RESUMEN
Reduction-oxidation (redox) chemistry plays a vital role in human homeostasis. These reactions play critical roles in energy generation, as part of innate immunity, and in the generation of secondary messengers with various functions such as cell cycle progression or the release of neurotransmitters. Despite this cornerstone role, if left unchecked, the body can overproduce reactive oxygen species (ROS) or reactive nitrogen species (RNS). When these overwhelm endogenous antioxidant systems, oxidative stress (OS) occurs. In neonates, OS has been associated with retinopathy of prematurity (ROP), leukomalacia, and bronchopulmonary dysplasia (BPD). Given its broad spectrum of effects, research has started to examine whether OS plays a role in necrotizing enterocolitis (NEC). In this paper, we will discuss the basics of redox chemistry and how the human body keeps these in check. We will then discuss what happens when these go awry, focusing mostly on NEC in neonates.
Asunto(s)
Enterocolitis Necrotizante , Oxidación-Reducción , Estrés Oxidativo , Especies de Nitrógeno Reactivo , Especies Reactivas de Oxígeno , Humanos , Enterocolitis Necrotizante/metabolismo , Enterocolitis Necrotizante/patología , Especies Reactivas de Oxígeno/metabolismo , Recién Nacido , Especies de Nitrógeno Reactivo/metabolismo , Antioxidantes/metabolismo , AnimalesRESUMEN
OBJECTIVES: To perform a comparative analysis of the extended APPROPRIATE trial of measures of reactive nitrogen species and antioxidant capacity in patients having resistant hypertension with controlled hypertension and healthy controls. RESULTS: Mean serum NO2- and NOx levels were significantly lower and mean AOC was significantly higher in patients with controlled hypertension (n = 38) and healthy controls (n = 38) compared to resistant hypertension (RHTN) patients (n = 40) at the pre-intervention stage (p < 0.001). The serum NO2-, NOx and AOC levels of both controlled hypertension and healthy controls were comparable to those of the RHTN patients following treatment with propranolol (n = 18). Considering all samples (n = 114) we noted that there were significant weak and moderate positive correlations between NO2- levels with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (r = 0.396, p < 0.001 and r = 0.292, p = 0.004) as well as total NOx levels with SBP and DBP (r = 0.636 and r = 0.480 respectively, p < 0.001). Conversely, there was a significant negative correlation between AOC levels with SBP and DBP (r= -0.846 and r = -0.626 respectively, p < 0.001).
Asunto(s)
Antihipertensivos , Antioxidantes , Hipertensión , Propranolol , Especies de Nitrógeno Reactivo , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/sangre , Hipertensión/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Antioxidantes/metabolismo , Propranolol/uso terapéutico , Propranolol/farmacología , Antihipertensivos/uso terapéutico , Estudios de Casos y Controles , Especies de Nitrógeno Reactivo/sangre , Especies de Nitrógeno Reactivo/metabolismo , Presión Sanguínea/efectos de los fármacos , Adulto , Estudios de Seguimiento , AncianoRESUMEN
Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.
Asunto(s)
Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Animales , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Administración Oral , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Catequina/análogos & derivados , Catequina/química , Catequina/administración & dosificación , Catequina/farmacología , Galio/química , Galio/farmacología , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Colitis/tratamiento farmacológico , Humanos , Especies de Nitrógeno Reactivo/metabolismoRESUMEN
Soil salinity is a major constraint for sustainable agricultural productivity, which together with the incessant climate change may be transformed into a severe threat to the global food security. It is, therefore, a serious concern that needs to be addressed expeditiously. The overproduction and accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the key events occurring during salt stress, consequently employing nitro-oxidative stress and programmed cell death in plants. However, very sporadic studies have been performed concerning different aspects of nitro-oxidative stress in plants under salinity stress. The ability of plants to tolerate salinity is associated with their ability to maintain the cellular redox equilibrium mediated by both non-enzymatic and enzymatic antioxidant defense mechanisms. The present review emphasizes the mechanisms of ROS and RNS generation in plants, providing a detailed evaluation of how redox homeostasis is conserved through their effective removal. The uniqueness of this article stems from its incorporation of expression analyses of candidate genes for different antioxidant enzymes involved in ROS and RNS detoxification across various developmental stages and tissues of rice, utilizing publicly available microarray data. It underscores the utilization of modern biotechnological methods to improve salinity tolerance in crops, employing different antioxidants as markers. The review also explores how various transcription factors contribute to plants' ability to tolerate salinity by either activating or repressing the expression of stress-responsive genes. In summary, the review offers a thorough insight into the nitro-oxidative homeostasis strategy for extenuating salinity stress in plants.
