Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

Cell Proliferation, Год журнала: 2023, Номер 56(9)

Опубликована: Март 13, 2023

Abstract Low back pain (LBP) is a leading cause of labour loss and disability worldwide, it also imposes severe economic burden on patients society. Among symptomatic LBP, approximately 40% caused by intervertebral disc degeneration (IDD). IDD the pathological basis many spinal degenerative diseases such as herniation stenosis. Currently, therapeutic approaches for mainly include conservative treatment surgical treatment, neither which can solve problem from root terminating process (IVD). Therefore, further exploring pathogenic mechanisms adopting targeted strategies one current research hotspots. complex pathophysiological processes IDD, oxidative stress considered main factor. The delicate balance between reactive oxygen species (ROS) antioxidants essential maintaining normal function survival IVD cells. Excessive ROS levels damage to macromolecules nucleic acids, lipids, proteins cells, affect cellular activities functions, ultimately lead cell senescence or death. This review discusses potential role in understand provides IDD.

Язык: Английский

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An integrated view of lipid metabolism in ferroptosis revisited via lipidomic analysis

Experimental & Molecular Medicine, Год журнала: 2023, Номер 55(8), С. 1620 - 1631

Опубликована: Авг. 23, 2023

Abstract Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. This process contributes to cellular and tissue damage in various human diseases, such as cardiovascular neurodegeneration, liver disease, cancer. Although polyunsaturated fatty acids (PUFAs) membrane phospholipids are preferentially oxidized, saturated/monounsaturated (SFAs/MUFAs) also influence peroxidation ferroptosis. In this review, we first explain how cells differentially synthesize SFA/MUFAs PUFAs they control acid pools via uptake β-oxidation, impacting Furthermore, discuss stored different lipids, diacyl or ether with head groups; triglycerides; cholesterols. Moreover, these released from molecules. summary, provide an integrated view the diverse dynamic metabolic processes context ferroptosis revisiting lipidomic studies. Thus, review development therapeutic strategies for ferroptosis-related diseases.

Язык: Английский

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Melatonin-Derived Carbon Dots with Free Radical Scavenging Property for Effective Periodontitis Treatment via the Nrf2/HO-1 Pathway

ACS Nano, Год журнала: 2024, Номер 18(11), С. 8307 - 8324

Опубликована: Март 4, 2024

Periodontitis is a chronic inflammatory disease closely associated with reactive oxygen species (ROS) involvement. Eliminating ROS to control the periodontal microenvironment and alleviate response could potentially serve as an efficacious therapy for periodontitis. Melatonin (MT), renowned its potent antioxidant anti-inflammatory characteristics, frequently employed scavenger in diseases. However, therapeutic efficacy of MT remains unsatisfactory due low water solubility poor bioavailability. Carbon dots have emerged promising innovative nanomaterial facile synthesis, environmental friendliness, cost. In this study, melatonin-derived carbon (MT-CDs) were successfully synthesized via hydrothermal method. The MT-CDs good biocompatibility feature excellent ROS-scavenging capacity without additional modification. vitro experiments proved that efficiently regulated intracellular ROS, which maintained mitochondrial homeostasis suppressed production mediators. Furthermore, findings from mouse model periodontitis indicated significantly inhibited deterioration alveolar bone reduced osteoclast activation inflammation, thereby contributing regeneration damaged tissue. terms mechanism, may scavenge preventing cellular damage factors by regulating nuclear factor erythroid 2-related 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. will offer vital understanding advancement secure effective platforms more biomedical applications.

Язык: Английский

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Turmeric‐Derived Nanoparticles Functionalized Aerogel Regulates Multicellular Networks to Promote Diabetic Wound Healing

Advanced Science, Год журнала: 2024, Номер 11(18)

Опубликована: Март 5, 2024

Abstract Regulation of excessive inflammation and impaired cell proliferation is crucial for healing diabetic wounds. Although plant‐to‐mammalian regulation offers effective approaches chronic wound management, the development a potent plant‐based therapeutic presents challenges. This study aims to validate efficacy turmeric‐derived nanoparticles (TDNPs) loaded with natural bioactive compounds. TDNPs can alleviate oxidative stress, promote fibroblast migration, reprogram macrophage polarization. Restoration fibroblast–macrophage communication network by stimulates cellular regeneration, in turn enhancing healing. To address are an ultralight‐weight, high swelling ratio, breathable aerogel (AG) constructed cellulose nanofibers sodium alginate backbones obtain TDNPs@AG (TAG). TAG features shape‐customized accessibility, water‐adaptable tissue adhesiveness, capacity sustained release TDNPs, exhibiting outstanding performance facilitating vivo highlights potential regenerative medicine their applicability as promising solution clinical settings.

Язык: Английский

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Multifunctional Ac@ZIF-8/AgNPs nanoplatform with pH-responsive and ROS scavenging antibacterial properties promotes infected wound healing

Chemical Engineering Journal, Год журнала: 2024, Номер 489, С. 151485 - 151485

Опубликована: Апрель 20, 2024

Язык: Английский

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The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 15, 2023

Arachidonic and adrenic acids in the membrane play key roles ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism contributes to ferroptosis resistance. A metabolic drug screen reveals darapladib, an inhibitor of Lp-PLA2, synergistically induces presence GPX4 inhibitors. We show darapladib is able enhance under lipoprotein-deficient or serum-free conditions. Furthermore, find Lp-PLA2 located cytoplasm suppresses ferroptosis, suggesting a critical role for Lp-PLA2. Lipidomic analyses treatment deletion PLA2G7, which encodes generally enriches phosphatidylethanolamine species reduces lysophosphatidylethanolamine species. Moreover, combination with PACMA31 efficiently inhibits tumour growth xenograft model. Our study suggests inhibition potential therapeutic strategy cancer treatment.

