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.
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 KnockoutRESUMO
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.
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/patogenicidadeRESUMO
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 TandemRESUMO
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 VeroRESUMO
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/complicaçõesRESUMO
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 VeroRESUMO
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 & purificaçãoRESUMO
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.