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Functions of ROS at physiological level. Besides their direct functions in immune defense and cellular structure, ROS can act as second messengers. They oxidize the three main sulfur switches and indirectly influence pro-fibrotic signaling, autophagy, mitoptosis, pro-inflammatory signaling, apoptosis and cell proliferation. These processes are mediated by kinases, phosphatases and transcription factors, among others.
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Since the Great Oxidation Event, about 2.4 billion years ago, the Earth is immersed in an oxidizing atmosphere. Thus, it has been proposed that excess oxygen, originally a waste product of photosynthetic cyanobacteria, induced oxidative stress and the production of reactive oxygen species (ROS), which have since acted as fundamental drivers of biol...
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The lymphatic vascular system plays important roles in various physiological and pathological processes, and lack of lymphatic or lymphovenous valves always causes lymph or blood reflux, and can lead to lymphedema. However, the molecular mechanism underlying the valve formation is poorly understood. Here we report that the MAPK/Erk signaling needs...
Citations
... Reactive oxygen species (ROS) generated during oxidative stress can activate nuclear factor kappa B (NF-κB), a key transcription factor that promotes the expression of various pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). This link between oxidative stress and inflammation underscores the intricate interplay between oxidative damage and the immune response, contributing to the pathogenesis of various diseases [33]. Dapagliflozin exhibited a significant reduction in IL-1 beta, IL-6, and TNF-alpha, aligning with studies emphasizing its anti-inflammatory effects [34][35][36]. ...
This study was aimed to investigate the hepatoprotective potential of dapagliflozin and silymarin alone and in combination to combat carbon tetrachloride (CCl4)-induced hepatotoxicity and the anticipated mechanisms. Thirty female Wistar rats were randomly allocated into five different groups. All the experimental animals except the normal control (Group I) were administered CCl4. Additionally, Groups II, III, IV, and V were treated with gum acacia, silymarin, dapagliflozin, and a combination of dapagliflozin and silymarin, respectively, for 14 days. Dapagliflozin, silymarin alone, and in combination, significantly reduced (p < 0.05) serum levels of ALT, AST, AST:ALT ratio, and total bilirubin compared to CCl4-intoxicated control rats. There was a notable reduction (p < 0.05) observed in the levels of IL-1beta, IL-6, TNF-alpha, nitrites, and 4-hydroxynonenal, accompanied by an elevation in catalase, superoxide dismutase, glutathione peroxidase, nuclear erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver homogenates of the groups treated with dapagliflozin, silymarin alone, and in combination, as compared to the CCl4-intoxicated control group. Dapagliflozin in combination with silymarin showed a synergistic hepatoprotective effect. Our study reveals the profound hepatoprotective potential of dapagliflozin alone and in combination with silymarin in CCl4-intoxicated Wistar rats by modulating the Nrf2 and HO-1 signaling pathways.
... ROS disrupts cellular homeostasis via altering mitochondrial functions and lipid, protein, and nucleic metabolism while sustaining proinflammatory signals. [15] We quantified intracellular ROS production using the fluorescent probe CM-2′,7′-Dichlorodihydrofluorescein diacetate. A representative staining is presented in Figure 7A. ...
Background
Neutrophils are key mediators of inflammation during acute liver injury (ALI). Emerging evidence suggests that they also contribute to injury resolution and tissue repair. However, the different neutrophil subsets involved in these processes and their kinetics are undefined. Herein, we characterized neutrophil kinetics and heterogeneity during ALI.
Methods
We used the carbon tetrachloride model of ALI and employed flow cytometry, tissue imaging, and quantitative RT-PCR to characterize intrahepatic neutrophils during the necroinflammatory early and late repair phases of the wound healing response to ALI. We FACS sorted intrahepatic neutrophils at key time points and examined their transcriptional profiles using RNA-sequencing. Finally, we evaluated neutrophil protein translation, mitochondrial function and metabolism, reactive oxygen species content, and neutrophil extracellular traps generation.
