Bioengineered Versatile Heterojunctions as Stress Busters Targeting Matrix Degradation and Ferroptosis for Osteoarthritis Therapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Abstract Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of articular cartilage, with the underlying mechanism being inability chondrocytes to maintain homeostasis in response changing stress. The stress triggered excess ROS from various factors critical regulating chondrocyte survival and fate. In this study, 2D Mo 4/3 B 2‐ X MBene cerium‐gallic acid metal‐polyphenol network (MPN) together cartilage‐targeted shell hyaluronic WYRGRL (HW) are utilized development bio‐heterojunction MBene@MPN‐HW (MBM‐HW) through self‐assembly. MBM‐HW not only demonstrates superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme mimicking capabilities effectively scavenge ROS, but also exhibits dual‐responsive release cartilage‐targeting properties. Importantly, both vivo vitro experiments indicate that could alleviate oxidative stress, protect mitochondrial function, suppress cartilage matrix ferroptosis, thereby slowing progression OA. Mechanistically, it demonstrated attenuate Perk/eIF2α cascade mediated integrated restrain maintaining homeostasis. Overall, work underscores robust stress‐relieving capacity MBM‐HW, providing novel approach for treatment

Language: Английский

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From bench to bedside: targeting ferroptosis and mitochondrial damage in the treatment of diabetic cardiomyopathy

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Diabetic cardiomyopathy (DCM) is a common and fatal cardiac complication caused by diabetes, with its pathogenesis involving various forms of cell death mitochondrial dysfunction, particularly ferroptosis injury. Recent studies have indicated that damage play crucial roles in the onset progression DCM, though their precise regulatory mechanisms remain unclear. Of particular interest interaction between damage, as well synergistic effects, which are not fully understood. This review summarizes injury DCM explores molecular involved, an emphasis on interplay these two processes. Additionally, article offers overview targeted drugs shown to be effective cellular experiments, animal models, clinical trials, analyzing action potential side effects. The goal provide insights for future drug development applications. Moreover, challenges prospects multi-target combination therapies personalized medicine interventions practice offer strategic guidance comprehensive prevention management DCM.

Language: Английский

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Molecular Insights into Oxidative-Stress-Mediated Cardiomyopathy and Potential Therapeutic Strategies

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 670 - 670

Published: May 6, 2025

Cardiomyopathies comprise a heterogeneous group of cardiac disorders characterized by structural and functional abnormalities in the absence significant coronary artery disease, hypertension, valvular or congenital defects. Major subtypes include hypertrophic, dilated, arrhythmogenic, stress-induced cardiomyopathies. Oxidative stress (OS), resulting from an imbalance between reactive oxygen species (ROS) production antioxidant defenses, has emerged as key contributor to pathogenesis these conditions. ROS-mediated injury drives inflammation, protease activation, mitochondrial dysfunction, cardiomyocyte damage, thereby promoting remodeling decline. Although numerous studies implicate OS cardiomyopathy progression, precise molecular mechanisms remain incompletely defined. This review provides updated synthesis current findings on OS-related signaling pathways across subtypes, emphasizing emerging therapeutic targets within redox-regulatory networks. A deeper understanding may guide development targeted strategies improve clinical outcomes affected patients.

Language: Английский

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Proteomics-Based Exploration of the Hepatoprotective Mechanism of α-Lipoic Acid in Rats with Iron Overload-Induced Liver Injury

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4774 - 4774

Published: May 16, 2025

Excessive iron accumulation poses a significant threat to liver health, primarily through oxidative stress and autophagy dysregulation. α-Lipoic acid (ALA), natural antioxidant with hepatoprotective properties, may alleviate iron-induced damage, but its underlying mechanisms are not fully understood. This study utilized male Sprague Dawley rats BRL-3A cells explore the protective effects of ALA against overload in vivo vitro, respectively. treatment significantly reduced hepatic accumulation, improved morphology, alleviated ultrastructural damage rats. also function markers plasma, including alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), AST/ALT ratio. Furthermore, mitigated by lowering reactive oxygen species (ROS) malondialdehyde (MDA), while increasing enzyme activities glutathione peroxidase (GSH-Px) catalase (CAT). In cells, cell viability, decreased intracellular ROS, levels. Proteomics analysis indicates that NAD(P)H: quinone oxidoreductase 1 (NQO1) play critical role overload-induced Mechanistically, upregulated NQO1 expression downregulating autophagy-related proteins, light chain 3B (LC3B), lysosomal-associated membrane protein (LAMP1), cathepsin D (CTSD). Inhibition or knockdown abolished ALA’s effects, confirming reducing excessive autophagy. These findings highlight potential as therapeutic agent for managing toxicity chelation activation NQO1.

Language: Английский

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New Insights into Aspirin’s Anticancer Activity: The Predominant Role of Its Iron-Chelating Antioxidant Metabolites

Antioxidants, Journal Year: 2024, Volume and Issue: 14(1), P. 29 - 29

Published: Dec. 29, 2024

Epidemiological studies have suggested that following long-term, low-dose daily aspirin (LTLDA) administration for more than 5 years at 75–100 mg/day, 20–30% of patients (50–80 old) had a lower risk developing colorectal cancer (CRC) and about the same proportion in iron deficiency anemia (IDA). In cases IDA, an increase excretion is suspected, which caused by chelating metabolites (ACMs): salicylic acid, salicyluric 2,5-dihydroxybenzoic 2,3-dihydroxybenzoic acid. The ACMs constitute 70% administered dose much longer half-lives blood tissues. mechanisms reduction LTLDA users likely due to ACM’s targeting involved free radical damage, iron-containing toxins, proteins, associated metabolic pathways such as ferroptosis. from non-absorbed (about 30%) may also mitigate toxicity heme nitroso-heme other toxins food, are responsible cause cancer. mode action antioxidant pro-drug ACMs, with continuous presence users, increases prospect prophylaxis diseases. It anticancer effects depend primarily on iron-chelating activity ACMs. role diseases incomplete without considering its rapid biotransformation half-life

