Novel Findings about Double-Loaded Curcumin-in-HPβcyclodextrin-in Liposomes: Effects on the Lipid Bilayer and Drug Release

In this study, the encapsulation of curcumin (Cur) in “drug-in-cyclodextrin-in-liposomes (DCL)” by following the double-loading technique (DL) was proposed, giving rise to DCL–DL. The aim was to analyze the effect of cyclodextrin (CD) on the physicochemical, stability, and drug-release properties of liposomes. After selecting didodecyldimethylammonium bromide (DDAB) as the cationic lipid, DCL–DL was formulated by adding 2-hydroxypropyl-α/β/γ-CD (HPβCD)–Cur complexes into the aqueous phase. A competitive effect of cholesterol (Cho) for the CD cavity was found, so cholesteryl hemisuccinate (Chems) was used. The optimal composition of the DCL–DL bilayer was obtained by applying Taguchi methodology and regression analysis. Vesicles showed a lower drug encapsulation efficiency compared to conventional liposomes (CL) and CL containing HPβCD in the aqueous phase. However, the presence of HPβCD significantly increased vesicle deformability and Cur antioxidant activity over time. In addition, drug release profiles showed a sustained release after an initial burst effect, fitting to the Korsmeyer-Peppas kinetic model. Moreover, a direct correlation between the area under the curve (AUC) of dissolution profiles and flexibility of liposomes was obtained. It can be concluded that these “drug-in-cyclodextrin-in-deformable” liposomes in the presence of HPβCD may be a promising carrier for increasing the entrapment efficiency and stability of Cur without compromising the integrity of the liposome bilayer

Questões sobre território e pós-pandemia: Abordagens à sua complexidade

El sistema mundial en su actual estadio de la globalización atraviesan una profunda crisis que se expresa en este momento, entre otros factores, en la declaración de una pandemia con la aparición de un nuevo virus que se conoce como el síndrome respiratorio agudo grave, SARS-CoV-2, causante del Covid 19. Esta pandemia, como las diferentes zoonosis, son expresiones de la degradación de los ecosistemas como consecuencia de la ruptura de los equilibrios en la biodiversidad acelerada por la voracidad de la deforestación, las grandes obras de infraestructura, la mega minería, los incendios, el avance de la agricultura y la ganadería industrial, entre otras actividades. Este trabajo indaga sobre una problemática compleja a la cual considera resultante de la interrelación e interdefinición de múltiples procesos físicos, sociales, económicos, técnicos y políticos, orientados por una racionalidad instrumental y economicista que constituyen las formas dominantes de apropiación social de la naturaleza. La interrelación entre la crisis global del productivismo, la producción del territorio y el desarrollo de una pandemia es el problema de investigación que abordamos en este texto con la intención de aportar algunas preguntas para pensar el territorio y la pospandemia.O sistema mundial no seu atual estágio de globalização vive uma profunda crise que se expressa neste momento, entre outros fatores, na declaração de uma pandemia com o surgimento de um novo vírus conhecido como síndrome respiratória aguda grave, a SARSCoV-2, a causa da Covid 19. Esta pandemia, como as diferentes zoonoses, são expressões da degradação dos ecossistemas como consequência da quebra dos equilíbrios da biodiversidade acelerada pela voracidade do desmatamento, grandes obras de infraestrutura, megamineração, queimadas, o avanço da agricultura e da pecuária industrial, entre outras atividades. Este trabalho explora um problema complexo que é considerado o resultado das formas dominantes de apropriação social da natureza e da inter-relação e interdefinição de múltiplos processos físicos, sociais, econômicos, técnicos e políticos. A inter-relação entre a crise global do produtivismo, a produção do território e o desenvolvimento de uma pandemia é o problema de pesquisa que abordamos neste texto com o intuito de contribuir com algumas questões para pensar o território e a póspandemia.Fil: Fernández Equiza, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto de Geografía, Historia y Ciencias Sociales. Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto de Geografía, Historia y Ciencias Sociales; ArgentinaFil: Álvarez, Álvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto de Geografía, Historia y Ciencias Sociales. Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto de Geografía, Historia y Ciencias Sociales; Argentin

Preguntas sobre territorio y pospandemia. Aproximaciones a su complejidad

El sistema mundial en su actual estadio de la globalización atraviesan una profunda crisis que se expresa en este momento, entre otros factores, en la declaración de una pandemia con la aparición de un nuevo virus que se conoce como el síndrome respiratorio agudo grave, SARS-CoV-2, causante del Covid 19. Esta pandemia, como las diferentes zoonosis, son expresiones de la degradación de los ecosistemas como consecuencia de la ruptura de los equilibrios en la biodiversidad acelerada por la voracidad de la deforestación, las grandes obras de infraestructura, la mega minería, los incendios, el avance de la agricultura y la ganadería industrial, entre otras actividades. Este trabajo indaga sobre una problemática compleja a la cual considera resultante de la interrelación e interdefinición de múltiples procesos físicos, sociales, económicos, técnicos y políticos, orientados por una racionalidad instrumental y economicista que constituyen las formas dominantes de apropiación social de la naturaleza. La interrelación entre la crisis global del productivismo, la producción del territorio y el desarrollo de una pandemia es el problema de investigación que abordamos en este texto con la intención de aportar algunas preguntas para pensar el territorio y la pospandemia.publishedVersionFil: Fernández Equíza, Ana María. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Humanas; Argentina.Fil: Álvarez, Álvaro. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Humanas; Argentina

