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1.
ACS Appl Mater Interfaces ; 13(33): 39126-39134, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34383476

RESUMO

The usage of exogenous antioxidant materials to relieve oxidative stress offers an important strategy for the therapy of oxidative stress-induced injuries. However, the fabrication processes toward the antioxidant materials usually require the involvement of extra metal ions and organic agents, as well as sophisticated purification steps, which might cause tremendous environmental stress and induce unpredictable side effects in vivo. To address these issues, herein, we proposed a novel strategy to fabricate green nanoparticles for efficiently modulating oxidative stress, which was facilely prepared from tea polyphenol extracts (originated from green tea) via a green enzymatic polymerization-based chemistry method. The resulting nanoparticles possessed a uniform spherical morphology and good stability in water and biomedium and demonstrated excellent radical scavenging properties. These nanoparticle scavengers could effectively prevent intracellular oxidative damage, accelerate wound recovery, and protect the kidneys from reactive oxygen species damaging in the acute kidney injury model. We hope this work will inspire the further development of more types of green nanoparticles for antioxidant therapies via similar synthetic strategies using green biomass materials.


Assuntos
Injúria Renal Aguda/prevenção & controle , Antioxidantes/química , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/química , Chá/química , Células 3T3 , Células A549 , Animais , Antioxidantes/farmacologia , Catecóis/química , Sobrevivência Celular/efeitos dos fármacos , Feminino , Sequestradores de Radicais Livres/metabolismo , Química Verde , Peroxidase do Rábano Silvestre/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica , Cicatrização/efeitos dos fármacos
2.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445329

RESUMO

Melatonin is registered to treat circadian rhythm sleep-wake disorders and insomnia in patients aged 55 years and over. The essential role of the circadian sleep rhythm in the deterioration of sleep quality during COVID-19 confinement and the lack of an adverse effect of melatonin on respiratory drive indicate that melatonin has the potential to be a recommended treatment for sleep disturbances related to COVID-19. This review article describes the effects of melatonin additional to its sleep-related effects, which make this drug an attractive therapeutic option for treating patients with COVID-19. The preclinical data suggest that melatonin may inhibit COVID-19 progression. It may lower the risk of the entrance of the SARS-CoV-2 virus into cells, reduce uncontrolled hyper-inflammation and the activation of immune cells, limit the damage of tissues and multiorgan failure due to the action of free radicals, and reduce ventilator-induced lung injury and the risk of disability resulting from fibrotic changes within the lungs. Melatonin may also increase the efficacy of COVID-19 vaccination. The high safety profile of melatonin and its potential anti-SARS-CoV-2 effects make this molecule a preferable drug for treating sleep disturbances in COVID-19 patients. However, randomized clinical trials are needed to verify the clinical usefulness of melatonin in the treatment of COVID-19.


Assuntos
COVID-19/tratamento farmacológico , Melatonina/farmacologia , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Vacinas contra COVID-19/farmacologia , Citocinas/metabolismo , Sequestradores de Radicais Livres/metabolismo , Humanos , Melatonina/uso terapêutico , Sistema Renina-Angiotensina , Transtornos do Sono-Vigília/tratamento farmacológico
3.
Molecules ; 26(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34279445

RESUMO

Melatonin and several of its metabolites are interfering with reactive nitrogen. With the notion of prevailing melatonin formation in tissues that exceeds by far the quantities in blood, metabolites come into focus that are poorly found in the circulation. Apart from their antioxidant actions, both melatonin and N1-acetyl-5-methoxykynuramine (AMK) downregulate inducible and inhibit neuronal NO synthases, and additionally scavenge NO. However, the NO adduct of melatonin redonates NO, whereas AMK forms with NO a stable product. Many other melatonin metabolites formed in oxidative processes also contain nitrosylatable sites. Moreover, AMK readily scavenges products of the CO2-adduct of peroxynitrite such as carbonate radicals and NO2. Protein AMKylation seems to be involved in protective actions.


