Kidney diseases, represented by chronic kidney disease (CKD) and acute kidney injury (AKI), pose significant global public health challenges due to their complex pathogenesis and limited therapeutic options. In recent years, epigenetic regulation-including DNA methylation, histone modifications, and non-coding RNAs-has been shown to play a crucial role in the progression of kidney diseases, offering new directions for therapeutic strategies. Natural herbal compounds have emerged as a research focus for modulating epigenetic mechanisms owing to their multi-target effects, low toxicity, and broad bioactivity. This review outlines the regulatory functions of epigenetic mechanisms across various kidney diseases and illustrates how natural herbal compounds can mitigate renal injury via multi-target epigenetic modulation. These compounds have been shown to reverse renal fibrosis, attenuate inflammatory responses, suppress oxidative stress, and protect podocytes and renal tubular epithelial cells by targeting DNA methyltransferases, histone-modifying enzymes, and non-coding RNAs, including microRNAs and long non-coding RNAs. However, challenges such as limited bioavailability and insufficiently elucidated in vivo mechanisms impede clinical translation. Future research should prioritize structural optimization, advanced delivery systems, and investigations into gut microbiome interactions to enhance therapeutic applicability. Overall, this review highlights the promise of epigenetics-based therapeutic strategies using herbal active ingredients for kidney disease intervention, though further validation and optimization are needed for clinical application.
Qiu-xiang Bai, Kang Luo, Long-hao Jia et al.· Seminars in Nephrology· 0 citations
Traditional human blood vessel organoids, built primarily around endothelial monocultures, fail to replicate the multicellular architecture and dynamic immunological functions of native microvasculature. This review synthesizes an emerging paradigm shift toward third-generation, multi-lineage, and immune-competent vascular organoids. Multicellular integration, combining perivascular mural lineages (pericytes and vascular smooth muscle cells) with functional immune populations (macrophages, microglia, and lymphocytes), is delineated. Its role in reinstating baseline barrier tightness, contractility, and tissue-level immunosurveillance is highlighted. Critical bioengineering workflows are examined, with emphasis on fluidic shear stress in microfluidic platforms, the spatial precision afforded by three-dimensional (3D) bioprinting, and multiplex CRISPR gene editing. These technologies resolve lineage-specific media conflicts and enable off-the-shelf, hypoimmunogenic vascular constructs. Furthermore, the capacity of these systems to recapitulate complex pathophysiology is evaluated. Such pathophysiology includes complement-driven immunothrombosis in SARS-CoV-2 infection, neurovascular degeneration in Alzheimer’s disease, genetic small-vessel disorders, and tumor-immune barriers that govern chimeric antigen receptor T (CAR-T) cell infiltration. Finally, persistent translational hurdles are outlined, including metabolic bottlenecks, diffusion limits, scale‑up challenges, and the lack of large‑animal efficacy and safety data. Strategies that may help transition these models from research tools toward clinically relevant platforms are also discussed.
