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51.
Janay?Stefany?Carneiro?Araujo Bruno?Cruz?de?Souza David?Bacelar?Costa Junior Larissa de Mattos?Oliveira Isis?Bugia?Santana Angelo?Amancio?Duarte Pedro?Sousa?Lacerda Manoelito Coelho?dos?Santos Junior Franco?Henrique?Andrade?LeiteEmail author 《Journal of molecular modeling》2018,24(8):220
Malaria is the world’s most widespread protozoan infection, being responsible for more than 445,000 annual deaths. Among the malaria parasites, Plasmodium falciparum is the most prevalent and lethal. In this context, the search for new antimalarial drugs is urgently needed. P. falciparum superoxide dismutase (PfSOD) is an important enzyme involved in the defense mechanism against oxidative stress. The goal of this study was to identify through hierarchical screening on pharmacophore models and molecular dynamics (MD), promising allosteric PfSOD inhibitors that do not show structural requirements for human inhibition. MD simulations of 1000 ps were performed on PfSOD using GROMACS 5.1.2. For this, the AMBER99SB-ILDN force field was adapted to describe the metal-containing system. The simulations indicated stability in the developed system. Therefore, a covariance matrix was generated, in which it was possible to identify residues with correlated and anticorrelated movements with the active site. These results were associated with the results found in the predictor of allosteric sites, AlloSitePro, which affirmed the ability of these residues to delimit an allosteric site. Then, after successive filtering of the Sigma-Aldrich® compounds database for HsSOD1 and PfSOD pharmacophores, 152 compounds were selected, also obeying Lipinski’s rule of 5. Further filtering of those compounds based on molecular docking results, toxicity essays, availability, and price filtering led to the selection of a best compound, which was then submitted to MD simulations of 20,000 ps on the allosteric site. The study concludes that the ZINC00626080 compound could be assayed against SODs. 相似文献
52.
Larissa?de Mattos?Oliveira Janay?Stefany?Carneiro?Araújo David?Bacelar?Costa Junior Isis?Bugia?Santana Angelo?Amancio?Duarte Franco?Henrique?Andrade?Leite Raquel?Guimar?es?Benevides Manoelito?Coelho dos?Santos JuniorEmail authorView authors OrcID profile 《Journal of molecular modeling》2018,24(11):314
Leishmaniasis is caused by protozoa of the genus Leishmania spp. and is considered the second most important protozoa in the world due to the number of cases and mortality. Despite its importance in terms of public health, the treatment of patients is limited and has mostly low levels of efficacy and safety. Farnesyl pyrophosphate synthase (FPPS) acts in the early stages of isoprenoid synthesis, and is important for maintaining the integrity of the lipid bilayer of the parasite that causes the disease. The aim of this work was to identify one potential inhibitor of the FPPS of Leishmania major through virtual screening by pharmacophore modeling and docking. A total of 85,000 compounds from a natural products database (ZINC15) was submitted for virtual hierarchical screening, and the top ranked molecule in both methods was analyzed by intermolecular interaction profile and 20 ns molecular dynamics simulations. These results showed a promising compound from natural products that mimic the major interactions present in the substrate/inhibitor. 相似文献
53.
A Schubach T Cuzzi-Maya A V Oliveira A Sartori M P de Oliveira-Neto M S Mattos M L Araújo W J Souza F Haddad M de A Perez R S Pacheco H Momen S G Coutinho M C de Almeida Marzochi K B Marzochi S C da Costa 《Memórias do Instituto Oswaldo Cruz》2001,96(7):987-996
Cutaneous biopsies (n = 94) obtained from 88 patients with American tegumentary leishmaniasis were studied by conventional and immunohistochemical techniques. Specimens were distributed as active lesions of cutaneous leishmaniasis (n = 53) (Group I), cicatricial lesions of cutaneous leishmaniasis (n = 35) (Group II) and suggestive scars of healed mucosal leishmaniasis patients (n = 6) (Group III). In addition, active cutaneous lesions of other etiology (n = 24) (Group C1) and cutaneous scars not related to leishmaniasis (n = 10) (Group C2) were also included in the protocol. Amastigotes in Group I biopsies were detected by routine histopathological exam (30.2%), imprint (28.2%), culture (43.4%), immunofluorescence (41.4%) and immunoperoxidase (58.5%) techniques; and by the five methods together (79.3%). In Group II, 5.7% of cultures were positive. Leishmanial antigen was also seen in the cytoplasm of macrophages and giant cells (cellular pattern), vessel walls (vascular pattern) and dermal nerves (neural pattern). Positive reaction was detected in 49 (92.5%), 20 (57%) and 4 (67%) biopsies of Groups I, II and III, respectively. Antigen persistency in cicatricial tissue may be related to immunoprotection or, on the contrary, to the development of late lesions. We suggest that the cellular, vascular and neural patterns could be applied in the immunodiagnosis of active and cicatricial lesions in which leishmaniasis is suspected. 相似文献
54.
Maria Luisa Gomes Deise Mara M de Mattos Rosimeire S Freitas Glaucio F Diré Elaine A C Lima Sonia Maria S Souza Mario Bernardo-Filho 《Cellular and molecular biology, including cyto-enzymology》2002,48(7):757-759
We have reported that drugs alter the biodistribution of radiopharmaceuticals used in diagnostic imaging in nuclear medicine. Knowledge of such altered biodistribution is important in making diagnostic from scintigraphy. Mitomycin-C is used as component of many chemotherapeutic regimens to treat different tumors. The biological activities of mitomycin-C can be explained by its ability to inhibit deoxyribonucleic acid synthesis. Since patients on chemotherapeutic treatment can be submitted to nuclear medicine procedures, we studied the mitomycin-C effect on the bioavailability of the technetium-99m-labelled sodium pyrophosphate (9mTc-PYP) using an animal model. Mitomycin (0.45 mg) was administered by ocular plexus way Balb/c mice. One hour after the last dose, 99mTc-PYP (7.4 MBq) was administered and after 0.5 hr the animals (n = 15) were rapidly sacrificed. The organs were isolated, the radioactivity counted in a well counter and the percentage of radioactivity (%ATI) calculated. The results have shown that in the treated animals the %ATI has been decreased in spleen, thymus, heart and brain and increased in lung, liver and bone. The effect of this chemotherapeutic drug on the 99mTc-PYP biodistribution was statistically significant (Wilcoxon test, p < 0.05) and it could be explained by the metabolization or therapeutic action of mitomycin-C. 相似文献
55.
Ecophysiology of six selected shrub species in different plant communities at the periphery of the Atlantic Forest of SE-Brazil 总被引:2,自引:1,他引:1
Heitor Monteiro Duarte Arthur Geßler Fabio Rubio Scarano Augusto Csar Franco Eduardo Arcoverde de Mattos M. Nahm Heinz Rennenberg Pablo Jos Francisco Pena Rodrigues Henrique Leo Teixeira Zaluar Ulrich Lüttge 《Flora》2005,200(5):456-476
The Atlantic rain forest of Brazil is one of the 25 biodiversity hotspots of the world. It is surrounded by distinct marginal plant communities which are floristically related to the rain forest. We performed an in situ ecophysiological study of six shrub and tree species which are abundant in one or more of these marginal ecosystems. They formed three pairs of taxonomically related species, which, however, differed in geographic distribution and/or habitat preference. We aimed to answer the following questions: (1) Do habitat generalists and specialists differ in ecophysiological behaviour? (2) Are there general trends responsive to site characteristics, irrespective of taxonomic affiliation? (3) In which variables between-site intraspecific variation is more often detected? Plants chosen were the Clusiaceae Calophyllum brasiliense Cambess (swamp forest specialist) and Rheedia brasiliensis (Mart.) Planch &; Triana (a generalist plant, occurring in swamp forests and dry, sandy coastal vegetation); the Myrsinaceae Myrsine parvifolia A.DC. (widespread in sandy plains) and Myrsine gardneriana A.DC. (widespread in high-altitude habitats); and the Euphorbiaceae Styllingia dichotoma Muell. Arg. (a coastal inselberg specialist) and Croton compressus Lam. (a generalist found in coastal inselbergs and dry forests). We compared measurements of photosynthesis (chlorophyll fluorescence parameters), stable isotope (δ13C, δ15N) and metabolic carbon and nitrogen compounds. Generalists and specialists did not always differ in ecophysiological behaviour: for instance, while widespread generalists such as M. parvifolia and C. compressus were ecophysiologically versatile, R. brasiliense appeared to perform below optimum in all sampled habitats. Light and water were abiotic factors which apparently explained most of the variation found. Overall, ecophysiological responses were often more clearly related to individual species rather than to taxonomic affinities in higher hierarchies (family, genus) or habitat. These results are discussed as a further indication of high biodiversity even in habitats marginal to the rain forest hotspot. 相似文献
56.
57.
