The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

Identifying the Preoperative Radiological Risk Features in Patients with Leptomeningeal Carcinomatosis Undergoing Cerebrospinal Fluid Drainage.

BACKGROUND: Patients with leptomeningeal carcinomatosis (LMC) experience a poor prognosis and rapid progression, and cerebrospinal fluid drainage (CSFD) is used to manage intracranial hypertension and hydrocephalus in LMC patients. This study aims to describe a novel discovery of preoperative radiological features in patients who underwent CSFD for LMC. METHODS: A retrospective review was conducted during the past 5 years of LMC patients with intracranial hypertension and hydrocephalus who underwent CSFD. We evaluated the patients' preoperative radiological features, clinical characteristics, and survival times. RESULTS: A total of 36 patients were included. Of the 36 patients, 34 underwent ventriculoperitoneal shunting, and 2 patients underwent only external ventricular drainage due to rapid progression. The median preoperative Karnofsky performance scale score was 40.0 (interquartile range [IQR], 20.0-40.0). The median survival time after surgery was 5 months (IQR, 0.00-10.43 months). Of the 36 patients, 24 (66.7%) had supratentorial cerebral edema before surgery, including 14 patients (38.9%) with features of disproportionately enlarged subarachnoid space hydrocephalus (DESH). Four patients (11.1%) exhibited cerebellar swelling and had a median survival time of 0.27 month (IQR, 0.00-0.56 month). Nine patients (25%) have enhancement lesions on the cerebellum. The survival curve analysis shows that patients with features of cerebellar enhancement have shorter survival times than other patients. Patients with DESH features have longer survival times compared with those with global cerebral edema. CONCLUSIONS: Patients with radiological features of cerebellar enhancement have shorter postoperative survival than other patients; however, those with supratentorial cerebral edema, especially features of DESH, could benefit from CSFD. Patients with cerebellar swelling should avoid undergoing CSFD.

Juglone induces ferroptosis in glioblastoma cells by inhibiting the Nrf2-GPX4 axis through the phosphorylation of p38MAPK.

BACKGROUND: Ferroptosis, a non-apoptotic form of cell death induced by accumulation of free iron ions and lipid peroxidation, its importance for cancer treatment is gradually being recognized. Research on the anti-cancer mechanism of juglone is accumulating. However, the specific mechanism by which it directs glioblastoma (GBM) to death is unknown. METHODS: We used in vitro and in vivo experiments to explore the anti-GBM effect generated by juglone through the ferroptosis pathway. RESULTS: Juglone mainly causes cell death by inducing ferroptosis. Mechanistically, juglone can significantly activate the phosphorylation of p38MAPK. According to transcriptome sequencing and protein interaction analysis, the Nrf2-GPX4 signaling pathway is identified as the primary pathway through which juglone mediates ferroptosis. In vitro and in vivo experiments further verified that juglone induces the ferroptosis of GBM by activating the phosphorylation of p38MAPK and negatively regulating the Nrf2-GPX4 signaling pathway. CONCLUSION: Juglone induces ferroptosis and inhibits the growth of GBM by targeting the Nrf2/Gpx4 signaling pathway and thus holds promise as a novel ferroptosis inducer or anti-GBM drug.

Identification of prognostic risk score of disulfidptosis-related genes and molecular subtypes in glioma.

Background: Programmed cell death is closely related to glioma. As a novel kind of cell death, the mechanism of disulfidptosis in glioma remains unclear. Therefore, it is of great importance to study the role of disulfidptosis-related genes (DRGs) in glioma. Methods: We first investigated the genetic and transcriptional alterations of 15 DRGs. Two consensus cluster analyses were used to evaluate the association between DRGs and glioma subtypes. In addition, we constructed prognostic DRG risk scores to predict overall survival (OS) in glioma patients. Furthermore, we developed a nomogram to enhance the clinical utility of the DRG risk score. Finally, the expression levels of DRGs were verified by immunohistochemistry (IHC) staining. Results: Most DRGs (14/15) were dysregulated in gliomas. The 15 DRGs were rarely mutated in gliomas, and only 50 of 987 samples (5.07 %) showed gene mutations. However, most of them had copy number variation (CNV) deletions or amplifications. Two distinct molecular subtypes were identified by cluster analysis, and DRG alterations were found to be related to the clinical characteristics, prognosis, and tumor immune microenvironment (TIME). The DRG risk score model based on 12 genes was developed and showed good performance in predicting OS. The nomogram confirmed that the risk score had a particularly strong influence on the prognosis of glioma. Furthermore, we discovered that low DRG scores, low tumor mutation burden, and immunosuppression were features of patients with better prognoses. Conclusion: The DRG risk model can be used for the evaluation of clinical characteristics, prognosis prediction, and TIME estimation of glioma patients. These DRGs may be potential therapeutic targets in glioma.

