A Strategy Utilizing Protein-Protein Interaction Hubs for the Treatment of Cancer Diseases.

We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient's overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.

Treatment with Bixin-Loaded Polymeric Nanoparticles Prevents Cigarette Smoke-Induced Acute Lung Inflammation and Oxidative Stress in Mice.

The use of annatto pigments has been evaluated as a therapeutic strategy in animal models of several health disorders. Beneficial effects were generally attributed to the inhibition of oxidative stress. Bixin is the main pigment present in annatto seeds and has emerged as an important scavenger of reactive oxygen (ROS) and nitrogen species (RNS). However, this carotenoid is highly hydrophobic, affecting its therapeutic applicability. Therefore, bixin represents an attractive target for nanotechnology to improve its pharmacokinetic parameters. In this study, we prepared bixin nanoparticles (npBX) and evaluated if they could prevent pulmonary inflammation and oxidative stress induced by cigarette smoke (CS). C57BL/6 mice were exposed to CS and treated daily (by gavage) with different concentrations of npBX (6, 12 and 18%) or blank nanoparticles (npBL, 18%). The negative control group was sham smoked and received 18% npBL. On day 6, the animals were euthanized, and bronchoalveolar lavage fluid (BALF), as well as lungs, were collected for analysis. CS exposure led to an increase in ROS and nitrite production, which was absent in animals treated with npBX. In addition, npBX treatment significantly reduced leukocyte numbers and TNF-α levels in the BALF of CS-exposed mice, and it strongly inhibited CS-induced increases in MDA and PNK in lung homogenates. Interestingly, npBX protective effects against oxidative stress seemed not to act via Nrf2 activation in the CS + npBX 18% group. In conclusion, npBX prevented oxidative stress and acute lung inflammation in a murine model of CS-induced acute lung inflammation.

Starch, inulin and maltodextrin as encapsulating agents affect the quality and stability of jussara pulp microparticles.

The influence of encapsulating carbohydrates (EC) with varying properties on the technological and functional properties of jussara pulp microparticles produced by spray drying were evaluated using experimental design. Microparticles produced with sodium octenyl succinate (OSA) starch at 0.5 core to EC ratio and with mixtures of inulin and maltodextrin at 1.0 and 2.0 core to EC ratio showed darker color, and higher anthocyanins contents and antioxidant activity. Seven microparticles showing high water solubility and desirable surface morphology. Hygroscopicity (10.7% and 11.5%) and wettability (41s and 43s) were improved when OSA starch and mixtures of inulin and maltodextrin were used. The anthocyanins contents and color of the microparticles did not change when exposed to light at 50°C for 38days. Finally, microparticles produced at 1.0 core to EC ratio with 2/3 OSA starch, 1/6 inulin and 1/6 maltodextrin were selected. These microparticles may be applied as colorant in numerous foods, whilst adding prebiotic fiber and anthocyanins.

Spray-dried extract from the Amazonian adaptogenic plant Ampelozizyphus amazonicus Ducke (Saracura-mirá): Chemical composition and immunomodulatory properties.

Ampelozizyphus amazonicus Ducke is a medicinal plant used in the Amazon region to prepare a drink with tonic, immunomodulatory and adaptogenic properties. Due to the growing interest in dietary supplements with these properties and, to provide a new functional ingredient, barks from A. amazonicus were extracted. The extract was spray dried without drying adjuvants, resulting in a powder (SARF), which was characterized by its physico-chemical properties and proximate, mineral and saponin contents. The SARF saponins were characterized by ultra-high-performance liquid chromatography/high resolution accurate mass spectrometry (HPLC-HRMSn) analysis. The SARF particles tended to have a spherical shape and a unimodal size distribution. The particles also had good rehydration characteristics and high saponin content (33%). The effect of SARF on antibody production was investigated, and we found that SARF increased the basal levels of anti-ovalbumin, anti-LPS and anti-dextran IgM antibodies, and the anti-dextran IgG antibodies in unimmunized mice. No increase in antibody titers was observed after SARF treatment in immunized mice. These results suggest that SARF could be an interesting new functional ingredient for food applications or pharmaceutical products.

