Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 353 - 353

Published: Feb. 2, 2024

Ischemia reperfusion (I/R) is a common pathological process which occurs mostly in organs like the heart, brain, kidney, and lung. The injury caused by I/R gradually becomes one of main causes fatal diseases, an urgent clinical problem to be solved. Although great progress has been made therapeutic methods, including surgical, drug, gene therapy, transplant therapy for injury, development effective methods cure remains worldwide challenge. In recent years, exosomes have attracted much attention their important roles immune response, antigen presentation, cell migration, differentiation, tumor invasion. Meanwhile, shown potential treatment organs. study exosome-mediated signaling pathway can not only help reveal mechanism behind promoting recovery, but also provide theoretical basis application exosomes. Here, we review research utilizing various from different types promote healing focusing on classical pathways such as PI3K/Akt, NF-κB, Nrf2, PTEN, Wnt, MAPK, toll-like receptor, AMPK. results suggest that regulate these reduce oxidative stress, responses, decrease expression inflammatory cytokines, tissue repair, making competitive emerging vector treating damage

Language: Английский

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miR-208a-3p regulated by circUQCRC2 suppresses ischemia/reperfusion-induced acute kidney injury by inhibiting CELF2-mediated tubular epithelial cell apoptosis, inflammation and ferroptosis

Shock, Journal Year: 2024, Volume and Issue: 61(6), P. 942 - 950

Published: April 26, 2024

ABSTRACT Background : Acute kidney injury (AKI) is a prevalent clinical syndrome with persistent dysfunction. Renal ischemia/reperfusion (I/R) major cause of AKI. miR-208a-3p overexpression attenuated myocardial I/R injury. This study aims to investigate the role and mechanism in I/R-induced Methods AKI models were established using hypoxia/reoxygenation (H/R)-exposed tubule epithelial cell HK-2 mice. The function investigated by gain- or loss-of-function methods real-time PCR, CCK-8, flow cytometry, ELISA, western blot, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, detection Fe 2+ , reactive oxygen species, blood urea nitrogen creatinine, luciferase reporter assay. Results expression was suppressed, while CELF2 circular RNA ubiquinol-cytochrome c reductase core protein 2 (circUQCRC2) increased both models. upregulation circUQCRC2 silencing viability, decreased levels proinflammatory cytokines (TNF-α, IL-1β, IL-6), reduced apoptosis contents elevated GPX4 SLC7A11, ACSL4 H/R-stimulated cells. In addition, improved alleviating renal injury, apoptosis, inflammation, ferroptosis mouse model. target gene miR-208a-3p, which negatively modulated circUQCRC2. Overexpression blocked on H/R-treated Moreover, effects downregulation H/R-injured cells also reversed inhibitor. Conclusions regulated could attenuate inhibiting CELF2-mediated tubular inflammation ferroptosis. provides potential therapeutic targets for

Language: Английский

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Circadian Clock Gene Bmal1: A Molecular Bridge from AKI to CKD

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 77 - 77

Published: Jan. 7, 2025

Acute kidney injury (AKI) and chronic disease (CKD) represent two frequently observed clinical conditions. AKI is characterized by an abrupt decrease in glomerular filtration rate (GFR), generally associated with elevated serum creatinine (sCr), blood urea nitrogen (BUN), electrolyte imbalances. This condition usually persists for approximately a week, causing transient reduction function. If these abnormalities continue beyond 90 days, the redefined as or may advance to end-stage renal (ESRD). Recent research increasingly indicates that maladaptive repair mechanisms after significantly contribute development of CKD. Thus, implementing early interventions halt progression from CKD has potential markedly improve patient outcomes. Although considerable been conducted, exact linking are complex, effective treatments remain limited. Kidney function influenced circadian rhythms, gene Bmal1 being vital managing cycles. involved both In this study, we conducted retrospective analysis Bmal1's role CKD, reviewed recent advancements, investigated how influences pathological underlying Additionally, highlighted gaps existing examined therapeutic target management. work aims provide meaningful insights future studies on transition goal identifying approaches mitigate progression.

Language: Английский

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Integration of transcriptome and Mendelian randomization analyses in exploring the extracellular vesicle-related biomarkers of diabetic kidney disease

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

Published: Feb. 17, 2025

Background Diabetic Kidney Disease (DKD) is a common complication in patients with diabetes, and its pathogenesis remains incompletely understood. Recent studies have suggested that extracellular vesicles (EVs) may play significant role the initiation progression of DKD. This study aimed to identify biomarkers associated EVs DKD through bioinformatics Mendelian randomization (MR) analysis.

