Rescuing Nucleus Pulposus Cells from ROS Toxic Microenvironment via Mitochondria‐Targeted Carbon Dot‐Supported Prussian Blue to Alleviate Intervertebral Disc Degeneration

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(8)

Published: Jan. 15, 2024

Abstract Intervertebral disc degeneration (IVDD) is invariably accompanied by excessive accumulation of reactive oxygen species (ROS), resulting in progressive deterioration mitochondrial function and senescence nucleus pulposus cells (NPCs). Significantly, the main ROS production site non‐immune mitochondria, suggesting mitochondria a feasible therapeutic target to reverse IVDD. Triphenylphosphine (TPP), which known as mitochondrial‐tropic ligands, utilized modify carbon dot‐supported Prussian blue (CD‐PB) scavenge superfluous intro‐cellular maintain NPCs at normal redox levels. CD‐PB‐TPP can effectively escape from lysosomal phagocytosis, permitting efficient targeting. After strikingly lessening via exerting antioxidant enzyme‐like activities, such superoxide dismutase, catalase, rescues damaged senescence, catabolism, inflammatory reaction vitro. Imaging evaluation tissue morphology assessment vivo suggest that height index, mean grey values tissue, histological are significantly improved IVDD model after locally performed. In conclusion, this study demonstrates ROS‐induced dysfunction leads possesses enormous potential rescue pathological process through removal targeting supplying neoteric strategy for treatment.

Language: Английский

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Rescuing Nucleus Pulposus Cells From Senescence via Dual‐Functional Greigite Nanozyme to Alleviate Intervertebral Disc Degeneration

Advanced Science, Journal Year: 2023, Volume and Issue: 10(25)

Published: July 3, 2023

High levels of reactive oxygen species (ROS) lead to progressive deterioration mitochondrial function, resulting in tissue degeneration. In this study, ROS accumulation induced nucleus pulposus cells (NPCs) senescence is observed degenerative human and rat intervertebral disc, suggesting as a new therapeutic target reverse disc degeneration (IVDD). By targeting this, dual-functional greigite nanozyme successfully constructed, which shows the ability release abundant polysulfides presents strong superoxide dismutase catalase activities, both function scavenge maintain at physical redox level. significantly lowering level, rescues damaged IVDD models vitro vivo, NPCs from alleviated inflammatory response. Furthermore, RNA-sequencing reveals ROS-p53-p21 axis responsible for cellular senescence-induced IVDD. Activation abolishes rescued phenotype, well response nanozyme, confirms role nanozyme's conclusion, study demonstrates that ROS-induced leads holds potential process, providing novel strategy management.

Language: Английский

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Bioenergetic dysfunction in the pathogenesis of intervertebral disc degeneration

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107119 - 107119

Published: Feb. 28, 2024

Intervertebral disc (IVD) degeneration is a frequent cause of low back pain and the most common disability. Treatments for symptomatic IVD degeneration, including conservative treatments such as analgesics, physical therapy, anti-inflammatories surgeries, are aimed at alleviating neurological symptoms. However, there no effective to prevent or delay degeneration. Previous studies have identified risk factors aging, inflammation, genetic factors, mechanical overload, nutrient deprivation smoking, but metabolic dysfunction has not been highlighted. IVDs largest avascular structures in human body determine hypoxic glycolytic features nucleus pulposus (NP) cells. Accumulating evidence demonstrated that intracellular associated with comprehensive review lacking. Here, by reviewing physiological IVDs, pathological processes changes functions genes we highlight pathway intact mitochondrial function essential homeostasis. In degenerated NPs, glycolysis downregulated. Boosting HIF1α overexpression protects against Moreover, correlations between diseases diabetes, obesity their underlying molecular mechanisms discussed. Hyperglycemia diabetic leads cell senescence, senescence-associated phenotype (SASP), apoptosis catabolism extracellualr matrix IVDs. Correcting global disorders insulin GLP-1 receptor agonist administration beneficial diabetes Overall, summarized recent progress investigations on contributions provide new perspective correcting may be treating

Language: Английский

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An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain

ACS Nano, Journal Year: 2024, Volume and Issue: 18(4), P. 3053 - 3072

Published: Jan. 18, 2024

The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation reactive oxygen species (ROS) inflammation is primary pathophysiologic change in degenerative lesions. This pathological state associated with M1 macrophages, apoptosis nucleus pulposus cells (NPC), the ingrowth pain-related sensory nerves. To address discogenic pain, we developed MnO2@TMNP, nanomaterial encapsulated MnO2 nanoparticles TrkA-overexpressed macrophage cell membrane (TMNP). Consequently, this engineered showed high efficiency binding various inflammatory factors nerve growth factors, which inhibited inflammation-induced NPC apoptosis, matrix degradation, ingrowth. Furthermore, provided specific targeting to macrophages for delivery nanoparticles. effectively scavenged intracellular ROS prevented polarization. Supportively, found MnO2@TMNP promoted regeneration, leading downregulated grades rat injured model. Both mechanical thermal hyperalgesia were alleviated by was attributed reduced calcitonin gene-related peptide (CGRP) substance P expression dorsal root ganglion Glial Fibrillary Acidic Protein (GFAP) Fos Proto-Oncogene (c-FOS) signaling spinal cord. We confirmed immune microenvironment intervertebral discs progression degeneration, resulting relieved pain.

