RESUMO
Plant immunity is activated upon pathogen perception and often affects growth and yield when it is constitutively active. How plants fine-tune immune homeostasis in their natural habitats remains elusive. Here, we discover a conserved immune suppression network in cereals that orchestrates immune homeostasis, centering on a Ca2+-sensor, RESISTANCE OF RICE TO DISEASES1 (ROD1). ROD1 promotes reactive oxygen species (ROS) scavenging by stimulating catalase activity, and its protein stability is regulated by ubiquitination. ROD1 disruption confers resistance to multiple pathogens, whereas a natural ROD1 allele prevalent in indica rice with agroecology-specific distribution enhances resistance without yield penalty. The fungal effector AvrPiz-t structurally mimics ROD1 and activates the same ROS-scavenging cascade to suppress host immunity and promote virulence. We thus reveal a molecular framework adopted by both host and pathogen that integrates Ca2+ sensing and ROS homeostasis to suppress plant immunity, suggesting a principle for breeding disease-resistant, high-yield crops.
Assuntos
Cálcio/metabolismo , Sequestradores de Radicais Livres/metabolismo , Proteínas Fúngicas/metabolismo , Oryza/imunologia , Imunidade Vegetal , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sistemas CRISPR-Cas/genética , Membrana Celular/metabolismo , Resistência à Doença/genética , Modelos Biológicos , Oryza/genética , Doenças das Plantas/imunologia , Proteínas de Plantas/genética , Ligação Proteica , Estabilidade Proteica , Reprodução , Especificidade da Espécie , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Zea mays/imunologiaRESUMO
The mammalian heart has a remarkable regenerative capacity for a short period of time after birth, after which the majority of cardiomyocytes permanently exit cell cycle. We sought to determine the primary postnatal event that results in cardiomyocyte cell-cycle arrest. We hypothesized that transition to the oxygen-rich postnatal environment is the upstream signal that results in cell-cycle arrest of cardiomyocytes. Here, we show that reactive oxygen species (ROS), oxidative DNA damage, and DNA damage response (DDR) markers significantly increase in the heart during the first postnatal week. Intriguingly, postnatal hypoxemia, ROS scavenging, or inhibition of DDR all prolong the postnatal proliferative window of cardiomyocytes, whereas hyperoxemia and ROS generators shorten it. These findings uncover a protective mechanism that mediates cardiomyocyte cell-cycle arrest in exchange for utilization of oxygen-dependent aerobic metabolism. Reduction of mitochondrial-dependent oxidative stress should be an important component of cardiomyocyte proliferation-based therapeutic approaches.
Assuntos
Pontos de Checagem do Ciclo Celular , Miócitos Cardíacos/citologia , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Dano ao DNA , Sequestradores de Radicais Livres/farmacologia , Camundongos , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Peixe-ZebraRESUMO
The accumulation of excessive reactive oxygen species (ROS) and recurrent infections with drug-resistant bacteria pose significant challenges in diabetic wound infections, often leading to impediments in wound healing. Addressing this, there is a critical demand for novel strategies dedicated to treating and preventing diabetic wounds infected with drug-resistant bacteria. Herein, 2D tantalum carbide nanosheets (Ta4C3 NSs) have been synthesized through an efficient and straightforward approach, leading to the development of a new, effective nanoplatform endowed with notable photothermal properties, biosafety, and diverse ROS scavenging capabilities, alongside immunogenic attributes for diabetic wound treatment and prevention of recurrent drug-resistant bacterial infections. The Ta4C3 NSs exhibit remarkable photothermal performance, effectively eliminating methicillin-resistant Staphylococcus aureus (MRSA) and excessive ROS, thus promoting diabetic wound healing. Furthermore, Ta4C3 NSs enhance dendritic cell activation, further triggering T helper 1 (TH1)/TH2 immune responses, leading to pathogen-specific immune memory against recurrent MRSA infections. This nanoplatform, with its significant photothermal and immunomodulatory effects, holds vast potential in the treatment and prevention of drug-resistant bacterial infections in diabetic wounds.
Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Cicatrização/efeitos dos fármacos , Nanoestruturas/química , Camundongos , Terapia Fototérmica/métodos , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/uso terapêuticoRESUMO
Postoperative adhesion is a noteworthy clinical complication in abdominal surgery due to the existing physical barriers are unsatisfactory and inefficient in preventing its occurrence. In this work, an elaborate nanoparticle-in-microgel system (nMGel) is presented for postoperative adhesion prevention. nMGel is facilely formed by crosslinking manganese dioxide (MnO2) nanoparticles-loaded gelatin microspheres with polydopamine using a modified emulsification-chemical crosslinking method, generating a nano-micron spherical hydrogel. After drying, powdery nMGel with sprayability can perfectly cover irregular wounds and maintains robust tissue adhesiveness even in a wet environment. Additionally, nMGel possesses prominent antioxidant and free radical scavenging activity, which protects cell viability and preserves cell biological functions in an oxidative microenvironment. Furthermore, nMGel displays superior hemostatic property as demonstrated in mouse tail amputation models and liver trauma models. Importantly, nMGel can be conveniently administrated in a mouse cecal defect model to prevent adhesion between the injured cecum and the peritoneum by reducing inflammation, oxidative stress, collagen synthesis, and angiogenesis. Thus, the bioactive nMGel offers a practical and efficient approach for ameliorating postsurgical adhesion.
Assuntos
Nanopartículas , Espécies Reativas de Oxigênio , Animais , Nanopartículas/química , Aderências Teciduais/prevenção & controle , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Óxidos/química , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Adesivos/química , Adesivos/farmacologia , Humanos , Complicações Pós-Operatórias/prevenção & controle , Polímeros/químicaRESUMO
In view of the increased levels of reactive oxygen species (ROS) that disturb the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), the repair of diabetic bone defects remains a great challenge. Herein, a factor-free hydrogel is reported with ROS scavenging and responsive degradation properties for enhanced diabetic bone healing. These hydrogels contain ROS-cleavable thioketal (TK) linkers and ultraviolet (UV)-responsive norbornene (NB) groups conjugated with 8-arm PEG macromers, which are formed via UV crosslinking-mediated gelation. Upon reacting with high levels of ROS in the bone defect microenvironment, ROS-cleavable TK linkers are destroyed, allowing the responsive degradation of hydrogels, which promotes the migration of BMSCs. Moreover, ROS levels are reduced through hydrogel-mediated ROS scavenging to reverse BMSC differentiation from adipogenic to osteogenic phenotype. As such, a favorable microenvironment is created after simultaneous ROS scavenging and hydrogel degradation, leading to the effective repair of bone defects in diabetic mouse models, even without the addition of growth factors. Thus, this study presents a responsive hydrogel platform that regulates ROS scavenging and stromal degradation in bone engineering.
Assuntos
Diferenciação Celular , Hidrogéis , Células-Tronco Mesenquimais , Osteogênese , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Hidrogéis/química , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Camundongos , Diferenciação Celular/efeitos dos fármacos , Diabetes Mellitus Experimental , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Cicatrização/efeitos dos fármacos , Osso e Ossos , MasculinoRESUMO
Iron homeostasis is vital for normal physiology, but in the majority of circumstances, like iron overload, this equilibrium is upset leading to free iron in the plasma. This condition with excess iron is known as hemochromatosis, which has been linked to many side effects, including cancer and liver cirrhosis. The current research aimed to investigate active molecules from Streptomyces sp. isolated from the extreme environment of Bahawalpur deserts. The strain was characterized using 16 S rRNA sequencing. Chemical analysis of the ethyl acetate cure extract revealed the presence of phenols, flavonoids, alkaloids, and tannins. Multiple ultraviolet (UV) active metabolites that were essential for the stated pharmacological activities were also demonstrated by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Additionally, Gas chromatography/mass spectrometry (GC-MS) analysis revealed the primary constituents of the extract to compose of phenol and ester compounds. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to assess the extract's antioxidant capacity, and the results showed a good half-maximal inhibitory concentration (IC50) value of 0.034 µg/mL in comparison to the positive control ascorbic acid's 0.12 µg/mL. In addition, iron chelation activity of extract showed significant chelation potential at 250 and 125 µg/mL, while 62.5 µg/mL showed only mild chelation of the ferrous ion using ethylene diamine tetra acetic acid (EDTA) as a positive control. Likewise, the extract's cytotoxicity was analyzed through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using varying concentrations of the extract and showed 51% cytotoxicity at 350 µg/mL and 65% inhibition of cell growth at 700 µg/mL, respectively. The bioactive compounds from Streptomyces sp. demonstrated strong antioxidant and iron chelating potentials and can prolong the cell survival in extreme environment.
