Gliomas are complex and heterogeneous central nervous system tumors with poor prognosis. Despite the increasing development of aggressive combination therapies, the prognosis of glioma is generally unsatisfactory. Exosomal microRNA (miRNA) has been successfully used in other diseases as a reliable biomarker and even therapeutic target. Recent studies show that exosomal miRNA plays an important role in glioma occurrence, development, invasion, metastasis, and treatment resistance. However, the association of exosomal miRNA between glioma has not been systemically characterized. This will provide a theoretical basis for us to further explore the relationship between exosomal miRNAs and glioma and also has a positive clinical significance in the innovative diagnosis and treatment of glioma.

Neurodevelopmental disorders are mostly studied using mice as models. However, the mouse brain lacks similar cell types and structures as those of the human brain. In recent years, emergence of three‐dimensional brain organoids derived from human embryonic stem cells or induced pluripotent stem cells allows for controlled monitoring and evaluation of early neurodevelopmental processes and has opened a window for studying various aspects of human brain development. However, such organoids lack original anatomical structure of the brain during maturation, and neurodevelopmental maturation processes that rely on unique cellular interactions and neural network connections are limited. Consequently, organoids are difficult to be used extensively and effectively while modelling later stages of human brain development and disease progression. To address this problem, several methods and technologies have emerged that aim to enhance the sophisticated regulation of brain organoids developmental processes through bioengineering approaches, which may alleviate some of the current limitations. This review discusses recent advances and application areas of human brain organoid culture methods, aiming to generalize optimization strategies for organoid systems, improve the ability to mimic human brain development, and enhance the application value of organoids.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brain metastases. This process can be plausibly explained by the “seed and soil” hypothesis, which essentially states that tumor cells can interact with various components of the central nervous system microenvironment to produce adaptive changes; it is this interaction that determines the development of brain metastases. As a novel form of intercellular communication, exosomes play a key role in the brain metastasis microenvironment and carry various bioactive molecules that regulate receptor cell activity. In this paper, we review the roles and prospects of brain metastatic tumor cells, the brain metastatic tumor microenvironment, and exosomes in the development and clinical management of brain metastases.

Background: The role of epigenetic modulation in immunity is receiving increased recognition—particularly in the context of RNA N6-methyladenosine (m6A) modifications. Nevertheless, it is still uncertain whether m6A methylation plays a role in the onset and progression of intracranial aneurysms (IAs). This study aimed to establish the function of m6A RNA methylation in IA, as well as its correlation with the immunological microenvironment.Methods: Our study included a total of 97 samples (64 IA, 33 normal) in the training set and 60 samples (44 IA, 16 normal) in the validation set to systematically assess the pattern of RNA modifications mediated by 22 m6A regulators. The effects of m6A modifications on immune microenvironment features, i.e., immune response gene sets, human leukocyte antigen (HLA) genes, and infiltrating immune cells were explored. We employed Lasso, machine learning, and logistic regression for the purpose of identifying an m6A regulator gene signature of IA with external data validation. For the unsupervised clustering analysis of m6A modification patterns in IA, consensus clustering methods were employed. Enrichment analysis was used to assess immune response activity along with other functional pathways. The identification of m6A methylation markers was identified based on a protein–protein interaction network and weighted gene co-expression network analysis.Results: We identified an m6A regulator signature of IGFBP2, IGFBP1, IGF2BP2, YTHDF3, ALKBH5, RBM15B, LRPPRC, and ELAVL1, which could easily distinguish individuals with IA from healthy individuals. Unsupervised clustering revealed three m6A modification patterns. Gene enrichment analysis illustrated that the tight junction, p53 pathway, and NOTCH signaling pathway varied significantly in m6A modifier patterns. In addition, the three m6A modification patterns showed significant differences in m6A regulator expression, immune microenvironment, and bio-functional pathways. Furthermore, macrophages, activated T cells, and other immune cells were strongly correlated with m6A regulators. Eight m6A indicators were discovered—each with a statistically significant correlation with IA—suggesting their potential as prognostic biological markers.Conclusion: Our study demonstrates that m6A RNA methylation and the immunological microenvironment are both intricately correlated with the onset and progression of IA. The novel insight into patterns of m6A modification offers a foundation for the development of innovative treatment approaches for IA.

N7-methylguanosine (m7G) modification signature has recently emerged as a crucial regulator of tumor progression and treatment in cancer. However, there is limited information available on the genomic profile of lower-grade gliomas (LGGs) related to m7G methylation modification genes’ function in tumorigenesis and progression. In this study, we employed bioinformatics methods to characterize m7G modifications in individuals with LGG from The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). We used gene set enrichment analysis (GSEA), single sample GSEA (ssGSEA), CIBERSORT algorithm, ESTIMATE algorithm, and TIDE to evaluate the association between m7G modification patterns, tumor microenvironment (TME) cell infiltration properties, and immune infiltration markers. The m7G scoring scheme using principal component analysis (PCA) was employed to investigate the m7G modification patterns quantitatively. We examined the m7G modification hub genes' expression levels in normal samples, refractory epilepsy samples, and LGG samples using immunohistochemistry, western-blotting, and qRT-PCR. Our findings revealed that individuals with LGG could be categorized into two groups based on m7G scores (high and low) according to the properties of m7G. Moreover, we observed that high m7G score was associated with significant clinical benefit and prolonged survival duration in the anti-PD-1 cohort, while low m7G score was associated with improved prognostic outcomes and increased likelihood of complete or partial response in the anti-PD-L1 cohort. Different m7G subtypes also showed varying Tumor Mutational Burden (TMB) and immune profiles and might have distinct responses to immunotherapy. Furthermore, we identified five potential genetic markers that were highly correlated with the m7G score signature index. These findings provide insight into the features and classification associated with m7G methylation modifications and may aid in improving the clinical outcome of LGG.