Assuntos
Antioxidantes/metabolismo , Sequestradores de Radicais Livres/metabolismo , Melatonina/metabolismo , Compostos de Nitrogênio/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Animais , Humanos , Cinuramina/análogos & derivados , Cinuramina/metabolismo , Oxirredução
4.
ACS Appl Mater Interfaces ; 13(26): 30261-30273, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34169710

RESUMO

At present, the complex pathogenesis, the difficult-to-overcome blood-brain barrier (BBB), the development of the disease course which cannot be prevented, and other problems are serious challenges in the treatment of Alzheimer's disease (AD). In order to enhance the therapeutic effect of drugs through BBB, we synthesized simple and easy-to-obtain selenium quantum dots (SeQDs), with a multitarget therapeutic effect. This new type of SeQDs has an ultrasmall size and can quickly penetrate the BBB. According to the fluorescence characteristics of SeQDs, we can diagnose and track AD. The experimental results show that SeQDs have strong free-radical scavenging activity, protect cells from oxidative stress induced by different stimuli, and show broad-spectrum antioxidant activity. The SeQDs can not only effectively inhibit Aß aggregation and significantly reduce Aß-mediated cytotoxicity, thus preventing AD cascade reaction, but also effectively reduce tau protein phosphorylation by down-regulating PHF1 and CP13 and further reduce oxidative stress, restore mitochondrial functions, and maintain nerve cell stability and protect nerve cells from oxidative stress. In vivo studies demonstrate that SeQDs can continuously accumulate in the brain after rapid passage of BBB and can quickly alleviate AD, significantly improve the memory impairment of AD mice, and improve their learning and memory ability. Therefore, the use of SeQDs in the treatment of AD has great advantages compared with traditional single-target drugs and provides a new direction for the combination of prevention and treatment of neurodegenerative diseases.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Sequestradores de Radicais Livres/uso terapêutico , Inflamação/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Pontos Quânticos/uso terapêutico , Doença de Alzheimer/complicações , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Barreira Hematoencefálica/fisiologia , Linhagem Celular Tumoral , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/metabolismo , Humanos , Inflamação/etiologia , Masculino , Memória/efeitos dos fármacos , Camundongos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , Teste de Campo Aberto/efeitos dos fármacos , Tamanho da Partícula , Fosforilação/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Pontos Quânticos/química , Pontos Quânticos/metabolismo , Selênio/química , Selênio/metabolismo , Selênio/uso terapêutico , Proteínas tau/metabolismo
5.
Molecules ; 26(9)2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34065080

RESUMO

The crude ethanol extract of the whole plant of Alternanthera philoxeroides (Mart.) Griseb was investigated for its potential as antidementia, induced by estrogen deprivation, based on in vitro antioxidant activity, ß-amyloid aggregation inhibition and cholinesterase inhibitory activity, as well as in vivo Morris water maze task (MWMT), novel object recognition task (NORT), and Y-maze task. To better understand the effect of the extract, oxidative stress-induced brain membrane damage through lipid peroxidation in the whole brain was also investigated. Additionally, expressions of neuroinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and estrogen receptor-mediated facilitation genes such as PI3K and AKT mRNA in the hippocampus and frontal cortex were also evaluated. These effects were confirmed by the determination of its serum metabolites by NMR metabolomic analysis. Both the crude extract of A. philoxeroides and its flavone constituents were found to inhibit ß-amyloid (Aß) aggregation.


Assuntos
Demência/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Metabolômica , Extratos Vegetais/farmacologia , Amaranthaceae/química , Peptídeos beta-Amiloides/química , Animais , Cognição/efeitos dos fármacos , Demência/prevenção & controle , Etanol/química , Etanol/farmacologia , Feminino , Flavonas/química , Sequestradores de Radicais Livres/metabolismo , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Medicina Tradicional do Leste Asiático , Metaboloma , Camundongos , Camundongos Endogâmicos ICR , Ovariectomia , Análise de Componente Principal , Fator de Necrose Tumoral alfa/metabolismo
6.
Carbohydr Polym ; 263: 118005, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33858565

RESUMO

High pressure processing (HPP) has become a promising strategy for extracting bioactive constituents. In this study, the impact of HPP treatment at various pH values (2.0, 8.0, and 12.0) on the macromolecular, structural, antioxidant capacity, rheological characteristics and gel properties of citrus pectic polysaccharide was investigated. The results showed that pressure and pH significantly affected the yield and Rhamnogalacturonan I (RG-I) characterizations. The yields of high pressure extraction at pH 12 (28.13 %-33.95 %) were significantly higher than the yields at pH 2 (14.85 %-16.11 %) and pH 8 (8.75 %-9.65 %). The yield of HPP (500 MPa/10 min) assisted alkali extraction is more than 2 times of that of HPP assisted acid extraction. The RG-I structure ratio of HPP-alkali extraction pectic polysaccharide (74.51 %) was significantly higher than that of traditional pectin (41.83 %). The results showed that HPP assisted alkali is a potential pectic polysaccharide extraction technology.


