Biofortificação de selênio no crescimento de alho e avaliação de acúmulo de outros elementos nutrientes

Selenium (Se) is an essential element for humans and has anti-cancer function. Garlic can accumulate Se, so it is an option to Se supplementation in the human diet. The aim of this research was to study Se uptake and accumulation during garlic growth. Four doses of Na2 SeO4 and Na2 SeO3 solution were applied in the substrate (0, 5, 10 and 15 kg ha-1 Se) for one time in August 2014, with a random plot design and 3 replicates on garlic clone Rubi INTA. Three harvests were made, in September, October and December 2014. After each harvest, leaves, bulbs and roots were separated and conditioned (peeled and chopped), lyophilized, and finally acid-digested prior to Se, Mg, Zn, Mn, Cu, Fe, P and S determination by inductively coupled plasma mass spectrometry (ICP-MS). The Se accumulation was proportional to Se doses and did not affect garlic growth. Also, Se distribution among different organs was related to the garlic growth cycle. The Se presence decreased accumulation of Mg, Mn, Cu, Fe, P and S but increased Zn accumulation in plants. Garlic can be an important Se source to humans but it is important to consider Se-doses for biofortification.O selênio (Se) é elemento essencial para os seres humanos e é considerado anticancerígeno. Alho pode acumular Se, sendo, por isso, uma opção para a suplementação de Se na dieta humana. Assim, o objetivo deste trabalho foi estudar a captação e acúmulo de selênio durante o crescimento do alho e avaliar os efeitos da fortificação de Se. Quatro doses da solução de Se, nas formas de Na2 SeO4 e Na2 SeO3 foram aplicadas ao substrato em agosto de 2014 (0, 5, 10 e 15 kg ha-1 de Se) de uma única vez, em delineamento de parcela aleatória e 3 repetições no clone de alho Rubi INTA. Três colheitas foram feitas, em setembro, outubro e dezembro de 2014. Após cada colheita, as folhas, bulbos e raízes das amostras de alho resultantes de cada tratamento foram separadas e acondicionadas (descascadas e picadas), liofilizadas, e, finalmente, digeridas com ácido antes da determinação de Mg, Zn, Mn, Cu, Fe, P e S por espectrometria de massa com plasma indutivamente acoplado (ICP-MS). Os resultados confirmaram que o acúmulo de Se foi proporcional à magnitude das doses, e não afetou significativamente o crescimento do alho. Além disso, a distribuição de Se entre os diferentes compartimentos da planta foi relacionada ao ciclo de crescimento da planta de alho. A fortificação do alho com Se causou mudanças significativas, e induziu o acúmulo e distribuição de diferentes nutrientes, como Zn, Mg, Mn, Cu, Fe, P e S, mas aumentou o acúmulo de Zn nas plantas. O alho pode ser considerado fonte importante de Se para aumentar a ingestão deste elemento na dieta humana, mas é importante considerar as doses de Se para a biofortificação.Fil: Pérez, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Química Analítica para Investigación y Desarrollo; ArgentinaFil: Lipinski, Víctor Mario. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Mendoza-San Juan. Estación Experimental Agropecuaria La Consulta; ArgentinaFil: Filippini, Maria Flavia Ramona. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Química Analítica para Investigación y Desarrollo; ArgentinaFil: Chacón Madrid, Katherine. Universidade Estadual Do Campinas. Instituto de Química.; BrasilFil: Arruda, Marco Aurelio Z.. Universidade Estadual Do Campinas. Instituto de Química.; BrasilFil: Wuilloud, Rodolfo German. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Química Analítica para Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentin

Molecular dynamics and physical stability of amorphous nimesulide drug and its binary drug-polymer systems

yesIn this paper we study the effectiveness of three well known polymers: inulin, Soluplus and PVP in stabilizing amorphous form of nimesulide (NMS) drug. The re-crystallization tendency of pure drug as well as measured drug-polymer systems were examined at isothermal conditions by using broadband dielectric spectroscopy (BDS), and at non-isothermal conditions by differential scanning calorimetry (DSC). Our investigation has shown that the crystallization half-life time of pure NMS at 328 K is equal to 33 minutes. We found that this time can be prolonged to 40 years after adding to NMS 20% of PVP polymer. This polymer proved to be the best NMS’s stabilizer, while the worst stabilization effect was found after adding the inulin to NMS. Additionally, our DSC, BDS and FTIR studies indicate that for suppression of NMS’s re-crystallization in NMS-PVP system, the two mechanisms are responsible: the polymeric steric hindrances as well as the antiplastization effect excerted by the excipient.The authors J.K., Z.W., K.G. and M.P., are grateful for the financial support received within the Project No. 2015/16/W/NZ7/00404 (SYMFONIA 3) from the National Science Centre, Poland. H.M. and L.T. are supported by Science Foundation Ireland under grant No. 12/RC/2275 (Synthesis and Solid State Pharmaceuticals Centre)

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

TrkB is highly expressed in NSCLC and mediates BDNF-induced the activation of Pyk2 signaling and the invasion of A549 cells

