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1.
J Orthop Surg (Hong Kong) ; 32(2): 10225536241273556, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39208247

RESUMO

OBJECTIVE: Activation of gap junction channels can induce neuropathic pain. Octanol can limit the conductance of gap junctions containing connexin 43 proteins. Thus, this study focused on the roles of octanol in chronic constriction injury (CCI)-induced peripheral neuropathy in mice and its mechanisms of action. METHODS: Male mice were assigned into control, sham, CCI, CCI + Octanol-20 mg/kg, CCI + Octanol-40 mg/kg and CCI + Octanol-80 mg/kg groups. CCI was performed by applying three loose ligations to mouse sciatic nerve, and the mice with CCI was administered with 20 mg/kg, 40 mg/kg, or 80 mg/kg octanol. The neuropathic pain development was examined by assessing thermal withdrawal latency, paw withdrawal mechanical threshold, and sciatic functional index. Histopathological changes were evaluated by hematoxylin and eosin staining. The phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) was examined by western blotting. The expression of Akt and mTOR was also evaluated by immunofluorescence staining. RESULTS: Octanol alleviated the CCI-induced mechanical and thermal hyperalgesia and sciatic functional loss. Additionally, octanol relieved the CCI-induced abnormal histopathological changes. Mechanistically, octanol inactivated the Akt/mTOR pathway in the mice with CCI. CONCLUSION: In conclusion, octanol can alleviate CCI-induced peripheral neuropathic by regulating the Akt/mTOR pathway and might be a novel pharmacological intervention for neuropathic pain.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Neuropatia Ciática , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Serina-Treonina Quinases TOR/metabolismo , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/metabolismo , Nervo Isquiático/lesões , Octanóis/farmacologia , Modelos Animais de Doenças , Neuralgia/etiologia , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Camundongos Endogâmicos C57BL
2.
Int J Mol Sci ; 25(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38927995

RESUMO

Neural precursor cells (NPCs) that persist in the postnatal/adult subventricular zone (SVZ) express connexins that form hemichannels and gap junctions. Gap junctional communication plays a role in NPC proliferation and differentiation during development, but its relevance on postnatal age remains to be elucidated. In this work we aimed to evaluate the effect of the blockade of gap junctional communication on proliferation and cell fate of NPCs obtained from the SVZ of postnatal rats. NPCs were isolated and expanded in culture as neurospheres. Electron microscopy revealed the existence of gap junctions among neurosphere cells. Treatment of cultures with octanol, a broad-spectrum gap junction blocker, or with Gap27, a specific blocker for gap junctions formed by connexin43, produced a significant decrease in bromodeoxyuridine incorporation. Octanol treatment also exerted a dose-dependent antiproliferative effect on glioblastoma cells. To analyze possible actions on NPC fate, cells were seeded in the absence of mitogens. Treatment with octanol led to an increase in the percentage of astrocytes and oligodendrocyte precursors, whereas the percentage of neurons remained unchanged. Gap27 treatment, in contrast, did not modify the differentiation pattern of SVZ NPCs. Our results indicate that general blockade of gap junctions with octanol induces significant effects on the behavior of postnatal SVZ NPCs, by reducing proliferation and promoting glial differentiation.


Assuntos
Diferenciação Celular , Proliferação de Células , Junções Comunicantes , Células-Tronco Neurais , Neuroglia , Octanóis , Animais , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Proliferação de Células/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Ratos , Octanóis/farmacologia , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neuroglia/citologia , Células Cultivadas , Ventrículos Laterais/citologia , Ventrículos Laterais/metabolismo , Ventrículos Laterais/efeitos dos fármacos , Conexina 43/metabolismo , Ratos Wistar , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/citologia , Animais Recém-Nascidos , Humanos
3.
Appl Microbiol Biotechnol ; 106(12): 4787-4799, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35759038

RESUMO

Morels (Morchella spp.) are of great economic and scientific value. Paecilomyces penicillatus can cause white mold disease (WMD) widely emerging on morel ascocarps and is also a potential factor causing morel fructification failure. 1-octen-3-ol is a mushroom volatile compound with broad-spectrum antimicrobial activities. This study aimed to control the morel disease caused by P. penicillatus through suppressing P. penicillatus in the soil cultivated with Morchella sextelata using 1-octen-3-ol. Safe concentration of 1-octen-3-ol was estimated by comparing its inhibitory effect against P. penicillatus and M. sextelata, respectively, with mycelium-growth experiments on agar plates. The results showed that M. sextelata possesses a higher tolerance to 1-octen-3-ol than P. penicillatus with a 1-octen-3-ol concentration between 0 and 200 µL/L. Based on that, a sandy soil was supplemented with low (50 µL/L) or high concentration (200 µL/L) of 1-octen-3-ol. The effects of 1-octen-3-ol on soil microbial communities, WMD incidence, and morel yield were investigated. Compared to the non-supplemented control group, the incidence of WMD and the proportion of Paecilomyces in the soils of low- and high-concentration treatment groups were significantly decreased, corresponding to a significant increase in morel ascocarp yield. It suggests that 1-octen-3-ol effectively suppressed P. penicillatus in the soil, thereby reducing the severity of WMD and improving the morel yield. The diversity of soil bacterial communities was also altered by 1-octen-3-ol supplement. The proportion of Rhodococcus spp. in the soil was positively correlated with the 1-octen-3-ol concentration and ascocarp yield, suggesting its potential role in improving morel yield. KEY POINTS: • A novel method for morel disease suppression was proposed. • Paecilomyces in soil affects white mold disease and fructification yield of morel. • 1-Octen-3-ol suppresses Paecilomyces and alters bacterial community in soil.


