Hypoxia activates macrophage-NLRP3 inflammasome promoting atherosclerosis via PFKFB3-driven glycolysis.

The onset and progression of atherosclerosis are closely linked to the involvement of macrophages. While the contribution of NLRP3 inflammasome activation to the creation of a local highly inflammatory microenvironment is well recognized, the precise triggers remain unclear. In this study, we aimed to investigate the regulatory mechanism of NLRP3 inflammasome activation in response to hypoxia-induced glycolysis involving PFKFB3 in the development of atherosclerosis. To develop an atherosclerosis model, we selected ApoE knockout mice treated with a high-fat western diet. We then quantified the expression of HIF-1α, PFKFB3, and NLRP3. In addition, we administered the PFKFB3 inhibitor PFK158 during atherosclerosis modeling. The glycolytic activity was subsequently determined through 18F-FDG micro-PET/CT, ex vivo glucose uptake, and ECAR analysis. Furthermore, we employed lipopolysaccharide (LPS) and TNF-α to induce the differentiation of bone marrow-derived macrophages (BMDMs) into M1-like phenotypes under both hypoxic and normoxic conditions. Our histological analyses revealed the accumulation of PFKFB3 in human atherosclerotic plaques, demonstrating colocalization with NLRP3 expression and macrophages. Treatment with PFK158 reduced glycolytic activity and NLRP3 inflammasome activation, thereby mitigating the occurrence of atherosclerosis. Mechanistically, hypoxia promoted glycolytic reprogramming and NLRP3 inflammasome activation in BMDMs. Subsequent blocking of either HIF-1α or PFKFB3 downregulated the NLRP3/Caspase-1/IL-1ß pathway in hypoxic BMDMs. Our study demonstrated that the HIF-1α/PFKFB3/NLRP3 axis serves as a crucial mechanism for macrophage inflammation activation in the emergence of atherosclerosis. The therapeutic potential of PFKFB3 inhibition may represent a promising strategy for atheroprotection.

Nomogram incorporating preoperative MRI-VASARI features for differentiating intracranial extraventricular ependymoma from glioblastoma.

Background: Intracranial extraventricular ependymoma (IEE) and glioblastoma (GBM) may have similar imaging findings but different prognosis. This study aimed to develop and validate a nomogram based on magnetic resonance imaging (MRI) Visually AcceSAble Rembrandt Images (VASARI) features for preoperatively differentiating IEE from GBM. Methods: The clinical data and the MRI-VASARI features of patients with confirmed IEE (n=114) and confirmed GBM (n=258) in a multicenter cohort were retrospectively analyzed. Predictive models for differentiating IEE from GBM were built using a multivariate logistic regression method. A nomogram was generated and the performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Results: The predictors identified in this study consisted of six VASARI features and four clinical features. Compared with the individual models, the combined model incorporating clinical and VASARI features had the highest area under the curve (AUC) value [training set: 0.99, 95% confidence interval (CI): 0.98-1.00; validation set: 0.97, 95% CI: 0.94-1.00] in comparison to the clinical model. The nomogram was well calibrated with significant clinical benefit according to the calibration curve and decision curve analyses. Conclusions: The nomogram combining clinical and MRI-VASARI characteristics was robust for differentiating IEE from GBM preoperatively and may potentially assist in diagnosis and treatment of brain tumors.

Magnetic resonance imaging findings of intracranial extraventricular ependymoma: A retrospective multi-center cohort study of 114 cases.

BACKGROUND: Intracranial extraventricular ependymoma (IEE) is an ependymoma located in the brain parenchyma outside the ventricles. IEE has overlapping clinical and imaging characteristics with glioblastoma multiforme (GBM) but different treatment strategy and prognosis. Therefore, an accurate preoperative diagnosis is necessary for optimizing therapy for IEE. METHODS: A retrospective multicenter cohort of IEE and GBM was identified. MR imaging characteristics assessed with the Visually Accessible Rembrandt Images (VASARI) feature set and clinicopathological findings were recorded. Independent predictors for IEE were identified using multivariate logistic regression, which was used to construct a diagnostic score for differentiating IEE from GBM. RESULTS: Compared to GBM, IEE tended to occur in younger patients. Multivariate logistic regression analysis identified seven independent predictors for IEE. Among them, 3 predictors including tumor necrosis rate (F7), age, and tumor-enhancing margin thickness (F11), demonstrated higher diagnostic performance with an Area Under Curve (AUC) of more than 70% in distinguishing IEE from GBM. The AUC was 0.85, 0.78, and 0.70, with sensitivity of 92.98%, 72.81%, and 96.49%, and specificity of 65.50%, 73.64%, and 43.41%, for F7, age, and F11, respectively. CONCLUSION: We identified specific MR imaging features such as tumor necrosis and thickness of enhancing tumor margins that could help to differentiate IEE from GBM. Our study results should be helpful to assist in diagnosis and clinical management of this rare brain tumor.

