Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.351
Filtrar
1.
Parasite ; 28: 11, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33576739

RESUMO

Egress plays a vital role in the life cycle of apicomplexan parasites including Eimeria tenella, which has been attracting attention from various research groups. Many recent studies have focused on early egress induced by immune molecules to develop a new method of apicomplexan parasite elimination. In this study, we investigated whether nitric oxide (NO), an immune molecule produced by different types of cells in response to cytokine stimulation, could induce early egress of eimerian sporozoites in vitro. Eimeria tenella sporozoites were extracted and cultured in primary chicken kidney cells. The number of sporozoites egressed from infected cells was analyzed by flow cytometry after treatment with NO released by sodium nitroferricyanide (II) dihydrate. The results showed that exogenous NO stimulated the rapid egress of E. tenella sporozoites from primary chicken kidney cells before replication of the parasite. We also found that egress was dependent on intra-parasitic calcium ion (Ca2+) levels and no damage occurred to host cells after egress. The virulence of egressed sporozoites was significantly lower than that of fresh sporozoites. The results of this study contribute to a novel field examining the interactions between apicomplexan parasites and their host cells, as well as that of the clearance of intracellular pathogens by the host immune system.


Assuntos
Eimeria tenella/fisiologia , Rim/parasitologia , Óxido Nítrico/farmacologia , Esporozoítos/efeitos dos fármacos , Animais , Cálcio , Células Cultivadas , Galinhas , Eimeria tenella/efeitos dos fármacos , Esporozoítos/fisiologia
2.
Arq. bras. cardiol ; 115(4): 669-677, out. 2020. tab, graf
Artigo em Português | LILACS, Sec. Est. Saúde SP | ID: biblio-1131333

RESUMO

Resumo Fundamento: Diversos estudos têm mostrado que as classes de diterpenos exercem efeito significativo no sistema cardiovascular. Os diterpenos, em particular, estão entre os principais compostos associados às propriedades cardiovasculares, como a propriedade vasorrelaxante, inotrópica, diurética e a atividade hipotensora. Embora o mecanismo de vasorrelaxamento do manool seja visível, seu efeito sobre a pressão arterial (PA) ainda é desconhecido. Objetivo: Avaliar o efeito hipotensor in vivo do manool e verificar o efeito de vasorrelaxamento ex vivo em anéis aórticos de ratos. Métodos: Os animais foram divididos aleatoriamente em dois grupos: normotensos e hipertensos. O grupo normotenso foi submetido à cirurgia sham e adotou-se o modelo 2R1C para o grupo hipertenso. Realizou-se monitoramento invasivo da PA para testes com manool em diferentes doses (10, 20 e 40 mg/kg). Foram obtidas curvas de concentração-resposta para o manool nos anéis aórticos, com endotélio pré-contraído com fenilefrina (Phe) após incubação com Nω-nitro-L-arginina metil éster (L-NAME) ou oxadiazolo[4,3-a]quinoxalina-1-ona (ODQ). Os níveis plasmáticos de óxido nítrico (NOx) foram medidos por ensaio de quimioluminescência. Resultados: Após a administração de manool, a PA se reduziu nos grupos normotenso e hipertenso, e esse efeito foi inibido pelo L-NAME em animais hipertensos apenas na dose de 10 mg/kg. O manool ex vivo promoveu vasorrelaxamento, inibido pela incubação de L-NAME e ODQ ou remoção do endotélio. Os níveis plasmáticos de NOx aumentaram no grupo hipertenso após a administração de manool. O manool induz o relaxamento vascular dependente do endotélio na aorta de ratos, mediado pela via de sinalização NO/cGMP e redução da PA, e também pelo aumento plasmático de NOx. Esses efeitos combinados podem estar envolvidos na modulação da resistência periférica, contribuindo para o efeito anti-hipertensivo do diterpeno. Conclusão: Esses efeitos em conjunto podem estar envolvidos na modulação da resistência periférica, contribuindo para o efeito anti-hipertensivo do diterpeno.