Assuntos
Agaricales , Paecilomyces , Bactérias , Octanóis/farmacologia , Solo
4.
Plant Cell Environ ; 45(1): 236-247, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34708407

RESUMO

Upon sensing attack by pathogens and insect herbivores, plants release complex mixtures of volatile compounds. Here, we show that the infection of lima bean (Phaseolus lunatus L.) plants with the non-host bacterial pathogen Pseudomonas syringae pv. tomato led to the production of microbe-induced plant volatiles (MIPVs). Surprisingly, the bacterial type III secretion system, which injects effector proteins directly into the plant cytosol to subvert host functions, was found to prime both intra- and inter-specific defense responses in neighbouring wild tobacco (Nicotiana benthamiana) plants. Screening of each of 16 effectors using the Pseudomonas fluorescens effector-to-host analyser revealed that an effector, HopP1, was responsible for immune activation in receiver tobacco plants. Further study demonstrated that 1-octen-3-ol, 3-octanone and 3-octanol are novel MIPVs emitted by the lima bean plant in a HopP1-dependent manner. Exposure to synthetic 1-octen-3-ol activated immunity in tobacco plants against a virulent pathogen Pseudomonas syringae pv. tabaci. Our results show for the first time that a bacterial type III effector can trigger the emission of C8 plant volatiles that mediate defense priming via plant-plant interactions. These results provide novel insights into the role of airborne chemicals in bacterial pathogen-induced inter-specific plant-plant interactions.


Assuntos
Interações Hospedeiro-Patógeno/fisiologia , Imunidade Vegetal , Pseudomonas syringae/patogenicidade , Sistemas de Secreção Tipo III/fisiologia , Compostos Orgânicos Voláteis/metabolismo , Ar , Capsicum/fisiologia , Cucumis sativus/fisiologia , Regulação da Expressão Gênica de Plantas , Octanóis/farmacologia , Phaseolus/fisiologia , Imunidade Vegetal/efeitos dos fármacos , Transdução de Sinais , Nicotiana/fisiologia , Compostos Orgânicos Voláteis/farmacologia
5.
Sci Rep ; 10(1): 11116, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632328

RESUMO

In fungi, contactless interactions are mediated via the exchange of volatile organic compounds (VOCs). As these pair-wise interactions are fundamental to complex ecosystem, we examined the effects of inter-species VOCs trade-offs in Aspergillus flavus development. First, we exposed A. flavus to the A. oryzae volatilome (Treatment-1) with highest relative abundance of 1-Octen-3-ol (~ 4.53 folds) among the C-8 VOCs. Further, we examined the effects of gradient titers of 1-Octen-3-ol (Treatment-2: 100-400 ppm/day) in a range that elicits natural interactions. On 7-day, VOC-treated A. flavus displayed significantly reduced growth and sclerotial counts (p < 0.01) coupled with higher conidial density (T2100-200 ppm/day, p < 0.01) and α-amylase secretion (T2200 ppm/day, p < 0.01), compared to the untreated sets. Similar phenotypic trends except for α-amylases were evident for 9-day incubated A. flavus in T2. The corresponding metabolomics data displayed a clustered pattern of secondary metabolite profiles for VOC-treated A. flavus (PC1-18.03%; PC2-10.67%). Notably, a higher relative abundance of aflatoxin B1 with lower levels of most anthraquinones, indole-terpenoids, and oxylipins was evident in VOC-treated A. flavus. The observed correlations among the VOC-treatments, phenotypes, and altered metabolomes altogether suggest that the distant exposure to the gradient titers of 1-Octen-3-ol elicits an attenuated developmental response in A. flavus characterized by heightened virulence.


