Exploring the subtle and novel renal pathological changes in diabetic nephropathy using clustering analysis with deep learning

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

Published: Jan. 15, 2025

To decrease the number of chronic kidney disease (CKD), early diagnosis diabetic is required. We performed invariant information clustering (IIC)-based on glomerular images obtained from nephrectomized kidneys patients with and without diabetes. also used visualizing techniques (gradient-weighted class activation mapping (Grad-CAM) generative adversarial networks (GAN)) to identify novel pathological changes light microscopy in nephropathy. Overall, 13,251 (7,799 diabetes cases 5,542 non-diabetes cases) 45 Kanazawa Medical University were clustered into 10 clusters by IIC. Diabetic that mainly contained (Clusters 0, 1, 2) non-diabetic 8 9) distinguished t-distributed stochastic neighbor embedding (t-SNE) analysis. Grad-CAM demonstrated outer portions capillaries had characteristic lesions. Cycle-GAN showed compared Bowman's space, smaller tufts was a lesion clusters. These findings might be subtle

Language: Английский

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Nrf2 alleviates acute ischemic stroke induced ferroptosis via regulating xCT/GPX4 pathway

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 231, P. 153 - 162

Published: Feb. 27, 2025

Language: Английский

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Crosstalk between ferroptosis and innate immune in diabetic kidney disease: mechanisms and therapeutic implications

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Diabetic kidney disease (DKD) is a prevalent complication of diabetes mellitus (DM), and its incidence increasing alongside the number cases. Effective treatment long-term management DKD present significant challenges; thus, deeper understanding pathogenesis essential to address this issue. Chronic inflammation abnormal cell death in closely associate with development. Recently, there has been considerable attention focused on immune infiltration into renal tissues inflammatory response’s role progression. Concurrently, ferroptosis—a novel form death—has emerged as critical factor pathogenesis, leading increased glomerular filtration permeability, proteinuria, tubular injury, interstitial fibrosis, other pathological processes. The cardiorenal benefits SGLT2 inhibitors (SGLT2-i) patients have demonstrated through numerous large clinical trials. Moreover, further exploratory experiments indicate these drugs may ameliorate serum urinary markers inflammation, such TNF-α, inhibit ferroptosis models. Consequently, investigating interplay between innate responses for guiding future drug This review presents an overview within context DKD, beginning core mechanisms delving potential roles We will also analyze how aberrant cells, molecules, signaling pathways contribute Finally, we discuss interactions responses, well targeted therapeutic agents, based current evidence. By analyzing immunity aim provide insights development area.

Language: Английский

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Bardoxolone methyl improves survival and reduces clinical measures of kidney injury in tumor-bearing mice treated with cisplatin

AAPS Open, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 3, 2025

Abstract Objective Acute kidney injury (AKI) occurs in approximately one-third of patients treated with cisplatin and there is an outstanding need for mitigation strategies to decrease the frequency severity cisplatin-induced AKI. This study evaluated bardoxolone methyl (BARD) as a nephroprotectant multidose, tumor-bearing mouse model BARD attractive therapeutic intervention due its ability protect against nephrotoxicity by activating Nrf2 previous reports suggesting anti-tumorigenic effects. Methods In this study, CMT167 mice were four weekly doses or without survival, tumor growth, clinical histological measures Kidney and/or function quantification urinary molecule-1 (KIM-1) serum creatinine (SCr) levels well histopathology. Results Compared receiving alone, co-treatment significantly enhanced survival ( p = 0.01). Moreover, prevented elevation KIM-1 concentrations early one week after treatment < 0.01) – response that was observed throughout 4-week period. Cisplatin increased SCr weeks, which co-administration decreased burden compared vehicle-treated 0.05 two doses) not altered co-treatment. Conclusions Overall, results demonstrate has potential improve reduce cisplatin, it could be used mitigate

Language: Английский

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Multi-Omic Analysis Reveals Genetic Determinants and Therapeutic Targets of Chronic Kidney Disease and Kidney Function

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6033 - 6033

Published: May 30, 2024

Chronic kidney disease (CKD) presents a significant global health challenge, characterized by complex pathophysiology. This study utilized multi-omic approach, integrating genomic data from the CKDGen consortium alongside transcriptomic, metabolomic, and proteomic to elucidate genetic underpinnings identify therapeutic targets for CKD function. We employed range of analytical methods including cross-tissue transcriptome-wide association studies (TWASs), Mendelian randomization (MR), summary-based MR (SMR), molecular docking. These analyses collectively identified 146 associations with Key Golgi apparatus-related genes (GARGs) 41 potential drug were highlighted, MAP3K11 emerging as gene TWAS data, underscoring its target. Capsaicin displayed promising drug–target interactions in docking analyses. Additionally, metabolome- proteome-wide (PWMR) revealed 33 unique metabolites critical inflammatory proteins such FGF5 that are significantly linked colocalized insights deepen our understanding pathogenesis highlight novel treatment prevention.

Language: Английский

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PDK4-mediated Nrf2 inactivation contributes to oxidative stress and diabetic kidney injury

Cellular Signalling, Journal Year: 2024, Volume and Issue: 121, P. 111282 - 111282

Published: July 5, 2024

Language: Английский

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Oxidative Stress in Renal Health

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 144 - 144

Published: Jan. 26, 2025

Oxidative stress is caused by the increase in reactive oxygen species (ROS) and nitrogen (RNS) inside cells [...]

Language: Английский

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Di-Dang-Tang suppresses ferroptosis in the hippocampal CA1 region by targeting PGK1/NRF2/GPX4 signaling pathway to exert neuroprotection in vascular dementia

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114233 - 114233

Published: Feb. 12, 2025

Language: Английский

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Health position paper and redox perspectives – Bench to Bedside Transition for Pharmacological Regulation of NRF2 in Noncommunicable Diseases

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103569 - 103569

Published: March 1, 2025

Nuclear factor erythroid 2-related 2 (NRF2) is a redox-activated transcription regulating cellular defense against oxidative stress, thereby playing pivotal role in maintaining homeostasis. Its dysregulation implicated the progression of wide array human diseases, making NRF2 compelling target for therapeutic interventions. However, challenges persist drug discovery and safe targeting NRF2, as unresolved questions remain especially regarding its context-specific diseases off-target effects. This comprehensive review discusses dualistic disease pathophysiology, covering protective and/or destructive roles autoimmune, respiratory, cardiovascular, metabolic well digestive system cancer. Additionally, we also development drugs that either activate or inhibit discuss main barriers translating NRF2-based therapies from bench to bedside, consider ways monitor activation vivo.

Language: Английский

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Keap1-independent Nrf2 regulation: a novel therapeutic target for treating kidney disease

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103593 - 103593

Published: March 12, 2025

Language: Английский

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