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1.
J Basic Microbiol ; 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38064123

RESUMO

Under adverse environmental conditions, microorganisms are able to enter a state of cellular dormancy which consists of cell cycle arrest and interruption of multiplication. This process ensures their perpetuation in the infected host organism and enables the spread of disease. Throughout biological evolution, dormancy allowed microorganisms to persist in a harsh niche until favorable conditions for their reactivation were re-established. Here, we propose to discuss the dormancy of bacteria and protozoa pathogens focusing on the potential mechanisms and components associated with dormancy.

2.
Glycobiology ; 31(10): 1378-1389, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34192330

RESUMO

Leishmania (L.) amazonensis is one of the species responsible for the development of cutaneous leishmaniasis in South America. After entering the vertebrate host, L. (L.) amazonensis invades mainly neutrophils, macrophages and dendritic cells. Studies have shown that gal-3 acts as a pattern recognition receptor. However, the role of this protein in the context of L. (L.) amazonensis infection remains unclear. Here, we investigated the impact of gal-3 expression on experimental infection by L. (L.) amazonensis. Our data showed that gal-3 plays a role in controlling parasite invasion, replication and the formation of endocytic vesicles. Moreover, mice with gal-3 deficiency showed an exacerbated inflammatory response. Taken together, our data shed light to a critical role of gal-3 in the host response to infection by L. (L.) amazonensis.


Assuntos
Galectina 3/metabolismo , Leishmania/metabolismo , Leishmaniose Cutânea/metabolismo , Animais , Feminino , Galectina 3/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
3.
Microb Pathog ; 135: 103618, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310832

RESUMO

P21 is a protein secreted by Trypanosoma cruzi (T. cruzi). Previous studies have shown a spectrum of biological activities performed by P21 such as induction of phagocytosis, leukocyte chemotaxis and inhibition of angiogenesis. However, the activity of P21 in T. cruzi infection remains unknown. Here, we reported the role of P21 in mice harboring late T. cruzi infection. Treatment with recombinant P21 protein (rP21) reduced parasite load and angiogenesis, and induced fibrosis in the cardiac tissue of infected mice. In addition, rP21 reduced the growth of epimastigotes, inhibited intracellular replication of amastigotes and modulated the parasite cell cycle. Our data suggest that P21 controls parasite replication in the host, supporting the survival of both parasite and host.


Assuntos
Doença de Chagas/imunologia , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/fisiologia , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Ciclo Celular , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Modelos Animais de Doenças , Fibrose , Coração , Interações Hospedeiro-Parasita , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Proteínas de Protozoários/genética , Proteínas Recombinantes , Trypanosoma cruzi/genética , Trypanosoma cruzi/patogenicidade
4.
ScientificWorldJournal ; 2019: 9423658, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30853865

RESUMO

The species Inga laurina is native to the Brazilian Cerrado. There are no studies about the chemical composition and biological activities of extracts of this endangered species. The ethanolic extract and its successive fractions are rich in phenolic compounds and presented good antifungal activities. HPLC/MS-MS/MS and H1/C13 analysis led to the identification of seventeen compounds, most of which are gallic acid derivatives, myricetin and quercetin glycosides. The ethyl acetate fraction (EAF) contained high levels of total phenolics, expressed in milligrams of gallic acid equivalents per gram of extract (475.3 ± 1.9 mg GAE gextract -1) and flavonoids expressed in milligrams of quercetin equivalents per gram of extract (359.3 ± 10.6 mg QE gextract -1). This fraction was active against fungi of the Candida genus. The EAF showed MIC value 11.7 µg mL-1 against C. glabrata and a selectivity index of 1.6 against Vero cells. The flavonol glycoside myricetin-3-O-rhamnoside was isolated for the first time from the Inga laurina. These results make I. laurina a promising plant as a source of pharmaceutical and biological active antifungal compounds.


