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1.
J Hazard Mater ; 448: 130813, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36706487

RESUMO

This review gathered and analyzed data about (i) the Cd-induced impacts on seed germination and seedling vigor, and (ii) the use of different priming agents to mitigate Cd-induced impacts on the early plant development. Critical evaluation of the obtained data revealed intriguing results. First, seeds of diverse species can endure exposures to Cd. Such endurance is exhibited as maintenance of or even improvement in the seed germination and vigor (up to 15% and 70%, respectively). Second, the main factors influencing seed tolerance to Cd toxicity are related to temporal variations in anatomical, physiological, and/or biochemical features. Third, Cd can trigger diverse transgenerational effects on plants by shaping seed endophytes, by modulating seed provisioning with resources and regulatory elements, and/or by altering seed (epi)genomics. Fourth, different chemical, biological and physical priming agents can mitigate Cd-induced impacts on seeds, sometimes enhancing their performance over the control (reference) values. Overall, this review shows that the impacts of Cd on seed germination and vigor encompass not only negative outcomes but also neutral and positive ones, depending upon the Cd dose, media properties, plant species and genotypes, plant developmental stage and organ, and management approaches. Increasing our understanding of plant tolerance mechanisms against the growing background Cd pollution is relevant to support breeding programs, agricultural practices, and health-environmental policies.


Assuntos
Germinação , Plântula , Cádmio/toxicidade , Sementes
2.
Environ Sci Technol ; 56(17): 11991-12002, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35968681

RESUMO

A widespread increase in intense phytoplankton blooms has been noted in lakes worldwide since the 1980s, with the summertime peak intensity amplifying in most lakes. Such blooms cause annual economic losses of multibillion USD and present a major challenge, affecting 11 out of the 17 United Nations Sustainable Development Goals. Here, we evaluate recent scientific evidence for hormetic effects of emerging contaminants and regulated pollutants on Microcystis sp., the most notorious cyanobacteria forming harmful algal blooms and releasing phycotoxins in eutrophic freshwater systems. This new evidence leads to the conclusion that pollution is linked to algal bloom intensification. Concentrations of contaminants that are considerably smaller than the threshold for toxicity enhance the formation of harmful colonies, increase the production of phycotoxins and their release into the environment, and lower the efficacy of algaecides to control algal blooms. The low-dose enhancement of microcystins is attributed to the up-regulation of a protein controlling microcystin release (McyH) and various microcystin synthetases in tandem with the global nitrogen regulator Ycf28, nonribosomal peptide synthetases, and several ATP-binding cassette transport proteins. Given that colony formation and phycotoxin production and release are enhanced by contaminant concentrations smaller than the toxicological threshold and are widely occurring in the environment, the effect of contaminants on harmful algal blooms is more prevalent than previously thought. Climate change and nutrient enrichment, known mechanisms underpinning algal blooms, are thus joined by low-level pollutants as another causal mechanism.


Assuntos
Cianobactérias , Poluentes Ambientais , Microcystis , Cianobactérias/metabolismo , Poluentes Ambientais/metabolismo , Proliferação Nociva de Algas , Lagos/microbiologia , Microcistinas/metabolismo , Microcystis/metabolismo
3.
Oncoimmunology ; 9(1): 1846915, 2020 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-33344042

RESUMO

Immune checkpoint blockade (ICB) has demonstrated an impressive outcome in patients with metastatic melanoma, yet, durable complete response; even with Ipilimumab/Nivolumab combo are under 30%. Primary and acquired resistance in response to ICB is commonly due to a tumor immune escape mechanism dictated by the tumor microenvironment (TME). Macrophage Migratory Inhibition Factor (MIF) has emerged as an immunosuppressive factor secreted in the TME. We have previously demonstrated that blockade of the MIF-CD74 signaling on macrophages and dendritic cells restored the anti-tumor immune response against melanoma. Here, we report that inhibition of the MIF-CD74 axis combined with ipilimumab could render resistant melanoma to better respond to anti-CTLA-4 treatment. We provide evidence that blocking the MIF-CD74 signaling potentiates CD8+ T-cells infiltration and drives pro-inflammatory M1 conversion of macrophages in the TME. Furthermore, MIF inhibition resulted in reprogramming the metabolic pathway by reducing lactate production, HIF-1α and PD-L1 expression in the resistant melanoma cells. Melanoma patient data extracted from the TCGA database supports the hypothesis that high MIF expression strongly correlates with poor response to ICB therapy. Our findings provide a rationale for combining anti-CTLA-4 with MIF inhibitors as a potential strategy to overcome resistance to ICB therapy in melanoma, turning a "cold" tumor into a "hot" one mediated by the activation of innate immunity and reprogramming of tumor metabolism and reduced PD-L1 expression in melanoma cells.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Melanoma , Humanos , Inibidores de Checkpoint Imunológico , Oxirredutases Intramoleculares/uso terapêutico , Ipilimumab/uso terapêutico , Fatores Inibidores da Migração de Macrófagos/uso terapêutico , Melanoma/tratamento farmacológico , Microambiente Tumoral
4.
An Acad Bras Cienc ; 92(suppl 1): e20180484, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32756834

