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ACS Biomaterials Science & Engineering May 2024Manganese dioxide (MnO) nanomaterials can react with trace hydrogen peroxide (HO) to produce paramagnetic manganese (Mn) and oxygen (O), which can be used for magnetic... (Review)
Review
Manganese dioxide (MnO) nanomaterials can react with trace hydrogen peroxide (HO) to produce paramagnetic manganese (Mn) and oxygen (O), which can be used for magnetic resonance imaging and alleviate the hypoxic environment of tumors, respectively. MnO nanomaterials also can oxidize glutathione (GSH) to produce oxidized glutathione (GSSG) to break the balance of intracellular redox reactions. As a consequence of the sensitivity of the tumor microenvironment to MnO-based nanomaterials, these materials can be used as multifunctional diagnostic and therapeutic platforms for tumor imaging and treatment. Importantly, when MnO nanomaterials are implanted along with other therapeutics, synergetic tumor therapy can be achieved. In addition to tumor treatment, MnO-based nanomaterials display promising prospects for tissue repair, organ protection, and the treatment of other diseases. Herein, we provide a thorough review of recent progress in the use of MnO-based nanomaterials for biomedical applications, which may be helpful for the design and clinical translation of next-generation MnO nanomaterials.
Topics: Manganese Compounds; Oxides; Humans; Nanostructures; Animals; Neoplasms; Magnetic Resonance Imaging; Tumor Microenvironment
PubMed: 38588342
DOI: 10.1021/acsbiomaterials.3c01852 -
Chemistry (Weinheim An Der Bergstrasse,... Aug 2023Steroids are highly prevalent structures in small-molecule therapeutics, with the level of oxidation being key to their biological activity and physicochemical... (Review)
Review
Steroids are highly prevalent structures in small-molecule therapeutics, with the level of oxidation being key to their biological activity and physicochemical properties. These C(sp )-rich tetracycles contain many stereocentres, which are important for creating specific vectors and protein binding orientations. Therefore, the ability to hydroxylate steroids with a high degree of regio-, chemo- and stereoselectivity is essential for researchers working in this field. This review will cover three main methods for the hydroxylation of steroidal C(sp )-H bonds: biocatalysis, metal-catalysed C-H hydroxylation and organic oxidants, such as dioxiranes and oxaziridines.
Topics: Hydroxylation; Oxidation-Reduction; Oxidants; Steroids; Biocatalysis
PubMed: 37235530
DOI: 10.1002/chem.202301066 -
Veterinary Parasitology Oct 2023Piroplasmida is an order of economically important blood parasites, including Babesia, Theileria, and Cytauxzoon, transmitted to mammals by ticks. Oxidative stress is a... (Review)
Review
Piroplasmida is an order of economically important blood parasites, including Babesia, Theileria, and Cytauxzoon, transmitted to mammals by ticks. Oxidative stress is a state in which the balance between oxidants and antioxidants is disturbed so that antioxidants cannot compensate for the harmful effects of oxidants. Due to the high concentration of oxygen and hemoglobin in red blood cells (RBCs), these are among the first cells exposed to oxidative damage. When RBCs are exposed to oxidative stress, their hemoglobin is oxidized, and lipid peroxidation leads to membrane instability, deformation, hemolysis, and anemia. Oxidative stress has a fundamental role in the pathogenesis of these parasites. In the present review article, we collected studies on the oxidative stress caused by Piroplasmida in domestic animals. What is obtained from the total review of studies conducted on piroplasmosis revealed that in these infections, the host faces oxidative stress, and the resultant oxidative injury plays a fundamental role in their pathogenicity. Further studies are needed to be carried out on the more precise role of oxidative stress, the use of more sensitive diagnostic biomarkers, and the possible therapeutic role of antioxidant agents in piroplasmosis.
Topics: Animals; Babesiosis; Animals, Domestic; Piroplasmida; Oxidative Stress; Antioxidants; Hemoglobins; Oxidants; Mammals
PubMed: 37643565
DOI: 10.1016/j.vetpar.2023.110011 -
Redox Biology Jul 2023Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells... (Review)
Review
Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells generally represent a higher oxidant level, which suggests a dual therapeutic strategy by regulating redox status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, pro-oxidant therapy exhibits a great anti-cancer capability, attributing to a higher oxidant accumulation within cancer cells, whereas antioxidant therapy to restore redox homeostasis has been claimed to fail in several clinical practices. Targeting the redox vulnerability of cancer cells by pro-oxidants capable of generating excessive reactive oxygen species (ROS) has surfaced as an important anti-cancer strategy. However, multiple adverse effects caused by the indiscriminate attacks of uncontrolled drug-induced OS on normal tissues and the drug-tolerant capacity of some certain cancer cells greatly limit their further applications. Herein, we review several representative oxidative anti-cancer drugs and summarize their side effects on normal tissues and organs, emphasizing that seeking a balance between pro-oxidant therapy and oxidative damage is of great value in exploiting next-generation OS-based anti-cancer chemotherapeutics.