Abstract Background: Many studies have shown that the diterpenoid classes exert a significant effect on the cardiovascular system. Diterpenes, in particular, are among the main compound links to cardiovascular properties such as vasorelaxant, inotropic, diuretic and hypotensive activity. While the manool vasorelaxation mechanism is visible, its effect on blood pressure (BP) is still unknown. Objective: To evaluate the in vivo hypotensive effect of manool and check the ex vivo vasorelaxation effect in rat aortic rings. Methods: The animals were divided randomly into two groups: normotensive and hypertensive. The normotensive group was sham-operated, and the 2K1C model was adopted for the hypertensive group. Invasive BP monitoring was performed for manool tests at different doses (10, 20 and 40 mg/kg). Concentration-response curves for manool were obtained in the aorta rings, with endothelium, pre-contracted with phenylephrine (Phe) after incubation with Nω-nitro-L-arginine methyl ester(L-NAME) or oxadiazole [4,3-a]quinoxalin-1-one (ODQ). Nitric oxide (NOx) plasma levels were measured by chemiluminescence assay. Results: After manool administration, BP was reduced in normotensive and hypertensive groups, and this effect was inhibited by L-NAME in hypertensive animals only in 10 mg/kg dose. Ex vivo manool promoted vasorelaxation, which was inhibited by L-NAME and ODQ incubation or endothelium removal. NOx plasma levels increased in the hypertensive group after manool administration. Manool elicits endothelium-dependent vascular relaxation in rat aorta mediated by the NO/cGMP signaling pathway and BP reduction, also by NOx plasma increase. These combined effects could be involved in modulating peripheral resistance, contributing to the antihypertensive effect of diterpene. Conclusion: These effects together could be involved in modulating peripheral resistance, contributing to the antihypertensive effect of diterpene.


Assuntos
Animais , Ratos , Pressão Arterial , Hipertensão/tratamento farmacológico , Aorta Torácica , Vasodilatação , Vasodilatadores/farmacologia , Pressão Sanguínea , Endotélio Vascular , Diterpenos/farmacologia , Óxido Nítrico/farmacologia
3.
Chemosphere ; 259: 127356, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32650176

RESUMO

Growth of the most important nitrogen fixing cyanobacterium Nostoc muscorum is reported to be badly affected by the application of insecticides. To overcome their damaging effects, several strategies are being used. Out of these, some works on kinetin (KN, a synthetic cytokinin) has been recognized that it can overcome toxicity of insecticides in cyanobacteria. Besides this, it is now known that every hormone needs certain second messengers such as nitric oxide (NO) for its action. But implication of NO in KN-mediated regulation of insecticide toxicity is yet to be investigated. Hence in the current study, we have investigated the possible involvement of NO in KN-mediated regulation of cypermethrin toxicity in the cyanobacterium Nostoc muscorum. Cypermethrin decreased growth of Nostoc muscorum which was accompanied by decreased pigment contents and altered photosystem II (PS II) photochemistry that resulted in inhibition of photosynthetic process but KN significantly ameliorated cypermethrin toxicity. Cypermethrin induced production of free radicals (in-vivo and in-vitro) and weakened defensive mechanism (enzymatic and non-enzymatic defense system) which was restored by KN. Further, the results revealed that NG-nitro-l-arginine methyl ester (l-NAME, an inhibitor of nitric oxide synthase) worsened the effect of cypermethrin toxicity even in the presence of KN while 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO, a scavenger of NO) reversed KN-mediated amelioration even in the presence of sodium nitroprusside (SNP, an NO donor), suggesting that endogenous NO is required for mitigation of cypermethrin toxicity. Overall, our results first time show that endogenous NO is essential for KN-mediated mitigation of cypermethrin toxicity in the Nostoc muscorum.