RESUMO

The objective of this study was to investigate and characterize cowpea (Vigna unguiculata) genotypes for total grain protein content, storage protein fractions (globulin, albumin, prolamin, basic and acid glutelins), and phytate and minerals contents. Eighteen cowpea genotypes were selected. Total grain protein content varied from 21.4% to 29.2%, for BRS Marataoã and Paulistinha genotypes, respectively. The variation in the concentration of each protein fraction was significant (P<0.05) only for glutelins (basic and acid). The genotypes studied exhibited great similarity in the PAGE electrophoretic profile of the grain protein fractions and also in the mineral content. BRS Paraguaçu genotype exhibited higher Zn content than thegenotypes that have been previously recommended for this characteristic. The lowest phytate grain content was observed in four of the 18 genotypes studied, which also exhibited high protein contents. Although the results did not converge to the selection of a few genotypes, some specific differences were detected that which may be further explored. Considering total grain protein, mineral and phytate contents, the genotype Paulistinha revealed a better balance unveiling high grain total protein content, low grain phytate content and more homogeneous mineral composition.


Assuntos
Vigna , Grão Comestível , Genótipo , Minerais , Ácido Fítico , Vigna/genética
5.
Bioorg Med Chem Lett ; 30(16): 127349, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32631547

RESUMO

Dehydrodieugenol B and five related natural neolignans were isolated from the Brazilian plant species Nectandra leucantha. Three of these compounds were shown to be active against murine (B16F10) and human (A2058) melanoma cells but non-toxic to human fibroblasts (T75). These results stimulated the preparation of a series of 23 semi-synthetic derivatives in order to explore structure-activity relationships and study the biological potential of these derivatives against B16F10 and A2058 cell lines. These structurally-related neolignan derivatives were analyzed by multivariate statistics and machine learning, which indicated that the most important characteristics were related to their three-dimensional structure and, mainly, to the substituents on the neolignan skeleton. The results suggested that the presence of hydroxyl or alkoxyl groups at positions 3, 4 and 5 (with appropriate sidechains) promoted an increase in electropological and charge density, which seem to be important for biological activity against murine (B16F10) and human (A2058) melanoma cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Desenho de Fármacos , Lignanas/farmacologia , Animais , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lignanas/síntese química , Lignanas/química , Aprendizado de Máquina , Camundongos , Estrutura Molecular , Análise Multivariada , Relação Estrutura-Atividade
6.
J Pathol ; 250(4): 420-439, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31960425