Assuntos
Aspergillus/crescimento & desenvolvimento , Aspergillus/metabolismo , Metaboloma/efeitos dos fármacos , Octanóis/farmacologia , Compostos Orgânicos Voláteis/metabolismo , Aspergillus/classificação , Aspergillus/efeitos dos fármacos , Compostos Orgânicos Voláteis/análise
6.
J Vector Ecol ; 45(1): 45-56, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32492275

RESUMO

Effective surveillance is essential for protecting livestock from Culicoides biting midges and the viruses they transmit. The objective of this study was to determine how the baiting system used in traps (UV, incandescent light, incandescent light with CO2 , and incandescent light with CO2 and 1-octen-3-ol) influences estimates of midge population abundance, parity, and diel activity. This was achieved through a standardized trapping protocol conducted in three habitats in Sweden. UV light traps caught the most Culicoides species and more C. obsoletus complex females than incandescent light traps. Traps baited with CO2 plus 1-octen-3-ol caught more female C. impunctatus than incandescent light traps. No consistent effect of bait type was found on C. obsoletus parity rate, as estimated from the proportion of midges with presence or absence of pigmentation. Midge activity, as reflected by trap catches, peaked between -3 h and +3 h relative to sunset, with UV traps catching significantly more female C. obsoletus complex and C. impunctatus at and after sunset than before sunset. We conclude that baiting system can influence biting midge collections, even using identical traps. Effective surveillance may require more than one bait type and kairomones to attract species that do not feed exclusively on cattle.


Assuntos
Ceratopogonidae/efeitos dos fármacos , Ceratopogonidae/efeitos da radiação , Luz , Raios Ultravioleta , Animais , Dióxido de Carbono/farmacologia , Feminino , Controle de Insetos , Octanóis/farmacologia , Feromônios , Suécia
7.
Nature ; 583(7816): 415-420, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32555456

RESUMO

Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms1. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts2,3. However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans, the neuromodulator tyramine produced by commensal Providencia bacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine ß-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis in Providencia, and show that these genes are necessary for the modulation of host behaviour. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.


Assuntos
Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/fisiologia , Comportamento Alimentar/fisiologia , Intestinos/microbiologia , Neurotransmissores/metabolismo , Providencia/metabolismo , Olfato/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Microbioma Gastrointestinal/fisiologia , Metabolômica , Mutação , Octanóis/farmacologia , Octopamina/biossíntese , Octopamina/metabolismo , Providencia/enzimologia , Providencia/fisiologia , Receptores de Amina Biogênica/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Células Receptoras Sensoriais/metabolismo , Olfato/efeitos dos fármacos , Tiramina/biossíntese , Tiramina/metabolismo , Tirosina Descarboxilase/deficiência , Tirosina Descarboxilase/genética
8.
Food Microbiol ; 91: 103502, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32539966

RESUMO

Myxobacteria have excellent biocontrol activity against various phytopathogens due to their rich spectrum of secondary metabolites and active predatory characteristics. In this study, the mycelial growth of Fusarium oxysporum f. sp. cucumerinum (FOC) was found to be significantly inhibited by volatile compounds (VOCs) produced by Corallococcus sp. EGB. A total of 32 compounds were identified among the VOCs produced by strain EGB, of which isooctanol exhibited the highest antifungal activity, with dosages of 3.75 and 4.0 µL/plate being sufficient to suppress FOC and Penicillum digitatum, respectively. Isooctanol was found to damage the cell wall and cell membranes of FOC and P. digitatum. Apoptosis-like cell death of FOC and P. digitatum induced by isooctanol was observed subsequently due to the accumulation of reactive oxygen species (ROS). The transcription level of genes related to cell wall integrity (CWI) pathway and redox reactions were significantly upregulated by 15- to 40-fold, indicating the stress caused by isooctanol. Postharvest storage experiments showed that the disease severity of post-harvest oranges infected with P. digitatum could be significantly reduced by isooctanol at 114.2 µL/L.


Assuntos
Antifúngicos/farmacologia , Myxococcales/metabolismo , Compostos Orgânicos Voláteis/farmacologia , Antifúngicos/metabolismo , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Citrus sinensis/microbiologia , Armazenamento de Alimentos , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Fusarium/metabolismo , Viabilidade Microbiana/efeitos dos fármacos , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Octanóis/metabolismo , Octanóis/farmacologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Espécies Reativas de Oxigênio/metabolismo , Compostos Orgânicos Voláteis/metabolismo
9.
Microb Pathog ; 135: 103604, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31247257