Asunto(s)
Homeostasis , Especies de Nitrógeno Reactivo , Especies Reactivas de Oxígeno , Tolerancia a la Sal , Especies Reactivas de Oxígeno/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Tolerancia a la Sal/genética , Regulación de la Expresión Génica de las Plantas , Estrés Oxidativo , Antioxidantes/metabolismo , Oxidación-Reducción , Plantas/metabolismo , SalinidadRESUMEN
The Oryza genus, containing Oryza sativa L., is quintessential to sustain global food security. This genus has a lot of sophisticated molecular mechanisms to cope with environmental stress, particularly during vulnerable stages like flowering. Recent studies have found key involvements and genetic modifications that increase resilience to stress, including exogenous application of melatonin, allantoin, and trehalose as well as OsSAPK3 and OsAAI1 in the genetic realm. Due to climate change and anthropogenic reasons, there is a rise in sea level which raises a concern of salinity stress. It is tackled through osmotic adjustment and ion homeostasis, mediated by genes like P5CS, P5CR, GSH1, GSH2, and SPS, and ion transporters like NHX, NKT, and SKC, respectively. Oxidative damage is reduced by a complex action of antioxidants, scavenging RONS. A complex action of genes mediates cold stress with studies highlighting the roles of OsWRKY71, microRNA2871b, OsDOF1, and OsICE1. There is a need to research the mechanism of action of proteins like OsRbohA in ROS control and the action of regulatory genes in stress response. This is highly relevant due to the changing climate which will raise a lot of environmental changes that will adversely affect production and global food security if certain countermeasures are not taken. Overall, this study aims to unravel the molecular intricacies of ROS and RNS signaling networks in Oryza plants under stress conditions, with the ultimate goal of informing strategies for enhancing stress tolerance and crop performance in this important agricultural genus.
Asunto(s)
Regulación de la Expresión Génica de las Plantas , Oryza , Especies de Nitrógeno Reactivo , Especies Reactivas de Oxígeno , Transducción de Señal , Estrés Fisiológico , Oryza/genética , Oryza/metabolismo , Oryza/fisiología , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico/genética , Especies de Nitrógeno Reactivo/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genéticaRESUMEN
MAIN CONCLUSION: Reactive nitrogen species mitigate the deteriorative effect of accelerated seed ageing by affecting the glutathione concentration and activities of GR and GPX-like. The treatment of apple (Malus domestica Borkh.) embryos isolated from accelerated aged seeds with nitric oxide-derived compounds increases their vigour and is linked to the alleviation of the negative effect of excessive oxidation processes. Reduced form of glutathione (GSH) is involved in the maintenance of redox potential. Glutathione peroxidase-like (GPX-like) uses GSH and converts it to oxidised form (GSSG), while glutathione reductase (GR) reduces GSSG into GSH. The aim of this work was to investigate the impact of the short-time NOx treatment of embryos isolated from apple seeds subjected to accelerated ageing on glutathione-related parameters. Apple seeds were subjected to accelerated ageing for 7, 14 or 21 days. Isolated embryos were shortly treated with NOx and cultured for 48 h. During ageing, in the axes of apple embryos, GSH and GSSG levels as well as half-cell reduction potential remained stable, while GR and GPX-like activities decreased. However, the positive effect of NOx in the vigour preservation of embryos isolated from prolonged aged seeds is linked to the increased total glutathione pool, and above all, higher GSH content. Moreover, NOx increased the level of transcripts encoding GPX-like and stimulated enzymatic activity. The obtained results indicate that high seed vigour related to the mode of action of NO and its derivatives is closely linked to the maintenance of higher GSH levels.
Asunto(s)
Glutatión , Malus , Semillas , Malus/genética , Malus/metabolismo , Semillas/metabolismo , Semillas/genética , Glutatión/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Reductasa/genética , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/genética , Oxidación-Reducción , Óxido Nítrico/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
KEY MESSAGE: Plants respond to environmental challenges by producing reactive species such as ROS and RNS, which play critical roles in signaling pathways that lead to adaptation and survival strategies. Understanding these pathways, as well as their detection methods and effects on plant development and metabolism, provides insight into increasing crop tolerance to combined stresses. Plants encounter various environmental stresses (abiotic and biotic) that affect plant growth and development. Plants sense biotic and abiotic stresses by producing different molecules, including reactive species, that act as signaling molecules and stimulate secondary messengers and subsequent gene transcription. Reactive oxygen and nitrogen species (ROS and RNS) are produced in both physiological and pathological conditions in the plasma membranes, chloroplasts, mitochondria, and endoplasmic reticulum. Various techniques, including spectroscopy, chromatography, and fluorescence methods, are used to detect highly reactive, short-half-life ROS and RNS either directly or indirectly. In this review, we highlight the roles of ROS and RNS in seed germination, root development, senescence, mineral nutrition, and post-harvest control. In addition, we provide information on the specialized metabolism involved in plant growth and development. Secondary metabolites, including alkaloids, flavonoids, and terpenoids, are produced in low concentrations in plants for signaling and metabolism. Strategies for improving crop performance under combined drought and pathogen stress conditions are discussed in this review.
Asunto(s)
Plantas , Especies de Nitrógeno Reactivo , Especies Reactivas de Oxígeno , Transducción de Señal , Estrés Fisiológico , Especies Reactivas de Oxígeno/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Plantas/metabolismo , Fenómenos Fisiológicos de las Plantas , Desarrollo de la PlantaRESUMEN
Bitter taste receptors (TAS2Rs) are not only responsible for taste perception in the oral cavity, but are spread throughout the body, generating a widespread chemosensory system. In humans, 25 subtypes have been identified and are differentially expressed in tissues and organs, including in the immune system. In fact, several TAS2R subtypes have been detected in neutrophils, lymphocytes, B and T cells, NK cells, and monocytes/macrophages, in which they regulate various protective functions of the innate immune system. Given its recognized anti-inflammatory and antioxidant activity, and the generally protective role of bitter taste receptors, in this work, we studied TAS2R46's potential in the protection of human monocyte/macrophage DNA from stress-induced damage. Through both direct and indirect assays and a single-cell gel electrophoresis assay, we demonstrated that absinthin, a specific TAS2R46 agonist, counteracts the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and reduces DNA damage in both cell types. Even though the release of ROS from monocytes/macrophages is fundamental for contrast pathogen agents, supraphysiological ROS production impairs their function, finally leading to cell death. Our results highlight TAS2R46 as a novel player involved in the protection of monocytes and macrophages from oxidative stress damage, while simultaneously supporting their antimicrobial activity.
Asunto(s)
Macrófagos , Monocitos , Estrés Oxidativo , Especies Reactivas de Oxígeno , Receptores Acoplados a Proteínas G , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Monocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Macrófagos/metabolismo , Daño del ADN , Especies de Nitrógeno Reactivo/metabolismoRESUMEN
Acute ischemic stroke (AIS) is one of the most predominant causes of mortality and disability in China. Significant uncertainties in stroke diagnosis and time of onset have resulted in inconsistent evidence on the association between ambient air pollution and the risk of AIS. The present study aimed to evaluate the impact of air pollution on AIS onset based on high time-resolution air pollution data and a stroke-specific registry across the past five years. Hourly concentrations of PM2.5, PM10, O3, SO2, CO, NO2 and nitrous acid (HONO) were monitored from 2017 to 2021, with which a distributed lag non-linear model and conditional logistic regression models coupled with a time-stratified case-crossover design were applied to 106,623 AIS cases recorded in the Shanghai Stroke Service (4S) database during the study period. Results from the conditional logistic regression models indicate that acute exposure to PM2.5, PM10, SO2, NO2 and HONO was found to be associated with AIS onset, respectively. The corresponding cumulative excessive risks of AIS onset were 0.8 %, 1 %, 2.4 %, 2.1 % and 1.8 % for each interquartile range increase in the respective concentration. The longest lag-effect (up to 13 h) was observed for reactive nitrogen species (RNS), such as NO2 and HONO, which remained robust in two-pollutant models. Similar important role of RNS in AIS onset were confirmed by the distributed lag non-linear model. By demonstrating the transient effect of ambient air pollution on AIS, especially the relationships between RNS and AIS for the first time, our study provides stringent evidence for future mitigation strategies for pollution emission and public health.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Accidente Cerebrovascular Isquémico , Especies de Nitrógeno Reactivo , China/epidemiología , Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Humanos , Accidente Cerebrovascular Isquémico/epidemiología , Material Particulado/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Masculino , Femenino , AncianoRESUMEN
Exogenous electrical stimulation has attracted considerable attention due to the advantages of microelectric induction and subsequent biological effects such as actin reorganization and reactive oxygen species (ROS) generation. Herein, an injectable hydrogel of BPR-ARG@Gel (BAG) with pyroelectric BPR nanoparticle loading and l-arginine (ARG) introduction was fabricated for advanced cancer therapy in vivo. Due to the photothermal effect, the holes and electrons in BPR nanoparticles were separated to produce an open-circuit voltage and consequently catalyze water H2O to generate toxic superoxide (â¢O2-) and hydroxyl radicals (â¢OH). These ROS substances further oxidize ARG to produce NO for synergistic tumor treatments. The mice experiments indicated that the employment of BAG hydrogel incorporation with a near-infrared laser downregulated the heat shock protein and recruited immune cells with 5-fold-enhanced expression of proinflammatory cytokines of interferon-γ. It was also noteworthy that the injectable hydrogel of BAG substantially induced the generation of reactive oxygen/nitrogen species (ROS/RNS) with reliable biosafety and strong tumor inhibition. Overall, these findings have provided potentially new inspirations and a feasible strategy to translate this multifunctional hydrogel toward tumor therapy in a pyroelectric stimulation manner.
Asunto(s)
Hidrogeles , Especies Reactivas de Oxígeno , Animales , Ratones , Especies Reactivas de Oxígeno/metabolismo , Hidrogeles/química , Hidrogeles/farmacología , Catálisis , Rayos Infrarrojos , Humanos , Arginina/química , Especies de Nitrógeno Reactivo/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias/patología , Línea Celular Tumoral , Nanopartículas/química , Ratones Endogámicos BALB C , Antineoplásicos/química , Antineoplásicos/farmacologíaRESUMEN
Cold atmospheric plasma (CAP) has emerged as an innovative tool with broad medical applications, including ovarian cancer (OC) treatment. By bringing CAP in close proximity to liquids such as water or cell culture media, solutions containing reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated, called plasma-activated media (PAM). In this systematic review, we conduct an in-depth analysis of studies focusing on PAM interactions with biological substrates. We elucidate the diverse mechanisms involved in the activation of different media and the complex network of chemical reactions underlying the generation and consumption of the prominent reactive species. Furthermore, we highlight the promises of PAM in advancing biomedical applications, such as its stability for extended periods under appropriate storage conditions. We also examine the application of PAM as an anti-cancer and anti-metastatic treatment for OC, with a particular emphasis on its ability to induce apoptosis via distinct signaling pathways, inhibit cell growth, suppress cell motility, and enhance the therapeutic effects of chemotherapy. Finally, the future outlook of PAM therapy in biomedical applications is speculated, with emphasis on the safety issues relevant to clinical translation.
Asunto(s)
Neoplasias Ováricas , Gases em Plasma , Especies de Nitrógeno Reactivo , Especies Reactivas de Oxígeno , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Femenino , Gases em Plasma/farmacología , Gases em Plasma/uso terapéutico , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medios de Cultivo , Movimiento Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Invasion and adhesion of neutrophils into tissues and their concomitant secretion play an important role in the development of vascular pathologies, including abdominal aortic aneurysm (AAA). Chronic administration of angiotensin II is used to initiate AAA formation in mice. The role of aldosterone in this process is being studied. We conducted for the first time a complex comparative study of the effects of angiotensin II and aldosterone on the adhesion of human neutrophils to fibronectin and the concomitant secretion of proteins, free amino acids as well as reactive oxygen (ROS) and nitrogen (NO) species. Neither angiotensin II nor aldosterone affected the attachment of neutrophils to fibronectin and the concomitant production of ROS. We showed for the first time that aldosterone stimulated the release of amino acid hydroxylysine, a product of lysyl hydroxylase, the activity of which is positively correlated with cell invasiveness. Aldosterone also initiates the secretion of matrix metalloproteinase 9 (MMP-9) and cathepsin G, which may reorganize the extracellular matrix and stimulate the recruitment and adhesion of neutrophils to the aortic walls. Angiotensin II did not affect protein secretion. It may contribute to neutrophil-induced vascular injury by inhibiting the production of NO or by increasing the secretion of isoleucine. Our results suggest that it is aldosterone-induced neutrophil secretion that may play a significant role in neutrophil-induced vascular wall destruction in angiotensin II-induced AAA or other vascular complications.
Asunto(s)
Aldosterona , Angiotensina II , Adhesión Celular , Neutrófilos , Especies Reactivas de Oxígeno , Humanos , Angiotensina II/metabolismo , Angiotensina II/farmacología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Aldosterona/metabolismo , Adhesión Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Fibronectinas/metabolismo , Células Cultivadas , Catepsina G/metabolismo , Aminoácidos/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patologíaRESUMEN
Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that affects the digestive system and includes Crohn's disease (CD) and ulcerative colitis (UC). Although the exact etiology of IBD remains uncertain, dysfunctional immunoregulation of the gut is believed to be the main culprit. Amongst the immunoregulatory factors, reactive oxygen species (ROS) and reactive nitrogen species (RNS), components of the oxidative stress event, are produced at abnormally high levels in IBD. Their destructive effects may contribute to the disease's initiation and propagation, as they damage the gut lining and activate inflammatory signaling pathways, further exacerbating the inflammation. Oxidative stress markers, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serum-free thiols (R-SH), can be measured in the blood and stool of patients with IBD. These markers are elevated in patients with IBD, and their levels correlate with the severity of the disease. Thus, oxidative stress markers can be used not only in IBD diagnosis but also in monitoring the response to treatment. It can also be targeted in IBD treatment through the use of antioxidants, including vitamin C, vitamin E, glutathione, and N-acetylcysteine. In this review, we summarize the role of oxidative stress in the pathophysiology of IBD, its diagnostic targets, and the potential application of antioxidant therapies to manage and treat IBD.
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Enfermedades Inflamatorias del Intestino , Estrés Oxidativo , Humanos , Estrés Oxidativo/fisiología , Enfermedades Inflamatorias del Intestino/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Biomarcadores/metabolismo , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Especies de Nitrógeno Reactivo/metabolismo , AnimalesRESUMEN
Reactive oxygen species (ROS), reactive sulfur species (RSS), metal ions, and nitrogen species (RNS) play important roles in a variety of biological processes, such as a signal transduction, inflammation, and neurodegenerative damage. These species, while essential for certain functions, can also induce stress-related diseases. The interrelation between ROS, RSS, Metal ions and RNS underscores the importance of quantifying their concentrations in live cells, tissues, and organisms. The review emphasizes the use of small-molecule-based fluorescent/chemodosimeter probes to effectively measure and map the species' distribution with high temporal and spatial precision, paying particular attention to in vitro and in vivo environments. These probes are recognized as valuable tools contributing to breakthroughs in modern redox biology. The review specifically addresses the relationship of HOCl/ClOâ¾ (hypochlorous acid/Hypochlorite) with other reactive species. (Dual sensing probes).
