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Synthetic or natural cationic polymers, such as polyacrylamide and chitosan, are exploited as coagulants due to their characteristics, such as a high positive surface charge. Due to variations in culture conditions, such as species and cell concentration, different interactions of coagulants with microalgae occur, affecting the efficiency of biomass recovery. Thus, in this study, the separation efficiency of biomass of the microalgae Scenedesmus obliquus was evaluated by coagulation-flocculation with the synthetic polymer polyacrylamide and natural polymer chitosan to optimize the dose and pH by means of a rotational central composite design. Biomass removal efficiencies greater than 90% and greater than 70% were observed for the synthetic polymer and chitosan, respectively. Notably, the reduced optical density and biological nature of microalgae make the use of response surface methodology challenging. Optimal regions with doses of 12.8 mg of synthetic polymer and 5.0 mg of chitosan were obtained per liter of microalgae sample. An optimal pH of 6.5, falling within the natural range of culture conditions was indicated for both coagulants, minimizing reagent costs. The interaction with microalgae and the potential application of chitosan and other natural coagulants that are efficient and economically viable should be explored. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most aggressive and lethal among the primary brain tumors, with a low survival rate and resistance to radio and chemotherapy. The P2Y12 is an adenosine diphosphate (ADP) purinergic chemoreceptor, found mainly in platelets. In cancer cells, its activation has been described to induce proliferation and metastasis. Bearing in mind the need to find new treatments for GBM, this study aimed to investigate the role of the P2Y12R in the proliferation and migration of GBM cells, as well as to evaluate the expression of this receptor in patients' data obtained from the TCGA data bank. Here, we used the P2Y12R antagonist, ticagrelor, which belongs to the antiplatelet agent's class. The different GBM cells (cell line and patient-derived cells) were treated with ticagrelor, with the agonist, ADP, or both, and the effects on cell proliferation, colony formation, ADP hydrolysis, cell cycle and death, migration, and cell adhesion were analyzed. The results showed that ticagrelor decreased the viability and the proliferation of GBM cells. P2Y12R antagonism also reduced colony formation and migration potentials, with alterations on the expression of metalloproteinases, and induced autophagy in GBM cells. Changes were observed at the cell cycle level, and only the U251 cell line showed a significant reduction in the ADP hydrolysis profile. TCGA data analysis showed a higher expression of P2Y12R in gliomas samples when compared to the other tumors. These data demonstrate the importance of the P2Y12 receptor in gliomas development and reinforce its potential as a pharmacological target for glioma treatment. [ABSTRACT FROM AUTHOR]

Healthcare-associated infections (HAIs) represent a global challenge and an even more staggering concern when related to microorganisms capable of resisting and surviving for long periods in the environment, such as Acinetobacter spp. Strategies that allow a reduction of pathogens from hospital environments represent an additional barrier in infection control protocols, minimizing transmission to hospitalized patients. Considering the antimicrobial properties of copper, here, the bacterial load and the presence of Acinetobacter spp. were monitored on high handling surfaces covered by 99.9% copper films on intensive and non-intensive care unit bedrooms in a tertiary care hospital. Firstly, copper-coated films were able to inhibit the adhesion and biofilm formation of A. baumannii strains in in vitro assays. On the other hand, Acinetobacter spp. were isolated from both copper-coated and uncoated surfaces in the hospital, although the majority was detected on surfaces without copper. All carbapenem-resistant A. baumannii isolates identified harbored the blaoxa-23 gene, while the A. nosocomialis isolates were susceptible to most antimicrobials tested. All isolates were susceptible to polymyxin B. Regarding the total aerobic bacteria, surfaces with copper-coated films presented lower total loads than those detected for controls. Copper coating films may be a workable strategy to mitigate HAIs, given their potential in reducing bacterial loads in nosocomial environments, including threatening pathogens like A. baumannii. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most malignant and deadly brain tumor. GBM cells overexpress the CD73 enzyme, which controls the level of extracellular adenosine, an immunosuppressive molecule. Studies have shown that some nonsteroidal anti-inflammatory drugs (NSAIDs) and methotrexate (MTX) have antiproliferative and modulatory effects on CD73 in vitro and in vivo. However, it remains unclear whether the antiproliferative effects of MTX and NSAIDS in GBM cells are mediated by increases in CD73 expression and adenosine formation. The aim of this study was to evaluate the effect of the NSAIDs, naproxen, piroxicam, meloxicam, ibuprofen, sodium diclofenac, acetylsalicylic acid, nimesulide, and ketoprofen on CD73 expression in GBM and mononuclear cells. In addition, we sought to understand whether the effects of MTX may be mediated by CD73 expression and activity. Cell viability and CD73 expression were evaluated in C6 and mononuclear cells after exposure to NSAIDs. For analysis of the mechanism of action of MTX, GBM cells were treated with APCP (CD73 inhibitor), dipyridamole (inhibitor of adenosine uptake), ABT-702 (adenosine kinase enzyme inhibitor), or caffeine (P1 adenosine receptor antagonist), before treatment with MTX and AMP, in the presence or not of mononuclear cells. In summary, only MTX increased the expression of CD73 in GBM cells decreasing cells viability by mechanisms independent of the adenosinergic system. Further studies are needed to understand the role of MTX in the GBM microenvironment. [ABSTRACT FROM AUTHOR]

