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1.
Chem Commun (Camb) ; 60(42): 5546-5549, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38700121

RESUMO

Airborne nanoplastics can enter alveolar cells and trigger intracellular oxidative stress primarily. Herein, taking advantage of the high electrochemical resolution of SiC@Pt nanoelectrodes, we achieved the quantitative discrimination of the major ROS/RNS within A549 cells, disclosed the sources of their precursors, and observed that the NO (RNS precursor) level significantly increased, whereas O2˙- (ROS precursor) remained relatively stable during the nanoplastics exposure. This establishes that iNOS or mitochondrion-targeted treatment may be a preventive or therapeutic strategy for nanoplastic-induced lung injury.


Assuntos
Técnicas Eletroquímicas , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Espécies Reativas de Nitrogênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Eletrodos
2.
J Environ Manage ; 359: 121043, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38723497

RESUMO

Fertilizer-intensive agriculture leads to emissions of reactive nitrogen (Nr), posing threats to climate via nitrous oxide (N2O) and to air quality and human health via nitric oxide (NO) and ammonia (NH3) that form ozone and particulate matter (PM) downwind. Adding nitrification inhibitors (NIs) to fertilizers can mitigate N2O and NO emissions but may stimulate NH3 emissions. Quantifying the net effects of these trade-offs requires spatially resolving changes in emissions and associated impacts. We introduce an assessment framework to quantify such trade-off effects. It deploys an agroecosystem model with enhanced capabilities to predict emissions of Nr with or without the use of NIs, and a social cost of greenhouse gas to monetize the impacts of N2O on climate. The framework also incorporates reduced-complexity air quality and health models to monetize associated impacts of NO and NH3 emissions on human health downwind via ozone and PM. Evaluation of our model against available field measurements showed that it captured the direction of emission changes but underestimated reductions in N2O and overestimated increases in NH3 emissions. The model estimated that, averaged over applicable U.S. agricultural soils, NIs could reduce N2O and NO emissions by an average of 11% and 16%, respectively, while stimulating NH3 emissions by 87%. Impacts are largest in regions with moderate soil temperatures and occur mostly within two to three months of N fertilizer and NI application. An alternative estimate of NI-induced emission changes was obtained by multiplying the baseline emissions from the agroecosystem model by the reported relative changes in Nr emissions suggested from a global meta-analysis: -44% for N2O, -24% for NO and +20% for NH3. Monetized assessments indicate that on an annual scale, NI-induced harms from increased NH3 emissions outweigh (8.5-33.8 times) the benefits of reducing NO and N2O emissions in all agricultural regions, according to model-based estimates. Even under meta-analysis-based estimates, NI-induced damages exceed benefits by a factor of 1.1-4. Our study highlights the importance of considering multiple pollutants when assessing NIs, and underscores the need to mitigate NH3 emissions. Further field studies are needed to evaluate the robustness of multi-pollutant assessments.


Assuntos
Agricultura , Fertilizantes , Nitrificação , Óxido Nitroso , Fertilizantes/análise , Óxido Nitroso/análise , Poluentes Atmosféricos/análise , Ozônio/análise , Amônia/análise , Espécies Reativas de Nitrogênio/análise , Nitrogênio/análise , Poluição do Ar/análise
3.
Arch Toxicol ; 98(6): 1573-1580, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38573336

RESUMO

Dietary exposure to N-nitrosamines has recently been assessed by the European Food Safety Authority (EFSA) to result in margins of exposure that are conceived to indicate concern with respect to human health risk. However, evidence from more than half a century of international research shows that N-nitroso compounds (NOC) can also be formed endogenously. In this commentary of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG), the complex metabolic and physiological biokinetics network of nitrate, nitrite and reactive nitrogen species is discussed with emphasis on its influence on endogenous NOC formation. Pioneering approaches to monitor endogenous NOC have been based on steady-state levels of N-nitrosodimethylamine (NDMA) in human blood and on DNA adduct levels in blood cells. Further NOC have not been considered yet to a comparable extent, although their generation from endogenous or exogenous precursors is to be expected. The evidence available to date indicates that endogenous NDMA exposure could exceed dietary exposure by about 2-3 orders of magnitude. These findings require consolidation by refined toxicokinetics and DNA adduct monitoring data to achieve a credible and comprehensive human health risk assessment.


