Extracellular vesicles: Illuminating renal pathophysiology and therapeutic frontiers.

Extracellular vesicles (EVs) are minute sacs released by cells into the extracellular milieu, harboring an array of biomolecules including proteins, nucleic acids, and lipids. Notably, a large number of studies have demonstrated the important involvement of EVs in both physiological and pathological aspects of renal function. EVs can facilitate communication between different renal cells, but it is important to recognize their dual role: they can either transmit beneficial information or lead to renal damage and worsening of existing conditions. The composition of EVs in the context of the kidneys offers valuable insights into the intricate mechanisms underlying specific renal functions or disease states. In addition, mesenchymal stem cell-derived EVs have the potential to alleviate acute and chronic kidney diseases. More importantly, the innate nanoparticle properties of EVs, coupled with their engineering potential, make them effective tools for drug delivery and therapeutic intervention. In this review, we focus on the intricate biological functions of EVs in the kidney. In addition, we explore the emerging role of EVs as diagnostic tools and innovative therapeutic agents in a range of renal diseases.

Roles of extracellular vesicles in ageing-related chronic kidney disease: Demon or angel.

Ageing is a universal and unavoidable phenomenon that significantly increases the risk of developing chronic kidney disease (CKD). It has been reported that ageing is associated with functional disruption and structural damage to the kidneys. Extracellular vesicles (EVs), which are nanoscale membranous vesicles containing lipids, proteins, and nucleic acids, are secreted by cells into the extracellular spaces. They have diverse functions such as repairing and regenerating different forms of ageing-related CKD and playing a crucial role in intercellular communication. This paper reviews the etiology of ageing in CKD, with particular attention paid to the roles of EVs as carriers of ageing signals and anti-ageing therapeutic strategies in CKD. In this regard, the double-edged role of EVs in ageing-related CKD is examined, along with the potential for their application in clinical settings.

hucMSC-sEVs-Derived 14-3-3ζ Serves as a Bridge between YAP and Autophagy in Diabetic Kidney Disease.

As nanoscale membranous vesicles, human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hucMSC-sEVs) have attracted extensive attention in the field of tissue regeneration. Under the premise that the mechanisms of hucMSC-sEVs on the treatment of diabetic kidney disease (DKD) have not been revealed clearly, we constructed DKD rat model with success. After tail vein injection, hucMSC-sEVs effectively reduced blood glucose, maintained body weight and improved renal function in DKD rats. Notably, we found that hucMSC-sEVs suppressed YAP expression in renal cortical regions. Further in vitro experiments, we confirmed that the expression of YAP in the nucleus of renal podocytes was increased, and the level of autophagy was inhibited in the high-glucose environment, which could be reversed by intervention with hucMSC-sEVs. We screened out the key protein 14-3-3ζ, which could not only promote YAP cytoplasmic retention instead of entering the nucleus, but also enhance the level of autophagy in the cytoplasm. Ultimately, excessive YAP protein was removed by autophagy, a classic way of protein degradation. In conclusion, our study provides new strategies for the prevention of DKD and proposes the possibility of hucMSC-sEVs becoming a new treatment for DKD in the future.

Au Nanoclusters Ameliorate Shigella Infectious Colitis by Inducing Oxidative Stress.

BACKGROUND: Shigella infection has always been a global burden, and it particularly threatens children between the ages of 1 and 5 years. Economically underdeveloped countries are dominated by Shigella flexneri infection. The most effective method to treat Shigella is antibiotics, but with the abuse of antibiotics and the prevalence of multidrug resistance, we urgently need a relatively safe non-antibiotic treatment to replace it. Ultrasmall Au nanoclusters (NCs) have special physical and chemical properties and can better interact with and be internalized by bacteria to disrupt the metabolic balance. The purpose of this study was to explore whether Au NCs may be a substitute for antibiotics to treat Shigella infections. METHODS: Au NCs and Shigella Sf301, R2448, and RII-1 were cocultured in vitro to evaluate the bactericidal ability of Au NCs. The degree of damage and mode of action of Au NCs in Shigella were clearly observed in images of scanning electron microscopy (SEM). In vivo experiments were conducted to observe the changes in body weight, clinical disease activity index (DAI) and colon (including length and histopathological sections) of mice treated with Au NCs. The effect of Au NCs was analysed by measuring the content of lipocalin-2 (LCN2) and Shigella in faeces. Next, the changes in Shigella biofilm activity, the release of reactive oxygen species (ROS), the changes in metabolism-related and membrane-related genes, and the effect of Au NCs on the body weight of mice were determined to further analyse the mechanism of action and effect. RESULTS: Au NCs (100 µM) interfered with oxidative metabolism genes, induced a substantial increase in ROS levels, interacted with the cell membrane to destroy it, significantly killed Shigella, and effectively alleviated the intestinal damage caused by Shigella in mice. The activity of the biofilm formed by Shigella was reduced. CONCLUSION: The effective antibacterial effect and good safety suggest that Au NCs represent a good potential alternative to antibiotics to treat Shigella infections.