Assuntos
Antioxidantes , Quelantes de Ferro , Microbiologia do Solo , Streptomyces , Streptomyces/química , Streptomyces/metabolismo , Quelantes de Ferro/farmacologia , Quelantes de Ferro/química , Antioxidantes/farmacologia , Antioxidantes/química , Humanos , RNA Ribossômico 16S/genética , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Fenóis/química , Fenóis/farmacologia , Taninos/farmacologia , Taninos/química , Ferro/metabolismo , Ferro/química , Clima Desértico , Flavonoides/farmacologia , Flavonoides/química , Sobrevivência Celular/efeitos dos fármacos , Alcaloides/farmacologia , Alcaloides/químicaRESUMO
MicroRNAs are essential in plant development and stress resistance, but their specific roles in drought stress require further investigation. Here, we have uncovered that a Populus-specific microRNAs (miRNA), miR6445, targeting NAC (NAM, ATAF, and CUC) family genes, is involved in regulating drought tolerance of poplar. The expression level of miR6445 was significantly upregulated under drought stress; concomitantly, seven targeted NAC genes showed significant downregulation. Silencing the expression of miR6445 by short tandem target mimic technology significantly decreased the drought tolerance in poplar. Furthermore, 5' RACE experiments confirmed that miR6445 directly targeted NAC029. The overexpression lines of PtrNAC029 (OE-NAC029) showed increased sensitivity to drought compared with knockout lines (Crispr-NAC029), consistent with the drought-sensitive phenotype observed in miR6445-silenced strains. PtrNAC029 was further verified to directly bind to the promoters of glutathione S-transferase U23 (GSTU23) and inhibit its expression. Both Crispr-NAC029 and PtrGSTU23 overexpressing plants showed higher levels of PtrGSTU23 transcript and GST activity while accumulating less reactive oxygen species (ROS). Moreover, poplars overexpressing GSTU23 demonstrated enhanced drought tolerance. Taken together, our research reveals the crucial role of the miR6445-NAC029-GSTU23 module in enhancing poplar drought tolerance by regulating ROS homeostasis. This finding provides new molecular targets for improving the drought resistance of trees.
Assuntos
Resistência à Seca , Glutationa Transferase , MicroRNAs , Proteínas de Plantas , Populus , Espécies Reativas de Oxigênio , Adaptação Fisiológica , Sequência de Bases , Sequestradores de Radicais Livres/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Populus/genética , Populus/fisiologia , Populus/enzimologia , Regiões Promotoras Genéticas/genética , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/genéticaRESUMO
DNA origami nanostructures (DONs) are able to scavenge reactive oxygen species (ROS) and their scavenging efficiency toward ROS radicals was shown to be comparable to that of genomic DNA. Herein, we demonstrate that DONs are highly efficient singlet oxygen quenchers outperforming double-stranded (ds) DNA by several orders of magnitude. To this end, a ROS mixture rich in singlet oxygen is generated by light irradiation of the photosensitizer methylene blue and its cytotoxic effect on Escherichia coli cells is quantified in the presence and absence of DONs. DONs are found to be vastly superior to dsDNA in protecting the bacteria from ROS-induced damage and even surpass established ROS scavengers. At a concentration of 15â nM, DONs are about 50 000 times more efficient ROS scavengers than dsDNA at an equivalent concentration. This is attributed to the dominant role of singlet oxygen, which has a long diffusion length and reacts specifically with guanine. The dense packing of the available guanines into the small volume of the DON increases the overall quenching probability compared to a linear dsDNA with the same number of base pairs. DONs thus have great potential to alleviate oxidative stress caused by singlet oxygen in diverse therapeutic settings.