Assuntos
Antifúngicos/farmacologia , Citotoxinas/farmacologia , Fabaceae/química , Extratos Vegetais/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Citotoxinas/química , Citotoxinas/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Proantocianidinas/química , Proantocianidinas/isolamento & purificação , Espectrometria de Massas em Tandem
5.
Prostate ; 78(10): 731-742, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29635803

RESUMO

BACKGROUND: A potential association between obesity and prostate cancer has been proposed. Metformin, an antidiabetes drug, has antiproliferative effects being proposed for cancer treatment. However, under intense proliferative stimulation conditions such as those found in obesity, its efficacy is still uncertain. Thus, we analyzed the effects of saturated fatty acid and/or insulin under high concentrations, with or without metformin, on the proliferation and migration of prostate cells. METHODS: Human prostate epithelial cell lines non-tumor (PNT1A) and tumor (PC3) were treated with control media (DMEM, C), palmitate (100 µM, HF), and/or insulin (50 µU, HI) with or without metformin (100 µM) for 24 or 48 h. RESULTS: Both PNT1A and PC3 cells had greater proliferation when treated with HF, while HI treatment stimulated only PNT1A. Metformin inhibited cell proliferation caused by HF in both cell lines, but it did not block the proliferative action of HI in PNT1A cells. PNT1A increased cell migration after all treatments, while only HF influenced PC3; metformin inhibited the migration stimulated by all obese microenvironments. Both HF and HI treatments in PNT1A and HF treatment in PC3 augmented vimentin expression, resulting in a higher epithelial-mesenchymal transition (which, in turn, could influence cell migration). Metformin inhibited vimentin expression in both normal and tumor cells. Although HF treatment had increased AMPK activation, it also increased the levels of activated ERK1/2, which could be responsible for high cell proliferation in both cell lines. In contrast, HI decreased AMPK activation in both cell lines, whereas it increased ERK1/2 levels in PNT1A and decreased them in PC3 (reflecting greater cell proliferation only in non-tumor cells). Metformin maintained high activation of AMPK and decreased ERK1/2 levels after HF in both cell lines and only after HI in PNT1A, which was able to decrease the cell proliferation triggered by these treatments. CONCLUSIONS: Higher concentrations of palmitate on PC3 cells and palmitate and insulin on PNT1A cells stimulate cellular activities that could favor cancer progression. Metformin inhibited most of these stimuli, showing the efficacy of this drug for cancer adjuvant therapy in obese patients (a group at increased risk for the development of prostrate cancer).


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Insulina/farmacologia , Metformina/farmacologia , Ácido Palmítico/farmacologia , Próstata/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Obesidade/complicações
6.
Molecules ; 19(4): 4560-77, 2014 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-24731985

RESUMO

The seasonal chemical composition of essential oils from Inga laurina was determined by GC/MS. In the stem bark's essential oil extracted during the dry season, the presence of terpenoids (30.05%) stood out, and phytol (9.76%) was the major compound identified. For the stem bark oil obtained during the rainy season, in addition to terpenoids (26.63%), a large amount of fatty acids (46.84%) were identified, in particular palmitic acid (25.40%). Regarding the leaves' essential oil obtained in the dry season, esters (42.35%) were the main components. The main ester present was (Z)-hex-3-enyl benzoate (10.15%) and the major compound of this oil was (Z)-hex-3-en-1-ol (14.23%). Terpenoids (33.84%), long-chain alkanes (27.04%) and fatty acids (21.72%) were the main components of the essential oil from leaves in the rainy season. Phytol (33.21%), nonacosane (21.95%) and palmitic acid (15.20%) were the major compounds identified. The antimicrobial activity against aerobic and anaerobic oral bacteria was evaluated by the microdilution broth method and cytotoxic activity was carried out with Vero cells. The essential oils from the rainy season showed a better inhibition of the bacterial growth with Minimal Inhibitory Concentrations (MIC) values of 25 or 50 µg·mL⁻¹ for aerobic bacteria, and high selectivity against bacteria was observed. The large amount of fatty acids in rainy season oils may be related to the better inhibitory effects observed.