Results
We detected 2 temporarily distinct waves of neutrophils during (1) necroinflammation (at 24 hours after injury) and (2) late repair (at 72 hours). Early neutrophils were proinflammatory, characterized by: (1) upregulation of inflammatory cytokines, (2) activation of the noncanonical NF-κB pathway, (3) reduction of protein translation, (4) decreased oxidative phosphorylation, and (5) higher propensity to generate reactive oxygen species and neutrophil extracellular traps. In contrast, late neutrophils were prorepair and enriched in genes and pathways associated with tissue repair and angiogenesis. Finally, early proinflammatory neutrophils were characterized by the expression of a short isoform of C-X-C chemokine receptor 5, while the late prorepair neutrophils were characterized by the expression of C-X-C chemokine receptor 4.
Conclusions
This study underscores the phenotypic and functional heterogeneity of neutrophils and their dual role in inflammation and tissue repair during ALI.
... Mitochondrial damage stands as the primary instigator of cellular oxidative stress [6]. Persistent opening of the mitochondrial permeability transition pore (mPTP) results in an influx of Ca 2+ and escalated ROS levels. ...
Purpose: Adhesion between calcium oxalate crystals and renal tubular epithelial cells is a vital cause of renal stone formation; however, the drugs that inhibit crystal adhesion and the mechanism of inhibition have yet to be explored. Methods: The cell injury model was constructed using nano-COM crystals, and changes in oxidative stress levels, endoplasmic reticulum (ER) stress levels, downstream p38 MAPK protein expression, apoptosis, adhesion protein osteopontin expression, and cell–crystal adhesion were examined in the presence of Laminarin polysaccharide (DLP) and sulfated DLP (SDLP) under protected and unprotected conditions. Results: Both DLP and SDLP inhibited nano-COM damage to human kidney proximal tubular epithelial cell (HK-2), increased cell viability, decreased ROS levels, reduced the opening of mitochondrial membrane permeability transition pore, markedly reduced ER Ca2+ ion concentration and adhesion molecule OPN expression, down-regulated the expression of ER stress signature proteins including CHOP, Caspase 12, and p38 MAPK, and decreased the apoptosis rate of cells. SDLP has a better protective effect on cells than DLP. Conclusions: SDLP protects HK-2 cells from nano-COM crystal-induced apoptosis by reducing oxidative and ER stress levels and their downstream factors, thereby reducing crystal–cell adhesion interactions and the risks of kidney stone formation.
... When excessive ROS levels are present inside a cell, these highly reactive molecules result in non-specific oxidation of nucleic acids, lipids, and other macromolecules, including DNA adducts, lipid peroxidation, and protein carbonylation [4,5]. All of these damaged biomolecules, when existing in large amounts without being efficiently repaired or eliminated in time, eventually lead to cell death [6]. In addition, the damaged biomolecules, for example, 8-oxodG, which is the most commonly formed DNA adduct under high levels of ROS, have been shown to enhance carcinogenesis [7][8][9]. ...
... In addition to catalase, glutathione peroxidase can also reduce hydrogen peroxide to water. It has also been reported that GSH also reduced lipid hydroperoxides that led to DNA adducts 8-oxo-2′-deoxyguanosine to alcohols [6]. The FoxO family of transcription factors has been shown to regulate and promote antioxidant defense through post-translational modifications [31][32][33]. ...
