Evaluating the Potential of Quantitative Susceptibility Mapping for Detecting Iron Deposition of Renal Fibrosis in a Rabbit Model

Journal of Magnetic Resonance Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Background As ferroptosis is a key factor in renal fibrosis (RF), iron deposition monitoring may help evaluating RF. The capability of quantitative susceptibility mapping (QSM) for detecting RF remains uncertain. Purpose To investigate the potential QSM to detect Study Type Animal model. Model Eighty New Zealand rabbits were randomly divided into control (N = 10) and 70) groups, consisting baseline, 7, 14, 21, 28 days 12 each), longitudinal subgroups. was induced via unilateral arteria stenosis. Field Strength/Sequence 3 T, with gradient echo, arterial spin labeling echo. Assessment Bilateral kidney values ( χ ) cortex CO outer medulla OM evaluated histopathology. Statistical Tests Analysis variance, Kruskal–Wallis, Spearman's correlation, area under receiver operating characteristic curve (AUC). P < 0.05 significant. Results In fibrotic kidneys, decreased at 7 ([−6.69 ± 0.98] × 10 −2 ppm) increased during 14–28 ([−1.85 2.11], [0.14 0.58], [1.99 0.60] ppm, respectively), while had opposite trend. Both significantly correlated histopathology (| r | 0.674–0.849). AUC distinguishing degrees 0.692–0.993. contralateral initially ([−6.67 0.84] then recovered baseline ([−4.81 0.89] ppm), 7–28 ([2.58 1.40], [2.25 1.83], [2.49 [2.43 1.32] respectively) higher than ([0.54 0.18] ppm). Data Conclusion Different patterns observed values, suggesting Plain Language Summary Renal (RF) common outcome most diseases, leading scarring loss function. Increasing evidence suggests that abnormal metabolism plays an important role This study used technique called measure levels Specifically, advanced exhibited concentrations, moderate strong correlations between demonstrated could accurately changes assess severity. Overall, shows promise as tool progression. Evidence Level 2 Technical Efficacy Stage

Language: Английский

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Negative air ions alleviate nicotine-induced renal damage of spontaneously hypertensive rats via inhibiting oxidative stress and TGF-β/Smad pathway

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 291, P. 117882 - 117882

Published: Feb. 1, 2025

Nicotine can lead to renal damage in hypertension patients. Negative air ions (NAIs) is a natural antioxidant. However, rare research focus on the effect of NAIs nicotine aggravated oxidative and hypertensive kidney damage. We used spontaneously rat (SHR) model investigate molecular mechanisms for nicotine-exacerbated intervention NAIs. 8-week-old male rats were injected with or nicotine+ 6 h/d 4.5 × 104 5 NAIs/cm3 1 month 3 months, continuous observation systolic blood pressure (SBP). Urine collected test injury, inflammation stress levels, tissues harvested pathology analysis further assays using RT-qPCR, Western blot, immunohistochemistry. Our results showed that exacerbated SBP damage, elevated serum levels interleukin-6 (IL-6) tumor necrosis factor-α (TNF-α) SHR. After months 1.5 mg/kg exposure, urea nitrogen (BUN) transforming growth factor beta (TGF-β1) SHR increased by 1.3 times 16.3 times, respectively. In addition, was significantly along activation TGF-β/Smad pathway promotion epithelial mesenchymal transition (EMT), key factors reflected higher expression NADPH oxidase (NOX2), α-SMA N-cadherin proteins mRNA fibronectin-1 (FN1) Twist. intervention, BUN, urinary creatinine ratio, TGF-β1, endothelin (ET-1) malondialdehyde (MDA) decreased close without we also observed EMT related down-regulated. attenuated fibrosis process through inhibiting pathway. suggest could be proposed new approach adjuvant therapy chronic disease smokers hypertension.

Language: Английский

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Ferroptosis in organ fibrosis: Mechanisms and therapeutic approaches

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 151, P. 114341 - 114341

Published: March 1, 2025

Language: Английский

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Formononetin: a review of its source, pharmacology, drug combination, toxicity, derivatives, and drug delivery systems

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

Published: March 3, 2025

Formononetin (FMN) is a common natural metabolite that can be extracted and isolated from some botanical drugs. In recent years, FMN has garnered increasing attention due to its beneficial biological activities. this paper, we systematically summarize the sources of provide comprehensive review pharmacological activities molecular mechanisms, co-administration, toxicity, derivatives, drug delivery systems in last 5 years. The study results found wide range neurological disorders, organ damage cancer, showing great potential for clinical application broad prospects. Researchers are exploring various types systems, including nanoparticle carriers, ligand modifications polymer microspheres. These advanced enhance stability FMN, prolong release time vivo , improve targeting, thereby optimizing therapeutic efficacy reducing side effects, greatly improving bioavailability. conclusion, with considerable research value, diverse make it promising candidate development medical research.

