Glioma is one of the most common types of malignant primary central nervous system tumor, and prognosis for this disease is poor. As autophagic drugs have been reported to induce glioma cell death, we investigated the potential prognostic role of autophagy‐associated long non‐coding RNA (lncRNA) in glioma patients. In this study, we obtained 879 lncRNAs and 216 autophagy genes from the Chinese Glioma Genome Atlas microarray, and found that 402 lncRNAs are correlated with the autophagy genes. Subsequently, 10 autophagy‐associated lncRNAs with prognostic value (PCBP1‐AS1, TP53TG1, DHRS4‐AS1, ZNF674‐AS1, GABPB1‐AS1, DDX11‐AS1, SBF2‐AS1, MIR4453HG, MAPKAPK5‐AS1 and COX10‐AS1) were identified in glioma patients using multivariate Cox regression analyses. A prognostic signature was then established based on these prognostic lncRNAs, dividing patients into low‐risk and high‐risk groups. The overall survival time was shorter in the high‐risk group than that in the low‐risk group [hazard ratio (HR) = 5.307, 95% CI: 4.195–8.305; P < 0.0001]. Gene set enrichment analysis revealed that the gene sets were significantly enriched in cancer‐related pathways, including interleukin (IL) 6/Janus kinase/signal transducer and activator of transcription (STAT) 3 signaling, tumor necrosis factor α signaling via nuclear factor κB, IL2/STAT5 signaling, the p53 pathway and the KRAS signaling pathway. The Cancer Genome Atlas dataset was used to validate that high‐risk patients have worse survival outcomes than low‐risk patients (HR = 1.544, 95% CI: 1.110–2.231; P = 0.031). In summary, our signature of 10 autophagy‐related lncRNAs has prognostic potential for glioma, and these autophagy‐related lncRNAs may play a key role in glioma biology.

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-1β 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.

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.

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.

Objective: The present study used the RNA sequencing (RNA-seq) dataset to identify prognostic snoRNAs and construct a prognostic signature of The Cancer Genome Atla (TCGA) lower grade glioma (LGG) cohort, and comprehensive analysis of this signature. Methods: RNA-seq dataset of 488 patients from TCGA LGG cohort were included in this study. Comprehensive analysis including function enrichment, gene set enrichment analysis (GSEA), immune infiltration, cancer immune microenvironment, and connectivity map (CMap) were used to evaluate the snoRNAs prognostic signature. Results: We identified 21 LGG prognostic snoRNAs and constructed a novel eleven-snoRNA prognostic signature for LGG patients. Survival analysis suggests that this signature is an independent prognostic risk factor for LGG, and the prognosis of LGG patients with a high-risk phenotype is poor (adjusted P = 0.003, adjusted hazard ratio = 2.076, 95% confidence interval = 1.290–3.340). GSEA and functional enrichment analysis suggest that this signature may be involved in the following biological processes and signaling pathways: such as cell cycle, Wnt, mitogen-activated protein kinase, janus kinase/signal transducer and activator of tran-ions, T cell receptor, nuclear factor-kappa B signaling pathway. CMap analysis screened out ten targeted therapy drugs for this signature: 15-delta prostaglandin J2, MG-262, vorinostat, 5155877, puromycin, anisomycin, withaferin A, ciclopirox, chloropyrazine and megestrol. We also found that high- and low-risk score phenotypes of LGG patients have significant differences in immune infiltration and cancer immune microenvironment. Conclusions: The present study identified a novel eleven-snoRNA prognostic signature of LGG and performed a integrative analysis of its molecular mechanisms and relationship with tumor immunity.

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.