Identification and validation of prognostic genes and immune landscape signatures based on a fatty acid oxidation­related risk score model in glioma.

Fatty acid oxidation (FAO) plays a crucial role in glioma metabolism and its interaction with the immune microenvironment. The aim of the present study was to investigate the relationship between FAO-related genes and glioma by constructing gene clusters using a glioma cohort. A total of 287 differentially expressed genes related to FAO were identified and the top 50 genes were selected based on their P-values. Subsequently, patients were classified into two distinct gene subtypes (A and B) based on these genes. Scores for each patient were calculated using the 50 genes and the patients were divided into the high and low-score groups accordingly. Patients in subtype B exhibited higher tumor grades and poor prognostic factors such as older age and worse survival rates. The high-score subgroup had unfavorable indicators, including isocitrate dehydrogenase 1 wild-type, high tumor grade and 1p19q non-codeleted, while immune checkpoint expression was generally higher in the high-score subgroup. The constructed scoring model was validated using an external dataset, and the tissue inhibitor of metalloproteinase 1 gene was identified through protein interaction analysis, suggesting its potential involvement in glioma malignancy and promotion of glioblastoma proliferation. In conclusion, FAO-related genes may contribute to tumor development through immune mechanisms and the present study may provide novel insights for potential therapeutic strategies in glioma treatment.

Risk Factors for Post-Operative Pulmonary Infection in Patients With Brain Tumors: A Systematic Review and Meta-Analysis.

Background: This study aims to analyze the risk factors for post-operative pulmonary infection in patients with brain tumors by meta-analysis to provide a reference for its prevention. Methods: PubMed, Embase, Web of Science, Cochrane Library, Ovid, and four Chinese databases (CNKI, SinoMed, VIP, and Wanfang databases) were searched for studies covering risk factors of pulmonary infection in patients with brain tumors, limited to the duration from the dates of inception of the respective databases to December 31, 2022. The Newcastle-Ottawa scale was used to assess the evidence. A meta-analysis of the factors affecting the incidence of pulmonary infection was performed using Revman 5.4 software. Results: Twelve studies were selected, covering 35,615 patients with brain tumors, among whom pulmonary infection occurred in 1,635 cases with an accumulated incidence of 4.6%, including 38 related risk factors. Meta-analysis results indicated: history of chronic pulmonary disease (odds ratio [OR], 5.74; 95% confidence interval [CI], 1.34-24.51; p = 0.02], diabetes mellitus (OR, 1.58; 95% CI, 1.29-1.95; p < 0.0001), history of cardiovascular disease (OR, 3.97; 95% CI, 2.18-7.24; p < 0.00001), age ≥60 years (OR, 1.55; 95% CI, 1.12-2.15; p = 0.009)], operation time ≥3 hours (OR, 1.03; 95% CI, 1.00-1.05; p = 0.03], Glasgow Coma Scale (GCS) score <13 (OR, 3.5; 95% CI, 1.90-6.46; p < 0.0001), and the American Society of Anesthesiologists classification (ASA) ≥3 (OR, 2.03; 95% CI, 1.68-2.46; p < 0.00001) as independent risk factors. Conclusions: History of chronic pulmonary disease, diabetes mellitus, history of cardiovascular disease, age ≥60 years, operation time ≥3 hours, GCS score <13, and the ASA grade ≥3 are independent risk factors for post-operative pulmonary infection in patients with brain tumors, which nursing staff should be aware of.

