Jinbao Zong

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.

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.

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.

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.