Assuntos
Adutos de DNA , Exposição Dietética , Dimetilnitrosamina , Nitrosaminas , Humanos , Medição de Risco , Nitrosaminas/toxicidade , Nitrosaminas/farmacocinética , Exposição Dietética/efeitos adversos , Dimetilnitrosamina/toxicidade , Contaminação de Alimentos , Inocuidade dos Alimentos , Animais , Nitritos/toxicidade , Nitratos/toxicidade , Nitratos/farmacocinética , Espécies Reativas de Nitrogênio/metabolismo
4.
Talanta ; 274: 126004, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38564824

RESUMO

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological applications.


Assuntos
Corantes Fluorescentes , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Rodaminas , Corantes Fluorescentes/química , Rodaminas/química , Espécies Reativas de Nitrogênio/análise , Humanos , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/análise , Imagem Óptica , Animais , Enxofre/química , Enxofre/análise
5.
Redox Biol ; 72: 103123, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615489

RESUMO

Redox signaling, a mode of signal transduction that involves the transfer of electrons from a nucleophilic to electrophilic molecule, has emerged as an essential regulator of inflammatory macrophages. Redox reactions are driven by reactive oxygen/nitrogen species (ROS and RNS) and redox-sensitive metabolites such as fumarate and itaconate, which can post-translationally modify specific cysteine residues in target proteins. In the past decade our understanding of how ROS, RNS, and redox-sensitive metabolites control macrophage function has expanded dramatically. In this review, we discuss the latest evidence of how ROS, RNS, and metabolites regulate macrophage function and how this is dysregulated with disease. We highlight the key tools to assess redox signaling and important questions that remain.


Assuntos
Macrófagos , Oxirredução , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Transdução de Sinais , Succinatos , Macrófagos/metabolismo , Humanos , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais
6.
ACS Appl Mater Interfaces ; 16(13): 16232-16242, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38507798

RESUMO

The development of self-powered sterilizers has garnered significant attention in the scientific and engineering fields. However, there remains an urgent need to improve their sterilization efficiency. In this study, we present a self-powered sterilizer with superior antibacterial capability by maximizing the utilization of breakdown discharge generated by a soft-contact freestanding rotary triboelectric nanogenerator (FR-TENG). To achieve this, a collaborative optimization strategy is proposed, encompassing the structural design of the FR-TENG, the implementation of double voltage rectification, and manipulation of the gaseous phase. Through a comprehensive analysis of antibacterial rates and microscopic images, the effectiveness of the self-powered sterilizer against various types of bacteria, including Gram-positive and Gram-negative species, as well as mixed bacteria in natural seawater, is demonstrated. Further investigations into bacterial morphologies and solution compositions reveal that the synergistic effect between electroporation and the generation of reactive oxygen/nitrogen species contributes to efficient sterilization. Additionally, controlled trials and molecular dynamics simulations are conducted to quantitatively elucidate the synergistic antibacterial effect between electroporation and reactive oxygen/nitrogen species. This study highlights the effectiveness of the collaborative optimization strategy in enhancing the sterilization efficiency of self-powered sterilizers while providing valuable insights into the synergistic antibacterial mechanisms of physical and chemical sterilization.