Assuntos
Anti-Infecciosos/química , Citotoxinas/química , Fabaceae/química , Óleos Voláteis/química , Óleos de Plantas/química , Animais , Anti-Infecciosos/farmacologia , Bactérias Aeróbias/efeitos dos fármacos , Bactérias Aeróbias/crescimento & desenvolvimento , Bactérias Anaeróbias/efeitos dos fármacos , Bactérias Anaeróbias/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Citotoxinas/farmacologia , Ésteres , Ácidos Graxos/classificação , Ácidos Graxos/isolamento & purificação , Óleos Voláteis/farmacologia , Especificidade de Órgãos , Casca de Planta/química , Folhas de Planta/química , Óleos de Plantas/farmacologia , Estações do Ano , Terpenos/classificação , Terpenos/isolamento & purificação , Células Vero
7.
Molecules ; 18(4): 4588-98, 2013 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-23599016

RESUMO

The chemical composition of the essential oils from leaves, bark and wood of Cassia bakeriana Craib. was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Alcohols, aldehydes and fatty acids were the major components in leaf and bark oil, while wood essential oil was rich in fatty acids. Terpenes such as linalool, (E)-nerolidol and phytol were present in low concentrations. The antimicrobial activity against aerobic and anaerobic oral bacteria was evaluated using the microdilution method, as was the cell viability test carried out with Vero cells. The oils from leaves and bark showed high antimicrobial activity, with minimum inhibitory concentrations between 62.5 and 125 µg·mL⁻¹ for most of the tested bacteria, including Streptococcus mutans, the main etiological agent of dental caries. Leaves oil displayed the lowest cytotoxic effect (EC50 of 153 µg·mL⁻¹), while wood oil exhibited the highest toxicity to Vero cells. C. bakeriana oils are thus a source of biologically active compounds against aerobic and anaerobic oral microorganisms. This study is the first report on the chemical composition, antimicrobial activity and cytotoxicity of C. bakeriana.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias Aeróbias/efeitos dos fármacos , Bactérias Anaeróbias/efeitos dos fármacos , Cassia/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Animais , Anti-Infecciosos/toxicidade , Proliferação de Células/efeitos dos fármacos , Chlorocebus aethiops , Cárie Dentária/microbiologia , Testes de Sensibilidade Microbiana , Óleos Voláteis/toxicidade , Streptococcus mutans/efeitos dos fármacos , Células Vero
8.
ACS Omega ; 5(3): 1363-1370, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32010806

RESUMO

Scheelea phalerata Mart. ex Spreng (Arecaceae) is a palm tree found in the Brazilian cerrado. There are no topics related to volatile oils from S. phalerata leaves in the literature. This work determines its chemical composition and evaluates the biological activity under two different seasonal conditions (dry and rainy seasons). The dry essential oil yield was 0.034 ± 0.001% and the rainy essential oil yield was 0.011 ± 0.003%. Both essential oils presented different qualitative and quantitative compositions (99.4 and 98.5%). The main constituents of the dry essential oil were phytol (36.7%), nonadecane (9.7%), linolenic acid (9.1%), (Z)-hex-3-en-1-ol (4.2%), and squalene (4.0%). The main constituents of the rainy essential oil were phytol (26.1%), palmitic acid (18.7%), hexan-1-ol (15.6%), (Z)-hex-3-en-1-ol (9.7%), and oleic acid (4.0%). The antileishmanial activity against promastigotes of Leishmania amazonensis was observed only for the rainy season essential oil (IC50 value of 165.05 ± 33.26 µg mL-1). A molecular docking study showed that alcohols exert a paramount efficacy and that the action of some essential oil compounds may be similar to that of amphotericin B. Still, only the essential oil from the dry season showed moderate antibacterial activity against S. sanguinis (MICs 200-400 µg mL-1). The cytotoxicity against Vero cells was identical (>512) for both essential oils. The novel data here for both chemical characterization and biological activity, in particular, evidence that the action of these compounds is similar to that of amphotericin B, provide valuable information to the drug-discovery field.

9.
Mol Biochem Parasitol ; 165(1): 19-31, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19393159

RESUMO

Surface adhesion proteins are essential for Trypanosoma cruzi invasion of mammalian cells. Here we show that Dispersed Gene Family-1 (DGF-1) members, previously identified as nuclear repeated sequences present in several chromosomes and comprising the third largest T. cruzi specific gene family, have conserved adhesin motifs including four segments with significant similarity to human beta 7 integrin. Flow cytometry and biotinylation assays with anti-DGF-1 antibodies indicated that, as expected, DGF-1 members are expressed on the trypomastigote surface. The DGF-1 genealogy, inferred using T. cruzi Genome Project data and network phylogeny algorithms, suggests that this gene family is separated in at least three groups with differential distribution of functional domains. To identify which members of this gene family are expressed we used a combined approach of RT-PCR and codon usage profiles, showing that expressed members have a very biased codon usage favoring GC, whereas non-expressed members have a homogeneous distribution. Shannon information entropy was used to measure sequence variability and revealed four major high entropy segments in the extracellular domain of DGF-1 overlapping with important putative functional modules of the predicted proteins. Testing for natural selection, however, indicated that these high entropy segments were not under positive selection, which contradicts the notion that positive selection is the cause of high variability in specific domains of a protein relative to other less variable regions in the same molecule. We conjectured that members of the DGF-1 family might be associated with the ability of T. cruzi to bind extracellular matrix proteins, such as fibronectin and laminin, and speculated on mechanisms that would be generating the localized diversity in these molecules in the absence of selection.


