Capillary pruning couples tissue perfusion and oxygenation with cardiomyocyte maturation in the postnatal mouse heart.

Introduction: Removal of poorly perfused capillaries by pruning contributes to remodeling the microvasculature to optimize oxygen and nutrient delivery. Blood flow drives this process by promoting the intravascular migration of endothelial cells in developing networks, such as in the yolk sac, zebrafish brain or postnatal mouse retina. Methods: In this study, we have implemented innovative tools to recognize capillary pruning in the complex 3D coronary microvasculature of the postnatal mouse heart. We have also experimentally tested the impact of decreasing pruning on the structure and function of this network by altering blood flow with two different vasodilators: losartan and prazosin. Results: Although both drugs reduced capillary pruning, a combination of experiments based on ex vivo imaging, proteomics, electron microscopy and in vivo functional approaches showed that losartan treatment resulted in an inefficient coronary network, reduced myocardial oxygenation and metabolic changes that delayed the arrest of cardiomyocyte proliferation, in contrast to the effects of prazosin, probably due to its concomitant promotion of capillary expansion. Discussion: Our work demonstrates that capillary pruning contributes to proper maturation and function of the heart and that manipulation of blood flow may be a novel strategy to refine the microvasculature and improve tissue perfusion after damage.

Stress Corrosion Cracking of 316L Stainless Steel Additively Manufactured with Sinter-Based Material Extrusion.

This study investigates the stress corrosion cracking (SCC) behavior of type 316L stainless steel (SS316L) produced with sinter-based material extrusion additive manufacturing (AM). Sinter-based material extrusion AM produces SS316L with microstructures and mechanical properties comparable to its wrought counterpart in the annealed condition. However, despite extensive research on SCC of SS316L, little is known about the SCC of sinter-based AM SS316L. This study focuses on the influence of sintered microstructures on SCC initiation and crack-branching susceptibility. Custom-made C-rings were exposed to different stress levels in acidic chloride solutions at various temperatures. Solution-annealed (SA) and cold-drawn (CD) wrought SS316L were also tested to understand the SCC behavior of SS316L better. Results showed that sinter-based AM SS316L was more susceptible to SCC initiation than SA wrought SS316L but more resistant than CD wrought SS316L, as determined by the crack initiation time. Sinter-based AM SS316L showed a noticeably lower tendency for crack-branching than both wrought SS316L counterparts. The investigation was supported by comprehensive pre- and post-test microanalysis using light optical microscopy, scanning electron microscopy, electron backscatter diffraction, and micro-computed tomography.

Crystallographic Texture and Substructural Phenomena in 316 Stainless Steel Printed by Selective Laser Melting.

There is a fast-growing interest in the use of selective laser melting (SLM) for metal/alloy additive manufacturing. Our current knowledge of SLM-printed 316 stainless steel (SS316) is limited and sometimes appears sporadic, presumably due to the complex interdependent effects of a large number of process variables of the SLM processing. This is reflected in the discrepant findings in the crystallographic textures and microstructures in this investigation compared to those reported in the literature, which also vary among themselves. The as-printed material is macroscopically asymmetric in terms of both structure and crystallographic texture. The <101> and <111> crystallographic directions align parallel with the SLM scanning direction (SD) and build direction (BD), respectively. Likewise, some characteristic low-angle boundary features have been reported to be crystallographic, while this investigation unequivocally proves them to be non-crystallographic, since they always maintain an identical alignment with the SLM laser scanning direction, irrespective of the matrix material's crystal orientation. There are also 500 ± 200 nm columnar or cellular features, depending on the cross-section, which are generally found all over the sample. These columnar or cellular features are formed with walls made of dense packing of dislocations entangled with Mn-, Si- and O-enriched amorphous inclusions. They remain stable after ASM solution treatments at a temperature of 1050 °C, and therefore, are capable of hindering boundary migration events of recrystallization and grain growth. Thus, the nanoscale structures can be retained at high temperatures. Large 2-4 µm inclusions form during the solution treatment, within which the chemical and phase distribution are heterogeneous.

