Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain.

Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging, exerting complex influences on the pathophysiological processes of diseases that manifest upon it. Using a combination of single-cell RNA sequencing, cytometry by time of flight, and various immunological assays, we investigated the characteristics of immunosenescence in the peripheral blood of aged mice and its impact on the cerebral immune environment after ischemic stroke. Our results revealed some features of immunosenescence. We observed an increase in neutrophil counts, concurrent with accelerated neutrophil aging, characterized by altered expression of aging-associated markers like CD62L and consequential changes in neutrophil-mediated immune functions. Monocytes/macrophages in aged mice exhibited enhanced antigen-presentation capabilities. T cell profiles shifted from naive to effector or memory states, with a specific rise in T helper 1 cells and T helper 17 cells subpopulations and increased regulatory T cell activation in CD4 T cells. Furthermore, regulatory CD8 T cells marked by Klra decreased with aging, while a subpopulation of exhausted-like CD8 T cells expanded, retaining potent immunostimulatory and proinflammatory functions. Critically, these inherent disparities not only persisted but were further amplified within the ischemic hemispheres following stroke. In summary, our comprehensive insights into the key attributes of peripheral immunosenescence provide a vital theoretical foundation for understanding not only ischemic strokes but also other age-associated diseases.

The Critical Role of RNA m6A Methylation in Gliomas: Targeting the Hallmarks of Cancer.

Gliomas are the most common central cancer with high aggressive-capacity and poor prognosis, remaining to be the threat of most patients. With the blood-brain barrier and highly malignant progression, the efficacy of high-intensity treatment is limited. The N6-methyladenine (m6A) modification is found in rRNA, snRNA, miRNA, lncRNA, and mRNA, influencing the metabolism and translation of these RNAs and consequently regulating the proliferation, metastasis, apoptosis, etc. of glioma cells. The key role that m6A modification in gliomas has played makes it a prospective target for diagnosis and treatment. However, with studying deeper in m6A modification and gliomas, the conclusion and mechanism are abundant and complex. This review focused on the dysregulation of m6A regulators and m6A modification of key genes and pathways in Hallmarks of gliomas. Furthermore, the potential of exploiting m6A modification for gliomas diagnosis and therapeutics was also discussed. This review will summarize the recent studies about m6A modification, revealing that m6A modification plays an important role in the malignant progression, angiogenesis, microenvironment, and genome instability in gliomas by exploring the interaction and network between m6A modification-related regulators and classical tumor-related genes. And it might provide some clue for the molecular mechanism, diagnosis, and treatment of gliomas.