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1.
Toxicol Lett ; 337: 91-97, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33197555

RESUMO

Snakebite is a neglected tropical disease with a massive global burden of injury and death. The best current treatments, antivenoms, are plagued by a number of logistical issues that limit supply and access in remote or poor regions. We explore the anticoagulant properties of venoms from the genus Micrurus (coral snakes), which have been largely unstudied, as well as the effectiveness of antivenom and a small-molecule phospholipase inhibitor-varespladib-at counteracting these effects. Our in vitro results suggest that these venoms likely interfere with the formation or function of the prothrombinase complex. We find that the anticoagulant potency varies widely across the genus and is especially pronounced in M. laticollaris. This variation does not appear to correspond to previously described patterns regarding the relative expression of the three-finger toxin and phospholipase A2 (PLA2) toxin families within the venoms of this genus. The coral snake antivenom Coralmyn, is largely unable to ameliorate these effects except for M. ibiboboca. Varespladib on the other hand completely abolished the anticoagulant activity of every venom. This is consistent with the growing body of results showing that varespladib may be an effective treatment for a wide range of toxicity caused by PLA2 toxins from many different snake species. Varespladib is a particularly attractive candidate to help alleviate the burden of snakebite because it is an approved drug that possesses several logistical advantages over antivenom including temperature stability and oral availability.


Assuntos
Anticoagulantes/toxicidade , Cobras Corais , Venenos Elapídicos/toxicidade , Acetatos/farmacologia , Acetatos/uso terapêutico , Animais , Coagulação Sanguínea/efeitos dos fármacos , Venenos Elapídicos/antagonistas & inibidores , Humanos , Indóis/farmacologia , Indóis/uso terapêutico , Camundongos , Inibidores de Fosfolipase A2/farmacologia , Inibidores de Fosfolipase A2/uso terapêutico , Receptores da Fosfolipase A2/efeitos dos fármacos , Mordeduras de Serpentes/tratamento farmacológico , Especificidade da Espécie , Tromboplastina/metabolismo , Tempo de Coagulação do Sangue Total
2.
Antiviral Res ; 185: 104996, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309540

RESUMO

Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5%. To date, there is an unmet need for vaccines and specific therapeutics for this disease. Available treatments are either supportive medications in use for other diseases or those lacking specificity requiring higher doses. The viral infection mode is initiated by the attachment of the viral spike glycoprotein to the human Dipeptidyl Peptidase IV (DPP4). Our attempts to screen antivirals against MERS led us to identify montelukast sodium hydrate (MSH), an FDA-approved anti-asthma drug, as an agent attenuating MERS-CoV infection. We showed that MSH directly binds to MERS-CoV-Receptor-Binding Domain (RBD) and inhibits its molecular interaction with DPP4 in a dose-dependent manner. Our cell-based inhibition assays using MERS pseudovirions demonstrated that viral infection was significantly inhibited by MSH and was further validated using infectious MERS-CoV culture. Thus, we propose MSH as a potential candidate for therapeutic developments against MERS-CoV infections.


Assuntos
Acetatos/farmacologia , Antivirais/farmacologia , Ciclopropanos/farmacologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Quinolinas/farmacologia , Sulfetos/farmacologia , Animais , Antiasmáticos/farmacologia , Proteínas de Transporte/efeitos dos fármacos , Chlorocebus aethiops , Infecções por Coronavirus/tratamento farmacológico , Indutores do Citocromo P-450 CYP1A2/farmacologia , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Reposicionamento de Medicamentos , Células HEK293 , Humanos , Antagonistas de Leucotrienos/farmacologia , Receptores Virais/genética , Receptores Virais/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero , Internalização do Vírus/efeitos dos fármacos
3.
Food Chem ; 338: 127846, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32836001