RESUMO

Immunotherapy using immune checkpoint inhibitors (ICIs) induces durable responses in many metastatic cancers. Metastatic uveal melanoma (mUM), typically occurring in the liver, is one of the most refractory tumours to ICIs and has dismal outcomes. Monosomy 3 (M3), polysomy 8q, and BAP1 loss in primary uveal melanoma (pUM) are associated with poor prognoses. The presence of tumour-infiltrating lymphocytes (TILs) within pUM and surrounding mUM - and some evidence of clinical responses to adoptive TIL transfer - strongly suggests that UMs are indeed immunogenic despite their low mutational burden. The mechanisms that suppress TILs in pUM and mUM are unknown. We show that BAP1 loss is correlated with upregulation of several genes associated with suppressive immune responses, some of which build an immune suppressive axis, including HLA-DR, CD38, and CD74. Further, single-cell analysis of pUM by mass cytometry confirmed the expression of these and other markers revealing important functions of infiltrating immune cells in UM, most being regulatory CD8+ T lymphocytes and tumour-associated macrophages (TAMs). Transcriptomic analysis of hepatic mUM revealed similar immune profiles to pUM with BAP1 loss, including the expression of IDO1. At the protein level, we observed TAMs and TILs entrapped within peritumoural fibrotic areas surrounding mUM, with increased expression of IDO1, PD-L1, and ß-catenin (CTNNB1), suggesting tumour-driven immune exclusion and hence the immunotherapy resistance. These findings aid the understanding of how the immune response is organised in BAP1 - mUM, which will further enable functional validation of detected biomarkers and the development of focused immunotherapeutic approaches. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Assuntos
Melanoma/metabolismo , Mutação/genética , Microambiente Tumoral , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Neoplasias Uveais/metabolismo , Biomarcadores Tumorais/genética , Humanos , Fatores Imunológicos , Imunossupressores , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/metabolismo , Melanoma/genética , Linfócitos T/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo , Neoplasias Uveais/genética
7.
J Hazard Mater ; 384: 121434, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31812481

RESUMO

Tolerance level to cadmium (Cd) toxicity is generally associated with reductions of the internal Cd accumulation in living organisms. In plants, Cd exposure frequently triggers negative effects on their growth and productivity. However, an increased number of studies has reported the improved performance of some plant species (or their accessions/genotypes/varieties/cultivars/clones) to Cd exposure, despite Cd accumulation in their roots and shoots. These results indicate that plants have developed protective strategies to neutralize the side-effects from Cd toxicity or, more controversially, mechanisms that employ Cd as beneficial element. Here, we gathered information about Cd-induced hormetic effects on plants, and explored the potential mechanisms that allow them to have a better performance under Cd exposure. The promotion of plant development depends on both direct and indirect Cd-induced alterations in the metabolism of plants and their surround environment. In addition, the mechanisms behind the positive Cd-induced transgenerational effects were also discussed in the present paper.


Assuntos
Cádmio/farmacologia , Hormese , Magnoliopsida/efeitos dos fármacos , Cádmio/toxicidade , Hormese/efeitos dos fármacos , Magnoliopsida/crescimento & desenvolvimento , Magnoliopsida/metabolismo
8.
Braz J Microbiol ; 51(1): 77-86, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31758345

RESUMO

Leifsonia xyli subsp. xyli (Lxx) colonizes the xylem vessels of sugarcane, a plant niche where microorganisms are highly exposed to oxidative and osmotic stresses. This study performed an in silico analysis of the genome of Lxx and characterized 16 genes related to the detoxification of oxidative species (peroxidases, O2- dismutases, and methionine reductases) and to the production and transport of osmolytes and analyzed their expression in vitro after 30, 60, and 120 min of exposure to H2O2 or PEG. The PAGE activity of superoxide dismutase (Mn-SOD as confirmed by inhibition tests) and of catalase (CAT) and the accumulation of trehalose were also assessed. Exposure to H2O2 increased the expression of most oxidative-responsive genes and decreased the expression of those related to osmotic responses, whereas the opposite occurred after exposure to PEG. The isoform profiles of CAT and Mn-SOD shifted in response to H2O2 but not to PEG and Lxx cells accumulated more trehalose over time after exposure to PEG compared with non-exposed cells. The experimental results validated the in silico analysis and indicated that this obligate endophytic parasite has multiple and functional mechanisms to combat the stresses imposed by its host.


Assuntos
Actinobacteria/genética , Pressão Osmótica , Estresse Oxidativo/genética , Saccharum/microbiologia , Actinobacteria/patogenicidade , Actinobacteria/fisiologia , Catalase/metabolismo , Interações entre Hospedeiro e Microrganismos , Peroxidação de Lipídeos , Doenças das Plantas/microbiologia , Superóxido Dismutase/metabolismo
9.
Front Oncol ; 9: 25, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740361

