Glioblastoma (GBM), as one of the most common and aggressive primary brain tumors, pose significant challenges in diagnosis and treatment, highlighting the urgent need for the identification of novel biomarkers, NFKBIE, which may play a critical role in tumor progression, immune modulation, and therapeutic response. We investigated the role of NFKBIE in GBM through both bioinformatics analysis and experimental validation. Initially, bioinformatics analysis based on public databases revealed significant differential expression of NFKBIE across various cancer types, particularly in GBM, where elevated expression was correlated with poor patient prognosis, including overall survival, disease-specific survival, and progression-free survival. Furthermore, genetic alterations in NFKBIE, such as copy number variations (CNVs) and tumor mutational burden (TMB), were significantly associated with tumor progression. In the experimental validation phase, we utilized small interfering RNA (siRNA) technology to silence NFKBIE expression in GBM cell lines, including U87 and T98G. Functional assays were then performed to assess the impact of NFKBIE knockdown. Cell proliferation assays, including CCK-8 and clonogenic assays, demonstrated that silencing NFKBIE significantly inhibited the proliferation of GBM cells. Migration and invasion assays, including wound healing and Transwell assays, further confirmed that NFKBIE knockdown markedly suppressed the migratory and invasive abilities of GBM cells. Additionally, apoptosis assays, such as TUNEL staining, revealed that NFKBIE silencing significantly promoted apoptosis in GBM cells. Western blot analysis confirmed the changes in the expression of key markers associated with proliferation, stemness, migration, invasion, and apoptosis. Furthermore, in a mouse xenograft model, NFKBIE knockdown significantly slowed tumor growth. Histological analysis of the excised tumors confirmed that reduced NFKBIE expression was closely associated with the inhibition of tumor growth. Notably, NFKBIE silencing also led to the downregulation of components of the Hedgehog signaling pathway, suggesting that NFKBIE may regulate tumor progression through modulation of this critical pathway. In conclusion, high NFKBIE expression is strongly associated with GBM progression and poor prognosis, and targeting its expression may offer a promising therapeutic strategy for GBM treatment.

Background: Recent studies have shown that curcumin can reduce the symptoms of hydrocephalus. However, the underlying mechanisms remain unclear. Our previous studies demonstrated that E2F transcription factor 4 (E2F4) protein plays an important role in hydrocephalus; hence, we hypothesized that E2F4 may involve in curcumin mediated anti-hydrocephalus benefits. Methods: E2F4 expression and functions in different human tissues and cell lines were determined and analyzed using the all RNA-seq and ChIP-seq sample and signature search database and ChIP-atlas database. Hydrocephalus mouse model was established through stereotactic injection of shE2F4 into frontal cortex. Mice were treated with curcumin, and then hydrocephalus severity, the expression of E2F4, and downstream targets were analyzed. Results: E2F4 was highly expressed in the nervous system, which was downregulated in the bran of hydrocephalus patients. Knockdown E2F4 in mice could mimic the phenotype of human hydrocephalus. Upon curcumin administration, E2F4 expression level was increased, and the hydrocephalus severity score was significantly decreased in mouse model. Mechanistically, curcumin attenuated hydrocephalus through activating E2F4 signaling pathway. Conclusion: Curcumin suppresses hydrocephalus progression via activation of E2F4, which could be a target for hydrocephalus treatment.

Brain metastasis is a devastating clinical condition globally as one of the most common central nervous system malignancies. The current study aimed to assess the effect of defibrotide, an Food and Drug Administration-approved drug, against brain metastasis and the underlying molecular mechanisms. Two tumor cell lines with high brain metastasis potential, PC-9 and 231-BR, were subjected to defibrotide treatment of increasing dosage. The metastasis capacity of the tumor cells was evaluated by cell invasion and migration assays. Western blotting was employed to determine the levels of tight junction proteins in the blood-brain barrier (BBB) including Occludin, Zo-1, and Claudin-5, as well as metastasis-related proteins including CXCR4, MMP-2, and MMP-9. The in-vitro observations were further verified in nude mice, by monitoring the growth of xenograft tumors, mouse survival and brain metastasis foci following defibrotide treatment. Defibrotide inhibited proliferation, migration, invasion, and promotes lactate dehydrogenase release of brain metastatic tumor cells, elevated the levels of BBB tight junction proteins and metastasis-related proteins. Such beneficial role of defibrotide was mediated by its inhibitory action on the SDF-1/CXCR4 signaling axis both in vitro and in vivo , as CXCR4 agonist SDF1α negated the anti-tumoral effect of defibrotide on mouse xenograft tumor growth, mouse survival and brain metastasis. Defibrotide inhibits brain metastasis through activating the adenosine A2A receptors, which in turn inhibits the SDF-1/CXCR4 signaling axis. Our study hereby proposes defibrotide as a new and promising candidate drug against brain metastasis of multiple organ origins.

