Abstract Biomarkers play a pivotal role in contemporary medical research, particularly in the early diagnosis of diseases and personalized treatment. Although previous studies have systematically reviewed markers across various disease domains, an integrated framework that connects major physiological systems, encompasses multiple organs, and spans a broad spectrum of diseases is still lacking. In the context of modern health challenges, marked by the high prevalence of chronic diseases and widespread comorbidities, establishing a panoramic biomarker navigation system is imperative. This review offers the initial comprehensive elucidation of the biomarker interaction networks across diverse systems, organs, and diseases, and delineates the operational framework for establishing a “biomarker navigation system”. The core contribution of this work is a transition from ‘knowledge enumeration’ to a more integrated, systems‐level approach. This provides new perspectives in systems biology for understanding the shared pathological foundations of comorbidities. Furthermore, it provides a theoretical basis for a reorientation in medicine, from a focus on ‘treating existing diseases’ to ‘preventive interventions’ and from ‘single‐disease management’ to a comprehensive, systems‐based approach. To facilitate the exploration and application of this system–organ–disease–biomarker network, we developed the “Human Biomarker Navigator” web platform (http://www.hbiomarker.com), which allows researchers and clinicians to efficiently retrieve the functional characteristics and clinical significance of diverse biomarkers across different disease contexts.
Meng-Yao Li, Qian Zhang, Zi-Jie Wang et al.· iMeta· 1 citation
Background/Objectives: Renal ischemia–reperfusion injury (IRI) and infection-associated renal damage are characterized by persistent inflammation, oxidative stress, microvascular dysfunction, and impaired tissue regeneration, creating a hostile microenvironment that limits effective repair. We developed an injectable, photocrosslinkable methacrylated chitosan (CSMA) hydrogel for the localized co-delivery of cerium oxide nanoparticles (CeO2NPs) and vascular endothelial growth factor (VEGF), aiming to integrate redox modulation, antibacterial activity, and regenerative support. Methods: Gelation, microstructure, rheology, degradation, and CeO2NP/VEGF were characterized. Tubular epithelial and fibroblast migration and endothelial network formation, angiogenic gene expression, and antibacterial activity against Staphylococcus aureus and Escherichia coli were evaluated in vitro. Theraputic performance was assessed by renal surface application in a rat renal IRI model and catheter-mediated interavsical administration in an ascending urinary tract infection model. Systematic biocompatibility was evaluated separately in a 14-day subcutaneous implantation study. Renal response were further investigated using transcriptomic and targeted molecular analyses. Results: The CSMA/VEGF/CeO2NPs hydrogel exhibited rapid in situ gelation, interconnected porous architecture, stable viscoelasticity, gradual degradation, and sustained release of both CeO2NPs and VEGF. The formulation enhanced tubular epithelial and fibroblast migration, promoted endothelial network formation and angiogenic gene expression and effectively inhibited both S. aureus and E. coli. In a surgically controlled rat renal IRI model, direct renal-surface application of the hydrogel reduced tubular injury, inflammatory infiltration, and fibrotic remodeling. In a separate ascending urinary tract infection model, catheter-based intravesical administration reduced the ascending renal bacterial burden and infection-associated inflammatory injury. No detectable adverse systemic effects observed under the tested conditions over the 14-day observation period in the subcutaneous implantation. Transcriptomic analyses further revealed that CSMA/VEGF/CeO2NPs treatment was associated with marked remodeling of the renal injury microenvironment, characterized by suppression of antigen presentation and immune activation pathways, alongside restoration of metabolic programs associated with amino acid, lipid, and purine metabolism. These molecular changes were accompanied by downregulation of CIITA/CD74/MHC-II signaling, recovery of metabolic regulators AGXT and ACOX1, modulation of Hippo/YAP- and ECM-associated pathways, and preservation of renal structural markers including nephrin and WT1. Conclusions: The localized CSMA-mediated co-delivery of CSMA/VEGF/CeO2NPs hydrogel promotes renal repair through resolution of maladaptive immune activation, metabolic reprogramming, angiogenic enhancement, and preservation of renal structural integrity, providing a promising biomaterial strategy for the treatment of ischemic and infection-associated renal injuries.
Qing Sun, Yang Fu, Tian-Wei Wang et al.· Pharmaceutics· 0 citations
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