RESUMO

Cold storage is widely used for delaying ripening and senescence; however, fruit aroma diminishes noticeably after long-term cold storage. The esters synthesized by the lipoxygenase (LOX) pathway are responsible for 'Nanguo' pear aroma. As methyl jasmonate (MeJA) is known to act on various fruit qualities, we investigated whether it acts via the LOX pathway in cold-stored 'Nanguo' pears. MeJA treatment increased the content of volatile esters and unsaturated fatty acids and the activities of alcohol acyltransferase, alcohol dehydrogenase, and LOX. It also up-regulated the expression of key genes (PuAAT, PuADH3, PuADH5, PuADH9, PuLOX1, and PuLOX3) in the LOX pathway and that of transcription factors (PuMYB21-like, PuMYB108-like, PuWRKY61, PuWRKY72, and PuWRKY31), whose genes were differentially expressed in preliminary transcriptome analysis. Therefore, considering its effects on LOX pathway-related genes and transcription factors, MeJA may be useful in preventing cold-storage-induced decline in ester biosynthesis, aroma, and consequently the quality of cold-stored 'Nanguo' pears.


Assuntos
Acetatos/farmacologia , Ciclopentanos/farmacologia , Ésteres/metabolismo , Armazenamento de Alimentos/métodos , Oxilipinas/farmacologia , Pyrus/efeitos dos fármacos , Compostos Orgânicos Voláteis/metabolismo , Ácidos Graxos Insaturados/análise , Frutas/química , Frutas/efeitos dos fármacos , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Lipoxigenase/genética , Lipoxigenase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas/genética , Proteínas/metabolismo , Pyrus/química , Pyrus/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
4.
Food Chem ; 338: 128044, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32932092

RESUMO

The effects of preharvest treatments with 0.1 mM methyl jasmonate (MeJA) and 0.5 mM salicylic acid (SA) on quality parameters of lemon fruit and their relationship with antioxidant systems, gene expression and bioactive compounds at harvest and during cold storage were evaluated. Results showed that total antioxidant activity, total phenolic content and the major individual phenolics (hesperidin and eriocitrin) were always higher in treated fruit than in controls. The activity of the antioxidant enzymes catalase, peroxidase and ascorbate peroxidase was also increased at harvest by SA and MeJA treatments, especially the last enzyme, for which the expression of its codifying gene was also enhanced. In addition, treated fruit had lower weight and firmness losses, respiration rate and production of ethylene than controls. Moreover, sugars and organic acids were maintained at higher concentration in flavedo and juice as a consequence of preharvest SA and MeJA treatments, showing an effect on maintaining fruit quality properties.


Assuntos
Acetatos/farmacologia , Antioxidantes/metabolismo , Citrus/efeitos dos fármacos , Ciclopentanos/farmacologia , Armazenamento de Alimentos/métodos , Oxilipinas/farmacologia , Ácido Salicílico/farmacologia , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Citrus/química , Citrus/metabolismo , Temperatura Baixa , Frutas/química , Frutas/efeitos dos fármacos , Frutas/metabolismo , Peroxidase/metabolismo , Fenóis/análise
5.
Acta Cir Bras ; 35(9): e202000905, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33084735

RESUMO

PURPOSE: To determine the nephroprotective effect of NAC and Montelukast Sodium administration against the development of renal damage associated with long warm renal ischemia. METHODS: Twenty-seven rats were randomly divided into 3 study groups, which received NAC, montelukast and placebo, and 3 rats were included in the sham-treated control group. Medications were given 3 days before the procedure. DMSA renal scintigraphy was performed before and after surgery. The right renal pedicle was occluded for 45 min to induce ischemia and then subjected to reperfusion for 6 h (I/R groups). RESULTS: On pathological examination, the mean pathological scores of the montelukast and NAC groups were significantly lower than those of the placebo group. (p <0.05). In biochemical examination, significant differences were found in all parameter levels between the placebo group and the montelukast and NAC groups. (p <0.05) When postoperative DMSA renal scintigraphy measurements and renal function levels were compared, significant differences were found between the montelukast and NAC groups and the placebo and sham groups. CONCLUSION: The administration of NAC and montelukast sodium was seen to have a nephroprotective effect against the development of renal damage associated with warm renal ischemia.


Assuntos
Acetatos , Acetilcisteína , Quinolinas , Traumatismo por Reperfusão , Acetatos/farmacologia , Acetilcisteína/farmacologia , Animais , Rim/irrigação sanguínea , Quinolinas/farmacologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/prevenção & controle , Succímero , Tomografia Computadorizada por Raios X
6.
J Med Chem ; 63(22): 13526-13545, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-32902984

RESUMO

GPR84 is a medium chain free fatty acid-binding G-protein-coupled receptor associated with inflammatory and fibrotic diseases. As the only reported antagonist of GPR84 (PBI-4050) that displays relatively low potency and selectivity, a clear need exists for an improved modulator. Structural optimization of GPR84 antagonist hit 1, identified through high-throughput screening, led to the identification of potent and selective GPR84 inhibitor GLPG1205 (36). Compared with the initial hit, 36 showed improved potency in a guanosine 5'-O-[γ-thio]triphosphate assay, exhibited metabolic stability, and lacked activity against phosphodiesterase-4. This novel pharmacological tool allowed investigation of the therapeutic potential of GPR84 inhibition. At once-daily doses of 3 and 10 mg/kg, GLPG1205 reduced disease activity index score and neutrophil infiltration in a mouse dextran sodium sulfate-induced chronic inflammatory bowel disease model, with efficacy similar to positive-control compound sulfasalazine. The drug discovery steps leading to GLPG1205 identification, currently under phase II clinical investigation, are described herein.


Assuntos
Descoberta de Drogas/métodos , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/metabolismo , Acetatos/química , Acetatos/farmacologia , Regulação Alostérica/efeitos dos fármacos , Regulação Alostérica/fisiologia , Animais , Células CACO-2 , Células Cultivadas , Cães , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Ratos , Ratos Sprague-Dawley
7.
Life Sci ; 260: 118452, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956660

RESUMO

Asthma is a chronic inflammatory and allergic disease that is mainly characterized by reversible airway obstruction and bronchial hyperresponsiveness. The incidence of asthma is increasing with more than 350 million people worldwide are affected. Up to now, there is no therapeutic option for asthma and most of the prescribed drugs aim to ameliorate the symptoms of the disease especially during the acute exacerbations after trigger exposure. Asthma is a heterogonous disease that involves interactions between inflammatory mediators and cellular components within the disease microenvironment including inflammatory and structural cells. Cysteinyl leukotrienes (cys-LTs) are inflammatory lipid mediators that have potent roles in asthma pathogenesis. CysLTs consisting of LTC4, LTD4, and LTE4 are mainly secreted by leukocytes and act through three main G-protein coupled receptors (CysLT1R, CysLT2R, and CysLT3R). LTD4 is the most potent bronchoconstrictor which gives it the priority to be discussed in detail in this review. LTD4 binds with high affinity to CysLT1R and many studies showed that using CysLT1R antagonists such as montelukast has a beneficial effect for asthmatics especially in corticosteroid refractory cases. Since asthma is a heterogeneous inflammatory disease of many cell types involved in the disease pathogenies and LTD4 has a special role in inflammation and bronchoconstriction, this review highlights the role of LTD4 on each cellular component in asthma and the benefits of using CysLT1R antagonists in ameliorating LTD4-induced effects.


Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Asma/metabolismo , Asma/patologia , Hipersensibilidade/metabolismo , Leucotrieno D4/metabolismo , Acetatos/farmacologia , Remodelação das Vias Aéreas/efeitos dos fármacos , Animais , Asma/etiologia , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/patologia , Cisteína/metabolismo , Expressão Gênica , Humanos , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/etiologia , Mediadores da Inflamação/metabolismo , Antagonistas de Leucotrienos/farmacologia , Leucotrieno D4/toxicidade , Leucotrienos/metabolismo , Quinolinas/farmacologia , Receptores de Leucotrienos/metabolismo , Compostos de Tosil/farmacologia
8.
Int J Nanomedicine ; 15: 6593-6603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982220

RESUMO

Purpose: Micro-arc oxidation (MAO) is a fast and effective method to prepare nanoporous coatings with high biological activity and bonding strength. Simple micro/nano-coatings cannot fully meet the requirements of osteogenesis. To further improve the biological activity of a titanium surface, we successfully added biological magnesium (Mg2+) to a coating by micro-arc oxidation and evaluated the optimal magnesium concentration in the electrolyte, biocompatibility, cell adhesion, proliferation, and osteogenesis in vitro. Methods: Nanoporous titanium coatings with different concentrations of magnesium were prepared by micro-arc oxidation and characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The Mg2+ release ability of the magnesium-incorporated nanoporous titanium coatings was determined by inductively coupled plasma emission spectrometry (ICP-OES). The cytotoxicity of the magnesium-incorporated nanoporous titanium coatings was detected with live/dead double-staining tests. A CCK-8 assay was employed to evaluate cell proliferation, and FITC-phalloidin was used to determine the structure of the cytoskeleton by staining ß-actin. Alkaline phosphatase (ALP) activity was evaluated by alizarin red S (ARS) staining to determine the effect of the coatings on osteogenic differentiation in vitro. The mRNA expression of osteogenic differentiation-related markers was measured using qRT-PCR. Results: EDS analyses revealed the successful addition of magnesium to the microporous coatings. The best magnesium concentration of the electrolyte for preparing the new coating was determined. The results showed that the nano-coatings prepared using the electrolyte with 2 g/L magnesium acetate best promoted the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Conclusion: These results suggest that the new titanium metal coating with a dual effect of promoting bone morphology and supplying the biological ion Mg2+ can be beneficial for rapid osseointegration.


Assuntos
Acetatos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Compostos de Magnésio/farmacologia , Osseointegração/efeitos dos fármacos , Acetatos/química , Animais , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Magnésio/química , Magnésio/farmacocinética , Compostos de Magnésio/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Nanoporos , Osseointegração/fisiologia , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Oxirredução , Próteses e Implantes , Ratos Sprague-Dawley , Espectrometria por Raios X , Propriedades de Superfície
9.
Toxicon ; 187: 101-104, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889027

RESUMO

The phospholipase A2 (PLA2) inhibitors varespladib (LY315920) and its orally available derivative methyl-varespladib (LY333013) have been proposed as potential therapies for the treatment of snakebite envenomings in which toxicity depends on the action of PLA2s. In this study, the ability of LY315920 to abrogate the effect of the potent neurotoxic venom of Oxyuranus scutellatus (taipan) was assessed using the mouse phrenic nerve-diaphragm preparation. LY315920 inhibited the venom when (a) incubated with venom before addition to the medium; (b) added to the medium before addition of venom, and; (c) added to the medium within 30 min after addition of venom, and even after the onset of decline in twitch response. This contrasts with previous results with antivenom using the same experimental model, in which the window of time when antibodies are effective is shorter than 10 min. It is proposed that such differences may depend either on the higher affinity of the inhibitor for PLA2s or on the possibility that LY315920 reaches the cytosol of the nerve terminals, inhibiting neurotoxins that have been internalized. Our findings bear implications on the therapeutic potential of varespladib in neurotoxic snakebite envenomings mediated by presynaptically-acting PLA2s.


Assuntos
Acetatos/farmacologia , Venenos Elapídicos/toxicidade , Indóis/farmacologia , Bloqueio Neuromuscular/métodos , Antivenenos , Doenças Neuromusculares , Junção Neuromuscular , Síndromes Neurotóxicas , Neurotoxinas , Mordeduras de Serpentes
10.
Sci Rep ; 10(1): 15166, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938968

RESUMO

Holm oak trees (Quercus ilex L.) mortality is increasing worryingly in the Mediterranean area in the last years. To a large degree this mortality is caused by the oomycete Phytophthora spp., which is responsible for forest decline and dieback in evergreen oak forest areas of the southwestern Iberian Peninsula. This study is based on the possibility of applying chemical elicitors or filtered oomycete extracts to holm oak somatic embryos (SE) in order to induce epigenetic memory, priming, that may increase tolerance to the pathogen in future infections. To this end, we first examined the effect of priming treatments on SE development and its oxidative stress state, to avoid elicitors that may cause damage to embryogenic tissues. Both, the sterile oomycete extracts and the chemical elicitor methyl jasmonate (MeJA) did not produce any detrimental effect on SE growth and development, unlike the elicitors benzothiadiazole (BTH) and p-aminobenzoic acid (PABA) that reduced the relative weight gain and resulted in necrotic and deformed SE when were applied at high concentrations (25 µM BTH or 50 µM PABA) in accordance with their high malondialdehyde content. No significant differences among elicitation treatments were found in dual culture bioassays, although those SEs elicited with 50 µM MeJA increased H2O2 production after challenged against active oomycete indicating the activation of stress response. Since this elicitation treatment did not produce any adverse effect in the embryogenic process we suggest that could be used in further priming experiments to produce holm oak plants adapted to biotic stress.


Assuntos
Phytophthora/patogenicidade , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Quercus/embriologia , Quercus/microbiologia , Ácido 4-Aminobenzoico/toxicidade , Acetatos/farmacologia , Ciclopentanos/farmacologia , Florestas , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Oxilipinas/farmacologia , Phytophthora/química , Proteínas/farmacologia , Quercus/efeitos dos fármacos , Sementes/efeitos dos fármacos , Sementes/embriologia , Sementes/metabolismo , Espanha , Tiadiazóis/toxicidade
11.
Am J Respir Cell Mol Biol ; 63(6): 748-757, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32822237

RESUMO

Electronic-cigarette, or vaping, product use-associated lung injury (EVALI) is a syndrome of acute respiratory failure characterized by monocytic and neutrophilic alveolar inflammation. Epidemiological and clinical evidence suggests a role of vitamin E acetate (VEA) in the development of EVALI, yet it remains unclear whether VEA has direct pulmonary toxicity. To test the hypotheses that aerosolized VEA causes lung injury in mice and directly injures human alveolar epithelial cells, we exposed adult mice and primary human alveolar epithelial type II (AT II) cells to an aerosol of VEA generated by a device designed for vaping oils. Outcome measures in mice included lung edema, BAL analysis, histology, and inflammatory cytokines; in vitro outcomes included cell death, cytokine release, cellular uptake of VEA, and gene-expression analysis. Comparison exposures in both models included the popular nicotine-containing JUUL aerosol. We discovered that VEA caused dose-dependent increases in lung water and BAL protein compared with control and JUUL-exposed mice in association with increased BAL neutrophils, oil-laden macrophages, multinucleated giant cells, and inflammatory cytokines. VEA aerosol was also toxic to AT II cells, causing increased cell death and the release of monocyte and neutrophil chemokines. VEA was directly absorbed by AT II cells, resulting in the differential gene expression of several inflammatory biological pathways. Given the epidemiological and clinical characteristics of the EVALI outbreak, these results suggest that VEA plays an important causal role.


Assuntos
Acetatos/farmacologia , Lesão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Camundongos Endogâmicos C57BL , Nicotina/farmacologia , Vaping , Vitamina E/análise
12.
Plant Physiol Biochem ; 155: 676-682, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32861034

RESUMO

The investigation of dehydrins participation in MeJA-induced protection of wheat plants (Triticum aestivum L.) from drought stress was performed. The dehydration was designed by the presence of mannitol in increasing concentration (3, 4, and 5%) in the growth medium of wheat seedlings. Pre-treatment of 3-days-old seedlings with 0.1 µM MeJA reduced the level of drought-induced growth retardation as well as membrane structures lesions. Exogenous MeJA enhanced accumulation of the TADHN dehydrin transcripts and dehydrin proteins with Mw 28 and 55 kDa in wheat seedlings under normal conditions and additionally increased their expression during dehydration. The obtained data may indicate the dehydrins involvement in MeJA protective effect on wheat plants from the damages caused by water deficit.


Assuntos
Acetatos/farmacologia , Ciclopentanos/farmacologia , Desidratação , Oxilipinas/farmacologia , Proteínas de Plantas/fisiologia , Triticum/fisiologia , Secas , Água
14.
Sci Rep ; 10(1): 11472, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32651431

RESUMO

Crosstalk between salicylic acid (SA) and jasmonic acid (JA) signaling plays an important role in regulation of plant senescence. Our previous work found that SA could delay methyl jasmonate (MeJA)-induced leaf senescence in a concentration-dependent manner. Here, the effect of low concentration of SA (LCSA) application on MeJA-induced leaf senescence was further assessed. High-throughput sequencing (RNA-Seq) results showed that LCSA did not have dominant effects on the genetic regulatory pathways of basal metabolism like nitrogen metabolism, photosynthesis and glycolysis. The ClusterONE was applied to identify discrete gene modules based on protein-protein interaction (PPI) network. Interestingly, an autophagy-related (ATG) module was identified in the differentially expressed genes (DEGs) that exclusively induced by MeJA together with LCSA. RT-qPCR confirmed that the expression of most of the determined ATG genes were upregulated by LCSA. Remarkably, in contrast to wild type (Col-0), LCSA cannot alleviate the leaf yellowing phenotype in autophagy defective mutants (atg5-1 and atg7-2) upon MeJA treatment. Confocal results showed that LCSA increased the number of autophagic bodies accumulated in the vacuole during MeJA-induced leaf senescence. Collectively, our work revealed up-regulation of autophagy by LCSA as a key regulator to alleviate MeJA-induced leaf senescence.


Assuntos
Envelhecimento/genética , Autofagia/genética , Folhas de Planta/genética , Ácido Salicílico/metabolismo , Acetatos/farmacologia , Autofagia/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/genética , Ciclopentanos/metabolismo , Ciclopentanos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oxilipinas/metabolismo , Oxilipinas/farmacologia , Folhas de Planta/crescimento & desenvolvimento , RNA-Seq , Transdução de Sinais/efeitos dos fármacos
15.
Physiol Plant ; 170(3): 398-414, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32691420

RESUMO

Methyl jasmonate (MeJA) is an airborne signaling phytohormone that can induce changes in endogenous jasmonates (JAs) and cause photosynthetic responses. However, the response of these two aspects of citrus plants at different MeJA concentrations is still unclear. Four MeJA concentrations were used in two citrus varieties, Huangguogan (C. reticulata × C. sinensis) and Shiranuhi [C. reticulata × (C. reticulata × C. sinensis)], to investigate the effects of MeJA dose on the endogenous JAs pathway and photosynthetic capacity. We observed that MeJA acted in a dose-dependent manner, and its stimulation in citrus leaves showed a bidirectional character at different concentrations. This work demonstrates that MeJA at only a concentration of 2.2 mM or less contributed to the activation of magnesium protoporphyrin IX methyltransferase (ChlM, EC 2.1.1.11) and protochlorophyllide oxidoreductase (POR, EC 1.3.1.11) and the simultaneous accumulation of Chl a and Chl b, which in turn contributed to an improved photosynthetic capacity and PSII photochemistry efficiency of citrus. Meanwhile, the inhibition of endogenous JAs synthesis by exogenous MeJA was observed. This was achieved by reducing the ratio of monogalactosyl diacylglycerol (MGDG) to diagalactosyl diacylglycerol (DGDG) and inhibiting the activities of key enzymes in JAs synthesis, especially 12-oxo-phytodienoic acid reductase (OPR, EC 1.3.1.42). Another noteworthy finding is that there may exist a JA-independent pathway that could regulate 12-oxo-phytodienoic acid (OPDA) synthesis. This study jointly analyzed the internal hormone regulation mechanism and the external physiological response, as well as revealed the effects of exogenous MeJA on promoting the photosynthesis and inhibiting the endogenous JAs synthesis.


Assuntos
Citrus , Acetatos/farmacologia , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Fotossíntese
16.
Toxicol Lett ; 332: 118-129, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659471

RESUMO

Silver-based antimicrobials are widely used topically to treat infections associated with multi-drug resistant (MDR) pathogens. Expanding this topical use to aerosols to treat lung infections requires understanding and preventing silver toxicity in the respiratory tract. A key mechanism resulting in silver-induced toxicity is the production of reactive oxygen species (ROS). In this study, we have verified ROS generation in silver-treated bronchial epithelial cells prompting evaluation of three antioxidants, N-acetyl cysteine (NAC), ascorbic acid, and melatonin, to identify potential prophylactic agents. Among them, NAC was the only candidate that abrogated the ROS generation in response to silver acetate exposure resulting in the rescue of these cells from silver-associated toxicity. Further, this protective effect directly translated to preservation of metabolic activity, as demonstrated by the normal levels of citric acid cycle metabolites in NAC-pretreated silver acetate-exposed cells. Because the citric acid cycle remained functional, silver-exposed cells pre-incubated with NAC demonstrated significantly higher levels of adenosine triphosphate levels compared with NAC-free controls. Moreover, we found that this prodigious capacity of NAC to rescue silver acetate-exposed cells was due not only to its antioxidant activity, but also to its ability to directly bind silver. Despite binding to silver, NAC did not alter the antimicrobial activity of silver acetate.


Assuntos
Acetilcisteína/farmacologia , Antibacterianos/farmacologia , Depuradores de Radicais Livres/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Prata/farmacologia , Prata/toxicidade , Acetatos/farmacologia , Trifosfato de Adenosina/metabolismo , Ácido Ascórbico/farmacologia , Linhagem Celular , Cromatografia Gasosa-Espectrometria de Massas , Glutationa/metabolismo , Humanos , Melatonina/farmacologia , Testes de Sensibilidade Microbiana , Compostos de Prata/farmacologia , Superóxidos/metabolismo
17.
PLoS One ; 15(7): e0236565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730299

RESUMO

Flavonoids are key components of licorice plant that directly affect its medicinal quality. Importantly, the MYB family of transcription factors serves to regulate the synthesis of flavonoids in plants. The MYB transcription factors represent one of the largest families of transcription factors in plants and play important roles in the process of plant growth and development. MYB gene expression is induced by a number of plant hormones, including the lipid-based hormone jasmonate (JA). Methyl jasmonate (MeJA) is an endogenous plant growth regulator that can induce the JA signaling pathway, which functions to regulate the synthesis of secondary metabolites, including flavonoids. In this study, MeJA was added to licorice cell suspensions, and RNA-seq analysis was performed to identify the differentially expressed genes. As a result, the MYB transcription factors GlMYB4 and GlMYB88 were demonstrated to respond significantly to MeJA induction. Subsequently, the GlMYB4 and GlMYB88 protein were shown to localize to the cell nucleus, and it was verified that GlMYB4 and GlMYB88 could positively regulate the synthesis of flavonoids in licorice cells. Overall, this research helps illustrate the molecular regulation of licorice flavonoid biosynthesis induced by MeJA.


Assuntos
Acetatos/farmacologia , Ciclopentanos/farmacologia , Flavonoides/biossíntese , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glycyrrhiza uralensis/metabolismo , Oxilipinas/farmacologia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Flavonoides/química , Glycyrrhiza uralensis/química , Glycyrrhiza uralensis/crescimento & desenvolvimento , Filogenia , Folhas de Planta/metabolismo , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Caules de Planta/metabolismo , Fatores de Transcrição/classificação , Fatores de Transcrição/genética
18.
Sci Rep ; 10(1): 9322, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32518304

RESUMO

The effects of jasmonic acid (JA) and methyl jasmonate (Me-JA) on photosynthetic efficiency and expression of some photosystem (PSII) related in different cultivars of Brassica oleracea L. (var. italica, capitata, and botrytis) were investigated. Plants raised from seeds subjected to a pre-sowing soaking treatment of varying concentrations of JA and Me-JA showed enhanced photosynthetic efficiency in terms of qP and chlorophyll fluorescence. Maximum quantum efficiency of PSII (Fv/Fm) was increased over that in the control seedlings. This enhancement was more pronounced in the Me-JA-treated seedlings compared to that in JA-treated ones. The expression of PSII genes was differentially regulated among the three varieties of B. oleracea. The gene PsbI up-upregulated in var. botrytis after treatment of JA and Me-JA, whereas PsbL up-regulated in capitata and botrytis after supplementation of JA. The gene PsbM showed many fold enhancements in these expressions in italica and botrytis after treatment with JA. However, the expression of the gene PsbM increased by both JA and Me-JA treatments. PsbTc(p) and PsbTc(n) were also found to be differentially expressed which revealed specificity with the variety chosen as well as JA or Me-JA treatments. The RuBP carboxylase activity remained unaffected by either JA or Me-JA supplementation in all three varieties of B. oleracea L. The data suggest that exogenous application of JA and Me-JA to seeds before germination could influence the assembly, stability, and repair of PS II in the three varieties of B. oleracea examined. Furthermore, this improvement in the PS II machinery enhanced the photosynthetic efficiency of the system and improved the photosynthetic productivity in terms of saccharides accumulation.


Assuntos
Acetatos/farmacologia , Brassica/efeitos dos fármacos , Brassica/fisiologia , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Complexo de Proteína do Fotossistema II/genética , Brassica/genética , Brassica/crescimento & desenvolvimento , Metabolismo dos Carboidratos/efeitos dos fármacos , Carotenoides/metabolismo , Clorofila/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Ribulose-Bifosfato Carboxilase/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Sementes/metabolismo , Açúcares/metabolismo
19.
Sci Rep ; 10(1): 8884, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483287

RESUMO

Capparis spinosa is an edible medicinal plant which is considered as an excellent source of rutin. Rutin is a glycoside of the flavonoid quercetin that has been reported to have a beneficial role in controlling various diseases such as hypertension, arteriosclerosis, diabetes, and obesity. In this study, the partial cDNA of four genes involved in the rutin biosynthetic pathway including 4-coumaroyl CoA ligase (4CL), flavonoid 3'-hydroxylase (F3'H), flavonol synthase (FLS) and flavonol-3-O-glucoside L-rhamnosyltransferase (RT) were identified in C.spinosa plants for the first time. The protein sequences of these genes shared high similarity with the same proteins in other plant species. Subsequently, the expression patterns of these genes as well as rutin accumulation in C.spinosa leaves treated with different concentrations of salicylic acid (SA) and methyl jasmonate (MeJA) and also in different tissues of Caper plants treated with 100 mgL-1 SA and 150 µM MeJA were evaluated. The expression of all four genes was clearly up-regulated and rutin contents increased in response to MeJA and SA treatments after 24 h. The highest rutin contents (5.30 mgg-1 DW and 13.27 mgg-1 DW), as well as the highest expression levels of all four genes, were obtained using 100 mgL-1 SA and 150 µM MeJA, respectively. Among the different tissues, the highest rutin content was observed in young leaves treated with 150 µM MeJA, which corresponded to the expression of related genes, especially RT, as a key gene in the rutin biosynthetic pathway. These results suggest that rutin content in various tissues of C. spinosa can be enhanced to a significant extent by MeJA and SA treatments and the gene expression patterns of rutin-biosynthesis-related genes are regulated by these elicitors.


Assuntos
Vias Biossintéticas/efeitos dos fármacos , Capparis/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , Reguladores de Crescimento de Planta/farmacologia , Rutina/biossíntese , Acetatos/farmacologia , Sequência de Aminoácidos , Capparis/efeitos dos fármacos , Capparis/genética , Capparis/metabolismo , Ciclopentanos/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Especificidade de Órgãos , Oxilipinas/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Ácido Salicílico/farmacologia , Regulação para Cima
20.
Environ Sci Pollut Res Int ; 27(27): 33723-33731, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32529628

RESUMO

Lead (Pb) is an environmental toxicant; its consumption can induce renal deficits. In this study, we explored the possible protective efficiency of Moringa oleifera extract (MOE) against lead acetate (PbAc)-mediated reprotoxicity. Four experimental groups of seven rats each were used: control, PbAc, MOE, and MOE+PbAc groups. All groups were given their respective treatment for 4 weeks. PbAc impaired the oxidative/antioxidative balance in the renal tissue, as shown by the decreased antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase) and increased oxidants (lipid peroxidation and nitric oxide). Additionally, PbAc enhanced the progression of kidney inflammation by increasing tumor necrosis factor-alpha, interleukin-1 beta, and nuclear factor kappa B associated with upregulation of inducible nitric oxide synthase. Moreover, a dysregulation in the apoptotic-regulating proteins (Bax, caspase-3, and Bcl2) were recorded upon PbAc exposure. Remarkably, MOE oral administration restored redox homeostasis, suppressed the inflammatory and apoptotic responses in the kidney tissue. Our findings point out that MOE could be used as an alternative remedy to overcome the adverse effects of Pb exposure, which may be due to its potent antioxidant, anti-inflammatory, and anti-apoptotic effects.


Assuntos
Antioxidantes/farmacologia , Moringa oleifera , Compostos Organometálicos , Acetatos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Chumbo/toxicidade , Compostos Organometálicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
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