A Nomogram Model for Stratifying the Risk of Recurrence in Patients with Meningioma After Surgery.

BACKGROUND: Here, we aimed to investigate the clinical parameters affecting the recurrence of meningiomas, and to construct a predictive nomogram model, so as to predict the recurrence-free survival (RFS) of meningiomas more accurately. METHODS: The Clinical, imaging, and pathological data of 155 primary meningioma patients treated surgically from January 2014 to March 2021 were retrospectively analyzed. Independent prognostic factors affecting postoperative recurrence of meningioma were identified by univariate and multivariate Cox regression analyses. A predictive nomogram was established based on independent influence parameters. Subsequently, time-dependent receiver operating characteristic curve, calibration curve, and Kaplan-Meier method were utilized to evaluate the predictive ability of the model. RESULTS: The multivariate Cox regression analysis showed that tumor size, Ki-67 index, and resection extent had independent prognostic significance, and these parameters were subsequently used to construct a predictive nomogram. Receiver operating characteristic curves indicated that the model was more accurate in predicting RFS than independent factors. Calibration curves suggested that the predicted RFS were similar to the actual observed RFS. In the Kaplan-Meier analysis, the RFS of high-risk cases was obviously shorter than that of low-risk cases. CONCLUSIONS: The tumor size, Ki-67 index, and extent of resection were independent factors affecting the RFS of meningioma. The predictive nomogram based on these factors can be used as an effective method to stratify the recurrence risk of meningioma and provide a reference for patients to choose personalized treatment.

Construction of a pyroptosis-related lncRNAs signature for predicting prognosis and immunotherapy response in glioma.

Recent studies have proved that pyroptosis-related long non-coding RNAs (PRlncRNAs) are closely linked to tumor progression, prognosis, and immunity. Here, we systematically evaluated the correlation of PRlncRNAs with glioma prognosis. This study included 3 glioma cohorts (The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Gravendeel). Through Pearson correlation analysis, PRlncRNAs were screened from these 3 cohorts. Univariate Cox regression analysis was then carried out to determine the prognostic PRlncRNAs. A pyroptosis-related lncRNAs signature (PRLS) was then built by least absolute shrinkage and selection operator and multivariate Cox analyses. We systematically evaluated the correlation of the PRLS with the prognosis, immune features, and tumor mutation burden in glioma. A total of 14 prognostic PRlncRNAs overlapped in all cohorts and were selected as candidate lncRNAs. Based on The Cancer Genome Atlas cohort, a PRLS containing 7 PRlncRNAs was built. In all cohorts, the PRLS was proved to be a good predictor of glioma prognosis, with a higher risk score related to a poorer prognosis. We observed obvious differences in the immune microenvironment, immune cell infiltration level, and immune checkpoint expression in low- and high-risk subgroups. Compared with low-risk cases, high-risk cases had lower Tumor Immune Dysfunction and Exclusion scores and greater tumor mutation burden, indicating that high-risk cases can be more sensitive to immunotherapy. A nomogram combining PRLS and clinical parameters was constructed, which showed more robust and accurate predictive power. In conclusion, the PRLS is a potentially useful indicator for predicting prognosis and response to immunotherapy in glioma. Our findings may provide a useful insight into clinically individualized treatment strategies for patients.

[Retracted] Suppressive effect of microRNA­138 on the proliferation and invasion of osteosarcoma cells via targeting SIRT1.

[This retracts the article DOI: 10.3892/etm.2017.4426.].

The dual function of microglial polarization and its treatment targets in ischemic stroke.

Stroke is the leading cause of disability and death worldwide, with ischemic stroke occurring in ~5% of the global population every year. Recently, many studies have been conducted on the inflammatory response after stroke. Microglial/macrophage polarization has a dual function and is critical to the pathology of ischemic stroke. Microglial/macrophage activation is important in reducing neuronal apoptosis, enhancing neurogenesis, and promoting functional recovery after ischemic stroke. In this review, we investigate the physiological characteristics and functions of microglia in the brain, the activation and phenotypic polarization of microglia and macrophages after stroke, the signaling mechanisms of polarization states, and the contribution of microglia to brain pathology and repair. We summarize recent advances in stroke-related microglia research, highlighting breakthroughs in therapeutic strategies for microglial responses after stroke, thereby providing new ideas for the treatment of ischemic stroke.