Purpose: The lack of approaches to consider the economic-life cycle environmental performance of cropping systems at experimental stage and the absence of evaluations regarding alternative mango systems are issues addressed in this paper. In this study, an approach for assessing the environmental-economic performance of alternative crop systems, at the experimental stage, is proposed and applied to the mango experiment in Brazil. This approach may be used in other assessments of cropping systems at experimental stage. Methods: The proposed approach encompasses three consecutive evaluations: agronomic and environmental-economic. Initially, the agronomic evaluation statistically compares the yield of alternative cropping systems (treatments in the experiment). Next, a treatment is selected among those with significant better yield and compared to the treatment representing the conventional system, considering environmental and economic criteria. The environmental criteria are the carbon and water footprints of the selected treatments, according to ISO 14067 and 14,046, while the economic is profitability (revenue minus costs with labor and inputs). This approach was applied to evaluate an 8-year mango experiment in the Sao Francisco Valley, Brazil, which intercropped mango trees with two types of plant mixtures (cover crops with different plant mixes), applying two soil management systems (tillage and no-tillage). Results and discussion: The agronomic assessment that statistically compared yields showed that four treatments (T1, T2, T4, and T5) obtained higher yields than those representing the conventional system (T3 and T6). Treatment T4 was selected among the ones with higher yields, and compared with T6 (conventional system), considering the economic and environmental criteria. The economic analysis showed that in 30 years (expected orchard life time), T4 generates a profit that is 44% higher than T6. Regarding the environmental analysis, T4 presents a 16% lower carbon footprint and from 16 to 435% lower water footprint than T6, according to the impact category considered. The scenario where land use changed from an annual crop (melon) to mango orchard further reduced both carbon and water footprints of mangoes produced in T4. Conclusions: The application of the proposed approach to the mango experiment resulted in the reduction of time and data requirements when evaluating the economic-environmental performance of mango alternative cropping systems, allowing the selection of best performing treatment. The assessment of economic-environmental performance showed that treatments with plant mixtures used as cover crops between lines of mango trees, independently of the type of mix used or the soil management applied, enhance the overall performance of mango production. [ABSTRACT FROM AUTHOR]

Purpose: Bevacizumab (BCZ) is a recombinant monoclonal antibody that inhibits the biological activity of the vascular endothelial growth factor, which has an important role in angiogenesis for tumoral growth and progression. In this way, our objective was to develop chitosan-coated lipid-core nanocapsules functionalized with BCZ by an organometallic complex using gold-III. Methods: The formulation was produced and characterized in relation to physicochemical characteristics. Furthermore, the antitumoral and antiangiogenic activities were evaluated against C6 glioma cell line and chicken embryo chorioallantoic membrane (CAM), respectively. Results: Final formulation showed nanometric size, narrow polydispersity, positive zeta potential and gold clusters size lower than 2 nm. BCZ in aqueous solution (0.01–0.10 μmol L−1) did not show cytotoxic activity in vitro against C6 glioma cell line; although, MLNC-Au-BCZ showed cytotoxicity with a median inhibition concentration of 30 nmol L−1 of BCZ. Moreover, MLNC-Au-BCZ demonstrated cellular internalization dependent on incubation time and BCZ concentration. BCZ solution did not induce significant apoptosis as compared to MLNC-Au-BCZ within 24 h of treatment. CAM assay evidenced potent antiangiogenic activity for MLNC-Au-BCZ, representing a decrease of 5.6 times in BCZ dose comparing to BCZ solution. Conclusion: MLNC-Au-BCZ is a promising product for the treatment of solid tumors. [ABSTRACT FROM AUTHOR]

Paracoccidiodomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. The disease requires long and complicated treatment. The aim of this review is to address the fungal virulence factors that could be the target of the development of new drugs for PCM treatment. Virulence factors favoring the process of fungal infection and pathogenicity are considered as a microbial attribute associated with host susceptibility. P. brasiliensis has some known virulence factors which are 43 kDa glycoprotein (gp 43) which is an important fungal antigen, 70 kDa glycoprotein (gp 70), the carbohydrates constituting the fungal cell wall α-1,3, glucan and β-1,3-glucan, cell adhesion molecules and the presence of melanin pigments. The discovery and development of drugs that interact with these factors, such as inhibitors of β-1,3-glucan, reduced synthesis of gp 43, inhibitors of melanin production, is of great importance for the treatment of PCM. The study of virulence factors favors the understanding of pathogen–host relationships, aiming to evaluate the possibility of developing new therapeutic targets and mechanisms that these molecules play in the infectious process, favoring the design of a more specific treatment for this disease. [ABSTRACT FROM AUTHOR]

Invasive fungal infections are a global health problem, mainly in hospitals, where year by year hundreds of patients die because of these infections. Commensal yeasts may become pathogenic to human beings, affecting mainly immunocompromised patients. During infectious processes, the immune system uses phagocytes to eliminate invader microorganisms. In order to prevent or neutralize phagocyte attacks, pathogenic yeasts can use virulence factors to survive, as well as to colonize and infect the host. In this review, we describe how Candida spp., mainly Candida albicans, interact with phagocytes and use several factors that contribute to immune evasion. Polymorphism, biofilm formation, gene expression and enzyme production mediate distinct functions such as adhesion, invasion, oxidative stress response, proteolysis and escape from phagocytes. Fungal and human cells have similar structures and mechanisms that decrease the number of potential targets for antifungal drugs. Therefore, research on host–pathogen interaction may aid in the discovery of new targets and in the development of new drugs or treatments for these diseases and thus to save lives. [ABSTRACT FROM AUTHOR]

Purpose: Awareness regarding carbon and water footprint has gained visibility, encouraging actions towards compliance with the main available standards by fruit producers. This study presents the carbon and water footprint of packed mango produced in Vale do São Francisco, the main irrigated valley in Brazil. It provides an approach to identify the critical processes and opportunities for improvements in the conventional crop system that may support producers in the task of developing future site-specific assessments. Methods: This assessment followed ISO 14046 and ISO 14067 for water and carbon footprints, respectively, as well as specific requirements of product category rule (PCR) 013 for fruits and nuts and Publicly Available Specification (PAS) 2051-1 for horticulture products. Primary data was collected for nursery (seedling), land use change, crop production, and packaging, considering five exported mango varieties: Palmer, Keitt, Kent, Haden, and Tommy Atkins. The carbon footprint assessment was based on the impact category climate change, while water footprint encompassed the following categories: water scarcity, marine and freshwater eutrophication, human toxicity (carcinogenic and non-carcinogenic), and freshwater ecotoxicity. The footprint analysis was performed for 1 kg of packed mango. Results and discussion: The three main processes responsible for both footprints were related to crop production: fertilizer and electricity production as well as mango cropping. Moving from Caatinga vegetation to mango orchards increased carbon storage but was not enough to offset the impact on climate change. For water footprint, it was observed that the total volume of applied irrigation water was already below technical requirements and cannot be reduced, the same occurring for nitrogen fertilization. Scenario analysis showed that the use of alternative electricity sources and the reuse of wastewater brought no major improvement in results. Furthermore, the choice of local or country level characterization factors for water scarcity changed results significantly. Discussions are made regarding (i) the relevance of mango footprints when compared to other irrigated fruits, (ii) possibilities for improving mango footprint performance, (iii) the need for updating product category rules for fruits, and (iv) the quality of provided inventories and results. Conclusions: The comparison of mango footprints with previous studies of irrigated fruits showed that mango performance is similar or better than many irrigated fruits, cultivated all over the world. Moreover, footprints may be further reduced if mango orchards are established in previously deforested land or areas occupied with annual crops and if improvements are made in the irrigation and fertilization practices at each mango production stage. [ABSTRACT FROM AUTHOR]

