IKIP downregulates THBS1/FAK signaling to suppress migration and invasion by glioblastoma cells.

Background: Inhibitor of NF-κB kinase-interacting protein (IKIP) is known to promote proliferation of glioblastoma (GBM) cells, but how it affects migration and invasion by those cells is unclear. Methods: We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases. We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays, and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved. Results: Based on data from our clinical samples and from public databases, IKIP was overexpressed in GBM tumors, and its expression level correlated inversely with survival. IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays, whereas IKIP knockdown exerted the opposite effects. IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue. The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling. Conclusions: IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.

The Mechanism of Astragaloside IV in NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome-mediated Pyroptosis after Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke. OBJECTIVES: This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH. METHODS: The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed. The levels of interleukin-1 beta (IL-1ß), IL-18, tumor necrosis factor-alpha, interferon-gamma, and IL-10 were detected by enzyme-linked immunosorbent assay. The levels of Kruppel-like factor 2 (KLF2), NOD-like receptor family pyrin domain containing 3 (NLRP3), GSDMD-N, and cleaved-caspase-1 were detected by reverse transcription-quantitative polymerase chain reaction and Western blot assay. The binding relationship between KLF2 and NLRP3 was verified by chromatin-immunoprecipitation and dual-luciferase assays. KLF2 inhibition or NLRP3 overexpression was achieved in mice to observe pathological changes. RESULTS: The decreased neurological function, increased water content, severe pathological damage, and inflammatory response were observed in mice after ICH, with increased levels of NLRP3/GSDMD-N/cleaved-caspase-1/IL-1ß/IL-18 and poorly-expressed KLF2 in brain tissue. After AS-IV treatment, the neurological dysfunction, high brain water content, inflammatory response, and pyroptosis were alleviated, while KLF2 expression was increased. KLF2 bonded to the NLRP3 promoter region and inhibited its transcription. Down-regulation of KLF2 or upregulation of NLRP3 reversed the effect of AS-IV on inhibiting pyroptosis and reducing inflammatory injury in mice after ICH. CONCLUSION: AS-IV inhibited NLRP3-mediated pyroptosis by promoting KLF2 expression and alleviated inflammatory injury in mice after ICH.

[Characteristics performance of laryngopharyngeal reflux in narrow band imaging].

Objective:To study the application value of narrow-band imaging in the diagnosis of laryngopharyngeal reflux. Methods:A total of 275 patients admitted to the inpatient department or laryngoscopy room of the Otolaryngology Head and Neck Surgery Department of the First Affiliated Hospital of Harbin Medical University from September 2022 to April 2023 due to throat discomfort were selected as the research subjects. All of them completed RSI, RFS scoring scales and electronic laryngoscopy（including ordinary white light and NBI）. According to the expert consensus of LPRD in 2022, RSI and RFS scoring scale were used as diagnostic criteria to divide them into LPR group and non-LPR group. Chi-square test was used to analyze the differences of positive rates of characteristic manifestations under NBI among different groups. The consistency of NBI and scale diagnostic methods was analyzed by Kappa, and RSI and RFS scoring were used as diagnostic criteria, The diagnostic efficiency of NBI method was analyzed. Results:There were 190 people in the LPR group, 157 of whom showed characteristic performance under the NBI mode, with a positive rate of 82.6%（157/190）; there were 85 people in the non-LPR group, with a positive rate of 18.8%（16/85）. There was a statistically significant difference in the positive rate between the two groups（χ²=102.47, P<0.05）. The consistency rate between RSI, RFS and NBI was 82.2%（226/275）. Kappa consistency analysis was used, and Kappa=0.605（P<0.05）, indicating good consistency between the two diagnostic methods. Using RSI and RFS as diagnostic criteria for LPR, the sensitivity of NBI diagnostic method was 82.6%（157/190）, specificity 81.2%（69/85）, positive predictive value 90.8%（157/173） and negative predictive value 67.6%（69/102）. Conclusion:Narrow-band imaging, as a new endoscopic imaging technique, can show small changes in mucosal surface micro vessels and play an important role in the diagnosis of laryngopharyngeal reflux.

Comparison of clinical efficacy and safety between interventional embolization and craniotomy clipping for anterior circulation aneurysms.