Assuntos
Citrus/química , Pectinas/isolamento & purificação , Polissacarídeos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Sequestradores de Radicais Livres/metabolismo , Frutas/química , Concentração de Íons de Hidrogênio , Peso Molecular , Monossacarídeos/análise , Pectinas/análise , Pectinas/química , Polissacarídeos/análise , Polissacarídeos/química , Polissacarídeos/metabolismo , Pressão , Espectroscopia de Prótons por Ressonância Magnética , Reologia , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
7.
J Chromatogr Sci ; 59(5): 412-418, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33723580

RESUMO

Calycosin and formononetin were efficiently extracted from Astragali Radix and purified by high-speed countercurrent chromatography. Calycosin and formononetin could be hydrolyzed from calycosin-7-glucoside and ononin, respectively. The best extraction conditions were realized by single factor and orthogonal experiments, which were 100% ethanol, 2.5 mol/L hydrochloric acid, 1:40 ratio of solid to liquid, extracted 2 h and one time. The two-phase solvent system of n-hexane-ethyl acetate-ethanol-water (3:5:3:5, v/v) was selected for the purification of calycosin, and 1.3 mg calycosin (the purity was 95.8% and the recovery was 85.9%) was obtained from 264.9-mg crude extraction. The two-phase solvent system of n-hexane-ethyl acetate-ethanol-water (4:5:4:5, v/v) was selected for the purification of formononetin, and 2.0 mg formononetin (the purity was 98.9% and the recovery was 84.4%) was obtained from 248.9-mg crude extraction. Their structures were identified by HPLC, melting points, UV, FTIR, ESI-MS, 1H NMR and 13C NMR spectrum. According to the antioxidant activity assay, the scavenging abilities of calycosin to 1,1-diphenyl-2-picrylhydrazyl and hydroxyl free radicals (·OH) were stronger. The scavenging effect of formononetin was not demonstrated.


Assuntos
Distribuição Contracorrente/métodos , Medicamentos de Ervas Chinesas/química , Isoflavonas/isolamento & purificação , Extração Líquido-Líquido/métodos , Cromatografia Líquida de Alta Pressão , Sequestradores de Radicais Livres/análise , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/metabolismo , Isoflavonas/análise , Isoflavonas/metabolismo
8.
Molecules ; 26(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33671020

RESUMO

The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC50) 1.63-4.62 µM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.


Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Carbazóis/química , Inibidores da Colinesterase/química , Donepezila/química , Fármacos Neuroprotetores/química , Animais , Barreira Hematoencefálica/metabolismo , Carbazóis/farmacologia , Inibidores da Colinesterase/farmacologia , Donepezila/farmacologia , Desenho de Fármacos , Quimioterapia Combinada , Sequestradores de Radicais Livres/metabolismo , Glucose/metabolismo , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Ratos Sprague-Dawley
9.
Molecules ; 26(4)2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33567661

RESUMO

The study was undertaken to investigate the antioxidant, genotoxic, and cytotoxic potentialities of phyto-fabricated zinc oxide nanoparticles (ZnO-NPs) from Ipomoea obscura (L.) Ker Gawl. aqueous leaf extract. The UV-visible spectral analysis of the ZnO-NPs showed an absorption peak at 304 nm with a bandgap energy of 3.54 eV, which are characteristics of zinc nanoparticles. Moreover, the particles were of nano-size (~24.26 nm) with 88.11% purity and were agglomerated as observed through Scanning Electron Microscopy (SEM). The phyto-fabricated ZnO-NPs offered radical scavenging activity (RSA) in a dose-dependent manner with an IC50 of 0.45 mg mL-1. In addition, the genotoxicity studies of ZnO-NPs carried out on onion root tips revealed that the particles were able to significantly inhibit the cell division at the mitotic stage with a mitotic index of 39.49%. Further, the cytotoxic studies on HT-29 cells showed that the phyto-fabricated ZnO-NPs could arrest the cell division as early as in the G0/G1 phase (with 92.14%) with 73.14% cells showing early apoptotic symptoms after 24 h of incubation. The results of the study affirm the ability of phyto-fabricated ZnO-NPs from aqueous leaf extract of I. obscura is beneficial in the cytotoxic application.


