Glioblastoma (GBM) (IDH-wildtype), the most prevalent and malignant primary brain tumor in adults, continues to pose a major therapeutic challenge in neuro-oncology. Despite significant advancements in cancer diagnosis and treatment technologies, conventional therapies remain largely ineffective against this tumor, urgently necessitating breakthrough treatment strategies. This comprehensive review critically examines recent advances in targeting ferroptosis, an iron-dependent form of non-apoptotic cell death mediated through reactive oxygen species (ROS) accumulation and lipid membrane peroxidation, for therapeutic intervention in GBM. The key aspects analyzed encompass the unique molecular mechanisms that distinguish ferroptosis from apoptosis and necrosis, along with its regulatory networks in GBM. The analysis also explores the therapeutic potential of targeting critical ferroptosis pathways, including dysregulated iron metabolism, impaired antioxidant defenses, and abnormal lipid peroxidation. Additionally, it examines the synergistic effects and molecular basis of combining ferroptosis inducers with chemo-radiotherapy or immunotherapy. Finally, the study highlights innovative applications of nano-drug delivery technologies in overcoming blood-brain barrier (BBB) limitations and enhancing the precision of ferroptosis-targeted therapy. Notably, this review provides a comprehensive analysis of the interplay between ferroptosis regulation and the tumor immune microenvironment, highlighting a promising ‘ferroptosis-immunotherapy’ combination strategy with clinical translation potential for GBM treatment. While challenges persist regarding incomplete understanding of regulatory networks and nanocarrier biosafety issues, this review not only provides a theoretical framework for comprehending ferroptosis-mediated anti-GBM mechanisms but also outlines future research directions, including in-depth dissection of ferroptosis signaling hubs, development of intelligent nano-delivery systems, and establishment of preclinical safety evaluation protocols. These findings are expected to provide revolutionary therapeutic targets for achieving precision treatment of GBM.

It has been reported that carbonic anhydrase I (CA1) is a target for the diagnosis and therapy of atherosclerosis (AS) since CA1 can promote AS aortic calcification. We also found that methazolamide (MTZ), a drug for glaucoma treatment and an inhibitor of carbonic anhydrases, can treat AS by inhibiting calcification in aortic tissues. This study focused on the therapeutic mechanism of MTZ and the pathogenic mechanism of AS. In this study, a routine AS animal model was established in ApoE−/− mice, which were treated with MTZ. The aortic tissues were analyzed using single‐cell sequencing. MTZ significantly increased the proportions of B‐1/MZB B cells with high expressions of Nr4A1 and Ccr7, CD8+CD122+ Treg‐like cells with high Nr4A1 expression, and smooth muscle cells with high Tpm2 expression. These cells or their marker genes were reported to exert immunosuppressive, anti‐proinflammatory, and atheroprotective effects. MTZ also decreased the proportions of endothelial cells with high expressions of Retn, Apoc1, Lcn2, Mt1, Serpina3, Lpl, and Lgals3; nonclassical CD14+CD16++ monocytes with high expressions of Mt1, Tyrobp, Lgals3, and Cxcl2; and Spp1+ macrophages with high expressions of Mmp‐12, Trem2, Mt1, Lgals3, Cxcl2, and Lpl. These cells or their marker genes have been reported to promote inflammation, calcification, tissue remodeling, and atherogenesis. A significant decrease in the proportion of CD8+CD183 (CXCR3)+ T cells, the counterpart of murine CD8+CD122+ T cells, was detected in the peripheral blood of newly diagnosed AS patients rather than in that of patients receiving anti‐AS treatments. These results suggest that MTZ can treat AS by increasing immunosuppressive cells and decreasing expressions of genes related to inflammation, calcification, and tissue remodeling.

Preeclampsia is a multisystem progressive condition and is one of the most serious complications of pregnancy. Owing to its unclear pathogenesis, there are no precise and effective therapeutic targets for preeclampsia, and the only available treatment strategy is to terminate the pregnancy and eliminate the clinical symptoms. In recent years, non-coding RNAs have become a hotspot in preeclampsia research and have shown promise as effective biomarkers for the early diagnosis of preeclampsia over conventional biochemical markers. PIWI-interacting RNAs, novel small non-coding RNA that interact with PIWI proteins, are involved in the pathogenesis of various diseases at the transcriptional or post-transcriptional level. However, the mechanisms underlying the role of PIWI-interacting RNAs in the pathogenesis of preeclampsia remain unclear. In this review, we discuss the findings of existing studies on PIWI-interacting RNA biogenesis, functions, and their possible roles in preeclampsia, providing novel insights into the potential application of PIWI-interacting RNAs in the early diagnosis and clinical treatment of preeclampsia.

