Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by progressive enlargement of fluid-filled cysts derived from renal tubular epithelial cells, which has become the fourth leading cause of end-stage renal diseases. Currently, treatment options for ADPKD remain limited. The purpose of this study was to discover an effective therapeutic drug for ADPKD. With virtual screening, Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney-specific Pkd1 knockout mouse (PKD) model, we identified obacunone as a candidate compound for ADPKD drug discovery from a natural antioxidant compound library. In vitro experiments showed that obacunone significantly inhibited cyst formation and expansion of MDCK cysts and embryonic kidney cysts in a dose-dependent manner. In vivo, obacunone treatment significantly reduced the renal cyst development in PKD mice. Western blot and morphological analysis revealed that obacunone served as a NRF2 activator in ADPKD, which suppressed lipid peroxidation by up-regulating GPX4 and finally restrained excessive cell proliferation by down-regulating mTOR and MAPK signaling pathways. Experimental data demonstrated obacunone as an effective renal cyst inhibitor for ADPKD, indicating that obacunone might be developed into a therapeutic drug for ADPKD treatment.

Imaging during acute episodes of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) primarily shows reversible cortical edema. However, the mechanisms underlying such cortical lesions in MELAS remain unclear. Analyzing MRI findings of MELAS could provide clues to these mechanisms. We reviewed the medical records and imaging data of MELAS patients treated at Peking University First Hospital from 2013 to 2024. 61 MRI scans from 55 patients were included in this study. The spatial distribution of SLLs was analyzed based on high-resolution cortical segmentation. Next, we established a non-negative independent component analysis (nnICA) model to separate independent SLL components. Then we assessed correlation of synaptic density and lesion load using Spearman's rho test. Finally, a simple diffusion model was used to fit the spreading behavior of SLLs. The cortical probability map shows a peak involvement frequency of 0.46 observed in the left temporo-occipital lobe. Distribution of SLLs showed no bias between left and right hemisphere. Then we identified 8 independent cortical components of SLLs. The Probability Map showed a positive correlation with synaptic density map (Spearman's rho = 0.32, p < 0.001). Additionally, the Directed-Effect Coefficient exhibited a good proportional relationship with the Dilation Coefficient (y = 0.50x+0.00, r = 0.76). Analysis of structural MRI data suggests that MELAS SLLs exhibit a pattern of free spreading within regions and restricted spreading between regions on the cortex. The identified components indicate the presence of potential boundaries. We also showed that lesion spreading was often hindered in areas with sparse synaptic density.