Assuntos
Ipomoea/metabolismo , Nanopartículas/química , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Compostos de Bifenilo/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/metabolismo , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/toxicidade , Química Verde , Células HT29 , Humanos , Testes de Mutagenicidade , Cebolas/efeitos dos fármacos , Cebolas/genética , Picratos/química , Óxido de Zinco/metabolismo , Óxido de Zinco/toxicidade
10.
PLoS One ; 16(1): e0243292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33434207

RESUMO

Two winter rapeseed cultivars, "NS" (cold tolerant) and "NF" (cold sensitive), were used to reveal the morphological, physiological, and proteomic characteristics in leaves of plants after treatment at -4°C for 12 h(T1) and 24 h(T2), and at room temperature(T0), to understand the molecular mechanisms of cold tolerance. Antioxidant activity and osmotic adjustment ability were higher, and plasma membrane injury was less obvious, in NS than in NF under cold stress. We detected different abundant proteins (DAPs) related to cold tolerance in winter rapeseed through data-independent acquisition (DIA). Compared with NF, A total of 1,235 and 1,543 DAPs were identified in the NSs under T1 and T2, respectively. Compared with NF, 911 proteins were more abundant in NS only after cold treatment. Some of these proteins were related to ROS scavenging through four metabolic pathways: lysine degradation; phenylalanine, tyrosine, and tryptophan; flavonoid biosynthesis; and ubiquinone and other terpenoid-quinone biosynthesis. Analysis of these proteins in the four candidate pathways revealed that they were rapidly accumulated to quickly enhance ROS scavenging and improve the cold tolerance of NS. These proteins were noticeably more abundant during the early stage of cold stress, which was critical for avoiding ROS damage.


Assuntos
Adaptação Fisiológica , Brassica napus/metabolismo , Brassica napus/fisiologia , Temperatura Baixa , Sequestradores de Radicais Livres/metabolismo , Proteômica , Espécies Reativas de Oxigênio/metabolismo , Estações do Ano , Brassica napus/anatomia & histologia , Brassica napus/genética , Ontologia Genética , Anotação de Sequência Molecular , Proteínas de Plantas/metabolismo , Reprodutibilidade dos Testes , Plântula/fisiologia , Transcrição Genética
11.
Life Sci ; 271: 119070, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33465388

RESUMO

AIMS: In vivo biodistribution of radio labeled ZrO2 nanoparticles is addressed for better imaging, therapy and diagnosis. Nanoparticles are synthesized by microwave assisted sol-gel technique using Fe3O4 as a stabilizer. Antioxidant assay, hemolytic activity in human blood and biodistribution in rabbits was explored to study the therapeutical as well as in vivo targeted diagnostic applications of as synthesized nanoparticles. MAIN METHODS: Fe3O4 stabilized zirconia nanoparticles are synthesized using microwave assisted sol-gel method. Microwave (MW) powers are varied in the range of 100 to 1000 W. As synthesized nanoparticles are evaluated using different characterizations such as X-ray diffractometer, scanning electron microscope, Raman spectroscopy, impedance analyzer, Vickers micro hardness indenter, FTIR, and UV-Vis spectroscopy. In vitro activity of synthesized nanoparticles is checked in freshly extracted human blood serum. To study biodistribution of Fe3O4 stabilized zirconia nanoparticles in rabbit, technetium-99 m was used for labeling purpose. The labeling efficacy and stability of labeled nanoparticles are also measured with instant thin layer chromatography (ITLC) method. Intravenous injection of 99mTc-Fe3O4 stabilized zirconia nanoparticles (0.2 ml), containing 110 MBq of radioactivity, is performed to study the biodistribution; nanoparticles are injected into the ear vein of animal (rabbit). KEY FINDINGS: Zirconia (ZrO2) nanoparticles (NPs) are stabilized using Fe3O4 that were prepared by means of microwave assisted sol-gel method. Crystallite size (~20 nm) agrees well with the values required to stabilize tetragonal zirconia (t-ZrO2). Volume shrinkage results in high value of hardness (~1369). Dielectric constant values, compatible for biomedical application, are observed for tetragonally stabilized samples. Low value of hemolytic response is observed for Fe3O4 stabilized ZrO2 NPs. 99mTc radio labeled ZrO2 NPs proved to be potential candidate to study biodistribution. Biodistribution studies show stability of radiolabeled NPs in the original suspension as well as in blood serum. CT scan of rabbit is performed for several times to check the biodistribution of NPs with time and survival of rabbit. Results suggest that these NPs can also be used as targeted nanoparticles as well as variants of drug payload carrier. SIGNIFICANCE: Results signify that Fe3O4 stabilized ZrO2 nanoparticles synthesized by microwave assisted sol-gel method may be considered as "all-rounder" nanoplatform and are safe enough to be used in diagnostic as well as therapeutic purposes.