Preoperative Magnetic Resonance Imaging Radiomics for Predicting Early Recurrence of Glioblastoma.

PURPOSE: Early recurrence of glioblastoma after standard treatment makes patient care challenging. This study aimed to assess preoperative magnetic resonance imaging (MRI) radiomics for predicting early recurrence of glioblastoma. PATIENTS AND METHODS: A total of 122 patients (training cohort: n = 86; validation cohort: n = 36) with pathologically confirmed glioblastoma were included in this retrospective study. Preoperative brain MRI images were analyzed for both radiomics and the Visually Accessible Rembrandt Image (VASARI) features of glioblastoma. Models incorporating MRI radiomics, the VASARI parameters, and clinical variables were developed and presented in a nomogram. Performance was assessed based on calibration, discrimination, and clinical usefulness. RESULTS: The nomogram consisting of the radiomic signatures, the VASARI parameters, and blood urea nitrogen (BUN) values showed good discrimination between the patients with early recurrence and those with later recurrence, with an area under the curve of 0.85 (95% CI, 0.77-0.94) in the training cohort and 0.84 [95% CI, 0.71-0.97] in the validation cohort. Decision curve analysis demonstrated favorable clinical application of the nomogram. CONCLUSION: This study showed the potential usefulness of preoperative brain MRI radiomics in predicting the early recurrence of glioblastoma, which should be helpful in personalized management of glioblastoma.

[Chondrosarcoma original from the zygomatic arch: A case report and literature review].

Chondrosarcoma original from the zygomatic arch is a very rare disease with high malignancy. Surgery is the main means of treatment at present for duo to its poor sensitivity to radiochemotherapy. We reported a young patient who was recovery well in a 4-years follow-up without radiochemotherapy after a total resection of the tumor.

[Curative effect of surgery on moyamoya disease: an analysis of 47 patients].

OBJECTIVE: To evaluate the effect of surgery on 47 patients with moyamoya disease by retrospective analysis.
 Methods: A total of 47 patients with moyamoya disease were enrolled from August, 2010 to According to the improved treatment in August, 2013, all cases were divided into two groups: a pre-improved group and a post-improved group. According to different surgical methods, they were divided into two subgroups: an indirect revascularization subgroup and a combined revascularization subgroup.
 Results: The cerebral ischemia in 77.4% of patients was relieved after the surgery. There was significant difference in outcomes of patients between the pre-improved group and the post-improved group (P<0.05), while there was no significant difference between the pre-improved indirect revascularization subgroup and the pre-improved combined revascularization subgroup. There was also no significant difference between the post-improved indirect revascularization subgroup and the post-improved combined revascularization subgroups (P>0.05).
 Conclusion: Surgical treatment can improve the outcomes of patients with moyamoya disease, but there is no significant difference in surgical effects between indirect and combined revascularization.

Decreased expression of the SPOP gene is associated with poor prognosis in glioma.

This study suggests that speckle-type POZ protein (SPOP) may be a tumor suppressor gene and its prognostic value in human glioma. Real-time quantitative RT-PCR (qRT­PCR), western blotting, and immunohistochemical staining were used to examine SPOP expression in glioma tissues and normal brain (NB) tissues. The relationships between the SPOP expression levels, the clinicopathological factors, and patient survival were investigated. The molecular mechanisms of SPOP expression and its effects on cell viability, migration and invasion were also explored by MTT assay, wound-healing assays and Transwell assay. SPOP mRNA and protein levels were downregulated in glioma tissues compared to NB. Immunohistochemical staining results showed low expression in 62.2% (61/98) of glioma samples, while high expression in 75% (9/12) of NB samples, and the difference was statistically significant (P=0.014). In addition, decreased SPOP was associated disease progression in glioma samples, the expression level of SPOP was positively correlated with mean tumor diameter (MTD) (P=0.021) and the status of tumor grade and histological type (WHO I, II, III and IV) (P=0.032) in glioma patients. Additionally, the overall survival of patients with low SPOP expression was significantly worse than that of SPOP-high patients (P=0.001). In vitro overexpression of SPOP markedly inhibited cell viability, migration and invasion in vitro. These findings suggest that SPOP has potential use as novel biomarker of glioma and may serve as an independent predictive factor for prognosis of glioma patients.