Reactive oxygen species (ROS) participate in almost all disorders, including cancer. Many factors, including aging, a high-fat diet, a stressful lifestyle, smoking, infection, genetic mutations, etc., lead to elevated levels of ROS. Prostate cancer, the most prevalent type of cancer in senior American men and the second leading cause of cancer mortality in American men, results from chronic oxidative stress. The doubled incident rate as well as the doubled mortality numbers of prostate cancer have persisted in African Americans in comparison with Caucasian Americans and other racial groups, indicating a prostate cancer disparity in African American men. In this review, we mainly focus on the latest findings on ROS in prostate cancer development and progression within the last five years to update our understanding in this area, as several comprehensive literature reviews addressing oxidative stress and/or inflammation in prostate cancer before 2020 are available. In addition to other known factors such as socioeconomic disadvantage, cultural mistrust of the health care system, etc. that are long-existing in the African American group, we also summarize the latest evidence that demonstrated high systemic oxidative stress and inflammation in African Americans for their potential contribution to the racial prostate cancer disparity in this population.
... Heart Increasing of atrial natriuretic peptide and nitric oxide, reduction of blood pressure (Kim et al., 2013;Richards et al., 2014;Drucker, 2016;Baggio et al., 2018;Pandey et al., 2023) Increasing of diuresis and natriuresis, reduction of blood pressure (Mazidi et al., 2017;Dominguez Rieg and Rieg, 2019) Suppression of oxidative stress (Drucker, 2016;Helmstädter et al., 2020;Baylan et al., 2022) Suppression of oxidative stress (Frati et al., 2017;Checa and Aran, 2020;Chen et al., 2022;Elrakaybi et al., 2022) Inhibition of pro-inflammatory cytokines, NLRP3 inflammasome, promotion of M2 macrophage phenotype (Hogan et al., 2014;Bułdak et al., 2016;Bruen et al., 2017;Luo et al., 2019;Yu et al., 2019;Püschel et al., 2022) Inhibition of pro-inflammatory cytokines, NLRP3 inflammasome, promotion of M2 macrophage phenotype (Lee et al., 2017;Ye et al., 2017;Byrne et al., 2020;Kim et al., 2020) Energetic shift from fatty acid to glucose oxidation (Bao et al., 2011) Modulation of myocardial hypertrophy and fibrosis (Bay et al., 2013;Croteau et al., 2021) Activation of SIRT1 signaling (Luo et al., 2019) Regulation of sodium and calcium homeostasis (Cappetta et al., 2020;Uthman et al., 2022) Inhibition of RAAS pathway (Kim et al., 2013;Jensen et al., 2020;Martins et al., 2020) Inhibition of RAAS and sympathetic neurohormonal pathways (Salvatore et al., 2022) Brain Reduction of neuroinflammation, decrease of microglia activation, promotion of M2 macrophage phenotype (Hogan et al., 2014;Bułdak et al., 2016;Bruen et al., 2017;Yu et al., 2019;Zhang et al., 2021a;Püschel et al., 2022) Reduction of NLRP3 inflammasome, decrease of microglia activation, promotion of M2 macrophage phenotype (Lin et al., 2014;Iannantuoni et al., 2019;Xu et al., 2019;Lee et al., 2020;Lonnemann et al., 2020;Lee et al., 2021;Khedr et al., 2024) Reduction of amyloid-β plaque deposition and tau hyperphosphorylation (Li et al., 2012;Long-Smith et al., 2013;McClean and Hölscher, 2014;McClean et al., 2015;Cai et al., 2018) Reduction of amyloid-β plaque deposition and tau hyperphosphorylation (Huang et al., 2016;Cenini and Voos, 2019;Lonnemann et al., 2020) Activation of brain-derived neurotrophic factor (Du et al., 2022) Activition of brain-derived neurotrophic factor (Arab et al., 2021) Enhancement glucose metabolism (Bomba et al., 2013;Zheng et al., 2021) Interference with mTOR signaling (Packer, 2020;Stanciu et al., 2021;Samman et al., 2023) FIGURE 1 ...
... Oxidative stress and inflammation significantly and interdependently contribute to the onset and progression of cardiovascular diseases (Frati et al., 2017). Inflammation can induce acute or chronic oxidative stress via cytosolic protein kinase C and calcium release; vice versa, oxidative stress is a positive modulator of the inflammatory response through NLRP3 inflammasome and NF-κB (Checa and Aran, 2020;Chen et al., 2022). SGLT2 inhibitors exhibit considerable potential as antiinflammatory agents, through indirect mechanisms that involve metabolic improvement, oxidative stress reduction, as well as direct modulation of inflammatory pathways (Elrakaybi et al., 2022). ...