Hoffmann C Ellenberger C Mattos RC Aupperle H Dhein S Stief B Schoon HA 《Animal reproduction science》2009,111(2-4):261-278
This paper describes the histomorphological and immunohistochemical characterisation of phenotypic variations of endometrosis as well as potential etiological factors which may influence disease progression. In total, 779 endometrial biopsies were examined. These biopsies were taken in the breeding and non-breeding season (n=509), on defined days during the estrous cycle (n=70) and before and after experimentally induced bacterial endometritis (n=200). In addition to conventional histopathology, selected biopsies were investigated using alcianblue staining as well as immunohistochemical methods for the detection of steroid hormone receptors, Ki-67-antigen, vimentin, desmin, fibronectin, smooth-muscle-alpha-actin and laminin. The equine endometrosis can be divided into a destructive and a non-destructive form. Based on the morphology of the stromal cells involved, an active or inactive state can be distinguished in fibrotic foci. In all types of endometrosis, fibrotic stromal cells show a distinctly reduced expression of steroid hormone receptors in comparison to the intact stroma, indicating their dedifferentiation. However, the steroid hormone receptor expression of involved glandular epithelia seems to depend on the activity of the fibrosis. These results suggest an independency of all fibrotic foci from the hormonal control mechanism of the uterus. The characteristical features of destructive endometrosis are a large number of smooth-muscle-alpha-actin containing myofibroblasts, a pronounced epithelial vimentin expression, excessive extracellular matrix accumulation and a progressive alteration of the basal lamina. Furthermore, the frequently seen cystic glandular dilatation and mechanical destruction of the uterine glands may occur due to the contractibility of the myofibroblasts involved. As shown in this study, a simultaneous endometritis can cause a temporary activation of fibrotic stromal cells. However, cyclic and seasonal endocrine changes seem to have no effects on progression of the disease. It can be concluded that the various types of endometrosis represent different stages in the fibrotic process, possibly leading to the destruction of the glands and subsequently resulting in the development of a stromal fibrosis. 相似文献
58.
Arnon D. Jurberg Tiana Gonçalves Tatiane A. Costa Ana Carolina A. de Mattos Bernardo M. Pascarelli Pedro Paulo A. de Manso Marcelo Ribeiro-Alves Marcelo Pelajo-Machado José M. Peralta Paulo Marcos Z. Coelho Henrique L. Lenzi 《Development genes and evolution》2009,219(5):219-234
Schistosomiasis is a water-borne parasitic illness caused by neoophoran trematodes of the genus Schistosoma. Using classical histological techniques and whole-mount preparations, the present work describes the embryonic development
of Schistosoma mansoni eggs in the murine host and compares it with eggs maintained under in vitro conditions. Two pre-embryonic stages occur inside
the female worm: the prezygotic stage is characterized by the release of mature oocytes from the female ovary until its fertilization.
The zygotic stage encompasses the migration of the zygote through the ootype, where the eggshell is formed, to the uterus.
Fully formed eggs are laid still undeveloped, without having suffered any cleavage. In the outside environment, eight embryonic
stages can be defined: stage 1 refers to early cleavages and the beginning of yolk fusion. Stage 2 represents late cleavage,
with the formation of a stereoblastula and the onset of outer envelope differentiation. Stage 3 is defined by the elongation
of the embryonic primordium and the onset of inner envelope formation. At stage 4, the first organ primordia arise. During
stages 5 to 7, tissue and organ differentiation occurs (neural mass, epidermis, terebratorium, musculature, and miracidial
glands). Stage 7 is characterized by the nuclear condensation of neurons of the central neural mass. Stage 8 refers to the
fully formed larva, presenting muscular contraction, cilia, and flame-cell beating. This staging system was compared to a
previous classification and could underlie further studies on egg histoproteomics (morphological localizome). The differentiation
of embryonic structures and their probable roles in granulomatogenesis are discussed herein.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
59.
Aluísio M. Fonseca Francisco Jose Q. Monte Maria da Conceio F. de Oliveira Marcos C. de Mattos Geoffrey A. Cordell Raimundo Braz-Filho Telma L.G. Lemos 《Journal of Molecular Catalysis .B, Enzymatic》2009,57(1-4):78-82
A series of aliphatic and aromatic aldehydes and ketones was reduced using plant cell preparations from coconut juice, Cocos nucifera, also called ACC (água-de-coco do Ceará). The reduced products were typically obtained in excellent yields (%) and with very high enantiomeric excess. Esters, amides, and nitrobenzene, yielded acids, amines and an azoxyderivative with satisfactory results. 相似文献
60.
Aparecida Resende F de Andrade Barcala CA da Silva Faria MC Kato FH Cunha WR Tavares DC 《Life sciences》2006,79(13):1268-1273
Ursolic acid (UA) and oleanolic acid (OA) are triterpenoid compounds found in food, medicinal herbs and various other plants in free form or bound to glycosides. Both substances are known for their antimicrobial, hepatoprotective, anti-inflammatory, antiallergic, antiviral and cytotoxic activities. In the present study, we evaluated the antimutagenic potential of UA and OA using the micronucleus test in peripheral blood and bone marrow of Balb/c mice. The animals were divided into 10 treatment groups: mice treated with UA (80 mg/kg b.w.); OA (80 mg/kg b.w.); a mixture of UA and OA (80 mg/kg b.w.); the antineoplastic agent doxorubicin (DXR, 90 mg/kg b.w.); DMSO and DXR; UA and DXR; OA and DXR; UA, OA and DXR, and negative and solvent controls. UA, OA and a mixture of UA and OA were administered to the animals by gavage, followed by the intraperitoneal injection of DXR. The results showed a significant reduction in micronucleus frequency in the groups concomitantly treated with the triterpenoid compounds and DXR compared to that treated with DXR alone. The present results demonstrate the antimutagenic activity of UA and OA under the experimental conditions used in this study. 相似文献