Assuntos
Genes de Protozoários/genética , Trypanosoma cruzi/genética , Trypanosoma cruzi/metabolismo , Sequência de Aminoácidos , Animais , Códon/genética , Ordem dos Genes , Variação Genética , Humanos , Cadeias beta de Integrinas/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Dados de Sequência Molecular , Filogenia , Proteínas de Protozoários/química , Seleção Genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Trypanosoma cruzi/classificação
10.
Subcell Biochem ; 47: 101-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18512345

RESUMO

Trypanosoma cruzi is the protozoan parasite that causes Chagas' disease, a highly prevalent vector-borne disease in Latin America. Chagas' disease is a major public health problem in endemic regions with an estimated 18 million people are infected with T. cruzi and another 100 million at risk (http://www.who.int/ctd/chagas/disease.htm). During its life cycle, T. cruzi alternates between triatomine insect vectors and mammalian hosts. While feeding on host's blood, infected triatomines release in their feces highly motile and infective metacyclic trypomastigotes that may initiate infection. Metacyclic trypomastigotes promptly invade host cells (including gastric mucosa) and once free in the cytoplasm, differentiate into amastigotes that replicate by binary fission. Just before disruption of the parasite-laden cell, amastigotes differentiate back into trypomastigotes which are then released into the tissue spaces and access the circulation. Circulating trypomastigotes that disseminate the infection in the mammalian host may be taken up by feeding triatomines and may also transform, extracellularly, into amastigote-like forms. Unlike their intracellular counterparts, these amastigote-like forms, henceforth called amastigotes, are capable of infecting host cells. Studies in which the mechanisms of amastigote invasion of host cells have been compared to metacyclic trypomastigote entry have revealed interesting differences regarding the involvement of the target cell actin microfilament system.


Assuntos
Actinas/metabolismo , Estágios do Ciclo de Vida/fisiologia , Trypanosoma cruzi/fisiologia , Citoesqueleto de Actina/fisiologia , Citoesqueleto de Actina/ultraestrutura , Animais , Chlorocebus aethiops , Células HeLa , Interações Hospedeiro-Parasita , Humanos , Trypanosoma cruzi/ultraestrutura , Células Vero
11.
J Pharm Pharmacol ; 70(11): 1541-1552, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30136729

RESUMO

OBJECTIVES: This work aimed to evaluate the antifungal and cytotoxic activity of the EtOH extract and fractions of Banisteriopsis argyrophylla leaves, and to perform the identification of these bioactive metabolites. METHODS: The EtOAc fraction (EAF) obtained from the ethanolic extract of B. argyrophylla leaves showed better antifungal potential against Candida spp. In this fraction, ten flavonoids have been identified by UHPLC-ESI-MSn . Then, EAF was submitted to column chromatography to give four new fractions (A1-A4). The cytotoxicity was determined against Vero cells. KEY FINDINGS: The EAF showed better antifungal potential against Candida spp. with minimum inhibitory concentrations (MICs) between 31.25 and 93.75 µg/ml. The (-)-catechin (fraction A1) showed a MIC of 2.83 µg/ml against Candida glabrata. Fractions A2, A3 and A4 were rich in quercetins and kaempferols and showed good inhibitory concentrations (5.86-46.87 µg/ml) against C. albicans, C. glabrata and C. tropicalis. CONCLUSIONS: The EtOH extract, fractions and the isolated (-)-catechin showed lower toxicity to Vero cells than cisplatin, used as a positive control. Thus, the leaves of B. argyrophylla are a promising source of antifungal agents.


