Targeting ferroptosis opens new avenues for the development of novel therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 21, 2023

Abstract Ferroptosis is an iron-dependent form of regulated cell death with distinct characteristics, including altered iron homeostasis, reduced defense against oxidative stress, and abnormal lipid peroxidation. Recent studies have provided compelling evidence supporting the notion that ferroptosis plays a key pathogenic role in many diseases such as various cancer types, neurodegenerative disease, involving tissue and/or organ injury, inflammatory infectious diseases. Although precise regulatory networks underlie are largely unknown, particularly respect to initiation progression diseases, recognized bona fide target for further development treatment prevention strategies. Over past decade, considerable progress has been made developing pharmacological agonists antagonists these ferroptosis-related conditions. Here, we provide detailed overview our current knowledge regarding ferroptosis, its pathological roles, regulation during disease progression. Focusing on use chemical tools preclinical studies, also summarize recent advances targeting across growing spectrum ferroptosis-associated Finally, discuss new challenges opportunities potential strategy treating

Язык: Английский

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Applications of Gold and Silver Nanoparticles in Theranostics

Applied Biochemistry and Biotechnology, Год журнала: 2022, Номер 194(9), С. 4187 - 4219

Опубликована: Май 13, 2022

Язык: Английский

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Nitric Oxide Synthases in Rheumatoid Arthritis

Molecules, Год журнала: 2023, Номер 28(11), С. 4414 - 4414

Опубликована: Май 29, 2023

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe joint damage and disability. However, the specific mechanism of RA has not been thoroughly clarified over past decade. Nitric oxide (NO), a kind gas messenger molecule with many molecular targets, demonstrated to have significant roles in histopathology homeostasis. Three nitric synthases (NOS) are related producing NO regulating generation NO. Based on latest studies, NOS/NO signaling pathways play key role pathogenesis RA. Overproduction can induce release inflammatory cytokines act as free radical accumulate trigger oxidative stress, which involve Therefore, targeting NOS its upstream downstream may be effective approach managing This review clearly summarizes pathway, pathological changes RA, involvement conventional novel drugs based that still clinical trials good therapeutic potential recent years, aim provide theoretical basis for further exploration pathogenesis, prevention treatment

Язык: Английский

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Evolving strategies in the treatment of rheumatoid arthritis: a historical perspective

Reumatologia/Rheumatology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by joint inflammation, degradation of cartilage and bone, potential effects. This paper provides comprehensive historical overview RA treatment, tracing the evolution from ancient empirical methods to modern targeted therapies. Advancements in understanding RA’s immunopathology have led development conventional, biological, disease-modifying antirheumatic drugs, including tumor necrosis factor  inhibitors Janus kinase inhibitors. These innovations been pivotal transforming management, allowing for more personalized effective treatment strategies. The progression reflects shift symptomatic management interventions aimed at underlying mechanisms disease. has not only improved clinical outcomes but also enhanced quality life those affected RA, underscoring importance ongoing research adaptation therapeutic

Язык: Английский

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Redox proteome analysis of auranofin exposed ovarian cancer cells (A2780)

Redox Biology, Год журнала: 2022, Номер 52, С. 102294 - 102294

Опубликована: Март 22, 2022

The effects of Auranofin (AF) on protein expression and oxidation in A2780 cancer cells were investigated through a strategy based simultaneous proteomics redox determinations. Bioinformatics analysis the data supports view that most critical cellular changes elicited by AF treatment consist thioredoxin reductase inhibition, alteration cell state, impairment mitochondrial functions, metabolic associated with conversion to glycolytic phenotype, induction ER stress. occurrence above was extensively validated performing direct biochemical assays. Our are consistent concept produces its multitarget mechanism mainly affects metabolism functions results into severe Results discussed context current mechanistic knowledge existing AF.

Язык: Английский

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1,3,5-Triaza-7-phosphaadamantane and Cyclohexyl Groups Impart to Di-Iron(I) Complex Aqueous Solubility and Stability, and Prominent Anticancer Activity in Cellular and Animal Models

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(13), С. 11138 - 11151

Опубликована: Июль 1, 2024

Using a multigram-scalable synthesis, we obtained nine dinuclear complexes based on nonendogenous iron(I) centers and featuring variable aminocarbyne P-ligands. One compound from the series (FEACYP) emerged for its strong cytotoxicity in vitro against four human cancer cell lines, surpassing activity of cisplatin by 3–6 times three with an average selectivity index 6.2 compared to noncancerous HEK293 cells. FEACYP demonstrated outstanding water solubility (15 g/L) stability physiological-like solutions. It confirmed superior antiproliferative when tested 3D spheroids pancreatic cells showed capacity inhibit thioredoxin reductase (TrxR) similar auranofin. In vivo treatment murine LLC carcinoma (8 mg kg–1 dose) led excellent tumor growth suppression (88%) day 15, no signs systemic toxicity only limited body weight loss.