Assuntos
Citocininas/farmacologia , Nostoc muscorum/fisiologia , Reguladores de Crescimento de Planta/farmacologia , Polissacarídeos Bacterianos/metabolismo , Piretrinas/toxicidade , Cianobactérias/metabolismo , Homeostase/efeitos dos fármacos , Inseticidas/farmacologia , Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Nostoc muscorum/efeitos dos fármacos , Nostoc muscorum/metabolismo , Fotoquímica , Fotossíntese/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/metabolismo , Espécies Reativas de Oxigênio/farmacologia
4.
Food Chem ; 332: 127416, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619946

RESUMO

Water bamboo shoots quickly deteriorate after harvest as a result of rapid lignification and softening. Nitric oxide (NO) has been used to extend the postharvest life of several other vegetables. Here, we examined the effect of NO on the storage of water bamboo shoots at 4℃ for 28 days. Without NO, fresh weight and firmness decreased quickly, while the cellulose and lignin contents increased sharply during storage. NO treatment delayed softening by maintaining the integrity of the cell wall and inhibiting the degradation of protopectin and the expressions of pectin methylesterase and polygalacturonase. NO treatment also delayed cellulose synthesis by increasing cellulase activity. NO treatment decreased the synthesis of lignin by inhibiting the activities of phenylalanine ammonia-lyase, cinnamyl alcohol dehydrogenase, laccase and peroxidase. These results indicate that NO treatment is effective at suppressing the softening and lignification of water bamboo shoots during postharvest storage.


Assuntos
Armazenamento de Alimentos/métodos , Óxido Nítrico/farmacologia , Poaceae/efeitos dos fármacos , Hidrolases de Éster Carboxílico/metabolismo , Parede Celular/efeitos dos fármacos , Parede Celular/ultraestrutura , Celulase/metabolismo , Celulose/metabolismo , Temperatura Baixa , Lignina/metabolismo , Microscopia Eletrônica de Varredura , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/metabolismo , Poaceae/metabolismo , Poligalacturonase/metabolismo
5.
In Vivo ; 34(3 Suppl): 1567-1588, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503814

RESUMO

BACKGROUND: On March 11, 2020, the World Health Organization (WHO) declared the outbreak of coronavirus disease (COVID-19) a pandemic. Since then, thousands of people have suffered and died, making the need for a treatment of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) more crucial than ever. MATERIALS AND METHODS: The authors carried out a search in PubMed, ClinicalTrials.gov and New England Journal of Medicine (NEJM) for COVID-19 to provide information on the most promising treatments against SARS-CoV-2. RESULTS: Possible COVID-19 agents with promising efficacy and favorable safety profile were identified. The results support the combination of copper, N-acetylcysteine (NAC), colchicine and nitric oxide (NO) with candidate antiviral agents, remdesivir or EIDD-2801, as a treatment for patients positive for SARS-CoV-2. CONCLUSION: The authors propose to study the effects of the combination of copper, NAC, colchicine, NO and currently used experimental antiviral agents, remdesivir or EIDD-2801, as a potential treatment scheme for SARS-COV-2.


Assuntos
Acetilcisteína/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Colchicina/uso terapêutico , Cobre/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Óxido Nítrico/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ribonucleosídeos/uso terapêutico , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacologia , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Alanina/administração & dosagem , Alanina/farmacologia , Alanina/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Antivirais/administração & dosagem , Antivirais/farmacologia , Autofagia/efeitos dos fármacos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Colchicina/administração & dosagem , Colchicina/farmacologia , Cobre/administração & dosagem , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Citidina/análogos & derivados , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Hidroxilaminas , Inflamação , Óxido Nítrico/administração & dosagem , Óxido Nítrico/farmacologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Pró-Fármacos/administração & dosagem , Pró-Fármacos/uso terapêutico , Ribonucleosídeos/administração & dosagem , Ribonucleosídeos/farmacologia , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
7.
Nitric Oxide ; 103: 1-3, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32590117