RESUMO

The present study describes the possibility of using some essential oils and monoterpens as bioagents against the growth of Ralstonia solanacearum, a causal bacterium of potato brown rot disease. Eight isolates of the bacterium were recovered from infected potato tubers, showing typical symptoms of the disease, Isolates were identified as R.solanacearum phylotype II, based on biochemical and physiological characteristics, as well as, at the molecular level through PCR analysis. Three essential oils extracted from Corymbia citriodora (leaves), Cupressus sempervirens (aerial parts), and Lantana camara (aerial parts) were evaluated for their antibacterial activity against eight isolates of R. solanacearum phylotype II. Results demonstrated that L. camara essential oil (concentration 5000 µg/mL) had the highest effects against the RsMo2, RsSc1 and Rs48, with inhibition zone (IZ) values of 17.33, 16.33, and 17.50 mm, respectively, also against Rs2 (IZ 14.33 mm), and RsIs2 (IZ 16 mm). C. citriodora oil showed the highest activity against RsBe2 (IZ 14 mm), RsFr4 (IZ 13.66 mm) and RsNe1 (IZ 13.66 mm). Gas Chromatography-Mass Spectrometry (GC-MS-FID) analyzed the chemical composition of these essential oils. It was proved that L. camara leaves contains mainly trans-caryophyllene (16.24%) and α-humulene (9.55%), in C. citriodora oil were α-citronellal (56.55%), α-citronellol (14.89%), and citronellol acetate (13.04%), and in Cup. sempervirens aerial parts were cedrol (22.17%), and Δ3-carene (18.59%). Five monoterpenes were evaluated against the most resistance Ralstonia isolate RsFr5 to the three studied essential oils and found that limonene had the highest effect against it compared with the lowest thymol. The results proved the strong bio effects of the essential oil from L. camara leaves as a natural product contained monoterpenes that can inhibit the growth of tested R. solanacearum phylotype II isolates.


Assuntos
Antibacterianos/farmacologia , Monoterpenos/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Ralstonia solanacearum/efeitos dos fármacos , Solanum tuberosum/microbiologia , Monoterpenos Acíclicos , Aldeídos/isolamento & purificação , Aldeídos/farmacologia , Antibacterianos/isolamento & purificação , Cupressus/química , DNA Bacteriano/análise , Cromatografia Gasosa-Espectrometria de Massas , Lantana/química , Testes de Sensibilidade Microbiana , Sesquiterpenos Monocíclicos , Monoterpenos/isolamento & purificação , Myrtaceae/química , Octanóis/isolamento & purificação , Octanóis/farmacologia , Óleos Voláteis/isolamento & purificação , Doenças das Plantas/microbiologia , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Ralstonia solanacearum/crescimento & desenvolvimento , Ralstonia solanacearum/isolamento & purificação , Ralstonia solanacearum/fisiologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia
10.
Pharmazie ; 74(3): 136-141, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30961677

RESUMO

In a previous study, it was shown, that shed snake skin is a good alternative model membrane for the human stratum corneum (SC). In this study, the influence of the enhancers dimethyl sulfoxide (DMSO), 1,2-propanediol, 1,3-butanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol in a concentration of 10 % on the permeation of l-prolyl- l-lysyl-l-α-glutamyl-l-lysin (PKEK) through shed snake skin was conducted. Pharmacokinetic parameters (diffusion coefficient, permeation coefficient, t-lag, Flux) were calculated. All examinations were performed on the skin of an individual and thus allowed a very good comparability of the data. All enhancers have overcome the shed snake skin and could be proven in the acceptor. DMSO does not affect the permeability of the membrane. Nevertheless, PKEK permeates faster in the presence of DMSO than PKEK being used alone. PKEK permeated the same, no matter if an auxiliary material was added or not. Without their addition, in all other enhancers no significant difference towards permeation could be determined.


Assuntos
Portadores de Fármacos/administração & dosagem , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacocinética , Pele/efeitos dos fármacos , Pele/metabolismo , Serpentes/metabolismo , Administração Cutânea , Animais , Butileno Glicóis/farmacologia , Coloides/administração & dosagem , Difusão , Dimetil Sulfóxido/farmacologia , Portadores de Fármacos/química , Composição de Medicamentos , Glicóis/farmacologia , Hexanos/farmacologia , Modelos Animais , Octanóis/farmacologia , Oligopeptídeos/química , Pentanos/farmacologia , Permeabilidade/efeitos dos fármacos , Propilenoglicol/farmacologia , Absorção Cutânea/efeitos dos fármacos , Tensoativos/administração & dosagem , Tensoativos/química , Tensoativos/farmacocinética
11.
Mycotoxin Res ; 35(4): 329-340, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31025195

RESUMO

1-Octen-3-ol is one of the most abundant volatile compounds associated with fungi and functions as a germination and growth inhibitor in several species. By investigating its effect on the biosynthesis of patulin, a mycotoxin made by Penicillium expansum, it was found that a sub-inhibitory level of volatile 1-octen-3-ol increased accumulation of patulin on a medium that normally suppresses the mycotoxin. Transcriptomic sequencing and comparisons of control and treated P. expansum grown on potato dextrose agar (PDA; patulin permissive) or secondary medium agar (SMA; patulin suppressive) revealed that the expression of gox2, a gene encoding a glucose oxidase, was significantly affected, decreasing 10-fold on PDA and increasing 85-fold on SMA. Thirty other genes, mostly involved in transmembrane transport, oxidation-reduction, and carbohydrate metabolism were also differently expressed on the two media. Transcription factors previously found to be involved in regulation of patulin biosynthesis were not significantly affected despite 1-octen-3-ol increasing patulin production on SMA. Further study is needed to determine the relationship between the upregulation of patulin biosynthesis genes and gox2 on SMA, and to identify the molecular mechanism by which 1-octen-3-ol induced this effect.


