. Certain correlations were observed between the two data sets. Finally, 11 common pathways were discovered in association analysis, and 138 common genes were screened out in these common pathways. Six genes showed significant differences in terms of survival in both TCGA and CGGA. In addition, orexin A inhibited the proliferation, migration, and invasion of glioma in vitro and in vivo. Conclusion: Eleven common KEGG pathways with six common genes were found among different omics participations, revealing the underlying mechanisms in different omics and providing theoretical basis and reference for multi-omics research on drug treatment.

Mast cell activation mediates blood-brain barrier impairment and cognitive dysfunction in septic mice in a histamine-dependent pathway.

Introduction: Sepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction resulting from a systemic inflammatory response to infection; however, its pathophysiology remains unclear. Sepsis-induced neuroinflammation and blood-brain barrier (BBB) disruption are crucial factors in brain function disturbance in SAE. Mast cells (MCs) activation plays an important role in several neuroinflammation models; however, its role in SAE has not been comprehensively investigated. Methods: We first established a SAE model by cecal ligation puncture (CLP) surgery and checked the activation of MCs. MCs activation was checked using immumohistochemical staining and Toluidine Blue staining. We administrated cromolyn (10mg/ml), a MC stabilizer, to rescue the septic mice. Brain cytokines levels were measured using biochemical assays. BBB disruption was assessed by measuring levels of key tight-junction (TJ) proteins. Cognitive function of mice was analyzed by Y maze and open field test. Transwell cultures of brain microvascular endothelial cells (BMVECs) co-cultured with MCs were used to assess the interaction of BMVECs and MCs. Results: Results showed that MCs were overactivated in the hippocampus of CLP-induced SAE mice. Cromolyn intracerebroventricular (i.c.v) injection substantially inhibited the MCs activation and neuroinflammation responses, ameliorated BBB impairment, improved the survival rate and alleviated cognitive dysfunction in septic mice. In vitro experiments, we revealed that MCs activation increased the sensitivity of BMVECs against to lipopolysaccharide (LPS) challenge. Furthermore, we found that the histamine/histamine 1 receptor (H1R) mediated the interaction between MCs and BMVECs, and amplifies the LPS-induced inflammatory responses in BMVECs by modulating the TLR2/4-MAPK signaling pathway. Conclusions: MCs activation could mediate BBB impairment and cognitive dysfunction in septic mice in a histamine-dependent pathway.

The Hounsfield Unit of Perihematomal Edema Is Associated With Poor Clinical Outcomes in Intracerebral Hemorrhage.

BACKGROUND: Hounsfield unit (HU) of perihematomal edema (PHE) may be a predictor of prognosis of intracerebral hemorrhage (ICH). Our study evaluated whether PHE mean HU at the 72 hours after ICH predicts outcome, and how it compares against other PHE measures. METHODS: Patients with ICH from a tertiary medical institution were included. PHE was segmented by the semiautomatic plane method to measure volume and mean HU. Outcomes of interest was poor 90-day prognosis (modified Rankin Scale score ≥3). Logistic regression was used to assess relationships with outcome. RESULTS: Data from a total of 159 patients with ICH were collected. The median mean HU of PHE at 72 hours was 22.1 (IQR: 19.2-25.0). Binary logistic regression showed that the 72-hour PHE mean HU was negatively correlated with the poor prognosis of patients with ICH (OR 0.59, 95% CI 0.47-0.75, P < 0.05). The receiver operator curves of meaningful indicators revealed that the area under the curve (AUC) of PHE mean HU at 72 hours was larger and the difference of AUC between PHE mean HU with PHE absolute volume or extension distance were statistically significant (P < 0.05). The 72-hour PHE mean HU has a higher value in predicting adverse prognosis of patients with ICH. CONCLUSIONS: The PHE mean HU at 72 hours was negatively correlated with the poor prognosis of patients with ICH. The prediction ability of PHE mean HU at 72 hours was better than PHE absolute volume and extension distance, contributing to a rather good index for predicting outcome of ICH.