Assuntos
Antifúngicos/farmacologia , Banisteriopsis , Candida/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta , Animais , Antifúngicos/isolamento & purificação , Antifúngicos/toxicidade , Banisteriopsis/química , Candida/classificação , Candida/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta/química , Células Vero
12.
Sci Rep ; 7(1): 7077, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28765552

RESUMO

Phospholipases A2 (PLA2s) overexpression is closely associated with the malignant potential of breast cancers. Here, we showed for the first the antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 cell. Firstly, γCdcPLI was more cytotoxic to MDA-MB-231 breast cancer cells than other cell lines (MCF-7, HeLa, PC3 and A549) and did not affect the viability of non-tumorigenic breast cell (MCF 10A). In addition, γCdcPLI induced modulation of important mediators of apoptosis pathways such as p53, MAPK-ERK, BIRC5 and MDM2. γCdcPLI decreased MDA-MB-231 adhesion, migration and invasion. Interestingly, the γCdcPLI also inhibited the adhesion and migration of endothelial cells and blocked angiogenesis by inhibiting tube formation by HUVECs in vitro and sprouting elongation on aortic ring assay ex vivo. Furthermore, γCdcPLI reduced the production of vascular endothelial growth factor (VEGF). γCdcPLI was also able to decrease PGE2 levels in MDA-MB-231 and inhibited gene and protein expression of the PI3K/Akt pathway. In conclusion, γCdcPLI showed in vitro antitumoral, antimestatatic and anti-angiogenic potential effects and could be an attractive approach for futures studies in cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama , Lipoproteínas/farmacologia , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Inibidores de Fosfolipase A2/farmacologia , Antineoplásicos/isolamento & purificação , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Venenos de Crotalídeos/química , Células Endoteliais/efeitos dos fármacos , Humanos , Lipoproteínas/isolamento & purificação , Modelos Biológicos , Neovascularização Patológica , Inibidores de Fosfolipase A2/isolamento & purificação
13.
Artigo em Inglês | MEDLINE | ID: mdl-29164071

RESUMO

Trypanosoma cruzi interacts with host cells, including cardiomyocytes, and induces the production of cytokines, chemokines, metalloproteinases, and glycan-binding proteins. Among the glycan-binding proteins is Galectin-3 (Gal-3), which is upregulated after T. cruzi infection. Gal-3 is a member of the lectin family with affinity for ß-galactose containing molecules; it can be found in both the nucleus and the cytoplasm and can be either membrane-associated or secreted. This lectin is involved in several immunoregulatory and parasite infection process. Here, we explored the consequences of Gal-3 deficiency during acute and chronic T. cruzi experimental infection. Our results demonstrated that lack of Gal-3 enhanced in vitro replication of intracellular parasites, increased in vivo systemic parasitaemia, and reduced leukocyte recruitment. Moreover, we observed decreased secretion of pro-inflammatory cytokines in spleen and heart of infected Gal-3 knockout mice. Lack of Gal-3 also led to elevated mast cell recruitment and fibrosis of heart tissue. In conclusion, galectin-3 expression plays a pivotal role in controlling T. cruzi infection, preventing heart damage and fibrosis.


Assuntos
Doença de Chagas/imunologia , Doença de Chagas/patologia , Galectina 3/imunologia , Galectina 3/metabolismo , Imunidade Inata/imunologia , Trypanosoma cruzi/imunologia , Animais , Sobrevivência Celular , Doença de Chagas/parasitologia , Chlorocebus aethiops , Colágeno/análise , Citocinas/metabolismo , Modelos Animais de Doenças , Fibrose/imunologia , Fibrose/prevenção & controle , Galactosídeos , Galectina 3/genética , Coração , Interações Hospedeiro-Parasita , Macrófagos Peritoneais/parasitologia , Masculino , Mastócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Parasitemia , Baço/imunologia , Trypanosoma cruzi/patogenicidade , Células Vero
14.
Artigo em Inglês | MEDLINE | ID: mdl-27921011

RESUMO

Cell invasion by the intracellular protozoans requires interaction of proteins from both the host and the parasite. Many parasites establish chronic infections, showing they have the potential to escape the immune system; for example, Trypanosoma cruzi is an intracellular parasite that causes Chagas disease. Parasite internalization into host cell requires secreted and surface molecules, such as microvesicles. The release of microvesicles and other vesicles, such as exosomes, by different eukaryotic organisms was first observed in the late twentieth century. The characterization and function of these vesicles have recently been the focus of several investigations. In this review, we discuss the release of microvesicles by T. cruzi. The molecular content of these vesicles is composed of several molecules that take place during parasite-host cell interaction and contribute to the parasite-driven mechanism of evasion from the host immune system. These new findings appear to have a profound impact on the comprehension of T. cruzi biology and highlight novel potential strategies for developing more efficient therapeutic approaches.


