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Updated: Aug 12, 2025

Estimation of Urinary Nanocrystals in Humans using Calcium Fluorophore Labeling and Nanoparticle Tracking Analysis
Published on: February 9, 2021
Lemon-Derived Extracellular Vesicle-like Nanoparticles Block the Progression of Kidney Stones by Antagonizing
Lei Zhang1, Simin Li1, Minghui Cong1
1Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Abstract:
Kidney stones, represented by the calcium oxalate (CaOx) type, are highly prevalent and recrudescent. Cumulative evidence shows regular consumption of lemonade intervenes with stone development. However, the detailed mechanism remains obscure. Here, extracellular vesicle-like nanoparticles (LEVNs) isolated from lemonade are demonstrated to traffick from the gut to the kidney, primarily enriched in tubule cells. Oral administration of LEVNs significantly alleviates the progression of kidney stones in rats. Mechanistically, in addition to altering the crystallization of CaOx toward a less stable subtype, LEVNs suppress the CaOx-induced endoplasmic reticulum stress response of tubule cells, as indicated by homeostasis of specific signaling molecules and restoration of subcellular function, thus indirectly inhibiting stone formation. To exercise this regulation, endocytosed LEVNs traffick along the microtubules throughout the cytoplasm and are eventually recruited into lysosomes. In conclusion, this study reveals a LEVNs-mediated mechanism against renal calculi and provides positive evidence for consumption of lemonade preventing stone formation.
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