Язык: Английский

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Nanotechnology-empowered combination therapy for rheumatoid arthritis: principles, strategies, and challenges

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

Опубликована: Июль 22, 2024

Abstract Rheumatoid arthritis (RA) is an autoimmune disease with multifactorial etiology and intricate pathogenesis. In RA, repeated monotherapy frequently associated inadequate efficacy, drug resistance, severe side effects. Therefore, a shift has occurred in clinical practice toward combination therapy. However, conventional therapy encounters several hindrances, including low selectivity to arthritic joints, short half-lives, varying pharmacokinetics among coupled drugs. Emerging nanotechnology offers incomparable opportunity for developing advanced against RA. First, it allows co-delivering multiple drugs augmented physicochemical properties, targeted delivery capabilities, controlled release profiles. Second, enables therapeutic nanomaterials development, thereby expanding regimens include multifunctional nanomedicines. Lastly, facilitates the construction of all-in-one nanoplatforms assembled modalities, such as phototherapy, sonodynamic therapy, imaging. Thus, promising solution current bottleneck both RA treatment diagnosis. This review summarizes rationale, advantages, recent advances nano-empowered It also discusses safety considerations, drug–drug interactions, potential translation. Additionally, provides design tips outlook on future developments The objective this achieve comprehensive understanding mechanisms underlying unlock maximum nanotechnology, facilitating smooth transition research findings from laboratory practice.

Язык: Английский

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Auranofin-Loaded Chitosan Nanoparticles Demonstrate Potency against Triple-Negative Breast Cancer

ACS Applied Bio Materials, Год журнала: 2024, Номер 7(3), С. 2012 - 2022

Опубликована: Март 7, 2024

Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including FDA-approved drug, auranofin have shown promise effective anticancer agents against several tumors. To improve solubility bioavailability auranofin, we hypothesized that nanodelivery using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance activity TNBC by comparing best nanoformulation with free drug. The selection was based on synthesis various PEG copolymers via formaldehyde-mediated engraftment onto form [chitosan-g-PEG] copolymer. Furthermore, altered physiochemical properties copolymer formaldehyde ratio towards (CP 1–4 NPs). Following recruitment polymer surface, explored how this process influenced stiffness nanoparticle atomic force microscopy (AFM), factor crucial for in vitro vivo studies. Our objective ensure full functionality inherent parent maintained without allowing overshadow chitosan's unique cationic while improving neutral pH. Hence, CP 2 NP chosen. demonstrate efficacy good carrier administered dose 3 mg/kg contrast which given at 5 mg/kg. In studies revealed potency encapsulated cells severe necrotic effect following treatment superior auranofin. conclusion, chitosan-g-PEG potential be an excellent system increasing its effectiveness potentially reducing limitations.

Язык: Английский

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The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 31, 2024

Abstract Checkpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i’s) in combination with chemotherapy have shown promising results preclinical studies but displayed minimal efficacy substantial toxicity clinical trials. To explore combinatorial strategies that can overcome these limitations, we perform an unbiased high-throughput screen a non-small lung cancer (NSCLC) line and identify thioredoxin1 (Trx1), major component of the mammalian antioxidant-system, as determinant CHK1i sensitivity. We establish role redox recycling RRM1, larger subunit ribonucleotide reductase (RNR), depletion deoxynucleotide pool this Trx1-mediated Further, TrxR inhibitor auranofin, approved anti-rheumatoid arthritis drug, shows synergistic interaction via interruption pool. Together, show pharmacological to treat NSCLC relies on regulatory link between Trx system RNR activity.

Язык: Английский

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Role of Protein Disulfide Isomerase in Mediating Sulfasalazine-Induced Ferroptosis in HT22 Cells: The PDI−NOS−NO−ROS/Lipid-ROS Cascade

Archives of Biochemistry and Biophysics, Год журнала: 2025, Номер unknown, С. 110366 - 110366

Опубликована: Фев. 1, 2025

Язык: Английский

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