Language: Английский

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Is High-Dose Ubiquinone Therapy Before Cardiac Surgery Enough to Reduce the Incidence of Cardiac Surgery-Associated Acute Kidney Injury? A Randomized Controlled Trial

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 243 - 243

Published: Feb. 19, 2025

Cardiac surgery-related acute kidney injury (CS-AKI) is a decrease in function after open-heart surgery, affecting up to 50% of patients. The pathophysiology CS-AKI involves ischemia-reperfusion injury, inflammation, and oxidative stress. Ubiquinone potent antioxidant, we hypothesized that it could both the incidence severity CS-AKI. intervention group received ubiquinone (8 mg/kg/day) divided into three daily doses, while control placebo. primary outcome was CS-AKI, which manifested as an increase creatinine ≥26.5 µmol/L or urine output below 0.5 mL/kg/h for 6 h. Out 73 patients, 39.7% (N = 29) developed including 35.3% 43.6% placebo (X2(1,N 73) 0.4931, p 0.4825). secondary outcomes revealed experienced reduced postoperative bleeding, with median (IQR) drainage 320 mL (230-415) compared 420 (242.5-747.5) (t(35.84) 2.055, 0.047). hs-TnI level 239.5 ng/mL (113.25-382.75) surgery 366 (234.5-672.5) (p 0.024). In conclusion, there no significant difference between groups. Postoperative bleeding were significantly among patients receiving ubiquinone.

Language: Английский

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Acute kidney injury and energy metabolism

Clinica Chimica Acta, Journal Year: 2025, Volume and Issue: 570, P. 120208 - 120208

Published: Feb. 20, 2025

Language: Английский

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Role of peroxisomes in the pathogenesis and therapy of renal fibrosis

Metabolism, Journal Year: 2025, Volume and Issue: 166, P. 156173 - 156173

Published: Feb. 22, 2025

Language: Английский

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Mitigating Remote Organ-Induced Brain Injury in Renal Ischemia-Reperfusion: The Role of Oleuropein in Inhibiting Oxidative Stress, Inflammation, Ferroptosis, and Apoptosis in Male Rats

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 8, 2025

Language: Английский

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Engineered ATP-Loaded Extracellular Vesicles Derived from Mesenchymal Stromal Cells: A Novel Strategy to Counteract Cell ATP Depletion in an In Vitro Model

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3424 - 3424

Published: April 5, 2025

The use of adenosine triphosphate (ATP) has shown promising effects in alleviating ischemic damage across various tissues. However, the penetration ATP into kidney tubular cells presents a challenge due to their unique anatomical and physiological properties. In this study, we introduce novel bioinspired drug delivery system utilizing extracellular vesicles (EVs) derived from mesenchymal stromal (MSCs) engineered carry ATP. ATP-loaded liposomes (ATP-LPs) EVs (ATP-EVs) were prepared using microfluidic technology, followed by characterization morphology (DLS, NTA, SEM, TEM), content, release rate at 37 °C (pH 7.4). Additionally, efficacy ATP-LPs ATP-EVs was evaluated vitro on renal (HK2 cells) under chemically induced ischemia. results indicated successful enrichment EVs, with showing no significant changes or size compared naïve EVs. Notably, demonstrated superior retention ATP-LPs, protecting degradation environment. an ATP-depleted HK2 cell model, only effectively restored levels, preserving viability reducing apoptotic gene expression (BCL2-BAX). This study is first successfully demonstrate direct as carriers.

Language: Английский

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Sodium aescinate protects renal ischemia-reperfusion and pyroptosis through AKT/NLRP3 signaling pathway

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

Published: April 22, 2025

Renal ischemia-reperfusion injury (RIRI) is a common cause of acute renal injury. Studies have shown that sodium aescinate (SA) may serve as potential therapeutic agent, although its exact mechanism remains unclear. This study first evaluated the efficacy SA using mouse model. Subsequently, was elucidated through systematic bioinformatics, and finally validated in vitro vivo experiments. The results demonstrated has protective effect on function mice with RIRI. Bioinformatic analysis indicated pyroptosis pathway significantly activated during injury, immunohistochemistry showed level upregulated Administration able to reduce expression pyroptosis-related proteins (GSDMD, NLRP3, IL-1β) In experiments further confirmed exerts an anti-pyroptotic by inhibiting AKT/NLRP3 signaling pathway. Ultimately, mitigates kidney IRI suppressing failure inhibition

Language: Английский

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