Assuntos
Compostos Férricos/metabolismo , Sequestradores de Radicais Livres/metabolismo , Micro-Ondas , Nanopartículas/metabolismo , Radioimunodetecção/métodos , Zircônio/metabolismo , Animais , Compostos Férricos/síntese química , Humanos , Nanopartículas/química , Coelhos , Tecnécio/metabolismo , Distribuição Tecidual/fisiologia , Difração de Raios X/métodos , Zircônio/química
12.
J Neurosci ; 41(3): 538-554, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33239403

RESUMO

Alzheimer's disease (AD) is characterized by progressive neurodegeneration in the cerebral cortex, histopathologically hallmarked by amyloid ß (Aß) extracellular plaques and intracellular neurofibrillary tangles, constituted by hyperphosphorylated tau protein. Correlation between these pathologic features and dementia has been challenged by the emergence of "nondemented with Alzheimer's neuropathology" (NDAN) individuals, cognitively intact despite displaying pathologic features of AD. The existence of these subjects suggests that some unknown mechanisms are triggered to resist Aß-mediated detrimental events. Aß accumulation affects mitochondrial redox balance, increasing oxidative stress status, which in turn is proposed as a primary culprit in AD pathogenesis. To clarify the relationship linking Aß, oxidative stress, and cognitive impairment, we performed a comparative study on AD, NDAN, and aged-matched human postmortem frontal cortices of either sex. We quantitatively analyzed immunofluorescence distribution of oxidative damage markers, and of SOD2 (superoxide dismutase 2), PGC1α [peroxisome proliferator-activated receptor (PPAR) γ-coactivator 1α], PPARα, and catalase as key factors in antioxidant response, as well as the expression of miRNA-485, as a PGC1α upstream regulator. Our results confirm dramatic redox imbalance, associated with impaired antioxidant defenses in AD brain. By contrast, NDAN individuals display low oxidative damage, which is associated with high levels of scavenging systems, possibly resulting from a lack of PGC1α miRNA-485-related inhibition. Comparative analyses in neurons and astrocytes further highlighted cell-specific mechanisms to counteract redox imbalance. Overall, our data emphasize the importance of transcriptional and post-transcriptional regulation of antioxidant response in AD. This suggests that an efficient PGC1α-dependent "safety mechanism" may prevent Aß-mediated oxidative stress, supporting neuroprotective therapies aimed at ameliorating defects in antioxidant response pathways in AD patients.


Assuntos
Doença de Alzheimer/patologia , Antioxidantes/metabolismo , Demência/patologia , Estresse Oxidativo , Córtex Pré-Frontal/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Astrócitos/enzimologia , Autopsia , Demência/metabolismo , Feminino , Sequestradores de Radicais Livres/metabolismo , Humanos , Masculino , MicroRNAs/genética , Neurônios/enzimologia , Oxirredução , PPAR gama/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Córtex Pré-Frontal/metabolismo
13.
Plant Signal Behav ; 16(3): 1866312, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33369514

RESUMO

WUSCHEL-related homeobox (WOX) transcription factors play essential roles in key developmental processes and in response to different abiotic stresses. In a recent study, we have refined a molecular regulation mechanism that drought-induced PagERF35 directly activates the expression of PagWOX11/12a thus to promote root elongation and biomass, especially under drought conditions, and resulting in enhanced drought tolerance in poplar. In this study, we further found that PagWOX11/12a overexpression significantly enhanced drought tolerance and improved survival rate. Interestingly, transgenic poplars overexpressing PagWOX11/12a exhibited higher ability in scavenging reactive oxygen species (ROS) under drought stress. Combined with these and previous findings, we proposed the mechanism that PagWOX11/12a could not only promote root elongation and biomass growth to increase drought tolerance but also improve plant drought tolerance by regulating ROS level through possibly modulating the expression of ROS scavenging related genes.


