A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Feb. 29, 2024

Abstract Diabetic osteoporosis (DOP) is a significant complication that poses continuous threat to the bone health of patients with diabetes; however, currently, there are no effective treatment strategies. In diabetes, increased levels ferroptosis affect osteogenic commitment and differentiation mesenchymal stem cells (BMSCs), leading skeletal changes. To address this issue, we aimed target propose novel therapeutic approach for DOP. We synthesized ferroptosis-suppressing nanoparticles, which could deliver curcumin, natural compound, marrow using tetrahedral framework nucleic acid (tFNA). This delivery system demonstrated excellent curcumin bioavailability stability, as well synergistic properties tFNA. Both in vitro vivo experiments revealed nanoparticles enhance mitochondrial function by activating nuclear factor E2-related 2 (NRF2)/glutathione peroxidase 4 (GPX4) pathway, inhibiting ferroptosis, promoting BMSCs diabetic microenvironment, reducing trabecular loss, increasing formation. These findings suggest curcumin-containing DNA tetrahedron-based have promising potential DOP other ferroptosis-related diseases.

Language: Английский

---

Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

---

Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(3), P. 579 - 615

Published: Jan. 24, 2024

Abstract This article provides an overview of the background knowledge ferroptosis in nervous system, as well key role nuclear factor E2-related 2 (Nrf2) regulating ferroptosis. The takes Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), and amyotrophic lateral sclerosis (ALS) starting point to explore close association between Nrf2 ferroptosis, which is clear significant importance for understanding mechanism neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links pathogenesis NDs. As progresses, damage antioxidant excessive OS, altered expression levels, especially inhibition by lipid peroxidation inhibitors adaptive enhancement signaling, demonstrate potential clinical significance detecting identifying targeted therapy neuronal loss mitochondrial dysfunction. These findings provide new insights possibilities treatment prevention

Language: Английский

---

Inhalation exposure to polystyrene nanoplastics induces chronic obstructive pulmonary disease-like lung injury in mice through multi-dimensional assessment

Environmental Pollution, Journal Year: 2024, Volume and Issue: 347, P. 123633 - 123633

Published: Feb. 27, 2024

Language: Английский

---

Ferritinophagy Mediated by Oxidative Stress-Driven Mitochondrial Damage Is Involved in the Polystyrene Nanoparticles-Induced Ferroptosis of Lung Injury

ACS Nano, Journal Year: 2023, Volume and Issue: 17(24), P. 24988 - 25004

Published: Dec. 12, 2023

Nanoplastics are a common type of contaminant in the air. However, no investigations have focused on toxic mechanism lung injury induced by nanoplastic exposure. In present study, polystyrene nanoplastics (PS-NPs) caused ferroptosis epithelial cells, which could be alleviated ferrostatin-1, deferoxamine, and N-acetylcysteine. Further investigation found that PS-NPs disturbed mitochondrial structure function triggered autophagy. Mechanistically, oxidative stress-derived damage contributed to ferroptosis, autophagy-dependent ferritinophagy was pivotal intermediate link, resulting ferritin degradation iron ion release. Furthermore, inhibition using ferrostatin-1 pulmonary systemic toxicity reverse mouse inhalation. Most importantly, lung-on-a-chip further used clarify role PS-NPs-induced visualizing stress, alveolar-capillary barrier dysfunction at organ level. summary, our study indicated an important for nanoplastics-induced through different inhalation models, three-dimensional-based lung-on-a-chip, providing insightful reference assessment nanoplastics.

Language: Английский

---

Inhibiting the compensatory elevation of xCT collaborates with disulfiram/copper-induced GSH consumption for cascade ferroptosis and cuproptosis

Redox Biology, Journal Year: 2023, Volume and Issue: 69, P. 103007 - 103007

Published: Dec. 19, 2023

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors and fourth leading cause cancer-related death globally, which characterized by complicated pathophysiology, high recurrence rate, poor prognosis. Our previous study has demonstrated that disulfiram (DSF)/Cu could be repurposed for treatment HCC inducing ferroptosis. However, effectiveness DSF/Cu may compromised compensatory mechanisms weaken its sensitivity. The underlying these responses are currently unknown. Herein, we found induces endoplasmic reticulum stress with disrupted ER structures, increased Ca2+ level activated expression ATF4. Further studies verified both ferroptosis cuproptosis, accompanied depletion GSH, elevation lipid peroxides, increase xCT. Comparing it interesting to note GSH acts at crossing point regulation network therefore, hypothesized xCT a key aspect therapeutic target. Mechanically, knockdown ATF4 facilitated DSF/Cu-induced cell exacerbated generation peroxides under challenge DSF/Cu. was unable block reduction. Notably, induced accumulation ubiquitinated proteins, promoted half-life protein, dramatically dampened ubiquitination–proteasome mediated degradation Moreover, pharmacologically genetically suppressing death. In conclusion, current work provides an in-depth mechanism describes framework further understanding crosstalk between cuproptosis. Inhibiting renders cells more susceptible DSF/Cu, provide promising synergistic strategy sensitize tumor therapy overcome drug resistance, as activates different programmed