Comparison of administration routes for adipose-derived stem cells in the treatment of middle cerebral artery occlusion in rats.

Given that adult adipose tissue is an abundant, accessible and safe source of stem cells, the use of adipose-derived stem cells (ADSCs) provides a promising approach in ischemic stroke. The delivery route, however, for transplantation of ADSCs in clinical application remains controversial regarding the time window, cell type, safety issues, 'first pass' effect and therapeutic effect. To determine the optimal administration route in transplantation of ADSCs, we compared the therapeutic effect of the three mainly used administration routes of ADSCs in a middle cerebral artery occlusion (MCAO) rat model. Cells isolated from the adipose tissue of adult rodents were differentiated and characterized in vitro, and further transplanted in vivo by intravenous, intra-arterial or intra-ventricular delivery. The infarct volume, expression of neurotrophic factors and the neurobehavioral improvements were evaluated after the equal dose of BrdU labeled ADSCs transplantation. Our results indicated that the equal dose of ADSCs delivered intravenously were effective in improving the neurological outcome and reducing the infarct volume after ischemic brain injury in long term duration in contrast to intra-arterial and intra-ventricular delivery. At 1-7 days after transplantation, the increased expression levels of BDNF, VEGF, bFGF, Bcl-2, IL-10 and decreased levels of caspase-3 and TNF-α in the intra-ventricular and intra-arterial groups were significant in contrast to the intravenous group. There was no significant difference among the three groups after 7 days. Our findings suggest that compared with the intra-ventricular delivery, intravascular injection allows higher dose injection with fewer invasions and appears to be optimal in application with regard to therapeutic efficacy, safety and feasibility.

[Microsurgery techniques for insular glioma].

OBJECTIVE: To explore the microsurgical techniques for insular glioma without damaging its surrounding normal structures. METHODS: We retrospectively analyzed 54 patients with insular gliomas who underwent microsurgical operation by trans-syvian fissure approach between May, 2003 and August, 2008 in Xiangya Hospital. We discussed the techniques in the operation and summarized how to protect the key blood vessels, distinguish and protect the surrounding normal structures. RESULTS: There were 36 complete removals,14 secondary complete removals, and 4 partial removals.Six patients had complications after the craniotomy who had temporal speech disorder (aphasia mostly began to recover about 10 days after the craniotomy),4 patients had opposite side paralysis worsening (3 recovered normally and 1 improved after 6 months),4 had light paralysis, and another 3 had paralysis and speech disorder. CONCLUSION: The microsurgery by means of trans-syvian fissure approach can well expose the anatomical relation between tumor and its surrounding structures,so that we can remove the tumor and protect the surrounding normal tissues as much as we can.

[CoCl2-induced chemotherapy resistance in SW480 cells and its mechanism].

OBJECTIVE: To observe the proliferation of SW480 cells exposed to different concentrations of CoCl2, and to examine the expression of hypoxiainducible factor-1 alpha (HIF-1alpha) and heme oxygenase-1 (HO-1) during hypoxia to explore the chemotherapy resistance effect and role of HIF-1alpha and HO-1. METHODS: Methyl thiazolyl tetrazolium (MTF) method was used to detect the proliferation of SW480 cells in the presence of fluorouracil (FU). RT-PCR was applied to examine the expression of HIF-1alpha and HO-1 mRNA in hypoxia. RESULTS: SW480 cells were proliferated at a slow rate, and had a strong resistance to FU with the increase of CoCl2. RT-PCR showed that the up-regulated expression of HIF-1alpha and HO-1 mRNA was consistent with the dose-effect curve and time-effect curve. CONCLUSION: The hypoxia induced by CoCl2 can inhibit the proliferation of SW480, and it can also decrease the sensitivity of the cell to FU. The mechanism is probably related to the up-regulated expression of HIF-1alpha and HO-1 mRNA.