In vitro evaluation of a morphine polymeric complex: flowability behavior and dissolution study

The purpose of this research was to perform a granulometrical and flow properties study of a morphine polymeric complex and determine the influence of 3 variables—particle size of complex, pH value, and ionic strength of the dissolution medium—on the dissolution behavior. The morphineEudragit L complex was produced in aqueous medium from morphine hydrochloride saturated solution and Eudragit L 30D diluted until 12% wt/vol and partially neutralized (40%). To determine the rheological behavior of the complex, several rheological tests were developed: bulk and tapped densities, Hausner ratio, angle of repose, and flow rate. The results corresponding to the technological study suggest that the 100- to 250-µm fraction can be considered as free flowing powder. In relation to the dissolution behavior of the complex, the results indicate that the ionic strength has been detected as the most influencing factor when values below physiological conditions are used. In conclusion, no technological problems for the production of further solid dosage forms are expected. Furthermore, no changes in the dissolution profiles of the complex have been detected when ionic strength values are inside the physiological range

Strategies to improve the robustness of acentrosomal spindle formation in female meiosis

In meiosis, centrosomes are so important because they organize microtubules and nucleation of the spindle for a correct chromosomal segregation in eukaryotics cells. Human female oocytes lack centrosomes, so microtubules must self-assembly, which can cause mistakes in the process and diseases to the embryo. To study the molecular mechanisms supporting acentrosomal spindle, we are using the fission yeast Saccharomyces pombe as model scenario. In this organism, spindle pole bodies (SPBs), the functional equivalents of centrosomes, are sitting on the nuclear envelope (NE), which is dissasembled in each cell cycle by activating proteins like Sad1 and Bqt1, that mediate chromosome-NE contacts (Pineda-Santaella & Fernández-Álvarez, 2019). Based on these findings, our aims are making the acentrosomal spindle more robust and minimizing chromosomal segregation errors. In order to get then, we want to analyze the effects of overexpression of Cls1p, a cytoplasmic linker associated protein (CLASP) that stabilizes specific groups of MTs in S. pombe and has two homologous proteins in humans, CLASP1 and CLASP2. They contribute to the formation and maintenance of the spindle midzone by promoting MT rescue events (Al-Bassam et al., 2010). On the other hand, there are another important proteins in this process, like Klp6, a kind of kinesin-8, whose homologous proteins in humans are Kif18A, Kif18B, and Kif19. An in vivo study suggets that Klp6 binds to the tubulin triggering the birth of new MTs and promoting nucleation and catastrophe at the growing MT tip (Erent et al., 2012). Deletion or knockdown of Klp6 leads to longer spindles and defects in its assembly and position in many cases (Gergely et al., 2017), but we suggest that a longer acentrosomal spindle could also be stronger and more stable. So, we also pretend to observe the impact of deletion of klp6 on the spindle behavior and chromosome movements. To perform that experiments, we have obtained two different mutants for klp6 and cls1 in a bqt1Δ sad1.2 background by crossing some strains with these characteristics and we are studying what happens in the cell nucleus by fluorescent microscopy, using a DeltaVision microscope. As a result, we expect that chromosomal segregation in mutants for cls1 and klp6 will be more efficient with respect to the mutant control, which has only bqt1Δ sad1.2, and, ultimately, improve the meiotic process in this context

Inhibition of VEGF-Induced VEGFR-2 Activation and HUVEC Migration by Melatonin and Other Bioactive Indolic Compounds

