Vitamin D receptor alleviates lipid peroxidation in diabetic nephropathy by regulating ACLY/Nrf2/Keap1 pathway DOI
Yueyi Zhou, Qin Liao, Dan Li

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(18)

Published: Sept. 20, 2024

Abstract The membrane lipid damage caused by reactive oxygen species(ROS) and various peroxides, namely peroxidation, plays an important role in the progression of diabetic nephropathy (DN).We previously reported that vitamin D receptor(VDR) active DN mice modulating autophagy disorders. However, it is unclear whether ATP‐citrate lyase (ACLY)/NF‐E2‐related factor‐2 (Nrf2)/Kelch‐like ECH‐associated protein 1 (Keap1) pathway associated with reduction peroxidation VDR model. We found mouse model, knockout significantly aggravated mitochondrial morphological DN, increased expression ACLY, promoted accumulation ROS, products Malondialdehyde(MDA) 4‐hydroxy‐2‐nonenal (4‐HNE),consumed Nrf2/Keap1 system, thus increasing peroxidation. overexpression intervention agonist paricalcitol (Pari) can reduce above damage. On other hand, cellular experiments have shown Pari elevated ACLY ROS induced advanced glycation end (AGE). partially eliminated positive effects agonist. Next, we verified transcriptional regulation through chromatin immunoprecipitation (ChIP)‐qPCR dual luciferase experiments. Moreover, AGE models, knockdown decreased production, while Nrf2 inhibitor ML385 weakened protective effect downregulation. In summary, negatively regulates transcription, thereby affecting state system regulating inhibiting kidney injury DN.

Language: Английский

Integrated multi-omics with machine learning to uncover the intricacies of kidney disease DOI Creative Commons
Xinze Liu,

Jingxuan Shi,

Yuanyuan Jiao

et al.

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(5)

Published: July 25, 2024

The development of omics technologies has driven a profound expansion in the scale biological data and increased complexity internal dimensions, prompting utilization machine learning (ML) as powerful toolkit for extracting knowledge understanding underlying patterns. Kidney disease represents one major growing global health threats with intricate pathogenic mechanisms lack precise molecular pathology-based therapeutic modalities. Accordingly, there is need advanced high-throughput approaches to capture implicit features complement current experiments statistics. This review aims delineate strategies integrating multi-omics appropriate ML methods, highlighting key clinical translational scenarios, including predicting progression risks improve medical decision-making, comprehensively mechanisms, practical applications image recognition renal digital pathology. Examining benefits challenges integration efforts expected shed light on kidney advance practice.

Language: Английский

Citations

8
Pathogenesis-directed therapy of methylphenidate-induced oxidative heart damage in rats DOI Creative Commons
İzzet Emir, Seval Bulut, Bahadır Süleyman

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

The current study aimed to investigate the protective effects of adenosine triphosphate (ATP), metyrosine, and melatonin on possible methylphenidate cardiotoxicity in rats using biochemical histopathological methods. Thirty were separated into five groups: healthy (HG), (MP), ATP + (ATMP), metyrosine (MSMP), (MLMP). (5 mg/kg) was given intraperitoneally once daily, (50 orally twice (10 daily. Methylphenidate administered daily for 1 h after ATP, melatonin. protocol repeated 30 days. Subsequently, blood samples taken from tail veins animals measure adrenaline, noradrenaline, dopamine, troponin I (TP I) creatine kinase MB (CK-MB) levels; then euthanized heart tissues extracted. Tissues analyzed malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT) histopathologically. In MP group, MDA, TP I, CK-MB levels increased (p < 0.001) tGSH, SOD, CAT decreased compared HG, histopathologic damage developed. Oxidant lower antioxidant higher ATMP, MSMP, MLMP groups group 0.001). Catecholamine measured MSMP 0.05), with lowest being melatonin, metirozin applications effective different degrees preventing changes. This may guide clinical trials prevent methylphenidate-induced myocardial injury.

Language: Английский

Citations

0
ETV5-Mediated Transcriptional Repression of DDIT4 Blocks Macrophage Pro-Inflammatory Activation in Diabetic Atherosclerosis DOI

Lili Shi,

Tingting Sun, Di Huo

et al.

Cardiovascular Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

Language: Английский

Citations

0
Study on drug-mediated protein–protein interaction in single living cells by fluorescence cross-correlation spectroscopy DOI
Wei Zhang, Xinwei Lu, Jicun Ren

et al.

The Analyst, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Drug-mediated protein–protein interaction and drug–protein form the basis of drug development pharmacological research.

Language: Английский

Citations

0
Identification of potential anti aging drugs and targets in chronic kidney disease DOI Creative Commons
Qian Zhang, Bing Bai, Liang Ran

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 3, 2025

Chronic kidney disease (CKD) is highly prevalent, incurable, and lacks effective treatments. Aging closely linked to various diseases. In this study, we combined CKD aging using bioinformatics approaches identify potential anti drugs therapeutic targets for CKD. We analyzed datasets GSE37171 GSE66494 from the GEO database, identifying 317 differentially expressed genes (DEGs). By intersecting these DEGs with related genes, identified 23 associated differential (ARDEGs). A protein-protein interaction (PPI) network was constructed STRING top 10 hub ARDEGs were Cytoscape software. Potential drugs, including Cinnamaldehyde, through ceRNA transcription factor regulatory networks, as well DGldb database. Among key in patient samples SOD2, FGF21, FOS, RELA, DDIT4, BMI1, DUSP6, LGALS3, CXCR2, CEBPB. Cinnamaldehyde other found target pathways, suggesting their delay progression modulating pathways. Finally, verified low-expression of DDIT4 two unilateral ureteral obstruction (UUO) animal model. Additionally, shown reduce expression fibrosis markers such fibronectin (FN) α-smooth muscle actin (α-SMA) HK2 cells under TGF-β1 stimulation. This study provides a foundational understanding molecular offers new directions developing therapies treat

Language: Английский

Citations

0
Vitamin D receptor alleviates lipid peroxidation in diabetic nephropathy by regulating ACLY/Nrf2/Keap1 pathway DOI
Yueyi Zhou, Qin Liao, Dan Li

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(18)

Published: Sept. 20, 2024

Abstract The membrane lipid damage caused by reactive oxygen species(ROS) and various peroxides, namely peroxidation, plays an important role in the progression of diabetic nephropathy (DN).We previously reported that vitamin D receptor(VDR) active DN mice modulating autophagy disorders. However, it is unclear whether ATP‐citrate lyase (ACLY)/NF‐E2‐related factor‐2 (Nrf2)/Kelch‐like ECH‐associated protein 1 (Keap1) pathway associated with reduction peroxidation VDR model. We found mouse model, knockout significantly aggravated mitochondrial morphological DN, increased expression ACLY, promoted accumulation ROS, products Malondialdehyde(MDA) 4‐hydroxy‐2‐nonenal (4‐HNE),consumed Nrf2/Keap1 system, thus increasing peroxidation. overexpression intervention agonist paricalcitol (Pari) can reduce above damage. On other hand, cellular experiments have shown Pari elevated ACLY ROS induced advanced glycation end (AGE). partially eliminated positive effects agonist. Next, we verified transcriptional regulation through chromatin immunoprecipitation (ChIP)‐qPCR dual luciferase experiments. Moreover, AGE models, knockdown decreased production, while Nrf2 inhibitor ML385 weakened protective effect downregulation. In summary, negatively regulates transcription, thereby affecting state system regulating inhibiting kidney injury DN.

Language: Английский

Citations

1