Language: Английский

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Critical Role of Ferroptosis in Viral Infection and Host Responses

Virology, Journal Year: 2025, Volume and Issue: 606, P. 110485 - 110485

Published: March 8, 2025

Language: Английский

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The Roxadustat (FG-4592) ameliorates tubulointerstitial fibrosis by promoting intact FGF23 cleavage

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 25, 2025

Abstract Background Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) represents a novel therapeutic approach for renal anemia, prevalent complication of chronic kidney disease (CKD). However, the effects HIF-PHI on functional outcomes remain poorly characterized. Here, potential FG-4592, an orally administered HIF-PHI, fibrosis were explored systematically. Methods In this study, CKD rat model was established through subtotal 5/6 nephrectomy. Rats either FG-4592 or vehicle control via oral gavage three times weekly 12 consecutive weeks. Additionally, recombinant FGF23 continuously delivered subcutaneously implanted Alzet osmotic minipumps 28 days. Results Interestingly, we found that CKD-induced anemia significantly ameliorated in rats with treatment. Meanwhile, markedly alleviated histopathological changes and tubulointerstitial (TIF) observed administration. Notably, serum levels intact (iFGF23) reduced following administration rats. This finding subsequently validated patients receiving Roxadustat therapy. Mechanistically, illustrated inhibition iFGF23-WNT5A pathway exact mechanism by which TIF. Further, also demonstrated transcriptional activation Furin enzyme molecular FG-4592-mediated iFGF23 cleavage. Conclusions attenuates TIF Furin-mediated proteolytic cleavage iFGF23. These findings provide mechanistic insights into HIF-PHI-mediated protection establish theoretical framework clinical translation.

Language: Английский

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F-box only protein 10 protects against kidney tubulointerstitial fibrosis by inhibiting ACSL4-mediated lipid peroxidation and ferroptosis

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111841 - 111841

Published: April 1, 2025

Language: Английский

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Protective effects and mechanisms of cynaroside on renal fibrosis in mice with unilateral ureteral obstruction

Redox Report, Journal Year: 2025, Volume and Issue: 30(1)

Published: May 5, 2025

Renal fibrosis is a key factor in the progression of chronic kidney disease (CKD), and current treatments remain inadequate. In this study, we investigated therapeutic effects cynaroside (Cyn), natural flavonoid, mouse model renal induced by unilateral ureteral obstruction. Cyn treatment significantly ameliorated tubular injury interstitial while improving function. Mechanistically, inhibited expression fibrosis-related proteins suppressed Smad2/3 phosphorylation. Additionally, reduced myofibroblast accumulation inhibiting epithelial-mesenchymal transition, as indicated increased E-cadherin decreased levels mesenchymal markers. also oxidative stress downregulating prooxidant enzyme NADPH oxidase 4 restoring antioxidant enzymes. Furthermore, attenuated ferroptosis regulating proteins, including acyl-CoA synthetase long-chain family member 4, transferrin receptor 1, glutathione peroxidase levels. alleviated endoplasmic reticulum stress, evidenced downregulation markers such glucose-regulated protein 78 activating transcription 6, inflammation, confirmed macrophage infiltration lower cytokine production. Overall, demonstrated broad protective against modulating ferroptosis, ER positioning it potential agent for CKD management.

Language: Английский

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Ferroptosis and renal fibrosis: mechanistic insights and emerging therapeutic targets

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: May 6, 2025

Ferroptosis is a regulated, iron-dependent form of cell death driven by lipid peroxidation and distinct from apoptosis, necroptosis, pyroptosis. Recent studies implicate ferroptosis as central contributor to the pathogenesis renal fibrosis, hallmark chronic kidney disease associated with high morbidity progression end-stage failure. This review synthesizes current evidence linking ferroptotic signaling fibrotic remodeling in kidney, focusing on iron metabolism dysregulation, glutathione peroxidase 4 (GPX4) inactivation, peroxide accumulation, ferroptosis-regulatory pathways such FSP1-CoQ10-NAD(P)H GCH1-BH4. We detail how tubular epithelial cells modulates pro-fibrotic cytokine release, macrophage recruitment, TGF-β1-driven extracellular matrix deposition. Moreover, we explore therapeutic vulnerability highlighting promising agents including chelators, GPX4 activators, anti-lipid peroxidants, exosome-based gene delivery systems. By consolidating emerging preclinical data, this provides comprehensive mechanistic framework identifies translational opportunities for targeting disease.

Language: Английский

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Mitigating Oxidative Stress and Inflammation: The Protective Role of β-lapachone in Kidney Disease

Inflammation, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 18

Published: Jan. 1, 2025

Language: Английский

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