Carbonic anhydrase I (CA1) has been reported to be a diagnostic and therapeutic target for atherosclerosis (AS). This study aimed to verify the essential role of CA1 in AS progression in CA1-overexpressing mice. A ApoE [-/-] CA1-overexpressing knock-in mouse model was constructed via CRISPR/Cas9-mediated genome engineering. AS was then induced in these transgenic mice via the administration of a high-fat diet, and a second group simultaneously received treatment with methazolamide (MTZ), a carbonic anhydrase inhibitor. Compared with ApoE [-/-] mice without CA1 overexpression, CA1-overexpressing mice had a greater average body weight, regardless of whether their treatment with MTZ or their AS induction status. Sudan IV, hematoxylin and eosin and Oil Red O staining revealed more plaques and fat deposits in the cardiac aortas of CA1-overexpressing mice than in those of ordinary ApoE-/- mice when AS was induced. Moreover, the atherogenic index; low-density lipoprotein, total cholesterol and triglyceride levels were significantly elevated, and high-density lipoprotein levels were declined in the peripheral blood of CA1-overexpressing mice than in that of ordinary ApoE [-/-] mice, regardless of whether these animals were induced to AS. Immunohistochemistry, Von Kossa staining and fluorescence immunohistochemistry revealed increases in CA1 expression, calcium deposition and M1 macrophages in the aortic tissues of CA1-overexpressing mice with AS. MTZ treatment significantly suppressed AS pathologies in the above experiments. These findings revealed aggravated AS in ApoE [-/-] CA1-overexpressing mice and suggest that CA1 aggravates AS by increasing M1-type macrophages, a proinflammatory macrophage subtype.

The important immunoregulatory roles of regulatory T cells (Tregs) include fostering tolerance to infections, controlling immune surveillance, and curtailing autoimmunity. Years of research have not only generated abundant knowledge in the field of Treg biology but also enabled the initial application of Tregs in cell therapy. However, most data in this field are obtained from laboratory animals and in vitro experiments. This review provides an updated summary and the latest understanding of Treg-targeting cell therapy. We introduce the unique traits of Tregs, review animal experiments and clinical trials on Treg injections, discuss limitations of Treg applications, and consider future perspectives on Treg-based therapies. Overall, the safety and potential efficacy of Tregs will broaden the scope of cell-based treatments.

Asthma is a heterogeneous airway inflammatory disease that can be classified according to the inflammatory phenotype. The pathogenesis, clinical features, response to hormone therapy, and prognosis of different inflammatory phenotypes differ significantly. This condition also refers to age-related chronic ailments. Here, we intend to identify the function of aging-related genes in different inflammatory phenotypes of asthma using bioinformatic analyses. Initially, the research adopted the GSEA analysis to understand the fundamental mechanisms that govern different inflammatory phenotypes of asthma pathogenesis and use the CIBERSORT algorithm to assess the immune cell composition. The differentially expressed genes (DEGs) of eosinophilic asthma (EA), neutrophilic asthma (NA), and paucigranulocytic asthma (PGA) were identified through the limma R package. Aging-related genes, screened from multiple databases, were intersected with DEGs of asthma to obtain the asthma-aging-related DEGs. Then, the GO and KEGG pathway enrichment analyses showed that the NA- and EA-aging-related DEGs are involved in the various cytokine-mediated signaling pathways. PPI network and correlation analysis were performed to identify and evaluate the correlation of the hub genes. Further, the clinical characteristics of asthma-aging-related DEGs were explored through ROC analysis. 3 and 12 aging-related DEGs in EA and NA patients show high diagnostic accuracy, respectively (AUC >0.7). This study provided valuable insights into aging-related gene therapy for phenotype-specific asthma. Moreover, the study suggests that effective interventions against asthma may operate by disrupting the detrimental cycle of "aging induces metabolic diseases, which exacerbate aging".