Assuntos
Secas , Sequestradores de Radicais Livres/metabolismo , Genes Homeobox , Proteínas de Plantas/genética , Populus/genética , Espécies Reativas de Oxigênio/metabolismo , Modelos Biológicos , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética
14.
Sci Rep ; 10(1): 22313, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33339881

RESUMO

In light of Medical Hydrology, thermal waters (TW) are all-natural mineral waters that emerge inside a thermal resort and have therapeutic applications. Their beneficial effect has been empirically recognized for centuries, being indicated for symptom alleviation and/or treatment of several diseases, almost all associated with inflammation. Indeed, an anti-inflammatory effect has been attributed to many different Portuguese TW but there is no scientific validation supporting this empiric knowledge. In the present study, we aimed to investigate the anti-inflammatory properties of 14 TW pertaining to thermal centers located in the Central Region of Portugal, and grouped according to their ionic profile. Mouse macrophage cells stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 agonist, were exposed to culture medium prepared in TW. Metabolism, nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression levels and the scavenging capacity of TW, were investigated in vitro. 11 out of 14 TW reduced NO production and/or iNOS expression, and/or scavenging activity, in macrophages exposed to LPS. The sulphated/calcic TW did not show any effect on at least one of the inflammatory parameters evaluated. Two sulphurous/bicarbonate/sodic TW and the sulphurous/chlorinated/sodic TW promoted an increase in NO production and/or iNOS expression. Our results validate, for the first time, the anti-inflammatory properties of Portuguese TW, supporting their therapeutic use in the treatment of inflammation-related diseases and promoting their putative application in cosmetic products and medical devices.


Assuntos
Anti-Inflamatórios/farmacologia , Água Subterrânea/química , Temperatura Alta/uso terapêutico , Inflamação/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Linhagem Celular , Sequestradores de Radicais Livres/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Camundongos , Óxido Nítrico/genética , Óxido Nítrico Sintase Tipo II/genética , Portugal , Dermatopatias/genética , Dermatopatias/patologia
15.
BMC Plant Biol ; 20(1): 499, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138787

RESUMO

BACKGROUND: Red amaranth (Amaranthus gangeticus L.) has great diversity in Bangladesh, India, and South East Asia with multipurpose uses. The bright red-violet colored A. gangeticus is a popular and low-cost leafy vegetable in the Asian continent including Bangladesh and India because of attractive leaf color, taste, adequate nutraceuticals, phenolic compounds, and sole source of betalains. The natural colors and phenolic compounds of this species have a significant role in promoting the health-benefit including the scavenging capacity of radicals, the colorant of food products, and play a vital role in the industry of foods. However, phenolic profiles and radical scavenging activity of this species have not been evaluated. Hence, for the first time, four selected advance lines of A. gangeticus were characterized for phenolic profiles, antioxidant constituents, and antioxidant potentiality. RESULTS: A. gangeticus genotypes are abundant sources of phenolic profiles and antioxidant constituents with good radical quenching capacity that differed across the genotypes. Twenty-five phenolic acids and flavonoids, such as protocatechuic acid, salicylic acid, gentisic acid, gallic acid, ß-resorcylic acid, vanillic acid, p-hydroxybenzoic acid, chlorogenic acid, ellagic acid, syringic acid, ferulic acid, kaempferol, m-coumaric acid, trans-cinnamic acid, quercetin, p-coumaric acid, apigenin, caffeic acid, rutin, sinapic acid, isoquercetin, naringenin, myricetin, catechin, and hyperoside were identified in A. gangeticus accessions. A. gangeticus accessions LS7 and LS9 demonstrated ample phenolic acids, flavonoids, antioxidant constituents, and antioxidant potentiality. It revealed from the correlation study that antioxidant components of A. gangeticus genotypes exhibited good radical scavenging activities. The genotypes LS7 and LS9 could be directly used as phenolic profiles, antioxidant constituents, and antioxidant activity enrich cultivars. CONCLUSIONS: The identified compounds of phenolic acids and flavonoids in A. gangeticus privilege the comprehensive study of pharmacology. The basic information on phenolic profiles and antioxidant constituents achieved in the present study will provide the scientist's forum for the scientific assessment of these compounds in A. gangeticus.