RESUMO

It has long been suggested that NO may inhibit an early stage in viral replication. Furthermore, in vitro tests have shown that NO inhibits the replication cycle of severe acute respiratory syndrome coronavirus. Despite smoking being listed as a risk factor to contract Covid-19, only a low proportion of the smokers suffered from SARS-corona infection in China 2003, and from Covid-19 in China, Europe and the US. We hypothesize, that the intermittent bursts of high NO concentration in cigarette smoke may be a mechanism in protecting against the virus. Mainstream smoke from cigarettes contains NO at peak concentrations of between about 250 ppm and 1350 ppm in each puff as compared to medicinal use of no more than 80 to a maximum of 160 ppm. The diffusion of NO through the cell wall to reach the virus should be significantly more effective at the very high NO concentration in the smoke, according to classic laws of physics. The only oxide of nitrogen in the mainstream smoke is NO, and the NO2 concentration that is inhaled is very low or undetectable, and methemoglobin levels are lower in smokers than non-smokers, reasonably explained by the breaths of air in between the puffs that wash out the NO. Specialized iNO machines can now be developed to provide the drug intermittently in short bursts at high concentration dose, which would then provide both a preventative drug for those at high risk, as well as an effective treatment, without the health hazards associated with smoking.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Óxido Nítrico/farmacologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Substâncias Protetoras/farmacologia , Administração por Inalação , Infecções por Coronavirus/tratamento farmacológico , Feminino , Humanos , Masculino , Óxido Nítrico/administração & dosagem , Substâncias Protetoras/administração & dosagem , Fumantes , Fumar
8.
J Biotechnol ; 318: 68-77, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32416108

RESUMO

Unprecedented anthropogenic activities have led to contamination of soil and water with toxic metals that present a great threat to crop yields. This situation has compelled researchers to understand metal toxicity responses in order to develop strategies to curtail toxic metal-mediated losses in crop yields. Past decade has witnessed tremendous developments with regard to the role of nitric oxide (NO) in regulating abiotic stresses including toxic metal in crop plants. However, mechanisms related with NO-mediated mitigation of metal toxicity are still less known, and thus investigation in this domain remains underway. Therefore, in this study potential of NO along with its mechanisms of action in mitigating hexavalent chromium [Cr(VI)] toxicity in tomato roots were investigated. Root length and dry weight were declined by Cr(VI) which coincided with increased accumulation of Cr. Major amount of Cr was in the cell wall fraction followed by soluble (including vacuoles) and cell organelles fraction and thus, leading to the cell death in roots. Further, Cr(VI) also declined endogenous NO by inhibiting nitric oxide synthase like activity, and down-regulated ascorbate-glutathione cycle and glutathione biosynthesis, but stimulated oxidative stress markers. In contrast, exogenous addition of NO (as a sodium nitroprusside) reduced toxic effects of Cr(VI) in tomato roots by decreasing Cr accumulation as well as triggering sequestration of Cr into vacuoles and thus collectively protect root from cell death. Moreover, NO also up-regulated ascorbate-glutathione cycle and glutathione biosynthesis, and stimulated phytochelatins, but greatly declined oxidative stress markers. Interestingly, addition of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) further worsened Cr(VI) toxicity, and Cr(VI) toxicity alleviatory effect of NO was partly reversed by the addition of c-PTIO, suggesting that NO has a crucial role in rendering Cr(VI) toxicity tolerance in tomato roots. Collectively, results suggest that NO mitigates Cr(VI) toxicity in tomato roots by reducing Cr and oxidative stress markers accumulation, triggering sequestration of Cr into vacuoles, and up-regulating ascorbate-glutathione cycle and glutathione biosynthesis, and phytochelatins.


Assuntos
Ácido Ascórbico/metabolismo , Cromo/toxicidade , Glutationa/metabolismo , Lycopersicon esculentum/efeitos dos fármacos , Óxido Nítrico/farmacologia , Metabolismo dos Carboidratos/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Cromo/metabolismo , Lycopersicon esculentum/crescimento & desenvolvimento , Lycopersicon esculentum/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoquelatinas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismo
9.
Plant Physiol Biochem ; 151: 729-742, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32353678