CNPY4 is a potential promising prognostic-related biomarker and correlated with immune infiltrates in gliomas.

Glioblastomas are classified into primary and secondary; primary glioblastomas develop rapidly and aggressively, whereas secondary glioblastomas are more common in grade II and III gliomas. Here, we aimed to demonstrate the role of the CNPY4 gene as a potential biomarker in immune infiltration in gliomas. Based on gene expression profile interaction analysis (GEPIA), we studied the survival model of CNPY4 and evaluated its effect on patients with glioma. The glioma dataset was downloaded from The Cancer Genome Atlas (TCGA) database. Logistic regression was used to analyze the relationship between clinical data and CNPY4 expression. Univariate and multivariate Cox proportional-hazards models were used to compare clinical features and patient survival. The relationship between CNPY4 and immune infiltration in glioma was studied using GEPIA and CIBERSORT online tools. TCGA data were analyzed using gene set enrichment analysis (GSEA). Finally, TIMER was used to analyze the expression and immune infiltration of CNPY4 in glioma to study the cumulative survival rate. Univariate logistic regression analysis showed that increased CNPY4 expression was associated with tumor age, grade, IDH status, and 1p/19q codeletion. Multivariate analysis showed that that downregulation of CNPY4 expression was an independent and satisfactory prognostic factor. CNPY4 expression was correlated with the infiltration level of dendritic cells in glioblastoma. In contrast, in low-grade gliomas, the infiltration level of B cells, dendritic cells, macrophages, neutrophils, and CD4+ T cells was significantly correlated with CNPY4 expression. The GSEA results showed that CNPY4 played an immunoregulatory role in immune-related phenotypic pathways between lymphoid and nonlymphoid cells. The intestinal immune networks for IgA production, rabbit thyroid disease, primary immunodeficiencies, and cancer immunotherapy were enriched by PD-1 blockade. High CNPY4 expression is a biomarker of glioma prognosis and is associated with the immune invasion of glioma.

Expression and Prognostic Value of Melanoma-Associated Antigen D2 in Gliomas.

INTRODUCTION: The melanoma-associated antigen D2 (MAGED2) is one of the melanoma-associated antigen family members. It is commonly overexpressed in a variety of malignancies. However, the mechanism and function of MAGED2 in glioma remain unknown. METHODS: The MAGED2 expression level and the correlations between clinical characteristics were analyzed with the data from the CGGA and TCGA datasets. MAGED2 expression in 98 glioma tissues was measured using RT-qPCR, Western blot, and immunohistochemistry. CCK-8, colony formation, and EdU assays were used to assess the effect of MAGED2 on U251-MG cell proliferation. Flow cytometry was used to track changes in the cell cycle and cell apoptosis following plasmid transfection with CRISPRi. RESULTS: MAGED2 was shown to be highly expressed in glioma tissues, and high MAGED2 expression predicted poor prognosis. Furthermore, MAGED2 knockdown significantly inhibited the proliferation of U251-MG cells by preventing cell cycle arrest at the G0/G1 phase and triggering apoptosis. In line with in vitro findings, the results of the xenograft experiment and immunohistochemistry also showed that MAGED2 suppression inhibited tumor development and decreased Ki-67 expression levels. CONCLUSIONS: MAGED2 may be a possible biomarker for glioma and an important prognostic factor for glioma patients.

Establishment and Validation of a Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Lower-Grade Glioma.