Language: Английский

---

Supramolecular self-assembly of EGCG-selenomethionine nanodrug for treating osteoarthritis

Bioactive Materials, Journal Year: 2023, Volume and Issue: 32, P. 164 - 176

Published: Oct. 9, 2023

Osteoarthritis (OA) has emerged as a significant health concern among the elderly population, with increasing attention paid to ferroptosis-induced OA in recent years. However, prolonged use of nonsteroidal anti-inflammatory drugs or corticosteroids can lead series side effects and limited therapeutic efficacy. This study aimed employ Mannich condensation reaction between epigallocatechin-3-gallate (EGCG) selenomethionine (SeMet) efficiently synthesize polyphenol-based nanodrugs aqueous media for treating OA. Molecular biology experiments demonstrated that EGCG-based (ES NDs) could effectively reduce glutathione peroxidase 4 (GPX4) inactivation, abnormal Fe2+ accumulation, lipid peroxidation induced by oxidative stress, which ameliorated metabolic disorder chondrocytes other multiple pathological processes triggered ferroptosis. Moreover, imaging histopathological analysis destabilization medial meniscus model mice confirmed ES NDs exhibiting relieving The intra-articular delivery represents promising approach joint inflammatory diseases.

Language: Английский

---

P21 resists ferroptosis in osteoarthritic chondrocytes by regulating GPX4 protein stability

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 212, P. 336 - 348

Published: Jan. 2, 2024

Ferroptosis is involved in the pathogenesis of osteoarthritis (OA) while suppression chondrocyte ferroptosis has a beneficial effect on OA. However, molecular mechanism OA remains to be elucidated. P21, an indicator aging, been reported inhibit ferroptosis, but relationship between P21 and unclear. Here, we aimed investigate expression function chondrocytes, involvement regulation chondrocytes. First, demonstrated that high was observed cartilage from patients destabilized medial meniscus (DMM) mice, osteoarthritic chondrocytes induced by IL-1β, FAC erastin. knockdown exacerbated reduction Col2a1 promoted upregulation MMP13 Meanwhile, degradation DMM-induced mouse models decreased GPX4 vivo. Furthermore, sensitized erastin, which closely associated with accumulation lipid peroxides. In mechanism, regulated stability protein, independent NRF2. found significantly affected recruitment linear ubiquitin chain assembly complex (LUBAC) level M1-linked ubiquitination GPX4. Overall, our results suggest plays essential anti-ferroptosis role regulating

Language: Английский

---

Zooming in and Out of Programmed Cell Death in Osteoarthritis: A Scientometric and Visualized Analysis

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 2479 - 2498

Published: April 1, 2024

During the past decade, mounting evidence has increasingly linked programmed cell death (PCD) to progression and development of osteoarthritis (OA).There is a significant need for thorough scientometric analysis that recapitulates relationship between PCD OA.This study aimed collect articles reviews focusing on in OA, extracting data from January 1st, 2013, October 31st, 2023, using Web Science.Various tools, including VOSviewer, CiteSpace, Pajek, Scimago Graphica, R package, were employed visualization analyses.Notably, China, USA, South Korea emerged as major contributors, collectively responsible more than 85% published papers significantly influencing research this field.Among different institutions, Shanghai Jiao Tong University, Xi'an Zhejiang University exhibited highest productivity.Prolific authors included Wang Wei, Jing, Zhang Li

Language: Английский

---

Targeting ferroptosis unveils a new era for traditional Chinese medicine: a scientific metrology study

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

Published: Feb. 14, 2024

In the past 11 years, there has been a surge in studies exploring regulatory effect of Traditional Chinese Medicine (TCM) on ferroptosis. However, significant gap persists comprehensive scientometric analysis and scientific mapping research, especially tracking evolution, primary contributors, emerging research focal points. This study aims to comprehensively update advancements targeting ferroptosis with various TCMs during previous years. The data, covering period from 1 January 2012, 30 November 2023, were retrieved Web Science database. For in-depth visualized analyses, series advanced analytical instruments employed. findings highlight China’s predominant role, accounting for 71.99% total publications significantly shaping this domain. Noteworthy productivity was observed at institutions, including Guangzhou University Medicine, Chengdu Zhejiang University. Thomas Efferth emerged as foremost author within field, while Frontiers Pharmacology boasted highest publication count. pinpointed hepatocellular carcinoma, chemical drug-induced liver injury, mitochondrial diseases, acute kidney failure most critical disorders addressed realm. offers bibliometric evaluation, enhancing our understanding present status TCM therapy managing ferroptosis-related diseases. Consequently, it aids both seasoned researchers newcomers by accelerating access vital information fostering innovative concept extraction specialized field.

Language: Английский

---