RESUMO

Nitric oxide (NO) has signalling roles in plant stress responses. Cadmium (Cd) and arsenic (As) soil pollutants alter plant development, mainly the root-system, by increasing NO-content, triggering reactive oxygen species (ROS), and forming peroxynitrite by NO-reaction with the superoxide anion. Interactions of NO with ROS and peroxynitrite seem important for plant tolerance to heavy metal(oid)s, but the mechanisms underlying this process remain unclear. Our goal was to investigate NO-involvement in rice (Oryza sativa L.) root-system after exposure to Cd or As, to highlight possible differences in NO-behaviour between the two pollutants. To the aim, morpho-histological, chemical and epifluorescence analyses were carried out on roots of different origin in the root-system, under exposure to Cd or As, combined or not with sodium nitroprusside (SNP), a NO-donor compound. Results show that increased intracellular NO levels alleviate the root-system alterations induced by Cd, i.e., inhibition of adventitious root elongation and lateral root formation, increment in lignin deposition in the sclerenchyma/endodermis cell-walls, but, even if reducing As-induced endodermis lignification, do not recover the majority of the As-damages, i.e., enhancement of AR-elongation, reduction of LR-formation, anomalous tissue-proliferation. However, NO decreases both Cd and As uptake, without affecting the pollutants translocation-capability from roots to shoots. Moreover, NO reduces the Cd-induced, but not the As-induced, ROS levels by triggering peroxynitrite production. Altogether, results highlight a different behaviour of NO in modulating rice root-system response to the toxicity of the heavy metal Cd and the metalloid As, which depends by the NO-interaction with the specific pollutant.


Assuntos
Arsênico , Cádmio , Óxido Nítrico , Oryza , Raízes de Plantas , Arsênico/toxicidade , Cádmio/toxicidade , Óxido Nítrico/farmacologia , Oryza/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Poluentes do Solo/toxicidade
10.
Med Sci Monit ; 26: e925679, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32454510

RESUMO

Nitric oxide (NO) represents a key signaling molecule in multiple regulatory pathways underlying vascular, metabolic, immune, and neurological function across animal phyla. Our brief critical discussion is focused on the multiple roles of the NO signaling pathways in the maintenance of basal physiological states of readiness in diverse cell types mediating innate immunological functions and in the facilitation of proinflammatory-mediated adaptive immunological responses associated with viral infections. Prior studies have reinforced the critical importance of constitutive NO signaling pathways in the homeostatic maintenance of the vascular endothelium, and state-dependent changes in innate immunological responses have been associated with a functional override of NO-mediated inhibitory tone. Accordingly, convergent lines of evidence suggest that dysregulation of NO signaling pathways, as well as canonical oxidative effects of inducible NO, may provide a permissive cellular environment for viral entry and replication. In immunologically compromised individuals, functional override and chronic rundown of inhibitory NO signaling systems promote aberrant expression of unregulated proinflammatory pathways resulting in widespread metabolic insufficiencies and structural damage to autonomous cellular and organ structures. We contend that restoration of normative NO tone via combined pharmaceutical, dietary, or complex behavioral interventions may partially reverse deleterious physiological conditions brought about by viral infection linked to unregulated adaptive immune responses.


Assuntos
Antivirais/farmacologia , Óxido Nítrico/farmacologia , Vírus da SARS/imunologia , Animais , Humanos , Inflamação/metabolismo , Inflamação/patologia , Oxirredução , Vírus da SARS/efeitos dos fármacos , Transdução de Sinais
12.
Langmuir ; 36(16): 4396-4404, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32255641

RESUMO

Tissue-engineered vascular graft (TEVG) is a promising alternative to meet the clinical demand of organ shortages. Herein, human hair keratin was extracted by the reduction method, followed by modification with zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) through thiol-Michael addition to improve blood clotting nature. Then, phosphobetainized keratin (PK) was coelectrospun with poly(ε-caprolactone) (PCL) to afford PCL/PK mats with a ratio of 7:3. The surface morphology, chemical structure, and wettability of these mats were characterized. The biocomposite mats selectively enhanced adhesion, migration, and growth of endothelial cells (ECs) while suppressed proliferation of smooth muscle cells (SMCs) in the presence of glutathione (GSH) and GSNO due to the catalytic generation of NO. In addition, these mats exhibited good blood anticoagulant activity by reducing platelet adhesion, prolonging blood clotting time, and inhibiting hemolysis. Taken together, these NO-generating PCL/PK mats have potential applications as a scaffold for vascular tissue engineering with rapid endothelialization and reduced SMC proliferation.