Objective: To investigate the clinical efficacy and safety of interventional embolization in the treatment of anterior circulation aneurysms. Methods: Eighty patients with anterior circulation aneurysms admitted to People's Hospital of Leshan from June 2019 to December 2021 were retrospectively analyzed. According to the different surgical methods, they were divided into two groups: the observation group and the control group. Patients in the observation group were given interventional embolization, while those in the control group were given craniotomy clipping. The surgical efficacy, postoperative neurological function and quality of life, surgical prognosis and surgical complications of the two groups were compared. Results: The intraoperative blood loss and hospitalization time in the observation group were lower than those in the control group (p<0.05). The scores of the Hunt-Hess and modified Rankin scale in the observation group were significantly lower than those in the control group three months after surgery (p<0.05). The good prognosis rate of the observation group was higher than that of the control group (p<0.05). Moreover, the complication rate of the observation group was 12.50%, which was significantly lower than 32.50% in the control group (p<0.05). Conclusion: Interventional embolization shows the advantages of minimally invasive procedures such as shorter operative times and shorter hospital stays. It has better clinical safety because it can significantly improve the neurological function and quality of life of patients, improve the prognosis of patients, and reduce the incidence of complications.

Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme.

Immunogenic cell death (ICD), a unique form of cancer cell death, has therapeutic potential in anti-tumour immunotherapy. The aim of this study is to explore the predictive potential of ICD in the prognosis and immunotherapy outcomes of glioblastoma multiforme (GBM). RNA sequencing data and clinical information were downloaded from three databases. Unsupervised consistency clustering analysis was used to identify ICD-related clusters and gene clusters. Additionally, the ICD scores were determined using principal component analysis and the Boruta algorithm via dimensionality reduction techniques. Subsequently, three ICD-related clusters and three gene clusters with different prognoses were identified, with differences in specific tumour immune infiltration-related lymphocytes in these clusters. Moreover, the ICD score was well differentiated among patients with GBM, and the ICD score was considered an independent prognostic factor for patients with GBM. Furthermore, two datasets were used for the external validation of ICD scores as predictors of prognosis and immunotherapy outcomes. The validation analysis suggested that patients with high ICD scores had a worse prognosis. Additionally, a higher proportion of patients with high ICD scores were non-responsive to immunotherapy. Thus, the ICD score has the potential as a biomarker to predict the prognosis and immunotherapy outcomes of patients with GBM.

Silencing of ALOX15 reduces ferroptosis and inflammation induced by cerebral ischemia-reperfusion by regulating PHD2/HIF2α signaling pathway.

OBJECTIVE: To investigate the potential mechanism of arachidonic acid deoxyribozyme 15 (ALOX15) in ferroptosis and inflammation induced by cerebral ischemia reperfusion injury. METHODS: The mice and cell models of cerebral ischemia-reperfusion injury were constructed. Western Blot was used to detect the protein expression levels of ALOX15, glutathione peroxidase (GPX4), hypoxia-inducible factor-2α (HIF-2α), prolyl hydroxylase (PHD) and inflammatory factors (NLRP3, IL-1ß, IL-18) in brain tissues and cells. Cell proliferation activity was detected by CCK-8 method. LDH assay was used to detect the release of lactate dehydrogenase. TTC staining was used to observe cerebral infarction. RESULTS: In cerebral ischemia-reperfusion mice and cell models, the expression of ALOX15 protein was increased, the expression of GPX4, a key marker of ferroptosis was decreased, and silencing of ALOX15 down-regulated the GPX4 expression. HIF-2α expression was down-regulated in animal and cell models of cerebral ischemia reperfusion, and silencing of ALOX15 increased the HIF-2α expression by inhibiting PHD2 expression. Inhibition of ALOX15 expression reduced inflammatory factors levels (NLRP3, IL-1ß, and IL-18) in cerebral ischemia. Inhibitor of PHD2 (IXOC-4) alleviating brain injury and cell death induced by cerebral ischemia reperfusion and stabilize HIF-2α expression in vivo. CONCLUSION: The expression of ALOX15 was up-regulated in cerebral ischemia-reperfusion animals and cells model. Inhibition of ALOX15 up-regulated the GPX4 expression, and promoted HIF-2α expression by inhibiting PHD2, thus alleviating ferroptosis and inflammation caused by cerebral ischemia-reperfusion injury.

The protective role of circ_0016760 downregulation against sevoflurane­induced neurological impairment via modulating miR­145 expression in aged rats.

