Separation and preparation of nanoparticles of urban dust for biological studies.

Nanoparticles (NPs) of urban dust pose a potential threat to public health. Nevertheless, this issue remains largely unexplored due to a lack of biological research related to these NPs. This may be attributed to the complexity of the separation, characterization, analysis, and subsequent preparation of NPs of urban dust for biological studies.

Mitochondrial lipid peroxidation is necessary but not sufficient for induction of ferroptosis.

Ferroptosis, a form of regulated cell death mediated by lipid peroxidation (LPO), has become the subject of intense research due to its potential therapeutic applications in cancer chemotherapy as well as its pathophysiological role in ischemic organ injury. The role of mitochondrial lipid peroxidation (LPO) in ferroptosis remains poorly understood. We show that supplementation of exogenous iron in the form of ferric ammonium citrate (FAC) in combination with buthionine sulfoximine (BSO, an inhibitor of glutathione biosynthesis) induces mitochondrial lipid peroxidation that precedes ferroptosis in normal human fibroblasts.

Mitochondrial fragmentation in early differentiation of human MB135 myoblasts: Role of mitochondrial ROS production in the absence of depolarization.

Aims: Study of the role of mitochondria-generated reactive oxygen species (mtROS) and mitochondrial polarization in mitochondrial fragmentation at the initial stages of myogenesis.

Main Methods: Mitochondrial morphology, Drp1 protein phosphorylation, mitochondrial electron transport chain components content, mtROS and mitochondrial lipid peroxidation levels, and mitochondrial polarization were evaluated on days 1 and 2 of human MB135 myoblasts differentiation. A mitochondria-targeted antioxidant SkQ1 was used to elucidate the effect of mtROS on mitochondria.

Exogenous Iron Induces Mitochondrial Lipid Peroxidation, Lipofuscin Accumulation, and Ferroptosis in H9c2 Cardiomyocytes.

Lipid peroxidation plays an important role in various pathologies and aging, at least partially mediated by ferroptosis. The role of mitochondrial lipid peroxidation during ferroptosis remains poorly understood. We show that supplementation of exogenous iron in the form of ferric ammonium citrate at submillimolar doses induces production of reactive oxygen species (ROS) and lipid peroxidation in mitochondria that precede ferroptosis in H9c2 cardiomyocytes.

Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria ; the way to manipulate neutrophil swarming.

Neutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, stimulates the formation of swarms of neutrophils surrounding pathogens. Here we describe a complex redox regulation that either stimulates or inhibits fMLP-induced leukotriene synthesis in an experimental model of neutrophils interacting with .

The critical role of mitochondrial lipid peroxidation in ferroptosis: insights from recent studies.

Ferroptosis is a regulated form of necrotic cell death reliant on iron-catalyzed lipid peroxidation. Although the precise involvement of mitochondria in ferroptosis remains incompletely elucidated, recent research indicates that mitochondrial oxidative events wield a pivotal influence in this mechanism. This article centers on the most recent discoveries, spotlighting the significance of mitochondrial lipid peroxidation in the occurrence of ferroptosis.

Role of Mitochondria in the Regulation of Effector Functions of Granulocytes.

Granulocytes (neutrophils, eosinophils, and basophils) are the most abundant circulating cells in the innate immune system. Circulating granulocytes, primarily neutrophils, can cross the endothelial barrier and activate various effector mechanisms to combat invasive pathogens. Eosinophils and basophils also play an important role in allergic reactions and antiparasitic defense.

Six Functions of Respiration: Isn't It Time to Take Control over ROS Production in Mitochondria, and Aging Along with It?

Cellular respiration is associated with at least six distinct but intertwined biological functions. (1) biosynthesis of ATP from ADP and inorganic phosphate, (2) consumption of respiratory substrates, (3) support of membrane transport, (4) conversion of respiratory energy to heat, (5) removal of oxygen to prevent oxidative damage, and (6) generation of reactive oxygen species (ROS) as signaling molecules. Here we focus on function #6, which helps the organism control its mitochondria.

Current perspectives of mitochondria-targeted antioxidants in cancer prevention and treatment.

Oxidative stress nearly always accompanies all stages of cancer development. At the early stages, antioxidants may help to reduce reactive oxygen species (ROS) production and exhibit anticarcinogenic effects. In the later stages, ROS involvement becomes more complex.

Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis.

Many muscular pathologies are associated with oxidative stress and elevated levels of the tumor necrosis factor (TNF) that cause muscle protein catabolism and impair myogenesis. Myogenesis defects caused by TNF are mediated in part by reactive oxygen species (ROS), including those produced by mitochondria (mitoROS), but the mechanism of their pathological action is not fully understood. We hypothesized that mitoROS act by triggering and enhancing mitophagy, an important tool for remodelling the mitochondrial reticulum during myogenesis.

Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis.