Tofo gotoso en dorso nasal: reporte de caso / Nasal gouty tophus: case report

La gota es el trastorno del metabolismo de las purinas que se caracteriza por acumulación de ácido úrico por aumento de su producción o por disminución de su excreción. Con el paso del tiempo, el exceso de urato monosódico permite que se deposite en diferentes tejidos del organismo; siendo particularmente infrecuente la presentación de tofos a nivel facial. Paciente masculino adulto de 56 años, con antecedente de gota hace 38 años y presencia de tofos gotosos a nivel de miembros superiores e inferiores que acude por cuadro de 4 años de evolución de lesión indurada, levemente dolorosa a nivel de tercio medio de dorso nasal que ha ido aumentando de tamaño, que causa deformidad de pirámide nasal y leve sensación de obstrucción nasal bilateral por lo que se planifica resolución quirúrgica. El análisis histopatológico de las muestras enviadas bajo exéresis quirúrgica confirma que tejido enviado corresponde a tofo gotoso. Los tofos gotosos pueden aparecer en diferentes tejidos, como cartílagos, membranas y líquido sinovial, superficies articulares, siendo excepcionalmente raro, en el miocardio, válvulas mitral y aórtica, ojos, nariz y médula espinal. El lugar de presentación puede ser muy variable, al igual que su tamaño

Gout is a purine metabolism disorder characterized by accumulation of uric acid due to increased production or decreased excretion. Over time, excess monosodium urate allows it to be accumulated in different body tissues, although the occurrence in the facial area is particularly infrequent. A 56- year-old male patient with a gout antecedent from 38 years ago that presented gouty tophi at the level of the upper and lower limbs seek medical advice due to an indurated slightly painful lesion at the level of the middle third of the nasal dorsum that started 4 years before and has been increasing in size. The lesion was causing nasal pyramid deformity and a slight sensation of bilateral nasal obstruction, for which surgical resolution is planned. The histopathological analysis of the samples sent under surgical exeresis confirms that the tissue sample corresponds to gouty tophi. Gouty tophi can appear in different tissues, such as cartilage, membranes and synovial fluid, joint surfaces, being exceptionally rare in the myocardium, mitral and aortic valves, eyes, nose and spinal cord. The place of presentation can be very variable, as well as its size

Remodeling of the Microvasculature: May the Blood Flow Be With You.

The vasculature ensures optimal delivery of nutrients and oxygen throughout the body, and to achieve this function it must continually adapt to varying tissue demands. Newly formed vascular plexuses during development are immature and require dynamic remodeling to generate well-patterned functional networks. This is achieved by remodeling of the capillaries preserving those which are functional and eliminating other ones. A balanced and dynamically regulated capillary remodeling will therefore ensure optimal distribution of blood and nutrients to the tissues. This is particularly important in pathological contexts in which deficient or excessive vascular remodeling may worsen tissue perfusion and hamper tissue repair. Blood flow is a major determinant of microvascular reshaping since capillaries are pruned when relatively less perfused and they split when exposed to high flow in order to shape the microvascular network for optimal tissue perfusion and oxygenation. The molecular machinery underlying blood flow sensing by endothelial cells is being deciphered, but much less is known about how this translates into endothelial cell responses as alignment, polarization and directed migration to drive capillary remodeling, particularly in vivo. Part of this knowledge is theoretical from computational models since blood flow hemodynamics are not easily recapitulated by in vitro or ex vivo approaches. Moreover, these events are difficult to visualize in vivo due to their infrequency and briefness. Studies had been limited to postnatal mouse retina and vascular beds in zebrafish but new tools as advanced microscopy and image analysis are strengthening our understanding of capillary remodeling. In this review we introduce the concept of remodeling of the microvasculature and its relevance in physiology and pathology. We summarize the current knowledge on the mechanisms contributing to capillary regression and to capillary splitting highlighting the key role of blood flow to orchestrate these processes. Finally, we comment the potential and possibilities that microfluidics offers to this field. Since capillary remodeling mechanisms are often reactivated in prevalent pathologies as cancer and cardiovascular disease, all this knowledge could be eventually used to improve the functionality of capillary networks in diseased tissues and promote their repair.

New Eunicellin-Type Diterpenes from the Panamanian Octocoral Briareum Asbestinum.

Gorgonian octocorals are considered a prolific source of secondary metabolites with a wide range of biological activities, including anti-inflammatory activity. In particular, the genus Briareum is known for producing a wealth of diterpenes with complex chemical structures. The chemical study of the methanolic extract of Briareum asbestinum collected in Bocas del Toro, on the Caribbean side of Panama, led to the isolation of three new eunicellin-type diterpenes: briarellin T (1), asbestinin 27 (2), asbestinin 28 (3) and the previously described asbestinin 17 (4). The structures of the new compounds were determined by extensive NMR analyses and HRMS. Anti-inflammatory activity assays showed a significant reduction of the pro-inflammatory cytokines TNF-α, IL-6, IL-1ß and IL-8 as well as a downregulation of COX-2 expression in LPS-stimulated THP-1 macrophages. These findings support the potential use of these marine compounds as therapeutic agents in the treatment of inflammatory diseases.