RESUMO

Microtubules are important drug targets in tumor cells, owing to their role in supporting and determining the cell shape, organelle movement and cell division. The complementarity-determining regions (CDRs) of immunoglobulins have been reported to be a source of anti-tumor peptide sequences, independently of the original antibody specificity for a given antigen. We found that, the anti-Lewis B mAb light-chain CDR1 synthetic peptide Rb44, interacted with microtubules and induced depolymerization, with subsequent degradation of actin filaments, leading to depolarization of mitochondrial membrane-potential, increase of ROS, cell cycle arrest at G2/M, cleavage of caspase-9, caspase-3 and PARP, upregulation of Bax and downregulation of Bcl-2, altogether resulting in intrinsic apoptosis of melanoma cells. The in vitro inhibition of angiogenesis was also an Rb44 effect. Peritumoral injection of Rb44L1 delayed growth of subcutaneously grafted melanoma cells in a syngeneic mouse model. L1-CDRs from immunoglobulins and their interactions with tubulin-dimers were explored to interpret effects on microtubule stability. The opening motion of tubulin monomers allowed for efficient L1-CDR docking, impairment of dimer formation and microtubule dissociation. We conclude that Rb44 VL-CDR1 is a novel peptide that acts on melanoma microtubule network causing cell apoptosis in vitro and melanoma growth inhibition in vivo.

10.
Anticancer Agents Med Chem ; 19(3): 389-401, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30417795

RESUMO

BACKGROUND: BRN2 transcription factor is associated with the development of malignant melanoma. The cytotoxic activities and cell death mechanism against B16F10-Nex2 cells were determined with synthetic peptide R18H derived from the POU domain of the BRN2 transcription factor. OBJECTIVE: To determine the cell death mechanisms and in vivo activity of peptide R18H derived from the POU domain of the BRN2 transcription factor against B16F10-Nex2 cells. METHODS: Cell viability was determined by the MTT method. C57Bl/6 mice were challenged with B16F10-Nex2 cells and treated with R18H. To identify the type of cell death, we used TUNEL assay, Annexin V and PI, Hoechst, DHE, and determination of caspase activation and cytochrome c release. Transmission electron microscopy was performed to verify morphological alterations after peptide treatment. RESULTS: Peptide R18H displayed antitumor activity in the first hours of treatment and the EC50% was calculated for 2 and 24h, being 0.76 ± 0.045 mM and 0.559 ± 0.053 mM, respectively. After 24h apoptosis was evident, based on DNA degradation, chromatin condensation, increase of superoxide anion production, phosphatidylserine translocation, activation of caspases 3 and 8, and release of extracellular cytochrome c in B16F10-Nex2 cells. The peptide cytotoxic activity was not affected by necroptosis inhibitors and treated cells did not release LDH in the extracellular medium. Moreover, in vivo antitumor activity was observed following treatment with peptide R18H. CONCLUSION: Peptide R18H from BRN2 transcription factor induced apoptosis in B16F10-Nex2 and displayed antitumor activity in vivo.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas de Homeodomínio/química , Melanoma/tratamento farmacológico , Melanoma/patologia , Fatores do Domínio POU/química , Peptídeos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Melanoma/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Estrutura Molecular , Peptídeos/síntese química , Peptídeos/química , Relação Estrutura-Atividade
11.
Front Immunol ; 10: 3122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32010152

RESUMO

The cyclic VHCDR3-derived peptide (Rb9) from RebMab200 antibody, directed to a NaPi2B phosphate-transport protein, displayed anti-metastatic melanoma activity at 50-300 µg intraperitoneally injected in syngeneic mice. Immune deficient mice failed to respond to the peptide protective effect. Rb9 induced increased CD8+ T and low Foxp3+ T cell infiltration in lung metastases and high IFN-γ and low TGF-ß in lymphoid organs. The peptide co-localized with F-actin and a nuclear site in dendritic cells and specifically bound to MIF and CD74 in a dot-blot setting. Murine bone-marrow dendritic cells preincubated with Rb9 for 6 h were treated with MIF for short time periods. The modulated responses showed stimulation of CD74 and inhibition of pPI3K, pERK, and pNF-κB as compared to MIF alone. Rb9 in a melanoma-conditioned medium, stimulated the M1 type conversion in bone marrow-macrophages. Functional aspects of Rb9 in vivo were studied in therapeutic and prophylactic protocols using a melanoma metastatic model. In both protocols Rb9 exhibited a marked anti-melanoma protection. Human dendritic cells were also investigated showing increased expression of surface markers in response to Rb9 incubation. Rb9 either stimulated or slightly inhibited moDCs submitted to inhibitory (TGF-ß and IL-10) or activating (LPS) conditions, respectively. Lymphocyte proliferation was obtained with moDCs stimulated by Rb9 and tumor cell lysate. In moDCs from cancer patients Rb9 exerted immunomodulatory activities depending on their functional status. The peptide may inhibit over-stimulated cells, stimulate poorly activated and suppressed cells, or cause instead, little phenotypic and functional alterations. Recently, the interaction MIF-CD74 has been associated to PD-L1 expression and IFN-γ, suggesting a target for melanoma treatment. The effects described for Rb9 and the protection against metastatic melanoma may suggest the possibility of a peptide reagent that could be relevant when associated to modern immunotherapeutic procedures.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares , Melanoma Experimental , Peptídeos Cíclicos/farmacologia , Animais , Linfócitos T CD8-Positivos/patologia , Células Dendríticas/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/prevenção & controle , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos SCID , Metástase Neoplásica , Proteínas de Neoplasias/imunologia
12.
Front Immunol ; 9: 1132, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29875777