Assuntos
Materiais Biocompatíveis/química , Queratinas/química , Óxido Nítrico/farmacologia , Poliésteres/química , Tecidos Suporte/química , Catálise , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cabelo/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Metacrilatos/química , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Adesividade Plaquetária/efeitos dos fármacos , Engenharia Tecidual
13.
Clin Podiatr Med Surg ; 37(2): 231-246, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32146980

RESUMO

Gaseous nitric oxide under increased atmospheric pressure (gNOp) has shown ability to kill multidrug-resistant bacteria in an in vitro model and in a live mammalian (porcine) model. Factors impacting the kill rate of the multidrug-resistant bacteria include atmospheric pressures, concentration of gaseous NO, flow rate, and duration of application. Using successful in vitro parameters, gNOp showed multilog reduction of bacteria in a live mammalian (porcine) model. The in vitro testing system, using the EpiDerm-FT skin model (stem cell grown skin), was used to develop an infected wound model for Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant S aureus.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Óxido Nítrico/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Úlcera Cutânea/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Pressão Atmosférica , Modelos Animais de Doenças , Farmacorresistência Bacteriana Múltipla , Úlcera Cutânea/etiologia , Suínos
14.
J Biotechnol ; 313: 29-38, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32151644

RESUMO

The involvement of two extremely important signalling molecules, nitric oxide (NO) and abscisic acid (ABA) has been employed by plants to facilitate the adaptive/tolerate response during stressful conditions. However, the interactive role of exogenously applied NO and ABA is very less studied at physiological, biochemical and molecular levels. The present study therefore, evaluated the effects of individual and simultaneous addition of exogenous NO donor SNP (100µM) and ABA (10µM) on photosynthesis, Calvin-Benson cycle enzymes, S-assimilation enzymes, oxidative stress components, and genotoxicity in Brassica juncea cv. Varuna, exposed to polyethylene glycol (PEG)-induced drought stress. Results showed that a loss induced by PEG was significantly surpassed by the application of NO or/and ABA with PEG for chlorophyll content, net photosynthestic rate (Pn), internal CO2 concentration (Ci), stomatal conductance (gs), transpiration rate (Tr), maximum photosystem II (PSII) efficiency (Fv/Fm), actual PSII efficiency (ΦPSII), intrinsic PSII efficiency (Fv´/ Fm´), photochemical quenching (qP), non-photochemical quenching (NPQ), electron transport chain (ETC), ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCo), glyceraldehyde-3-phosphate dehydrogenase (GapDH), phosphoribulokinase (PRK), ATP-sulfurylase (ATP-S), and serine acetyltransferase (SAT) activities. The genomic template stability (GTS) (measured as changes in RAPD profiles) was significantly affected and showed varying degrees of DNA polymorphism, highest in PEG and lowest in PEG + NO and PEG + NO + ABA. Furthermore, the changes in RAPD profiles showed consistent results when compared with various photosynthetic and oxidative parameters. Altogether, this study concluded that supplementation of individual NO and together with ABA was more effective than individual ABA in alleviating PEG-induced drought stress in B. juncea L. seedlings.


