Cardiovascular diseases represent a major public health problem and are the leading causes of death worldwide, with ischemic heart disease leading the causes of death worldwide. In general, the heart will suffer an injury, a heart attack, which will heal through a fibrous tissue that will serve as a mechanical support to prevent rupture of the cardiac wall, causing changes in the architecture and ventricular geometry, which may lead to insufficiency Cardiac. The major problem in this regard is that adult cardiomyocytes do not proliferate spontaneously, however, studies have demonstrated that cardiomyocyte proliferation and cardiac regeneration are possible. Data obtained by our research group indicate that angiotensin- (1-7), an endogenous peptide, has the potential to induce cardiomyocyte proliferation; The central objective is to investigate whether Ang- (1-7) promotes cardiomyocyte proliferation and cardiac regeneration. For this, Wistar rats 250-300g and Approved by the Committee on Ethics in the Use of Animals of the Center of Biotechnology of the Federal University of Paraíba, under the protocol CEUA nº 0204/13. Two measures of cardiac hypertrophy were used. The first is the ratio of the weight of the heart to the length of the tibia, and the second is the ratio of the weight of the heart to the body weight. As a result, the first reason did not demonstrate any anti-hypertrophic response. In the second reason, the result was satisfactory. The method of enzymatic dissociation of cardiac tissue was used. The method is based on retrograde perfusion through the aortic artery using a collagenase-containing digestion solution. Thus, we conclude that the results indicate an antihypertrophic effect of Ang- (1-7) and that RNA extractions were satisfactory in order to obtain materials with good quantity and quality.

Inhibitor of nuclear factor kappa B kinase beta subunit (IKK-B) and extracellular signal-regulated kinase 1 (IKK-B) are two proteins involved in cytokine intracellular signaling pathways, which have a great importance due to their anti-inflammatory role. In this work, from the ChemBL database were obtained 775 and 48 structures with activity against IKK-B (CHEMBL1991) and ERK1 (CHEMBL3385) respectively. The compounds were classified using values of pIC_50, presenting a range of 4.29 (from 5.01 to 9.30) for IKK-B and 3.10 (From 5.05 to 8.15) for ERK-1. From SMILES codes, 2D structures were generated in Standardizer and after calculated 1064 two-dimensional molecular descriptors in Dragon 7 software. Obtained results were imported to Knime 3.1.0 software. All variables were submitted to autoscaling and after were partitioned to generate two groups, a training group composed by the 80% of the whole molecules set and a test group composed by the remaining 20%. (Q)SAR models was performed using a Random Forest algorithm.  Models were evaluated through cross validation (leave-one-out), Q ²_LOO = 0.69 and 0.66 as well as external test, Q ²_ext = 0.74 and 0.58 for IKK-B and ERK1 respectively. Finally, pIC50 value of 179 benzylisoquinoline alkaloids were predicted in the (Q)SAR models found 4 compound with the highest activity for each one protein studied.

Carbon nanotubes (CNTs) present important electronic, mechanical and optical properties. These properties can be different compared to the pristine nanotube when its surface is functionalized. These changes can be explored in research and application areas such as building nanodevices that act like sensors and filters. Following this idea, in this work we made a systematic study of the influence of two type of functionalization groups −OH and −COOH at different concentrations (5, 10, 15, 20 and 25%) of the surface atoms (higher concentrations were avoided due to possible steric effects). The methodology used consists in create an script that add, randomly, the functionalization groups to the surface of a (10,0) single wall CNT. In this way, we generated 10.000 structures for each concentration and selected the representative ones according the disorder created. To accomplish this, the quasi-entropy of each generated  structure was calculated using the USPEX software. All the calculations were performed using semiempirical PM7 method as implemented in the software MOPAC. For the representative structures, the highest occupied molecular orbital energy (∈H), the lowest unoccupied molecular orbital energy (∈L), the electronic gap (∆E), the chemical potential (µ), the molecular hardness (η), the electrophilicity index (ω) and the electrostatic potential were calculated. Other parameters like heat of formation, entropy, area and volume were also determined. From the obtained results we were able to correlate each calculated property with the type and concentration of the functionalization groups. From these correlations it is possible to select a priori type of functionalization and its concentration accordingly the desired property.

