The Forkhead-box (FOX) transcription factors, as one of the largest gene families in humans, play key roles in cancer. Although studies have suggested that several FOX transcription factors have a significant impact on cancer, the functions of most of the FOX genes in cancer remain elusive. In the study, the expression of 43 FOX genes in 63 kinds of cancer diseases (including many subtypes of same cancer) and in response to 60 chemical substances was obtained from the Gene Expression Atlas database of the European Bioinformatics Institute. Based on the high degree of overlap in FOXO family members differentially expressed in various cancers and their particular responses to chemotherapeutic drugs, our data disclosed the FOX genes that played an important role in the development and progression of cancer. More importantly, we predicted the role of one or several combinatorial FOX genes in the diagnosis and prognostic assessment of a specific cancer and evaluated the potential of a certain anticancer drug therapy for this type of cancer by integrating patterns of FOX genes expression with anticancer drugs sensitivity.

Interferon Regulatory Factors (IRFs) are critical modulators of immune and inflammatory responses, yet their roles in Alzheimer’s disease (AD) and other neurodegenerative disorders remain incompletely understood. While IRFs are recognized for their regulatory functions in neuroinflammation, microglial activation, and neuronal survival, their dual roles as both drivers of pathological inflammation and mediators of neuroprotective pathways underscore a sophisticated regulatory paradox in neurodegenerative disorders. This review aims to synthesize current evidence on IRF-mediated neuroinflammation in AD and related diseases, focusing on the multifaceted functions of key IRF family members, including IRF1, IRF3, and IRF7. We critically evaluate their divergent roles: IRF1 and IRF3, for instance, exacerbate neuroinflammatory cascades and amyloid-beta (Aβ) pathology in AD, whereas IRF7 may paradoxically suppress inflammation under specific conditions. Additionally, we explore IRF dysregulation in Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease, emphasizing shared and distinct mechanisms across neurodegenerative disorders. Restoring IRF balance through genetic manipulation, small-molecule inhibitors, or microbiome-derived modulators could attenuate neuroinflammation, enhance Aβ clearance, and protect neuronal integrity. Ultimately, this work provides a framework for future research to harness IRF signaling pathways in the development of precision therapies for AD and other neurodegenerative diseases.

The interferon regulatory factor (IRF) family exerts dual regulatory roles in vascular inflammation. Pro-inflammatory IRF1/3/5/7 drive endothelial dysfunction, macrophage M1 polarization, vascular smooth muscle cell (VSMC) transdifferentiation, and adaptive immune amplification via nuclear factor-κB (NF-κB), NOD-like receptor pyrin domain-containing 3 (NLRP3), cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. Conversely, IRF4/8 mediate anti-inflammatory effects by promoting M2 polarization, reverse cholesterol transport, and dendritic cell regulation. In atherosclerosis, IRFs display spatiotemporal specificity: endothelial IRF3 in early stages, macrophage IRF1/5 in mid-stages, and smooth muscle IRF7/IRF8 in late stages, supporting phase-specific precision interventions—early IRF3 blockade, mid-stage modulation of IRF5/IRF4 balance, and late combined inhibition of IRF7/8 to stabilize plaques. IRFs also critically participate in hypertensive remodeling, acute coronary syndrome, heart failure, and aortic aneurysm through conserved innate and adaptive immune axes, highlighting their potential as cross-disease biomarkers and therapeutic targets. Major challenges include network redundancy and functional compensation, necessitating single-cell multi-omics and targeted delivery systems for spatiotemporally precise, individualized modulation.