The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single‐organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan‐organ diseases and interorgan communication remains insufficiently explored. This review integrates multidisciplinary evidence to elucidate the biological functions of OS in cellular signaling, homeostasis, and cross‐organ crosstalk. It systematically dissects OS‐driven molecular mechanisms and pathophysiological networks across 10 major organ systems, including the nervous, cardiovascular, oncological, hepatic, and renal systems. Furthermore, it critically examines OS‐related therapeutic targets, including antioxidant and ROS‐generating enzymes, and explores synergistic redox‐based therapeutic strategies. By moving beyond traditional single‐organ paradigms, this review constructs a holistic framework to decode the systemic impact of OS, offering novel insights into disease mechanisms and therapeutic innovations. Ultimately, it lays the foundation for precision medicine approaches aimed at mitigating OS‐driven diseases and improving multiorgan health outcomes.

Ferroptosis, an iron‐dependent cell death pathway driven by lipid peroxidation, has emerged as a critical pathophysiological mechanism linking cancer and inflammatory diseases. The seemingly distinct pathologies exhibit shared microenvironmental hallmarks—oxidative stress, immune dysregulation, and metabolic reprogramming—that converge on ferroptosis regulation. This review synthesizes how ferroptosis operates at the intersection of these diseases, acting as both a tumor‐suppressive mechanism and a driver of inflammatory tissue damage. In cancer, ferroptosis eliminates therapy‐resistant cells but paradoxically facilitates metastasis through lipid peroxidation byproducts that remodel the tumor microenvironment and suppress antitumor immunity. In chronic inflammatory diseases—from atherosclerosis to rheumatoid arthritis—ferroptosis amplifies neuroinflammatory cascades while simultaneously exposing vulnerabilities for therapeutic targeting. Central to this duality are shared regulatory nodes, including nuclear factor kappa B‐driven inflammation, NOD‐like receptor family pyrin domain‐containing 3 inflammasome activation, and GPX4 dysfunction. Therapeutically, ferroptosis induction shows promise against therapy‐resistant cancers but risks exacerbating inflammatory damage, underscoring the need for precision modulation. Emerging strategies—nanoparticle‐based inducers, immunotherapy combinations, and biomarker‐guided patient stratification—aim to balance prodeath efficacy against off‐target toxicity. By dissecting the ferroptosis–inflammation–cancer axis, this review provides a unified framework for understanding disease pathogenesis and advancing therapies for conditions resistant to conventional treatments. Future research must prioritize spatial mapping of ferroptosis dynamics, mechanistic crosstalk with immune checkpoints, and combinatorial regimens that exploit ferroptosis vulnerabilities while mitigating its inflammatory consequences.

Acute kidney injury (AKI) remains a critical condition with limited therapeutic options, predominantly managed by renal replacement therapy. The challenge of developing targeted treatments persists. We integrated genetic data related to druggable proteins and gene expression with AKI genome-wide association study (GWAS) findings. Based on multi-omics Mendelian randomization (MR), we identified the potential causal influence of 5,883 unique proteins and genes on AKI. We also performed using reverse MR and external cohort-based analysis to verify the robustness of this causal relationship. Expression patterns of these targets were examined using bulk transcriptome and single-cell transcriptome data. In addition, drug repurposing analyses were conducted to explore the potential of existing medications. We also constructed a molecular interaction network to explore the interplay between identified targets and known drugs. Genetically predicted levels of seven proteins and twelve genes were associated with an increased risk of AKI. Of these, six targets (NCF1, TNFRSF1B, APEH, ACADSB, ADD1, and FAM3B) were prioritized based on robust evidence and validated in independent cohorts. Reverse MR showed a one-way causal relationship of targets. These targets are predominantly expressed in proximal tubular cells, endothelial cells, collecting duct-principal cells, and immune cells within both AKI-affected and normal tissues. Several promising drug repurposing opportunities were identified, such as telmisartan-NCF1, calcitriol-ACADSB, and ethinyl estradiol-ACADSB. The molecular interaction mapping and pathway integration analysis provided further insights, suggesting potential strategies for combinatorial therapies. This extensive investigation identified several promising therapeutic targets for AKI and highlighted opportunities for drug repurposing. These findings offer valuable insights that could shape future research and the development of targeted treatments.

Bladder cancer (BCa), marked by clinical heterogeneity and late diagnosis, remains a global health challenge. The limitations of conventional diagnostics have spurred the advancement of liquid biopsy approaches, which offer minimally invasive tools for early detection, prognosis, and therapeutic monitoring. This review highlights key components of liquid biopsy in BCa, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and metabolomics—especially urinary volatile organic compounds (VOCs). Each modality contributes distinct insights into tumor biology: CTCs and ctDNA provide information on tumor genetics and dynamics; exosomes reflect microenvironmental signaling and lipid metabolism; and urinary VOC profiling enables metabolic characterization and early-stage discrimination. We explore how these dimensions complement each other in tracking disease progression, predicting recurrence, and guiding personalized therapy. Emphasis is placed on recent technological advances, clinical utility, and future integration into practice. This multidimensional perspective underscores the transformative potential of liquid biopsy in improving BCa outcomes.

Despite growing recognition of immune involvement in kidney stone disease (KSD), its immunogenetic basis remains unclear. We applied a cell type-stratified immunogenetic framework, integrating single-cell cis-expression quantitative trait loci (cis-eQTL) data from the OneK1K immune atlas, to identify gene-cell type associations across four anatomical KSD subtypes. This approach revealed 80 colocalized gene-cell type pairs with strong genetic support. Natural killer (NK) cells and CD4⁺ naive/central memory T cells emerged as major contributors to disease risk, with consistent associations observed for BCR-NK cells and RGS14-CD4⁺/CD8⁺ T cells across all KSD subtypes. Functional and network analyses highlighted roles for MHC class II antigen presentation and T cell activation, implicating adaptive immunity in pathogenesis. Prioritized genes showed pleiotropic links to renal function, inflammation, and mineral metabolism—for example, RGS14 was associated with improved eGFR and reduced urinary citrate; GPX1 with impaired renal function and elevated CRP; HCG25 and DGKD with higher calcium and uric acid. Clinical complication mapping further implicated these targets in osteoporosis, hypertension, and systemic inflammation. A multi-domain prioritization identified seven top targets—RGS14, BCR, PRR3, HIST1H2BG, SLC44A4, POU5F1, and CTSS—as clinically actionable. These insights may inform future strategies for risk stratification, early detection, and immune-targeted intervention in KSD.

The therapeutic efficacy of immune checkpoint blockade is frequently compromised by the profound spatial heterogeneity of solid tumors, where distinct ecol