Metals to combat antimicrobial resistance

Nature Reviews Chemistry, Год журнала: 2023, Номер 7(3), С. 202 - 224

Опубликована: Фев. 8, 2023

Bacteria, similar to most organisms, have a love–hate relationship with metals: specific metal may be essential for survival yet toxic in certain forms and concentrations. Metal ions long history of antimicrobial activity received increasing attention recent years owing the rise resistance. The search antibacterial agents now encompasses ions, nanoparticles complexes (‘metalloantibiotics’). Although advanced clinic, metalloantibiotics are vast underexplored group compounds that could lead much-needed new class antibiotics. This Review summarizes developments this growing field, focusing on advances development metalloantibiotics, particular, those which mechanism action has been investigated. We also provide an overview alternative uses combat bacterial infections, including photodynamic therapy radionuclide diagnosis infections. Metals their promising source Their 3D geometry potential multiple mechanisms important assets; however, substantial investment research is needed advance them clinic.

Язык: Английский

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Inhibition of ferroptosis by up-regulating Nrf2 delayed the progression of diabetic nephropathy

Free Radical Biology and Medicine, Год журнала: 2020, Номер 162, С. 435 - 449

Опубликована: Ноя. 2, 2020

Язык: Английский

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Altered Iron Metabolism and Impact in Cancer Biology, Metastasis, and Immunology

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Апрель 9, 2020

Iron is an essential nutrient that plays a complex role in cancer biology. metabolism must be tightly controlled within cells. Whilst fundamental to many cellular processes and required for cell survival, excess labile iron toxic Increased associated with malignant transformation, progression, drug resistance immune evasion. Depleting intracellular stores, either the use of chelating agents or mimicking endogenous regulation mechanisms such as microRNAs, present attractive therapeutic opportunities, some which are currently under clinical investigation. Alternatively, overload can result form regulated death, ferroptosis, activated cells presenting alternative anti-cancer strategy. This review focuses on alterations enable meet metabolic demands during different stages tumorigenesis relation metastasis response. The strength current evidence considered, gaps knowledge highlighted controversies relating targeting potential discussed. key question we address this whether modulation represents useful approach treating metastatic disease it could employed combination existing targeted drugs immune-based therapies enhance their efficacy.

Язык: Английский

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Impaired lysosomal acidification triggers iron deficiency and inflammation in vivo

eLife, Год журнала: 2019, Номер 8

Опубликована: Дек. 3, 2019

Lysosomal acidification is a key feature of healthy cells. Inability to maintain lysosomal acidic pH associated with aging and neurodegenerative diseases. However, the mechanisms elicited by impaired remain poorly understood. We show here that inhibition triggers cellular iron deficiency, which results in mitochondrial function non-apoptotic cell death. These effects are recovered supplying via lysosome-independent pathway. Notably, deficiency sufficient trigger inflammatory signaling cultured primary neurons. Using mouse model acidification, we observed robust response brain, verified vivo magnetic resonance imaging. Furthermore, brains these mice present pervasive signature instability DNA (mtDNA), both corrected supplementation diet iron. Our highlight novel mechanism linking malfunction inflammation vivo.

Язык: Английский

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Inorganic Biomaterials for Regenerative Medicine

ACS Applied Materials & Interfaces, Год журнала: 2020, Номер 12(5), С. 5319 - 5344

Опубликована: Янв. 28, 2020

Regenerative medicine leverages the innate potential of human body to efficiently repair and regenerate damaged tissues using engineered biomaterials. By designing responsive biomaterials with appropriate biophysical biochemical characteristics, cellular response can be modulated direct tissue healing. Recently, inorganic have been shown regulate responses including cell–cell cell–matrix interactions. Moreover, ions released from these mineral-based play a vital role in defining cell identity, as well driving tissue-specific functions. The intrinsic properties biomaterials, such release bioactive (e.g., Ca, Mg, Sr, Si, B, Fe, Cu, Zn, Cr, Co, Mo, Mn, Au, Ag, V, Eu, La), leveraged induce phenotypic changes cells or modulate immune microenvironment healing regeneration. Biophysical characteristics topography, charge, size, electrostatic interactions, stiffness by addition micro- nanoparticles polymeric networks also an important their biological response. In this Review, we discuss recent emergence harness regenerative body. Specifically, will various effects inorganic-based materials directing for applications.