Background: The prognosis of lower-grade glioma (LGG) is highly variable, and more accurate predictors are still needed. The aim of our study was to explore the prognostic value of ferroptosis-related long non-coding RNAs (lncRNAs) in LGG and to develop a novel risk signature for predicting survival with LGG. Methods: We first integrated multiple datasets to screen for prognostic ferroptosis-related lncRNAs in LGG. A least absolute shrinkage and selection operator (LASSO) analysis was then utilized to develop a risk signature for prognostic prediction. Based on the results of multivariate Cox analysis, a prognostic nomogram model for LGG was constructed. Finally, functional enrichment analysis, single-sample gene set enrichment analysis (ssGSEA), immunity, and m6A correlation analyses were conducted to explore the possible mechanisms by which these ferroptosis-related lncRNAs affect survival with LGG. Results: A total of 11 ferroptosis-related lncRNAs related to the prognosis of LGG were identified. Based on prognostic lncRNAs, a risk signature consisting of 8 lncRNAs was constructed and demonstrated good predictive performance in both the training and validation cohorts. Correlation analysis suggested that the risk signature was closely linked to clinical features. The nomogram model we constructed by combining the risk signature and clinical parameters proved to be more accurate in predicting the prognosis of LGG. In addition, there were differences in the levels of immune cell infiltration, immune-related functions, immune checkpoints, and m6A-related gene expression between the high- and low-risk groups. Conclusion: In summary, our ferroptosis-related lncRNA signature exhibits good performance in predicting the prognosis of LGG. This study may provide useful insight into the treatment of LGG.

Comprehensive Analysis of Phagocytosis-Related Regulators to Aid Prognostic Prediction and Immunotherapy in Patients with Low-Grade Glioma.

Antibody-dependent cellular phagocytosis- (ADCP-) related regulators (PRs) have been confirmed an important role in immunotherapy. However, the characterization of specific PRs in low-grade glioma (LGG) has not been comprehensively explored. In this study, we retrieved RNA-seq and CRISPR-Cas9 data to identify specific PRs in LGG patients and constructed a PRs-signature using the LASSO-Cox algorithm. The ROC analysis and Kaplan-Meier analysis showed that PRs-signature had a good predictive effect, and the multivariate Cox regression analysis showed that PRs-risk scores were independent prognostic factors correlated with overall survival (OS). In addition, CIBERSORT, ssGSEA, and MCP counter algorithms were used to explore immune cell content in different risk groups, especially in the correlation between macrophages and specific PRs. Finally, mRNA expression was upregulated in the high-risk group compared with the low-risk group at most immune checkpoints and proinflammatory factors. In conclusion, we constructed a prediction model for prognostic management and revealed the cross-talk between specific PRs and immunotherapy in LGG patients.

Identification of an m6A RNA Methylation Regulator Risk Score Model for Prediction of Clinical Prognosis in Astrocytoma.

Astrocytoma (AS) is the most ubiquitous primary malignancy of the central nervous system (CNS). The vital involvement of the N6-methyladenosine (m6A) RNA modification in the growth of multiple human tumors is known. This study entailed probing m6A regulators with AS prognosis to construct a risk prediction model (RS) for potential clinical use. A total of 579 AS patients' (of the Chinese Glioma Genome Atlas,CGGA) data and the expression of 12 published m6A-related genes were included in this study. Cox and selection operator (LASSO) regression analyses for independent prognostic factors and multifactor Cox analysis established an R.S. model to predict the AS patient prognosis. This was subject to verification employing 331 samples from the TCGA data set followed by gene ontology and pathway enrichment study with gene set enrichment analysis (GSEA). The R.S. constructed with three m6A genes inclusive of WTAP, RBM15, and YTHDF2 emerged as independent prognostic factors in AS patients with vital involvement in the advancement and development of the malignancy. In a nutshell, this work reported an m6A-related gene risk model to predict the prognosis of AS patients to pave the way for discerning diagnostic and prognostic biomarkers. Further corroboration employing relevant wet-lab assays of this model is warranted.

Met-RANTES preserves the blood-brain barrier through inhibiting CCR1/SRC/Rac1 pathway after intracerebral hemorrhage in mice.