Assuntos
DNA , Escherichia coli , Azul de Metileno , Nanoestruturas , Espécies Reativas de Oxigênio , Oxigênio Singlete , Oxigênio Singlete/química , DNA/química , Nanoestruturas/química , Escherichia coli/química , Azul de Metileno/química , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/química , Fármacos Fotossensibilizantes/química , Estresse Oxidativo , Sequestradores de Radicais Livres/químicaRESUMO
Marine algae are a rich source of aromatic secondary metabolites, with bromophenols (BPs) receiving particular attention due to their health benefits. Despite extensive research on BPs, the understanding of their antioxidant potential, as well as their mechanisms of action at the molecular level, remains incomplete. This study utilized density functional theory (DFT) to systematically elucidate the antioxidant and pro-oxidant mechanisms of the main BP scaffolds under physiological conditions. It was found that BPs exhibit potent antioxidant capacity in both polar and lipid environments. In lipid media, the formal hydrogen transfer mechanism has been identified as the exclusive antiradical pathway. The position of bromine atoms significantly influenced the activity, particularly in scaffolds containing one hydroxyl group. However, no significant effect was observed in scaffolds with two hydroxyl groups. In water, monodeprotonated BPs showed key radical scavenging activity, with different mechanisms favored depending on the configuration of the hydroxyl groups. Additionally, BPs, particularly those bearing a catechol moiety, exhibit secondary antioxidant activity by reducing the production of hydroxyl radicals via the ascorbic acid anion pathway. These findings provide further validation of the potent antioxidant properties of BPs and shed light on their mechanism of action in physiological environments.
Assuntos
Antioxidantes , Teoria da Densidade Funcional , Fenóis , Antioxidantes/química , Antioxidantes/farmacologia , Fenóis/química , Fenóis/farmacologia , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologiaRESUMO
Bipolaris setariae is known to cause brown stripe disease in sugarcane, resulting in significant yield losses. Silicon (Si) has the potential to enhance plant growth and biotic resistance. In this study, the impact of Si on brown stripe disease was investigated across susceptible and resistant sugarcane varieties, utilizing four Si concentrations (0, 15, 30, and 45 g per barrel of Na2SiO3·5H2O). Si significantly reduced the incidence of brown stripe disease (7.41-59.23%) and alleviated damage to sugarcane growth parameters, photosynthetic parameters, and photosynthetic pigments. Submicroscopic observations revealed that Si induced the accumulation of silicified cells in leaves, reduced spore accumulation, decreased stomatal size, and protected organelles from B. setariae damage. In addition, Si increased the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase), reduced reactive oxygen species production (malondialdehyde and hydrogen peroxide) and modulated the expression of genes associated with hormone signalling (PR1, TGA, AOS, AOC, LOX, PYL8, and SnRK2), leading to the accumulation of abscisic acid and jasmonic acid and inhibiting SA synthesis. Si also activated the activity of metabolism-related enzymes (polyphenol oxidase and phenylalanine ammonia lyase) and the gene expression of PAL-dependent genes (PAL, C4H, and 4CL), regulating the accumulation of metabolites, such as chlorogenic acid and lignin. The antifungal test showed that chlorogenic acid (15ug µL-1) had a significant inhibitory effect on the growth of B. setariae. This study is the first to demonstrate the inhibitory effect of Si on B. setariae in sugarcane, highlighting Si as a promising and environmentally friendly strategy for managing brown stripe disease.
Assuntos
Doenças das Plantas , Reguladores de Crescimento de Plantas , Espécies Reativas de Oxigênio , Saccharum , Silício , Saccharum/efeitos dos fármacos , Saccharum/metabolismo , Saccharum/microbiologia , Saccharum/genética , Saccharum/crescimento & desenvolvimento , Silício/farmacologia , Silício/metabolismo , Doenças das Plantas/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/microbiologia , Folhas de Planta/genética , Ascomicetos/fisiologia , Ascomicetos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Sequestradores de Radicais Livres/metabolismoRESUMO
Reactive oxygen species (ROS) play important roles in regulating various physiological functions in the human body, however, excessive ROS can cause serious damage to the human body, considering the various limitations of natural enzymes as scavengers of ROS in the body, the development of better materials for the scavenging of ROS is of great significance to the biomedical field, and nanozymes, as a kind of nanomaterials which can show the activity of natural enzymes. Have a good potential for the development in the area of ROS scavenging. Metal-organic frameworks (MOFs), which are porous crystalline materials with a periodic network structure composed of metal nodes and organic ligands, have been developed with a variety of active nanozymes including catalase-like, superoxide dismutase-like, and glutathione peroxidase-like enzymes due to the adjustability of active sites, structural diversity, excellent biocompatibility, and they have shown a wide range of applications and prospects. In the present review, we first introduce three representative natural enzymes for ROS scavenging in the human body, methods for the detection of relevant enzyme-like activities and mechanisms of enzyme-like clearance are discussed, meanwhile, we systematically summarize the progress of the research on MOF-based nanozymes, including the design strategy, mechanism of action, and medical application, etc. Finally, the current challenges of MOF-based nanozymes are summarized, and the future development direction is anticipated. We hope that this review can contribute to the research of MOF-based nanozymes in the medical field related to the scavenging of ROS.