Assuntos
Endocitose , Interações Hospedeiro-Parasita , Vesículas Secretórias/metabolismo , Trypanosoma cruzi/fisiologia , Fatores de Virulência/metabolismo , Trypanosoma cruzi/metabolismo
15.
Infect Dis Poverty ; 5: 29, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-27025459

RESUMO

BACKGROUND: Leishmaniasis causes alterations and lesions in the genital system, which leads to azoospermia and testicular atrophy in animals during the chronic phase of the infection. The aim of this study was to reveal the kinetics of Leishmania chagasi infection in the genital system of male golden hamsters (Mesocricetus auratus). METHODS: Animals were intraperitoneally inoculated with amastigotes from L. chagasi. At different time points animals were euthanized and genital organs processed for histo-pathological, qPCR, cytokines and testosterone detection assays. RESULTS: Our results showed a high parasite load in testis, followed by an increase of pro-inflammatory cytokines IL1-ß, TNF-α and IFN-γ, and testosterone. Subsequently, IL-4 expression was upregulated and basal parasite persistence in testis was observed using the experimental approach. CONCLUSION: Extracellular amastigotes migrated to the epididymis posing as a potential major factor of parasite persistence and venereal transmission of L. chagasi infection in hamsters.


Assuntos
Genitália Masculina/parasitologia , Leishmania/fisiologia , Leishmaniose Visceral/parasitologia , Animais , Cricetinae , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Genitália Masculina/patologia , Humanos , Cinética , Leishmania/química , Leishmania/genética , Leishmania/crescimento & desenvolvimento , Leishmaniose Visceral/genética , Leishmaniose Visceral/metabolismo , Leishmaniose Visceral/patologia , Masculino , Mesocricetus
16.
Acta Trop ; 157: 42-53, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26827742

RESUMO

Trypanosoma cruzi has high biological and biochemical diversity and variable tissue tropism. Here we aimed to verify the kinetics of cytokine and chemokine in situ secretion in animals infected with two distinct T. cruzi strains after oral inoculation. Also, we investigated parasite migration, residence and pathological damage in stomach, heart and spleen. Our results showed that host immune response against T. cruzi infection is an intricate phenomenon that depends on the parasite strain, on the infected organ and on the time point of the infection. We believe that a wide comprehension of host immune response will potentially provide basis for the development of immunotherapeutic strategies in order to clear parasitism and minimize tissue injury. In this context, we find that KC poses as a possible tool to be used.


Assuntos
Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Quimiocinas/metabolismo , Citocinas/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Trypanosoma cruzi/imunologia , Animais , Doença de Chagas/veterinária , Feminino , Coração/parasitologia , Camundongos , RNA Mensageiro/metabolismo , Baço/parasitologia , Estômago/parasitologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-25960759

RESUMO

Many essential oils (EOs) of different plant species possess interesting antimicrobial effects on buccal microorganisms and cytotoxic properties. EOs of Kielmeyera coriacea Mart. & Zucc. were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). The EO from leaves is rich in sesquiterpenes hydrocarbons and oxygenated sesquiterpenes. The three major compounds identified were germacrene-D (24.2%), (E)-caryophyllene (15.5%), and bicyclogermacrene (11.6%). The inner bark EO is composed mainly of sesquiterpenes hydrocarbons and the major components are alpha-copaene (14.9%) and alpha-(E)-bergamotene (13.0%). The outer bark EO is composed mainly of oxygenated sesquiterpenes and long-chain alkanes, and the major components are alpha-eudesmol (4.2%) and nonacosane (5.8%). The wood EO is mainly composed of long-chain alkanes and fatty acids, and the major components are nonacosane (9.7%) and palmitic acid (16.2%). The inner bark EO showed the strongest antimicrobial activity against the anaerobic bacteria Prevotella nigrescens (minimum inhibitory concentration-MIC of 50 µg mL(-1)). The outer bark and wood EOs showed MICs of 100 µg mL(-1) for all aerobic microorganisms tested. The EOs presented low toxicity to Vero cells. These results suggest that K. coriacea, a Brazilian plant, provide initial evidence of a new and alternative source of substances with medicinal interest.