Heart failure and cognitive impairment emerge as public health problems that need to be addressed due to the aging global population. The conditions that often coexist are strongly related to advancing age and multimorbidity. Epidemiological evidence indicates that cardiovascular disease and neurodegenerative processes shares similar aspects, in term of prevalence, age distribution, and mortality. Type 2 diabetes increasingly represents a risk factor associated not only to cardiometabolic pathologies but also to neurological conditions. The pathophysiological features of type 2 diabetes and its metabolic complications (hyperglycemia, hyperinsulinemia, and insulin resistance) play a crucial role in the development and progression of both heart failure and cognitive dysfunction. This connection has opened to a potential new strategy, in which new classes of anti-diabetic medications, such as glucagon-like peptide-1 receptor (GLP-1R) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, are able to reduce the overall risk of cardiovascular events and neuronal damage, showing additional protective effects beyond glycemic control. The pleiotropic effects of GLP-1R agonists and SGLT2 inhibitors have been extensively investigated. They exert direct and indirect cardioprotective and neuroprotective actions, by reducing inflammation, oxidative stress, ions overload, and restoring insulin signaling. Nonetheless, the specificity of pathways and their contribution has not been fully elucidated, and this underlines the urgency for more comprehensive research.
... Low-level local ROS are significant because they regulate critical transcription factors (NFκB/IκB, Nrf2/KEAP1, AP-1, p53, HIF-1) and act as redox-signaling molecules in a variety of pathways involved in ensuring the maintenance of cellular homeostasis molecules in a variety of pathways involved in ensuring the maintenance of cellular homeostasis (MAPK/ERK, PTK/PTP, PI3K-AKT-mTOR). As a result, ROS have the ability to influence several cellular processes, such as apoptosis, migration, differentiation, and proliferation [2]. ROS can work by directly interacting with certain receptors or by redox-activating signaling pathway components including transcription factors, protein phosphatases, and kinases. ...
The antioxidant defense mechanisms play a critical role in mitigating the deleterious effects of reactive oxygen species (ROS). Catalase stands out as a paramount enzymatic antioxidant. It efficiently catalyzes the decomposition of hydrogen peroxide (H 2 O 2) into water and oxygen, a potentially harmful byproduct of cellular metabolism. This reaction detoxifies H 2 O 2 and prevents oxidative damage. Catalase has been extensively studied as a therapeutic antioxidant. Its applications range from direct supplementation in conditions characterized by oxidative stress to gene therapy approaches to enhance endogenous catalase activity. The enzyme's stability, bioavailability, and the specificity of its delivery to target tissues are significant hurdles. Furthermore, studies employing conventional catalase formulations often face issues related to enzyme purity, activity, and longevity in the biological milieu. Addressing these challenges necessitates rigorous scientific inquiry and well-designed clinical trials. Such trials must be underpinned by sound experimental designs, incorporating advanced catalase formulations or novel delivery systems that can overcome existing limitations. Enhancing catalase's stability, specificity, and longevity in vivo could unlock its full therapeutic potential. It is necessary to understand the role of catalase in disease-specific contexts, paving the way for precision antioxidant therapy that could significantly impact the treatment of diseases associated with oxidative stress.
... PMs trigger pro-inflammatory signals through a Reactive Oxygen Species-dependent mechanism [94]. Oxidative stress, characterized by an imbalance between oxidants and antioxidants, can cause cell damage by oxidizing nucleic acids, proteins, and lipids, leading to cell death via apoptosis or necrosis [95]. There is much high-quality evidence in the literature from in vivo studies that chronic exposure to PM 2.5 increases serum Interleucin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-α), total cholesterol (TC), and Low-density lipoprotein C (LDL-C) levels, increases the expression of oxidative stress-related genes, causes progression of atherosclerosis, and leads to increased inflammation and redox levels in mice [95]. ...
