Cartilage Endplate‐Targeted Engineered Exosome Releasing and Acid Neutralizing Hydrogel Reverses Intervertebral Disc Degeneration

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 14(2)

Published: Nov. 18, 2024

Abstract Cartilage endplate cell (CEPC) and nucleus pulposus (NPC) inflammation are critical factors that contribute to intervertebral disc degeneration (IVDD). Recent evidence indicated iron ion influx, reactive oxygen species (ROS), the cGAS‐STING pathway involved in CEPC inflammatory degeneration. Moreover, cytokines produced by degenerating CEPCs lactic acid accumulation within microenvironment significantly NPC inflammation. Consequently, simultaneous alleviation of correction acidic anticipated reverse IVDD. Herein, CEPC‐targeted engineered exosomes loaded with salvianolic A incorporated into a CaCO 3 /chitosan hydrogel, forming composite gel, CAP‐sEXOs@Gel. Notably, CAP‐sEXOs@Gel shows long local retention, realizes slow release CAP‐sEXOs specific uptake CEPCs. After CEPCs, reduce intracellular ROS inhibiting hypoxia‐inducible factor‐2α (HIF‐2α)/TfR1 expression. Iron influx inhibition maintenance normal mitochondrial function reduced mtDNA leakage, suppresing pathway. Additionally, component neutralizes H + , thereby alleviating Collectively, this novel hydrogel demonstrates ability concurrently inhibit inflammation, presenting promising therapeutic approach for

Language: Английский

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The main molecular mechanisms of ferroptosis and its role in chronic kidney disease

Cellular Signalling, Journal Year: 2024, Volume and Issue: 121, P. 111256 - 111256

Published: June 13, 2024

The term ferroptosis, coined in 2012, has been widely applied various disease research fields. Ferroptosis is a newly regulated form of cell death distinct from apoptosis, necrosis, and autophagy, the mechanisms which have extensively studied. Chronic kidney disease, characterized by renal dysfunction, common severely affecting human health, with its occurrence development influenced multiple factors leading to dysfunction systems. It often lacks obvious clinical symptoms early stages, thus, diagnosis typically made later complicating treatment. While on ferroptosis acute injury continuous progress, studies association between chronic remain limited. This review aims summarize investigate mechanism regulation attempt elucidate role disease.

Language: Английский

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Advances in the study of key cells and signaling pathways in renal fibrosis and the interventional role of Chinese medicines

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 2, 2024

Renal fibrosis (RF) is a pathological process characterized by the excessive accumulation of extracellular matrix (ECM), which triggers repair cascade in response to stimuli and pathogenic factors, leading activation molecular signaling pathways involved fibrosis. This article discusses key cells, molecules, implicated pathogenesis RF, with particular focus on tubular epithelial cells (TECs), cellular senescence, ferroptosis, autophagy, epithelial-mesenchymal transition (EMT), transforming growth factor-β(TGF-β)/Smad signaling. These factors drive core regulatory that significantly influence RF. A comprehensive understanding their roles essential. Through literature review, we explore recent advancements traditional Chinese medicine (TCM) aimed at reducing RF inhibiting chronic kidney disease (CKD). We summarize, analyze, elaborate important role herbs aiming provide new directions for application prevention treatment, as well scientific guidance clinical practices.

Language: Английский

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SALVIANOLIC ACID A ATTENUATES ANGIOTENSIN II-INDUCED CARDIAC FIBROSIS THROUGH REGULATING THE TXNIP SIGNALING PATHWAY

Shock, Journal Year: 2024, Volume and Issue: 61(5), P. 748 - 757

Published: April 15, 2024

ABSTRACT Cardiac fibrosis, characterized by excessive collagen accumulation in heart tissues, poses a significant clinical challenge various diseases and complications. Although salvianolic acid A (Sal A) from Danshen ( Salvia miltiorrhiza ) has shown promise the treatment of ischemic disease, myocardial infarction, atherosclerosis, its effects on cardiac fibrosis remain unexplored. Our study investigated efficacy Sal reducing elucidated underlying molecular mechanisms. We observed that demonstrated cardioprotective against Angiotensin II (Ang II)-induced remodeling showing dose-dependent reduction mice suppression fibroblast proliferation fibrotic protein expression vitro . RNA sequencing revealed counteracted Ang II-induced upregulation Txnip, subsequent experiments indicated it acts through inflammasome ROS pathways. These findings establish antifibrotic A, notably attenuated Txnip overexpression, highlight role modulating inflammation oxidative stress This underscores importance further research similar compounds, especially regarding their stress, which are key factors cardiovascular diseases.

Language: Английский

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Integration of proteomics and metabolomics analysis investigate mechanism of As-induced immune injury in rat spleen

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 284, P. 116913 - 116913

Published: Aug. 28, 2024

Arsenic (As) is a widespread metalloid and human carcinogen found in the natural environment, multiple toxic effects have been shown to be associated with As exposure. can accumulated spleen, largest peripheral lymphatic organ, long-term exposure lead splenic injury. In this study, Sprague-Dawley (SD) rat model of As-poisoned was established, aiming explore molecular mechanism As-induced immune injury through combined analysis proteomics metabolomics rats' spleen. After feeding rats diet (50 mg/kg) for 90 days, spleen tissue group damaged, level significantly higher than that control (P < 0.001), inflammatory cytokine interleukin-6 (IL-6) decreased 0.01). Proteomics results showed total 134 differentially expressed proteins (DEPs) 0.05 fold change > 1.2) 182 metabolites (DEMs) (VIP >1 P 0.05) were identified spleens poisoned compared (As/Ctrl). The proteomic highlight role hypoxia-inducible factors (HIF), killer cell mediated cytotoxicity, ribosomes. major pathways metabolic disruption included arachidonic acid (AA) metabolism, glycerophospholipid metabolism folate single-carbon pool. integrated these two omics suggested Hmox1, Stat3, acid, phosphatidylcholine leukotriene B4 may play key roles by indicate cause damage rats. Through metabolomic analysis, their mechanisms obtained, which provided basis further understanding caused

Language: Английский

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Comprehensive review of perioperative factors influencing ferroptosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117375 - 117375

Published: Sept. 14, 2024

Language: Английский

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Emerging roles of N6-methyladenosine in arsenic-induced toxicity

Heliyon, Journal Year: 2024, Volume and Issue: 10(22), P. e40473 - e40473

Published: Nov. 1, 2024

Arsenic can cause extensive toxic damage after entering the body of humans and animals by altering a variety events. As most common form methylation modification RNA in eukaryotic cells, N

Language: Английский

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