Topics: Humans; Antioxidants; Reactive Oxygen Species; Oxidative Stress; Oxidation-Reduction; Oxidants; Neoplasms
PubMed: 37224697
DOI: 10.1016/j.redox.2023.102754 -
Neurobiology of Disease Mar 2024Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced by the action of gut microbiota and the hepatic enzyme Flavin Mono‑oxygenase 3 (FMO3).... (Review)
Review
Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced by the action of gut microbiota and the hepatic enzyme Flavin Mono‑oxygenase 3 (FMO3). TMAO level has a positive correlation with the risk of cardiovascular events, including stroke, and their level is influenced mainly by dietary choice and the action of liver enzyme FMO3. TMAO plays a role in the development of atherosclerosis plaque, which is one of the causative factors of the stroke event. Preclinical and clinical investigations on the TMAO and associated stroke risk, severity, and outcomes are summarised in this review. In addition, mechanisms of TMAO-driven vascular dysfunction are also discussed, such as inflammation, oxidative stress, thrombus and foam cell formation, altered cholesterol and bile acid metabolism, etc. Post-stroke inflammatory cascades involving activation of immune cells, i.e., microglia and astrocytes, result in Blood-brain-barrier (BBB) disruption, allowing TMAO to infiltrate the brain and further aggravate inflammation. This event occurs as a result of the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway through the release of inflammatory cytokines and chemokines that further aggravate the BBB and initiate further recruitment of immune cells in the brain. Thus, it's likely that maintaining TMAO levels and associated gut microbiota could be a promising approach for treating and improving stroke complications.
Topics: Humans; Stroke; Inflammation; Oxides; Methylamines
PubMed: 38286388
DOI: 10.1016/j.nbd.2024.106423 -
Biomolecules & Biomedicine Nov 2023Current research supports the evidence that the gut microbiome (GM), which consist of gut microbiota and their biologically active metabolites, is associated with... (Review)
Review
Current research supports the evidence that the gut microbiome (GM), which consist of gut microbiota and their biologically active metabolites, is associated with atherosclerosis development. Trimethylamine-N-oxide (TMAO), a metabolite produced by the GM through trimethylamine (TMA) oxidation, significantly enhances the formation and vulnerability of atherosclerotic plaques. TMAO promotes inflammation and oxidative stress in endothelial cells, leading to vascular dysfunction and plaque formation. Dimethyl-1-butanol (DMB), iodomethylcholine (IMC) and fluoromethylcholine (FMC) have been recognized for their ability to reduce plasma TMAO by inhibiting trimethylamine lyase, a bacterial enzyme involved in the choline cleavage anaerobic process, thus reducing TMA formation. Conversely, indole-3-carbinol (I3C) and trigonelline inhibit TMA oxidation by inhibiting flavin-containing monooxygenase-3 (FMO3), resulting in reduced plasma TMAO. The combined use of inhibitors of choline trimethylamine lyase and flavin-containing monooxygenase-3 could provide novel therapeutic strategies for cardiovascular disease prevention by stabilizing existing atherosclerotic plaques. This review aims to present the current evidence of the roles of TMA/TMAO in atherosclerosis as well as its potential therapeutic prevention aspects.
Topics: Humans; Plaque, Atherosclerotic; Endothelial Cells; Atherosclerosis; Lyases; Choline; Oxides
PubMed: 37337893
DOI: 10.17305/bb.2023.8893 -
Mechanisms of Ageing and Development Dec 2023Oxidative stress plays an important role in the skin aging process; however, the mechanisms are not fully elucidated. Especially the changes in various types of skin...
Oxidative stress plays an important role in the skin aging process; however, the mechanisms are not fully elucidated. Especially the changes in various types of skin cells with aging and the key oxidative stress-related genes that play a regulatory role are not clear. In this study, single-cell RNA sequencing data and microarray transcriptome data were used to explore the changes in oxidative stress response and oxidant detoxification capacity of skin cells during aging and oxidative stress-related genes potentially involved in regulating skin aging were searched. The oxidative stress response and oxidant detoxification ability were weakened in the elderly compared with those of the young. Among the different types of skin cells, keratinocytes, melanocytes, vascular endothelial cells, fibroblasts, and lymphatic endothelial cells exhibited a stronger oxidative stress response and oxidant detoxification ability, while immune cells exhibited a weaker oxidative stress response and detoxification capacity. During aging, the oxidative stress response and oxidant detoxification capacity of keratinocytes, fibroblasts, macrophages, and vascular endothelial cells were significantly weakened. Annexin A1 (ANXA1) and Apolipoprotein E (APOE) may be key oxidative stress-related genes affecting skin aging.