Assuntos
Líquidos Corporais , Eletroporação , Antibacterianos/farmacologia , Nitrogênio , Oxigênio , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio
7.
Artigo em Inglês | MEDLINE | ID: mdl-38521444

RESUMO

Hypometabolism is a common strategy employed by resilient species to withstand environmental stressors that would be life-threatening for other organisms. Under conditions such as hypoxia/anoxia, temperature and salinity stress, or seasonal changes (e.g. hibernation, estivation), stress-tolerant species down-regulate pathways to decrease energy expenditures until the return of less challenging conditions. However, it is with the return of these more favorable conditions and the reactivation of basal metabolic rates that a strong increase of reactive oxygen and nitrogen species (RONS) occurs, leading to oxidative stress. Over the last few decades, cases of species capable of enhancing antioxidant defenses during hypometabolic states have been reported across taxa and in response to a variety of stressors. Interpreted as an adaptive mechanism to counteract RONS formation during tissue hypometabolism and reactivation, this strategy was coined "Preparation for Oxidative Stress" (POS). Laboratory experiments have confirmed that over 100 species, spanning 9 animal phyla, apply this strategy to endure harsh environments. However, the challenge remains to confirm its occurrence in the natural environment and its wide applicability as a key survival element, through controlled experimentation in field and in natural conditions. Under such conditions, numerous confounding factors may complicate data interpretation, but this remains the only approach to provide an integrative look at the evolutionary aspects of ecophysiological adaptations. In this review, we provide an overview of representative cases where the POS strategy has been demonstrated among diverse species in natural environmental conditions, discussing the strengths and weaknesses of these results and conclusions.


Assuntos
Antioxidantes , Estresse Oxidativo , Animais , Estresse Oxidativo/fisiologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Meio Ambiente , Oxigênio , Hipóxia/metabolismo , Espécies Reativas de Nitrogênio
8.
Cell Immunol ; 399-400: 104811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38518686

RESUMO

Helicobacter pylori-associated stomach infection is a leading cause of gastric ulcer and related cancer. H. pylori modulates the functions of infiltrated immune cells to survive the killing by reactive oxygen and nitrogen species (ROS and RNS) produced by these cells. Uncontrolled immune responses further produce excess ROS and RNS which lead to mucosal damage. The persistent oxidative stress is a major cause of gastric cancer. H. pylori regulates nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs), nitric oxide synthase 2 (NOS2), and polyamines to control ROS and RNS release through lesser-known mechanisms. ROS and RNS produced by these pathways differentiate macrophages and T cells from protective to inflammatory phenotype. Pathogens-associated molecular patterns (PAMPs) induced ROS activates nuclear oligomerization domain (NOD), leucine rich repeats (LRR) and pyrin domain-containing protein 3 (NLRP3) inflammasome for the release of pro-inflammatory cytokines. This study evaluates the role of H. pylori secreted concentrated proteins (HPSCP) related oxidative stress role in NLRP3 inflammasome activation and macrophage differentiation. To perceive the role of ROS/RNS, THP-1 and AGS cells were treated with 10 µM diphenyleneiodonium (DPI), 50 µM salicyl hydroxamic acid (SHX), 5 µM Carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP), which are specific inhibitors of NADPH oxidase (NOX), Myeloperoxidase (MPO), and mitochondrial oxidative phosphorylation respectively. Cells were also treated with 10 µM of NOS2 inhibitor l-NMMA and 10 µM of N-acetyl cysteine (NAC), a free radical scavenger·H2O2 (100 µM) treated and untreated cells were used as positive controls and negative control respectively. The expression of gp91phox (NOX2), NOS2, NLRP3, CD86 and CD163 was analyzed through fluorescent microscopy. THP-1 macrophages growth was unaffected whereas the gastric epithelial AGS cells proliferated in response to higher concentration of HPSCP. ROS and myeloperoxidase (MPO) level increased in THP-1 cells and nitric oxide (NO) and lipid peroxidation significantly decreased in AGS cells. gp91phox expression was unchanged, whereas NOS2 and NLRP3 downregulated in response to HPSCP, but increased after inhibition of NO, ROS and MPO in THP-1 cells. HPSCP upregulated the expression of M1 and M2 macrophage markers, CD86 and CD163 respectively, which was decreased after the inhibition of ROS. This study concludes that there are multiple pathways which are generating ROS during H. pylori infection which further regulates other cellular processes. NO is closely associated with MPO and inhibition of NLRP3 inflammasome. The low levels of NO and MPO regulates gastrointestinal tract homeostasis and overcomes the inflammatory response of NLRP3. The ROS also plays crucial role in macrophage polarization hence alter the immune responses duing H. pylori pathogenesis.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Inflamassomos , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo , Espécies Reativas de Oxigênio , Humanos , Helicobacter pylori/imunologia , Espécies Reativas de Oxigênio/metabolismo , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/metabolismo , Inflamassomos/metabolismo , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Proteínas de Bactérias/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Células THP-1 , NADPH Oxidases/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Diferenciação Celular/imunologia
9.
Int J Mol Sci ; 25(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474253