Assuntos
Estruturas Metalorgânicas , Espécies Reativas de Oxigênio , Estruturas Metalorgânicas/química , Espécies Reativas de Oxigênio/metabolismo , Humanos , Sequestradores de Radicais Livres/química , Nanoestruturas/química , Catalase/química , Catalase/metabolismo , Animais , Superóxido Dismutase/metabolismo , Superóxido Dismutase/químicaRESUMO
Phenothiazines (PTZs) are an emerging group of molecules showing effectiveness toward redox signaling and reduction of oxidative injury to cells, via the activation on Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Nrf2). Although several electrophilic and indirect Nrf2 activators have been reported, the risk of "off-target" effect due to the complexity of their molecular mechanisms of action, has aroused research interest toward non-electrophilic and direct modulators of Nrf2 pathway, such as PTZs. This review represents the first overview on the roles of PTZs as non-electrophilic Nrf2 activator and free radical scavengers, as well as on their potential therapeutic effects in oxidative stress-mediated diseases. Here, we provide a collective and comprehensive information on the PTZs ability to scavenge free radicals and activate the Nrf2 signaling pathway, with the aim to broaden the knowledge of their therapeutic potentials and to stimulate innovative research ideas.
Assuntos
Antioxidantes , Fator 2 Relacionado a NF-E2 , Fenotiazinas , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Sequestradores de Radicais Livres , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de Sinais , Fenotiazinas/farmacologiaRESUMO
Coumarins represent a diverse class of natural compounds whose importance in pharmaceutical and agri-food sectors has motivated multiple novel synthetic derivatives with broad applicability. The phenolic moiety in 4-hydroxycoumarins underscores their potential to modulate the equilibrium between free radicals and antioxidant species within biological systems. The aim of this work was to assess the antioxidant activity of 18 4-hydroxycoumarin coumarin derivatives, six of which are commercially available and the other 12 were synthesized and chemically characterized and described herein. The 4-hydroxycoumarins were prepared by a two steps synthetic strategy with satisfactory yields. Their antioxidant potential was evaluated through three in vitro methods, two free radical-scavenging assays (DPPH⢠and ABTSâ¢+) and a metal chelating activity assay. Six synthetic coumarins (4a, 4g, 4h, 4i, 4k, 4l) had a scavenging capacity of DPPH⢠higher than butylated hydroxytoluene (BHT) (IC50 = 0.58 mmol/L) and compound 4a (4-hydroxy-6-methoxy-2 H-chromen-2-one) with an IC50 = 0.05 mmol/L outperformed both BHT and ascorbic acid (IC50 = 0.06 mmol/L). Nine hydroxycoumarins had a scavenging capacity against ABTSâ¢+ greater (C3, 4a, 4c) or comparable (C1, C2, C4, C6, 4g, 4l) to Trolox (IC50 = 34.34 µmol/L). Meanwhile, the set had a modest ferrous chelation capacity, but most of them (C2, C5, C6, 4a, 4b, 4h, 4i, 4j, 4k, 4l) reached up to more than 20% chelating ability percentage. Collectively, this research work provides valuable structural insights that may determine the scavenging and metal chelating activity of 4-hydroxycoumarins. Notably, substitutions at the C6 position appeared to enhance scavenging potential, while the introduction of electron-withdrawing groups showed promise in augmenting chelation efficiency.