... Oxidative stress, characterized by an imbalance between oxidants and antioxidants, can cause cell damage by oxidizing nucleic acids, proteins, and lipids, leading to cell death via apoptosis or necrosis [95]. There is much high-quality evidence in the literature from in vivo studies that chronic exposure to PM 2.5 increases serum Interleucin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-α), total cholesterol (TC), and Low-density lipoprotein C (LDL-C) levels, increases the expression of oxidative stress-related genes, causes progression of atherosclerosis, and leads to increased inflammation and redox levels in mice [95]. Increasing the antioxidant capacity of exposed cells has been shown to reduce the harmful effects of PM 2.5 and PM 10 [96]. ...
Current evidence suggests that airborne pollutants have a detrimental effect on fetal growth through the emergence of small for gestational age (SGA) or term low birth weight (TLBW). The study’s objective was to critically evaluate the available literature on the association between environmental pollution and the incidence of SGA or TLBW occurrence. A comprehensive literature search was conducted across Pubmed/MEDLINE, Web of Science, Cochrane Library, EMBASE, and Google Scholar using predefined inclusion and exclusion criteria. The methodology adhered to the PRISMA guidelines. The systematic review protocol was registered in PROSPERO with ID number: CRD42022329624. As a result, 69 selected papers described the influence of environmental pollutants on SGA and TLBW occurrence with an Odds Ratios (ORs) of 1.138 for particulate matter ≤ 10 μm (PM10), 1.338 for particulate matter ≤ 2.5 μm (PM2.5), 1.173 for ozone (O3), 1.287 for sulfur dioxide (SO2), and 1.226 for carbon monoxide (CO). All eight studies analyzed validated that exposure to volatile organic compounds (VOCs) is a risk factor for SGA or TLBW. Pregnant women in the high-risk group of SGA occurrence, i.e., those living in urban areas or close to sources of pollution, are at an increased risk of complications. Understanding the exact exposure time of pregnant women could help improve prenatal care and timely intervention for fetuses with SGA. Nevertheless, the pervasive air pollution underscored in our findings suggests a pressing need for adaptive measures in everyday life to mitigate worldwide environmental pollution.
... These species, especially ROS, have a high preponderance in cell death by some mechanisms, including DNA damage culminating in extensive mutagenesis that leads to irreversible damage and, ultimately, the loss of viability. The induction of an apoptotic-like process and the inhibition of essential metabolic processes are other mechanisms of cell death by means of ROS [54,55]. It is also reported that silver ions cause the separation of paired DNA strands in bacteria and weaken the bond between protein and DNA, and ROS are generated as a consequence of this phenomenon [53]. ...
Tooth loss during the lifetime of an individual is common. A strategy to treat partial or complete edentulous patients is the placement of dental implants. However, dental implants are subject to bacterial colonization and biofilm formation, which cause an infection named peri-implantitis. The existing long-term treatments for peri-implantitis are generally inefficient. Thus, an electrical circuit was produced with zirconia (Zr) samples using a hot-pressing technique to impregnate silver (Ag) through channels and holes to create a path by LASER texturing. The obtained specimens were characterized according to vitro cytotoxicity, to ensure ZrAg non-toxicity. Furthermore, samples were inoculated with Staphylococcus aureus using 6.5 mA of alternating current (AC). The current was delivered using a potentiostat and the influence on the bacterial concentration was assessed. Using AC, the specimens displayed no bacterial adhesion (Log 7 reduction). The in vitro results presented in this study suggest that this kind of treatment can be an alternative and promising strategy to treat and overcome bacterial adhesion around dental implants that can evolve to biofilm.