RESUMO

The brain's unique characteristics make it exceptionally susceptible to oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) production, reactive nitrogen species (RNS) production, and antioxidant defense mechanisms. This review explores the factors contributing to the brain's vascular tone's vulnerability in the presence of oxidative damage, which can be of clinical interest in critically ill patients or those presenting acute brain injuries. The brain's high metabolic rate and inefficient electron transport chain in mitochondria lead to significant ROS generation. Moreover, non-replicating neuronal cells and low repair capacity increase susceptibility to oxidative insult. ROS can influence cerebral vascular tone and permeability, potentially impacting cerebral autoregulation. Different ROS species, including superoxide and hydrogen peroxide, exhibit vasodilatory or vasoconstrictive effects on cerebral blood vessels. RNS, particularly NO and peroxynitrite, also exert vasoactive effects. This review further investigates the neuroprotective effects of antioxidants, including superoxide dismutase (SOD), vitamin C, vitamin E, and the glutathione redox system. Various studies suggest that these antioxidants could be used as adjunct therapies to protect the cerebral vascular tone under conditions of high oxidative stress. Nevertheless, more extensive research is required to comprehensively grasp the relationship between oxidative stress and cerebrovascular tone, and explore the potential benefits of antioxidants as adjunctive therapies in critical illnesses and acute brain injuries.


Assuntos
Lesões Encefálicas , Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Oxigênio/farmacologia , Nitrogênio/farmacologia , Estresse Oxidativo , Antioxidantes/farmacologia , Espécies Reativas de Nitrogênio/metabolismo , Niacinamida/farmacologia , Lesões Encefálicas/tratamento farmacológico
10.
Adv Mater ; 36(19): e2304991, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38408365

RESUMO

The eradication of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge due to its development of biofilm-induced antibiotic resistance and impaired innate immunity, which often leads to frequent surgical failure. Here, the design, synthesis, and performance of X-ray-activated polymer-reinforced nanotherapeutics that modulate the immunological properties of infectious microenvironments to enhance chemoradiotherapy against multidrug-resistant bacterial deep-tissue infections are reported. Upon X-ray radiation, the proposed polymer-reinforced nanotherapeutic generates reactive oxygen species and reactive nitrogen species. To robustly eradicate MRSA biofilms at deep infection sites, these species can specifically bind to MRSA and penetrate biofilms for enhanced chemoradiotherapy treatment. X-ray-activated nanotherapeutics modulate the innate immunity of macrophages to prevent the recurrence of osteomyelitis. The remarkable anti-infection effects of these nanotherapeutics are validated using a rat osteomyelitis model. This study demonstrates the significant potential of a synergistic chemoradiotherapy and immunotherapy method for treating MRSA biofilm-infected osteomyelitis.


Assuntos
Biofilmes , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Polímeros , Infecções Estafilocócicas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Osteomielite/tratamento farmacológico , Osteomielite/terapia , Osteomielite/microbiologia , Animais , Infecções Estafilocócicas/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Ratos , Polímeros/química , Polímeros/farmacologia , Quimiorradioterapia/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Espécies Reativas de Nitrogênio/metabolismo
11.
Redox Biol ; 71: 103092, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38377788