Language: Английский

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Comparative evaluation of the effects of deferiprone and/or resveratrol in alleviating iron overload-induced tongue injury in rats

Tissue and Cell, Journal Year: 2024, Volume and Issue: 91, P. 102534 - 102534

Published: Aug. 24, 2024

Language: Английский

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Milk fortification with a complex of iron with ascorbic acid for control of iron deficiency anemia ‎

Journal Of Advanced Pharmacy Education And Research, Journal Year: 2024, Volume and Issue: 14(1), P. 77 - 83

Published: Jan. 1, 2024

Language: Английский

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Triazine‐Based Molecules for Metal Ion Detection: A Decade of Advances

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(37)

Published: Sept. 27, 2024

Abstract Triazine‐based molecules have emerged as promising candidates for developing selective and sensitive chemosensors metal ion detection. Their structural tunability facilitates the introduction of a variety functional groups, improving their binding affinity specificity toward ions. This review highlights various sensing mechanisms, including colorimetric fluorometric methods, provides insights into performance these sensors in terms sensitivity, selectivity, detection limits. The synthetic routes synthesizing are mentioned detail. Given reliability flexibility, triazine‐based poised to make significant contributions field both sensor analytical chemistry.

Language: Английский

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Clinical Features, Microbiological Characteristics, and Drug Sensitivity Analysis of Rare Human Spinal Pythiosis Strain

Journal of Fungi, Journal Year: 2024, Volume and Issue: 10(12), P. 812 - 812

Published: Nov. 22, 2024

Pythiosis, a rare and formidable infectious disease caused by Pythium insidiosum, is characterized profound uncertainties in achieving definitive diagnoses, suboptimal outcomes, an exceptionally high mortality rate. Here, we present case of human spinal pythiosis southern China. With advanced metagenomic sequencing technology, insidiosum was pinpointed as the causative pathogen. We discovered that inoculation either tissue fragments or homogenate yielded more successful results enabled moderate extension culture duration to 5-10 days through exhaustive comparison diverse conditions for general clinical specimens. A pronounced genetic affinity isolated strain towards MCC 13 detected after comprehensive whole-genome analysis. Antifungal agents exhibited negligible sensitivity antimicrobial susceptibility test. Conversely, antibacterial such oxazolidinones, tetracyclines, macrolides, amphenicols demonstrated varying degrees sensitivity, albeit with most their minimum inhibitory concentrations (MICs) substantially surpassing safe concentration ranges effective treatment. Notably, tigecycline stood out promising candidate, exhibiting favorable therapeutic effects at concentrations, making it potential drug choice control pythiosis. combined test suggested combinations tetracyclines synergistic effects, combination doxycycline trimethoprim-sulfamethoxazole (TMP-SMX) particular playing pivotal role. To our surprise, MICs iron chelators, specifically deferiprone deferoxamine, against were exceedingly low, which led speculation exogenous chelators may have competitively inhibited iron-chelating enzymes strain. The research derived from this single, has certain limitations, but considering there are currently no reports invasive infections deep organs humans above findings can offer novel insights into treatment Combination therapy based on especially tigecycline, use TMP-SMX, adjunctive represent approaches tackle challenges However, further studies, including similar cases vivo trials, still needed validate them. In addition, while paying attention potentials plans, should also closely monitor risks side arise excessive expanded related drugs during process.

Language: Английский

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Association of Serum Ferritin With Growth and Endocrine Function in Thalassemia Major Children in North India: An Observational Study

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 30, 2024

Background Thalassemia is the most common form of hereditary anemia caused by impaired synthesis one two globin chains in hemoglobin. A decrease beta-globin occurs beta-thalassemia, resulting a relative excess alpha-globin chains. major severe thalassemia, which requires frequent blood transfusions for survival. Consequently, natural course disease affected transfusion-related side effects. Repeated lead to accumulation iron tissues such as liver, heart, and endocrine glands. Serum ferritin biomarker overload. Endocrinopathies are among frequently observed complications thalassemia. Early recognition treatment important order prevent late irreversible sequelae improve quality life these patients. This study was conducted evaluate growth parameters function children with thalassemia their relation serum ferritin. Methods prospective observational included all patients between age groups six months 14 years transfusion-dependent We 62 admitted during period fulfilling eligibility criteria. The data analyzed using descriptive statistics making comparisons various groups. Spearman correlation analysis done assess thyroid hormone. difference means across tested Mann-Whitney U test Kruskal-Wallis more than Results mean participants 5.66 ± 3.77 years, largest group consisting aged three comprising 40.3% participants. majority were boys. showed high prevalence endocrinopathies thalassemic endocrinopathy short stature (37.1%), followed glucose tolerance (28.6%), subclinical hypothyroidism (14.5%), parathyroid dysfunction (14.5%). Overt diabetes pubertal delay not seen. statistically significant association found (p < 0.001), = thryroid-stimulating hormone (TSH) 0.004), 0.006). Conclusions present cohorts considerably high, presenting stature, tolerance, hypoparathyroidism, hypothyroidism. weak positive levels. Hence, irrespective levels, can have complications.

Language: Английский

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