18.
Artigo em Inglês | MEDLINE | ID: mdl-24918088

RESUMO

Enolase is secreted by Candida albicans and is present in its biofilms although its extracellular function is unknown. Here we show that extracellular enolase mediates the colonization of small intestine mucosa by C. albicans. Assays using intestinal mucosa disks show that C. albicans adhesion is inhibited, in a dose dependent mode, either by pretreatment of intestinal epithelium mucosa disks with recombinant C. albicans enolase (70% at 0.5 mg/ml enolase) or by pretreatment of C. albicans yeasts with anti-enolase antibodies (48% with 20 µg antiserum). Also using flow cytometry, immunoblots of conditioned media and confocal microscopy we demonstrate that enolase is present in biofilms and that the extracellular enolase is not an artifact due to cell lysis, but must represent functional secretion of a stable form. This is the first direct evidence that C. albicans' extracellular enolase mediates colonization on its primary translocation site. Also, because enolase is encoded by a single locus in C. albicans, its dual role peptide, as glycolytic enzyme and extracellular peptide, is a remarkable example of gene sharing in fungi.


Assuntos
Candida albicans/enzimologia , Candida albicans/fisiologia , Mucosa Intestinal/microbiologia , Fosfopiruvato Hidratase/metabolismo , Animais , Adesão Celular , Meios de Cultivo Condicionados , Citometria de Fluxo , Immunoblotting , Masculino , Camundongos Endogâmicos BALB C , Microscopia Confocal
19.
Sci. Rep. ; 7(7077)2017.
Artigo em Inglês | SES-SP, SES SP - Instituto Butantan, SES-SP | ID: but-ib15099

RESUMO

Phospholipases A(2) (PLA(2)s) overexpression is closely associated with the malignant potential of breast cancers. Here, we showed for the first the antitumoral effects of gamma CdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 cell. Firstly, gamma CdcPLI was more cytotoxic to MDA-MB-231 breast cancer cells than other cell lines ( MCF-7, HeLa, PC3 and A549) and did not affect the viability of non-tumorigenic breast cell (MCF 10A). In addition, gamma CdcPLI induced modulation of important mediators of apoptosis pathways such as p53, MAPK-ERK, BIRC5 and MDM2.gamma CdcPLI decreased MDA-MB-231 adhesion, migration and invasion. Interestingly, the gamma CdcPLI also inhibited the adhesion and migration of endothelial cells and blocked angiogenesis by inhibiting tube formation by HUVECs in vitro and sprouting elongation on aortic ring assay ex vivo. Furthermore,gamma CdcPLI reduced the production of vascular endothelial growth factor (VEGF).gamma CdcPLI was also able to decrease PGE2 levels in MDA-MB-231 and inhibited gene and protein expression of the PI3K/Akt pathway. In conclusion,gamma CdcPLI showed in vitro antitumoral, antimestatatic and anti-angiogenic potential effects and could be an attractive approach for futures studies in cancer therapy.

20.
PLoS One ; 7(12): e51384, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23251513

RESUMO

BACKGROUND: P21 is a secreted protein expressed in all developmental stages of Trypanosoma cruzi. The aim of this study was to determine the effect of the recombinant protein based on P21 (P21-His(6)) on inflammatory macrophages during phagocytosis. FINDINGS: Our results showed that P21-His(6) acts as a phagocytosis inducer by binding to CXCR4 chemokine receptor and activating actin polymerization in a way dependent onthe PI3-kinase signaling pathway. CONCLUSIONS: Thus, our results shed light on the notion that native P21 is a component related to T. cruzi evasion from the immune response and that CXCR4 may be involved in phagocytosis. P21-His(6) represents an important experimental control tool to study phagocytosis signaling pathways of different intracellular parasites and particles.


Assuntos
Fagocitose , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Receptores CXCR4/metabolismo , Proteínas Recombinantes/metabolismo
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