Assuntos
Amaranthus/metabolismo , Flavonoides/metabolismo , Folhas de Planta/metabolismo , Polifenóis/metabolismo , Amaranthus/química , Antioxidantes/análise , Antioxidantes/metabolismo , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Sequestradores de Radicais Livres/análise , Sequestradores de Radicais Livres/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Folhas de Planta/química , Polifenóis/análise
16.
Nat Commun ; 11(1): 4951, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009382

RESUMO

Immunogenic cell death (ICD) and tumour-infiltrating T lymphocytes are severely weakened by elevated reactive oxygen species (ROS) in the tumour microenvironment. It is therefore of critical importance to modulate the level of extracellular ROS for the reversal of immunosuppressive environment. Here, we present a tumour extracellular matrix (ECM) targeting ROS nanoscavenger masked by pH sensitive covalently crosslinked polyethylene glycol. The nanoscavenger anchors on the ECM to sweep away the ROS from tumour microenvironment to relieve the immunosuppressive ICD elicited by specific chemotherapy and prolong the survival of T cells for personalized cancer immunotherapy. In a breast cancer model, elimination of the ROS in tumour microenvironment elicited antitumour immunity and increased infiltration of T lymphocytes, resulting in highly potent antitumour effect. The study highlights a strategy to enhance the efficacy of cancer immunotherapy by scavenging extracellular ROS using advanced nanomaterials.


Assuntos
Antineoplásicos/farmacologia , Espaço Extracelular/metabolismo , Sequestradores de Radicais Livres/metabolismo , Morte Celular Imunogênica , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular Tumoral , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Proteína HMGB1/metabolismo , Morte Celular Imunogênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Polietilenoglicóis/química , Microambiente Tumoral/efeitos dos fármacos
17.
Commun Biol ; 3(1): 490, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895456

RESUMO

Lipid astaxanthin, a potent antioxidant known as a natural sunscreen, accumulates in eukaryotic microalgae and confers photoprotection. We previously identified a photooxidative stress-inducible water-soluble astaxanthin-binding carotenoprotein (AstaP) in a eukaryotic microalga (Coelastrella astaxanthina Ki-4) isolated from an extreme environment. The distribution in eukaryotic microalgae remains unknown. Here we identified three novel AstaP orthologs in a eukaryotic microalga, Scenedesmus sp. Oki-4N. The purified proteins, named AstaP-orange2, AstaP-pink1, and AstaP-pink2, were identified as secreted fasciclin proteins with potent 1O2 quenching activity in aqueous solution, which are characteristics shared with Ki-4 AstaP. Nonetheless, the absence of glycosylation in the AstaP-pinks, the presence of a glycosylphosphatidylinositol (GPI) anchor motif in AstaP-orange2, and highly acidic isoelectric points (pI = 3.6-4.7), differed significantly from that of AstaP-orange1 (pI = 10.5). These results provide unique examples on the use of water-soluble forms of astaxanthin in photosynthetic organisms as novel strategies for protecting single cells against severe photooxidative stresses.


Assuntos
Proteínas de Algas/metabolismo , Proteínas de Transporte/metabolismo , Luz , Microalgas/metabolismo , Estresse Oxidativo/efeitos da radiação , Água/química , Proteínas de Algas/química , Proteínas de Algas/isolamento & purificação , Sequência de Aminoácidos , Proteínas de Transporte/química , Proteínas de Transporte/isolamento & purificação , Cor , Sequestradores de Radicais Livres/metabolismo , Scenedesmus/metabolismo , Oxigênio Singlete/metabolismo , Solubilidade , Soluções , Xantofilas/metabolismo
18.
J Chem Phys ; 153(11): 114117, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32962380

RESUMO

Many natural substances and drugs are radical scavengers that prevent the oxidative damage to fundamental cell components. This process may occur via different mechanisms, among which, one of the most important, is hydrogen atom transfer. The feasibility of this process can be assessed in silico using quantum mechanics to compute ΔGHAT ○. This approach is accurate, but time consuming. The use of machine learning (ML) allows us to reduce tremendously the computational cost of the assessment of the scavenging properties of a potential antioxidant, almost without affecting the quality of the results. However, in many ML implementations, the description of the relevant features of a molecule in a machine-friendly language is still the most challenging aspect. In this work, we present a newly developed machine-readable molecular representation aimed at the application of automatized ML algorithms. In particular, we show an application on the calculation of ΔGHAT ○.