Excessive concentrations of vascular endothelial growth factor (VEGF) trigger angiogenesis, which causes complications such as the destabilization of atherosclerotic plaques and increased growth of tumors. This work focuses on the determination of the inhibitory activity of melatonin and other indolic related compounds on VEGF-induced VEGF receptor-2 (VEGFR-2) activation and an approximation to the molecular mechanism underlying the inhibition. Quantification of phosphorylated VEGFR-2 was measured by ELISA. Migration wound-healing assay was used to determine cell migration of human umbilical vein endothelial cells (HUVECs). This is the first time that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin are proved to significantly inhibit VEGF-induced VEGFR-2 activation in human umbilical vein endothelial cells and subsequent angiogenesis. 3-Indolacetic acid showed the highest inhibitory effect (IC50 value of 0.9704 mM), followed by 5-hydroxytryptophol (35% of inhibition at 0.1 mM), melatonin (30% of inhibition at 1 mM), and serotonin (24% of inhibition at 1 mM). An approximation to the molecular mechanism of the inhibition has been proposed, suggesting that indolic compounds might interact with the cell surface components of the endothelial membrane in a way that prevents VEGF from activating the receptor. Additionally, wound-healing assay revealed that exposure of HUVECs to melatonin and 3-indolacetic acid in the presence of VEGF significantly inhibited cell migration by 87% and 99%, respectively, after 24 h. These data demonstrate that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin would be good molecules for future exploitation as anti-VEGF signaling agents.España, Ministerio de Ciencia e Innovación AGL2013-47300-C3-2-

Efeito do tamanho das partículas de calcário nos teores de Ca, Mg e K no solo e em plantas forrageiras

Liming increases crop production through improved soil conditions in acidic soils. Among the effects of liming, increased availabilities of alkaline and alkaline-earth cations are worth mention. These availabilities may be affected by the particle size of applied limestone, which influences lime reactivity. The effects of particle size and application schedule of magnesium limestone were investigated on extractable Ca, Mg and K in soil, their concentrations in sward plants and dry-matter yield. Magnesium limestone of various particle sizes was applied to experimental plots at a rate of 3 t ha-1, a grass-clover sward was sown, and the plots were monitored during three years. The finest limestone (< 0.25 mm) in a single application yielded the highest soil Ca and Mg concentrations extracted by Mehlich-3 and NH4Cl. The same limestone split in three annual doses was less effective. Plots treated with the coarsest limestone (2-4 mm) did not differ from control plots. Liming had no effect on potassium, either in soil or plants. Soil concentrations of Ca, Mg and K extracted by Mehlich-3 and NH4Cl were correlated with each other (r = 0.76, 0.75 and 0.67, respectively). NH4Cl extracted more Ca than Mehlich-3, while the latter extracted more Mg and K than NH4Cl. Soil Ca, Mg and K extracted by NH4Cl were also correlated to water extractions. Mg concentration in plants correlated to soil Mg extracted by NH4Cl or by water. Neither the concentrations nor the total contents of Ca and K in plants correlated with extractable soil Ca and K. The total dry matter yield was not affected by liming. The yield of sown species was higher in plots treated with the finest limestone than in plots limed with the coarsest limestone. Cations extracted by water or NH4Cl explained the variance of dry matter yield.A aplicação de calcário em solos ácidos promove aumento da produção agrícola por meio da melhoria das condições do solo. Entre os efeitos da calagem, o aumento da disponibilidade de cátions alcalinos e alcalino-terrosos são dignos de menção. Essas disponibilidades podem ser afetadas pelo tamanho das partículas do calcário aplicado, que influencia a solubilidade do mesmo. Investigaram-se os efeitos da granulometria e épocas de aplicação de calcário magnesiano nos cátions trocáveis Ca, Mg e K extraidos no solo, nas suas concentrações em plantas crescidas cultivadas nesse solo e no rendimento das suas matérias secas. Vários tamanhos de partículas de calcário magnesiano foram aplicadas às parcelas experimentais, a uma taxa de 3 t ha-1, gramíneas e trevo foram plantados e as parcelas foram monitoradas durante três anos. O calcário mais fino (< 0,25 mm) em uma única aplicação proporcionou os maiores teores de Ca e Mg extraídos por Mehlich-3 e por NH4Cl. Este mesmo calcário quando aplicado parcelado em três doses anuais foi menos eficaz. Parcelas tratadas com o clacário mais grosseiro (2-4 mm) não diferiram da testemunha. A calagem não teve efeito sobre o potássio, quer seja no solo ou nas plantas. As concentrações no solo de Ca, Mg e K extraídos por Mehlich-3 e NH4Cl foram positivamente correlacionadas. O NH4Cl extraiu mais Ca do que o Mehlich-3, enquanto o segundo extraíu mais Mg e K do que o NH4Cl. O Ca, Mg e K extraídos pelo NH4Cl foram também correlacionados com extrações por água. Concentrações de Mg em plantas estão relacionadas com concentrações de Mg no solo extraídos pelo NH4Cl ou pela água. Nem as concentrações ou teores totais de Ca e K nas plantas correlacionaram-se com as concentrações extraídas de Ca e K do solo. O rendimento de matéria seca total não foi afetado pela calagem. A produtividade das espécies cultivadas foi maior nas parcelas tratadas com os calcários mais finos do que em parcelas com calcário mais grosseiro. Cátions extraídos pela água ou NH4Cl correlacionaram-se com a variação da produção de matéria seca.This research was supported by autonomous Government of GalicianS