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Colorantes Fluorescentes , Ácido Hipocloroso , Especies Reactivas de Oxígeno , Ácido Hipocloroso/análisis , Ácido Hipocloroso/química , Colorantes Fluorescentes/química , Humanos , Animales , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/análisis , Especies de Nitrógeno Reactivo/análisis , Especies de Nitrógeno Reactivo/química , Especies de Nitrógeno Reactivo/metabolismoRESUMEN
Selective generation of sufficient pyroptosis inducers at the tumor site without external stimulation holds immense significance for a longer duration of immunotherapy. Here, we report a cascade-amplified pyroptosis inducer CSCCPT/SNAP that utilizes reactive nitrogen species (RNS), self-supplied from the diffusion-controlled reaction between reactive oxygen species (ROS) and nitric oxide (NO) to potentiate pyroptosis and immunotherapy, while both endogenous mitochondrial ROS stimulated by released camptothecin and released NO initiate pyroptosis. Mechanistically, cascade amplification of the antitumor immune response is prompted by the cooperation of ROS and NO and enhanced by RNS with a long lifetime, which could be used as a pyroptosis trigger to effectively compensate for the inherent drawbacks of ROS, resulting in long-lasting pyroptosis for favoring immunotherapy. Tumor growth is efficiently inhibited in mouse melanoma tumors through the facilitation of reactive oxygen/nitrogen species (RONS)-NO synergy. In summary, our therapeutic approach utilizes supramolecular engineering and nanotechnology to integrate ROS producers and NO donors of tumor-specific stimulus responses into a system that guarantees synchronous generation of these two reactive species to elicit pyroptosis-evoked immune response, while using self-supplied RNS as a pyroptosis amplifier. RONS-NO synergy achieves enhanced and sustained pyroptosis and antitumor immune responses for robust cancer immunotherapy.
Asunto(s)
Inmunoterapia , Estrés Oxidativo , Piroptosis , Especies de Nitrógeno Reactivo , Microambiente Tumoral , Piroptosis/efectos de los fármacos , Animales , Especies de Nitrógeno Reactivo/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Melanoma Experimental/terapia , Melanoma Experimental/inmunología , Melanoma Experimental/patologíaRESUMEN
Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies.
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Neoplasias de la Mama , Ciclooxigenasa 2 , Progresión de la Enfermedad , Óxido Nítrico Sintasa de Tipo II , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Ciclooxigenasa 2/metabolismo , Femenino , Óxido Nítrico Sintasa de Tipo II/metabolismo , Microambiente Tumoral/efectos de los fármacos , Animales , Óxido Nítrico/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Especies de Nitrógeno Reactivo/metabolismoRESUMEN
The rapid perfusion of cerebral arteries leads to a significant increase in intracranial blood volume, exposing patients with traumatic brain injury to the risk of diffuse brain swelling or malignant brain herniation during decompressive craniectomy. The microcirculation and venous system are also involved in this process, but the precise mechanisms remain unclear. A physiological model of extremely high intracranial pressure was created in rats. This development triggered the TNF-α/NF-κB/iNOS axis in microglia, and released many inflammatory factors and reactive oxygen species/reactive nitrogen species, generating an excessive amount of peroxynitrite. Subsequently, the capillary wall cells especially pericytes exhibited severe degeneration and injury, the blood-brain barrier was disrupted, and a large number of blood cells were deposited within the microcirculation, resulting in a significant delay in the recovery of the microcirculation and venous blood flow compared to arterial flow, and this still persisted after decompressive craniectomy. Infliximab is a monoclonal antibody bound to TNF-α that effectively reduces the activity of TNF-α/NF-κB/iNOS axis. Treatment with Infliximab resulted in downregulation of inflammatory and oxidative-nitrative stress related factors, attenuation of capillary wall cells injury, and relative reduction of capillary hemostasis. These improved the delay in recovery of microcirculation and venous blood flow.
Asunto(s)
Hipertensión Intracraneal , Estrés Oxidativo , Animales , Ratas , Hipertensión Intracraneal/etiología , Hipertensión Intracraneal/tratamiento farmacológico , Masculino , Factor de Necrosis Tumoral alfa/metabolismo , Inflamación/metabolismo , Inflamación/patología , Microcirculación , Circulación Cerebrovascular , Ratas Sprague-Dawley , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Infliximab/farmacología , Infliximab/uso terapéutico , Modelos Animales de Enfermedad , Barrera Hematoencefálica/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Microglía/metabolismoRESUMEN
Oxidative stress results from the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in quantities exceeding the potential activity of the body's antioxidant system and is one of the risk factors for the development of vascular dysfunction in diabetes and exposure to ionizing radiation. Being the secondary products of normal aerobic metabolism in living organisms, ROS and RNS act as signaling molecules that play an important role in the regulation of vital organism functions. Meanwhile, in high concentrations, these compounds are toxic and disrupt various metabolic pathways. The various stress factors (hyperglycemia, gamma-irradiation, etc.) trigger free oxygen and nitrogen radicals accumulation in cells that are capable to damage almost all cellular components including ion channels and transporters such as Na+/K+-ATPase, BKCa, and TRP channels. Vascular dysfunctions are governed by interaction of ROS and RNS. For example, the reaction of ROS with NO produces peroxynitrite (ONOO-), which not only oxidizes DNA, cellular proteins, and lipids, but also disrupts important signaling pathways that regulate the cation channel functions in the vascular endothelium. Further increasing in ROS levels and formation of ONOO- leads to reduced NO bioavailability and causes endothelial dysfunction. Thus, imbalance of ROS and RNS and their affect on membrane ion channels plays an important role in the pathogenesis of vascular dysfunction associated with various disorders.