RESUMO

In this review, we explore how short-chain fatty acids (SCFAs) produced by the gut microbiome affect Parkinson's disease (PD) through their modulatory interactions with alpha-synuclein, neuroinflammation, and oxidative stress mediated by reactive oxygen and nitrogen species (ROS/RNS). In particular, SCFAs-such as acetate, propionate, and butyrate-are involved in gut-brain communication and can modulate alpha-synuclein aggregation, a hallmark of PD. The gut microbiome of patients with PD has lower levels of SCFAs than healthy individuals. Probiotics may be a potential strategy to restore SCFAs and alleviate PD symptoms, but the underlying mechanisms are not fully understood. Also in this review, we discuss how alpha-synuclein, present in the guts and brains of patients with PD, may induce neuroinflammation and oxidative stress via ROS/RNS. Alpha-synuclein is considered an early biomarker for PD and may link the gut-brain axis to the disease pathogenesis. Therefore, elucidating the role of SCFAs in the gut microbiome and their impact on alpha-synuclein-induced neuroinflammation in microglia and on ROS/RNS is crucial in PD pathogenesis and treatment.


Assuntos
Microbioma Gastrointestinal , Doença de Parkinson , Humanos , alfa-Sinucleína , Ácidos Graxos Voláteis , Doenças Neuroinflamatórias , Oxigênio , Doença de Parkinson/etiologia , Doença de Parkinson/terapia , Doença de Parkinson/patologia , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio
12.
Vascul Pharmacol ; 154: 107282, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38325566

RESUMO

Atherosclerosis is a chronic inflammatory disease in which fats, lipids, cholesterol, calcium, proliferating smooth muscle cells, and immune cells accumulate in the intima of the large arteries, forming atherosclerotic plaques. A complex interplay of various vascular and immune cells takes place during the initiation and progression of atherosclerosis. Multiple reports indicate that tight control of reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) production is critical for maintaining vascular health. Unrestricted ROS and RNS generation may lead to activation of various inflammatory signaling pathways, facilitating atherosclerosis. Given these deleterious consequences, it is important to understand how ROS and RNS affect the signaling processes involved in atherogenesis. Conversely, RSS appears to exhibit an atheroprotective potential and can alleviate the deleterious effects of ROS and RNS. Herein, we review the literature describing the effects of ROS, RNS, and RSS on vascular smooth muscle cells, endothelial cells, and macrophages and focus on how changes in their production affect the initiation and progression of atherosclerosis. This review also discusses the contribution of ROS, RNS, and RSS in mediating various post-translational modifications, such as oxidation, nitrosylation, and sulfation, of the molecules involved in inflammatory signaling.


Assuntos
Aterosclerose , Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Nitrogênio , Células Endoteliais/metabolismo , Transdução de Sinais , Espécies Reativas de Nitrogênio/metabolismo , Enxofre
13.
Luminescence ; 39(2): e4697, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38388787

RESUMO

As a high reactive oxygen species (ROS) and a reactive nitrogen species (RNS), peroxynitrite anion (ONOO- ) is widely present in organisms and plays influential roles in physiological and pathological processes. It is of great significance to develop effective fluorescent probes for imaging peroxynitrite variation in living systems. Herein we present a novel fluorescent probe TQC0 for monitoring ONOO- based on the iminocoumarin platform, and this probe was synthesized by the knoevenagel condensation between a dihydropyridine-salicylaldehyde derivative and 2-benzothiazole-acetonitrile, and subsequently masked with the boronate moiety. The obtained probe TQC0 exhibited a high signal-to-noise ratio (206-fold) and a quick 'turn-on' response (about 10 min) with great selectivity and sensitivity. Furthermore, the probe TQC0 was successfully applied for imaging ONOO- in living cells with low cytotoxicity.


Assuntos
Corantes Fluorescentes , Ácido Peroxinitroso , Razão Sinal-Ruído , Espécies Reativas de Nitrogênio , Imagem Óptica
14.
Science ; 383(6683): 607-611, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38330103

RESUMO

There is growing concern about sensory pollutants affecting ecological communities. Anthropogenically enhanced oxidants [ozone (O3) and nitrate radicals (NO3)] rapidly degrade floral scents, potentially reducing pollinator attraction to flowers. However, the physiological and behavioral impacts on pollinators and plant fitness are unknown. Using a nocturnal flower-moth system, we found that atmospherically relevant concentrations of NO3 eliminate flower visitation by moths, and the reaction of NO3 with a subset of monoterpenes is what reduces the scent's attractiveness. Global atmospheric models of floral scent oxidation reveal that pollinators in certain urban areas may have a reduced ability to perceive and navigate to flowers. These results illustrate the impact of anthropogenic pollutants on an animal's olfactory ability and indicate that such pollutants may be critical regulators of global pollination.