Assuntos
Ácido Abscísico/farmacologia , Mostardeira/fisiologia , Óxido Nítrico/farmacologia , Fotossíntese/efeitos dos fármacos , Reguladores de Crescimento de Planta/farmacologia , Transdução de Sinais/efeitos dos fármacos , Clorofila/metabolismo , Secas , Fluorescência , Mostardeira/efeitos dos fármacos , Mostardeira/genética , Polietilenoglicóis/farmacologia , Técnica de Amplificação ao Acaso de DNA Polimórfico , Plântula/efeitos dos fármacos , Plântula/fisiologia , Estresse Fisiológico
15.
Sci Adv ; 6(9): eaay5413, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32133403

RESUMO

Angiogenesis is stimulated by nitric oxide (NO) production in endothelial cells (ECs). Although proangiogenic actions of human mesenchymal stem cells (hMSCs) have been extensively studied, the mechanistic role of NO in this action remains obscure. Here, we used a gelatin hydrogel that releases NO upon crosslinking by a transglutaminase reaction ("NO gel"). Then, the source-specific behaviors of bone marrow versus adipose tissue-derived hMSCs (BMSCs versus ADSCs) were monitored in the NO gels. NO inhibition resulted in significant decreases in their angiogenic activities. The NO gel induced pericyte-like characteristics in BMSCs in contrast to EC differentiation in ADSCs, as evidenced by tube stabilization versus tube formation, 3D colocalization versus 2D coformation with EC tube networks, pericyte-like wound healing versus EC-like vasculogenesis in gel plugs, and pericyte versus EC marker production. These results provide previously unidentified insights into the effects of NO in regulating hMSC source-specific angiogenic mechanisms and their therapeutic applications.


Assuntos
Tecido Adiposo/metabolismo , Células da Medula Óssea/metabolismo , Hidrogéis , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Óxido Nítrico , Tecido Adiposo/citologia , Antígenos de Diferenciação/metabolismo , Células da Medula Óssea/citologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Gelatina/química , Gelatina/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Óxido Nítrico/química , Óxido Nítrico/farmacologia
16.
Sci Adv ; 6(9): eaaz0260, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32133408

RESUMO

Cytostasis is the most salient manifestation of the potent antimicrobial activity of nitric oxide (NO), yet the mechanism by which NO disrupts bacterial cell division is unknown. Here, we show that in respiring Escherichia coli, Salmonella, and Bacillus subtilis, NO arrests the first step in division, namely, the GTP-dependent assembly of the bacterial tubulin homolog FtsZ into a cytokinetic ring. FtsZ assembly fails in respiring cells because NO inactivates inosine 5'-monophosphate dehydrogenase in de novo purine nucleotide biosynthesis and quinol oxidases in the electron transport chain, leading to drastic depletion of nucleoside triphosphates, including the GTP needed for the polymerization of FtsZ. Despite inhibiting respiration and dissipating proton motive force, NO does not destroy Z ring formation and only modestly decreases nucleoside triphosphates in glycolytic cells, which obtain much of their ATP by substrate-level phosphorylation and overexpress inosine 5'-monophosphate dehydrogenase. Purine metabolism dictates the susceptibility of early morphogenic steps in cytokinesis to NO toxicity.


Assuntos
Bacillus subtilis/metabolismo , Citocinese/efeitos dos fármacos , Escherichia coli/metabolismo , Óxido Nítrico/farmacologia , Salmonella/metabolismo , Bacillus subtilis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Citocinese/genética , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Escherichia coli/genética , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/genética , Força Próton-Motriz/efeitos dos fármacos , Força Próton-Motriz/genética , Salmonella/genética
17.
ACS Appl Mater Interfaces ; 12(8): 9070-9079, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32009376

RESUMO

The development of nonfouling and antimicrobial materials has shown great promise for reducing thrombosis and infection associated with medical devices with aims of improving device safety and decreasing the frequency of antibiotic administration. Here, the design of an antimicrobial, anti-inflammatory, and antithrombotic vascular catheter is assessed in vivo over 7 d in a rabbit model. Antimicrobial and antithrombotic activity is achieved through the integration of a nitric oxide donor, while the nonfouling surface is achieved using a covalently bound phosphorylcholine-based polyzwitterionic copolymer topcoat. The effect of sterilization on the nonfouling nature and nitric oxide release is presented. The catheters reduced viability of Staphylococcus aureus in long-term studies (7 d in a CDC bioreactor) and inflammation in the 7 d rabbit model. Overall, this approach provides a robust method for decreasing thrombosis, inflammation, and infections associated with vascular catheters.


