Anti-angiogenic activity evaluation of secondary metabolites from Calycolpus moritzianus leaves

Angiogenesis is a crucial step in many pathological conditions like cancer, inflammation and metastasis formation; on these basis the search for antiangiogenic agents has widened. In order to identify new compounds able to interfere in the Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1, also known as Flt-1) recognition by VEGFs family members, we screened Calycolpus moritzianus (O. Berg) Burret leaves extracts by a competitive ELISA-based assay. MeOH and CHCl3 extracts and several their fractions demonstrated to be able to prevent VEGF or PlGF interaction with Flt-1, with an inhibition about 50% at concentration of 100 microg/mL. Phytochemical and pharmacological investigation of the active fractions led to the isolation of flavonoids, and terpenes.     

Synthesis,characterization, and investigations of antimicrobial activity of benzopyrans,benzofurans and spiro[4.5]decanes

In this study, the radical cyclization reactions of cyclic 1,3-dicarbonyl compounds (1a–c) and α,β-unsaturated alcohols (2a–d) through Mn(OAc)₃ were performed. A series of biologically interesting dihydropyrans (3–5) and dihydrofurans (6–18) were synthesized as a result of these reactions. Spiro compounds (19–20) were obtained from the reactions of 1,3-dicarbonyl compounds and (E)-2,4-diphenyl-but-3-en-2-ol (2e). The unique structure of compound 19 was also confirmed by X-ray crystallography. In addition, the antibacterial activities of synthesized compounds were screened against some bacteria. Their zone diameters showed better results than some known antibiotics.     

N-acylbenzotriazole mediated microwave assisted synthesis of protected and novel unprotected ferrocenoylamidoamino acids

In this study, crystalline and chirally stable carboxyl-protected and novel unprotected N-ferrocenoyl amino acid derivatives of Ser, Cys, Ala, Phe, Trp, Asp and Asn have been prepared. These amino acids undergo substitution reaction with 1-(ferrocenylcarbonyl)-1H-benzotriazole, 1, in partially aqueous media under microwave irradiation.     

On the Spatial Stability and Bifurcation of the Kirkendall Plane during Solid-State Interdiffusion

In a diffusion-controlled interaction, the Kirkendall plane, identified by inert particles placed at the initial interface between the reactants, need not be unique. The Kirkendall plane can microstructurally (spatially) be stable as well as unstable, and can, under predictable circumstances, bifurcate and even trifurcate. The movement of the Kirkendall markers during the interaction can be rationalized using the classical diffusion theory in terms of the Kirkendall velocity construction. The position of a Kirkendall plane is revealed in the reaction zone not only by the presence of inert markers, but also by a different crystal morphology developed on either side of the plane. The role of the Kirkendall plane in the morphogenesis of multiphase interdiffusion systems can be elucidated using equations of the interfacial reactions occurring in the diffusion zone. The appearance of one or more Kirkendall planes, characterized by morphology changes in the reaction layers is related to different nucleation sites of the product grains. The presence or absence of a Kirkendall plane in certain product phases provides insight into the initial stages of the reactive diffusion. Besides, the sometimes observed spatial (and temporal) patterns in a diffusion zone can be interpreted (and globally predicted) as a Kirkendall-effect mediated phenomenon. These conclusions will alter some previous notions about the diffusional growth of reaction layers and will influence the educational treatment in textbooks. It also will have strong technological implications, e.g., in the field of composite materials, thin-film electronic devices, etc.     

Differential expression of myogenic regulatory factor MyoD in pacu skeletal muscle (Piaractus mesopotamicus Holmberg 1887: Serrasalminae, Characidae, Teleostei) during juvenile and adult growth phases

Skeletal muscle is the edible part of the fish. It grows by hypertrophy and hyperplasia, events regulated by differential expression of myogenic regulatory factors (MRFs). The study of muscle growth mechanisms in fish is very important in fish farming development. Pacu (Piaractus mesopotamicus) is one of the most important food species farmed in Brazil and has been extensively used in Brazilian aquaculture programs. The aim of this study was to analyze hyperplasia and hypertrophy and the MRF MyoD expression pattern in skeletal muscle of pacu (P. mesopotamicus) during juvenile and adult growth stages. Juvenile (n = 5) and adult (n = 5) fish were anaesthetized, sacrificed, and weight (g) and total length (cm) determined. White dorsal region muscle samples were collected and immersed in liquid nitrogen. Transverse sections (10 μm thick) were stained with Haematoxilin–Eosin (HE) for morphological and morphometric analysis. Smallest fiber diameter from 100 muscle fibers per animal was calculated in each growth phase. These fibers were grouped into three classes (<20, 20–50, and >50 μm) to evaluate hypertrophy and hyperplasia in white skeletal muscle. MyoD gene expression was determined by semi-quantitative RT-PCR. PCR products were cloned and sequenced. Juvenile and adult pacu skeletal muscle had similar morphology. The large number of <20 μm diameter muscle fibers observed in juvenile fish confirms active hyperplasia. In adult fish, most fibers were over 50 μm diameter and denote more intense muscle fiber hypertrophy. The MyoD mRNA level in juveniles was higher than in adults. A consensus partial sequence for MyoD gene (338 base pairs) was obtained. The Pacu MyoD nucleotide sequence displayed high similarity among several vertebrates, including teleosts. The differential MyoD gene expression observed in pacu white muscle is possibly related to differences in growth patterns during the phases analyzed, with hyperplasia predominant in juveniles and hypertrophy in adult fish. These results should provide a foundation for understanding the molecular control of skeletal muscle growth in economically important Brazilian species, with a view to improving production quality.     

