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1.
Eur J Pharmacol ; 971: 176528, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38556118

ABSTRACT

Hyperuricemic nephropathy (HN) is characterized by renal fibrosis and tubular necrosis caused by elevated uric acid levels. Ferroptosis, an iron-dependent type of cell death, has been implicated in the pathogenesis of kidney diseases. The objective of this study was to explore the role of ferroptosis in HN and the impact of a ferroptosis inhibitor, ferrostatin-1 (Fer-1). The study combined adenine and potassium oxonate administration to establish a HN model in mice and treated HK-2 cells with uric acid to simulate HN conditions. The effects of Fer-1 on the renal function, fibrosis, and ferroptosis-associated molecules were investigated in HN mice and HK-2 cells treated with uric acid. The HN mice presented with renal dysfunction characterized by elevated tissue iron levels and diminished antioxidant capacity. There was a significant decrease in the mRNA and protein expression levels of SLC7A11, GPX4, FTL-1 and FTH-1 in HN mice. Conversely, treatment with Fer-1 reduced serum uric acid, serum creatinine, and blood urea nitrogen, while increasing uric acid levels in urine. Fer-1 administration also ameliorated renal tubule dilatation and reduced renal collagen deposition. Additionally, Fer-1 also upregulated the expression levels of SLC7A11, GPX4, FTL-1, and FTH-1, decreased malondialdehyde and iron levels, and enhanced glutathione in vivo and in vitro. Furthermore, we first found that Fer-1 exhibited a dose-dependent inhibition of URAT1, with the IC50 value of 7.37 ± 0.66 µM. Collectively, the current study demonstrated that Fer-1 effectively mitigated HN by suppressing ferroptosis, highlighting the potential of targeting ferroptosis as a therapeutic strategy for HN.


Subject(s)
Cyclohexylamines , Ferroptosis , Hyperuricemia , Kidney Diseases , Phenylenediamines , Mice , Animals , Uric Acid , Hyperuricemia/drug therapy , Hyperuricemia/metabolism , Kidney Diseases/drug therapy , Fibrosis , Iron
2.
IEEE Trans Image Process ; 30: 4637-4652, 2021.
Article in English | MEDLINE | ID: mdl-33886471

ABSTRACT

Due to the delay in the row-wise exposure and the lack of stable support when a photographer holds a CMOS camera, video jitter and rolling shutter distortion are closely coupled degradations in the captured videos. However, previous methods have rarely considered both phenomena and usually treat them separately, with stabilization approaches that are unable to handle the rolling shutter effect and rolling shutter removal algorithms that are incapable of addressing motion shake. To tackle this problem, we propose a novel method that simultaneously stabilizes and rectifies a rolling shutter shaky video. The key issue is to estimate both inter-frame motion and intra-frame motion. Specifically, for each pair of adjacent frames, we first estimate a set of spatially variant inter-frame motions using a neighbor-motion-aware local motion model, where the classical mesh-based model is improved by introducing a new constraint to enhance the neighbor motion consistency. Then, different from other 2D rolling shutter removal methods that assume the pixels in the same row have a single intra-frame motion, we build a novel mesh-based intra-frame motion calculation model to cope with the depth variation in a mesh row and obtain more faithful estimation results. Finally, temporal and spatial motion constraints and an adaptive weight assignment strategy are considered together to generate the optimal warping transformations for different motion situations. Experimental results demonstrate the effectiveness and superiority of the proposed method when compared with other state-of-the-art methods.

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