Assuntos
Poluentes Ambientais , Mariposas , Nitratos , Odorantes , Oenothera , Polinização , Espécies Reativas de Nitrogênio , Olfato , Animais , Flores/fisiologia , Mariposas/fisiologia , Feromônios , Polinização/fisiologia , Oenothera/fisiologia , Manduca/fisiologia , Poluição Ambiental
15.
ACS Macro Lett ; 13(3): 288-295, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38368530

RESUMO

We report a facile stimuli-responsive strategy to generate reactive oxygen and nitrogen species (ROS and RNS) in the biological milieu from a photocleavable water-soluble block copolymer under visible light irradiation (427 nm, 2.25 mW/cm2). An anthraquinone-based water-soluble polymeric nitric oxide (NO) donor (BCPx-NO) is synthesized, which exhibits NO release in the range of 40-65 µM within 10 h of photoirradiation with a half-life of 30-103 min. Additionally, BCPx-NO produces peroxynitrite (ONOO-) and singlet oxygen (1O2) under photoirradiation. To understand the mechanism of NO release and photolysis of the functional group under blue light, we prepared a small-molecule anthraquinone-based N-nitrosamine (NOD). The cellular investigation of the effect of spatiotemporally controlled ONOO- and 1O2 generation from the NO donor polymeric nanoparticles in a triple negative breast adenocarcinoma (MDA-MB-231) under visible light irradiation (white light, 5.83 mW/cm2; total dose 31.5 J/cm2) showed an IC50 of 0.6 mg/mL. The stimuli-responsive strategy using a photolabile water-soluble block copolymer employed to generate ROS and RNS in a biological setting widens the horizon for their potential in cancer therapy.


Assuntos
Neoplasias , Ácido Peroxinitroso , Humanos , Ácido Peroxinitroso/uso terapêutico , Espécies Reativas de Oxigênio/uso terapêutico , Polímeros/uso terapêutico , Espécies Reativas de Nitrogênio/uso terapêutico , Luz , Oxigênio/uso terapêutico , Óxido Nítrico/uso terapêutico , Antraquinonas/uso terapêutico , Neoplasias/tratamento farmacológico
16.
Acta Biomater ; 177: 347-360, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38373525

RESUMO

Colon mucosal overexpression of reactive oxygen and nitrogen species (RONS) accelerates the development of inflammatory bowel disease (IBD) and destroys the mucosa and its barrier. IBD can be alleviated by removing RONS from the inflamed colon. The preparation of strong and efficient nanoantioxidants remains a challenge despite the development of numerous nanoantioxidants. In this paper, Zn-TA nanoparticles with fine hollow microstructure (HZn-TA) were successfully prepared and could be effectively used to treat IBD. In the first step, ZIF-8 nanoparticles were synthesized by a one-pot method. On this basis, HZn-TA nanoparticles were etched by TA, and a multifunctional nanase was developed for the treatment of IBD. RONS, including reactive oxygen species (ROS) and nitric oxide (NO), can be eliminated to increase cell survival following Hydrogen peroxide (H2O2) stimulation, including reactive oxygen species (ROS) and nitric oxide (NO with hydrogen peroxide (H2O2). In a model for preventing and delaying acute colitis, clearance of RONS has been shown to reduce intestinal inflammation in mice by reducing colon damage, proinflammatory cytokine levels, the spleen index, and body weight. Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate zonula occludens protein 1 (ZO-1) and claudin-1 expression. Based on the results of this study, HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS. Therefore, we pioneered the application of HZn-TA nanoparticles for the treatment of IBD, which are capable of clearing RONS without significant adverse effects. STATEMENT OF SIGNIFICANCE: ➢ HZn-TA nanoparticles were successfully prepared and could be effectively used to treat IBD. ➢ Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate ZO-1 and claudin-1 expression. ➢ HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS.