Язык: Английский

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FSP1 confers ferroptosis resistance in KEAP1 mutant non-small cell lung carcinoma in NRF2-dependent and -independent manner

Cell Death and Disease, Год журнала: 2023, Номер 14(8)

Опубликована: Авг. 26, 2023

Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted thorough investigation genomic and transcriptomic data derived from hundreds human cancer lines primary tissue samples, with particular focus on non-small lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) subsequent nuclear factor erythroid 2-related 2 (NRF2, also known NFE2L2) activation strongly associated ferroptosis NSCLC. Additionally, AIFM2 gene, which encodes suppressor (FSP1), identified gene most significantly correlated resistance, followed multiple NRF2 targets. We found inhibition alone not sufficient reduce FSP1 levels promote ferroptosis, whereas effectively sensitized KEAP1-mutant NSCLC Furthermore, combined more intensely. Our findings imply is crucial whose expression partially dependent synergistically targeting both may be promising strategy for overcoming cancer.

Язык: Английский

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Disulfiram: A novel repurposed drug for cancer therapy

Chinese Medical Journal, Год журнала: 2024, Номер 137(12), С. 1389 - 1398

Опубликована: Янв. 26, 2024

Abstract Cancer is a major global health issue. Effective therapeutic strategies can prolong patients' survival and reduce the costs of treatment. Drug repurposing, which identifies new uses for approved drugs, promising approach with advantages reducing research costs, shortening development time, increasing efficiency safety. Disulfiram (DSF), Food Administration (FDA)-approved drug used to treat chronic alcoholism, has great potential as an anticancer by targeting diverse human malignancies. Several studies show antitumor effects DSF, particularly combination DSF copper (DSF/Cu), on wide range cancers such glioblastoma (GBM), breast cancer, liver pancreatic melanoma. In this review, we summarize mechanisms DSF/Cu, including induction intracellular reactive oxygen species (ROS) various cell death signaling pathways, inhibition proteasome activity, well nuclear factor-kappa B (NF-κB) signaling. Furthermore, highlight ability DSF/Cu target cancer stem cells (CSCs), provides prevent tumor recurrence metastasis. Strikingly, inhibits several molecular targets associated resistance, therefore it becoming novel option increase sensitivity chemo-resistant radio-resistant patients. Studies may shed light its improved application clinical

Язык: Английский

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Chondrocyte-targeted exosome-mediated delivery of Nrf2 alleviates cartilaginous endplate degeneration by modulating mitochondrial fission

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 24, 2024

Abstract Background Cartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead apoptosis during CEP IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis Despite their major success in drug delivery, full potential exosomes remains untapped. Materials methods In vitro vivo models were established using lipopolysaccharide (LPS). We designed genetically engineered (CAP-Nrf2-Exos) expressing chondrocyte-affinity peptide (CAP) on surface carrying antioxidant transcription factor nuclear E2-related 2 (Nrf2). The affinity between CAP-Nrf2-Exos was evaluated internalization assays imaging assays. qRT‒PCR, Western blotting immunofluorescence performed examine expression level Nrf2 subcellular localization Drp1. Mitochondrial function measured JC-1 probe MitoSOX Red. morphology visualized MitoTracker staining transmission electron microscopy (TEM). After subendplate injection exosomes, degree IVDD validated radiologically histologically. Results found cargo delivery efficiency after packaging increased modification. facilitated chondrocyte-targeted activated endogenous defence system cells. inhibited Drp1 S616 phosphorylation translocation, thereby preventing fragmentation dysfunction. LPS-induced cell alleviated CAP-Nrf2-Exo treatment. a rat model successfully attenuated exhibited better repair capacity than natural exosomes. Conclusion Collectively, our findings showed exosome-mediated effective strategy treating degeneration. Graphic abstract delivered into cells inhibiting Drp1-mediated

Язык: Английский

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Antioxidant-Rich Functional Foods and Exercise: Unlocking Metabolic Health Through Nrf2 and Related Pathways

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1098 - 1098

Опубликована: Янв. 27, 2025

This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web Science, PsycINFO, reference lists relevant up to 20 December 2024, highlighting central role Nrf2 pathway. As a critical regulator oxidative stress adaptation, mediates benefits these interventions. presents an innovative approach understanding regulation inflammation, its potential prevention treatment various diseases, including cancer, neurodegenerative disorders, cardiovascular pulmonary diabetes, inflammatory conditions, ageing, infections such as COVID-19. novelty this study is investigate bioactive compounds found (such polyphenols, flavonoids, vitamins) exercise-induced activation combined reveals their improve insulin sensitivity lipid metabolism reduce offering promising strategy for management chronic diseases. However, there are significant gaps current research, particularly regarding mechanisms interaction between diet, physical activity, activation, well long-term different populations, those with In addition, interactions other signalling pathways, AMPK, NF-κB, PI3K/Akt, collective contributions health explored. Furthermore, novel biomarkers presented assess impact strategies, NAD+/NADH ratio, GSH markers mitochondrial health. findings provide valuable insights into how integration antioxidant-rich diet regular can by activating related pathways represent strategies disorders. Further studies needed fully understand therapeutic interventions diseases stress, disease, cancer.

Язык: Английский

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