Dual-Color Photoconvertible Fluorescent Probes Based on Directed Photooxidation Induced Conversion for Bioimaging

We herein present a new concept to produce dual-color photoconvertible probes based on a mechanism called Directed Photooxidation Induced Conversion (DPIC). As a support of this mechanism, styryl-coumarins ( SCs ) bearing Aromatic Singlet Oxygen Reactive Moieties (ASORMs) like furan and pyrrole have been synthesized. SCs are bright fluorophores, which undergo a hypsochromic conversion upon visible light irradiation due to directed photooxidation of the ASORM that leads to the disruption of conjugation. SC-P , a yellow emitting probe bearing a pyrrole moiety, converts to a stable blue emitting coumarin with a 68 nm shift allowing the photoconversion and tracking of lipid droplet in live cells. This new approach might pave the way to a new generation of photoconvertible dyes for advanced bioimaging applications.     

Controlling the Assembly of Cellulose-Based Oligosaccharides through Sequence Modifications

Peptides and nucleic acids with programmable sequences are widely explored for the production of tunable, self-assembling functional materials. Herein we demonstrate that the primary sequence of oligosaccharides can be designed to access materials with tunable shapes and properties. Synthetic cellulose-based oligomers were assembled into 2D or 3D rod-like crystallites. Sequence modifications within the oligosaccharide core influenced the molecular packing and led to the formation of square-like assemblies based on the rare cellulose IV_II allomorph. In contrast, modifications at the termini generated elongated aggregates with tunable surfaces, resulting in self-healing supramolecular hydrogels.     

A New Bacterial Adenosine-Derived Nucleoside as an Example of RNA Modification Damage

The fields of RNA modification and RNA damage both exhibit a plethora of non-canonical nucleoside structures. While RNA modifications have evolved to improve RNA function, the term RNA damage implies detrimental effects. Based on stable isotope labelling and mass spectrometry, we report the identification and characterisation of 2-methylthio-1,N6-ethenoadenosine (ms²ϵA), which is related to 1,N6-ethenoadenine, a lesion resulting from exposure of nucleic acids to alkylating chemicals in vivo. In contrast, a sophisticated isoprene labelling scheme revealed that ms²ϵA biogenesis involves cleavage of a prenyl moiety in the known transfer RNA (tRNA) modification 2-methylthio-N6-isopentenyladenosine (ms²i⁶A). The relative abundance of ms²ϵA in tRNAs from translating ribosomes suggests reduced function in comparison to its parent RNA modification, establishing the nature of the new structure in a newly perceived overlap of the two previously separate fields, namely an RNA modification damage.     

Computational modeling of cardiac tissue with strongly coupled electromechanics and orthotropic viscoelastic effects

Modeling of complex mechanisms leading to the functioning of the heart has been an active field of research since decades. Difficulties associated with in vivo experiments motivate the utilization of computational models in order to gain a better appreciation of heart electromechanics. Although rate dependent behaviour of the orthotropic passive heart tissue has been comprehensively studied in the literature [1], effects of this phenomenon on fully coupled cardiac electromechanics are unrevealed yet. Therefore, this contribution is concerned with the investigation of viscous effects on the electromechanical response of the myocardium. To this end, we adopt the fully implicit finite element framework which strongly couples the mechanical and electrophysiological problem of the myocardium in a mono- and bi-domain setting [2,3], respectively. Viscous effects, however, are consistently embedded into this framework by making use of the orthotropic viscoelastic material model for the passive myocardium, which considers different relaxation mechanisms for the different orientation directions [5]. The performance of the proposed model is assessed by comparing finite element simulations of spiral waves in heart tissue for elastic and viscoelastic formulations. We further investigate the influence of viscosity on the defibrillation phenomenon by means of the finite element formulation of bidomain electrophysiology. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Quantitative nuclear magnetic resonance of chloride by an accurate internal standard approach

Chloride is the most common counterion used to improve aqueous solubility and enhance stability of small molecule active pharmaceutical ingredients. While several analytical techniques, such as titration, HPLC with charged aerosol detection, and ion chromatography, are currently utilized to assay the level of chloride, they have notable limitations, and these instruments may not be readily available. Here, we present a generally applicable ³⁵Cl solution NMR method to assay the level of chloride in pharmaceutical compounds. The method uses KClO₄ as an internal standard for improved accuracy in comparison with external standard methods, and it was found to be robust, linear over three orders of magnitude, precise (<3% RSD), and accurate (<0.5% absolute error).