Assuntos
Peróxido de Hidrogênio , Doenças Inflamatórias Intestinais , Polifenóis , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Oxigênio/metabolismo , Zinco/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Óxido Nítrico/metabolismo , Claudina-1/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo
17.
J Colloid Interface Sci ; 662: 413-425, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359505

RESUMO

Acute kidney injury (AKI) results from the rapid deterioration of renal function, which is mainly treated by transplantation and dialysis, and has a high mortality rate. Inflammation induced by excess reactive oxygen/nitrogen species (RONS) plays a crucial role in AKI. Although small molecule antioxidants have been utilized to alleviate AKI, low bioavailability and side-effect of these drugs tremendously limit their clinical use. Hence, we successfully construct ultra-small (2-4 nm) rhodium nanoparticles modified with l-serine (denoted as Rh-Ser). Our results show that Rh-Ser with multiple enzyme-mimicking activities, allows remove various RONS to protect damaged kidney cells. Additionally, the ultrasmall size of Rh-Ser is conducive to enrichment in the renal tubules, and the modification of l-serine enables Rh-Ser to bind to kidney injury molecule-1, which is highly expressed on the surface of damaged renal cells, thereby targeting the damaged kidney and increasing the retention time. Moreover, Rh-Ser allows the production of oxygen at the inflammatory site, thus further improving hypoxia and inhibiting pro-inflammatory macrophages to relieve inflammation, and increasing the survival rate of AKI mice from 0 to 80%, which exhibits a better therapeutic effect than that of small molecule drug. Photoacoustic and fluorescence imaging can effectively monitor and evaluate the enrichment and therapeutic effect of Rh-Ser. Our study provides a promising strategy for the targeted treatment of AKI via RONS scavenging and inflammatory regulation.


Assuntos
Injúria Renal Aguda , Ródio , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Oxigênio , Ródio/farmacologia , Espécies Reativas de Nitrogênio/efeitos adversos , Medicina de Precisão , Rim , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Inflamação/tratamento farmacológico , Serina
18.
Biomolecules ; 14(2)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38397431

RESUMO

Reactive oxygen and nitrogen species (ROS/RNS) are generated as a result of normal intracellular metabolism [...].


Assuntos
Oxigênio , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio/metabolismo , Oxirredução , Espécies Reativas de Nitrogênio/metabolismo , Biomarcadores/metabolismo , Estresse Oxidativo
19.
Adv Healthc Mater ; 13(11): e2303817, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38166174

RESUMO

Oxidative stress is a biochemical process that disrupts the redox balance due to an excess of oxidized substances within the cell. Oxidative stress is closely associated with a multitude of diseases and health issues, including cancer, diabetes, cardiovascular diseases, neurodegenerative disorders, inflammatory conditions, and aging. Therefore, the developing of antioxidant treatment strategies has emerged as a pivotal area of medical research. Hydrogels have garnered considerable attention due to their exceptional biocompatibility, adjustable physicochemical properties, and capabilities for drug delivery. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. In the pursuit of more effective treatments for oxidative stress-related diseases, there is an urgent need for advanced strategies for the fabrication of multifunctional antioxidant hydrogels. Consequently, the authors' focus will be on hydrogels that possess exceptional reactive oxygen species and reactive nitrogen species scavenging capabilities, and their role in oxidative stress therapy will be evaluated. Herein, the antioxidant mechanisms and the design strategies of antioxidant hydrogels and their applications in oxidative stress-related diseases are discussed systematically in order to provide critical insights for further advancements in the field.


Assuntos
Antioxidantes , Hidrogéis , Estresse Oxidativo , Animais , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Hidrogéis/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
J Nanobiotechnology ; 22(1): 17, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172992

RESUMO

There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials.


Assuntos
Produtos Biológicos , Doenças Inflamatórias Intestinais , Nanopartículas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Espécies Reativas de Nitrogênio/metabolismo
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