Assuntos
Antibacterianos , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres , Materiais Revestidos Biocompatíveis , Óxido Nítrico , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/crescimento & desenvolvimento , Trombose/prevenção & controle , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Óxido Nítrico/química , Óxido Nítrico/farmacologia , Coelhos
19.
Gene ; 737: 144479, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32068124

RESUMO

BACKGROUND: Cardiac and renal dysfunction are often co-morbid pathologies leading to worsening prognosis resulting in difficulty in therapy of left ventricular hypertrophy (LVH). The aim of the current study was to determine the changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and upon treatment with gasotransmitter including H2S (hydrogen sulphide), NO (nitric oxide) and combined (H2S + NO). METHODS: A total of 72 Wistar Kyoto rats (with equivalent male and female animals) were recruited in the present study where LVH rat models were treated with H2S and NO individually as well as with both combined. Cardiac and renal physical indices were recorded and relative gene expression were quantified. RESULTS: Both cardiac and renal physical indices were significantly modified with individual as well as combined H2S + NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNFα and IGF1, mRNAs to be significantly higher (P ≤ 0.05) in the myocardia and renal tissues of LVH rats, while individual and combined H2S + NO treatment resulted in lowering the gene expression to normal/near to normal levels. The cardiac remodeling genes MYH7, TGFß, SMAD4 and BRG1 expression were significantly up-regulated (P ≤ 0.05) in the myocardia of LVH where the combined H2S + NO treatment resulted in normal/near to normal expression more effectively as compared to individual treatments. In addition individual as well as combined H2S and NO treatment significantly decreased PKD1 expression in renal tissue, which was up-regulated in LVH rats (P ≤ 0.05). CONCLUSIONS: The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment of LVH rat model indicates important therapeutic potential of combined treatment with H2S + NO gasotransmitters in hypertension and cardiac hypertrophy when present as co-morbidity with renal complications.


Assuntos
Expressão Gênica/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Hipertensão Renal/genética , Hipertensão/genética , Hipertrofia Ventricular Esquerda/genética , Nefrite/genética , Óxido Nítrico/farmacologia , Remodelação Vascular/genética , Remodelação Ventricular/genética , Animais , Progressão da Doença , Feminino , Humanos , Sulfeto de Hidrogênio/sangue , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Endogâmicos WKY , Canais de Cátion TRPP/genética
20.
Carbohydr Polym ; 234: 115928, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32070544

RESUMO

We developed a co-delivery system of nitric oxide (NO) and antibiotic for the antibiotic-resistant bacterial infection therapy. The NO could disperse the bacterial biofilms and convert the bacteria into an antibiotic-susceptible planktonic form. Using the chitosan-graft-poly(amidoamine) dendrimer (CS-PAMAM) as the co-delivery system, methicillin (MET) and NO were conjugated successively to form CS-PAMAM-MET/NONOate. The positive CS-PAMAM could efficiently capture the negatively charged bacteria and PAMAM provide abundant reaction points for high payloads of NO and MET. The CS-PAMAM-MET/NONOate displayed effective and combined antibacterial activity to the E. coli and S. aureus. Particularly, for the MET-resistant S. aureus (MRSA), the CS-PAMAM-MET/NONOate displayed the synergistic antibacterial activity. In vivo wound healing assays also confirmed that CS-PAMAM-MET/NONOate could heal the infection formed by MRSA and then accelerate the wound healing effectively. Moreover, CS-PAMAM-MET/NONOate showed no toxicity towards 3T3 cells in vitro and rats in vivo, providing a readily but high-efficient strategy to drug-resistant bacterial infection therapy.


Assuntos
Antibacterianos/farmacologia , Quitosana/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Meticilina/farmacologia , Óxido Nítrico/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/síntese química , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Dendrímeros/química , Dendrímeros/farmacologia , Sistemas de Liberação de Medicamentos , Masculino , Meticilina/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Tamanho da Partícula , Poliaminas/química , Poliaminas/farmacologia , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/patologia , Propriedades de Superfície
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA