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1.
Avian Pathol ; 53(4): 229-241, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38323582

RESUMO

Marek's disease (MD) is a neoplastic disease that significantly affects the poultry industry. Long non-coding RNAs (lncRNAs) are crucial regulatory factors in various biological processes, including tumourigenesis. However, the involvement of novel lncRNAs in the course of MD virus (MDV) infection is still underexplored. Here, we present the first comprehensive characterization of differentially expressed lncRNAs in chicken spleen at different stages of MDV infection. A series of differentially expressed lncRNAs was identified at each stage of MDV infection through screening. Notably, our investigation revealed a novel lncRNA, lncRNA 803, which exhibited significant differential expression at different stages of MDV infection and was likely to be associated with the p53 pathway. Further analyses demonstrated that the overexpression of lncRNA 803 positively regulated the expression of p53 and TP53BP1 in DF-1 cells, leading to the inhibition of apoptosis. This is the first study to focus on the lncRNA expression profiles in chicken spleens during MDV pathogenesis. Our findings highlight the potential role of the p53-related novel lncRNA 803 in MD pathogenesis and provide valuable insights for decoding the molecular mechanism of MD pathogenesis involving non-coding RNA.RESEARCH HIGHLIGHTS Differentially expressed lncRNAs in spleens of chickens infected with Marek's disease virus at different stages were identified for the first time.The effects of novel lncRNA 803 on p53 pathway and apoptosis of DF-1 cells were reported for the first time.


Assuntos
Apoptose , Galinhas , Doença de Marek , Doenças das Aves Domésticas , RNA Longo não Codificante , Baço , Proteína Supressora de Tumor p53 , Animais , RNA Longo não Codificante/genética , Doença de Marek/virologia , Doença de Marek/genética , Galinhas/virologia , Baço/virologia , Baço/patologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular , Herpesvirus Galináceo 2/genética , Herpesvirus Galináceo 2/fisiologia
2.
New Phytol ; 242(2): 592-609, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402567

RESUMO

The plant hormone ethylene plays a critical role in fruit defense against Botrytis cinerea attack, but the underlying mechanisms remain poorly understood. Here, we showed that ethylene response factor SlERF.C1 acts as a key regulator to trigger the ethylene-mediated defense against B. cinerea in tomato fruits without compromising ripening. Knockout of SlERF.C1 increased fruit susceptibility to B. cinerea with no effect on ripening process, while overexpression enhanced resistance. RNA-Seq, transactivation assays, EMSA and ChIP-qPCR results indicated that SlERF.C1 activated the transcription of PR genes by binding to their promoters. Moreover, SlERF.C1 interacted with the mitogen-activated protein kinase SlMPK8 which allowed SlMPK8 to phosphorylate SlERF.C1 at the Ser174 residue and increases its transcriptional activity. Knocking out of SlMPK8 increased fruit susceptibility to B. cinerea, whereas overexpression enhanced resistance without affecting ripening. Furthermore, genetic crosses between SlMPK8-KO and SlERF.C1-OE lines reduced the resistance to B. cinerea attack in SlERF.C1-OE fruits. In addition, B. cinerea infection induced ethylene production which in turn triggered SlMPK8 transcription and enhanced the phosphorylation of SlERF.C1. Overall, our findings reveal the regulatory mechanism of the 'Ethylene-MPK8-ERF.C1-PR' module in resistance against B. cinerea and provide new insight into the manipulation of gray mold disease in fruits.


Assuntos
Frutas , Solanum lycopersicum , Frutas/metabolismo , Solanum lycopersicum/genética , Etilenos/metabolismo , Botrytis/fisiologia , Doenças das Plantas/genética , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas
3.
Res Vet Sci ; 164: 105047, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37837750

RESUMO

Marek's disease (MD) is a severe infectious and immunosuppressive neoplastic condition that significantly impacts the global poultry industry. Investigating the role of non-coding RNA in pathogenic mechanisms of MD virus (MDV) offers valuable insights for the effective prevention and management of MD. A higher expression of the novel lncRNA-9802 can be found in spleen tissues of MDV-infected chickens from our prior research, and there is a potential association between lncRNA-9802 and cell proliferation. In this study, we further demonstrated that over-expression of lncRNA-9802 could promote the proliferation of DF-1 cells. It has been established that lncRNA-9802 mediated its effects by binding to miR-1646, and further modulated the expression of the Bax and Bcl-2 genes. Deciphering the role of the recently discovered MD-associated lncRNA-9802/miR-1646 axis provides valuable theoretical basis for decoding the molecular mechanisms underlying MDV pathogenesis.


Assuntos
Herpesvirus Galináceo 2 , Doença de Marek , MicroRNAs , RNA Longo não Codificante , Animais , Proteína X Associada a bcl-2 , Proliferação de Células , Galinhas , Herpesvirus Galináceo 2/genética , Doença de Marek/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais
4.
Fitoterapia ; 170: 105630, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37536471

RESUMO

Artemisia anomala S. Moore exerts many pharmacological activities, including the removing of the blood stasis, relieving of the fever and analgesia, reducing the swelling and dampness. In this study, the extraction technology, chemical compositions and anti-inflammatory effect in vitro and mechanism of total flavonoids extract from Artemisia anomala S. Moore were studied. The optimal yield rate of total flavonoids extract was optimized by single factor experiments and response surface method, and the chemical constituents were analyzed by UPLC-QTOF-MS method; and the anti-inflammatory activity of the extract was evaluated with lipopolysaccharide induced RAW 264.7 cells. The highest extraction rate was 2.02% under these conditions of the concentration of ethanol 50%, the ultrasonic extraction time 30 min, and the ratio of solvent volume to material weight 20:1 (ml/g). In addition, the main components of total flavonoid extract were preliminarily identified and deduced based on mass spectrometry information and relevant literatures, and its stronger anti-inflammatory activity was demonstrated by reducing the phagocytosis, the content of nitric oxide and the level of related cytokines (tumor necrosis factor-α, interleukin-10, interleukin-6). Furthermore, it was further revealed that the anti-inflammatory effect of the extract was closely connected with the activation of TLR4-MyD88-NF-κB signalling pathway. This study indicated that the total flavonoids extract from Artemisia anomala S. Moore may be a better candidate anti-inflammatory natural medicine.

5.
Analyst ; 148(8): 1858-1866, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-36942467

RESUMO

Adenosine levels are important in various physiological and pathological activities, but detecting them is difficult because of interference from a complex matrix. This study designed a series of DNA oligomers rich in thymine to enrich adenosine. Their binding affinity (Kd range: 1.25-5.0 mM) to adenosine varied based on the DNA secondary structures, with a clamped hairpin structure showing the highest binding affinity. Compared to other designs, this clamped DNA hairpin underwent the least conformational change during adenosine binding. These DNAs also suppressed the precipitation of supersaturated adenine. Taken together, these results suggest that thymine-rich DNAs could be used to enrich and separate adenosine.


Assuntos
Adenosina , Timina , Timina/química , Conformação de Ácido Nucleico , DNA/química , Adenina/química
6.
Macromol Biosci ; 23(3): e2200453, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36542841

RESUMO

Antisense DNA oligonucleotide (AS) technology is a promising approach to regulate gene expression and cellular processes. For example, ASs can be used to capture the overexpressed, oncogenic miRNAs in tumors to suppress tumor growth. Among many challenges faced by AS approach is the degradation of ASs by nucleases under physiological conditions. Elongating the AS lifespan can substantially enhance the functions of AS. The paper reports a simple strategy to increase the stability of ASs. The authors discover that the ASs degrade quickly if their ends are in unpaired, single-stranded form, but much slower if their ends are in paired duplex form. It is conceivable to integrate this strategy with other strategies (such as chemical modification of ASs backbones) to maximally increase the ASs stabilities.


Assuntos
Neoplasias , Oligonucleotídeos Antissenso , DNA/genética , DNA Antissenso , Neoplasias/genética , Neoplasias/terapia , Oligonucleotídeos , Oligonucleotídeos Antissenso/genética
7.
Microorganisms ; 9(12)2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34946058

RESUMO

Plant hormones have been recently shown to exert an indirect influence on the recruitment of plant-associated microbiomes. However, it remains unclear the extent to which the disruption of the ethylene (ET) signaling pathway affects the assembly and functioning of plant-root microbiomes. In this study, the Never-ripe tomato mutant (Nr) was profiled for differences compared to the wild type (control). Tomato plants were subjected to root exudate profiling and the characterization of bacterial and fungal communities. Compared to the control, Nr revealed differences in the composition of root exudates, including lower amounts of esculetin, gallic acid, L-fucose, eicosapentaenoic acid, and higher amounts of ß-aldehyde. Interestingly, Nr significantly differed in the composition and functioning of the rhizosphere bacterial community. We also identified the taxa that occurred at relatively higher abundances in Nr, including the genus Lysobacter, which displayed a significant negative correlation with changes in eicosapentaenoic acid and esculetin, and a significant positive correlation with changes in ß-aldehyde. Taken together, our study provides evidence that a mutation in the ET receptor exerts predictable changes in the root-associated microbial taxa of tomato plants. These indirect effects can potentially be explored towards new strategies to engineer beneficial plant microbiomes via targeted changes in plant genetics and physiology.

8.
Plant Sci ; 313: 111063, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763857

RESUMO

Kiwifruit is known as 'the king of vitamin C' because of the high content of ascorbic acid (AsA) in the fruit. Deciphering the regulatory network and identification of the key regulators mediating AsA biosynthesis is vital for fruit nutrition and quality improvement. To date, however, the key transcription factors regulating AsA metabolism during kiwifruit developmental and ripening processes remains largely unknown. Here, we generated a putative transcriptional regulatory network mediating ascorbate metabolism by transcriptome co-expression analysis. Further studies identified an ethylene response factor AcERF91 from this regulatory network, which is highly co-expressed with a GDP-galactose phosphorylase encoding gene (AcGGP3) during fruit developmental and ripening processes. Through dual-luciferase reporter and yeast one-hybrid assays, it was shown that AcERF91 is able to bind and directly activate the activity of the AcGGP3 promoter. Furthermore, transient expression of AcERF91 in kiwifruit fruits resulted in a significant increase in AsA content and AcGGP3 transcript level, indicating a positive role of AcERF91 in controlling AsA accumulation via regulation of the expression of AcGGP3. Overall, our results provide a new insight into the regulation of AsA metabolism in kiwifruit.


Assuntos
Actinidia/genética , Actinidia/metabolismo , Ácido Ascórbico/metabolismo , Etilenos/metabolismo , Galactose/metabolismo , Guanosina Difosfato/metabolismo , Fosforilases/metabolismo , Ácido Ascórbico/genética , China , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Frutas/genética , Frutas/metabolismo , Galactose/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Guanosina Difosfato/genética , Fosforilases/genética
9.
J Ethnopharmacol ; 278: 114225, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34038799

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tribulus terrestris L., as an annual herb plant from Zygophyllaceae, exhibits many biological activities, and its main chemical constituents are saponins. However, the extraction process, chemical compositions, anti-inflammatory effect and mechanism of total saponins from Tribulus terrestris L. leaves are still unclear. AIM OF THE STUDY: The present study extensively evaluated the extraction process, major components, anti-inflammatory action and mechanism of Tribulus terrestris L. leaves saponins. MATERIALS AND METHODS: The ultrasonic extraction and response surface methods were adopted for optimization of extraction technology of total saponins from Tribulus terrestris L. leaves, and its compositions were detected with LC-MSn method. The anti-inflammatory activity of total saponins was studied by lipopolysaccharide induced RAW 264.7 cells and acute lung injury mice models. RESULTS: The ultrasonic extraction parameters of saponins fraction, including ethanol concentration 30%, extraction time 55 min, ratio of solvent to material 35:1 ml/g and extraction temperature 46 °C, were screened by response surface method with the extracting rate 5.49%, and thirty compositions were detected with LC-MSn method. Moreover, saponins fraction can play a stronger anti-inflammatory effect by reducing the phagocytic activity and pulmonary edema, and protection of morphology of RAW 264.7 cells and lung tissues, and decreasing the content of NO and TNF-α. Moreover, it was revealed that total saponins extract can exert the anti-inflammatory action by the inhibition of the activation of the TLR4-TRAF6-NF-κB signalling pathway. CONCLUSION: These studies imply that Tribulus terrestris L. leaves saponins may be an important anti-inflammatory drug in clinic.


Assuntos
Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Lipopolissacarídeos , Masculino , Camundongos , Extratos Vegetais/análise , Extratos Vegetais/química , Folhas de Planta , Células RAW 264.7 , Saponinas/química , Saponinas/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray , Tribulus/química , Ultrassom
10.
J Pharm Pharmacol ; 73(1): 110-117, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33791807

RESUMO

OBJECTIVES: Inflammation widely exists in many diseases and poses a great threat to human and animal health. Rutin, quercetin-3-rhamnosyl glucoside, has a variety of pharmacological effects, including anti-oxidant, anti-inflammatory, antibacterial, anticancer and radioresistance effects. The current study focused on evaluation of its anti-inflammatory activity and described the mechanism of rutin in lipopolysaccharide-induced RAW 264.7 cells. METHODS: The related gene and protein expression levels were investigated by quantification real-time PCR and western blotting, respectively. KEY FINDINGS: This study revealed that rutin can decrease inducible nitric oxide synthase (iNOS) gene and protein expression levels, effectively increase IκB gene expression, reduce toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumour necrosis factor receptor-associated factor 6 (TRAF6) and p65 gene expression and inhibit the phosphorylation of IκB and p65 and the proteins expression of TLR4, MyD88 and TRAF6. CONCLUSIONS: These results suggest that rutin might exert anti-inflammatory effect on LPS-stimulated RAW 264.7 cells and will be potentially useful as an adjuvant treatment for inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Rutina/farmacologia , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Fosforilação , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Células RAW 264.7 , Rutina/uso terapêutico , Transdução de Sinais
11.
Infect Drug Resist ; 13: 1697-1711, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606820

RESUMO

PURPOSE: This research aimed to investigate the antibacterial activity and potential mechanism of luteolin against T. pyogenes. MATERIALS AND METHODS: The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of luteolin against various T. pyogenes strains. The potential mechanism of action of luteolin was elucidated through testing and analysing the luteolin-induced alterations of T. pyogenes in several aspects, including cell wall, cell membrane, protein expression, nucleic acid content, topoisomerase activity and energy metabolism. RESULTS: The MIC values of luteolin against various T. pyogenes isolates and ATCC19411 were 78 µg/mL. The increased cell membrane permeability, destruction of cell wall integrity and TEM images after exposure to luteolin showed that the cell wall and membrane were damaged. The content of total protein and nucleic acid in T. pyogenes decreased significantly after treatment with luteolin (1/2 MIC) for 12, 24, and 36 h. Moreover, a hypochromic effect was observed in the absorption spectrum of luteolin when deoxyribonucleic acid (DNA) was added. In addition, after treatment with luteolin, a decrease in nicked or relaxed DNA content, which was catalysed by T. pyogenes-isolated DNA topoisomerase, was observed. In addition, the adenosine triphosphate (ATP) content in cells and the activity of succinate dehydrogenase (SDH) both decreased when T. pyogenes was exposed to different concentrations (1/4 MIC, 1/2 MIC, 1 MIC, 2 MIC) of luteolin for 1 h. CONCLUSION: Luteolin showed distinct antibacterial activity against T. pyogenes by multiple actions, which mainly include destroying the integrity of the cell wall and cell membrane, influencing the expression of proteins, inhibiting nucleic acid synthesis, and interfering with energy metabolism.

12.
J Agric Food Chem ; 68(31): 8223-8231, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32650643

RESUMO

Mulberry leaf is a common vegetable with a variety of beneficial effects, such as hypoglycemic activity. However, the underlying mechanism of its hypoglycemic effect have not been fully revealed. In this study, two flavonoid derivatives were isolated from mulberry leaves, a new geranylated flavonoid compound (1) and its structural analogue (2). The structures of compounds 1 and 2 were elucidated using spectroscopic analysis. To study the potential hypoglycemic properties of these compounds, their regulatory effects on protein tyrosine phosphatase 1B (PTP1B) were investigated. In comparison to oleanolic acid, compounds 1 and 2 showed significant inhibitory activities (IC50 = 4.53 ± 0.31 and 10.53 ± 1.76 µM) against PTP1B, the positive control (IC50 = 7.94 ± 0.76 µM). Molecular docking predicted the binding sites of compound 1 to PTP1B. In insulin-resistance HepG2 cell, compound 1 promoted glucose consumption in a dose-dependent manner. Furthermore, western blot and polymerase chain reaction analyses indicated that compound 1 might regulate glucose consumption through the PTP1B/IRS/PI3K/AKT pathway. In conclusion, geranylated flavonoids in mulberry leaves inhibite PTP1B and increase the glucose consumption in insulin-resistant cells. These findings provide an important basis for the use of mulberry leaf flavonoids as a dietary supplement to regulate glucose metabolism.


Assuntos
Flavonoides/química , Resistência à Insulina , Morus/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Inibidores de Proteínas Quinases/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Flavonoides/farmacologia , Glucose/metabolismo , Células Hep G2 , Humanos , Insulina/metabolismo , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Folhas de Planta/química , Inibidores de Proteínas Quinases/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo
13.
Pak J Pharm Sci ; 33(4): 1511-1517, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33583781

RESUMO

The extraction procedure and antioxidant activity were investigated for total proanthocyanidins extracts from Abutilon theophrasti Medic. leaves collected in August, September and October. The maximum extraction yield was achieved with 90% ethanol, 80°C of heating reflux temperature, 149.94 min of extraction time and 60(ml/g) of the ratio of solvent and material, which were optimized by Box-Behnken Design of response surface method. Spectrophotometric study displayed that total proanthocyanidins content was (0.44±0.02)% (0.52±0.01)% and (0.59±0.01)% for August, September and October samples, respectively. The proanthocyanidins extracts exhibited much stronger antioxidant activity to scavenge ABTS and DPPH free radicals, and reduce ferric power than the control synthetic antioxidant BHT. The present findings suggest that the proanthocyanidins extract from Abutilon theophrasti Medic. leaves was a very interesting candidate for the research and development of natural and healthy antioxidant for the pharmaceutical and food industries.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Malvaceae/química , Folhas de Planta/química , Proantocianidinas/química , Proantocianidinas/farmacologia , Etanol/química , Flavonoides/química , Flavonoides/farmacologia , Radicais Livres/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Solventes/química
14.
Heliyon ; 5(8): e02234, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31485505

RESUMO

Research on the extraction technology, component analysis, and antioxidant, antibacterial, analgesic and anti-inflammatory activities of flavonoids fraction from Tribulus terrestris L. leaves was carried out. The extraction process was optimized by response surface method, and the maximum yield 0.27% for flavonoids fraction was achieved with concentration of ethanol solution 25.87%, ratio of solvent to material 30:1 ml/g, and ultrasonic extraction time 27.93 min. Moreover, 14 compositions were identified separately from flavonoids fraction by HPLC-DAD-ESI-MS2. In addition, flavonoids fraction exhibited a better antioxidant activity demonstrated by assays of ABTS, DPPH radical scavenging activity and ferric reducing antioxidant power activity. Furthermore, the antibacterial, analgesic and anti-inflammatory activities of flavonoids fraction were also proved to be stronger. Therefore, the present findings suggest that flavonoids fraction from Tribulus terrestris L. leaves can be a very interesting candidate for the research and development of natural and healthy herbal medicine for the pharmaceutical and food industries.

15.
Pharm Biol ; 57(1): 514-518, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401916

RESUMO

Context: ALI is a common disease characterized by acute pulmonary inflammatory disorder. Abutilon theophrasti Medik. (Malvaceae), as a Chinese traditional medicine, is used for the treatment of inflammation. Its main constituents are flavonoid compounds. Objective: This study investigates the regulatory effect of a TFE from Abutilon theophrasti leaves on gene expression in LPS-induced ALI mice via the NF-κB and MAPK signaling pathways. Materials and methods: Kunming mice were intragastrically administered TFE (0.25, 0.5, 1.0 g/kg) for 5 days, and then ALI was induced via intranasal administration 40 µg of LPS in 10 µL PBS after intragastric administration on the 5th day, and PBS and DEX (2 mg/kg) were negative and positive control groups, respectively. Results: The relative expression of iNOS gene was 0.707, 0.507 and 0.483 for 0.25, 0.5 and 1.0 g/kg TFE, and COX-2 gene expression was also reduced after treatment by three concentrations of TFE with 0.768, 0.545, and 0.478. The mRNA expression levels of p65 were 0.61, 0.43 and 0.27 for 0.25, 0.5 and 1.0 g/kg TFE and IκB levels were increased in a dose-dependent manner with 3.99, 13.69 and 34.36. 0.5 and 1.0 g/kg TFE inhibited the expression of ERK1/2 with 0.59 and 0.38, p38MAPK with 0.62 and 0.54, and JNK with 0.37 and 0.29, and JNK mRNA expression was 0.60 for 0.25 g/kg TFE. Discussion and conclusion: These results indicate that the regulatory mechanisms of TFE on gene expression in LPS-induced ALI mice include inhibition of the NF-κB and MAPK signaling pathways.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Flavonoides/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Ciclo-Oxigenase 2/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Expressão Gênica/efeitos dos fármacos , Quinase I-kappa B/metabolismo , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Masculino , Malvaceae , Camundongos , Óxido Nítrico Sintase/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Folhas de Planta , Fator de Transcrição RelA/metabolismo
16.
New Phytol ; 222(2): 820-836, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30511456

RESUMO

Ethylene is the main hormone controlling climacteric fruit ripening; however, the mechanisms underlying the developmental transition leading to the initiation of the ripening process remain elusive, although the presumed role of active hormone interplay has often been postulated. To unravel the putative role of auxin in the unripe-to-ripe transition, we investigated the dynamics of auxin activity in tomato fruit and addressed the physiological significance of Sl-SAUR69, previously identified as a RIN target gene, using reverse genetics approaches. Auxin signalling undergoes dramatic decline at the onset of ripening in wild-type fruit, but not in the nonripening rin mutant. Sl-SAUR69 exhibits reduced expression in rin and its up-regulation results in premature initiation of ripening, whereas its down-regulation extends the time to ripening. Overexpression of Sl-SAUR69 reduces proton pump activity and polar auxin transport, and ectopic expression in Arabidopsis alters auxin transporter abundance, further arguing for its active role in the regulation of auxin transport. The data support a model in which Sl-SAUR69 represses auxin transport, thus generating auxin minima, which results in enhanced ethylene sensitivity. This defines a regulation loop, fed by ethylene and auxin as the main hormonal signals and by RIN and Sl-SAUR69 as modulators of the balance between the two hormones.


Assuntos
Etilenos/farmacologia , Frutas/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/metabolismo , RNA de Plantas/metabolismo , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/metabolismo , Arabidopsis/metabolismo , Transporte Biológico/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Frutas/efeitos dos fármacos , Frutas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Solanum lycopersicum/efeitos dos fármacos , Proteínas de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Bombas de Próton/metabolismo , Transdução de Sinais , Transcrição Gênica/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
17.
Biomed Chromatogr ; 33(4): e4474, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30577068

RESUMO

The current study focused on the extraction technology, components analysis, in vitro antioxidant and antibacterial activities of total flavonoids and fatty acids from Tribulus terrestris L. fruits. The extraction process of total flavonoids and fatty acids was optimized by the response surface method, and the compositions were identified from the two extracts by HPLC-DAD-ESI-MS- and GC-MS, respectively. In addition, the antioxidant and antibacterial activities were evaluated by assay of ABTS, DPPH radical scavenging activity, ferric reducing antioxidant power and minimal inhibitory concentration. The yields of total flavonoids and fatty acids were 0.46 and 9.76% under the optimized conditions. Moreover, nine and eight compositions were identified from the two extracts based on the related references, respectively. In addition, total flavonoids and fatty acids extracts both exhibited certain antioxidant and antibacterial activities. The present findings suggest that total flavonoids extracted from T. terrestris L. fruits comprised a more interesting candidate than fatty acids for the research and development of natural and healthy antioxidants and antibacterial agents for the pharmaceutical and food industries.


Assuntos
Antibacterianos/análise , Antioxidantes/análise , Ácidos Graxos/análise , Flavonoides/análise , Extratos Vegetais/análise , Tribulus/química , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Frutas/química , Cromatografia Gasosa-Espectrometria de Massas , Modelos Estatísticos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectrometria de Massas por Ionização por Electrospray
18.
Drug Deliv ; 25(1): 1886-1897, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30404541

RESUMO

Pneumococcal meningitis (PM), caused by Streptococcus pneumonia, remains a high-burden disease in developing countries. Antibiotic therapy has been limited due to the inefficiency of drug transport across the blood-brain barrier (BBB) and the emergence of drug-resistant strains. In our preliminary study, PEGylated nano-self-assemblies of bacitracin A (PEGylated Nano-BA12K) demonstrated a strong antibacterial potency against S. pneumonia. In this study, the potential application of this micelle for the treatment of both Penicillin-sensitive and -resistant PM was studied. To address BBB-targeting and -crossing issues, PEGylated Nano-BA12K was formulated with a specific brain-targeting peptide (rabies virus glycopeptide-29, RVG29) and a P-glycoprotein inhibitor (Pluronic® P85 unimers) to construct a mixed micellar system (RVG29-Nano-BAP85). RVG29-Nano-BAP85 demonstrated a strong antibacterial potency against 13 clinical isolates of S. pneumonia, even higher than that of Penicillin G, a conventional anti-PM agent. RVG29-Nano-BAP85 had more cellular uptake in brain capillary endothelial cells (BCECs) and higher BBB-crossing efficiency than single formulated Nano-BAs as shown in an in vitro BBB model. The enhanced BBB-permeability was attributed to the synergetic effect of RVG29 and P85 unimers through receptor-mediated transcytosis, exhaustion of ATP, and reduction in membrane microviscosity. In vivo results further demonstrated that RVG29-Nano-BAP85 was able to accumulate in brain parenchyma as confirmed by in vivo optical imaging. In addition, RVG29-Nano-BAP85 exhibited high therapeutic efficiencies in both Penicillin-sensitive and -resistant PM mouse models with negligible systemic toxicity. Collectively, RVG29-Nano-BAP85 could effectively overcome BBB barriers and suppressed the growth of both drug-sensitive and -resistant S. pneumonia in the brain tissues, which demonstrated its potential for the treatment of PM.


Assuntos
Antibacterianos/uso terapêutico , Bacitracina/uso terapêutico , Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Animais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Bacitracina/administração & dosagem , Bacitracina/efeitos adversos , Composição de Medicamentos , Farmacorresistência Bacteriana , Masculino , Meningite Pneumocócica/tratamento farmacológico , Camundongos , Micelas , Testes de Sensibilidade Microbiana , Nanopartículas , Penicilinas/farmacologia , Fragmentos de Peptídeos/química , Poloxâmero/química , Polietilenoglicóis/química , Streptococcus pneumoniae/efeitos dos fármacos , Distribuição Tecidual , Proteínas do Envelope Viral/química
19.
Plant Sci ; 274: 137-145, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30080597

RESUMO

Plants are sessile organisms, hence to face environmental constrains they developed strategies that rely on the activation of stress-response genes under the control of specific transcription factors. The plant hormone ethylene mediates physiological, developmental and stress responses through the activation of Ethylene Response Factors (ERFs) which belong to a large multigene family of transcription factors. While an increasing number of studies supports the involvement of ERFs in abiotic stress responses, so far the specific role of ERF family members in different abiotic stress conditions remains unexplored. The present work investigates the expression profile of a set of ERFs, representative of different ERF types, in tomato plants subjected to cold, heat, salt, drought and flooding conditions. The study revealed that a group of ERFs is preferentially associated with cold and heat stress responses while another set is expressed in response to salt, water and flooding stresses. Transactivation assays indicated that ERFs can regulate the expression of abiotic stress genes regardless of whether or not they harbor conserved GCC or DRE cis-elements in their promoter region. The outcome of the study provides clue on which ERFs should be targeted when aiming to improve adaptation to a particular stress type.


Assuntos
Proteínas de Plantas/fisiologia , Solanum lycopersicum/metabolismo , Estresse Fisiológico , Fatores de Transcrição/fisiologia , Resposta ao Choque Frio , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico , Proteínas de Plantas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Tolerância ao Sal , Estresse Fisiológico/fisiologia , Fatores de Transcrição/metabolismo , Água/metabolismo
20.
Mediators Inflamm ; 2018: 3508506, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29725269

RESUMO

The flavonoid fraction was extracted from the leaves of Abutilon theophrasti Medic., which are usually used as a traditional Chinese herbal medicine for the treatment of inflammation and joint pain. The current study focused on the extraction process, component analysis, and in vitro antioxidant, antibacterial, and anti-inflammatory activities of the flavonoid fraction as a part of ongoing research on bioactive substances from natural plant sources. This study evaluated the antioxidant activities via assays of DPPH radical scavenging capacity, ABTS radical scavenging capacity, and reducing power and investigated inhibitory activities against Escherichia coli, Salmonella, Staphylococcus aureus, and Streptococcus. Moreover, the inflammatory activity of the flavonoid fraction was estimated by measurement of the content of tumor necrosis factor alpha, interleukin-1-beta, interleukin-6, interleukin-10, nitric oxide, and cyclooxygenase-2 and the gene expression levels of several inflammation markers, such as inducible nitric oxide synthase and cyclooxygenase-2, in RAW 264.7 macrophages after LPS treatment. In addition, the underlying anti-inflammatory mechanisms, that is, the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, were also revealed from the gene and protein expression levels. Taken together, these results suggested that the flavonoid fraction might exert in vitro antioxidant, antibacterial, and anti-inflammatory effects on LPS-stimulated RAW 264.7 macrophages and will be potentially useful as an adjuvant treatment for oxidative stress and bacterial and inflammatory diseases.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Células RAW 264.7 , Salmonella/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus/efeitos dos fármacos , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/metabolismo
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