Assuntos
Meios de Cultura/química , Octanóis/farmacologia , Patulina/biossíntese , Penicillium/efeitos dos fármacos , Penicillium/metabolismo , Vias Biossintéticas , Perfilação da Expressão Gênica , Glucose Oxidase/genética , Penicillium/genética , Volatilização
12.
J Chem Ecol ; 45(5-6): 447-454, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989491

RESUMO

Males of several species in the large cerambycid beetle subfamily Lamiine, native to South and North America, are known to produce aggregation-sex pheromones composed of three related structures: the sesquiterpene catabolic product geranylacetone, its corresponding alcohol (known as fuscumol), and the acetate ester of the alcohol (fuscumol acetate). Here, we show that males of two lamiine species native to the eastern USA, Astylopsis macula (Say) and Leptostylus transversus (Gyllenhal) (both tribe Acanthocinini), produce pheromones composed of the structurally related (S)-6-methylhept-5-en-2-ol ([S]-sulcatol). Males of both species also produced 6-methylhept-5-en-2-one (sulcatone), and males of A. macula produced trace amounts of (R)-fuscumol acetate. Field experiments demonstrated that both species were attracted by (S)-sulcatol. Sulcatone was not attractive as a single component, nor did it influence attraction of A. macula to (S)-sulcatol, while its effect on L. transversus was unclear. Data from the field experiments, and a separate experiment using traps fitted with a timer mechanism that rotated trap jars, revealed that the two species overlap only slightly in both seasonal and daily flight period, thus minimizing interspecific attraction. Racemic fuscumol acetate and fuscumol antagonized attraction of both species to sulcatol. The identification of sulcatol as a cerambycid pheromone extends the known range of pheromone components in the subfamily Lamiinae.


Assuntos
Besouros/fisiologia , Octanóis/química , Atrativos Sexuais/química , Animais , Feminino , Masculino , Octanóis/farmacologia , Atrativos Sexuais/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Estereoisomerismo
13.
Cereb Cortex ; 29(8): 3363-3379, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-30169554

RESUMO

Subplate (SP) neurons exhibit spontaneous plateau depolarizations mediated by connexin hemichannels. Postnatal (P1-P6) mice show identical voltage pattern and drug-sensitivity as observed in slices from human fetal cortex; indicating that the mouse is a useful model for studying the cellular physiology of the developing neocortex. In mouse SP neurons, spontaneous plateau depolarizations were insensitive to blockers of: synaptic transmission (glutamatergic, GABAergic, or glycinergic), pannexins (probenecid), or calcium channels (mibefradil, verapamil, diltiazem); while highly sensitive to blockers of gap junctions (octanol), hemichannels (La3+, lindane, Gd3+), or glial metabolism (DLFC). Application of La3+ (100 µM) does not exert its effect on electrical activity by blocking calcium channels. Intracellular application of Gd3+ determined that Gd3+-sensitive pores (putative connexin hemichannels) reside on the membrane of SP neurons. Immunostaining of cortical sections (P1-P6) detected connexins 26, and 45 in neurons, but not connexins 32 and 36. Vimentin-positive glial cells were detected in the SP zone suggesting a potential physiological interaction between SP neurons and radial glia. SP spontaneous activity was reduced by blocking glial metabolism with DFLC or by blocking purinergic receptors by PPADS. Connexin hemichannels and ATP release from vimentin-positive glial cells may underlie spontaneous plateau depolarizations in the developing mammalian cortex.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Neuroglia/metabolismo , Neurônios/efeitos dos fármacos , Potenciais de Ação , Animais , Bicuculina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Citratos , Conexina 26 , Conexinas/metabolismo , Células Ependimogliais/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Gadolínio/farmacologia , Junções Comunicantes/metabolismo , Glicinérgicos/farmacologia , Hexaclorocicloexano/farmacologia , Lantânio/farmacologia , Camundongos , Neurônios/metabolismo , Octanóis/farmacologia , Técnicas de Patch-Clamp , Probenecid/farmacologia , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Quinoxalinas/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Estricnina/farmacologia , Valina/análogos & derivados , Valina/farmacologia , Vimentina/metabolismo , Proteína beta-1 de Junções Comunicantes , Proteína delta-2 de Junções Comunicantes
14.
Elife ; 72018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30576281

RESUMO

Habituation is the process that enables salience filtering, precipitating perceptual changes that alter the value of environmental stimuli. To discern the neuronal circuits underlying habituation to brief inconsequential stimuli, we developed a novel olfactory habituation paradigm, identifying two distinct phases of the response that engage distinct neuronal circuits. Responsiveness to the continuous odor stimulus is maintained initially, a phase we term habituation latency and requires Rutabaga Adenylyl-Cyclase-depended neurotransmission from GABAergic Antennal Lobe Interneurons and activation of excitatory Projection Neurons (PNs) and the Mushroom Bodies. In contrast, habituation depends on the inhibitory PNs of the middle Antenno-Cerebral Track, requires inner Antenno-Cerebral Track PN activation and defines a temporally distinct phase. Collectively, our data support the involvement of Lateral Horn excitatory and inhibitory stimulation in habituation. These results provide essential cellular substrates for future analyses of the molecular mechanisms that govern the duration and transition between these distinct temporal habituation phases. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).


Assuntos
Antenas de Artrópodes/fisiologia , Drosophila melanogaster/efeitos dos fármacos , Interneurônios/fisiologia , Corpos Pedunculados/fisiologia , Condutos Olfatórios/fisiologia , Neurônios Receptores Olfatórios/fisiologia , Olfato/fisiologia , Acetatos/farmacologia , Adenilil Ciclases/genética , Adenilil Ciclases/metabolismo , Animais , Antenas de Artrópodes/citologia , Antenas de Artrópodes/efeitos dos fármacos , Benzaldeídos/farmacologia , Diacetil/farmacologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Expressão Gênica , Hidroxiureia/toxicidade , Interneurônios/citologia , Interneurônios/efeitos dos fármacos , Corpos Pedunculados/citologia , Corpos Pedunculados/efeitos dos fármacos , Octanóis/farmacologia , Odorantes/análise , Condutos Olfatórios/citologia , Condutos Olfatórios/efeitos dos fármacos , Neurônios Receptores Olfatórios/citologia , Neurônios Receptores Olfatórios/efeitos dos fármacos , Transmissão Sináptica/fisiologia
15.
Int J Parasitol Drugs Drug Resist ; 8(3): 526-533, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30401619

RESUMO

The cys-loop superfamily of ligand-gated ion channels are well recognized as important drug targets for many invertebrate specific compounds. With the rise in resistance seen worldwide to existing anthelmintics, novel drug targets must be identified so new treatments can be developed. The acetylcholine-gated chloride channel (ACC) family is a unique family of cholinergic receptors that have been shown, using Caenorhabditis elegans as a model, to have potential as anti-parasitic drug targets. However, there is little known about the function of these receptors in parasitic nematodes. Here, we have identified an acc gene (hco-acc-1) from the sheep parasitic nematode Haemonchus contortus. While similar in sequence to the previously characterized C. elegans ACC-1 receptor, Hco-ACC-1 does not form a functional homomeric channel in Xenopus oocytes. Instead, co-expression of Hco-ACC-1 with a previously characterized subunit Hco-ACC-2 produced a functional heteromeric channel which was 3x more sensitive to acetylcholine compared to the Hco-ACC-2 homomeric channel. We have also found that Hco-ACC-1 can be functionally expressed in C. elegans. Overexpression of both cel-acc-1 and hco-acc-1 in both C. elegans N2 and acc-1 null mutants decreased the time for worms to initiate reversal avoidance to octanol. Moreover, antibodies were generated against the Hco-ACC-1 protein for use in immunolocalization studies. Hco-ACC-1 consistently localized to the anterior half of the pharynx, specifically in pharyngeal muscle tissue in H. contortus. On the other hand, expression of Hco-ACC-1 in C. elegans was restricted to neuronal tissue. Overall, this research has provided new insight into the potential role of ACC receptors in parasitic nematodes.


Assuntos
Acetilcolina/farmacologia , Canais de Cloreto/metabolismo , Haemonchus/metabolismo , Proteínas de Helminto/metabolismo , Receptores Colinérgicos/metabolismo , Acetilcolina/metabolismo , Animais , Anti-Helmínticos/metabolismo , Caenorhabditis elegans/genética , Canais de Cloreto/genética , Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína , Haemonchus/anatomia & histologia , Haemonchus/efeitos dos fármacos , Haemonchus/genética , Proteínas de Helminto/genética , Canais Iônicos de Abertura Ativada por Ligante/genética , Canais Iônicos de Abertura Ativada por Ligante/metabolismo , Octanóis/farmacologia , Oócitos/efeitos dos fármacos , Músculos Faríngeos/metabolismo , Receptores Colinérgicos/genética , Xenopus laevis/anatomia & histologia , Xenopus laevis/fisiologia
16.
Insect Biochem Mol Biol ; 101: 32-46, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30026095

