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1.
Water Res ; 177: 115756, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32294590

RESUMO

The occurrence and distribution of N-acyl homoserine lactones (AHLs) in membrane bioreactors (MBRs) treating wastewater has garnered much attention as they have been shown to play critical role in biofouling. There is a need to develop a single method capable of analysing AHLs in various wastewater with comparable and reliable performance. A novel and robust method was proposed for trace analysis of 11 AHLs in wastewater treatment systems treating domestic and industrial wastewater. This method utilised solid phase extraction (SPE) to extract AHLs from wastewater followed by liquid-liquid extraction (LLE) to extract AHLs from the SPE eluant, and used N-heptanoyl-dl-homoserine lactone (C7-HSL) as an internal standard. There was no need to prepare matrix-matched calibration curve for accurate quantification of AHLs in the liquid chromatography tandem mass chromatography (LC-MS/MS) analysis. The developed method was validated with six different types of domestic and industrial wastewater with regard to AHLs recoveries and matrix effects. For treated domestic and industrial wastewater, the relative recoveries ranged from 75% to 130% and the matrix effects ranged from 89% to 122%. This method exhibited remarkable improvement compared with single SPE. The results also indicated that inclusion of LLE after SPE could effectively alleviate matrix effects, which may be because of the removal of relatively hydrophilic interferences by using dichloromethane to extract AHLs from the SPE eluant composing of methanol and water. The limits of detection of the AHLs were all below 5 ng/L for the tested wastewater samples. The developed method of SPE-LLE with LC-MS/MS was applied to analyse AHLs in four lab-scale and one pilot-scale wastewater treatment systems. Wide spectrum of AHLs with alkanoyl chains ranging from C4 to C14 were detected with concentrations ranging from 2.7 to 299.2 ng/L. This method is capable of identifying and quantifying trace levels of AHLs in various wastewater treatment systems and can help us better understand the mechanisms of AHL-mediated quroum sensing in various wastewater treatment systems.


Assuntos
Homosserina , Águas Residuárias , 4-Butirolactona/análogos & derivados , Cromatografia Líquida , Extração em Fase Sólida , Espectrometria de Massas em Tandem
2.
PLoS One ; 15(2): e0227811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023266

RESUMO

Anopheles darlingi is the main vector of malaria in Brazil, characterized by a high level of anthropophilia and endophagy. Imidacloprid, thiacloprid, and acetamiprid are the most widespread insecticides of the neonicotinoid group. However, they produce adverse effects on the non-target insects. Flupyradifurone has been marketed as an alternative to non-fluorinated neonicotinoids. Neonicotinoids containing trifluoroacethyl substituent reveal increased insecticidal activity due to higher hydrophobicity and metabolic stability. We synthesized novel neonicotinoid insecticides containing fluorinated acceptor groups and their interactions were estimated with the nicotinic acetylcholine receptor (nAChR) binding site by molecular docking studies, to evaluate their larvicidal activity against A. darlingi, and to assess their outdoor photodegradation behavior. New neonicotinoid analogues were prepared and characterized by NMR and mass-spectrometry. The synthesized molecules were modelled by time-dependent density functional theory and analyzed, their interaction with nAChR was investigated by molecular docking. Their insecticide activity was tested on Anopheles larvae collected in suburban area of Manaus, Brazil. Four new fluorinated neonicotinoid analogs were prepared and tested against 3rd instars larvae of A. darlingi showing high larvicidal activity. Docking studies reveal binding modes of the synthesized compounds and suggest that their insecticidal potency is governed by specific interactions with the receptor binding site and enhanced lipophilicity. 2-Chloro-5-(2-trifluoromethyl-pyrrolidin-1-ylmethyl)pyridine 5 showed fast degradation in water maintaining high larvicidal activity. All obtained substances possessed high larvicidal activity in low concentrations in 48 hours of exposure, compared to commercial flupyradifurone. Such activity is connected to a unique binding pattern of the synthesized compounds to insect's nAChR and to their enhanced bioavailability owing to introduction of fluorinated amino-moieties. Therefore, the compounds in question have a high potential for application as control agents for insects transmitting tropical diseases, and they will be less persistent in the environment.


Assuntos
Anopheles/efeitos dos fármacos , Halogenação , Inseticidas/toxicidade , Simulação de Acoplamento Molecular , Neonicotinoides/toxicidade , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/toxicidade , Animais , Inseticidas/química , Larva/efeitos dos fármacos , Neonicotinoides/síntese química , Neonicotinoides/química , Piridinas/química , Piridinas/toxicidade , Espectrofotometria Ultravioleta , Eletricidade Estática
3.
J Agric Food Chem ; 68(8): 2516-2527, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32050067

RESUMO

In the Gram-negative bacterium Aeromonas hydrophila, N-acyl homoserine lactone (AHL)-mediated quorum sensing (QS) influences pathogenicity, protein secretion, and motility. However, the catalytic mechanism of AHL biosynthesis and the structural basis and substrate specificity for AhyI members remain unclear. In this study, we cloned the ahyI gene from the isolate A. hydrophila HX-3, and the overexpressed AhyI protein was confirmed to produce six types of AHLs by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, contrasting with previous reports that AhyI only produces N-butanoyl-l-homoserine lactone (C4-HSL) and N-hexanoyl-l-homoserine lactone (C6-HSL). The results of an in vitro biosynthetic assay showed that purified AhyI can catalyze the formation of C4-HSL using S-adenosyl-l-methionine (SAM) and butyryl-acyl carrier protein (ACP) as substrates and indicated that the fatty acyl substrate used in AhyI-mediated AHL synthesis is derived from acyl-ACP rather than acyl-CoA. The kinetic data of AhyI using butyryl-ACP as an acyl substrate indicated that the catalytic efficiency of the A. hydrophila HX-3 AhyI enzyme is within an order of magnitude compared to other LuxI homologues. In this study, for the first time, the tertiary structural modeling results of AhyI and those of molecular docking and structural and functional analyses showed the importance of several crucial residues, as well as the secondary structure with respect to acylation. A Phe125-Phe152 clamp grasps the terminal methyl group to assist in stabilizing the long acyl chains in a putative binding pocket. The stacking interactions within a strong hydrophobic environment, a hydrogen-bonding network, and a ß bulge presumably stabilize the ACP acyl chain for the attack of the SAM α-amine toward the thioester carbon, offering a relatively reasonable explanation for how AhyI can synthesize AHLs with diverse acyl-chain lengths. Moreover, Trp34 participates in forming the binding pocket for C4-ACP and becomes ordered upon SAM binding, providing a good basis for catalysis. The novel finding that AhyI can produce both short- and long-chain AHLs enhances current knowledge regarding the variety of AHLs produced by this enzyme. These structural data are expected to serve as a molecular rationale for AHL synthesis by AhyI.


Assuntos
Aeromonas hydrophila/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , Acil-Butirolactonas/química , Acil-Butirolactonas/metabolismo , Aeromonas hydrophila/química , Aeromonas hydrophila/genética , Aeromonas hydrophila/metabolismo , Proteínas de Bactérias/genética , S-Adenosilmetionina/metabolismo , Especificidade por Substrato , Espectrometria de Massas em Tandem
4.
Food Chem Toxicol ; 135: 110991, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765699

RESUMO

The goal of this research was to study the selective pro-apoptotic effect of ligustilide on prostate-cancer-associated fibroblast in the tumor microenvironment and the related molecular mechanisms. The effects of ligustilide on cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) isolated from the prostate were determined by MTT assay. Flow cytometry and cellular immunofluorescence were used to detect the effects of ligustilide on the cell cycle and apoptosis. Western blotting was used to detect the expression of apoptosis-related proteins after the action of ligustilide on CAFs. In the investigation, ligustilide had a selective pro-apoptotic effect on prostate-CAFs. After ligustilide treatment, the proportion of CAFs in the G2-M phase of the cell cycle increased, and the expression of apoptosis-related proteins (p-P53, Bcl-2, Caspase9 and Cytochrome C) changed. Ligustilide blocks the CAF cell cycle and induces the apoptosis of CAFs.


Assuntos
4-Butirolactona/análogos & derivados , Apoptose/efeitos dos fármacos , Fibroblastos Associados a Câncer/efeitos dos fármacos , Neoplasias da Próstata/patologia , Receptor 4 Toll-Like/metabolismo , 4-Butirolactona/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor 4 Toll-Like/genética , Microambiente Tumoral
5.
Water Res ; 169: 115193, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670083

RESUMO

The positive roles of N-acyl homoserine lactone (AHL)-mediated quorum sensing (QS) in aerobic granular sludge (AGS) have been widely acknowledged. However, it is not feasible to manipulate granulation via direct addition of AHL chemicals or AHL-producing strains. Here, several strains with high AHL-producing capacity were successfully isolated from AGS. These QS strains were cultivated, mixed as a consortium, and then divided into two groups: AHLs supernatant and bacterial cells encapsulated in sodium alginate (CEBs). The potential of QS regulation, via doses of AHLs supernatant and CEBs, in accelerating granulation was evaluated. Results clearly indicated that short-term (days 21-70) addition of AHLs supernatant led to a rapid specific growth rate (0.08 d-1), compact structure without filamentous bacteria overgrowth, excellent settlement performance (SVI10 37.2 mL/g), and a high integrity coefficient (4.4%) of the granules. Sustainable release of AHLs (mainly C6- and C8-HSL) was induced by exogenous AHLs, possibly attributed to the enrichment of the genera Aeromonas and Pseudomonas. Further, tryptophan and aromatic protein substances were produced to maintain structural stability, suggesting that short-term QS regulation had long-term positive effects on the characteristics of AGS. By comparison, the addition of CEBs posed negligible or negative impact on the granulation, as evidenced by the rupture of smaller aggregates and poor characteristics of AGS. Overall, augmentation of the signaling content via addition of AHLs supernatant from QS strains is an economical and feasible regulation strategy to accelerate granulation and sustain long-term structural stability.


Assuntos
4-Butirolactona , Percepção de Quorum , 4-Butirolactona/análogos & derivados , Acil-Butirolactonas , Bactérias , Esgotos
6.
Food Microbiol ; 86: 103356, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31703863

RESUMO

Quorum sensing (QS), bacterial cell-to-cell communication, is a gene regulatory mechanism that regulates virulence potential and biofilm formation in many pathogens. Aeromonas sobria, a common aquaculture pathogen, was isolated and identified by our laboratory from the deteriorated turbot, and its potential for virulence factors and biofilm production was regulated by QS system. In view of the interference with QS system, this study was aimed to investigate the effect of methyl anthranilate at sub-Minimum Inhibitory Concentrations (sub-MICs) on QS-regulated phenotypes in A. sobria. The results suggested that 0.5 µL/mL of methyl anthranilate evidently reduced biofilm formation (51.44%), swinging motility (74.86%), swarming motility (71.63%), protease activity (43.08%), and acyl-homoserine lactone (AHL) production. Furthermore, the real-time quantitative PCR (RT-qPCR) and in silico analysis showed that methyl anthranilate might inhibit QS system in A. sobria by interfering with the biosynthesis of AHL, as well as competitively binding with receptor protein. Therefore, our data indicated the feasibility of methyl anthranilate as a promising QS inhibitor and anti-biofilm agent for improving food safety.


Assuntos
Aeromonas/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , ortoaminobenzoatos/farmacologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , Aeromonas/genética , Aeromonas/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
7.
Pest Manag Sci ; 76(1): 111-117, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31309692

RESUMO

BACKGROUND: Sublethal exposure to neonicotinoids, a popular class of agricultural pesticides, can lead to behavioral effects that impact the health of pollinators. Therefore, new compounds, such as flupyradifurone (FPF), have recently been developed as 'safer' alternatives. FPF is an excitotoxic nicotinic acetylcholine receptor agonist, similar to neonicotinoids. Given the novelty of FPF, what data exist are focused mostly on assessing the effect of FPF on pollinator mortality. One important avenue for investigation is the potential effect of FPF on the sensitivity of nectar foragers, such as Apis mellifera, to sucrose concentrations. Neonicotinoids can alter this sucrose responsiveness and disrupt foraging. Compounding this effect, neonicotinoid-containing solutions are preferred by A. mellifera over pure sucrose solutions. We therefore conducted four studies, administering FPF under both acute and chronic conditions, and at field-realistic and higher than field-realistic doses, to assess the influence of FPF exposure on sucrose responsiveness and sucrose solutions with FPF in A. mellifera nectar foragers. RESULTS: We found no evidence that FPF exposure under acute or chronic field-realistic conditions significantly altered sucrose responsiveness, and we did not find that bees exposed to FPF consumed more of the solution. However, at the much higher median lethal dose (48 h), among bees that survived, FPF-exposed foragers responded to significantly lower concentrations of sucrose than controls and responded at significantly higher rates to all concentrations of sucrose than controls. CONCLUSION: We found no evidence that FPF alters the sucrose responsiveness of nectar foragers at field-realistic doses during winter or early spring, but caution and further investigation are warranted, particularly on the effects of FPF in conjunction with other stressors. © 2019 Society of Chemical Industry.


Assuntos
Abelhas , 4-Butirolactona/análogos & derivados , Animais , Inseticidas , Neonicotinoides , Piridinas , Sacarose
8.
Eur J Med Chem ; 187: 111969, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31865018

RESUMO

Compounds inducing adiponectin production have therapeutic potential for metabolic diseases. During screening, heme oxygenase-1-inducing marliolide derivatives were identified as adiponectin-inducing compounds. Although some marliolide derivatives were directly bound to peroxisome proliferator-activated receptor γ (PPARγ), the adiponectin-inducing activity did not correlate with the PPARγ binding affinity. The most potent adiponectin inducing compound, (E,4S,5S)-3-butylidene-dihydro-4-hydroxy-5-methylfuran-2(3H)-one (1a), exhibited the weakest PPARγ binding activity. A docking simulation suggested that two 1a molecules can be present in two different sites within the PPARγ-ligand-binding pocket (LBP). Based on the docking model, novel linked butanolide dimer compounds were synthesized. A linked butanolide dimer compound, (3E,3'E,4S,4'S,5S,5'S)-3,3'-(decane-1,10-diylidene)bis(4-hydroxy-5-methyldihydrofuran-2(3H)-one) (3a), promoted adiponectin production in human bone marrow mesenchymal stem cells (hBM-MSCs) as a novel PPARγ full agonist (EC50, 4.34 µM). This linked butanolide dimer study provides novel insight into PPARγ biology, suggesting that small molecules can form multiple ligand interactions within the PPARγ-LBP and thereby affect the functional outcomes of PPARγ activation.


Assuntos
4-Butirolactona/farmacologia , Adipogenia/efeitos dos fármacos , Adiponectina/biossíntese , Células-Tronco Mesenquimais/efeitos dos fármacos , PPAR gama/agonistas , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , Células Cultivadas , Dimerização , Relação Dose-Resposta a Droga , Humanos , Células-Tronco Mesenquimais/metabolismo , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , PPAR gama/metabolismo , Relação Estrutura-Atividade
9.
Chemosphere ; 245: 125363, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31877457

RESUMO

Biofouling is a limiting bottleneck in the development of membrane bioreactor (MBR) since the birth of this technology. Recently, the biofouling control strategy based on interfering with the bacterial quorum sensing (QS) system is highly desirable for biofouling control in MBR. In this study, three lab-scale parallel MBR systems were operated over 100 days to investigate the inhibitory effect of a metabolic uncoupler (3,3',4',5-tetrachlorosalicylanilide, TCS) on biofouling and the potential mechanism for biofouling control. Compared to the control MBR, the fouling cycle duration of MBR 2 with 100 µg/L TCS extended over two times. The attached biomass on membrane in MBR 2 decreased over 50% at the end of each operating period, which indicated that the addition of TCS significantly mitigated microorganisms accumulation on membrane. The content of interspecies QS signal (autoinducer-2) and intraspecific QS signals (N-octanoyl-dl-homoserine lactone, C8-HSL) was reduced by the TCS, suggesting the secretion of QS signals in MBR were affected by uncoupler. Although the addition of TCS induced brief fluctuations of extracellular proteins and polysaccharides, microorganisms seemed to rapidly acclimatize to the presence of TCS and then the secretion of extracellular polymeric substances (EPS) was inhibited by 100 µg/L TCS. The continuous operation of MBR was not be affected by the low-concentration uncoupler via the analysis of substrate removal and sludge growth. This study systematically evaluated the effect and inhibitory efficiency of TCS on biofouling, biomass accumulation, QS signals, EPS and treatment performances, demonstrating the feasibility of metabolic uncoupler for biofouling control in MBR.


Assuntos
Reatores Biológicos/microbiologia , Membranas Artificiais , Eliminação de Resíduos Líquidos/métodos , 4-Butirolactona/análogos & derivados , Bactérias , Incrustação Biológica , Membranas , Percepção de Quorum/efeitos dos fármacos , Esgotos/microbiologia
10.
Int J Mol Sci ; 20(24)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842355

RESUMO

Strigolactones (SLs) and karrikins (KARs) are both butenolide molecules that play essential roles in plant growth and development. SLs are phytohormones, with SLs having known functions within the plant they are produced in, while KARs are found in smoke emitted from burning plant matter and affect seeds and seedlings in areas of wildfire. It has been suggested that SL and KAR signaling may share similar mechanisms. The α/ß hydrolases DWARF14 (D14) and KARRIKIN INSENSITIVE 2 (KAI2), which act as receptors of SL and KAR, respectively, both interact with the F-box protein MORE AXILLARY GROWTH 2 (MAX2) in order to target SUPPRESSOR OF MAX2 1 (SMAX1)-LIKE/D53 family members for degradation via the 26S proteasome. Recent reports suggest that SLs and/or KARs are also involved in regulating plant responses and adaptation to various abiotic stresses, particularly nutrient deficiency, drought, salinity, and chilling. There is also crosstalk with other hormone signaling pathways, including auxin, gibberellic acid (GA), abscisic acid (ABA), cytokinin (CK), and ethylene (ET), under normal and abiotic stress conditions. This review briefly covers the biosynthetic and signaling pathways of SLs and KARs, compares their functions in plant growth and development, and reviews the effects of any crosstalk between SLs or KARs and other plant hormones at various stages of plant development. We also focus on the distinct responses, adaptations, and regulatory mechanisms related to SLs and/or KARs in response to various abiotic stresses. The review closes with discussion on ways to gain additional insights into the SL and KAR pathways and the crosstalk between these related phytohormones.


Assuntos
4-Butirolactona/análogos & derivados , Adaptação Biológica/efeitos dos fármacos , Furanos/metabolismo , Lactonas/metabolismo , Desenvolvimento Vegetal/efeitos dos fármacos , Reguladores de Crescimento de Planta/farmacologia , Piranos/metabolismo , Estresse Fisiológico/efeitos dos fármacos , 4-Butirolactona/farmacologia , Furanos/química , Lactonas/química , Fenômenos Fisiológicos Vegetais , Piranos/química , Transdução de Sinais , Relação Estrutura-Atividade
11.
Microbes Environ ; 34(4): 429-435, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31666459

RESUMO

The plant pathogen Pectobacterium carotovorum subsp. carotovorum (Pcc) regulates the expression of virulence factors by N-acylhomoserine lactone (AHL)-mediated quorum sensing. The LuxI family protein, ExpI, catalyzes AHL biosynthesis in Pcc. The structure of the predominant AHL produced by ExpI differs among Pcc strains, which may be divided into two quorum-sensing classes (QS classes) based on the AHL produced. In the present study, AHL produced by 282 Pcc strains were extracted and identified by LC-MS/MS. Seventy Pcc strains produced N-(3-oxooctanoyl)-l-homoserine lactone (3-oxo-C8-HSL) as the predominant AHL and were categorized into QS class I. Two hundred Pcc strains produced N-(3-oxohexanoyl)-l-homoserine lactone (3-oxo-C6-HSL) as the predominant AHL, and were categorized into QS class II-1. Twelve Pcc strains produced only small amounts of 3-oxo-C6-HSL, and were categorized into QS class II-2. The phylogenetic analysis revealed that the amino acid sequences of ExpI may be divided into two major clades (I and II). The Pcc strains categorized into ExpI clades I and II entirely matched QS classes I and II, respectively. A multiple alignment analysis demonstrated that only 6 amino acid substitutions were observed among ExpI from QS classes II-1 and II-2. Furthermore, many amino acid substitutions between QS classes I and II were concentrated at the C-terminal region. These amino acid substitutions are assumed to cause significant reductions in 3-oxo-C6-HSL in QS class II-2 or affect the substrate specificity of ExpI between QS classes I and II.


Assuntos
Acil-Butirolactonas/metabolismo , Variação Genética , Pectobacterium carotovorum/genética , Pectobacterium carotovorum/metabolismo , Doenças das Plantas/microbiologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/metabolismo , Acil-Butirolactonas/química , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Homosserina/análogos & derivados , Homosserina/química , Homosserina/metabolismo , Pectobacterium carotovorum/classificação , Filogenia , Percepção de Quorum
12.
Nat Ecol Evol ; 3(11): 1521-1524, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31666734

RESUMO

Recent research has shown that several managed bee species have specific P450 enzymes that are preadapted to confer intrinsic tolerance to some insecticides including certain neonicotinoids. However, the universality of this finding across managed bee pollinators is unclear. Here we show that the alfalfa leafcutter bee, Megachile rotundata, lacks such P450 enzymes and is >2,500-fold more sensitive to the neonicotinoid thiacloprid and 170-fold more sensitive to the butenolide insecticide flupyradifurone than other managed bee pollinators. These findings have important implications for the safe use of insecticides in crops where M. rotundata is used for pollination, and ensuring that regulatory pesticide risk assessment frameworks are protective of this species.


Assuntos
Inseticidas , 4-Butirolactona/análogos & derivados , Animais , Abelhas , Neonicotinoides , Polinização
13.
J Food Sci ; 84(12): 3573-3583, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31762036

RESUMO

Vascular smooth muscle cells (VSMCs) excessive migration, a basic change of pathological intimal thickening, can lead to serious cardiovascular diseases such as atherosclerosis, myocardial infarction, and stroke. Ligustilide (LIG), the main active ingredient of angelica volatile oil, has been demonstrated to exert protective effects on the cardiovascular and cerebrovascular, circulatory system, and immune function. However, whether it protects against intimal thickening and VSMCs excessive migration and its underlying mechanism remains largely unknown. The aim of this study is to investigate the effect of LIG on VSMCs migration and its underlying mechanism. The protective effect of LIG on VSMCs excessive migration was assessed using an atherosclerotic spontaneously hypertensive rat model and an angiotensin II (AngII)-induced VSMCs migration model. The results showed that LIG exerted a protective effect against pathological intimal thickening as demonstrated by decreasing VSMCs migration in vivo and in vitro. In vivo, intimal thickening and VSMCs migration were inhibited and LIG performed a suppressive effect on the expression of c-Myc protein while enhanced phenotypic transformation related proteins α-SMA expression. Meanwhile, the administration of LIG significantly lowered the blood pressure and blood lipids level in atherosclerotic spontaneously hypertensive rats. In vitro, LIG suppressed AngII-induced VSMCs migration and downregulated the expression of migration related protein c-Myc, MMP2, ROCK1, ROCK2, p-JNK, and JNK. These findings suggested the protective effect of LIG on VSMCs migration was associated with the decrement of c-Myc/MMP2 signaling pathway and ROCK-JNK signaling pathway. Thus, LIG may serve as a novel therapeutic agent for preventing cardiovascular disease.


Assuntos
4-Butirolactona/análogos & derivados , Aterosclerose/tratamento farmacológico , Aterosclerose/fisiopatologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , 4-Butirolactona/administração & dosagem , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo
14.
BMC Vet Res ; 15(1): 349, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623621

RESUMO

BACKGROUND: NSAIDs are accepted as the most predictably efficacious medical treatment of the clinical signs of osteoarthritis (OA). The marine-based fatty-acid compound PCSO-524 has been proposed as an adjunctive treatment for canine OA, however benefits of this agent is still controversial. The purpose of this study was to evaluate and compare the effectiveness of PCSO-524 combined with the NSAID firocoxib using force plate gait analysis, orthopedic assessment score (OAS) and canine brief pain inventory score (CBPI) in dogs with OA. A prospective, randomized, double-blinded study was conducted. Seventy-nine dogs that had hip and/or stifle OA were assigned randomly into three treatment groups: firocoxib, PCSO-524 and combination of firocoxib and PCSO-524, orally for 4 weeks. Peak vertical force (PVF, expressed as a percentage of bodyweight), OAS, CBPI, serum prostaglandin E2 concentration, hematology and blood chemistry values were evaluated before treatment (Day0), as well as at the second (Day14) and fourth week (Day28) during treatment. RESULTS: Within group analysis revealed significant increases in PVF over the 4-week treatment period for firocoxib, PCSO-524 and the combination (p < 0.05). Mean increases in PVF were 3.25 ± 4.13, 2.01 ± 3.86, 4.11 ± 4.69%BW (mean ± SD) respectively. The OAS showed non-significant change in all treatment groups. There were significant decreases in CBPI pain severity score (PSS) and CBPI pain interference scores (PIS) within some groups over time, however no significant differences were found between the groups. Significantly decreased serum PGE2 concentration (p < 0.05) was found in the combination group. Significant increases in BUN and creatinine (p < 0.05) compared to pre-treatment values were found in the firocoxib and combination groups but not in the PCSO-524 group at day28, but all values in all dogs remained within the normal ranges. CONCLUSIONS: The results of this study suggested combination of both PCSO-524 and firocoxib is more effective in alleviation of inflammation and improvement of weight bearing ability when compared to the uses of either PCSO-524 or firocoxib alone. Further clinical studies are needed to confirm this, and to determine if there is any benefit of PCSO-524 over placebo.


Assuntos
4-Butirolactona/análogos & derivados , Anti-Inflamatórios não Esteroides/uso terapêutico , Doenças do Cão/tratamento farmacológico , Ácidos Graxos Insaturados/uso terapêutico , Osteoartrite/veterinária , Sulfonas/uso terapêutico , 4-Butirolactona/uso terapêutico , Animais , Dinoprostona/sangue , Cães , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Marcha/efeitos dos fármacos , Masculino , Osteoartrite/complicações , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Dor/etiologia , Dor/veterinária , Medição da Dor/veterinária , Estudos Prospectivos
15.
Chem Pharm Bull (Tokyo) ; 67(10): 1088-1098, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582628

RESUMO

In this study, we synthesized four series of novel L-homoserine lactone analogs and evaluated their in vitro quorum sensing (QS) inhibitory activity against two biomonitor strains, Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PAO1. Studies of the structure-activity relationships of the set of L-homoserine lactone analogs indicated that phenylurea-containing N-dithiocarbamated homoserine lactones are more potent than (Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone (C30), a positive control for biofilm formation. In particular, compared with C30, QS inhibitor 11f significantly reduced the production of virulence factors (pyocyanin, elastase and rhamnolipid), swarming motility, the formation of biofilm and the mRNA level of QS-related genes regulated by the QS system of PAO1. These results reveal 11f as a potential lead compound for developing novel antibacterial quorum sensing inhibitors.


Assuntos
4-Butirolactona/análogos & derivados , Antibacterianos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , 4-Butirolactona/síntese química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Pseudomonas aeruginosa/crescimento & desenvolvimento , Percepção de Quorum/genética , Relação Estrutura-Atividade
16.
Nat Commun ; 10(1): 4129, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511505

RESUMO

Synthetic biology and metabolic engineering have expanded the possibilities for engineered cell-based systems. The addition of non-native biosynthetic and regulatory components can, however, overburden the reprogrammed cells. In order to avoid metabolic overload, an emerging area of focus is on engineering consortia, wherein cell subpopulations work together to carry out a desired function. This strategy requires regulation of the cell populations. Here, we design a synthetic co-culture controller consisting of cell-based signal translator and growth-controller modules that, when implemented, provide for autonomous regulation of the consortia composition. The system co-opts the orthogonal autoinducer AI-1 and AI-2 cell-cell signaling mechanisms of bacterial quorum sensing (QS) to enable cross-talk between strains and a QS signal-controlled growth rate controller to modulate relative population densities. We further develop a simple mathematical model that enables cell and system design for autonomous closed-loop control of population trajectories.


Assuntos
Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Técnicas de Cocultura/métodos , Transdução de Sinais , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , Bactérias/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Proliferação de Células/efeitos dos fármacos , Homosserina/análogos & derivados , Homosserina/farmacologia , Lactonas/farmacologia , Modelos Biológicos , Percepção de Quorum/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
17.
Molecules ; 24(18)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540241

RESUMO

Phytochemical investigation of the whole plant of Tradescantia albiflora Kunth led to the isolation and characterization of a butanolide, rosmarinosin B (1), that was isolated from natural sources for the first time, a new butenolide, 5-O-acetyl bracteanolide A (2), and a new apocarotenoid, 2ß-hydroxyisololiolide (11), together with 25 known compounds (compounds 3-10 and 12-28). The structures of the new compounds were elucidated by analysis of their spectroscopic data, including MS, 1D, and 2D NMR experiments, and comparison with literature data of known compounds. Furthermore, four butenolides 4a-4d were synthesized as novel derivatives of bracteanolide A. The isolates and the synthesized derivatives were evaluated for their preliminary anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW 264.7 cells. Among them, the synthesized butenolide derivative n-butyl bracteanolide A (4d) showed enhanced NO inhibitory activity compared to the original compound, with an IC50 value of 4.32 ± 0.09 µg/mL.


Assuntos
Anti-Inflamatórios/farmacologia , Furanos/farmacologia , Lipopolissacarídeos/efeitos adversos , Tradescantia/química , 4-Butirolactona/análogos & derivados , Animais , Anti-Inflamatórios/química , Furanos/química , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Células RAW 264.7
18.
Sci Total Environ ; 696: 133809, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31470321

RESUMO

Although adding long-term acyl homoserine lactone (AHL) over one month was highly instructive for the development of an AHL-based anaerobic granulation strategy, the role of long-term exogenous AHL at different concentrations in the granulation process was poorly understood due to commercial exogenous AHL's extremely high cost. In this study, organic synthesis of N-decanoyl-homoserine lactone (C10-HSL) was employed for the first time to drastically reduce the cost of the AHL addition. Daily dosages of exogenous C10-HSL at 50 nM, 500 nM and 5000 nM were separately added into anaerobic bioreactors to promote the granulation process for as long as 168 days. 50 nM C10-HSL showed a negligible effect on the granulation process while 5000 nM C10-HSL achieved the best performance with the highest chemical oxygen demand (COD) removal, largest granule size and best extracellular polymeric substance production. Bacterial analysis indicated that exogenous C10-HSL showed a concentration-related effect in bacterial community organization. Besides, addition of 5000 nM C10-HSL resulted in the greatest promotion of Methanosaeta which was extremely important to the formation of anaerobic granule. This study provides a foundation for the future application of long-term exogenous AHL manipulation to improve the granulation process in an engineered ecosystem.


Assuntos
4-Butirolactona/análogos & derivados , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Reatores Biológicos , Matriz Extracelular de Substâncias Poliméricas
19.
Artigo em Inglês | MEDLINE | ID: mdl-31434344

RESUMO

Despite the adverse effects of emerging ZnO nanoparticles (nano-ZnO) on wastewater biological nitrogen removal (BNR) systems being widely documented, strategies for mitigating nanoparticle (NP) toxicity impacts on nitrogen removal have not been adequately addressed. Herein, N-acyl-homoserine lactone (AHL)-based quorum sensing (QS) was investigated for its effects against nano-ZnO toxicity to a model nitrifier, Nitrosomonas europaea. The results indicated that AHL-attenuated nano-ZnO toxicity, which was inversely correlated with the increasing dosage of AHL from 0.01 to 1 µM. At 0.01 µM, AHL notably enhanced the tolerance of N. europaea cells to nano-ZnO stress, and the inhibited cell proliferation, membrane integrity, ammonia oxidation rate, ammonia monooxygenase activity and amoA gene expression significantly increased by 18.2 ± 2.1, 2.4 ± 0.9, 58.7 ± 7.1, 32.3 ± 1.7, and 7.3 ± 5.9%, respectively, after 6 h of incubation. However, increasing the AHL dosage compromised the QS-mediated effects and even aggravated the NPs' toxicity effects. Moreover, AHLs, at all tested concentrations, significantly increased superoxide dismutase activity, indicating the potential of QS regulations to enhance cellular anti-oxidative stress capacities when facing NP invasion. These results provide novel insights into the development of QS regulation strategies to reduce the impact of nanotoxicity on BNR systems.


Assuntos
4-Butirolactona/análogos & derivados , Nanopartículas Metálicas/química , Nitrosomonas europaea/efeitos dos fármacos , Transdução de Sinais , Óxido de Zinco/química , 4-Butirolactona/farmacologia , Nitrosomonas europaea/metabolismo , Oxirredução , Percepção de Quorum
20.
J Basic Microbiol ; 59(10): 1031-1039, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31402466

RESUMO

Quorum sensing (QS)-mediated biofilm-forming rhizobacteria are indispensable due to their competitiveness in the crop rhizosphere. In the present work, we have reported on the occurrence of diversified bacterial species capable of producing N-acyl homoserine lactone (AHL) as the QS signal in the roots of a rice plant grown under field conditions. The AHL-producing bacteria were directly isolated from the rice root by the biosensor reporter (Chromobacterium violaceum CV026) overlay method and characterized for biofilm production by the microtiter plate method. A total of 48 QS-positive bacterial isolates were purified from different aged (7, 20, 24, 26, and 36 days) rice seedlings. The in vitro biofilm production and genetic diversity as revealed by BOX-PCR fingerprinting showed high variability among the isolates. Most of the best biofilm-forming isolates produced a N-butyryl dl-homoserine lactone (a C4-AHL type) signal in the medium. The 16S ribosomal RNA (rRNA) gene sequence of these putative elite isolates identified that they were close to Aeromonas hydrophila (QS7-4; QS36-2), A. enteropelongenes (QS20-8), A. veronii (QS36-3), Enterobacter sp. (QS20-11), Klebsiella pneumoniae (QS24-6), Kosakonia cowanii (QS24-21), Providentia rettigeri (QS24-2), Sphingomonas aquatilis (QS24-17), and Pseudomonas sihuiensis (QS24-20). These strains profusely colonized the rice root upon inoculation and formed biofilms on the surface of the root under gnotobiotic conditions. Developing inoculants from these strains would ensure competitive colonization on the rhizoplane of the crop through their biofilm and thereby improve plant growth and health.


Assuntos
4-Butirolactona/análogos & derivados , Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Oryza/microbiologia , 4-Butirolactona/metabolismo , Bactérias/classificação , Bactérias/isolamento & purificação , Variação Genética , Oryza/crescimento & desenvolvimento , Filogenia , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Percepção de Quorum , RNA Ribossômico 16S/genética , Rizosfera
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