In this work it is described the synthesis, characterization and antimicrobial and toxicity evaluation of a series of analogs of piplartine, a piperamide found in Piper sp. The compounds structures were confirmed by infrared spectroscopy, H, C nuclear magnetic resonance, high resolution mass spectroscopy and were evaluated against strains of Candida spp., Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Derivative 24 was almost four-fold more potent (IC: 48.83 μM) and five-fold less toxic (SI > 3) than piplartine (IC: 189.2 μM; SI: 0.21) against Candida krusei, as well as two-fold more potent than fluconazole (IC: 104.48 μM). This compound was also active against Candida tropicalis at 97.67 μM. Benzoyl derivative 17 was three-fold more potent (IC: 85.2 μM) and more than five-fold less toxic (CC: 231.71 μM) than piplartine (IC: 315.33 μM and CC: 41.14 μM) against Staphylococcus aureus. Given these findings, we have found analogs of piplartine which can be assumed as prototypes for the optimization and the development of new antimicrobial (compounds 24 and 17) agents. [ABSTRACT FROM AUTHOR]

Six eugenol glycosides were prepared in order to assess their antifungal activity against Candida species. They were synthesized by glycosylation of eugenol with the appropriate glycosyl bromides followed by deacetylation with sodium methoxide in methanol and were evaluated in vitro for their antifungal activity through a Mueller-Hinton broth microdilution method. The peracetyl glycoside (derivative 4) was the most promising one since it was able to inhibit growth of C. albicans, C. tropicalis and C. glabrata with IC values much lower than that of the prototype eugenol. Derivative 4 showed to be 160.0 and 3.4 times more potent than eugenol and fluconazole, respectively, against C. glabrata with low cytotoxity (selectivity index of 45). Moreover, it was possible to verify the positive effect of gluco configuration and lipophilicity on antifungal activity, since glucose peracetyl derivatives were more active than the free sugars of galacto configuration. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of amphotericin B and voriconazole alone and in combination with one another were evaluated in immunodeficient mice (BALB/c-SCID) infected with a fluconazole-resistant strain of Cryptococcus neoformans var. grubii. The animals were infected intravenously with 3 × 10 cells and intraperitoneally treated with amphotericin B (1.5 mg/kg/day) in combination with voriconazole (40 mg/kg/days). Treatment began 1 day after inoculation and continued for 7 and 15 days post-inoculation. The treatments were evaluated by survival curves and yeast quantification (CFUs) in brain and lung tissues. Treatments for 15 days significantly promoted the survival of the animals compared to the control groups. Our results indicated that amphotericin B was effective in assuring longest-term survival of infected animals, but these animals still harbored the highest CFU of C. neoformans in lungs and brain at the end of the experiment. Voriconazole was not as effective alone, but in combination with amphotericin B, it prolonged survival for the second-longest time period and provided the lowest colonization of target organs by the fungus. None of the treatments were effective in complete eradication of the fungus in mice lungs and brain at the end of the experiment. [ABSTRACT FROM AUTHOR]

Candida species are the most common cause of opportunistic fungal infections. Rapid identification and novel approaches for the characterization of these fungi are of great interest to improve the diagnosis and the knowledge about their pathogenic properties. This study aimed to characterize clinical isolates of Candida spp. by proteomics (MALDI-TOF MS) and metabolomics (1H-NMR), and to correlate their metabolic profiles with Candida species, source of infection and different virulence associated parameters. In particular, 49 Candida strains from different sources (blood, n = 15; vagina, n = 18; respiratory tract, n = 16), belonging mainly to C. albicans complex (61%), C. glabrata (20%) and C. parapsilosis (12%) species were used. Several extracellular and intracellular metabolites showed significantly different concentrations among isolates recovered from different sources of infection, as well as among different Candida species. These metabolites were mainly related to the glycolysis or gluconeogenesis, tricarboxylic acid cycle, nucleic acid synthesis and amino acid and lipid metabolism. Moreover, we found specific metabolic fingerprints associated with the ability to form biofilm, the antifungal resistance (i.e. caspofungin and fluconazole) and the production of secreted aspartyl proteinase. In conclusion, 1H-NMR-based metabolomics can be useful to deepen Candida spp. virulence and pathogenicity properties. [ABSTRACT FROM AUTHOR]