RESUMO

The Oriental fruit fly, Bactrocera dorsalis, is a highly destructive pest of various fruits. The reproductive and host-finding behaviors of this species are affected by several plant semiochemicals that are perceived through chemosensory receptors. However, the chemosensory mechanisms by which this perception occurs have not been fully elucidated. We conducted RNA sequencing analysis of the chemosensory organs of B. dorsalis to identify the genes coding for chemosensory receptors. We identified 60 olfactory receptors (ORs), 17 gustatory receptors and 23 ionotropic receptors-including their homologs and variants-from the transcriptome of male antennae and proboscises. We functionally analyzed ten ORs co-expressed with the obligatory co-receptor ORCO in Xenopus oocytes to identify their ligands. We tested 24 compounds including attractants for several Bactrocera species and volatiles from the host fruits of B. dorsalis. We found that BdorOR13a co-expressed with ORCO responded robustly to 1-octen-3-ol. BdorOR82a co-expressed with ORCO responded significantly to geranyl acetate, but responded weakly to farnesenes (a mixture of isomers) and linalyl acetate. These four compounds were subsequently subjected to behavioral bioassays. When each of the aforementioned compound was presented in combination with a sphere model as a visual cue to adult flies, 1-octen-3-ol, geranyl acetate, and farnesenes significantly enhanced landing behavior in mated females, but not in unmated females or males. These results suggest that the ORs characterized in the present study are involved in the perception of plant volatiles that affect host-finding behavior in B. dorsalis.


Assuntos
Proteínas de Insetos/genética , Octanóis/farmacologia , Neurônios Receptores Olfatórios/fisiologia , Receptores Odorantes/genética , Tephritidae/fisiologia , Transcriptoma , Acetatos/química , Acetatos/farmacologia , Monoterpenos Acíclicos , Animais , Antenas de Artrópodes/citologia , Antenas de Artrópodes/efeitos dos fármacos , Antenas de Artrópodes/fisiologia , Bioensaio , Feminino , Regulação da Expressão Gênica , Proteínas de Insetos/metabolismo , Masculino , Monoterpenos/química , Monoterpenos/farmacologia , Octanóis/química , Neurônios Receptores Olfatórios/citologia , Neurônios Receptores Olfatórios/efeitos dos fármacos , Oócitos/citologia , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Técnicas de Patch-Clamp , Feromônios/química , Feromônios/farmacologia , Filogenia , Receptores Odorantes/classificação , Receptores Odorantes/metabolismo , Tephritidae/classificação , Tephritidae/citologia , Tephritidae/efeitos dos fármacos , Terpenos/química , Terpenos/farmacologia , Xenopus laevis
17.
Mol Biol Rep ; 45(4): 547-561, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29797173

RESUMO

Dimethyl octenol from chloroform extract and oleanene tetrol from water extract of Trianthema decandra (TD) were isolated and characterized by using HPLC, UV, FT-IR, NMR, LC-MS and CHNS, their structure were elucidated from their respective spectral data. The anti-inflammatory activity of chloroform extract, water extract, dimethyl octenol and oleanene tetrol of T. decandra were studied and underlying cellular and molecular mechanisms of action were investigated in vitro and in vivo using macrophage-like cell line (RAW264.7 cells) and type II collagen induced arthritis mice models. Nitric oxide production was inhibited and TNF-α secretion was supressed in stimulated RAW cells treated with the chloroform extract and dimethyl octenol of T. decandra. Further, the chloroform and water extract, dimethyl octenol and oleanene tetrol inhibited protein denaturation and stabilized HRBC membranes in vitro. Reduction in inflammation as a measure of paw diameter was recorded in all the treated animals when compared to control animals. Catalase, peroxidase and glutathione peroxidase levels significantly increased in the joint tissue of treated groups. The possible mechanism of action of these compounds was studied using in silico molecular docking methods with phospholipase A2 (PLA2), cycloxygenase-1 (COX-1) and cycloxygenase-2 (COX-2) as targets. Among the three target proteins, the inhibition of the inflammatory protein PLA2 and COX-2 towards dimethyl octenol and oleanene tetrol respectively. Our results contribute towards confirmation of the traditional use of TD and its compounds for the therapy of rheumatoid arthritis and other inflammatory joint disorders.


Assuntos
Octanóis/farmacologia , Ácido Oleanólico/análogos & derivados , Aizoaceae/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Artrite/tratamento farmacológico , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Macrófagos/metabolismo , Masculino , Camundongos , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Ácido Oleanólico/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Folhas de Planta , Células RAW 264.7/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
18.
Cont Lens Anterior Eye ; 41(1): 77-82, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29074306