Topics: Humans; Aged; Oxidants; Endothelial Cells; Skin; Oxidative Stress; Aging; Skin Aging
PubMed: 37827221
DOI: 10.1016/j.mad.2023.111878 -
Current Molecular Pharmacology 2024Ischemia-Reperfusion Injury (IRI) is a paradoxical phenomenon where removing the source of injury can cause additional damage. Ischemia reduces ATP production and... (Review)
Review
Ischemia-Reperfusion Injury (IRI) is a paradoxical phenomenon where removing the source of injury can cause additional damage. Ischemia reduces ATP production and intracellular pH, reducing oxidative reactions, increasing lactic acid release, and activating anaerobic metabolism. Reperfusion restores aerobic respiration and increases ROS production, leading to malfunction of transmembrane transport, activation of proteases, DNA dissolution, and protein denaturation, leading to apoptotic cell death. Nrf2 is a transcription factor that regulates cellular inflammation and oxidative responses. It is activated by oxidants and electrophiles and enhances detoxifying enzyme expression, maintaining redox homeostasis. It also activates ARE, which activates several ARE-regulated genes that favor cell survival by exhibiting resistance to oxidants and electrophiles. Nrf2 regulates the antioxidant defense system by producing phase II and antioxidant defense enzymes, including HO-1, NQO-1, gglutamylcysteine synthetase, and rate-limiting enzymes for glutathione synthesis. Nrf2 protects mitochondria from damage and supports mitochondrial function in stress conditions. Resveratrol is a stilbene-based compound with a wide variety of health benefits for humans, including antioxidant, anticarcinogenic, antitumor, and estrogenic/antiestrogenic. Resveratrol protects against IRI through several signaling pathways, including the Nrf2/ARE pathway. Here, we review the studies that investigated the mechanisms of resveratrol protection against IRI through modulation of the Nrf2 signaling pathway.
Topics: Humans; Resveratrol; Antioxidants; NF-E2-Related Factor 2; Reperfusion Injury; Oxidants
PubMed: 38389416
DOI: 10.2174/0118761429246578231130064830 -
Frontiers in Immunology 2024The innate immune response represents the first-line of defense against invading pathogens. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been... (Review)
Review
The innate immune response represents the first-line of defense against invading pathogens. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been implicated in various aspects of innate immune function, which involves respiratory bursts and inflammasome activation. These reactive species widely distributed within the cellular environment are short-lived intermediates that play a vital role in cellular signaling and proliferation and are likely to depend on their subcellular site of formation. NADPH oxidase complex of phagocytes is known to generate superoxide anion radical (O ) that functions as a precursor for antimicrobial hydrogen peroxide (HO) production, and HO is utilized by myeloperoxidase (MPO) to generate hypochlorous acid (HOCl) that mediates pathogen killing. HO modulates the expression of redox-responsive transcriptional factors, namely NF-kB, NRF2, and HIF-1, thereby mediating redox-based epigenetic modification. Survival and function of immune cells are under redox control and depend on intracellular and extracellular levels of ROS/RNS. The current review focuses on redox factors involved in the activation of immune response and the role of ROS in oxidative modification of proteins in macrophage polarization and neutrophil function.
Topics: Hydrogen Peroxide; Oxidation-Reduction; Superoxides; Oxidative Stress; Hypochlorous Acid; Immunity, Innate
PubMed: 38515749
DOI: 10.3389/fimmu.2024.1359600 -
Free Radical Biology & Medicine Nov 2023Iron(II) species can participate in the Fenton and Fenton-like reactions to generate the hydroxyl radical that can oxidatively damage biomolecules and induce oxidative... (Review)
Review
Iron(II) species can participate in the Fenton and Fenton-like reactions to generate the hydroxyl radical that can oxidatively damage biomolecules and induce oxidative stress in biological systems. Many diseases, including neurodegeneration, cardiovascular disease and cancer, are associated with oxidative stress. However, it is proposed recently that hydroxyl radical would not be generated from the Fenton reaction under physiological conditions and thus would not cause oxidative stress in biological systems. This proposal may cause confusion for understanding oxidative stress and can also have impact on therapeutic strategies for the diseases associated with oxidative stress. In this Mini-review, the up-to-date convincing evidences of hydroxyl radical generation from the physiologically relevant Fenton-like reactions of the iron(II) complexes with physiological ligands in human blood plasma, including histidine, citrate and phosphate, are succinctly reviewed. The oxidative damages caused by hydroxyl radical to biomolecules and cells are briefly summarized. These findings strongly challenge the above proposal.
Topics: Humans; Hydroxyl Radical; Iron; Oxidative Stress; Citrates; Ferrous Compounds; Hydrogen Peroxide; Oxidation-Reduction
PubMed: 37717792
DOI: 10.1016/j.freeradbiomed.2023.09.013