Regulatory T cells (Treg cells or Tregs), a subset of CD4⁺ T cells with immunosuppressive properties, are essential for immune homeostasis and self-tolerance. Characterized by their immunosuppressive capabilities and reliance on the transcription factor Foxp3 (Forkhead box protein P3), Tregs employ multiple mechanisms, including cytokine secretion, metabolic control, and cell contact inhibition, to restrain excessive immune activation to prevent autoimmunity while maintaining tissue repair processes. However, dysregulation in their frequency or function—whether deficiency or hyperactivity—is implicated in diverse pathologies, spanning autoimmune disorders, cancer progression, transplant rejection, and emerging associations with neurological and cardiovascular diseases. Thus, Treg-targeted strategies represent a promising approach for restoring immune balance under various conditions. This review synthesizes current knowledge on Treg biology, from their discovery and definition of markers to their new regulatory mechanisms. We further explore the roles of Tregs across diseases, emphasizing their context-dependent therapeutic potential. Strategies to deplete or inhibit Tregs in cancer immunotherapy contrast with approaches to expand or stabilize their function in autoimmunity and transplantation. However, challenges persist, including achieving tissue-specific targeting, ensuring the functional stability of engineered Tregs, and minimizing off-target effects. By integrating mechanistic insights with translational innovations, this review provides a roadmap for advancing Treg-based therapies, ultimately aiming to restore immune equilibrium in a disease-specific manner.

Background: Malignant glioma is a common primary tumor of the central nervous system. Brevican, an abundant extracellular matrix component in the adult brain, plays a critical role in the process of glioma. The mechanisms for the highly invasive behavior of gliomas are still poorly understood. The aim of this study was to examine whether brevican is a predictor of glioma and its roles in glioma cell motility. Methods: In this study, immunohistochemistry staining for brevican expression was performed in malignant gliomas and benign controls. We also explored the effects of brevican on cell adhesion and migration in brevican-overexpressed cells. Knockdown of brevican expression was achieved by stable transfection of U251 cells transduced with a construct encoding a short hairpin DNA directed against the brevican gene, which correspondingly, down-regulated the proliferation, invasion and spread of brevican-expressing cells. Moreover, the role of brevican in the growth and progression of glioma was demonstrated by in vivo studies. Results: Our results provide evidence for the molecular and cellular mechanisms that may underlie the motility-promoting role of brevican in the progression of glioma. The role of brevican as a target for immunotherapy might be taken into consideration in future studies. Conclusions: This study suggests that expression of brevican is associated with glioma cell adhesion, motility and tumor growth, and also is related to glioma cell differentiation, therefore it may be a marker for malignance degree of glioma

Hirudin is an anti-coagulation protein produced by the salivary glands of the medicinal leech Hirudomedicinalis. It is a powerful and specific thrombin inhibitor. The novel recombinant hirudin, RGD-hirudin, which contains an RGD motif, competitively inhibits the binding of fibrinogen to GPIIb/IIIa on platelets, thus inhibiting platelet aggregation while maintaining its anticoagulant activity. Recombinant RGD-hirudin and six mutant variants (Y3A, S50A, Q53A, D55A, E57A and I59A), designed based on molecular simulations, were expressed in Pichia pastoris. The proteins were refolded and purified to homogeneity as monomers by gel filtration and anion exchange chromatography. The anti-thrombin activity of the six mutants and RGD-hirudin was tested. Further, we evaluated the binding of the mutant variants and RGD-hirudin to thrombin using BIAcore surface plasmon resonance analysis (SPR). Kinetics and affinity constants showed that the K_D values of all six mutant proteins were higher than that of RGD-hirudin. These findings contribute to a novel understanding of the interaction between RGD-hirudin and thrombin.

A novel bispecific c-MET/PD-1 antibody with therapeutic potential in solid cancer A novel bispecific c-MET/PD-1 antibody with therapeutic potential in solid cancer

Bromodomain-containing protein 2 (Brd2) is a nuclear serine/threonine kinase involved in transcriptional regulation. In 3T3-L1 adipocytes, Brd2 normally co-represses PPARγ (peroxisome proliferator-activated receptor gamma) and inhibits adipogenesis. Here, we show that Brd2 over-expression in preadipocytes inhibits their differentiation into adipocytes, while Brd2 knockdown promotes adipogenic differentiation in vitro and forces cells to undergo adipogenesis independent of the MDI (methyisobutylxanthane, dexamethasone and insulin) induction. In this study, the two key transcription factors for adipogenesis, PPARγ and C/EBPα (CCAAT/enhancer binding protein-α) were persistently expressed during the differentiation of preadipocytes to mature adipocytes in Brd2 knockdown 3T3-L1 cells, but their expression was inhibited in cells in which Brd2 was overexpressed. To investigate the role of Brd2 in signal transduction we examined the expression of several signaling molecules involved in the regulation of gene expression and cell differentiation by immunoblotting assay. Down-regulation of Brd2 expression in 3T3-L1 cells led to a decrease in extracellular signal-regulated kinase1/2 (ERK1/2) activity and, conversely, the up-regulation of Brd2 leads to increase in ERK1/2 phosphorylation. Nevertheless, changes in Brd2 expression do not affect the activities of JNK and p38 MAPK. In addition, the phosphorylation of Rafs is not affected by changes in Brd2 expression in 3T3-L1 cells. MEK inhibitor UO126 partly restores differentiation of 3T3-L1 cells that overexpress Brd2. In conclusion, these results indicate that Brd2 regulates ERK1/2 activity independently of Raf signaling in 3T3-L1 adipocytes.