No genome-wide DNA methylation changes found associated with medium-term reduced graphene oxide exposure in human lung epithelial cells.

The presence of nanomaterials in our everyday life is ever increasing, and so too are concerns about the possible health consequences of exposure to them. While evidence of their biological activity is growing, there is still scant knowledge of the epigenetic mechanisms that could be at play in these processes. Moreover, the great variability in the chemical and physical structures of these compounds handicaps the study of their possible health risks. Here we have synthesized reduced graphene oxide (rGO) through the thermal exfoliation/reduction of graphite oxide, and characterized the resulting material. We have then made use of Illumina's MethylationEPIC arrays and bisulphite pyrosequencing to analyse the genome-wide and global DNA methylation dynamics associated with the medium-term exposure of human lung epithelial cells to rGO at concentrations of 1 and 10 µg/mL. The results show no genome-wide or global DNA methylation changes associated with either condition. Our observations thus suggest that medium-term rGO exposure does not have significant effects on the DNA methylation patterns of human lung epithelial cells.

Analysis of the antiparasitic and anticancer activity of the coconut palm (Cocos nucifera L. ARECACEAE) from the natural reserve of Punta Patiño, Darién.

Cocos nucifera (C. nucifera) (the coconut palm tree) has been traditionally used to fight a number of human diseases, but only a few studies have tested its components against parasites such as those that cause malaria. In this study, C. nucifera samples were collected from a private natural reserve in Punta Patiño, Darien, Panama. The husk, leaves, pulp, and milk of C. nucifera were extracted and evaluated against the parasites that cause Chagas' disease or American trypanosomiasis (Trypanosoma cruzi), leishmaniasis (Leishmania donovani) and malaria (Plasmodium falciparum), as well as against a line of breast cancer cells. While there was no activity in the rest of the tests, five and fifteen-minute aqueous decoctions of leaves showed antiplasmodial activity at 10% v/v concentration. Removal of some HPLC fractions resulted in loss of activity, pointing to the presence of synergy between the components of the decoction. Chemical molecules were separated and identified using an ultra-performance liquid chromatography (UPLC) approach coupled to tandem mass spectrometry (LC-MS/MS) using atmospheric pressure chemical ionization quadrupole-time of flight mass spectrometry (APCI-Q-TOF-MS) and molecular networking analysis, revealing the presence of compounds including polyphenol, flavone, sterol, fatty acid and chlorophyll families, among others.

A Marine Diterpenoid Modulates the Proteasome Activity in Murine Macrophages Stimulated with LPS.

The proteasome is an intracellular complex that degrades damaged or unfolded proteins and participates in the regulation of several processes. The immunoproteasome is a specialized form that is expressed in response to proinflammatory signals and is particularly abundant in immune cells. In a previous work, we found an anti-inflammatory effect in a diterpenoid extracted from the octocoral Pseudopterogorgia acerosa, here called compound 1. This compound prevented the degradation of inhibitor κB α (IκBα) and the subsequent activation of nuclear factor κB (NFκB), suggesting that this effect might be due to inhibition of the ubiquitin-proteasome system. Here we show that compound 1 inhibits the proteasomal chymotrypsin-like activity (CTL) of murine macrophages in the presence of lipopolysaccharide (LPS) but not in its absence. This effect might be due to the capacity of this compound to inhibit the activity of purified immunoproteasome. The compound inhibits the cell surface expression of major histocompatibility complex (MHC)-I molecules and the production of proinflammatory cytokines induced by LPS in vitro and in vivo, respectively. Molecular docking simulations predicted that compound 1 selectively binds to the catalytic site of immunoproteasome subunits ß1i and ß5i, which are responsible for the CTL activity. Taken together these findings suggest that the compound could be a selective inhibitor of the immunoproteasome, and hence could pave the way for its future evaluation as a candidate for the treatment of inflammatory disorders and autoimmune diseases.

Expression analysis of ST3GAL4 transcripts in cervical cancer cells.

ST3GAL4 gene expression is altered in different cancer types, including cervical cancer. Several mRNA transcripts have been reported for this gene; however, their expression levels in cervical cancer have not been analyzed. ST3GAL4 encodes for ß­galactosidase α­2,3­sialyltransferase 4, involved in the biosynthesis of the tumour antigens sLe(x) and sulfo­sLe(x). The present study evaluated the presence of three mRNA variants (V1, V2 and V3) in cervical cancer cell lines, detecting the three variants. Additionally, the expression level of the V1 transcript of the ST3GAL4 gene was determined by reverse transcription­quantitative polymerase chain reaction in cervical cell lines and in normal, premalignant and cervical cancer tissue. The V1 transcript of the ST3GAL4 demonstrated significant decreased expression in premalignant and malignant cervical tissues. The results suggested that deregulation of this gene could occur prior to the presence of cancer and demonstrated the importance of evaluating the expression level of V1, and its association with disease progression.

Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and Amyloid-ß Aggregation in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Brain inflammation plays a key role in the progression of AD. Deposition of senile plaques in the brain stimulates an inflammatory response with the overexpression of pro-inflammatory mediators, such as the neuroinflammatory cytokine. interleukin-6. Curcumin has been revealed to be a potential agent for treating AD following different neuroprotective mechanisms, such as inhibition of aggregation and decrease in brain inflammation. We synthesized new curcumin derivatives with the aim of providing good anti-aggregation capacity but also improved anti-inflammatory activity. Nine curcumin derivatives were synthesized by etherification and esterification of the aromatic region. From these derivatives, compound 8 exhibited an anti-inflammatory effect similar to curcumin, while compounds 3, 4, and 10 were more potent. Moreover, when the anti-aggregation activity is considered, compounds 3, 4, 5, 6, and 10 showed biological activity in vitro. Compound 4 exhibited a strong anti-aggregation effect higher than curcumin. Monofunctionalized curcumin derivatives showed better bioactivity than difunctionalized compounds. Moreover, the presence of bulky groups in the chemical structure of curcumin derivatives decreased bioactivity.

Dielectric behavior of ceramic-graphene composites around the percolation threshold.

Al2O3/graphene and BaTiO3/graphene composites with different concentrations of the conductive second phase, both below and above the percolation threshold, were prepared by the traditional ceramic processing route followed by spark plasma sintering. It is shown that the addition of graphene pins the grain growth of the ceramic matrix grains, leading to a change of the microstructure at low filler concentrations. As a consequence, the composites exhibit two percolation thresholds and their dielectric properties are not only determined by the dielectric properties of the constituents and their relative fractions but also the microstructure of the composite must be considered. Additionally, a giant increase of the dielectric constant has been found around the percolation thresholds in barium titanate-graphene composites. In particular, values of the dielectric constant up to 45,000 and 15,000 were found at 1 kHz in composites containing 0.4 and 0.6 wt. % graphene, respectively.

An approach to classification and capacitance expressions in electrochemical capacitors technology.

The proliferation of novel types and designs of electrochemical capacitors makes it necessary to obtain a better understanding of the behavior of these systems together with a more systematic classification of them. In this study a rational classification of supercapacitors based on the charge storage mechanism and the active material of each electrode is proposed. The internationally accepted terminology - the terms symmetric, asymmetric and hybrid - is also clarified in an attempt to standardize the current definitions and facilitate the systematic classification of each device. Additionally, the selection of suitable mathematical expressions to calculate the capacitance of each kind of system is rationalized throughout the discussion taking into account the behavioral characteristics of each electrode. An examination of the potential evolution profile of each electrode during the galvanostatic cycling of the supercapacitor is presented as a key tool for understanding the fundamental behavior of these devices.

Graphite felt modified with bismuth nanoparticles as negative electrode in a vanadium redox flow battery.

A graphite felt decorated with bismuth nanoparticles was studied as negative electrode in a vanadium redox flow battery (VRFB). The results confirm the excellent electrochemical performance of the bismuth modified electrode in terms of the reversibility of the V(3+) /V(2+) redox reactions and its long-term cycling performance. Moreover a mechanism that explains the role that Bi nanoparticles play in the redox reactions in this negative half-cell is proposed. Bi nanoparticles favor the formation of BiHx , an intermediate that reduces V(3+) to V(2+) and, therefore, inhibits the competitive irreversible reaction of hydrogen formation (responsible for the commonly observed loss of Coulombic efficiency of VRFBs). Thus, the total charge consumed during the cathodic sweep in this electrode is used to reduce V(3+) to V(2+) , resulting in a highly reversible and efficient process.

A pseudopterane diterpene isolated from the octocoral Pseudopterogorgia acerosa inhibits the inflammatory response mediated by TLR-ligands and TNF-alpha in macrophages.