... This includes regulation of HIFs, cellular proliferation and differentiation pathways such as the mitogen-activated protein kinase (MAPK) pathway, cellular growth through the phosphatidylinositol 3 kinase (PI3K) pathway and cellular apoptosis through the nuclear factor-κB (NF-κB) pathway. Furthermore, an increase in ROS production as a result of NADPH oxidase activation upon infection has been linked to the transcription of proinflammatory cytokines 127 . ...
Oxygen plays a crucial role in human embryogenesis, homeostasis, and tissue regeneration. Emerging engineered regenerative solutions call for novel oxygen delivery systems. To become a reality, these systems must consider physiological processes, oxygen release mechanisms and the target application. In this review, we explore the biological relevance of oxygen at both a cellular and tissue level, and the importance of its controlled delivery via engineered biomaterials and devices. Recent advances and upcoming trends in the field are also discussed with a focus on tissue-engineered constructs that could meet metabolic demands to facilitate regeneration.
... Recent statistics indicate that antibiotic-resistant infections contribute to over 35,000 deaths annually in the United States alone [6], while globally, they are responsible for approximately 700,000 deaths per year [7], resulting in heightened rates of illness and mortality. Simultaneously, the disruption of cellular equilibrium by the imbalance in reactive oxygen species (ROS) production establishes oxidative stress as a significant mechanism, with considerable implications for human health [8]. Uncontrolled oxidative stress can initiate a cascade of adverse effects, significantly elevating the risk of chronic conditions such as neurological disorders, cardiovascular diseases, cancer, and kidney disorders [8][9][10]. ...
... Simultaneously, the disruption of cellular equilibrium by the imbalance in reactive oxygen species (ROS) production establishes oxidative stress as a significant mechanism, with considerable implications for human health [8]. Uncontrolled oxidative stress can initiate a cascade of adverse effects, significantly elevating the risk of chronic conditions such as neurological disorders, cardiovascular diseases, cancer, and kidney disorders [8][9][10]. It was reported that ROS play a multifaceted role in bacterial survival, adaptation, and the development of MDR [11]. ...
Antibiotics play a crucial role in preserving and improving public health, saving millions of lives every year. However, their effectiveness is currently under threat due to the ability of bacteria to adapt and develop resistance to these treatments. Therefore, this study was carried out on two soil samples collected in two areas of Arba Aounate, Sidi Bennour province, Morocco, to identify natural antibiotic-producing Actinobacteria capable of combating multi-drug-resistant (MDR) bacteria. A primary screening revealed that of the 50 isolates, 16 exhibited antimicrobial activity against Pseudomonas aeruginosa ATCC 27,853, Staphylococcus aureus ATCC 25,923, Escherichia coli ATCC 25,922, and Candida albicans ATTC 60193. A secondary screening showed that of the 16 isolates, only EIZ1 and EIZ2 isolates displayed outstanding antimicrobial and antifungal activity against 6 MDR bacteria, including Escherichia coli 19L2418, Listeria monocytogenes, Proteus sp. 19K1313, Klebsiella pneumoniae 19K 929, Proteus vulgaris 16C1737, and Klebsiella pneumoniae 20B1572. These two isolates were also characterized culturally, morphologically, physiologically, and biochemically. Afterward, the amplification of 16S rRNA revealed that isolate EIZ2 was 99.06% strongly related to the genus Streptomyces. Furthermore, this extract exhibits strong antioxidant activity against DPPH and ABTS free radicals and elevated ferric-reducing antioxidant power. A significant (p < 0.0001) positive correlation was observed between antioxidant activities and total phenolic and flavonoid contents. A GC–MS analysis of the ethyl acetate extract revealed the presence of 10 compounds, mainly diethyl phthalate (97%) and benzeneacetic acid (94%). This research demonstrates that Streptomyces sp. strain EIZ2 represents a potential source of antimicrobial and antioxidant compounds. These compounds could offer considerable potential as therapeutic agents, paving the way for future developments in medical applications.