It is well known that the cholinergic deficiency contributes to the cognitive deterioration of Alzheimer’s Disease (AD) patients and that its pathways in the cerebral cortex are also compromised. In this work we use computational tools to design new and more powerful inhibitors of acetylcholinesterase (AChe). We made use of the de novo design and fragment-based drug design (FBDD). In the former approach, we started from reference drugs used in the AD treatment. These drugs were break into small pieces (fragments). These fragment were used as seed to grown new molecules or to be linked with other new fragments. In the latter approach, a library of fragments is docked in the active site of the enzyme. The interaction of each fragment is measured and they are organized by their affinity. The best ranked fragment are them linked between them to form new molecules with high degree of interaction with the active site of the enzyme. Using this strategy, we were able to produce a library of 2M new molecules. This library was filtered using as criterion the adsorption, distribution, metabolism and excretion (ADME) properties. The resulting library with around 6k molecules is filtered again using the Tanimoto similarity coefficient (structures with values greater than 0.85 were eliminated). The final library with 1.5k compound was submitted to docking studies. Finally, 10 compounds with better interaction energies than the reference compounds were obtained.

Natural phenolic acids such as galic, caffeic, ferulic and sinapic acids have received great attention due to their biological activities, such as antioxidant, anti-inflammatory and others. These properties place them as good candidates for the development of new controlled drug delivery systems. Among the various types of polymeric materials
applied in the development of controlled release systems, chitosan is highlighted by having a number of favourable features such as biocompatibility and biodegradability.
This work proposes an in silico molecular dynamics simulation of phenolic acids water solubility, their stability through HOMO-LUMO gap by DFT/B3LYP and the interaction of these phenolic compounds with chitosan by molecular docking study, aimed at producing new controlled release systems for drugs. The results showed that all investigated phenolic acids had adequate solubility and good interaction with chitosan and there was no significant difference in reactivity by HOMO-LUMO gap. It was concluded that all acids are good candidates for producing drug controlled release systems, because they presented adequate solubility and good stability when complexed 

The nuclear envelope (NE) needs to be reassembled after each mitotic cycle and also after fertilization, it is important to understand the regulation and dynamics of this universally conserved membrane fusion phenomenon. In this work we report the requirement of Class I PI3-Kinases for the NE formation in vitro, and its involvement in the fusion of male and female pronuclear membranes. We show for the first time that PtdIns(3,4,5)P₃ in vivo is located in the NE precursor membrane vesicles around the male pronucleus and at the vicinity of both male and female pronuclei prior to the fusion of membranes. Using coincidence amplified-FRET monitored by fluorescence lifetime imaging microscopy (FLIM) we determine the lipid-protein interaction between PtdIns(3,4,5)P₃ and the small GTPase Rab7 during pronuclear membrane fusion leading to zygote NE formation. Our work implies a direct role of polyphosphoinositides and their modifying enzymes in the NE assembly and the early stages of embryo formation.

Metabolisms represent highly organized systems characterized by strong regulations obeying to mass conservation law. This makes a whole chemical resource to be competitively shared between several biosynthesis components (ways) at both intra-and inter-molecular scales. Statistically, the whole shared-resource principle can be considered under a constant sum-unit constraint which represents the basis of simplex mixture rule. In this work, a new simplex-based chemometric approach was developed to extract scaffold information on different biosynthesis regulation factors responsible for the chemical structural diversity at atomic and molecular scales within a large metabolic system. This approach consisted in combining different (p) molecular clusters into a complete set of N mixtures containing a same constant (n) number of molecules which were randomly sampled by gradually varying the relative weights (n_j/n) of combined clusters j. The complete set of N combinations was initially given by the Scheffé’s mixture matrix. At the output of Scheffé’s design, each molecular mixture was represented by a theoretical average (barycentric) molecule which was trained by the characteristics of the different weighted clusters. The mixture design was iterated several (K) times by applying bootstrap technique leading to extensively explore chemical variability between and within clusters. Finally, the K response matrices issued from the K applications of Scheffé’s mixture design were averaged to obtain a smoothed matrix containing scaffold information on different regulation factors responsible for molecular diversification at inter- and intra- (atomic) molecular scales. This matrix was used as a backbone for graphical analysis of different positive and negative trends between atomic characteristics (chemical substitutions) at both mentioned scales. This new simplex approach was illustrated by cycloartane-based saponins of Astragalus genus by considering three desmosylation clusters (mono-, bi- and tridesmoside saponins) characterized by relative glycosylation levels of different aglycones’ carbons.