Language: Английский

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Role of oxidative stress in mitochondrial dysfunction and their implications in intervertebral disc degeneration: Mechanisms and therapeutic strategies

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 49, P. 181 - 206

Published: Oct. 16, 2024

Language: Английский

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CircSPG21 ameliorates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells and mitigates intervertebral disc degeneration through the miR-217/SIRT1 axis and mitophagy

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Language: Английский

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Interactive effects of elevated atmospheric CO2 and UV-B radiation: A multi-level study on marine diatom Skeletonema pseudocostatum

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 291, P. 117879 - 117879

Published: Feb. 1, 2025

Climate change as a result of increases in greenhouse gas emissions, such CO2, is causing significant alteration global environmental conditions, including ocean acidification (OA). Although the depletion ozone layer has reduced, penetration ultraviolet-B (UVB) radiation into oceans still remains an factor that may potentially enhance effects OA on biota. Improved understanding complex interactions between multiple stressors, UV-B and increased CO2 levels, thus important for safeguarding ecosystems developing effective conservation management strategies. A 72 h experiment was carried out to investigate combined UVB irradiance (0.5 W m-2) varying levels (350, 500, 1000 ppm) diatom Skeletonema pseudocostatum. The study aimed characterize potential at different biological organization, ROS formation, lipid peroxidation (LPO), photosynthesis, pigments, oxidative phosphorylation (OXPHOS) growth. findings indicate exposure elevated (500 alone resulted total carotenoid content growth S. pseudocostatum, but did not significantly impact photosystem efficiency, stress, OXPHOS. Sole induced inhibited photosynthesis OXPHOS processes, suppressed However, when co-exposed with synergistic impacts were observed reactive oxygen species (ROS), growth, while carotenoids reduced antagonistic manner. putative pathway proposed initial effort these stressors under future marine scenarios involving CO2.

Language: Английский

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The current insights of mitochondrial hormesis in the occurrence and treatment of bone and cartilage degeneration

Biological Research, Journal Year: 2024, Volume and Issue: 57(1)

Published: June 1, 2024

Abstract It is widely acknowledged that aging, mitochondrial dysfunction, and cellular phenotypic abnormalities are intricately associated with the degeneration of bone cartilage. Consequently, gaining a comprehensive understanding regulatory patterns governing function its underlying mechanisms holds promise for mitigating progression osteoarthritis, intervertebral disc degeneration, osteoporosis. Mitochondrial hormesis, referred to as mitohormesis, represents adaptive stress response mechanism wherein mitochondria restore homeostasis augment resistance capabilities against stimuli by generating reactive oxygen species (ROS), orchestrating unfolded protein reactions (UPRmt), inducing mitochondrial-derived peptides (MDP), instigating dynamic changes, activating mitophagy, all prompted low doses stressors. The varying nature, intensity, duration stimulus sources elicit divergent degrees responses, subsequently one or more signaling pathways initiate mitohormesis. This review focuses specifically on effector molecules networks while also scrutinizing extant dysfunction contributing cartilage through oxidative damage. Additionally, it underscores potential mechanical stimulation, intermittent dietary restrictions, hypoxic preconditioning, low-dose toxic compounds trigger thereby alleviating degeneration.

Language: Английский

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Chemical mitophagy modulators: Drug development strategies and novel regulatory mechanisms

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106835 - 106835

Published: June 20, 2023

Maintaining mitochondrial homeostasis is a potential therapeutic strategy for various diseases, including neurodegenerative cardiovascular metabolic disorders, and cancer. Selective degradation of mitochondria by autophagy (mitophagy) fundamental quality control mechanism conserved from yeast to humans. Indeed, small-molecule modulators mitophagy are valuable pharmaceutical tools that can be used dissect complex biological processes turn them into drugs. In the past few years, pharmacological regulation has shown promising efficacy in disease models. However, with increasing number chemical modulator studies, frequent methodological flaws observed, leading some studies draw unreliable or misleading conclusions. This review attempts (a) summarize molecular mechanisms mitophagy; (b) propose Mitophagy Modulator Characterization System (MMCS); (c) perform comprehensive analysis methods characterize modulators, covering publications over 20 years; (d) provide novel targets intervention mitophagy. We believe this will panorama current research on promote development safe robust introducing high standards.

Language: Английский

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Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging

Molecular Biology Reports, Journal Year: 2023, Volume and Issue: 50(10), P. 8005 - 8014

Published: Aug. 4, 2023

Language: Английский

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