Язык: Английский

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Identification of Frataxin as a regulator of ferroptosis

Redox Biology, Год журнала: 2020, Номер 32, С. 101483 - 101483

Опубликована: Март 2, 2020

Ferroptosis is a newly discovered form of non-apoptotic regulated cell death and characterized by iron-dependent lipid peroxidation. Due to the enhanced dependence on iron in cancer cells, induction ferroptosis becoming promising therapeutic strategy. However, precise underlying molecular mechanism regulation process remains largely unknown. In present study, we demonstrate that protein Frataxin (FXN) key regulator modulating homeostasis mitochondrial function. Suppression FXN expression specifically repressed proliferation, destroyed morphology, impeded Fe-S cluster assembly activated starvation stress. Moreover, suppression significantly erastin-induced through accelerating free accumulation, peroxidation resulted dramatic mitochondria morphological damage including fragmentation vanished cristae. addition, this type was confirmed be ferroptosis, since it could pharmacologically restored ferroptotic inhibitor Fer-1 or GSH, but not inhibitors apoptosis, necrosis. Vice versa, enforced blocked response ferroptosis. More importantly, pharmacological genetic blocking signal completely restore resistance knockdown cells xenograft graft vivo. This paper suggests novel modulator, as well potential provided target improve antitumor activity based

Язык: Английский

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Targeting iron metabolism in cancer therapy

Theranostics, Год журнала: 2021, Номер 11(17), С. 8412 - 8429

Опубликована: Янв. 1, 2021

Iron is a critical component of many cellular functions including DNA replication and repair, it essential for cell vitality.As an element, iron maintaining human health.However, excess can be highly toxic, resulting in oxidative damage.Many studies have observed significant associations between cancer, the association appears to more than just coincidental.The chief characteristic cancers, hyper-proliferation, makes them even dependent on normal cells.Cancer therapeutics are becoming as diverse disease itself.Targeting metabolism cancer cells emerging, formidable field therapeutics.It strategy that with regard specific targets various ways reach them.This review will discuss importance highlight which being explored medicine tomorrow.

Язык: Английский

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Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases

Cells, Год журнала: 2020, Номер 9(6), С. 1456 - 1456

Опубликована: Июнь 12, 2020

Iron is essential for all living organisms. Many iron-containing proteins and metabolic pathways play a key role in almost cellular physiological functions. The diversity of the activity function iron its associated pathologies based on bond formation with adjacent ligands overall structure complex or other biomolecules. control absorption, utilization, recycling excretion by ensures normal biologic activity. Abnormalities proteins, also processes can lead to an array diseases. These include deficiency, which affects more than quarter world’s population; hemoglobinopathies, are most common genetic disorders idiopathic hemochromatosis. catalyst free radical production oxidative stress implicated tissue damage pathologic conditions, cancer initiation progression, neurodegeneration many interaction dietary xenobiotic molecules, including drugs, may affect disease processes. Deferiprone, deferoxamine, deferasirox chelating drugs offer therapeutic solutions diseases metabolism overload cancer, detoxification metals pathology.

Язык: Английский

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Current Use of Fenton Reaction in Drugs and Food

Molecules, Год журнала: 2022, Номер 27(17), С. 5451 - 5451

Опубликована: Авг. 25, 2022

Iron is the most abundant mineral in human body and plays essential roles sustaining life, such as transport of oxygen to systemic organs. The Fenton reaction between iron hydrogen peroxide, generating hydroxyl radical, which highly reactive toxic living cells. "Ferroptosis", a programmed cell death closely involved, has recently received much attention. Furthermore, various applications have been reported medical nutritional fields, cancer treatment or sterilization. Here, this review summarizes recent growing interest usefulness its biological relevance through basic practical information reports.

Язык: Английский

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Disease-associated metabolic pathways affected by heavy metals and metalloid

Toxicology Reports, Год журнала: 2023, Номер 10, С. 554 - 570

Опубликована: Янв. 1, 2023

Increased exposure to environmental heavy metals and metalloids their associated toxicities has become a major threat human health. Hence, the association of these with chronic, age-related metabolic disorders gained much interest. The underlying molecular mechanisms that mediate effects are often complex incompletely understood. In this review, we summarize currently known disease-associated signaling pathways altered following different exposure, alongside brief summary impacts. main focus study is explore how affected chronic multifactorial diseases including diabetes, cardiovascular diseases, cancer, neurodegeneration, inflammation, allergic responses upon arsenic (As), cadmium (Cd), chromium (Cr), iron (Fe), mercury (Hg), nickel (Ni), vanadium (V). Although there considerable overlap among metalloids-affected cellular pathways, affect distinct as well. common may be explored further find targets for treatment pathologic conditions.

Язык: Английский

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