Sevoflurane can produce toxicity to the hippocampal tissues of brain, leading to nerve damage, causing learning and cognitive dysfunction. CircRNAs have been indicated to act as a key mediator in anesthetic neurotoxicity. This study focused on the effect of circ_0016760 on sevoflurane­induced neurological impairment. The GEO database (GSE147277) and RT­qPCR were used to predict and  measure the circ_0016760 expression. The interaction of circ_0016760 and miR­145 was verified by dual­luciferase reporter assay. The CCK­8 assay, flow cytometry, ELISA, ROS kit, MWM test were carried out to measure the cell viability, apoptosis, inflammation indicators, ROS level, and cognitive and memory function of the rats. Sevoflurane exacerbated neurotoxicity by restraining cell viability, inducing cell apoptosis, neuroinflammation, and ROS generation, and causing learning and cognitive dysfunction. Circ_0016760 expression was increased in POCD patients from the GEO database and upregulated after sevoflurane exposure. miR­145 was a target miRNA of circ_0016760. Silencing of circ_0016760 weakened the effect of sevoflurane on cell viability, cell apoptosis, inflammation­related factors, oxidative stress, which could be reversed by miR­145 inhibitor. The animal experiments results showed that circ_0016760 played a protective effect on regulating the cognitive behavior of sevoflurane­treated aged rats, expression of inflammation cytokine, and oxidative stress factors through targeting miR­145 in sevoflurane­treated aged rat's hippocampal neurons. Our results revealed that silencing of circ_0016760 attenuated sevoflurane­induced hippocampal neuron injury by regulating miR­145 expression, which may provide potential insights into the treatment of sevoflurane­induced neurological impairment.

Diagnostic accuracy of arterial spin labeling in differentiating between primary central nervous system lymphoma and high-grade glioma: a systematic review and meta-analysis.

BACKGROUND: Existing studies have confirmed the accuracy of arterial spin labeling (ASL) in differentiating between primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG). We aimed to consolidate the existing evidence with a meta-analysis. METHODS: Six literature databases were searched for relevant papers. After assessing the quality of studies, bivariate regression was performed, and the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, diagnostic odds ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve were calculated, along with the corresponding 95% confidence intervals (CIs). Deeks' test was used to determine risk of publication bias. RESULTS: Ten high-quality studies, comprising 151 patients with PCNSL and 455 with HGG, were included. The pooled SEN was 0.79 (95% CI: 0.72-0.85), pooled SPE was 0.90 (95% CI: 0.84-0.94), pooled PLR was 8.07 (95% CI: 5.01-13.02), pooled NLR was 0.23 (95% CI: 0.17-0.32), pooled diagnostic score was 3.56 (95% CI: 2.94-4.18), and pooled DOR was 35.10 (95% CI: 18.83-65.45). The AUC of SROC was 0.86 (95% CI: 0.83-0.89). No publication bias was found. CONCLUSIONS: ASL demonstrated high diagnostic accuracy in differentiating between PCNSL and HGG.

Seizure prophylaxis following aneurysmal subarachnoid haemorrhage (SPSAH): study protocol for a multicentre randomised placebo-controlled trial of short-term sodium valproate prophylaxis in patients with acute subarachnoid haemorrhage.

INTRODUCTION: Seizures are a common complication that leads to neurological deficits and affects outcomes after aneurysmal subarachnoid haemorrhage (aSAH). However, whether to use prophylactic anticonvulsants in patients with aSAH remains controversial. Our study aims to determine whether short-term (7 days) sodium valproate could prevent seizure occurrence and improve neurological function in patients with SAH caused by anterior circulation aneurysm rupture and treated with clipping. METHODS AND ANALYSIS: In this multicentre randomised evaluator-blind placebo-controlled trial, 182 eligible patients with good-grade aSAH planned for surgical clipping will be enrolled from four neurosurgical centres in China. In addition to standard care, patients will be randomly assigned to receive sodium valproate 20 mg/kg daily or matching placebo. After aneurysmal clipping, patients will be followed up at discharge, 90 days and 180 days. The primary outcomes are the incidence of early and late seizures. The secondary outcomes include aSAH-related complications, sodium valproate-related adverse effects, modified Rankin Scale (mRS) (on discharge, at 90 days, 180 days), rate of good outcome (defined as mRS 0-2), all-cause death (at 90 days, 180 days) and Montreal Cognitive Assessment score (at 180 days). All analyses are by intention-to-treat. ETHICS AND DISSEMINATION: This study will be conducted according to the principles of Declaration of Helsinki and good clinical practice guidelines. This trial involves human participants and has been approved by the ethics committee of West China Hospital. Informed consent will be achieved from each included patient and/or their legally authorised representative. Preliminary and final results from this study will be disseminated through manuscript publishing and international congresses presentations. Any protocol amendments will be approved by the ethics committee of West China Hospital and subsequently updated on ChiCTR. TRIAL REGISTRATION NUMBER: ChiCTR.org identifier: ChiCTR2100050161.

