Visceral leishmaniasis (VL) is a systemic transmissible disease that remains to be a major global health problem. The inflammatory response during VL is characterized by the release of several ...cytokines and other pro-inflammatory mediators. Triggering Receptor Expressed on Myeloid Cells (TREM) are a group of evolutionarily conserved membrane-bound surface receptors expressed on neutrophils and monocytes. Engagement of TREM-1 directs intracellular signaling events that drive cytokine production, degranulation, and phagocytosis. In certain inflammatory-associated diseases, TREM-1 can also be found as a soluble form (sTREM-1), which can negatively regulate TREM-1 receptor signaling. In these studies, we now find that high levels of circulating sTREM-1 correlate directly with VL disease severity. In particular, high levels of sTREM-1 were observed in non-survivor VL patients. Furthermore, these levels of sTREM-1 positively correlated with liver size and negatively correlated with leukocyte counts and hemoglobin concentration. Moreover, we found that neutrophils exposure
to
modulates TREM-1, DAP12, and IL-8 gene expression, while also increasing release of sTREM-1. Finally, results revealed that higher sTREM-1 levels are associated with increasing parasite ratio. Taken together, these studies suggest that
may modulate TREM-1 in neutrophils and high levels of this molecule is associated with severe VL.
Methanol is an important product in chemical industries, having many applications: solvent, fuel and mainly being a feedstock for a large number of industrial processes. As the search for a more ...sustainable synthesis process grows, the methanol synthesis loop from synthesis gas was studied. In this work, an optimization based on an environmental objective function was developed to reduce the total water consumption of the plant. The methanol synthesis plant and the utility plants of a cooling water system and steam generation cycle were modeled and simulated. A multi-objective optimization study was performed to obtain the optimal trade-off between the economic performance and the reduced water usage. Two distinct scenarios were considered: the integrated use of the steam produced in the reactor cooling and its exporting for profits. The results show that the optimized green design can reduce up to 18% of the water consumed by the process. The exported steam case study provided more economic benefits, while the integrated steam case attained a smaller water consumption indicator.
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Leishmaniasis remains a worldwide public health problem. The limited therapeutic options, drug toxicity and reports of resistance, reinforce the need for the development of new treatment options. ...Previously, we showed that 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), a Heat Shock Protein 90 (HSP90)-specific inhibitor, reduces L. (L.) amazonensis infection in vitro. Herein, we expand the current knowledge on the leishmanicidal activity of 17-AAG against cutaneous leishmaniasis, employing an experimental model of infection with L. (V.) braziliensis.
Exposure of axenic L. (V.) braziliensis promastigotes to 17-AAG resulted in direct dose-dependent parasite killing. These results were extended to L. (V.) braziliensis-infected macrophages, an effect that was dissociated from the production of nitric oxide (NO), superoxide (O(-2)) or inflammatory mediators such as TNF-α, IL-6 and MCP-1. The leishmanicidal effect was then demonstrated in vivo, employing BALB/c mice infected with L. braziliensis. In this model, 17-AAG treatment resulted in smaller skin lesions and parasite counts were also significantly reduced. Lastly, 17-AAG showed a similar effect to amphotericin B regarding the ability to reduce parasite viability.
17-AAG effectively inhibited the growth of L. braziliensis, both in vitro and in vivo. Given the chronicity of L. (V.) braziliensis infection and its association with mucocutaneous leishmaniasis, 17-AAG can be envisaged as a new chemotherapeutic alternative for cutaneous Leishmaniasis.
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•Simulation of three different acetone-methanol separation processes.•Simulation of utility plants: cooling water and steam generation for more realistic results.•Development of ...eco-indicators: CO2 emissions, energy and water consumptions.•Eco-indicators lumping in a single index for global eco-efficiency comparison.•The energetically integrated process evidences the highest potential of sustainable design.
The evaluation of environmental parameters of industrial processes plays a fundamental role in reducing not only their ecological impacts but also the costs associated with plant operations. In this regard, this work aims to evaluate, through eco-indicators and with the aid of computational simulation, the energy consumption, the CO2 emissions and the water consumption of three different acetone-methanol separation plants, namely, Pressure Swing Distillation, Conventional Extractive Distillation and Energetically Integrated Extractive Distillation. Said processes were compared to one another in terms of their environmental efficiencies by means of the Eco-efficiency Comparison Index (ECI) method, which demonstrated that the integrated process is the most ecologically friendly.
The effects of 25, 50, 75 and 100% of light intensity (137, 254, 406 and 543 μmol photons m ⁻² second ⁻¹, respectively) on aspects related to volatile synthesis in menthol mint were investigated. ...Fresh weight production, glandular trichome density and essential oil content showed a significant linear positive correlation with light intensity. Plants under low light intensity (25%) produced an essential oil with high levels of neomenthol, menthol and menthyl acetate. With 50 and 75% of light intensity plants showed an increase in expression of limonene synthase, limonene hydroxylase, (-)-isopiperitenol dehydrogenase, (+)-pulegone reductase and menthol dehydrogenase genes and an anticipation in oil maturity. With 25% of light intensity plants produced an essential oil with the best commercial profile. However, plants under 100% of light intensity produced more essential oil but with lower levels of menthol and higher levels of pulegone, that can be toxic for humans.
