Atopic dermatitis (AD) is caused by multiple factors that trigger chronic skin inflammation, including a defective skin barrier, immune cell activation, and microbial exposure. Although melatonin has an excellent biosafety profile and a potential to treat AD, there is limited clinical evidence from controlled trials that support the use of melatonin as an AD treatment. The delivery of melatonin via the transdermal delivery system is also a challenge in designing melatonin-based AD treatments. In this study, we generated melatonin-loaded extracellular vesicle-mimetic nanoparticles (^MelaNVs) to improve the transdermal delivery of melatonin and to evaluate their therapeutic potential in AD. The ^MelaNVs were spherical nanoparticles with an average size of 100 nm, which is the optimal size for the transdermal delivery of drugs. ^MelaNVs showed anti-inflammatory effects by suppressing the release of TNF-α and β-hexosaminidase in LPS-treated RAW264.7 cells and compound 48/80-treated RBL-2H3 cells, respectively. ^MelaNVs showed a superior suppressive effect compared to an equivalent concentration of free melatonin. Treating a 2,4-dinitrofluorobenzene (DNCB)-induced AD-like mouse model with ^MelaNVs improved AD by suppressing local inflammation, mast cell infiltration, and fibrosis. In addition, ^MelaNVs effectively suppressed serum IgE levels and regulated serum IFN-γ and IL-4 levels. Taken together, these results suggest that ^MelaNVs are novel and efficient transdermal delivery systems of melatonin and that ^MelaNVs can be used as a treatment to improve AD.

Dysregulation in mitophagy, in addition to contributing to imbalance in the mitochondrial dynamic, has been implicated in the development of renal fibrosis and progression of chronic kidney disease (CKD). However, the current understanding of the precise mechanisms behind the pathogenic loss of mitophagy remains unclear for developing cures for CKD. We found that miR-4516 is downregulated and its target SIAH3, an E3 ubiquitin protein ligase that reduces PINK1 accumulation to damaged mitochondria, is upregulated in the renal cortex of CKD mice. Here, we demonstrated that melatonin injection induces miR-4516 expression and suppresses SIAH3, and promotes PINK1/Parkin-mediated mitophagy. Furthermore, we demonstrated that melatonin injection attenuates the pathological features of CKD by improving mitochondrial homeostasis. Our data supports that mitochondrial autophagy regulation by activating miR-4516/SIAH3/PINK1 mitophagy signaling axis can be a viable new strategy for treating CKD.

A cellular prion protein (PrP^C) is a ubiquitous cell surface glycoprotein, and its physiological functions have been receiving increased attention. Endogenous PrP^C is present in various kidney tissues and undergoes glomerular filtration. In prion diseases, abnormal prion proteins are found to accumulate in renal tissues and filtered into urine. Urinary prion protein could serve as a diagnostic biomarker. PrP^C plays a role in cellular signaling pathways, reno-protective effects, and kidney iron uptake. PrP^C signaling affects mitochondrial function via the ERK pathway and is affected by the regulatory influence of microRNAs, small molecules, and signaling proteins. Targeting PrP^C in acute and chronic kidney disease could help improve iron homeostasis, ameliorate damage from ischemia/reperfusion injury, and enhance the efficacy of mesenchymal stem/stromal cell or extracellular vesicle-based therapeutic strategies. PrP^C may also be under the influence of BMP/Smad signaling and affect the progression of TGF-β-related renal fibrosis. PrP^C conveys TNF-α resistance in some renal cancers, and therefore, the coadministration of anti-PrP^C antibodies improves chemotherapy. PrP^C can be used to design antibody–drug conjugates, aptamer–drug conjugates, and customized tissue inhibitors of metalloproteinases to suppress cancer. With preclinical studies demonstrating promising results, further research on PrP^C in the kidney may lead to innovative PrP^C-based therapeutic strategies for renal disease.