Background: Neuroinflammation subsequent to traumatic brain injury (TBI) is important for the recovery of patients and is associated with neurodegenerative changes post-TBI. The tripartite motif containing 44 (TRIM44) protein is an E3 ligase involved in the regulation of immune function with no previously known link to TBI. This study explores the connection between TRIM44 and TBI. Methods: After induction of TBI in rats by control cortex injury, TRIM44 expressions were determined with quantitative real-time reverse transcription polymerase chain reaction and Western blot, and Toll-like receptor 4 (TLR4)-NF-κB signaling was examined by the expression of TLR4, p65 phosphorylation, and the specific NF-κB transcription activity. The effects of TRIM44 knockdown on inflammation, neurological function, and TLR4-NF-κB signaling in TBI rats were revealed by the detection of proinflammatory cytokines and TLR4-NF-κB signaling molecules, modified neurological severity score, brain water content, and Evans blue permeability. Results: We found that TRIM44 expression was significantly increased following TBI induction along with TLR4-NF-κB activation. Silencing of TRIM44 suppressed proinflammatory cytokine production, improved neurological outcomes, alleviated brain edema, and inhibited TLR4-NF-κB signaling in TBI rats. Conclusion: Our findings suggest that suppressing TRIM44 or modulation of relevant pathways may be a therapeutic strategy for TBI.

This study aimed to characterize the expression status and potentially mechanistic involvement of SNHG7 in pituitary adenoma. Relative expression of SNHG7 and miR-449a was analyzed by real-time PCR. Cell viability was measured with Cell Counting Kit-8 (CCK-8). Cell apoptosis was determined by PI/Annexin V double staining followed by flow cytometry analysis. Cell invasion and migration were analyzed by wound healing and transwell assays, respectively. The regulatory action of miR-449a on SNHG7 was interrogated by luciferase reporter assay. We also investigated the pro-tumor activity of SNHG7 with the MMQ xenograft tumor mouse model. We identified the aberrant up-regulation of SNHG7 in pituitary adenoma both in vivo and in vitro, which associated with poor survival outcome. siRNA-mediated SNHG7-knockdown decreased cell viability, increased apoptosis and compromised migration and invasion. We further predicted and validated that SNHG7 negatively regulated miR-449a via sponging. Concurrent inhibition of miR-449a restored cell viability, apoptosis, migration and invasion influenced by SNHG7-deficiency. Most importantly, we demonstrated that SNHG7-silencing delayed xenograft tumor progression, which was accompanied with increased miR-449a and decreased Ki67 intensity. Our study highlighted the essential oncogenic properties of the SNHG7/miR-449a axis in pituitary adenoma.

To explore the curative effect of early neuroendoscopic removal of intraventricular hematoma combined with endoscopic third ventriculostomy (ETV) on the thalamic hemorrhage broken into the ventricle. Methods Of 68 patients with thalamic hemorrhage broken into ventricles treated in our department from July, 2011 to July, 2015, 36 (observed group) were treated by neuroendoscopic hematoma removal of intraventricular hematomas combined with ETV and postoperative external ventricular drainage ( EVD), 32 (control group) by EVD combined with injection of urokinase into hematoma cavities. All the patients were postoperatively followed up from 12 to 26 months. The curative effects were compared between both the groups. Results The follow-up results showed that the effective rate (86.1%, 31/36) was significantly higher in the observed group and that (62.5%, 20/32) in the control group (P<0.05). Conclusion The treatment of thalamic hemorrhage broken into ventricles by neuroendoscopic surgery combined with ETV is safe and effective, because it can significantly reduce the incidence of shunt-dependent hydrocephalus and significantly improve the long-term prognosis in the patients with thalamic hemorrhage broken into ventricles.

目的 探讨神经内镜第三脑室底造瘘术(ETV)联合脉络丛烧灼术(CPC)对脑积水的治疗效果.方法 回顾性分析60例脑积水病人的临床资料,并根据手术方式分为观察组(ETV联合CPC)34例和对照组(ETV)26例,比较两组术后6、12个月的治疗效果.结果 术后6、12个月观察组有效率分别为88.2％、85.3％,对照组分别为65.4％、61.5％,差异均具有统计学意义(P<0.05).两组术后均未发生ETV和CPC相关并发症.结论 ETV联合CPC治疗脑积水安全有效,可明显提高有效率,显著改善病人远期预后.

Purpose To investigate the role of ICA II in subarachnoid hemorrhage (SAH)- related chronic hydrocephalus. Methods A two hemorrhage injection model of SAH was created in Sprague Dawley rats (6-8 weeks). A total of 125 rats were randomly assigned into five groups: Sham group, SAH group, SAH+ ICA II (1 mg/kg) group, SAH + ICA II (5 mg/kg) group, and SAH + ICA II (10 mg/kg) group. TGF-β1, phospho-Smad2/3, connective tissue growth factor (CTGF), and procollagen type I carboxy-terminal propeptide (PICP) were assessed via real-time PCR, Western blotting, and enzyme-linked immunosorbent assay. Lateral ventricular index, Masson staining, and Morris water maze tests were employed to evaluate subarachnoid fibrosis, hydrocephalus, and long term neurological function following SAH. Results ICA II (1, 5, 10 mg/kg) inhibited subarachnoid fibrosis, attenuated ventriculomegaly, and effectively suppressed SAH related chronic hydrocephalus. In addition, parallel reduced expression of members of the TGF-β1/Smad/CTGF signaling pathway were observed. Importantly, ICA II may improve long term neurocognitive deficits after SAH. Conclusion ICA II might suppress fibrosis via inhibition of TGF-β1/Smad/CTGF pathway, prevent the development of SAH related chronic hydrocephalus, and improve long term neurocognitive defects following SAH.