BACKGROUND: C-C chemokine receptor type 1 (CCR1) and its endogenous ligand, CCL5, participate in the pathogenesis of neuroinflammatory diseases. However, much remains unknown regarding CCL5/CCR1 signaling in blood-brain barrier (BBB) permeability after intracerebral hemorrhage (ICH). METHODS: A total of 250 CD1 male mice were used and ICH was induced via autologous whole blood injection. Either Met-RANTES, a selective CCR1 antagonist, or Met-RANTES combined with a Rac1 CRISPR activator was administered to the mice 1 h after ICH. Post-ICH assessments included neurobehavioral tests, brain water content, BBB integrity, hematoma volume, Western blot, and immunofluorescence staining. The CCR1 ligand, rCCL5, and SRC CRISPR knockout in naïve mice were used to further elucidate detrimental CCL5/CCR1/SRC signaling. RESULTS: Brain endogenous CCR1 and CCL5 were upregulated after ICH in mice with a peak at 24 h, and CCR1 was expressed in endothelial cells, astrocytes, and neurons. Met-R treatment reduced brain edema and neurobehavioral impairment, as well as preserved BBB integrity and tight junction protein expression in ICH mice. Met-R treatment decreased expression of p-SRC, Rac1, albumin, and MMP9, but increased claudin-5, occludin, and ZO-1 tight junction proteins after ICH. These effects were regressed using the Rac1 CRISPR activator. Administration of rCCL5 in naïve mice increased expression of p-SRC, Rac1, albumin, and MMP9, but decreased levels of claudin-5, occludin, and ZO-1 tight junction proteins. These effects in naïve mice were reversed with SRC CRISPR (KO). CONCLUSIONS: Our findings demonstrate that CCR5 inhibition by Met-R improves neurological deficits after ICH by preserving BBB integrity through inhibiting CCR1/SRC/Rac1 signaling pathway in mice. Thus, Met-R has therapeutic potential in the management of ICH patients.

Screening and Identification of Key Biomarkers in Lower Grade Glioma via Bioinformatical Analysis.

Lower-grade glioma (LGG) is a common type of central nervous system tumor. Due to its complicated pathogenesis, the choice and timing of adjuvant therapy after tumor treatment are controversial. This study explored and identified potential therapeutic targets for lower-grade. The bioinformatics method was employed to identify potential biomarkers and LGG molecular mechanisms. Firstly, we selected and downloaded GSE15824, GSE50161, and GSE86574 from the GEO database, which included 40 LGG tissue and 28 normal brain tissue samples. GEO and VENN software identified of 206 codifference expressed genes (DEGs). Secondly, we applied the DAVID online software to investigate the DEG biological function and KEGG pathway enrichment, as well as to build the protein interaction visualization network through Cytoscape and STRING website. Then, the MCODE plug is used in the analysis of 22 core genes. Thirdly, the 22 core genes were analyzed with UNCLA software, of which 18 genes were associated with a worse prognosis. Fourthly, GEPIA was used to analyze the 18 selected genes, and 14 genes were found to be a significantly different expression between LGGs and normal brain tumor samples. Fifthly, hierarchical gene clustering was used to examine the 14 important gene expression differences in different histologies, as well as analysis of the KEGG pathway. Five of these genes were shown to be abundant in the natural killer cell-mediated cytokines (NKCC) and phagosome pathways. The five key genes that may be affected by the immune microenvironment play a crucial role in LGG development.

A Novel Risk Signature with Seven Pyroptosis-Related Genes for Prognosis Prediction in Glioma.

BACKGROUND: Increasing evidence indicates that pyroptosis is closely linked to the occurrence and progression of cancer. However, the expression and prognostic role of most pyroptosis-related genes in glioma have not been fully elucidated. METHODS: Herein, we explored the expression profiles and prognostic value of 33 pyroptosis-related genes in glioma. LASSO (least absolute shrinkage and selection operator) regression analysis was then used to construct a risk signature to predict glioma outcomes in The Cancer Genome Atlas cohort. Furthermore, we constructed a nomogram based on independent prognostic factors and performed external validation. Finally, functional enrichment analysis was performed to explore the potential biological role of the pyroptosis-related signature in glioma. RESULTS: The expression of most pyroptosis-related genes (31/33) was significantly different between normal brain and glioma tissue. By univariate Cox regression analysis, 24 genes were found to be significantly correlated with glioma overall survival. Subsequently, we constructed a 7-gene risk signature in The Cancer Genome Atlas training cohort, which demonstrated good performance in predicting glioma survival through multidatabase validation. Moreover, a nomogram was established based on independent prognostic factors (age, World Health Organization grade, isocitrate dehydrogenase status, and signature) and confirmed to be more effective and accurate through internal evaluation and external validation. Finally, functional enrichment analyses suggested that the signature might be related to invasion ability and immune function. CONCLUSIONS: The risk signature based on 7 pyroptosis-related genes can effectively predict the clinical outcomes of patients with glioma. Our study provides novel insights for further understanding the association between pyroptosis-related genes and glioma prognosis.