Ferroptosis induced by erastin (an inhibitor of cystine transport) and butionine sulfoximine (an inhibitor of glutathione biosynthesis) was prevented by the mitochondria-targeted antioxidants SkQ1 and MitoTEMPO. These effects correlate with the prevention of mitochondrial lipid peroxidation, which precedes cell death. Methylene blue, a redox agent that inhibits the production of reactive oxygen species (ROS) in complex I of the mitochondrial electron transport chain, also inhibits ferroptosis and mitochondrial lipid peroxidation.

Innate Immunity and Phenoptosis.

The hypothesis is proposed that activation of innate immunity is the primary mechanism of phenoptosis (programmed death of an organism). In support of the hypothesis, we discuss (i) the data on active release of signaling molecules from the cell producing excessive inflammation; (ii) the data on contribution of mitochondrial production of reactive oxygen species to immune response.

Pulmonary Fibrosis and Progressive Pulmonary Fibrosis in a Prospective Registry of Interstitial Lung Diseases in Eastern Siberia.

Interstitial lung diseases (ILD) are part of a large heterogeneous group of diseases that differ in many ways (in their cause, clinical presentation, and response to therapy, etc.), but there are similar pathophysiological mechanisms involved in the development of the inflammation and/or fibrosis of the lungs. Currently, several criteria for pulmonary fibrosis (PF) and progressive pulmonary fibrosis (PPF) are proposed, and the information on the prevalence and characteristics of these conditions is limited.

Mitochondria-targeted antioxidant SkQ1 inhibits leukotriene synthesis in human neutrophils.

Leukotrienes are among the most potent mediators of inflammation, and inhibition of their biosynthesis, is becoming increasingly important in the treatment of many pathologies. In this work, we demonstrated that preincubation of human neutrophils with the mitochondria targeted antioxidant SkQ1 (100 nM) strongly inhibits leukotriene synthesis induced by three different stimuli: the Ca ionophore A23187, the chemotactic formyl-peptide fMLP in combination with cytocholasin B, and opsonized zymosan. The SkQ1 analogue lacking the antioxidant quinone moiety (C12TPP) was ineffective, suggesting that mitochondrial production of reactive oxygen species (ROS) is critical for activating of leukotriene synthesis in human neutrophils.

Mitochondria-Targeted Antioxidant SkQ1 Prevents the Development of Experimental Colitis in Mice and Impairment of the Barrier Function of the Intestinal Epithelium.

Mitochondria-targeted antioxidants have become promising candidates for the therapy of various pathologies. The mitochondria-targeted antioxidant SkQ1, which is a derivative of plastoquinone, has been successfully used in preclinical studies for the treatment of cardiovascular and renal diseases, and has demonstrated anti-inflammatory activity in a number of inflammatory disease models. The present work aimed to investigate the therapeutic potential of SkQ1 and CTPP, the analog of SkQ1 lacking the antioxidant quinone moiety, in the prevention of sodium dextran sulfate (DSS) experimental colitis and impairment of the barrier function of the intestinal epithelium in mice.

Extrusion of mitochondria: Garbage clearance or cell-cell communication signals?

Mitochondria are dynamic organelles that regulate various intracellular signaling pathways, including the mechanisms of programmed cell death, differentiation, inflammation, and so on. Mitochondria may be extruded as membrane enveloped or as free organelles during developmental processes, inflammatory activation, and in the process of "garbage clearance" of damaged mitochondria in postmitotic cells. Extracellular mitochondria can be engulfed by immune and nonimmune cells and trigger intracellular signaling leading to an inflammatory response.

Gram-Negative Bacteria Boost Leukotriene Synthesis Induced by Chemoattractant fMLP to Stimulate Neutrophil Swarming.

Leukotriene synthesis in neutrophils is critical for host survival during infection. In particular, leukotriene B (LTB) is a powerful neutrophil chemoattractant that plays a crucial role in neutrophil swarming. In this work, we demonstrated that preincubation of human neutrophils with strongly stimulated LTB production induced by the bacterial chemoattractant, peptide N-formyl-L-methionyl-L-leucyl-l-phenylalanine (fMLP), while the reverse sequence of additions was ineffective.

Analysis of genes regulated by DUX4 via oxidative stress reveals potential therapeutic targets for treatment of facioscapulohumeral dystrophy.

Muscles of patients with facioscapulohumeral dystrophy (FSHD) are characterized by sporadic DUX4 expression and oxidative stress which is at least partially induced by DUX4 protein. Nevertheless, targeting oxidative stress with antioxidants has a limited impact on FSHD patients, and the exact role of oxidative stress in the pathology of FSHD, as well as its interplay with the DUX4 expression, remain unclear. Here we set up a screen for genes that are upregulated by DUX4 via oxidative stress with the aim to target these genes rather than the oxidative stress itself.