Protective effect of phillyrin against cerebral ischemia/reperfusion injury in rats and oxidative stress-induced cell apoptosis and autophagy in neurons.

This study explored the role and potential molecular mechanism of phillyrin in cerebral ischemia/reperfusion (I/R) injury. The rat middle cerebral artery occlusion (MCAO)/R model was constructed, and cerebral infarction volume, brain water content, and neurological score were measured. Neuron morphological structures in brain tissues and primary neuron apoptosis were detected using hematoxylin and eosin (H&E) staining and Hoechst 33258 staining, respectively. In MCAO/R rats, phillyrin markedly reduced cerebral infarction volume, neurological score, and brain water content and inhibited neuron apoptosis. In vitro experiments showed that phillyrin remarkably increased viability and decreased lactate dehydrogenase (LDH) release of H2O2-injured neurons. Moreover, phillyrin remarkably downregulated the proportion of apoptosis-related protein B-associated X (Bax)/B-cell lymphoma protein 2 (Bcl-2) and reduced procaspase-3, phospho-Akt (p-Akt-1), and phosphorylation-mammalian target of rapamycin (p-mTOR) levels in H2O2-injured neurons. Furthermore, phosphatidylinositol-3 kinase (PI3K) inhibitor ZSTK474 weakened the effects of phillyrin on p-mTOR, p-Akt-1, characteristic proteins of autophagy 3-II (LC3-II) and beclin-1 levels, and H2O2-induced neuronal apoptosis and autophagy. Taken together, phillyrin alleviates I/R injury by inhibiting neuronal cell apoptosis and autophagy pathway, which may provide a new treatment strategy for cerebral I/R injury.

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/ß-Catenin and Sonic Hedgehog Pathways.

Neuroinflammation plays important roles in the pathogenesis and progression of altered neurodevelopment, sensorineural hearing loss, and certain neurodegenerative diseases. Hyperoside (quercetin-3-O-ß-D-galactoside) is an active compound isolated from Hypericum plants. In this study, we investigate the protective effect of hyperoside on neuroinflammation and its possible molecular mechanism. Lipopolysaccharide (LPS) and hyperoside were used to treat HT22 cells. The cell viability was measured by MTT assay. The cell apoptosis rate was measured by flow cytometry assay. The mRNA expression levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by quantitative reverse transcription polymerase chain reaction. The levels of oxidative stress indices superoxide dismutase (SOD), reactive oxygen species (ROS), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) were measured by the kits. The expression of neurotrophic factor and the relationship among hyperoside, silent mating type information regulation 2 homolog-1 (SIRT1) and Wnt/ß-catenin, and sonic hedgehog was examined by western blotting. In the LPS-induced HT22 cells, hyperoside promotes cell survival; alleviates the level of IL-1ß, IL-6, IL-8, TNF-α, ROS, MDA, Bax, and caspase-3; and increases the expression of CAT, SOD, GSH, Bcl-2, BDNF, TrkB, and NGF. In addition, hyperoside upregulated the expression of SIRT1. Further mechanistic investigation showed that hyperoside alleviated LPS-induced inflammation, oxidative stress, and apoptosis by upregulating SIRT1 to activate Wnt/ß-catenin and sonic hedgehog pathways. Taken together, our data suggested that hyperoside acts as a protector in neuroinflammation.

MiR-30b-5p modulates glioma cell proliferation by direct targeting MTDH.