Assuntos
Antioxidantes/química , Sequestradores de Radicais Livres/química , Aprendizado de Máquina , Modelos Químicos , Teoria Quântica , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Fluoxetina/análogos & derivados , Fluoxetina/química , Fluoxetina/farmacologia , Sequestradores de Radicais Livres/metabolismo , Sequestradores de Radicais Livres/farmacologia , Termodinâmica
19.
BMC Plant Biol ; 20(1): 421, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928106

RESUMO

BACKGROUND: Salt stress is one of the most damaging abiotic stresses in production of Upland cotton (Gossypium hirsutum). Upland cotton is defined as a medium salt-tolerant crop. Salinity hinders root development, shoots growth, and reduces the fiber quality. RESULTS: Our previous study verified a GhCIPK6a gene response to salt stress in G. hirsutum. The homologs of GhCIPK6a were analyzed in A2 (G. arboreum), D5 (G. raimondii), and AD1 (G. hirsutum) genomes. GhCIPK6a localized to the vacuole and cell membrane. The GhCBL1-GhCIPK6a and GhCBL8-GhCIPK6a complexes localized to the nucleus and cytomembrane. Overexpression of GhCIPK6a enhanced expression levels of co-expressed genes induced by salt stress, which scavenged ROS and involved in MAPK signaling pathways verified by RNA-seq analysis. Water absorption capacity and cell membrane stability of seeds from GhCIPK6a overexpressed lines was higher than that of wild-type seeds during imbibed germination stage. The seed germination rates and seedling field emergence percentages of GhCIPK6a overexpressed lines were higher than that of control line under salt stress. Moreover, overexpressing of GhCIPK6a in cotton increased lint percentage, and fiber length uniformity under salt stress. CONCLUSIONS: We verified the function of GhCIPK6a by transformation and RNA-seq analysis. GhCIPK6a overexpressed lines exhibited higher tolerance to abiotic stresses, which functioned by involving in ROS scavenging and MAPK pathways. Therefore, GhCIPK6a has the potential for cotton breeding to improve stress-tolerance.


Assuntos
Produtos Agrícolas/genética , Genes de Plantas , Gossypium/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Tolerância ao Sal/genética , Transdução de Sinais/genética , Sequestradores de Radicais Livres/metabolismo , Regulação da Expressão Gênica de Plantas , Espécies Reativas de Oxigênio/metabolismo , Salinidade , Análise de Sequência de DNA
20.
Eur J Med Chem ; 208: 112864, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32987314

RESUMO

A series of organoselenium compounds based on the hybridization of nonsteroidal antiinflammatory drugs (NSAIDs) scaffolds and Se functionalities (-SeCN and -SeCF3) were synthesized and characterized, and evaluated against four types of cancer cell lines, SW480 (human colon adenocarcinoma cells), HeLa (human cervical cancer cells), A549 (human lung carcinoma cells), MCF-7 (human breast adenocarcinoma cells). Interestingly, most of the investigated compounds showed active in reducing the viability of different cancer cell lines. The most active compound 3h showed IC50 values lower than 20 µM against the four cancer cell lines, particularly to SW480 and MCF-7 with IC 50 values of 4.9 and 3.4 µM, respectively. Furthermore, NSAIDs-SeCN derivatives (2h and 2i) and NSAIDs-SeCF3 derivatives (3h and 3i) were selected to investigate their ability to induce apoptosis in MCF-7 cells via modulation the expression of anti-apoptotic Bcl-2 protein, pro-inflammatory cytokines (IL-2) and proapoptotic caspase-3 protein. Moreover, the redox properties of the synthesized organoselenium candidates were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like assays. Taken together, these NSAIDs-Se candidates could provide promising new lead derivatives for further potential anticancer drug development.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Compostos Organosselênicos/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , DNA/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/metabolismo , Sequestradores de Radicais Livres/farmacologia , Humanos , Interleucina-2/metabolismo , Simulação de Acoplamento Molecular , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Tiorredoxina Redutase 1/metabolismo
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