Linhaça marrom e dourada: propriedades químicas e funcionais das sementes e dos óleos prensados a frio / Brown and golden flaxeed: chemical and functional properties of the seeds and the cold-pressed oils

O objetivo do estudo foi comparar a composição química e a capacidade antioxidante das sementes e dos óleos de linhaça marrom e dourada, e avaliar a estabilidade oxidativa dos óleos. Nas sementes, foram determinados: composição centesimal, capacidade antioxidante total e compostos fenólicos totais. Nos óleos, foram determinados: índice de acidez e peróxido, matéria insaponificável, composição em ácidos graxos, tocoferóis, capacidade antioxidante, compostos fenólicos totais e estabilidade oxidativa em quatro condições de estocagem por até um ano. Não houve diferenças significativas entre os tipos de sementes quanto às variáveis investigadas, e ainda entre os óleos quanto ao rendimento da prensagem, composição em ácidos graxos insaturados, índice de acidez, teores de insaponificáveis e compostos fenólicos totais. Apesar do declínio da estabilidade oxidativa de ambos os óleos durante o armazenamento, o óleo de linhaça marrom e os óleos estocados sob refrigeração apresentaram-se mais estáveis. O índice de peróxido foi maior no óleo de linhaça dourada. O teor de tocoferol total e capacidade antioxidante total foram maiores no óleo de linhaça marrom. Contudo, observou-se uma igualdade entre as sementes de ambas as variedades de linhaça e uma superioridade do óleo de linhaça marrom.

The aim of the study was to compare the chemical composition and antioxidant capacity of the brown and golden flaxseed and their cold-pressed oils, and evaluate the oxidative stability of oils. We determined the chemical composition, total antioxidant capacity and total phenolic compounds of the seeds. In the oils we determined acid and peroxide value, unsaponifiable matter, composition of fatty acids and tocopherols, phenolic compounds, antioxidant capacity and oxidative stability in four storage conditions up to one year. There were no significant differences between the flaxseed types in the analyzed properties and between the oils in terms of yield after pressing, composition of unsaturated fatty acids, acid value, unsaponifiables and phenolic compounds. The oxidative stability of both oils decreased with storage time, however the brown flaxseed oil and the oils stored under refrigeration were more stable. The peroxide value was higher in the golden flaxseed oil. The total tocopherol content and antioxidant capacity were higher in brown flaxseed oil. It was observed equality between the brown and golden flaxseed and a superiority of brown flaxseed oil.

Immunobiologic and antiinflammatory properties of a bark extract from Ampelozizyphus amazonicus Ducke.

Ampelozizyphus amazonicus is used in the treatment and prevention of malaria. The effect of an aqueous extract from this plant (SART) on the immune response was investigated by measuring immunoglobulin production induced by immunization with the antigen TNP-Ficoll in Plasmodium chabaudi-infected mice. SART treatment increased antigen-specific IgM and IgG levels in TNP-Ficoll-immunized mice. The B cell response during malarial infection was also modified by SART. There was an increase in total serum IgM and IgG and a decrease in the percentage of splenic plasma cells (CD138+ cells) in P. chabaudi-infected, SART-treated animals. SART (1, 3 or 10 mg/kg, p.o.) and the reference drug dexamethasone (5 mg/kg) were also tested in carrageenan-induced leukocyte migration to the subcutaneous air pouch (SAP). All SART doses significantly reduced leukocyte migration into the SAP. The protein concentration resulting from extravasation into the peritoneum was also significantly reduced. Our data indicate that SART possesses immunomodulatory properties, inducing an in vivo modification of the B lymphocyte response and anti-inflammatory properties, which are partly due to a reduction in cell migration and are most likely due to an inhibition of the production of inflammatory mediators. Preliminary HPLC-ESI-MS/MS analysis of SART shows a complex saponin profile with deprotonated molecule [M-H](-) ions in the range of m/z 800-1000.

Microcapsules of alginate/chitosan containing magnetic nanoparticles for controlled release of insulin.

The challenge of this work was to investigate the potential of alginate/chitosan beads containing magnetite nanoparticles as a drug delivery system. The insulin beads were prepared by dripping a solution of sodium alginate containing insulin into a CaCl(2) solution. Magnetite nanoparticles of 5 nm mean size were synthesized inside the alginate egg-box structure by co-precipitation of Fe(III) and Fe(II) in the presence of NH(4)OH. Quantitative analysis revealed that insulin encapsulation depends on the initial protein content and 35% of insulin was entrapped by alginate beads for a protein concentration of 10 wt%. It was verified that approximately 50% of the insulin was released to Milli-Q water in 800 h release experiments. The application of oscillating magnetic field increased three fold the insulin release. The results suggest that the alginate/chitosan system containing magnetite nanoparticles is a promising system for clinical applications of controlled release of insulin in the presence of an oscillating magnetic field in a subcutaneous implant approach.