Malignant glioma is the most common and lethal type of primary tumor of the central nervous system. The incidence of glioma is increasing year by year. In recent years, a variety of new treatment methods have emerged, among which gene therapy has become a hotspot. MicroRNAs (miRNAs) are a class of small non-coding single-strand RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding loosely complimentary sequences in the 3' untranslated regions (UTRs) of target mRNAs. Several miRNAs have been reported to modulate glioma progression. This study aimed to determine the function of miR-30b-5p in glioma and its underlying molecular mechanism. miR-30b-5p expression was significantly lower in gliomas than the normal brain tissues. Overexpression of miR-30b-5p was found to significantly inhibit glioma cell proliferation in vitro. Further, MTDH expression was significantly higher in the gliomas compared with the normal brain tissues. In addition, MTDH was validated as direct target of miR-30b-5p. Moreover, cellular proliferation was increased after MTDH overexpression in the glioma cells, which reversed the effects of miR-30b-5p. Taken together, these results reveal miR-30b-5p impacts glioma cell proliferation via direct targeting MTDH and could be a potential novel therapeutic target for the treatment of glioma.

Growth hormone-secreting adenoma coexisted with gangliocytoma: a rare case.

A gangliocytoma in the sellar region is extremely rare. We report a rare case of mixed gangliocytoma and growth hormone (GH)-secreting adenoma in a 50-year-old woman, who presented with acromegaly. Laboratory investigations revealed high levels of GH and insulinlike growth factor 1 (IGF-1). Sellar computed tomography scan and contrast enhanced magnetic resonance imaging (CE-MRI) showed a sellar mass. Based on clinical, biochemical, and radiologic evaluations, GH-secreting adenoma was diagnosed and operated by endonasal transsphenoidal approach achieving total removal of the tumor. After surgery, histopathological examination demonstrated mixed gangliocytoma and GH-secreting adenoma in the resected lesion. The clinical, radiological, and operative data are reviewed, as are the histological findings. To our knowledge, few cases of mixed gangliocytoma and GH-secreting adenoma have been reported.

Inhibition of BDNF production by MPP+ through up-regulation of miR-210-3p contributes to dopaminergic neuron damage in MPTP model.

The neurotrophin brain-derived neurotrophic factor (BDNF) has been involved in supporting of neuron survival. The observation of reduced level of BDNF in the substantia nigra (SN) of Parkinson's disease (PD) patients suggests its important role in neuron protection in PD pathogenesis. However, the mechanism underlying the down-regulation of BDNF in PD was largely unknown. In this study, we found that miR-210-3p is involved in the regulation of BDNF production by 1-methyl-4-phenylpyridinium (MPP+). MPP+ inhibits the BDNF production in SH-SY5Y cells through a transcription independent manner. Moreover, miR-210-3p, which targets BDNF mRNA, is up-regulated by MPP+ in SH-SY5Y cells. Importantly, inhibition of miR-210-3p prevents the reduction of BDNF production by MPP+ and improves the DA neuron survival in 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP) model. Together, we demonstrated up-regulation of miR-210-3p by MPP+ reduces the BDNF production and contributes to the DA neuron damage.

Tumor suppressive role of miR-194-5p in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is defined by the World Health Organization as the most aggressive form of grade IV glioma, characterized by unrestrained cellular proliferation. microRNAs (miRs) serve important roles in the pathogenesis of GBM. However, the function of miR­194­5p in GBM remains unknown. In the present study, the miR­194­5p levels in GBM tissues and cells were evaluated using the reverse transcription­quantitative polymerase chain reaction. Cellular proliferation was tested by MTT analysis. Cellular apoptosis was analyzed by fluorescence­activated cell sorting. The protein level of insulin­like growth factor 1 receptor, the target gene of miR­194­5p, was evaluated by western blotting. The interaction between miR­194­5p and the target gene was confirmed by the dual­luciferase reporter assay. It was demonstrated that miR­194­5p inhibited cell growth and promoted apoptosis. In conclusion, the results of the present study indicated the tumor suppressive role of miR­194­5p.

Metastatic Adenocarcinoma of Unknown Primary in the Bilateral Cerebellopontine Angles: Case Report and Review of the Literature.

Metastatic adenocarcinoma in bilateral cerebellopontine angles (CPA) is rare. We report a case and review the current literature in order to enhance recognition of metastatic adenocarcinoma in the cerebellopontine angle. A 44-year-old man was referred to the hospital with rightsided diminished hearing for 7 weeks, left-sided facial palsy for 2 weeks, and left-sided sensorineural hearing loss for 1 week. On Magnetic Resonance Imaging (MRI) two tumors in bilateral CPAs were detected. The left-sided tumor was resected and histopathological examination revealed an adenocarcinoma. Many investigations could not find the primary tumor. One should be careful with middle-aged or elderly patients with sudden progressive deficits in the VIII < sup > th < /sup > or VII < sup > th < /sup > cranial nerves, particularly in bilateral CPA.