RESUMO

Mounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. While immunotherapies have shown a remarkable success in melanoma treatment, patients develop resistance by mechanisms that include the establishment of an immune suppressive tumor microenvironment. Thus, understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that macrophages (MOs) and dendritic cells (DCs) are suppressed in metastatic melanoma and that the Ig-CDR-based peptide C36L1 is able to restore MOs and DCs' antitumorigenic and immunogenic functions and to inhibit metastatic growth in lungs. Specifically, C36L1 treatment is able to repolarize M2-like immunosuppressive MOs into M1-like antitumorigenic MOs, and increase the number of immunogenic DCs, and activated cytotoxic T cells, while reducing the number of regulatory T cells and monocytic myeloid-derived suppressor cells in metastatic lungs. Mechanistically, we find that C36L1 directly binds to the MIF receptor CD74 which is expressed on MOs and DCs, disturbing CD74 structural dynamics and inhibiting MIF signaling on these cells. Interfering with MIF-CD74 signaling on MOs and DCs leads to a decrease in the expression of immunosuppressive factors from MOs and an increase in the capacity of DCs to activate cytotoxic T cells. Our findings suggest that interfering with MIF-CD74 immunosuppressive signaling in MOs and DCs, using peptide-based immunotherapy can restore the antitumor immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the antitumor immune response in metastatic melanoma.


Assuntos
Antígenos de Diferenciação de Linfócitos B/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Imunidade , Macrófagos/imunologia , Macrófagos/metabolismo , Melanoma/imunologia , Melanoma/metabolismo , Receptores Imunológicos/metabolismo , Transdução de Sinais , Animais , Antígenos de Diferenciação de Linfócitos B/química , Antígenos de Histocompatibilidade Classe II/química , Fatores Inibidores da Migração de Macrófagos/metabolismo , Masculino , Melanoma/patologia , Melanoma Experimental , Camundongos , Modelos Biológicos , Modelos Moleculares , Metástase Neoplásica , Peptídeos/imunologia , Peptídeos/metabolismo , Ligação Proteica , Receptores Imunológicos/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
13.
An Acad Bras Cienc ; 90(2): 1749-1758, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29768574

RESUMO

In this study, we are presenting recommendations to the best agricultural use as well as for plant breeding of three millet cultivars namely ENA1 and ENA2, which have African origin, and BRS1501 originally from India. These cultivars were evaluated for growth, yield and grain quality traits. The morphological traits evaluated in this study indicated that the African genotypes ENA1 and ENA2 are better than the Indian genotype BRS1501 for no-till farming or to produce forage with 15% of crude protein at flowering and at harvest to produce stover (around 7% of crude protein content) for livestock feeding. The BRS1501 cultivar exhibited the highest values for total crude protein, albumins and prolamins, phytate and mineral contents in grains. ENA1 and ENA2 exhibited the highest values of globulin and glutelin contents. The electrophoretic patterns for storage proteins were similar across the three millets cultivars, except for a higher intensity of two glutelin bands with 21 and 24 kDa in BRS1501. Together, the results allow us to recommend BRS1501 for grain production and ENA1 and ENA2 for biomass production.