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Estrés Oxidativo , Especies Reactivas de Oxígeno , Humanos , Animales , Estrés Oxidativo/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Traumatismos por Radiación/metabolismo , Traumatismos por Radiación/fisiopatología , Traumatismos por Radiación/etiología , Estrés Nitrosativo/efectos de la radiación , Especies de Nitrógeno Reactivo/metabolismo , Transducción de Señal , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/fisiopatología , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatología , Radiación IonizanteRESUMEN
As well known, surface discharge cold plasma has efficient inactivation ability and a variety of RONS are main active particles for inactivation, but their synergistic mechanism is still not clear. Therefore, surface discharge cold plasma system was applied to treat Pseudomonas fluorescens to study bacterial inactivation mechanism and energy benefit. Results showed that energy efficiency was directly proportional to applied voltage and inversely proportional to initial concentration. Cold plasma treatment for 20 min was inactivated by approximately > 4-log10Pseudomonas fluorescens and application of â¢OH and 1O2 scavengers significantly improved survival rate. In addition, â¢OH and 1O2 destroyed cell membrane structure and membrane permeability, which promoted diffusion of RONS into cells and affecting energy metabolism and antioxidant capacity, leading to bacterial inactivation. Furthermore, accumulation of intracellular NO and ONOOH was related to infiltration of exogenous RNS, while accumulation of â¢OH, H2O2, 1O2, O2- was the result of joint action of endogenous and exogenous ROS. Transcriptome analysis revealed that different RONS of cold plasma were responsible for Pseudomonas fluorescens inactivation and related to activation of intracellular antioxidant defense system and regulation of genes expression related to amino acid metabolism and energy metabolism, which promoting cellular process, catalytic activity and other biochemical pathways.
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Gases em Plasma , Pseudomonas fluorescens , Especies Reactivas de Oxígeno , Pseudomonas fluorescens/metabolismo , Gases em Plasma/farmacología , Especies Reactivas de Oxígeno/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Microbiología del Agua , Viabilidad Microbiana/efectos de los fármacosRESUMEN
PURPOSE: We aimed to investigate early effects of exogenously administered adropin (AD) on neurological function, endothelial nitric oxide synthase (eNOS) expression, nitrite/nitrate levels, oxidative stress, and apoptosis in subarachnoid hemorrhage (SAH). METHODS: Following intracerebroventricular AD administration (10 µg/5 µl at a rate of 1 µl/min) SAH model was carried out in Sprague-Dawley rats by injection of autologous blood into the prechiasmatic cistern. The effects of AD were assessed 24 h following SAH. The modified Garcia score was employed to evaluate functional insufficiencies. Adropin and caspase-3 proteins were measured by ELISA, while nitrite/nitrate levels, total antioxidant capacity (TAC) and reactive oxygen/nitrogen species (ROS/RNS) were assayed by standard kits. eNOS expression and apoptotic neurons were detected by immunohistochemical analysis. RESULTS: The SAH group performed notably lower on the modified Garcia score compared to sham and SAH + AD groups. Adropin administration increased brain eNOS expression, nitrite/nitrate and AD levels compared to SHAM and SAH groups. SAH produced enhanced ROS/RNS generation and reduced antioxidant capacity in the brain. Adropin boosted brain TAC and diminished ROS/RNS production in SAH rats and no considerable change amongst SHAM and SAH + AD groups were detected. Apoptotic cells were notably increased in intensity and number after SAH and were reduced by AD administration. CONCLUSIONS: Adropin increases eNOS expression and reduces neurobehavioral deficits, oxidative stress, and apoptotic cell death in SAH model. Presented results indicate that AD provides protection in early brain injury associated with SAH.