RESUMO

PURPOSE: To compare the efficacy of Dr Organic Tea Tree Face Wash, OcuSoft Lids Scrub Plus and the BlephEx™ device at treating of Demodex folliculorum blepharitis. METHODS: Eighty-six subjects (33 males/36 females) were enrolled in a randomised controlled interventional treatment study. Subjects completed a dry eye symptom questionnaire and were assessed for presence of Demodex folliculorum. Subjects were divided into three groups according to treatment: Dr Organic Tea Tree Face Wash (A) (n=28), OcuSoft Lid Scrub Plus (B) (n=30), or in-house lid scrub with the BlephEx™ device before nightly lid scrubs with OcuSoft Lid Scrub Plus (C) (n=28). Subjects were advised to clean their eyelids nightly for four weeks. Each subject was re-assessed for symptoms and Demodex folliculorum blepharitis after two weeks and four weeks of treatment. RESULTS: The quantity of Demodex folliculorum was significantly reduced after four weeks of treatment in all three groups (p<0.05). Overall, there was no difference in efficacy between the three treatments (p>0.1). Symptoms reported by subjects were significantly improved after two and four weeks of treatment (p<0.05). Overall, there was no difference in efficacy between the three treatments to reduce symptoms after two or four weeks (p= 0.813 and p=0.646 respectively). CONCLUSION: All three methods tested have shown good ability to reduce Demodex folliculorum quantity, improve subjective symptoms and help treat Demodex folliculorum blepharitis.


Assuntos
Blefarite/terapia , Infecções Oculares Parasitárias/tratamento farmacológico , Pestanas/parasitologia , Infestações por Ácaros/tratamento farmacológico , Ácaros , Octanóis/farmacologia , Fitoterapia/métodos , Óleo de Melaleuca/uso terapêutico , Animais , Blefarite/diagnóstico , Blefarite/parasitologia , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/parasitologia , Feminino , Humanos , Masculino , Infestações por Ácaros/diagnóstico , Infestações por Ácaros/parasitologia
19.
Environ Entomol ; 46(5): 1041-1050, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28981656

RESUMO

In agricultural settings, examples of effective control strategies using repellent chemicals in integrated pest management (IPM) are relatively scarce compared to those using attractants. This may be partly due to a poor understanding of how repellents affect insect behavior once they are deployed. Here we attempt to identify potential hallmarks of repellent stimuli that are robust enough for practical use in the field. We explore the literature for success stories using repellents in IPM and we investigate the mechanisms of repellency for two chemical oviposition deterrents for controlling Drosophila suzukii Matsumura, a serious pest of small fruit crops. Drosophila suzukii causes injury by laying her eggs in ripening fruit and resulting larvae make fruit unmarketable. In caged choice tests, reduced oviposition was observed in red raspberry fruit treated with volatile 1-octen-3-ol and geosmin at two initial concentrations (10% and 1%) compared to untreated controls. We used video monitoring to observe fly behavior in these caged choice tests and investigate the mode of action for deterrence through the entire behavioral repertoire leading to oviposition. We observed fewer visitors and more time elapsed before flies first landed on 1-octen-3-ol-treated fruits than control fruits and concluded that this odor primarily inhibits behaviors that occur before D. suzukii comes in contact with a potential oviposition substrate (precontact). We observed some qualitative differences in precontact behavior of flies around geosmin-treated fruits; however, we concluded that this odor primarily inhibits behaviors that occur after D. suzukii comes in contact with treated fruits (postcontact). Field trials found reduced oviposition in red raspberry treated with 1-octen-3-ol and a combination of 1-octen-3-ol and geosmin, but no effect of geosmin alone. Recommendations for further study of repellents for practical use in the field are discussed.


Assuntos
Controle de Insetos/métodos , Repelentes de Insetos/farmacologia , Naftóis/farmacologia , Octanóis/farmacologia , Oviposição/efeitos dos fármacos , Animais , Drosophila , Feminino , Rubus
20.
J Oleo Sci ; 66(9): 1041-1049, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28794307

RESUMO

1-Octen-3-ol, known as mushroom alcohol, is a natural product extracted from fungi and plants. Its antimicrobial activities against five common food-related bacteria and two pathogenic fungi were evaluated in this paper, including Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Fusarium tricinctum and Fusarium oxysporum. The results showed that 1-octen-3-ol had a strong antibacterial activity against the tested bacteria, especially against Gram-positive bacteria, and it can also inhibit fungal growth and spore germination. The minimum inhibitory concentrations (MICs) for Gram-positive bacteria and Gram-negative bacteria were 1.0 and 2.0 mg/mL, respectively. The minimum bactericidal concentrations (MBCs) for Gram-positive bacteria and Gram-negative bacteria were 4.0 and 8.0 mg/mL, respectively. The completely inhibitory concentrations for fungal growth and spore germination were 8.0 and 2.0 mg/ml, respectively. Cell constituents' leakage and scanning electron microscope assays indicated that 1-octen-3-ol changed the permeability of the cell membrane. Discrepant antimicrobial activity between 1-octen-3-ol and 1-octen-3-one indicated that hydroxyl may play a decisive role in antimicrobial activity. It is suggested that 1-octen-3-ol, with attractive mushroom aroma and antimicrobial activity, has potential applications in control of pathogens.


Assuntos
Bacillus subtilis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Microbiologia de Alimentos , Fusarium/efeitos dos fármacos , Octanóis/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Antibacterianos , Antifúngicos , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Farmacorresistência Fúngica , Relação Estrutura-Atividade
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