Assuntos
Produtos Agrícolas/crescimento & desenvolvimento , Grão Comestível/química , Valor Nutritivo , Pennisetum/crescimento & desenvolvimento , Proteínas de Plantas/química , África , Aminoácidos/química , Biomassa , Brasil , Índia , Pennisetum/anatomia & histologia , Ácido Fítico/química , Característica Quantitativa Herdável
14.
Physiol Plant ; 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29667213

RESUMO

Antioxidant enzymatic responses in Citrus leaves under Cu-induced stress depends on rootstock genotypes. However, there is a lack of information about how woody plants recover growth capacity after exposure to elevated Cu and whether growth is affected by the redistribution of the metal to new vegetative parts and consequently whether photosynthesis is affected. Therefore, the biomass of plants and Cu concentrations in new leaf flushes were determined in young citrus trees grafted onto contrasting rootstocks [Swingle citrumelo (SW) and Rangpur lime (RL)]. Photosynthetic rate, chlorophyll fluorescence and antioxidant enzymatic systems were evaluated in plants previously grown in nutrient solution with Cu varying from low to high levels and with no added Cu. Both rootstocks exhibited reduced plant growth under Cu toxicity. However, trees grafted onto RL exhibited better growth recovery after Cu excess, which was dependent on the modulation of antioxidant enzyme activities in roots and leaves that maintained the integrity of the photosynthetic apparatus. In contrast, plants grafted onto SW exhibited a lower photosynthetic rate at the lowest available Cu concentration. Although the highest accumulation of Cu occurred in citrus roots, the redistribution of the nutrient to new vegetative parts was proportional to the Cu concentration in the roots.

15.
Biomed Pharmacother ; 103: 18-28, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29635124

RESUMO

Phosphoethanolamine (PEA) is a fundamental precursor during the biosynthesis of cell membranes phospholipids. In the past few years, it has been described as a potential antitumor agent. In previous studies, we demonstrated that PEA showed antitumor properties in vitro and in vivo in a wide range of tumor cell lines. Herein, we showed that PEA possesses cytotoxic properties and notably revealed to induce caspase-independent cell death. Of interest, we provided evidence that PEA inhibits melanoma cells proliferation through the reduction of C-RAF. Molecular docking of PEA evidenced that this compound indeed fits satisfactory in the binding site located between the dimers of C-RAF protein with 107,01 Šand score of -29,62. Also, PEA arrested A2058 cells at G2/M phase in the cell cycle. Moreover, cell proliferation, migration and adhesion capacities of A2058 cells were also inhibited by PEA. Most importantly, PEA inhibited tumor growth of melanoma tumors and prolonged survival rate of mice. Also, PEA induced a significant immune response in a syngeneic metastatic melanoma model. Taken together, these data indicate that PEA is a promising candidate for future developments in cancer field.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Etanolaminas/farmacologia , Melanoma/patologia , Proteínas Proto-Oncogênicas c-raf/metabolismo , Animais , Antineoplásicos/farmacologia , Sítios de Ligação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Etanolaminas/química , Humanos , Melanoma/enzimologia , Melanoma/imunologia , Melanoma Experimental/enzimologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Metástase Neoplásica , Fosforilação/efeitos dos fármacos , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
16.
PLoS One ; 13(4): e0196166, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29694403

RESUMO

The intense use of herbicides for weed control in agriculture causes selection pressure on soil microbiota and water ecosystems, possibly resulting in changes to microbial processes, such as biogeochemical cycles. These xenobiotics may increase the production of reactive oxygen species and consequently affect the survival of microorganisms, which need to develop strategies to adapt to these conditions and maintain their ecological functionality. This study analyzed the adaptive responses of bacterial isolates belonging to the same species, originating from two different environments (water and soil), and subjected to selection pressure by herbicides. The effects of herbicide Callisto and its active ingredient, mesotrione, induced different adaptation strategies on the cellular, enzymatic, and structural systems of two Bacillus megaterium isolates obtained from these environments. The lipid saturation patterns observed may have affected membrane permeability in response to this herbicide. Moreover, this may have led to different levels of responses involving superoxide dismutase and catalase activities, and enzyme polymorphisms. Due to these response systems, the strain isolated from water exhibited higher growth rates than did the soil strain, in evaluations made in oligotrophic culture media, which would be more like that found in semi-pristine aquatic environments. The influence of the intracellular oxidizing environments, which changed the mode of degradation of mesotrione in our experimental model and produced different metabolites, can also be observed in soil and water at sites related to agriculture. Since the different metabolites may present different levels of toxicity, we suggest that this fact should be considered in studies on the fate of agrochemicals in different environments.