<p>Abstract</p> <p>Background</p> <p>Aberrant regulation in the invasion of cancer cells is closely associated with their metastatic potentials. TrkB functions as a receptor tyrosine kinase and is considered to facilitate tumor metastasis. Pyk2 is a non-receptor tyrosine kinase and integrates signals in cell invasion. However, little is known about the expression of TrkB in NSCLC and whether Pyk2 is involved in TrkB-mediated invasion of A549 cells.</p> <p>Methods</p> <p>The expression of TrkB was investigated in NSCLC by immunohistochemical staining. Both HBE and A549 cells were treated with BDNF. The expression of TrkB, Pyk2 and ERK phosphorylations were assessed by western blot. Besides, A549 cells were transfected with TrkB-siRNA or Pyk2-siRNA, or treated with ERK inhibitor where indicated. Transwell assay was performed to evaluate cell invasion.</p> <p>Results</p> <p>40 cases (66.7%) of NSCLC were found higher expression of TrkB and patients with more TrkB expression had significant metastatic lymph nodes (p = 0.028). BDNF facilitated the invasion of A549 cells and the activations of Pyk2 in Tyr402 and ERK. However, the effects of BDNF were not observed in HBE cells with lower expression of TrkB. In addition, the increased Pyk2 and ERK activities induced by BDNF were significantly inhibited by blocking TrkB expression, so was the invasion of A549 cells. Knockdown studies revealed the essential role of Pyk2 for BDNF-induced cell invasion, since the invasion of A549 cells was abolished by Pyk2-siRNA. The application of ERK inhibitor also showed the suppressed ERK phosphorylation and cell invasion.</p> <p>Conclusion</p> <p>These data indicated that higher expression of TrkB in NSCLC was closely correlated with lymph node metastasis, and BDNF probably via TrkB/Pyk2/ERK promoted the invasion of A549 cells.</p

Identification of a better Homo sapiens Class II HDAC inhibitor through binding energy calculations and descriptor analysis

Human papillomaviruses (HPVs) are the most common on sexually transmitted viruses in the world. HPVs are responsible for a large spectrum of deseases, both benign and malignant. The certain types of HPV are involved in the development of cervical cancer. In attemps to find additional drugs in the treatment of cervical cancer, inhibitors of the histone deacetylases (HDAC) have received much attention due to their low cytotoxic profiles and the E6/E7 oncogene function of human papilomavirus can be completely by passed by HDAC inhibition. The histone deacetylase inhibitors can induce growth arrest, differentiation and apoptosis of cancer cells. HDAC class I and class II are considered the main targets for cancer. Therefore, the six HDACs class II was modeled and about two inhibitors (SAHA and TSA) were docked using AutoDock4.2, to each of the inhibitor in order to identify the pharmacological properties. Based on the results of docking, SAHA and TSA were able to bind with zinc ion in HDACs models as a drug target. SAHA was satisfied almost all the properties i.e., binding affinity, the Drug-Likeness value and Drug Score with 70% oral bioavailability and the carbonyl group of these compound fits well into the active site of the target where the zinc is present. Hence, SAHA could be developed as potential inhibitors of class II HDACs and valuable cervical cancer drug candidate

A physicochemical descriptor-based scoring scheme for effective and rapid filtering of kinase-like chemical space

<p>Abstract</p> <p>Background</p> <p>The current chemical space of known small molecules is estimated to exceed 10⁶⁰structures. Though the largest physical compound repositories contain only a few tens of millions of unique compounds, virtual screening of databases of this size is still difficult. In recent years, the application of physicochemical descriptor-based profiling, such as Lipinski's rule-of-five for drug-likeness and Oprea's criteria of lead-likeness, as early stage filters in drug discovery has gained widespread acceptance. In the current study, we outline a kinase-likeness scoring function based on known kinase inhibitors.</p> <p>Results</p> <p>The method employs a collection of 22,615 known kinase inhibitors from the ChEMBL database. A kinase-likeness score is computed using statistical analysis of nine key physicochemical descriptors for these inhibitors. Based on this score, the kinase-likeness of four publicly and commercially available databases, i.e., National Cancer Institute database (NCI), the Natural Products database (NPD), the National Institute of Health's Molecular Libraries Small Molecule Repository (MLSMR), and the World Drug Index (WDI) database, is analyzed. Three of these databases, i.e., NCI, NPD, and MLSMR are frequently used in the virtual screening of kinase inhibitors, while the fourth WDI database is for comparison since it covers a wide range of known chemical space. Based on the kinase-likeness score, a kinase-focused library is also developed and tested against three different kinase targets selected from three different branches of the human kinome tree.</p> <p>Conclusions</p> <p>Our proposed methodology is one of the first that explores how the narrow chemical space of kinase inhibitors and its relevant physicochemical information can be utilized to build kinase-focused libraries and prioritize pre-existing compound databases for screening. We have shown that focused libraries generated by filtering compounds using the kinase-likeness score have, on average, better docking scores than an equivalent number of randomly selected compounds. Beyond library design, our findings also impact the broader efforts to identify kinase inhibitors by screening pre-existing compound libraries. Currently, the NCI library is the most commonly used database for screening kinase inhibitors. Our research suggests that other libraries, such as MLSMR, are more kinase-like and should be given priority in kinase screenings.</p