Several diterpenoids isolated from terrestrial and marine environments have been identified as important anti-inflammatory agents. Although considerable progress has been made in the area of anti-inflammatory treatment, the search for more effective and safer compounds is a very active field of research. In this study we investigated the anti-inflammatory effects of a known pseudopterane diterpene (referred here as compound 1) isolated from the octocoral Pseudopterogorgia acerosa on the tumor necrosis factor- alpha (TNF-α) and TLRs- induced response in macrophages. Compound 1 inhibited the expression and secretion of the inflammatory mediators TNF-α, interleukin (IL)-6, IL-1ß, nitric oxide (NO), interferon gamma-induced protein 10 (IP-10), ciclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1) induced by LPS in primary murine macrophages. This effect was associated with the inhibition of IκBα degradation and subsequent activation of NFκB. Compound 1 also inhibited the expression of the co-stimulatory molecules CD80 and CD86, which is a hallmark of macrophage activation and consequent initiation of an adaptive immune response. The anti-inflammatory effect was not exclusive to LPS because compound 1 also inhibited the response of macrophages to TNF-α and TLR2 and TLR3 ligands. Taken together, these results indicate that compound 1 is an anti-inflammatory molecule, which modulates a variety of processes occurring in macrophage activation.

Surface area measurement of graphene oxide in aqueous solutions.

Graphene oxide (GO) forms persistent dispersions in aqueous solutions up to concentrations of 0.2 mg mL(-1). Addition of methylene blue (MB) to these aqueous dispersion of GO gives rise to the observation in optical spectroscopy of new absorption bands that are indicative of the formation of MB/GO conjugates. Four new absorption maxima have been characterized, and their intensity varies depending on the relative concentration of MB with respect to GO. Two of these bands appearing at 677 and 757 nm correspond to individual MB molecules adsorbed on neutral or acid sites of GO, respectively. Two other bands at 615 and 580 nm are attributable to adsorbed MB molecules showing interaction with other neighbor dye molecules at incomplete (615 nm) or complete (580 nm) surface coverage. Complete coverage of GO surface by MB causes the formation of a precipitate and the separation of the MB/GO conjugate. EDS mapping of carbon and sulfur atoms of MB/GO conjugate indicates the homogeneous distribution of MB molecules coating GO sheets. A simple and reliable protocol for surface area measurement and determination of the level of aggregation for GO dispersions in water has been proposed by determining the amount of MB that leads to the maximum intensity of the 580 nm band and precipitation of the MB/GO conjugate. Specific surface area as high as 736.6 m(2) g(-1) in the range of the theoretical value for GO has been experimentally measured for diluted GO solutions, but aggregation levels of 15% were estimated for GO concentration of 50 µg mL(-1).

High performance activated carbon for benzene/toluene adsorption from industrial wastewater.

A coal-tar-derived mesophase was chemically activated to produce a high surface area (~3200 m(2)/g) carbon with a porosity made up of both micropores and mesopores. Its adsorption capacities were found to be among the highest ever reported in literature, reaching values of 860 mg/g and 1200 mg/g for the adsorption of benzene and toluene, respectively, and 1200 mg/g for the combined adsorption of benzene and toluene from an industrial wastewater. Such high values imply that the entire pore system, including the mesopore fraction, is involved in the adsorption process. The almost complete pore filling is thought to be due to the high relative concentrations of the tested solutions, resulting from the low saturation concentration values for benzene and toluene, which were obtained by fitting the adsorption data to the BET equation in liquid phase. The kinetics of adsorption in the batch experiments which were conducted in a syringe-like adsorption chamber was observed to proceed in accordance with the pseudo-second order kinetic model. The combined presence of micropores and mesopores in the material is thought to be the key to the high kinetic performance, which was outstanding in a comparison with other porous materials reported in the literature.

Preparation of low toxicity pitches by thermal oxidative condensation of anthracene oil.

This article describes a novel industrial procedure for producing new pitches of low toxicity from anthracene oil, a byproduct of coal tar distillation. The procedure involves oxidative treatment in order to polymerize and condense the anthracene oil components followed by thermal treatment and distillation in order to obtain a pitch with the desired parameters. This sequence (oxidative treatment/thermal treatment/distillation) was repeated four times under reaction conditions of increasing severity in four cycles of anthracene oil processing to obtain the four pitches. The pitches had similar characteristics to those of standard binder coal tar pitches (e.g., softening point and wetting capacity). Because of the inherent composition of the parent anthracene oil, the pitches were found to be totally free of solid particles, i.e., primary quinoline insolubles and metals. The gas chromatography and gas chromatography/mass spectroscopy results revealed a consecutive decrease in toxicity with successive cycles of anthracene oil processing. Thus, the benzo[a]pyrene content decreased from 11.2 mg/g for the pitch in cycle one to 1.5 mg/g for the pitch with four processing cycles. The carcinogenicity of the pitches, evaluated on the basis of benzo[a]pyrene toxic equivalency factors, also followed the same tendency. The final carcinogenity values are nearly all lower than those of standard binder coal tar pitches.