Assuntos
Bacillus megaterium/crescimento & desenvolvimento , Cicloexanonas/farmacologia , Herbicidas/farmacologia , Microbiologia do Solo , Microbiologia da Água , Adaptação Fisiológica , Bacillus megaterium/classificação , Bacillus megaterium/efeitos dos fármacos , Bacillus megaterium/genética , Biodegradação Ambiental , Ecossistema , Peroxidação de Lipídeos/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
17.
Anticancer Agents Med Chem ; 18(6): 865-874, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29308743

RESUMO

BACKGROUND: Lung cancer is the most prevalent cancer and a high fatality disease. Despite of all available therapeutic approaches, drug resistance of chemotherapy agents for patients remain as an obstacle. New drugs integrating immunotherapeutic and conventional cytotoxic effects is a powerful strategy for the treatment of cancer to overcome this limitation. Antineoplastic phospholipids combine both of these activities by affecting lipid metabolism and signaling through lipid rafts. Therefore, they emerge as interesting scaffolds for designing new drugs. OBJECTIVE: We aimed to evaluate antineoplastic phospholipids as scaffolds for designing new drugs for lung cancer treatment. METHODS: The initial screening in A549 cells was performed by MTT assay. Others cytotoxic effects were evaluated in A549 cells by clonogenic assay, Matrigel 3D culture and flow cytometry analyses of cell cycle, apoptosis, mitochondrial membrane electronic potential and superoxide production. Immunological effects of ED were accessed on dendritic cells (DCs) and the expression of some markers were evaluated by flow cytometry. In vivo lung colonization analysis was performed after intravenously injection of A549 cells and daily treatment with ED. RESULTS: Herein, ED showed to be the most efficient compound concerning cytotoxic, thereby, ED was selected for following tests. ED showed a cytotoxic profile in both monolayer and 3D culture and also in vivo models using A549 cells. This profile is due to G0/G1 phase cellular arrest and apoptosis drove by mitochondrial membrane depolarization and superoxide overproduction. Moreover, ED modulated DCs toward an activated pattern by the increased expression of CD83 and a remarkable decreased expression of PD-L1/CD274 on DCs membrane. CONCLUSIONS: Thus, ED is an interesting antitumor drug prototype due to not only its direct cellular cytotoxicity but also given its immunological features.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Éteres Fosfolipídicos/farmacologia , Células A549 , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Conformação Molecular , Tamanho da Partícula , Éteres Fosfolipídicos/química , Relação Estrutura-Atividade , Propriedades de Superfície , Células Tumorais Cultivadas
18.
J Trace Elem Med Biol ; 44: 50-58, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28965600

RESUMO

The mitigation of Cd-stress through Si addition to Arabidopsis thaliana cultivation is evaluated in terms of total metal content, proteomic and enzymatic approaches. Four different treatment are evaluated: TC (control, without Si or Cd addition), T1 (with Si addition), T2 (with Cd addition), and T3 (with Si and Cd addition). Through the total determination of Cd and Si in Arabidopsis leaves, the Cd concentration decreased by half when T2 is compared with T3 treatment. In terms of proteomic approach, some differential protein species are achieved by comparative proteomics through 2-D DIGE of all treatments evaluated. Fifty six differential abundant proteins spots (abundance factor ≥1.5) are detected, and 32 of them accurately characterized and identified through nESI-LC-MS/MS. These proteins are differentially produced due to Cd and/or Si treatments, which mainly include proteins associated with disease/defense, energy and metabolism. The most difference in the abundance of proteins is found due to the presence or absence of Si in plants treated with Cd. Regarding the enzymatic approaches, a major increase is found on APX, CAT and GR activities (5.0, 3.5, and 1.5-fold, respectively). The same is observed for the MDA concentration because an increase of 3-fold is found when TC are compared to those treated with T2. However, when T3 plants are evaluated, the enzymes activities are similar to TC plants. Differences ranging from 6.5 to 21% are detected considering the activity of SOD in the treatments (T1-T3 x TC). The decreased activities of CAT, APX and GR and lower MDA concentration indicate a lower reactive oxygen species production in plants treated with Cd and Si. Based on a proteomics point of view it is possible to conclude that Si-Cd interactions occur at protein level and allow plants to respond effectively to the Cd toxicity, revealing the active involvement of Si on mechanisms involved in Si-induced Cd tolerance in Arabidopsis plants. Additionally, from an enzymatic point of view, it is possible to conclude that Si positively interferes diminishing the negative effects of Cd in Arabidopsis by decreasing the reactive oxygen species generation and increasing the antioxidative enzyme activity.