This work deals with the preparation of pyridine-3-carbohydrazide (isoniazid, inh) cocrystals with two α-hydroxycarboxylic acids. The interaction of glycolic acid (H2ga) or d,l-mandelic acid (H2ma) ...resulted in the formation of cocrystals or salts of composition (inh)·(H2ga) (1) and Hinh+Hma–·(H2ma) (2) when reacted with isoniazid. An N′-(propan-2-ylidene)isonicotinic hydrazide hemihydrate, (pinh)·1/2(H2O) (3), was also prepared by condensation of isoniazid with acetone in the presence of glycolic acid. These prepared compounds were well characterized by elemental analysis, and spectroscopic methods, and their three-dimensional molecular structure was determined by single crystal X-ray crystallography. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems. Finally, Hirshfeld surface analysis and Density-functional theory (DFT) calculations (including NCIplot and QTAIM analyses) have been performed to further characterize and rationalize the non-covalent interactions.
Corn grown as second-crop (safrinha) immediately after soybeans contributes to Brazil’s recent sustainable intensification of efforts to land spare and reduce deforestation. Brazil’s Mato Grosso ...state is very important for corn production with a large number of available hybrids for producers with different characteristics. Evaluating as many hybrids as possible increases the likelihood of identifying those that are more productive. Our experiment used a randomized block design to evaluate 20 corn hybrids for yield and quality in the western Cerrado savannah region of Mato Grosso state. There were significant differences in silage quality and grain yield between hybrids. Silage quality was correlated with higher grain yield. Corn grain yields for 10 higher-yielding hybrids (average = 11,425 kg/hectare) were significantly greater than the two lowest yielding hybrids (6974 and 8207 kg/hectare) and 64% more than the 2020 average in Mato Grosso. Precipitation was not limiting during our experiment but may be in the drier Cerrado area and during other years. Higher silage quality with lower lignin content and higher in vitro digestibility can improve beef productivity as Brazil transitions from extensive grazing to more intensified systems such as pasture supplementation. Increasing corn grain yields in Mato Grosso can hedge against lower crop yields elsewhere.
The initial development of the red‐bellied pacu Piaractus brachypomus is described using morphological, meristic and morphometric characteristics. A total of 127 individuals were analysed (47 in the ...yolk‐sac, 35 in pre‐flexion, five in flexion, 20 in post‐flexion and 20 in juvenile) with standard length varying between 2.92 and 48.61 mm. The larvae are born poorly developed and have a discoidal yolk at ~6.33 mm standard length. During early ontogeny, the mouth passes from terminal to subterminal and the anal opening reaches the vertical line over the midline region of the body. There are changes in body shape from long and moderate to deep, head length from small to large, and eye diameter from moderate to large. Dendritic chromatophores were present in the ventral, dorsal and upper part of the swim bladder in the early larval stages. Rounded spots are evident all over the body in juveniles. The total number of myomeres ranges from 39 to 41 (20–23 pre‐anal, 17–20 post‐anal). Through the morphometric relationships, it was evidenced that the greatest changes during the initial ontogeny of P. brachypomus occur in the transition from the post‐flexion stage to the juvenile period, indicating changes in behaviour, foraging and physiology.
Maleic anhydride may be obtained from different technological routes, being the selective oxidation of benzene and oxidation of butane the only ones that are currently in operation and, hence, ...represent competitive alternatives. In this paper, the said technologies are compared with regard to their economics and ecological performances in order to assert which one corresponds to the cleanest technology. The economics of each process was estimated on the basis of their respective cash flows, while the environmental comparison was carried out through the Eco-efficiency Comparison Index method by estimating six different categories of eco-indicators and seven life cycle metrics. To the best of our knowledge, such technologies have not been compared in terms of a joint evaluation of life cycle and eco-efficiency metrics, let alone considering the design of their respective utility plants. Finally, a sensitivity analysis was performed in order to analyze how the heuristic parameters for the utility plants considered in this work affect the estimation of the said indicators. The butane technology was shown to be more sustainable than the benzene process, since it was approximately 72% more profitable and 38% more eco-efficient than the latter.
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Nucleosomal histones are intracellular proteins that are highly conserved among Leishmania species. After parasite destruction or spontaneous lysis, exposure to these proteins elicits a strong host ...immune response. In the present study, we analyzed the protective capability of Leishmania infantum chagasi nucleosomal histones against L. braziliensis infection using different immunization strategies.
BALB/c mice were immunized with either a plasmid DNA cocktail (DNA) containing four Leishmania nucleosomal histones or with the DNA cocktail followed by the corresponding recombinant proteins plus CpG (DNA/Protein). Mice were later challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development, parasite load and the cellular immune response were analyzed five weeks after challenge. Immunization with either DNA alone or with DNA/Protein was able to inhibit lesion development. This finding was highlighted by the absence of infected macrophages in tissue sections. Further, parasite load at the infection site and in the draining lymph nodes was also significantly lower in vaccinated animals. This outcome was associated with increased expression of IFN-γ and down regulation of IL-4 at the infection site.
The data presented here demonstrate the potential use of L. infantum chagasi nucleosomal histones as targets for the development of vaccines against infection with L. braziliensis, as shown by the significant inhibition of disease development following a live challenge.
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