Molecular descriptors from atom weighted vectors (MD-AWV) are used in the prediction of aquatic toxicity of a large group of organic compounds of 392 benzene derivatives to the protozoo ciliate Tetrahymena pyriformis (log (IGC50) ⁻¹). These descriptors are calculated using the MD-LOVIs software and various Aggregation Operators are examined with the aim comparing their performances in predicting aquatic toxicity. Variability analysis is used to quantify the information content of these molecular descriptors by means of an information theory-based algorithm. Principal Component Analysis (PCA) is used to analyze the orthogonality of these descriptors and it is observed that MD-AWV provide linearly independent information from that of descriptors generated using the popular DRAGON package (0-2D). Multiple Linear Regression with Genetic Algorithms is used to obtain models of the structure–toxicity relationships; the best model shows values of Q²= 0.830 and R²=0.837 using six variables. Our models compare favorably with other previously published models that use the same data set. The obtained results suggest that MD-AWV provide an effective alternative for determining aquatic toxicity of benzene derivatives.

Agricultural activity is a feasible alternative in the Amazon as long as technologies are used to generate social, environmental and economic benefits without changing the ecology of the system. In the Amazon region has made ​​work that showed different distribution, geographic presence and incidence of various parasitic genera that affect cattle. The aim of the present study was to evaluate the association between age and nematodes in cattle under free grazing in Canton Arosemena Tola Province Napo - Ecuador. 147 cattle feces were sampled during March 2011 and November 2012. The collection of faeces was carried out during the early hours of the morning and were obtained directly from the rectum of the animal. Coproparasitological analyzes were performed at the Laboratory of Parasitological Diagnosis Vetetinario Chaco-Ecuador. Of the total number of sampled animals were divided into two groups: ≤ twelve months (31) and ≥ to twelve months of age (116). The relationship between nematodes and age was assessed with a test of homogeneity based on Chi-square statistics (P <0.05) and hypothesis test for continuous variables, Student t according to (P <0.05). In Bunostomun, Neoscaris, Trichostrongylus spp, Cooperia, Oesophagostomun, Stronyiloides and Ostertagia parasites are significant (Chi2 (P <0.0001) among children ages twelve months and older than twelve months. There is a very low presence of nematodes in animals older than one year, and 80% expressed no parasites. by contrast 70% of small animals has a high parasite load in the stage of development and growth, certainly impacting on the daily weight gain (ADP). We conclude that there is an association between the presence of nematodes and age of cattle.

Lactic acid bacteria isolated from diverse ecosystems are known as the most versatile microorganisms used as probiotic or functional foods.  In the recent years, lactobacillus species were exploited for the selection of strains with antimicrobial molecules to be used in bio-preservation of food products. In this study we isolated and identify Lactobacillus plantarum UTNCys3.4 strain from Solanum stramonifolium fruits of Ecuadorian Amazon rainforest and evaluated the spectrum of inhibiting several foodborne pathogens commonly found in local food. However, using agar-well diffusion bioassay, the crude supernatant fluid (CFS) derived Cys3.4 strain showing elevated antimicrobial activity against E. coli ATCC 25922, Salmonella enterica subsp. enterica ATCC 51741, E. coli O157:H7 UTNEc1, Enterococcus aeruginosa UTNEn1, Salmonella Typhi UTNSm2 and Shigella UTNShg1 was further characterized for the presence of bacteriocin-like molecules. The antimicrobial activity of CFS was stable after heating at the ranking 60 to 121°C for 30 min, the activity was activated by exposure at acidic pH of 2.0 to 6.0 and decline at 10.0, suggesting that the inhibitory activity is related with the presence of either inhibitory peptides or organic acids.  Its active principle was proteinaceous in nature since the bacteriocin was inactivated by proteolytic enzymes, while resistance to lysozyme indicated their non-lipid and carbohydrate moiety form. These compounds were detected after 3 hours of bacterial growth indicating that the peptides were primary metabolites which might act as a barrier against pathogen growth and can be further exploited industrially to explore their biopreservante properties.