Assuntos
Arabidopsis/enzimologia , Arabidopsis/crescimento & desenvolvimento , Cádmio/toxicidade , Metais/metabolismo , Proteômica , Silício/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Arabidopsis/efeitos dos fármacos , Arabidopsis/fisiologia , Cádmio/metabolismo , Eletroforese em Gel Bidimensional , Peroxidação de Lipídeos , Malondialdeído/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Ligação Proteica , Mapas de Interação de Proteínas , Silício/metabolismo
19.
J Proteome Res ; 16(10): 3688-3703, 2017 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-28836437

RESUMO

Sugar cane is an important crop for sugar and biofuel production. Its lignocellulosic biomass represents a promising option as feedstock for second-generation ethanol production. Nitrogen fertilization can affect differently tissues and its biopolymers, including the cell-wall polysaccharides and lignin. Lignin content and composition are the most important factors associated with biomass recalcitrance to convert cell-wall polysaccharides into fermentable sugars. Thus it is important to understand the metabolic relationship between nitrogen fertilization and lignin in this feedstock. In this study, a large-scale proteomics approach based on GeLC-MS/MS was employed to identify and relatively quantify proteins differently accumulated in two contrasting genotypes for lignin composition after excessive nitrogen fertilization. From the ∼1000 nonredundant proteins identified, 28 and 177 were differentially accumulated in response to nitrogen from IACSP04-065 and IACSP04-627 lines, respectively. These proteins were associated with several functional categories, including carbon metabolism, amino acid metabolism, protein turnover, and oxidative stress. Although nitrogen fertilization has not changed lignin content, phenolic acids and lignin composition were changed in both species but not in the same way. Sucrose and reducing sugars increased in plants of the genotype IACSP04-065 receiving nitrogen.


Assuntos
Biocombustíveis , Plantas Geneticamente Modificadas/genética , Proteoma/genética , Saccharum/genética , Biomassa , Carboidratos/química , Carboidratos/genética , Fermentação , Regulação da Expressão Gênica de Plantas , Genótipo , Lignina/química , Lignina/metabolismo , Nitrogênio/química , Nitrogênio/metabolismo , Oxidantes/química , Oxidantes/metabolismo , Fenótipo , Plantas Geneticamente Modificadas/metabolismo , Proteoma/química , Saccharum/metabolismo
20.
An Acad Bras Cienc ; 89(1 Suppl 0): 695-704, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28489193

RESUMO

Both the scientific community and society have shown interest in improving the content of amino acids, carbohydrates and mineral nutrients in maize because it represents an important staple food in many developing countries. Earlier studies demonstrated that the treatment of seeds using ascorbic acid (AsA-seed priming) enhanced soluble carbohydrates, proteins and soluble amino acids for other species. AsA seed priming in maize showed the potential for reducing abiotic stresses. The effects on grain quality have not been previously demonstrated. This study investigated the impacts of AsA seed priming on maize kernel quality of seeds produced by the plants generated from the primed seeds, based on the amino acid profile and carbohydrate and mineral nutrient contents. AsA seed priming improved the maize kernel quality with respect to the ascorbate content, boron allocation, total carbohydrate content and increased soluble amino acid levels, including serine, tyrosine, alanine, valine, glutamate, arginine, proline, aspartate, lysine and isoleucine, whereas soluble methionine was decreased. Therefore, AsA seed priming can represent a potential technique for improving maize grain quality.


Assuntos
Aminoácidos/análise , Ácido Ascórbico/farmacologia , Carboidratos/análise , Minerais/análise , Sementes/efeitos dos fármacos , Zea mays/química , Zea mays/efeitos dos fármacos
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