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51.
Felipe Gazos-Lopes Rafael Dias Mesquita Lívia Silva-Cardoso Raquel Senna Alan Barbosa Silveira Willy Jablonka Cecília Oliveira Cudischevitch Alan Brito Carneiro Ednildo Alcantara Machado Luize G. Lima Robson Queiroz Monteiro Roberto Henrique Nussenzveig Evelize Folly Alexandre Romeiro Jorick Vanbeselaere Lucia Mendon?a-Previato José Osvaldo Previato Jesus G. Valenzuela José Marcos Chaves Ribeiro Georgia Correa Atella Mário Alberto Cardoso Silva-Neto 《PloS one》2012,7(10)
Background
Rhodnius prolixus is a blood-sucking bug vector of Trypanosoma cruzi and T. rangeli. T. cruzi is transmitted by vector feces deposited close to the wound produced by insect mouthparts, whereas T. rangeli invades salivary glands and is inoculated into the host skin. Bug saliva contains a set of nitric oxide-binding proteins, called nitrophorins, which deliver NO to host vessels and ensure vasodilation and blood feeding. NO is generated by nitric oxide synthases (NOS) present in the epithelium of bug salivary glands. Thus, T. rangeli is in close contact with NO while in the salivary glands.Methodology/Principal Findings
Here we show by immunohistochemical, biochemical and molecular techniques that inositolphosphate-containing glycolipids from trypanosomatids downregulate NO synthesis in the salivary glands of R. prolixus. Injecting insects with T. rangeli-derived glycoinositolphospholipids (Tr GIPL) or T. cruzi-derived glycoinositolphospholipids (Tc GIPL) specifically decreased NO production. Salivary gland treatment with Tc GIPL blocks NO production without greatly affecting NOS mRNA levels. NOS protein is virtually absent from either Tr GIPL- or Tc GIPL-treated salivary glands. Evaluation of NO synthesis by using a fluorescent NO probe showed that T. rangeli-infected or Tc GIPL-treated glands do not show extensive labeling. The same effect is readily obtained by treatment of salivary glands with the classical protein tyrosine phosphatase (PTP) inhibitor, sodium orthovanadate (SO). This suggests that parasite GIPLs induce the inhibition of a salivary gland PTP. GIPLs specifically suppressed NO production and did not affect other anti-hemostatic properties of saliva, such as the anti-clotting and anti-platelet activities.Conclusions/Significance
Taken together, these data suggest that trypanosomatids have overcome NO generation using their surface GIPLs. Therefore, these molecules ensure parasite survival and may ultimately enhance parasite transmission. 相似文献52.
George Kluck Karla C. Régis Nuccia N.T. De Cicco Lívia Silva-Cardoso Miria G. Pereira Patrícia Fampa Alessandra C. Chagas-Lima Alexandre Romeiro Narcisa L. Cunha-Silva Georgia C. Atella 《Parasitology international》2018,67(2):97-106
Lipid uptake and metabolism by trypanosomatid parasites from vertebrate host blood have been well established in the literature. However, there is a lack of knowledge regarding the same aspects concerning the parasites that cross the hemolymph of their invertebrate hosts. We have investigated the lipid composition and metabolism of the insect trypanosomatid Herpetomonas muscarum by 3H- palmitic acid and phosphate (32Pi) and the parasite interaction with Lipophorin (Lp) the main lipid carrying protein of insect hemolymph. Gas chromatography-mass spectrometry (GC–MS) analyses were used to identify the fatty acids and sterols composition of H.muscarum. Furthermore, we investigated the Lp binding site in the plasma membrane of parasite by Immunolocalization. We showed that H. muscarum incorporated 3H-palmitic acid and inorganic phosphate (32Pi) which were readily used as precursor molecules of lipid biosynthetic pathways. Furthermore, H. muscarum was able to take up both protein and lipid moieties of Lp which could be used as nutrient sources. Moreover, we have also demonstrated for the first time the presence of a Lp binding site in the membrane of a parasite. Such results point out the role of describing the metabolic pathways of trypanosomatids in order to provide a better understanding of parasite-host interaction peculiarities. Such studies may enhance the potential form the identification of novel chemotherapeutic targets in harmful parasites. 相似文献
53.