Assuntos
4-Hidroxicumarinas , Antioxidantes , Sequestradores de Radicais Livres , 4-Hidroxicumarinas/química , 4-Hidroxicumarinas/farmacologia , 4-Hidroxicumarinas/síntese química , Antioxidantes/síntese química , Antioxidantes/farmacologia , Antioxidantes/química , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Picratos/química , Quelantes/química , Quelantes/farmacologia , Quelantes/síntese química , Compostos de Bifenilo/química , Ácidos Sulfônicos/química , Relação Estrutura-Atividade , BenzotiazóisRESUMO
With increasing proportion of the elderly in the population, age-related diseases (ARD) lead to a considerable healthcare burden to society. Prevention and treatment of ARD can decrease the negative impact of aging and the burden of disease. The aging rate is closely associated with the production of high levels of reactive oxygen species (ROS). ROS-mediated oxidative stress in aging triggers aging-related changes through lipid peroxidation, protein oxidation, and DNA oxidation. Antioxidants can control autoxidation by scavenging free radicals or inhibiting their formation, thereby reducing oxidative stress. Benefiting from significant advances in nanotechnology, a large number of nanomaterials with ROS-scavenging capabilities have been developed. ROS-scavenging nanomaterials can be divided into two categories: nanomaterials as carriers for delivering ROS-scavenging drugs, and nanomaterials themselves with ROS-scavenging activity. This study summarizes the current advances in ROS-scavenging nanomaterials for prevention and treatment of ARD, highlights the potential mechanisms of the nanomaterials used and discusses the challenges and prospects for their applications.
Assuntos
Envelhecimento , Sequestradores de Radicais Livres , Nanoestruturas , Estresse Oxidativo , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Humanos , Nanoestruturas/química , Envelhecimento/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/químicaRESUMO
Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1ß and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.
Assuntos
Lesão Pulmonar Aguda , Cério , Indóis , Polímeros , Espécies Reativas de Oxigênio , Cério/química , Cério/farmacologia , Animais , Lesão Pulmonar Aguda/tratamento farmacológico , Polímeros/química , Polímeros/farmacologia , Indóis/química , Indóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ratos , Camundongos , Masculino , Células RAW 264.7 , Pulmão/efeitos dos fármacos , Pulmão/patologia , Antioxidantes/farmacologia , Antioxidantes/química , Ratos Sprague-Dawley , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Raios Infravermelhos , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/uso terapêutico , Nanopartículas/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Citocinas/metabolismoRESUMO
Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.
Assuntos
Síndromes do Olho Seco , Soluções Oftálmicas , Espécies Reativas de Oxigênio , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , Síndromes do Olho Seco/tratamento farmacológico , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Córnea/efeitos dos fármacos , Córnea/metabolismo , Álcool de Polivinil/química , Humanos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Boratos/química , Nanopartículas/química , MasculinoRESUMO
Excessive production of reactive oxygen species (ROS) around titanium implants under diabetic conditions causes persistent inflammation, leading to poor osseointegration and even implant failure. Surface modification is an effective way to promote ROS clearance, alleviate inflammation, and stimulate bone formation. In this study, a multifunctional coating is fabricated by introducing cerium (Ce)-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) onto the titanium surface via an electrophoretic deposition method. The incorporation of Ce-MBGNs remarkably improves surface hydrophilicity by increasing the surface areas. The bioactive ions are appropriately released, thereby promoting mesenchymal stem cell proliferation and differentiation under diabetic conditions. The conversion between Ce(III) and Ce(IV) endows Ce-MBGNs coating with antioxidative nanoenzymes properties to scavenge diabetes-induced ROS, resulting in macrophage polarization towards the anti-inflammatory phenotype. The therapeutic effect of Ce-MBGNs-modified titanium implants is also verified in diabetic rats by inhibiting inflammatory responses and accelerating early osseointegration. Taken together, the findings reveal that the ROS-scavenging and immunomodulation activity of the Ce-MBGNs coating contributes to enhanced osseointegration, and provides a novel implant surface for diabetic patients.
