Melatonin-stimulated exosomes enhance the regenerative potential of chronic kidney disease-derived mesenchymal stem/stromal cells via cellular prion proteins

Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. Chronic kidney disease-induced pathophysiological conditions decrease efficacy of autologous mesenchymal stem/stromal cell (MSC)-based therapy by reducing MSC functionality. To enhance therapeutic potential in patients with CKD, we isolated exosomes derived from melatonin-treated healthy MSCs (MT exosomes) and assessed the biological functions of MT exosome–treated MSCs isolated from patients with CKD (CKD-MSCs). Treatment with melatonin increased the expression of cellular prion protein (PrP^C) in exosomes isolated from MSCs through the upregulation of miR-4516. Treatment with MT exosomes protected mitochondrial function, cellular senescence, and proliferative potential of CKD-MSCs. MT exosomes significantly increased the level of angiogenesis-associated proteins in CKD-MSCs. In a murine hindlimb ischemia model with CKD, MT exosome–treated CKD-MSCs improved functional recovery and vessel repair. These findings elucidate the regenerative potential of MT exosome–treated CKD-MSCs via the miR-4516-PrP^C signaling axis. This study suggests that the treatment of CKD-MSCs with MT exosomes might be a powerful strategy for developing autologous MSC-based therapeutics for patients with CKD. Furthermore, miR-4516 and PrP^C could be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases.     

Application of Various Additional Imaging Techniques for Thyroid Ultrasound: Direct Comparison of Combined Various Elastography and Doppler Parameters to Gray-Scale Ultrasound in Differential Diagnosis of Thyroid Nodules

This study was conducted to evaluate the role in the differential diagnosis of thyroid nodules of various elastographic and Doppler parameters when added to gray-scale ultrasonography (US). One-hundred seventy-one thyroid nodules (63 malignant, 108 benign) in 169 patients were included. Elastography (strain and shear wave elastography) and Doppler (power Doppler, superb microvascular imaging and microflow imaging) images of the same thyroid nodule were obtained using a single US machine. The diagnostic performance parameters of gray-scale US with and without elastography and those of Doppler US were calculated and compared. The specificity, positive predictive value and accuracy of gray-scale US were significantly higher than those of US combined with elastographic parameters (all p values?<?0.05). The area under the receiver operating characteristic curve for gray-scale US was 0.877, significantly higher than that for US combined with elastography patterns, shear wave elastography ratio (all p values?<?0.05) and Doppler parameters. Adding additional imaging modalities such as elastography and Doppler does not improve the diagnostic performance of gray-scale US in differentiating thyroid nodules.