Lessa JA Guerra JC de Miranda LF Romeiro CF Da Silva JG Mendes IC Speziali NL Souza-Fagundes EM Beraldo H 《Journal of inorganic biochemistry》2011,105(12):1729-1739
Complexes [Au(H2Ac4DH)Cl]?MeOH (1) [Au(H22Ac4Me)Cl]Cl (2) [Au(H22Ac4Ph)Cl]Cl?2H2O (3) and [Au(H22Bz4Ph)Cl]Cl (4) were obtained with 2-acetylpyridine thiosemicarbazone (H2Ac4DH), its N(4)-methyl (H2Ac4Me) and N(4)-phenyl (H2Ac4Ph) derivatives, as well as with N(4)-phenyl 2-benzoylpyridine thiosemicarbazone (H2Bz4Ph). The compounds were cytotoxic to Jurkat (immortalized line of T lymphocyte), HL-60 (acute myeloid leukemia), MCF-7 (human breast adenocarcinoma) and HCT-116 (colorectal carcinoma) tumor cell lines. Jurkat and HL-60 cells were more sensitive than MCF-7 and HCT-116 cells. Upon coordinating to the gold(I) metal centers in complexes (2) and (4), the cytotoxic activity of the H2Ac4Me and H2Bz4Ph ligands increased against the HL-60 and Jurkat tumor cell lines. 2 was more active than auranofin against both leukemia cells. Most of the studied compounds were less toxic than auranofin to peripheral blood mononuclear cells (PBMC). All compounds induced DNA fragmentation in HL-60 and Jurkat cells indicating their pro-apoptotic potential. Complex (2) strongly inhibited the activity of thioredoxin reductase (TrxR), which suggests inhibition of TrxR to be part of its mechanism of action. 相似文献
54.
In this work low temperature conversion (LTC) process was applied in a dried sludge from a petrochemical industry wastewater treatment station located in Rio de Janeiro, Brazil. The process was performed in two modes: continuous and batch-scale. This process produced a pyrolysis oil (continuous 14%; batch-scale 40% yield); pyrolytic char (continuous 46%; batch-scale 56% yield); gas and water. Pyrolysis oil fraction was analyzed by gas chromatographic mass spectrometry (GCMS) and the main components identified were toluene, ethylbenzene, styrene, isopropyl benzene, alpha-methylstyrene, butanenitrile and 1,3- biphenyl propane. Metals content, sulfur content and calorific value have been determined for the pyrolysis oil fraction. The results showed that the pyrolysis oil obtained could be used for industrial purposes and/or as energetic matrix. 相似文献
55.
Induced pluripotent stem(iPS) cells can be derived from human somatic cells by cellular reprogramming.This technology provides a potential source of non-controversial therapeutic cells for tissue repair,drug discovery,and opportunities for studying the molecular basis of human disease.Normally,mouse embryonic fibroblasts(MEFs) are used as feeder layers in the initial derivation of iPS lines.The purpose of this study was to determine whether SNL fibroblasts can be used to support the growth of human iPS cell... 相似文献
56.
Renata B. Lacerda Cleverton K.F. de Lima Leandro L. da Silva Nelilma C. Romeiro Ana Luisa P. Miranda Eliezer J. Barreiro Carlos A.M. Fraga 《Bioorganic & medicinal chemistry》2009,17(1):74-84
We describe herein the design, synthesis and pharmacological evaluation of novel 3-arylamine-imidazo[1,2-a]pyridine derivatives structurally designed as novel symbiotic prototypes presenting analgesic and anti-inflammatory properties. The derivatives obtained were submitted to in vivo assays of nociception, hyperalgesia and inflammation, and to in vitro assays of human PGHS-2 inhibition. These assays allowed the identification of compound LASSBio-1135 (3a) as an anti-inflammatory and analgesic symbiotic prototype. This compound inhibited moderately the human PGHS-2 enzyme activity (IC50 = 18.5 μM) and reverted the capsaicin-induced thermal hyperalgesia (100 μmol/kg, po) similarly to p38 MAPK inhibitor SB-203580 (2). Additionally, LASSBio-1135 (3a) presented activity similar to celecoxib (1) regarding the reduction of the carrageenan-induced rat paw edema (33% of inhibition at 100 μmol/kg, po). We also discovered derivatives LASSBio-1140 (3c) and LASSBio-1141 (3e) as analgesic and anti-inflammatory prototypes, which were able to attenuate the capsaicin-induced thermal hyperalgesia (100 μmol/kg, po) and reduce the carrageenan-induced paw edema (ED50 = 11.5 μmol/kg (3.3 mg/kg) and 14.5 μmol/kg (4.1 mg/kg), respectively), being both more active than celecoxib (1), despite the fact that their effects involve a different mechanism of action. Additionally, derivative LASSBio-1145 (3j) showed remarkable analgesic (ED50 = 22.7 μmol/kg (8.9 mg/kg)) and anti-inflammatory (ED50 = 8.7 μmol/kg (3.4 mg/kg)) profile in vivo (100 μmol/kg; po), in AcOH-induced abdominal constrictions in mice and carrageenan-induced rat paw edema models, respectively, being a novel orally-active anti-inflammatory drug candidate that acts as a selective PGHS-2 inhibitor (IC50 = 2.8 μM). 相似文献
57.
Biocontrol of tomato late blight with the combination of epiphytic antagonists and rhizobacteria 总被引:2,自引:0,他引:2
Valdir Loureno Júnior Luiz A. Maffia Reginaldo da Silva Romeiro Eduardo S.G. Mizubuti 《Biological Control》2006,38(3):331-340
Control of tomato late blight (LB) in Brazil is heavily based on chemicals. However, reduction in fungicide usage is required in both conventional and organic production systems. Assuming that biological control is an alternative for LB management, 208 epiphytic microorganisms and 23 rhizobacteria (RB) were isolated from conventional and organically grown tomato plants and tested for antagonistic activity against Phytophthora infestans. Based on in vitro inhibition of sporangia germination and detached leaflet bioassays, four EP microorganisms (Aspergillus sp., Cellulomonas flavigena, Candida sp., and Cryptococcus sp.) were selected. These microorganisms were applied either singly or combined on tomato plants treated or not with the RB Bacillus cereus. On control plants, LB progress rate (r), area under disease progress curve, and final disease severity were high. Lowest values of final severity were recorded on plants colonized by B. cereus and treated with C. flavigena, Candida sp. and Cryptococcus sp. There was no reduction on disease severity in plants treated only with RB. Biological control of LB resulted in low values of r and final severity. Integration of biological control with fungicides, cultural practices, and other measures can contribute to manage LB on tomato production systems. 相似文献
58.
Leonardo Moreira da Costa José Walkimar de Mesquita Carneiro Gilberto Alves Romeiro Lilian Weitzel Coelho Paes 《Journal of molecular modeling》2011,17(2):243-249
The affinity of the Ca2+ ion for a set of substituted carbonyl ligands was analyzed with both the DFT (B3LYP/6-31+G(d)) and semi-empirical (PM6) methods.
Two types of ligands were studied: a set of monosubstituted [O=CH(R)] and a set of disubstituted ligands [O=C(R)2] (R=H, F, Cl, Br, OH, OCH3, CH3, CN, NH2 and NO2), with R either directly bound to the carbonyl carbon atom or to the para position of a phenyl ring. The interaction energy was calculated to quantify the affinity of the Ca2+ cation for the ligands. Geometric and electronic parameters were correlated with the intensity of the metal-ligand interaction.
The electronic nature of the substituent is the main parameter that determines the interaction energy. Donor groups make the
interaction energy more negative (stabilizing the complex formed), while acceptor groups make the interaction energy less
negative (destabilizing the complex formed). 相似文献
59.
Jorge L.M. Tributino Carolina D. Duarte Rodrigo S. Corrêa Antonio C. Doriguetto Javier Ellena Nelilma C. Romeiro Newton G. Castro Ana Luisa P. Miranda Eliezer J. Barreiro Carlos A.M. Fraga 《Bioorganic & medicinal chemistry》2009,17(3):1125-1131
We described herein the molecular design of novel in vivo anti-inflammatory 6-methanesulfonamide-3,4-methylenedioxyphenyl-N-acylhydrazone derivatives (1) planned by applying the molecular hybridization approach. This work also points out to the discovery of LASSBio-930 (1c) as a novel anti-inflammatory and anti-hyperalgesic prototype, which was able to reduce carrageenan-induced rat paw edema with an ED50 of 97.8 μmol/kg, acting mainly as a non-selective COX inhibitor. 相似文献
60.
Patricia M.L. Dutra Felipe A. Dias Claudia O. Rodrigues Alexandre Romeiro Marcia Attias Wanderley De Souza Angela H.C.S. Lopes José Roberto Meyer-Fernandes 《Current microbiology》2001,43(4):288-292
In the present work we characterized the secreted phosphatase activity of the trypanosomatid parasite Herpetomonas muscarum muscarum. This housefly parasite hydrolyzed p-nitrophenylphosphate at a rate of 10.26 nmol Pi/mg protein/min. Classical inhibitors of acid phosphatases, such as sodium
orthovanadate (NaVO3), sodium fluoride (NaF), and ammonium molybdate promoted a decrease in this phosphatase activity. When the parasites were
assayed in the presence of sodium tartrate, an inhibitor of Leishmania spp-secreted acid phosphatases, this activity was drastically diminished. Cytochemical analysis showed the localization of
this enzyme on the external surface and in the flagellar pocket of these parasites. Sodium tartrate inhibited this reaction,
confirming the biochemical data. Platelet-activating factor (PAF) inhibited the phosphatase activity determined in the supernatant
of living H. m. muscarum.
Received: 2 February 2001 / Accepted: 5 March 2001 相似文献