Assuntos
Cério , Diabetes Mellitus Experimental , Células-Tronco Mesenquimais , Nanopartículas , Osseointegração , Espécies Reativas de Oxigênio , Titânio , Cério/química , Cério/farmacologia , Osseointegração/efeitos dos fármacos , Animais , Espécies Reativas de Oxigênio/metabolismo , Ratos , Titânio/química , Titânio/farmacologia , Nanopartículas/química , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Ratos Sprague-Dawley , Próteses e Implantes , Propriedades de Superfície , Porosidade , Proliferação de Células/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Camundongos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/químicaRESUMO
BACKGROUND: Koenigia alpina (All.) T.M.Schust. & Reveal (alpine knotweed) is a perennial herb belonging to the Polygonaceae family. Several studies have examined Polygonaceae species' potential applications as cosmeceutical materials; however, the potential of K. alpina as a cosmeceutical has not yet been studied. MATERIALS AND METHODS: Hydrogen peroxide (H2O2) and lipopolysaccharide were used to induce an inflammatory response in RAW 264.7 cells. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals and H2O2 were used to evaluate the free-radical scavenging activity of K. alpina extract and its protective effect against reactive oxygen species (ROS)-induced cell damage. The whitening, antiaging, and cell proliferation/migration effects of the extracts were evaluated via tyrosinase inhibition, collagenase/elastase inhibition, and wound healing assays, respectively. The anti-inflammatory effect was confirmed by evaluating nitric oxide (NO) production in RAW 264.7 cells. High-performance liquid chromatography (HPLC), UV, and MS/MS were used to determine the main components of the extract and fractions. RESULTS: The ethyl acetate (EA) fraction and its aglycone fraction showed very high free-radical scavenging activities (47.5 and 47.1 µg/mL, respectively). The extract/fractions also showed significant tyrosinase inhibition (IC50 = 0.38 mg/mL in EA fraction), collagenase inhibition (IC50 = 0.21 mg/mL in EA fraction), and elastase inhibition (IC50 = 0.57 mg/mL in aglycone fraction). NO production in lipopolysaccharide-induced RAW 264.7 cells was inhibited by the extract/fractions. The extract also promoted the closure of scratch wounds in HaCaT cells. The K. alpina extract/fractions contained cardamonin, quercetin, and quercitrin. CONCLUSION: K. alpina extracts/fractions showed antioxidant, antiaging, whitening, and anti-inflammatory activities, suggesting they may have potential as antiaging cosmeceuticals.
Assuntos
Anti-Inflamatórios , Extratos Vegetais , Extratos Vegetais/farmacologia , Camundongos , Animais , Células RAW 264.7 , Humanos , Anti-Inflamatórios/farmacologia , Polygonaceae/química , Óxido Nítrico/metabolismo , Proliferação de Células/efeitos dos fármacos , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Sequestradores de Radicais Livres/farmacologia , Cicatrização/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Compostos de Bifenilo , Preparações Clareadoras de Pele/farmacologia , Picratos , Monofenol Mono-Oxigenase/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Células HaCaTRESUMO
Sargassum muticum (SM) poses a serious environmental issue since it is a fast-expanding invasive species occupying key areas of the European shoreline, disrupting the autochthonous algae species, and disturbing the ecosystem. This problem has concerned the general population and the scientific community. Nevertheless, as macroalgae are recognized as a source of bioactive molecules, the abundance of SM presents an opportunity as a raw material. In this work, response surface methodology (RSM) was applied as a tool for the optimization of the extraction of bioactive compounds from SM by microwave-assisted extraction (MAE). Five different parameters were used as target functions: yield, total phenolic content (TPC); and the antioxidant measurements of 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and ß-carotene bleaching (BC). After the optimal extraction conditions were determined (time = 14.00 min; pressure = 11.03 bar; ethanol = 33.31%), the chemical composition and bioactivity of the optimum extract was evaluated to appraise its antioxidant capability to scavenge reactive species and as a potential antibacterial, antidiabetic, antiproliferation, and neuroprotective agent. The results lead to the conclusion that MAE crude extract has bioactive properties, being especially active as an antiproliferation agent and as a nitric oxide and superoxide radical scavenger.
Assuntos
Antioxidantes , Espécies Introduzidas , Micro-Ondas , Sargassum , Sargassum/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Fenóis/isolamento & purificação , Fenóis/farmacologia , Fenóis/química , HumanosRESUMO
Four new polyketides, namely furantides A-B (1-2), talamin E (3) and arugosinacid A (4), and two known polyketides were obtained from the mangrove-derived fungus Penicillium sp. HDN15-312 using the One Strain Many Compounds (OSMAC) strategy. Their chemical structures, including configurations, were elucidated by detailed analysis of extensive NMR spectra, HRESIMS and ECD. The DPPH radicals scavenging activity of 3, with an IC50 value of 6.79 µM, was better than vitamin C.