Autophagy regulates inflammation in intracerebral hemorrhage: Enemy or friend?

Intracerebral hemorrhage (ICH) is the second-largest stroke subtype and has a high mortality and disability rate. Secondary brain injury (SBI) is delayed after ICH. The main contributors to SBI are inflammation, oxidative stress, and excitotoxicity. Harmful substances from blood and hemolysis, such as hemoglobin, thrombin, and iron, induce SBI. When cells suffer stress, a critical protective mechanism called "autophagy" help to maintain the homeostasis of damaged cells, remove harmful substances or damaged organelles, and recycle them. Autophagy plays a critical role in the pathology of ICH, and its function remains controversial. Several lines of evidence demonstrate a pro-survival role for autophagy in ICH by facilitating the removal of damaged proteins and organelles. However, many studies have found that heme and iron can aggravate SBI by enhancing autophagy. Autophagy and inflammation are essential culprits in the progression of brain injury. It is a fascinating hypothesis that autophagy regulates inflammation in ICH-induced SBI. Autophagy could degrade and clear pro-IL-1ß and apoptosis-associated speck-like protein containing a CARD (ASC) to antagonize NLRP3-mediated inflammation. In addition, mitophagy can remove endogenous activators of inflammasomes, such as reactive oxygen species (ROS), inflammatory components, and cytokines, in damaged mitochondria. However, many studies support the idea that autophagy activates microglia and aggravates microglial inflammation via the toll-like receptor 4 (TLR4) pathway. In addition, autophagy can promote ICH-induced SBI through inflammasome-dependent NLRP6-mediated inflammation. Moreover, some resident cells in the brain are involved in autophagy in regulating inflammation after ICH. Some compounds or therapeutic targets that regulate inflammation by autophagy may represent promising candidates for the treatment of ICH-induced SBI. In conclusion, the mutual regulation of autophagy and inflammation in ICH is worth exploring. The control of inflammation by autophagy will hopefully prove to be an essential treatment target for ICH.

A nomogram combining inflammatory markers and clinical factors predicts survival in patients with diffuse glioma.

ABSTRACT: In this study, we aimed to investigate the prognostic value of neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio (PLR) in diffuse glioma, and to establish a prognostic nomogram accordingly.The hematologic and clinicopathological data of 162 patients with primary diffuse glioma who received surgical treatment from January 2012 to December 2018 were retrospectively analyzed. Receiver operator characteristic (ROC) curve was carried out to determine the optimal cut-off values for NLR, MLR, PLR, age, and Ki-67 index, respectively. Kaplan-Meier method was used to investigate the correlation between inflammatory indicators and prognosis of glioma patients. Univariate and multivariate Cox regression were performed to evaluate the independent prognostic value of each parameter in glioma. Then, a nomogram was developed to predict 1-, 3-, and 5-year postoperative survival in diffuse glioma patients based on independent prognostic factors. Subsequent time-dependent ROC curve, calibration curve, decision curve analysis (DCA), and concordance index (C-index) were performed to assess the predictive performance of the nomogram.The Kaplan-Meier curve indicated that patients with high levels of NLR, MLR, and PLR had a poor prognosis. In addition, we found that NLR level was associated with World Health Organization (WHO) grade and IDH status of glioma. The multivariate Cox analysis indicated that resection extent, WHO grade, and NLR level were independent prognostic factors, and we established a nomogram that included these three parameters. The evaluation of the nomogram indicated that the nomogram had a good predictive performance, and the addition of NLR could improve the accuracy.NLR, MLR, and PLR were prognostic factors of diffuse glioma. In addition, the nomogram including NLR was reliable for predicting survival of diffuse glioma patients.